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- Rebeiz, A. G., et al.
(author)
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Comparison of ST-segment resolution with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy versus fibrinolytic alone (data from four clinical trials)
- 2005
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In: Am J Cardiol. - 0002-9149. ; 95:5, s. 611-4
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Journal article (peer-reviewed)abstract
- We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed.
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- Johanson, Per, 1963, et al.
(author)
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An academic ECG core lab perspective of the FDA initiative for digital ECG capture and data management in large-scale clinical trials
- 2005
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In: Drug Information Journal. - 0092-8615. ; 39:4, s. 345-351
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Journal article (peer-reviewed)abstract
- Maximal utility of accessible data is attractive to all partners in clinical research, whether it directly improves patient care or more accurately allows identification of the safety and efficacy of a new drug or procedure. The Food and Drug Administration (FDA) has presented a guideline draft addressing digitization of electrocardiogram (ECG) data in clinical trials to improve the standards for collection, analysis, and storage of safety information on new medical therapies. This FDA initiative has led to discussions and collaboration among the FDA, the pharmaceutical industry, the electrocardiographj, manufacturers, and the academic as well as the nonacademic EGG core labs. In this article, we present a broad-based viewpoint from two groups of academic EGG core labs, the Alliance of Academic EGG Core Labs and the Virtual Electronic EGG Corelab International Consortium. We have chosen to widen the perspective from using digitized EGG data in safety trials only, as addressed by the FDA guideline draft, to a discussion on the possibilities and the potential problems when using digitized EGG data also in large clinical trials focusing on efficacy measurements. We conclude that the benefit of digital data mining is probably well worth an initial incremental effort and expense.
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- Kukulski, W, et al.
(author)
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The 5 angstrom structure of heterologously expressed plant aquaporin SoPIP2;1
- 2005
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In: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 350:4, s. 611-616
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Journal article (peer-reviewed)abstract
- SoPIP2;1 is one of the major integral proteins in spinach leaf plasma membranes. In the Xenopus oocyte expression system its water channel activity is regulated by phosphorylation at the C terminus and in the first cytosolic loop. To assess its structure, SoPIP2;1 was heterologously expressed in Pichia pastoris as a His-tagged protein and in the non-tagged form. Both forms were reconstituted into 2D crystals in the presence of lipids. Tubular crystals and double-layered crystalline sheets of non-tagged SoPIP2;1 were observed and analyzed by cryo-electron microscopy. Crystalline sheets were highly ordered and diffracted electrons to a resolution of 2.96 angstrom. High-resolution projection maps of tilted specimens provided a 3D structure at 5 angstrom resolution. Superposition of the SoPIP2;1 potential map with the atomic model of AQP1 demonstrates the generally well conserved overall structure of water channels. Differences concerning the extracellular loop A explain the particular crystal contacts between oppositely oriented membrane sheets of SoPIP2;1 2D crystals, and may have a function in rapid volume changes observed in stomatal guard cells or mesophyll protoplasts. This crystal packing arrangement provides access to the phosphorylated C terminus as well as the loop B phosphorylation site for studies of channel gating. (c) 2005 Elsevier Ltd. All rights reserved.
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- Bergh, Jan-Erik, et al.
(author)
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Insect DNA Exposed to Two Insecticides
- 2007
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In: International Conference Directions in Preventive Conservation Sibiu. - Sibiu, Rumänien.
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Conference paper (other academic/artistic)abstract
- Analyses of DNA is now a standard method in exploring taxonomical relationships between taxa or when studying intraspecific genetic variation. For these purposes museum specimen are often used. During their “museum history”, biological collections often have been treated with various insecticides to avoid museum pest attacks. There is a risk that some insecticides have more or less destroyed the specimen DNA, and thus it is important to know to what extent this happens to be able to estimate if old collection are useful for DNA screening and also to avoid future mistakes. Kigawa et al. (2003) showed that methyl bromide, methyl bromide/ethylene oxide (mixed), ethylene oxide, propylene oxide and methyl iodide all caused degradation of DNA in samples of mushroom and chicken muscle. We have tested possible negative effects on insect DNA from exposure of paradichlorobenzene and diclorvos. Species used were Schistocerca gregaria (Orthoptera), Musca domestica (Diptera), Dermestes hemeroidalis (Coleoptera), Periplaneta americana (Blattodea). The specimens were cut into two parts before completely dried in silica gel in closed containers for about 2 weeks. Three serials were set up in sealed, small glass containers for each species: (1) paradichlorobenzene (0.5g ±0.02g, representing saturated concentration); (2) diclorvos (0.5g ±0.02g, representing saturated concentration); and (3) no chemicals (blank). Each serial was sampled after 1 and 4 weeks. Immediately after sampling, the insect tissues were exposed to clean air for 8 hours in order to eliminate chemicals from the tissue before subsequent treatment. Together with the blank samples, the exposed tissues were stored in deep freezers before extracted for DNA after the last tissue sampling. After extraction, a 658 bp (base pair) COI gene fragment of the DNA was amplified using the forward and reverse primers HCO2198 (TAA ACT TCA GGG TGA CCA AAA AAT CA) and HCOout (CCA GGT AAA ATT AAA ATA TAA ACT TC), respectively. Electrophoresis of the PCR products was run for about 2h and presence or absence of the amplified COI gene fragment showed as band or absence of band in UV light. The gel was photographed for documentation of the results. For S. gregaria we did not obtain any clear results, probably because the primer did not work for the COI gene of this species. For the other three species no effect could be seen from the exposure of paradichlorobenzene, while dichlorvos destroyed the COI gene fragment after 28 days. For M. domestica a band was present after one week exposure. Our conclusion is that dichlorvos has a deteriorating effect on DNA. A more extensive experimental series on M. domestica has been started at the Swedish Museum of Natural History. Reference: Kigawa, R., Nochide, H., Kimura, H. and Miura, S., Effects of various fumigants, thermal methods and carbon dioxide treatment on DNA extraction and amplification: A case study on freeze-dried mushroom and free-dried muscle specimens. Collection Forum 2003, 18 (1-2): 74-89.
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- Ernstgard, L, et al.
(author)
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Acute effects of exposure to vapours of dioxane in humans
- 2006
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In: Human & experimental toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 25:12, s. 723-729
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Journal article (peer-reviewed)abstract
- Information on the acute effects associated with the handling of 1,4-dioxane is sparse. Our aim was to evaluate the acute effects of 1,4-dioxane vapours. In a screening study, six healthy volunteers rated symptoms on a visual analogue scale (VAS), while exposed to stepwise increasing levels of 1,4-dioxane, from 1 to 20 ppm. The initial study indicated no increased ratings at any of the exposure levels; we decided to use 20 ppm (72 mg/m3) as a tentative no observed adverse effect level (NOAEL). In the main study, six female and six male healthy volunteers were exposed to 0 (control exposure) and 20 ppm 1,4-dioxane vapour, for 2 hours at rest. The volunteers rated 10 symptoms on VAS before, during, and after the exposure. Blink frequency was monitored during exposure. Pulmonary function, and nasal swelling, was measured before, and at 0 and 3 hours after exposure. Inflammatory markers in plasma (C-reactive protein, and interleukin-6) were measured before and at 3 hours after exposure. In conclusion, exposure to 20 ppm 1,4-dioxane for 2 hours did not significantly affect symptom ratings, blink frequency, pulmonary function, nasal swelling, or inflammatory markers in the plasma of the 12 volunteers in our study.
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