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251.
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CP Cannon CM Gibson CH McCabe AA Adgey MJ Schweiger RF Sequeira G Grollier RP Giugliano M Frey HS Mueller RM Steingart WD Weaver F Van de Werf E Braunwald 《Canadian Metallurgical Quarterly》1998,98(25):2805-2814
BACKGROUND: Bolus thrombolytic therapy is a simplified means of administering thrombolysis that facilitates rapid time to treatment. TNK-tissue plasminogen activator (TNK-tPA) is a highly fibrin-specific single-bolus thrombolytic agent. METHODS AND RESULTS: In TIMI 10B, 886 patients with acute ST-elevation myocardial infarction presenting within 12 hours were randomized to receive either a single bolus of 30 or 50 mg TNK-tPA or front-loaded tPA and underwent immediate coronary angiography. The 50-mg dose was discontinued early because of increased intracranial hemorrhage and was replaced by a 40-mg dose, and heparin doses were decreased. TNK-tPA 40 mg and tPA produced similar rates of TIMI grade 3 flow at 90 minutes (62.8% versus 62.7%, respectively, P=NS); the rate for the 30-mg dose was significantly lower (54.3%, P=0.035) and was 65. 8% for the 50-mg dose (P=NS). A prespecified analysis of weight-based TNK-tPA dosing using median TIMI frame count demonstrated a dose response (P=0.001). Similar dose responses were observed for serious bleeding and intracranial hemorrhage, but significantly lower rates were observed for both TNK-tPA and tPA after the heparin doses were lowered and titration of the heparin was started at 6 hours. CONCLUSIONS: TNK-tPA, given as a single 40-mg bolus, achieved rates of TIMI grade 3 flow similar to those of the 90-minute bolus and infusion of tPA. Weight-adjusting TNK-tPA appears to be important in achieving optimal reperfusion; reduced heparin dosing appears to improve safety for both agents. Together with the safety results from the parallel Assessment of the Safety of a New Thrombolytic: TNK-tPA (ASSENT I) trial, an appropriate dose of this single-bolus thrombolytic agent has been identified for phase III testing. 相似文献
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VIu Amiiants GV Gromova AA Veres ZN Bidzhieva MA Kazarian VG Tolmachev 《Canadian Metallurgical Quarterly》1996,(6):7-9
Left ventricular myocardial contractility was found essential in dynamics of clinical IHD picture in patients on rehabilitation treatment at low mountain resorts. All the patients have previously undergone surgical myocardial revascularization. Patients with normal left ventricular myocardial contractility benefited most of all. 相似文献
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The sleep and waking and EEG power spectrum effects of the putative 5-HT1A antagonist NAN-190 (0.5 mg/kg, i.p.) were studied alone and in co-administration with the selective serotonin re-uptake inhibitor citalopram (5.0 mg/kg, i.p.) in the rat. Citalopram, as in a prior dose-response study, reduced REM sleep. In addition, a slight increase in NREM sleep was observed. Citalopram reduced NREM fronto-parietal (FP) EEG power density in the 5-20 Hz range. When administered alone, NAN-190 suppressed REM sleep in the first 2 h, and reduced SWS-2 in the first 4 after administration. NAN-190 also suppressed selectively NREM sleep slow-wave activity in both fronto-frontal (FF) and FP EEG power spectrum. When administered in combination with citalopram, an attenuation of the power density reduction in the 7-15 Hz range in the FF EEG of citalopram alone, was observed. However, the EEG power spectral density and REM sleep suppressive effects of NAN-190 were both augmented. The results are compatible with the notion that serotonin is involved in the modulation of the slow wave activity in the EEG during NREM sleep. The results are cordant with other data suggesting that postsynaptic 5-HT1A stimulation might increase slow wave activity in the NREM EEG, and that serotonergic stimulation of other receptor subtypes (possibly 5-HT2) may decrease slow wave activity in the NREM EEG. 相似文献
257.
AA Morris JW Taanman J Blake JM Cooper BD Lake M Malone S Love PT Clayton JV Leonard AH Schapira 《Canadian Metallurgical Quarterly》1998,28(4):556-563
BACKGROUND/AIMS: Liver failure in infancy can result from several disorders of the mitochondrial respiratory chain. In some patients, levels of mitochondrial DNA are markedly reduced, a phenomenon referred to as mitochondrial DNA depletion. To facilitate diagnosis of this condition, we have reviewed the clinical and pathological features in five patients with mitochondrial DNA depletion. METHODS: Cases were identified by preparing Southern blots of DNA from muscle and liver, hybridising with appropriate probes and quantifying mitochondrial DNA relative to nuclear DNA. RESULTS: All our patients with mitochondrial DNA depletion died of liver failure. Other problems included hypotonia, hypoglycaemia, neurological abnormalities (including Leigh syndrome) and cataracts. Liver histology showed geographic areas of fatty change, bile duct proliferation, collapse of liver architecture and fibrosis; some cells showed decreased cytochrome oxidase activity. Muscle from three patients showed mitochondrial proliferation, with loss of cytochrome oxidase activity in some fibres but not in others; in these cases, muscle mitochondrial DNA levels were less than 5% of the median control value. The remaining two patients (from a single pedigree) had normal muscle histology and histochemistry associated with less severe depletion of mitochondrial DNA in muscle. CONCLUSIONS: Liver failure is common in patients with mitochondrial DNA depletion. Associated clinical features often include neuromuscular disease. Liver and muscle histology can be helpful in making the diagnosis. Mitochondrial DNA levels should be measured whenever liver failure is thought to have resulted from respiratory chain disease. 相似文献
258.
AA Sosunov PP Krugliakov VN SHvalev G Guski IuV Postnov 《Canadian Metallurgical Quarterly》1997,59(2):32-37
Debridement of nonviable tissue is crucial to optimal wound healing, which can be impaired unless all necrotic tissue, exudate, and metabolic wastes have been removed from the wound. Debridement methods are classified as sharp, mechanical, chemical, and autolytic. This article describes methods of debridement and their outcomes. 相似文献
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SM Prince MZ Papiz AA Freer G McDermott AM Hawthornthwaite-Lawless RJ Cogdell NW Isaacs 《Canadian Metallurgical Quarterly》1997,268(2):412-423
The refined structure of the peripheral light-harvesting complex from Rhodopseudomonas acidophila strain 10050 reveals a membrane protein with protein-protein interactions in the trans-membrane region exclusively of a van der Waals nature. The dominant factors in the formation of the complex appear to be extramembranous hydrogen bonds (suggesting that each apoprotein must achieve a fold close to its final structure in order to oligomerize), protein-pigment and pigment-pigment interactions within the membrane-spanning region. The pigment molecules are known to play an important role in the formation of bacterial light-harvesters, and their extensive mediation of structural contacts within the membrane bears this out. Amino acid residues determining the secondary structure of the apoproteins influence the oligomeric state of the complex. The assembly of the pigment array is governed by the apoproteins of LH2. The particular environment of each of the pigment molecules is, however, influenced directly by few protein contacts. These contacts produce functional effects that are not attributable to a single cause, e.g. the arrangement of an overlapping cycle of chromophores not only provides energy delocalisation and storage properties, but also has consequences for oligomer size, pigment distortion modes and pigment chemical environment, all of which modify the precise function of the complex. The evaluation of site energies for the pigment array requires the consideration of a number of effects, including heterogeneous pigment distortions, charge distributions in the local environment and mechanical interactions. 相似文献