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排序方式: 共有6104条查询结果,搜索用时 15 毫秒
91.
JS Plummer KA Berryman C Cai WL Cody J DiMaio AM Doherty JJ Edmunds JX He DR Holland S Levesque DR Kent LS Narasimhan JR Rubin ST Rapundalo MA Siddiqui AJ Susser Y St-Denis PD Winocour 《Canadian Metallurgical Quarterly》1998,8(23):3409-3414
The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors is described. We have explored the SAR with modifications to the P1 site. The introduction of arginine mimetics at the P1 site led to potent and selective thrombin inhibitors. 相似文献
92.
S Maixner R Tandon A Eiser S Taylor JR DeQuardo J Shipley 《Canadian Metallurgical Quarterly》1998,155(11):1600-1602
OBJECTIVE: The authors sought to replicate and extend previous observations of improvement in some EEG sleep measures during the course of antipsychotic treatment in schizophrenia patients. METHOD: Fourteen medication-free patients with schizophrenia underwent 2 nights of sleep EEG monitoring before and after 3-4 weeks of treatment with clinically determined doses of haloperidol or thiothixene. RESULTS: Measures of sleep continuity improved consistently. REM latency increased, although five of 14 patients continued to exhibit short REM latencies (less than 60 minutes). Stage 3 sleep increased during neuroleptic treatment, while stage 4 sleep did not change. CONCLUSIONS: These data demonstrate partial improvement of some but not all EEG sleep measures in schizophrenic patients through the course of neuroleptic treatment. They suggest that shortened REM latency and disturbed sleep continuity might represent reversible state abnormalities, while reduced slow-wave sleep may represent a more persistent trait abnormality in schizophrenia. 相似文献
93.
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95.
TM Officer R Pellegrino V Brusasco JR Rodarte 《Canadian Metallurgical Quarterly》1998,85(5):1982-1988
We compared four algorithms by using least squares regression for determination of pulmonary resistance and dynamic elastance in subjects with emphysema, normal subjects, and subjects with asthma before and after bronchoconstriction. The four methods evaluated include 1) a single resistance and elastance, 2) separate resistances and elastances for each half breath, 3) separate inspiratory and expiratory resistances with a single elastance, and 4) separate inspiratory and expiratory resistances, an expiratory volume interaction term, and a single elastance. All methods gave comparable results in normal and asthmatic subjects. We found expiratory resistance was larger than inspiratory resistance in normal and asthmatic subjects during control conditions, but inspiratory resistance was higher than expiratory resistance in subjects who experienced severe bronchoconstriction in response to methacholine. In subjects who are flow limited, method 2 gives a higher inspiratory resistance than would be computed by assuming that the elastic pressure-volume curve passes through the zero-flow points. Methods 1 and 3 overestimate dynamic elastance and inspiratory resistance. Method 4 appears to identify flow limitation and dynamic hyperinflation and gives a good measure of inspiratory resistance and dynamic elastance. 相似文献
96.
R Hui JR Ball RD Macmillan FS Kenny OW Prall DH Campbell AL Cornish RA McClelland RJ Daly JF Forbes RW Blamey EA Musgrove JF Robertson RI Nicholson RL Sutherland 《Canadian Metallurgical Quarterly》1998,17(8):1053-1059
The EMS1 and CCND1 genes at chromosome 11q13 are amplified in about 15% of primary breast cancers but appear to confer different phenotypes in ER positive and ER negative tumours. Since there are no published data on EMS1 expression in large series of breast cancers we examined the relationship of EMS1 expression with EMS1 gene copy number and expression of mRNAs for cyclin D1 and ER. In a subset of 129 patients, where matched tumour RNA and DNA was available, EMS1 mRNA overexpression was associated predominantly with gene amplification (P = 0.0061), whereas cyclin D1 mRNA overexpression was not (P = 0.3142). In a more extensive series of 351 breast cancers, there was no correlation between cyclin D1 and EMS1 expression in the EMS1 and cyclin D1 overexpressors (P = 0.3503). Although an association between EMS1 mRNA expression and ER positivity was evident (P = 0.0232), when the samples were divided into quartiles of EMS1 or cyclin D1 mRNA expression, the increase in the proportion of ER positive tumours in the ascending EMS1 mRNA quartiles was not statistically significant (P = 0.0951). In marked contrast there was a significant stepwise increase in ER positivity in ascending quartiles of cyclin D1 mRNA (P = 0.030). A potential explanation for this difference was provided by the observation that in ER positive breast cancer cells oestradiol treatment resulted in increased cyclin D1 gene expression but was without effect on EMS1. The relationship between EMS1 expression and clinical outcome was examined in a subset of 234 patients with median follow-up of 74 months. High EMS1 expression was associated with age > 50 years (P = 0.0001), postmenopausal status (P = 0.0008), lymph node negativity (P = 0.019) and an apparent trend for worse prognosis in the ER negative subgroup. These data demonstrate that overexpression of EMS1 mRNA is largely due to EMS1 gene amplification, is independent of cyclin D1 and ER expression and, in contrast to cyclin D1, is not regulated by oestrogen. Independent overexpression of these genes may confer different phenotypes and disease outcomes in breast cancer as has been inferred from recent studies of EMS1 and CCND1 gene amplification. 相似文献
97.
JR Henkel G Apodaca Y Altschuler S Hardy OA Weisz 《Canadian Metallurgical Quarterly》1998,9(9):2477-2490
The function of acidification along the endocytic pathway is not well understood, in part because the perturbants used to modify compartmental pH have global effects and in some cases alter cytoplasmic pH. We have used a new approach to study the effect of pH perturbation on postendocytic traffic in polarized Madin-Darby canine kidney (MDCK) cells. Influenza M2 is a small membrane protein that functions as an acid-activated ion channel and can elevate the pH of the trans-Golgi network and endosomes. We used recombinant adenoviruses to express the M2 protein of influenza virus in polarized MDCK cells stably transfected with the polymeric immunoglobulin (Ig) receptor. Using indirect immunofluorescence and immunoelectron microscopy, M2 was found to be concentrated at the apical plasma membrane and in subapical vesicles; intracellular M2 colocalized partly with internalized IgA in apical recycling endosomes as well as with the trans-Golgi network marker TGN-38. Expression of M2 slowed the rate of IgA transcytosis across polarized MDCK monolayers. The delay in transport occurred after IgA reached the apical recycling endosome, consistent with the localization of intracellular M2. Apical recycling of IgA was also slowed in the presence of M2, whereas basolateral recycling of transferrin and degradation of IgA were unaffected. By contrast, ammonium chloride affected both apical IgA and basolateral transferrin release. Together, our data suggest that M2 expression selectively perturbs acidification in compartments involved in apical delivery without disrupting other postendocytic transport steps. 相似文献
98.
J Whittle CJ Lin JR Lave MJ Fine KM Delaney DZ Joyce WW Young WN Kapoor 《Canadian Metallurgical Quarterly》1998,36(7):977-987
OBJECTIVES: The authors describe the relation of provider characteristics to processes, costs, and outcomes of medical care for elderly patients hospitalized for community-acquired pneumonia. METHODS: Using Medicare claims data, Medicare beneficiaries discharged from Pennsylvania hospitals during 1990 with community-acquired pneumonia were identified. Claims data were used to ascertain mortality, readmissions, use of procedures and physician consultations, and the costs of care. The relationship of these measures to provider characteristics was analyzed using regression techniques to adjust for patient characteristics, including comorbidity and microbial etiology. RESULTS: Among 22,294 pneumonia episodes studied, 30-day mortality was 17.0%. After adjusting for patient characteristics, 30-day mortality and readmission rates were unrelated to hospital teaching status or urban location or to physician specialty. Use of procedures and physician consultations was more common and costs were 11% higher among patients discharged from teaching hospitals compared with nonteaching hospitals. Similarly, costs were 15% higher at urban hospitals compared with rural hospitals. General internists and medical subspecialists used more procedures and had higher costs than family practitioners. CONCLUSIONS: Processes and costs of care for community-acquired pneumonia varied by provider characteristics, but neither mortality nor readmission rates did. These differences cannot be explained by clinical variables in the database. Further studies should determine whether less costly patterns of care for pneumonia, and perhaps other conditions, could replace more costly ones without compromising patient outcomes. 相似文献
99.
BACKGROUND AND PURPOSE: Norway has the highest reported incidence of hip fractures in western Europe. Little is known about the epidemiology of falls in Norway where the winter season is long and dark. The objective of this work was to study reported falls and their consequences among elderly Norwegians living at home. METHODS: A cross-sectional design was used for the study. Interviews were performed in the homes of 431 subjects, aged 67-97 years, living at home. Information on falling was gathered through six questions: whether the subject had fallen during the last six months, and if so, how many falls they had, where the last fall occurred, its perceived reason, the activity the subject had been engaged in when the fall occurred, and the resulting injury. RESULTS: In all, 24.1% of subjects reported falling during the last six months, and 9.5% had suffered more than one fall. Falls were most frequently linked to external events (63.1%). Outdoor falls were more frequent (59.0%; 95% CI = 51.2-82.0) than indoor falls. Older subjects were associated with more frequent indoor falls (p < 0.05), but gender was not significant. Fifty-one per cent of subjects had fallen while walking and 53% had suffered an injury from the last fall. In 13.4% of the women and 16.2% of the men, the last fall had resulted in a fracture. CONCLUSIONS: Compared to the results of other studies from industrialized Western countries, a similar crude fall rate, similar frequency and similar type of injury were found. However, in contrast to other studies, no gender difference was observed with regard to falling, place of falling and fracture rate. 相似文献
100.
OBJECTIVE: Prednisolone reduced the progression of joint destruction over 2 yr in early, active rheumatoid arthritis. The response to discontinuation of prednisolone under double-blind conditions is now reported. METHODS: A randomized, double-blind, placebo-controlled trial of prednisolone 7.5 mg daily in addition to routine medication over 2 yr in 128 patients with early rheumatoid arthritis, using radiological progression (changes in the Larsen score) and the development of erosions as primary outcome measures. Study medication was blindly discontinued and follow-up maintained for a further year. Other assessments included disability, joint inflammation, pain and the acute-phase response. RESULTS: Similar results were obtained when all available radiographs were included for each year of assessment (maximum 114) and when only patients with radiographs at all time points were included (75 patients). In these 75, the mean progression in the prednisolone group was 0.21 Larsen units in year 1, 0.04 units in year 2 and 1.01 units in year 3 (P = 0.587, 0.913 and 0.039 for change within each year, respectively). The equivalent placebo group means were 2.34, 1.00 and 1.63 Larsen units (P = 0.001, 0.111 and 0.012; difference between groups: 2.13, 0.96 and 0.67 units, P = 0.082, 0.02 and 0.622). The percentage of hands which had erosions at each time point was: prednisolone group: 27.8, 29.2, 34.7 and 39.2; placebo group: 28.2, 48.7, 59.0 and 66.5. There was little evidence for a flare in clinical symptoms after discontinuation of prednisolone. CONCLUSION: Joint destruction resumed after discontinuation of prednisolone. This corroborates the previously reported therapeutic effect and challenges current concepts of disease pathogenesis. 相似文献