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991.
Three structural variants of the joining peptide (JP) fragment of POMC have been purified from human pituitaries. Ion exchange and reverse phase tissue extraction procedures were combined with reverse phase HPLC to achieve complete purification of each form of JP. Fragments resulting from tryptic hydrolysis of each form were characterized by amino acid analysis and fast atom bombardment mass spectrometry. The predominant form of human JP, accounting for about 50% of the total purified, was found to be conjugated to glutathione through the lone cysteine residue at position 9. The other two variants were identified as human JP with a free cysteine residue and human JP dimer and accounted for 35% and 15%, respectively, of the total purified. Recently, human JP-(1-18) has been suggested as having adrenal androgen-stimulating activity. None of the three JP variants or their respective 1-20 amino-terminal fragments resulting from tryptic hydrolysis showed any ability to promote the secretion of dehydroepiandrosterone sulfate by cultured human fetal adrenal cells. Similarly, no potentiation of the stimulatory effects of ACTH-(1-39) was observed. The three variants of human JP as well as JP purified from rat, porcine, and bovine pituitaries were tested for their ability to stimulate androgenic steroids from dispersed fetal rabbit adrenal cells. None showed any significant biological activity either in stimulating steroid secretion or in potentiating the action of ACTH-(1-39).  相似文献   
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Aims

Troponin levels are commonly elevated among patients hospitalized for heart failure (HF), but the prevalence and prognostic significance of early post‐discharge troponin elevation are unclear. This study sought to describe the frequency and prognostic value of pre‐discharge and post‐discharge troponin elevation, including persistent troponin elevation from the inpatient to outpatient settings.

Methods and results

The ASTRONAUT trial (NCT00894387; http://www.clinicaltrials.gov ) enrolled hospitalized HF patients with ejection fraction ≤40% and measured troponin I prior to discharge (i.e. study baseline) and at 1‐month follow‐up in a core laboratory (elevation defined as >0.04 ng/mL). This analysis included 1469 (91.0%) patients with pre‐discharge troponin data. Overall, 41.5% and 29.9% of patients had elevated pre‐discharge [median: 0.09 ng/mL; interquartile range (IQR): 0.06–0.19 ng/mL] and 1‐month (median: 0.09 ng/mL; IQR: 0.06–0.15 ng/mL) troponin levels, respectively. Among patients with pre‐discharge troponin elevation, 60.4% had persistent elevation at 1 month. After adjustment, pre‐discharge troponin elevation was not associated with 12‐month clinical outcomes. In contrast, 1‐month troponin elevation was independently predictive of increased all‐cause mortality [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.18–2.13] and cardiovascular mortality or HF hospitalization (HR 1.28, 95% CI 1.03–1.58) at 12 months. Associations between 1‐month troponin elevation and outcomes were similar among patients with newly elevated (i.e. normal pre‐discharge) and persistently elevated levels (interaction P ≥ 0.16). The prognostic value of 1‐month troponin elevation for 12‐month mortality was driven by a pronounced association among patients with coronary artery disease (interaction P = 0.009).

Conclusions

In this hospitalized HF population, troponin I elevation was common during index hospitalization and at 1‐month follow‐up. Elevated troponin I level at 1 month, but not pre‐discharge, was independently predictive of increased clinical events at 12 months. Early post‐discharge troponin I measurement may offer a practical means of risk stratification and should be investigated as a therapeutic target.
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Insulin-like effects of vanadate in isolated rat adipocytes   总被引:1,自引:0,他引:1  
Vanadate has been shown to have a number of insulin-like effects in various cells, including isolated rat adipocytes. In the present study we compared the activities of vanadate and insulin in isolated fat cells using a number of different assays of insulin-like activity. Both insulin and vanadate stimulated [2-3H]glucose incorporation into fat cell lipid in a dose-dependent manner, but the maximal effect of vanadate was markedly greater than that of insulin. At 10(-2) M vanadate the effect was 3-4 times as great as the maximal effect of insulin. This effect was dependent on specific glucose transport. Combinations of insulin and vanadate were not more effective than vanadate alone. Vanadate also produced antilipolysis with an effect somewhat greater than that of insulin. Using [U-14C]glucose both vanadate and insulin stimulated 14CO2 production and [14C]glucose incorporation into lipid, and again the effect of vanadate was greater than that of insulin. Vanadate had a greater effect on 14CO2 production than on [14C]glucose incorporation into lipid. When [1-14C]glucose was used vanadate again had a significantly greater effect on 14CO2 production than did insulin, but when [6-14C]glucose was used the effects of vanadate and insulin were equal. These results demonstrate that vanadate has insulin-like effects in isolated fat cells, but it selectively stimulates certain pathways to a greater extent than does insulin. The greater effect of vanadate than insulin appears to be primarily on the pentose phosphate shunt, suggesting that this agent may be useful for examination of this intracellular pathway in fat cells.  相似文献   
997.
BACKGROUND: A paced rhythm can mask the electrocardiographic features of an acute myocardial infarction, complicating timely recognition and treatment. OBJECTIVE: To evaluate characteristics, treatment, and outcomes among patients presenting with paced rhythms during myocardial infarction. DESIGN: Retrospective cohort study. SETTING: U.S. acute care hospitals. PATIENTS: 102 249 Medicare beneficiaries at least 65 years of age who were treated for acute myocardial infarction between 1994 and 1996. MEASUREMENTS: Provision of three treatments for acute myocardial infarction (emergent reperfusion, aspirin, and beta-blockers), death at 30 days, and long-term follow-up. RESULTS: 1954 patients (1.9%) presented with paced rhythms during myocardial infarction. These patients were older; were predominantly male; and had higher rates of congestive heart failure, diabetes, and previous infarction. They were significantly less likely to receive emergent reperfusion (relative risk [RR], 0.27 [95% CI, 0.22 to 0.33]), aspirin (RR at admission, 0.91 [CI, 0.88 to 0.94]; RR at discharge, 0.87 [CI, 0.83 to 0.92]), and beta-blockers at admission (RR, 0.89 [CI, 0.82 to 0.96]). In addition, there was a trend toward decreased use of beta-blockers at discharge (RR, 0.91 [CI, 0.76 to 1.06]). Crude mortality rates were higher among patients with paced rhythms than among those without at 30 days (25.8% vs. 21.3%; P = 0.001) and at 1 year (47.1% vs. 36.1%; P = 0.001). Among patients with paced rhythms, risk for death at 30 days decreased after adjustment for illness severity and decreased use of therapy (RR, 1.03 [CI, 0.93 to 1.14]). Patients with paced rhythms remained at additional risk for long-term mortality (hazard ratio, 1.12 [CI, 1.06 to 1.18]). CONCLUSIONS: Patients with paced rhythms were less likely than those without to receive treatment for acute myocardial infarction and had poorer short- and long-term outcomes. However, this mortality risk diminished after adjustment for treatment. This suggests that improved recognition and treatment of myocardial infarction may improve outcomes, particularly in the short term.  相似文献   
998.
AIMS: To evaluate the effect of the angiotensin receptor blocker candesartan on New York Heart Association (NYHA) functional class in a broad spectrum of patients with chronic heart failure (CHF). METHODS AND RESULTS: Patients in the CHARM Programme with symptomatic CHF were randomized to placebo (n=3796) or candesartan (n=3803) and followed for a median of 38 months. NYHA class was assessed at baseline, at two weekly intervals during dose titration and 4 monthly thereafter. Patients were classified as "better", "unchanged" or "worse" at the end of the study compared to baseline. Both a simple "last visit carried forward" (LVCF) analysis and "worst rank carried forward" (WRCF) analysis (where patients who died were allocated NYHA class V) were used. In the LVCF analysis, compared to placebo, more candesartan patients improved (35.4% versus 32.5%) and fewer worsened (9.0% versus 10.3%) in NYHA class (p=0.003). The WRCF analysis also showed a better overall change in NYHA class with candesartan compared to placebo. There was no heterogeneity in the response to candesartan between the CHARM component trials. CONCLUSIONS: Candesartan improves NYHA functional class to a similar extent to other proven treatments for CHF when added to these other treatments.  相似文献   
999.
AIMS: Age is one of the most powerful determinants of prognosis in myocardial infarction, but there is comparatively little recent data across the whole spectrum of acute coronary syndromes (ACS). We examined the impact of increasing age on clinical presentation and hospital outcome in a large sample of patients with ACS. METHODS AND RESULTS: Patients (n = 10 253) from the Euroheart ACS survey in 103 hospitals in 25 countries were investigated. There was a significant inverse association between the age and the likelihood of presenting with ST-elevation. For each decade of life, the odds of presenting with ST-elevation decreased by 0.82 [95% confidence interval (CI) 0.79-0.84]; P < 0.0001. Elderly patients were considerably less often treated by cardiologists, less extensively investigated, and, when presenting with ST-elevation ACS, less likely to be treated with reperfusion. Compared with patients <55 years, the odds ratios of hospital mortality were 1.87 (1.21-2.88) at age 55-64, 3.70 (2.51-5.44) at age 65-74, 6.23 (4.25-9.14) at age 75-84, and 14.5 (9.47-22.1) among patients > or =85 years, with no major differences across different types of admission or discharge diagnoses. CONCLUSION: Elderly ACS patients were less likely to present with ST-elevation but had substantial in-hospital mortality, yet they were markedly less intensively treated and investigated.  相似文献   
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We combined field and laboratory experimentation to evaluate the effects of nitrogen dioxide in a panel of Los Angeles area residents with chronic respiratory illness, 15 men and 11 women aged 47 to 69. All had heavy smoking history, chronic symptoms, and low FEV1; some also had low FVC. During the fall-winter high-NO2 season, they monitored themselves for 2-wk periods using spirometers in the home, passive NO2 sampling badges, and diaries to record time and activity patterns and clinical status. In the middle of each self-monitoring week they were exposed in a chamber, once to clean air and once to 0.3 ppm NO2. Chamber exposures were double blind, lasted 4 h, and included four 7-min exercise sessions with average ventilation rates near 25 L/min. Symptom reports and hourly forced expiratory function tests showed no statistically significant differences between clean air and NO2 chamber exposures, although peak flow showed a approximately 3% loss with NO2 relative to clean air during the first 2 h of exposure only (p = 0.056). No significant overall differences were found between field self-measurements and measurements of lung function in the chamber or between field measurements in clean air and NO2 exposure weeks. Field data showed that group average lung function and symptom levels were worse in the morning than later in the day (p < 0.005) but otherwise were stable over 2 wk. Even though most subjects smoked and stayed indoors 80 to 90% of the time, personal NO2 exposures correlated significantly with outdoor NO2 concentrations as reported by local monitoring stations.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
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