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BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.  相似文献   
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PURPOSE: Digoxin is the third most commonly prescribed drug, yet limited information exists about its use in outpatients. Therefore, 242 medical outpatients receiving digoxin at our hospital were studied to evaluate the appropriateness of its use, defined by: (1) current or past supraventricular arrhythmias and/or (2) left ventricular systolic dysfunction (ejection fraction less than 45 percent). PATIENTS AND METHODS: Charts of 242 patients receiving digoxin were obtained. The patients were divided into groups based upon their physician's stated indication for digoxin therapy. Patients with only a clinical diagnosis of congestive heart failure (CHF) underwent echocardiography or radionuclide angiography to quantify left ventricular systolic function. Those with documented supraventricular arrhythmias and/or those with confirmed left ventricular systolic dysfunction were classified as appropriate candidates for digoxin. RESULTS: Ninety-five percent of patients received digoxin for appropriate indications; 75 percent had confirmed supraventricular arrhythmias (27 percent also had CHF) and 20 percent with normal sinus rhythm had documented systolic dysfunction. However, physicians had difficulty in the clinical assessment of left ventricular function; 18 percent of patients with sinus rhythm and CHF by the Framingham scoring system and 20 percent of those with supraventricular arrhythmias and CHF had preserved systolic function. An S3 was present in 15 percent of patients with preserved ejection fraction and CHF and in 69 percent with low ejection fraction; hypertension was significantly more common in the former group. Noninvasive assessment of systolic function was obtained in 97 percent of patients independent of this study, yet some patients without supraventricular arrhythmias and with documented preservation of systolic function continued to receive the drug. CONCLUSION: Noninvasive assessment of left ventricular function, which appears to have become routine, is of value in the appropriate utilization of digoxin, since clinicians' assessment of left ventricular function may be inaccurate. Physicians also do not always discontinue digoxin therapy when indicated.  相似文献   
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A randomized controlled trial of sedation in the critically ill   总被引:2,自引:0,他引:2  
A randomized controlled trial comparing: a) a combination of oral chloral hydrate and promethazine to b) a continuous intravenous midazolam infusion, for maintenance sedation in critically ill children, was carried out. The level of sedation was assessed four hourly using a specifically devized sedation scale. Forty-four children entered the study of whom two were subsequently excluded. The number of satisfactory assessments (desired and actual levels of sedation equal) was significantly greater in the chloral hydrate and promethazine group (Chi-squared P <0.01; confidence intervals of the difference 0.06 to 0.20). The number of assessments at level 5 on the sedation scale (patient restless/distressed) was significantly greater in the midazolam group (Chi-squared P <0.05). The total number of satisfactory assessments in the two groups were only 61 and 48% respectively, suggesting that sedation can be considerably improved. Chloral hydrate and promethazine are more effective than midazolam as maintenance sedation in critically ill children. It is possible to prospectively study the efficacy of sedative drugs in critically ill children.  相似文献   
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The effects of several opioid agonists and antagonists were examined in pigeons performing under a delayed matching-to-sample procedure. The mu agonists morphine and l-methadone, the kappa agonists U 50,488 and ethylketocyclazocine, and the opioid antagonist naloxone had no effect on the accuracy of responding. These drugs were, however, behaviorally active as evidenced by the dose-dependent decreases in rates of responding associated with their administration. In contrast, the sigma agonists (+) N-allylnormetazocine and phencyclidine decreased the accuracy of responding in a dose-dependent fashion. The relative magnitude of these drug-induced decreases in accuracy were similar across the no delay (0-s), short (2-s), and long (8-s) delay intervals. For these drugs, accuracy-decreasing effects were obtained only at doses that reduced rates of responding. The results of the present investigation parallel those reported in pigeons responding under drug discrimination tasks, in which the discriminative stimulus properties produced by the mu and kappa agonists are similar to each other but distinguishable from those produced by the sigma agonists.Recipient of Research Scientist Development Award DA 00033 from the National Institute on Drug Abuse  相似文献   
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