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Process versus outcome in hypertension: a positive result.
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We studied the association between the outcome of antihypertensive care and three items of that care among 230 hypertensive steelworkers who were referred to 83 physicians. The first item was the decision to treat some patients but not others: 63% of the patients were prescribed antihypertensive drugs and the mean decrease in their diastolic blood pressure (DBP) was greater than that among untreated patients (12.2 +/- 0.84 vs 7.8 +/- 0.83 mm Hg [+/- SEM], p less than 0.001). The second item was the vigor of prescribed medication: Patients prescribed more vigorous treatments had lower DBP (p less than 0.005). Third, patient compliance was related to achieving a goal DBP of less than 90 mm Hg (p less than 0.05) and the product of prescribed vigor and compliance was highly associated with DBP response (p less than 0.0001). These results stand in contrast to those of previous studies that failed to detect associations between various other items of the care process and the outcome of antihypertensive care.
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10,000,302
The Canterbury Tales and cardiology.
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10,000,303
The effects of nifedipine on myocardial blood flow and contraction during ischemia in the dog.
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10,000,304
Nifedipine has been proposed as an agent to preserve viability and function of ischemic myocardium. We studied 23 open-chest dogs that underwent carotid-to-left anterior coronary artery perfusion with flow probe and perfusion pressure monitoring. Segment length was measured with ultrasonic crystals in the ischemic and nonischemic endocardium. Myocardial blood flow was measured with radioactive microspheres. Partial coronary occlusion was performed to 25 mm Hg diastolic perfusion pressure. Ten dogs received intracoronary nifedipine, 10 micrograms, and 13 dogs received i.v. nifedipine, 3 micrograms/kg/min. Nifedipine resulted in an increase in segmental shortening in both groups, but nonischemic zone shortening did not change in either group. Nifedipine did not affect myocardial blood flow in the ischemic zone, but increased flow in the nonischemic zone in the group that received i.v. nifedipine. Thus, nifedipine appears to have a direct beneficial effect on ischemic myocardium.
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10,000,305
Determinants of myocardial hemorrhage after coronary reperfusion in the anesthetized dog.
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10,000,306
Intramyocardial hemorrhage often occurs with reperfusion in experimental acute myocardial infarction and is thought to be associated with extension of necrosis. To determine if hemorrhage was associated with extension of necrosis, 20 anesthetized dogs were reperfused after 6 hours of circumflex coronary artery occlusion and 10 others had control occlusion with no reperfusion. Fifteen of the 20 reperfused dogs had gross hemorrhage and none of the control dogs did. In 12 reperfused and 10 control dogs, radioactive microspheres were injected after coronary occlusion to quantitate collateral flow and in the reperfusion group microspheres were injected to quantitative reflow. Complete flow data were available in eight reperfused and 10 control dogs. Twenty-four hours after coronary occlusion, 1-g segments of infarct and control regions were analyzed for hemorrhage, collateral flow and creatine kinase activity. Serial microscopic examination was performed in eight additional dogs reperfused after 6 hours to determine if hemorrhage occurs into otherwise microscopically normal myocardium. Pathologic examination indicated that hemorrhage did not occur into otherwise microscopically normal myocardium. In dogs with hemorrhage, the extent of hemorrhage was inversely related to myocardial creatine kinase concentration and collateral flow. Mean collateral flow in 47 hemorrhagic segments was 4.5 ml/100 g (4.2% of control). Mean creatine kinase in 36 hemorrhagic segments was 233 mIU/g (21% of control). No hemorrhage was found in areas with collateral flow more than 21% of control or creatine kinase more than 37% of control. Mean reflow in hemorrhagic segments was 78.5% of control flow. These studies indicate that hemorrhage on reperfusion is associated with severe myocardial necrosis and markedly depressed flow before reperfusion and thus occurs only into myocardium already markedly compromised at the time of reperfusion. There is no evidence for hemorrhage into areas that had normal or even moderately depressed flows before reperfusion.
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10,000,307
Thallium-201 kinetics in nonischemic canine myocardium.
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10,000,308
Effect of propranolol on myocardial perfusion images and exercise ejection fraction in men with coronary artery disease.
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10,000,309
Effect of the geometry of the left ventricle on the calculation of ejection fraction.
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10,000,310
We used a cylindrical model for the left ventricle contracting both radially and longitudinally to show how the ejection fraction is related to different variables that describe the ventricular geometry. The relations during ventricular contraction between wall thickening, midwall radius shortening and longitudinal shortening are used to derive precise formulas for the calculation of ventricular blood flow velocity and ejection fraction. Validation of the model is given by results from the literature and by a study of 40 patients. The formulas derived can be used to validate angiographic measurements or to assess more precisely blood flow velocity and ejection fraction from the M-mode echocardiogram. Ejection fraction is determined not only by the extent of myocardial shortening, but also by the relationship of ventricular wall thickness to ventricular cavity size.
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10,000,311
Noninvasive determination of left ventricular end-systolic stress: validation of the method and initial application.
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10,000,312
Calcium-entry blockers in coronary artery disease: introduction.
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10,000,313
Effect of diltiazem on myocardial blood flow.
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10,000,314
We examined the effects of diltiazem on transmural myocardial blood in the presence of a flow-limiting stenosis and during acute total coronary artery occlusion in awake, chronically instrumented dogs. Regional myocardial perfusion was estimated with left atrial injections of 15-mu-diameter radionuclide labeled microspheres. An electromagnetic flowmeter probe and hydraulic occluder were used to monitor blood flow and produce total and subtotal occlusions of the left circumflex coronary artery. A 10-second total arterial occlusion produced intense coronary vasodilation and a pronounced reactive hyperemic response. When a proximal coronary stenosis prevented reactive hyperemia, ischemic coronary vasodilation after a 10-second arterial occlusion caused transmural redistribution of blood flow toward the subepicardium. resulting in subendocardial underperfusion despite a normal net volume of arterial flow. Although diltiazem did not increase coronary collateral flow during acute arterial occlusion, it did blunt the vasodilation that occurred in response to a 10-second total coronary occlusion, and partially corrected the subendocardial underperfusion that occurred with a proximal flow-limiting coronary stenosis.
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10,000,315
Beneficial effects of nifedipine on regional myocardial blood flow in patients with coronary artery disease.
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Nifedipine inhibits the slow-channel calcium current, which plays a major role in vascular smooth-muscle contraction. However, the effect of nifedipine on regional myocardial blood flow (RMBF) in patients with coronary artery disease (CAD) is unknown. In 18 patients with chest pain syndromes, RMBF was determined with xenon-133 before and after nifedipine. In patients with CAD. 25 regions were analyzed distal to significant coronary obstruction(greater than 70% reduction in luminal diameter) and eight regions were analyzed in patients with normal coronary arteries. In patients with CAD, RMBF increased in 21 of 25 regions (average 17.4 /+- 5.7%,p less than 0.01), but decreased in all eight regions in patients with normal coronary arteries, by an average of 14.4 /+- 2.3% (p less than 0.01). The difference between groups was significant (p less than 0.01). In our patients with CAD, improved RMBF appears to be related to a decrease in coronary vascular tone and suggests a physiologic basis for the beneficial effect of nifedipine in ischemic heart disease.
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10,000,317
On the significance of host factors that affect drug disposition.
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10,000,318
Reports on drug disposition in man often overemphasize statistical analyses or correlation coefficients at the expense of clear statements on the biological meaning of an experiment. Moreover, the results of many such studies are presented as though they were immutable. In reality, the levels of statistical significance often depend on, and are intimately related to, numerous host factors. Results can fall anywhere within a broad spectrum of values determined by the host factors of the subjects selected for investigation. The investigator's objectives determine whether subjects are selected for uniformity or heterogeneity of these host factors. Since only a small number of subjects can be studied, it is unlikely that all critical host factors will be represented. Therefore, studies repeated elsewhere may not duplicate subject host factors with sufficient precision to allow a similar outcome. Thus, a full description of critical host factors is required for all subjects who serve in studies on drug disposition. This requirement is particularly important because many subjects suffering from diseases exhibit simultaneous changes in critical host factors, thereby modifying the dosage requirements for drug therapy. The number of host factors recognized as capable of influencing drug disposition has risen due to recent discoveries in this active field.
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10,000,319
Heparin kinetics determined by three assay methods.
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10,000,320
Heparin kinetics were determined in four normal subjects, each of whom received three different doses (25, 50, and 75 units/kg body weight) by intravenous injection. Multiple blood samples were collected after each dose and each plasma sample was assayed for heparin activity using three different assay methods. Two of these assays are based on coagulation tests, i.e., activated partial thromboplastin time and thrombin time, while the third is based on chemical neutralization of heparin using hexadimethrine bromide. Heparin kinetics showed pronounced dose-dependent changes, irrespective of the assay method used, which were characterized by increasing biologic half-life and decreasing total clearance (Cl) with increasing dose. No changes were noted in apparent volume of distribution (Vd). This data also showed that there were differences in kinetic parameters of heparin depending on the assay method. In general, values for total Cl and apparent Vd based on chemical neutralization were approximately 1.5 to 2.0 times these parameters based on coagulation tests. We conclude that the immediate mechanism of the dose-dependent heparin kinetics is decreasing total clearance with increasing dose and suggest that in vivo activation of the anticoagulant properties of heparin may explain the assay-dependent kinetics.
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10,000,321
Estimation of sympathetic activity in essential hypertension.
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10,000,322
The estimation of sympathetic nervous activity by measurement of plasma norepinephrine (NE) concentration assumes a constant relation between this and the synaptic cleft concentration. This assumption would be incorrect if the clearance of plasma NE could be varied without affecting its removal from the synaptic cleft, so we compared the clearance of plasma NE in mild hypertensives and normal subjects by measurement of its plasma concentration during a 0.5-hr infusion at 0.07 microgram/kg/min; there were no differences. The simultaneous infusion of isoproterenol, 0.02 microgram/kg/min, led to an increase in heart rate and NE clearance. There was partial inhibition of catechol-O-methyltransferase by a single oral dose of alpha-methyldopa, 250 mg, which reduced the clearance of both catecholamines (CAs) by about 20%. After the end of the infusions containing isoproterenol, the tachycardia persisted for more than 1 hr and declined more slowly in the hypertensives than the normals. In contrast, plasma concentrations of both CAs returned to basal values within a few minutes. The persistent tachycardia may be due to rerelease of isoproterenol into the synaptic cleft, since stimulation of sympathetic activity by assumption of the erect posture was associated with an exaggerated increase in heart rate (by 48/min after infusion and 23/min before infusion). The study therefore suggests that synaptic cleft and plasma CA concentrations can be independently manipulated and the relation between them may be different in hypertensive patients and normal control subjects.
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10,000,323
Sparteine metabolism in Canadian Caucasians.
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10,000,324
The capacity for sparteine (SP) metabolism was determined in 48 Caucasian subjects by measuring amounts of drug and dehydrogenated metabolites in urine after an oral dose of SP sulfate. Three phenotypes were recognized and were assumed to represent individuals homozygous for poor SP oxidation (group III) and those heterozygous (group II) and homozygous (group I) for extensive SP oxidation. Separation of groups I and II, although incomplete, was improved by alterations in the published analytic procedure. The pattern of deviations from the normal distribution was similar for both dehydrosparteine metabolites. This supports the hypothesis of a common intermediate, the formation of which is monogenically controlled. Correlation analysis of the two metabolites indicates the possibility of further metabolism of 5-dehydrosparteine.
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10,000,325
Sex differences in absorption kinetics of sodium salicylate.
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10,000,326
Sodium salicylate in aqueous solution (9 mg/kg) was given by oral and intravenous routes to normal male and female subjects. Because the bioavailability of salicylate was complete, salicylate was given orally in all subsequent experiments. There were sex differences in time required to attain peak salicylate concentration (tmax), but not in maximum plasma salicylate concentration (Cmax). There were no sex differences in apparent volume of distribution, plasma salicylate clearance, or area under the concentration-time curve. In female subjects, tmax tended to reach a nadir at the middle of the menstrual cycle, when gastric emptying time is shortest, whereas Cmax remained relatively unchanged throughout the menstrual cycle. Equilibrium dialysis studies on the binding of sodium salicylate and of 14C-racemic warfarin to plasma from 25 normal male and 25 normal female subjects of similar age disclosed no sex differences either in the extent of binding of these drugs or in serum albumin concentration. The possibility of sex differences in rates of gastrointestinal absorption of other drug should be investigated.
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10,000,327
Antipyrine disposition in milk and saliva of lactating women.
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10,000,328
Widely used to study hepatic drug metabolism, antipyrine rapidly distributes in total body water. Antipyrine distribution was studied in seven lactating women. Duration of lactation ranged from 2 to 19 mo. In all subjects the drug was rapidly absorbed; in five women peak concentrations were attained in milk and saliva by 1 hr and in the other two women by 3 hr (first point at which collections were made). In two women in whom antipyrine was measured at 10-min intervals during the first hour, peak concentrations in both milk and saliva were attained by 10 min after antipyrine. The time course for antipyrine disappearance from milk paralleled that from saliva for each subject. Antipyrine half-life (t1/2) varied from 5.6 to 20.3 hr for saliva (mean +/- SD = 11.5 +/- 4.8) and from 5.7 to 21.7 hr for milk (mean +/- SD = 11.6 +/- 5.4). In the two women with the shortest salivary antipyrine t1/2 (5.6 and 7.5 hr), antipyrine was readministered many months later, after they had stopped lactating. The salivary antipyrine t1/2 rose from 5.6 to 13.3 hr in one subject and from 7.5 to 14.6 hr in the other. The corresponding decrease in antipyrine clearance was 0.93 to 0.55 and 1.41 to 0.60 ml/min/kg. This observation suggests that in some subjects lactation may influence drug metabolism. The amount of antipyrine available to each nursing infant was estimated by assuming the the infant nursed 3 ounces every 4 hr for 24 hr after maternal antipyrine administration. The amount of antipyrine available to the nursing infant was calculated to range from 3.0 to 11.1 mg (mean +/- SD = 6.4 +/- 2.9 mg) or from 0.25% to 1.07% (mean +/- SD = 0.59 +/- 0.29%) of the maternal dose.
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-0.09556049853563309, -0.05292382091283798, 0.006549028214067221, 0.01161782443523407, 0.0873267725110054, -0.016648951917886734, 0.022405097261071205, 0.025620948523283005, 0.07986614108085632, -0.0352325513958931, 0.0037392661906778812, 0.03902850300073624, -0.05748368799686432, 0.0075774118304252625, 0.08885373175144196, 0.04871733859181404, -0.042211636900901794, -0.049601245671510696, -0.017938289791345596, -0.05235258862376213, 0.06990325450897217, 0.03866328299045563, 0.060995373874902725, -0.022558338940143585 ]
10,000,329
Age and renal clearance of cimetidine.
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10,000,330
In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high-pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6-hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4.8 +/- 2.0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1.9 microgram/ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1.25 microgram/ml. Thus, high cimetidine levels alone do not always induce dementia.
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10,000,331
Altered hydroxydesipramine concentrations in elderly depressed patients.
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10,000,332
Recent reports demonstrate that hydroxy metabolites of desipramine (DMI) have pharmacologic activity and do not just produce side effects. In patients treated with DMI, we determined the ratio of 2-hydroxydesipramine (2-OH-DMI) to drug at steady state. The ratios in the elderly patients were higher than in younger patients, and whereas plasma levels of 2-OH-DMI increased with age, urinary clearances decreased. The known decrease in glomerular filtration with age may explain the selective increase of 2-OH-DMI concentration in the elderly.
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10,000,333
Amiloride in primary hyperaldosteronism.
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10,000,334
Amiloride is a potassium-sparing diuretic used in spontaneous and diuretic-induced hypokalemia. The effect of amiloride was studied prospectively in 12 patients with primary hyperaldosteronism. Four patients had unilateral adrenal adenomas and eight had bilateral adrenal hyperplasia. All patients were hypertensive and their mean plasma potassium levels were low. Amiloride, 10 to 40 mg daily, was given for 6 mo. Mean plasma potassium levels rose (0.96 mEq/l, P less than 0.001) and remained normal throughout the study without potassium supplementation. Mean blood pressure was lowered by amiloride (22/10 mm Hg, P less than 0.001) but normotension required concomitant antihypertensive therapy in most patients. No significant adverse clinical or laboratory experiences could be directly attributed to amiloride therapy. There was no correlation between the response to therapy and the plasma aldosterone levels, aldosterone secretion rate, or presence of a unilateral adrenal adenoma. Our study demonstrates the efficacy of amiloride in the correction of hypokalemia and amelioration of hypertension in primary hyperaldosteronism.
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10,000,335
Alpha1-acid glycoprotein concentration and protein binding in trauma.
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10,000,336
Alpha 1-Acid glycoprotein (AAG) concentrations were measured every 2 to 3 days in eight trauma patients and seven healthy subjects for approximately 3 wk. Mean AAG concentrations in the trauma patients rose from 100 mg/dl to a peak value of 243 mg/dl at 10 to 14 days. AAG levels averaged more than 200 mg/dl at 15 to 21 days. Mean AAG concentration in healthy subjects was 70 mg/dl with little inter- or intraindividual variability. Lidocaine was added to all serum samples from four of the patients and to selected samples from all of the healthy subjects and protein binding was determined. The binding ratio (bound concentration/free concentration) correlated strongly with AAG concentration in the trauma patients (r = 0.92), in the healthy subjects (r = 0.84), and in both groups combined (r = 0.96). AAG concentration and binding ratio for each of the four patients individually also correlated (P less than 0.05 in all cases). The change in free fraction associated with this increase in AAG was approximately doubled in each patient. Similar findings with drugs commonly used in trauma patients would be expected to alter serum concentration-response relationships significantly.
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10,000,337
Coffee and caffeine and alcohol effects on psychomotor function.
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10,000,338
Interactions of alcohol and caffeine were studied in two double-blind and crossover trials in which several psychophysiologic functions and subjective effects were measured in healthy men. The effects of alcohol (1 gm/kg) with and without caffeine (200 or 500 mg) were measured in 10 subjects. Two doses (0.7 or 1.5 gm/kg) of alcohol alone and in combination with caffeine (250 + 250 mg) were similarly studied in another 10 subjects. Alcohol impaired psychomotor functions to an extent dependent on dose whereas caffeinated and decaffeinated coffee did not. Both kinds of coffee also failed to modify alcohol effects. Subjectively, caffeine was indistinguishable from placebo and no particular interaction of alcohol and caffeine was detected. Alcohol did elevate serum caffeine concentrations. We conclude that coffee does not counteract alcohol inebriation.
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-0.028248772025108337, 0.0021145471837371588, 0.03089217282831669, 0.022449404001235962, 0.012547556310892105, -0.047848183661699295, -0.011027920991182327, -0.004672541748732328, 0.05537949129939079, 0.1337014138698578, 0.059531066566705704, 0.051399484276771545, -0.008661044761538506, 0.05227835476398468, -0.012691421434283257, 0.04667714983224869, -0.05399809032678604, -0.1954762041568756, 0.11861385405063629, 0.005940904375165701, 0.028326133266091347, -0.09335844218730927 ]
10,000,339
Plasma protein binding of phencyclidine.
[ 0.014834149740636349, -0.08816844969987869, -0.12138514220714569, 0.02734476886689663, 0.0021356723736971617, 0.04312189295887947, 0.04070085659623146, 0.08034910261631012, 0.08932133764028549, 0.003140747547149658, 0.0665925070643425, -0.006122755818068981, 0.012125994078814983, 0.13751962780952454, -0.004638907499611378, 0.025656985118985176, -0.031148772686719894, 0.06779615581035614, -0.016802681609988213, -0.0013432421255856752, -0.04742850363254547, 0.044239241629838943, -0.024789821356534958, -0.0077062733471393585, -0.007396309170871973, 0.050865959376096725, 0.022829720750451088, -0.011530452407896519, -0.017740605399012566, -0.04548925533890724, 0.049711208790540695, 0.015720073133707047, -0.009946721605956554, 0.04647502675652504, 0.008921160362660885, 0.01708551123738289, -0.06902167201042175, -0.02385137975215912, 0.02280198410153389, 0.026692736893892288, 0.06375628709793091, -0.041123393923044205, 0.015984660014510155, -0.03301409259438515, 0.01844818703830242, 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-0.03811187669634819, 0.049658168107271194, 0.10017834603786469, 0.032144494354724884, -0.05632881075143814, 0.0030407211743295193, -0.02677982673048973, -0.10280945152044296, -0.019970547407865524, 0.0934109166264534, -0.03577142953872681, -0.039541974663734436, -0.01312944758683443, -0.0061925435438752174, 0.04906390234827995, -0.04268103092908859, 0.048478882759809494, 0.05164080858230591, 0.04103690758347511, -0.034299369901418686, -0.06426451355218887, 0.027288341894745827, 0.04812340810894966, 0.08052773773670197, 0.02595510333776474, 0.02611914835870266, -0.0664081871509552, -0.033461056649684906, 0.0679023414850235, -0.047801095992326736, 0.11586663126945496, -0.10840145498514175, -0.0760224387049675, 0.013469900004565716, 0.015648970380425453, -0.03911443427205086, -0.09094035625457764, -0.03704647719860077, -0.07362738251686096, -0.04367823526263237, -0.030767610296607018, -0.026033291593194008, -0.03377028554677963, 0.13124680519104004, 0.10549332946538925, 0.10920307785272598, -0.017376890406012535, 0.029796216636896133, -0.06224740296602249, 0.0036390828900039196, 0.0762953832745552, 0.05152435973286629, 0.05447188392281532, -0.019452564418315887, 0.07412217557430267, 0.025970328599214554, 0.03404204547405243, 0.07513353228569031, -0.020787697285413742, -0.05249176546931267, -0.06313367187976837, -0.000042708688852144405, 0.03656824305653572, -0.013221938163042068, -0.041822124272584915, 0.04716663435101509, 0.1238141655921936, 0.07683641463518143, -0.10793472081422806, 0.044540632516145706, -0.06197815760970116, 0.16129489243030548, 0.06893685460090637, -0.038797274231910706, -0.008269655518233776, -0.03548452630639076, -0.01590336486697197, -0.009335971437394619, 0.10688421130180359, -0.03872492164373398, -0.047175634652376175, -0.044346630573272705, -0.07618224620819092, 0.0325407050549984, 0.023572269827127457, 0.06872208416461945, -0.04115840792655945, -0.07105648517608643, 0.015375196002423763, -0.005225737579166889, 0.024417441338300705, -0.02636655978858471, 0.01037204172462225, 0.018520405516028404, -1.8350911901166e-8, 0.08166522532701492, -0.09284371882677078, 0.03604176267981529, -0.07470732182264328, 0.03558701276779175, 0.024196214973926544, -0.02351175807416439, 0.004792214836925268, -0.12046729773283005, 0.011703964322805405, 0.008225885219871998, -0.00869823433458805, -0.020936353132128716, 0.03006596490740776, 0.04243440553545952, 0.09190758317708969, -0.052758656442165375, -0.08616931736469269, -0.039324454963207245, -0.012486162595450878, -0.04739528149366379, -0.02595522068440914, -0.05707082897424698, -0.012928790412843227, 0.010295643471181393, -0.04545809328556061, 0.021505573764443398, -0.04110568016767502, -0.022778280079364777, -0.08562856912612915, 0.05437089502811432, -0.05534491315484047, -0.01008633803576231, -0.04353424534201622, 0.004694193601608276, 0.0069980924017727375, 0.023046530783176422, -0.05414271727204323, -0.0020492421463131905, 0.05402200669050217, -0.06918847560882568, -0.008472553454339504, -0.02022506296634674, -0.010844893753528595, 0.04376860707998276, 0.03698008880019188, 0.011556760407984257, 0.015515968203544617, -0.048208195716142654, -0.05731838941574097, -0.062382593750953674, -0.02575741894543171, -0.009273279458284378, -0.07800757884979248, -0.026461172848939896, 0.00539294583722949, -0.010024981573224068, -0.0362691804766655, 0.018410224467515945, -0.04655950888991356, -0.12697716057300568, 0.05059634521603584, 0.06577035784721375, -0.030108800157904625 ]
10,000,340
In healthy male subjects (n = 12) phencyclidine (PCP) free fraction was 22.0 +/- 2.8 % (mean +/- SD). In male patients with mild to moderate alcoholic liver disease (n = 16) free fraction (23.0 +/- 3.4%) was of the same order as in healthy subjects although age and the concentrations of albumin, bilirubin, and high-density lipoproteins were different (P less than 0.05). Free fraction (76.2 /+- 0.06%) in fatty acid free human serum albumin (HSA, 4.4 gm/dl) was far greater than in plasma. Both the increased binding of PCP in plasma over HSA and the lack of a difference in PCP binding between normals and patients was associated with alpha 1-acid glycoprotein (alpha 1-AGP). This protein is an acute-phase reactant that binds cationic drugs and rises nonspecifically in a variety of diseases. Free fraction of PCP in alpha 1-AGP (75 mg/dl) was 36.4 +/- 1.7%. Half of the variance in PCP binding can be accounted for (r = 0.67, P less than 0.01) from percentage of free PCP = 39.24 - 2.18 (albumin) - 0.094 (alpha 1-AGP). Male rats (n = 14, weight = 251 +/- 7 gm) were alternatively assigned to pretreatment with either saline or alpha 1-AGP (11.6 mg) by cardiac puncture. PCP brain concentrations were reduced (11%, P less than 0.05) in the protein-treated group 5 min after cardiac 3H-PCP (0.17 mg) administration, demonstrating that increased plasma protein binding can reduce free drug concentration during the distribution phase and, thereby, the rate and extent of drug distribution.
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10,000,341
Metoprolol withdrawal phenomena: mechanism and prevention.
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10,000,342
Eight patients taking metoprolol (300 mg/day) for essential hypertension were studied after abrupt withdrawal and placebo replacement of the drug. A 52% average rebound increase in cardiac chronotropic sensitivity to isoproterenol and 15% rebound rise in resting heart rate occurred in all patients between 2 to 8 days after metoprolol withdrawal (P less than 0.05). Holter monitoring showed no associated arrhythmia. A transient increase in blood pressure occurred in one patient and withdrawal-like symptoms were noted in three patients. There were no meaningful changes in plasma norepinephrine, epinephrine, thyroxine, or triiodothyronine. Seven of the eight patients were again studied serially after the same metoprolol dosing, during a prolonged low-dose withdrawal schedule (50 mg/day for 10 days) and during placebo. Prolonged low dose before complete metoprolol withdrawal decreased but did not completely prevent the changes observed after abrupt withdrawal. The observed rebound of cardiac beta-adrenergic sensitivity may have application to the mechanism and prevention of the beta-blocker syndrome in patients with angina.
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10,000,343
Cimetidine dynamics after single intravenous doses.
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10,000,344
Cimetidine dynamics were studied in nine multiple-trauma patients. Mean elimination half-life was 2.27 hr, mean volume of the central compartment was 0.29 l/kg, mean volume at steady state averaged 0.90 l/kg, and mean total body clearance was 9.02 ml/min/kg. After intravenous cimetidine, drug concentrated in gastric fluid reached a peak concentration in 3 hr. Gastric plasma cimetidine ratios after equilibration ranged between 3.0 and 4.3. There was a correlation between cimetidine gastric juice concentration and gastric pH (r = 0.50), but no correlation was found between plasma cimetidine concentration and pH (r = 0.13).
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10,000,345
Intravenous pirbuterol.
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10,000,346
Pirbuterol was given intravenously to nine normal men to determine the hemodynamic effects of intravenous injection of this rather selective beta 2-adrenoceptor agonist. Pirbuterol induced marked improvement of the echocardiographic (percent change in the dimension of the minor axis of the left ventricle during systole, ejection fraction, and velocity of left ventricular circumferential fiber shortening) and systolic time interval (preejection period interval, preejection period/left ventricular ejection time) indices of ventricular performance. The increase in stroke volume was indicated by elevation of systolic blood pressure and widening of pulse pressure. Vascular beta 2-receptor agonist effects were indicated by the fall in diastolic and mean systemic blood pressure and marked reduction in derived systemic vascular resistance. Dose-related positive chronotropic properties were observed without dysrhythmias. There was a good direct correlation between mean plasma pirbuterol concentration and dose. Because of the reported efficacy of oral doses, the direct relationship between plasma concentration and dosage, the positive inotropic properties, and the peripheral vasodilating effects of pirbuterol, investigation of the intravenous form of the drug in patients with severe decompensated low-output congestive heart failure seems warranted.
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10,000,347
Cefsulodin kinetics in healthy subjects after intramuscular and intravenous injection.
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10,000,348
We evaluated cefsulodin kinetics in normal subjects after 250-, 500-, and 1,000-mg, intramuscular injections and 500-, 1,000-, and 2,000-mg 30-min intravenous infusions. Twelve plasma and four urine samples were collected in the first 12 and 24 hr. Plasma samples were analyzed by a new, highly precise high-performance liquid chromatographic procedure developed in our laboratory and urine samples were analyzed microbiologically, using Pseudomonas aeruginosa as the test organism. Mean calculated peak plasma levels from the 250-, 500-, and 1,000-mg intramuscular doses were 5.46, 11.81, and 19.40 microgram/ml. After 500-, 1,000-, and 2,000-mg intravenous infusions peak levels were 32.7, 65.7, and 190.1 microgram/ml. Data from the intramuscular doses were fitted to a one-compartment open kinetic model, yielding a mean elimination half-life (t1/2) of 1.9 hr. Data from the intravenous infusions were fitted to a two-compartment open model, with a mean beta-phase t1/2 of 1.6 hr. Mean 0- to 24-hr urinary recoveries after the three intramuscular doses were 50.0%, 54.5%, and 51.2% of total dose; after the three intravenous doses they were 60.4%, 52.4%, and 54.0%. Cefsulodin kinetics were shown to be consistent and orderly.
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10,000,349
Anesthesia and the obese patient.
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10,000,350
Definitions and risks of obesity.
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10,000,351
Nursing care for the severely obese patient.
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10,000,352
Care of the morbidly obese person (BMI greater than or equal to 30) during the perioperative period is specific and differs from routine nursing care. Effective communication, preplanning, and psychologic and physiologic assessment, with appropriate intervention (pulmonary and circulatory), result in positive care outcomes. Preoperative care emphasizes both psychologic and physiologic support concurrent with evaluation of vital signs, fluid status, teaching, and administration of preoperative medications (see Table 1). Intra- and postoperative care incorporates the necessity of additional personnel, transport precautions, physical protection, positioning, oxygenation, and early ambulation coupled with accurate arterial blood gas sampling, intraarterial line care, and cardiopulmonary and fluid status monitoring (see Tables 2 and 5). New information regarding hypothermia and shivering documented to occur in the recovery room underlines the need for accurate core temperature monitoring (see Tables 3 and 4; Figs. 1 and 2). An assessment tool (see Fig. 3)--an effective reminder of important aspects of patient care in the recovery room and until hospital discharge--provides a systematic guide to facilitate nursing care, recording, and reporting.
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10,000,353
Pulmonary and cardiovascular derangements in the obese patient.
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10,000,354
The liver in obesity.
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10,000,355
Biochemical and biotransformation alterations in obesity.
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10,000,356
Anesthetic management of the morbidly obese patient.
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10,000,357
Anesthetic management should concentrate on various aspects of pre-, intra-, and postoperative care. Particular laboratory studies, such as arterial blood gases, electrocardiogram, selected pulmonary function tests (e.g., ERV), and serum hepatic profile, can be quite useful. Preoperatively, technical difficulties (intravenous and arterial cannulae, operative positioning, and airway assessment), psychologic considerations, and response to preanesthetic medications can be anticipated. Intraoperative concerns encompass the choice of regional versus general anesthesia, anesthetic biotransformation, and variables influencing intraoperative oxygenation (e.g., effects of general anesthesia, operative position, abdominal packing). Postoperative concerns are directed toward minimizing postoperative hypoxemia, peripheral phlebothrombosis, and fluid imbalances. Special caution is needed in operations subsequent to jejunoileal bypass surgery. Specific choices of anesthetic agents and techniques await further clinical and laboratory investigations in this unique subset of the population.
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10,000,358
Surgical treatment of morbid obesity.
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10,000,359
Effects of massive weight loss.
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10,000,360
Sphincter of Oddi motor activity: a comparison between patients with common bile duct stones and controls.
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10,000,361
A case of primary sclerosing cholangitis in childhood.
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10,000,362
Spontaneous bacterial peritonitis due to Clostridium tertium.
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10,000,363
Mallory-Weiss tear complicating upper endoscopy: case reports and review of the literature.
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10,000,364
Lymphomas involving the gastrointestinal tract.
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10,000,365
Hepatic transport kinetics: can traditional models open the black box?
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10,000,366
Is epigastric tenderness a sign of peptic ulcer disease?
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10,000,367
Smoking and ulcer healing.
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10,000,368
Alcohol hepatitis therapy.
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10,000,369
Hyperamylasemia in acute alcoholism.
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10,000,370
Acid output and ulcer healing.
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10,000,371
Pepsinogens I and II: purification from gastric mucosa and radioimmunoassay in serum.
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0.04869379103183746, 0.0029355466831475496, 0.008095969446003437, 0.020654737949371338, 0.050887856632471085, -0.05782429873943329, -0.01967417076230049, 0.02790239453315735, 0.022128872573375702, 0.01563118025660515, -0.028827419504523277, 0.02507442608475685, -0.038178764283657074, -0.02247837744653225, -0.02679337002336979, -0.01938403584063053, 0.015281480737030506, -0.01761651411652565, -0.0018116342835128307, -0.06439170986413956, 0.023623667657375336, -0.03482700511813164, 0.08903674781322479, -0.08258109539747238 ]
10,000,372
Pepsinogen I and pepsinogen II were purified from gastric mucosa and used to develop a radioimmunoassay for pepsinogen II and an improved radioimmunoassay for pepsinogen I. Each immunochemically homogeneous preparation contained only its characteristic components by radioelectophoretic analysis, and migrated as a singly band in polyacrylamide gel. The mean (+/- SD) level of serum pepsinogen II in 42 healthy control subjects was 10,8 +/- 3.8 ng/ml, significantly less (p less than 0.001) than the level of pepsinogen I, which was 62.9 +/- 22.2 ng/ml. The correlation between serum pepsinogen I and pepsinogen II was highly significant (r = 0.700, p less than 0.001) in these subjects. In 20 patients with pernicious anemia the mean serum pepsinogen II level was 10.6 +/- 2.5 ng/ml, not different from normal, but significantly higher (p less than 0.001) than the level of pepsinogen I which was 5.9 +/- 4.7 ng/ml. IN 10 patients with total gastrectomy, serum pepsinogen I was 3.9 +/- 3.1 ng/ml and serum pepsinogen II was 3.2 +/- 3.1 ng/ml; both values were significantly lower (p less than 0.001) than the corresponding levels in pernicious anemia. The predominance of pepsinogen I in the serum of healthy control subjects suggests that either the gastric chief cell normally releases more pepsinogen I than pepsinogen II into the circulation or that pepsinogen I has longer metabolic clearance rate than pepsinogen II. The marked decrease in serum pepsinogen I in patients with pernicious anemia is best explained by a loss of gastric chief cells due to severe atropic gastritis of te fundic glands. The normal distribution of serum pepsinogen II levels in these patients may reflect an increased number of pyloric glands due to pyloric gland metaplasia of the proximal stomach.
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10,000,373
Estrogen predisposes to cholecystectomy but not to stones.
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10,000,374
The effect of estrogen treatment on risk for cholecystectomy, cholelithiasis, peptic ulcer, and other disorders was investigated using autopsy data from a study of patients randomized to hormonal therapy for prostatic cancer. Treatment with diethylstilbestrol, a nonsteroidal estrogen, was associated with an increased number of cholecystectomies but was unrelated to the presence of cholelithiasis at autopsy. These findings support previous reports of an association between steroidal estrogen use and cholecystectomy, but the risk estimate was more than three times that previously reported. Despite this risk and ample experimental evidence demonstrating that estrogen increases bile lithogenicity, no relationship between estrogen use and cholelithiasis was observed. The absence of such a relationship could not be readily explained by the study size, dose, or duration of estrogen treatment, treatment after leaving the study, or the frequency of preexisting stones. Given these findings the increases cholecystectomy risk may have resulted from estrogen related symptomatology mimicking gallbladder disease or an actual pathophysiologic effect of estrogen on the gallbladder, perhaps involving impaired emptying. In addition, estrogens, orchiectomy, or both were associated with a decreased frequency of peptic ulcer, supporting reports of the efficacy of estrogen in the treatment of peptic ulcer.
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10,000,375
Gastric emptying as a determinant of the oral glucose tolerance test.
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10,000,376
Intraindividual variation in the results of repeated oral glucose tolerance tests in normal subjects is well recognized but incompletely explained. The present studies show that such variation can be produced by ingestion of the glucose solution during different phases of the normal fasting activity cycle of the upper gut. Such variation is not seen when glucose is administered intraduodenally during the same phases of activity. Gastric emptying shows similar variation with the activity cycle; larger volumes of solution were emptied from the stomach during activity than quiescence, thus presenting greater quantities of glucose solution to the small intestine for absorption. Metoclopramide and hyoscine butylbromide, drugs known to influence the rate of gastric emptying, reduced the variation in the glucose tolerance test. The data suggest na possible use of the glucose tolerance test for the assessment of gastric emptying.
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10,000,377
Identification of NH2-terminal fragments of big gastrin in plasma.
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10,000,378
Molecular forms of gastrin in human plasma were studied by radioimmunoassay using antisera specific for the NH2-terminus of big gastrin (gastrin 34). A plasma enzyme system that destroys immunoreactivity of NH2-terminal fragments of gastrin 34, but not of gastrin 34 itself, has been demonstrated and shown to be inhibited by phenanthroline. Endogenous immunoreactive human plasma gastrin that had been concentrated by immunoaffinity adsorption and separated by gel filtration was shown to consist of gastrin 34, together with peptides corresponding to its NH2-terminal tryptic peptide and a shorter NH2-terminal fragment. The latter material does not occur in antral extracts and cannot be generated by in vitro incubation of plasma and antral extracts, suggesting that it is produced by passage through a capillary bed of gastrin 34 or its NH2-terminal tryptic peptide or both. The results are of significance in understanding the mechanisms of secretion and metabolism of different forms of gastrin.
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10,000,379
Converting a stomach to a uterus: the microscopic structure of the stomach of the gastric brooding frog Rheobatrachus silus.
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10,000,380
Rheobatrachus silus is a rare aquatic frog of eastern Australia. The female ingests the eggs after fertilization and broods them in the stomach until fully formed. "Gastric brooding" takes place in the fundus and proximal part of the body of the stomach, which dilates to accommodate the growing young. The surface epithelium becomes attenuated and the cells contain fewer mucus droplets. The acini of the glands are less numerous because of stretching, and they contain oxyntic cells that show evidence of profound suppression or regression. Morphometric studies on the limited number of samples show that the oxyntic cells are attenuated with few surface projections, sparse tubulovesicular reticulum, and a few pepsinogen granules and mitochondria. Eight days after ejection of the young, and 4 days after feeding commences, the lining shows a return of gastric pits and glands. The oxyntic cells show many surface projections and a proliferation of the tubulovesicular reticulum and mitochondria. These findings suggest that the eggs, tadpoles, and juvenile frogs release a substance, or substances, that inhibit acid secretion immediately after the eggs are ingested and that persist throughout brooding.
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10,000,381
Free-market system is still the best answer.
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10,000,382
Serum primary bile acids in Gilbert's syndrome.
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10,000,383
We studied some aspects of bile acid metabolism in 25 patients affected by Gilbert's syndrome, 5 patients with hemolytic anemia, and 25 control subjects in order to assess whether bile acids as well as bilirubin are affected in unconjugated hyperbilirubinemic conditions. We measured serum cholic and chenodeoxycholic acid conjugates fasting and postprandially, the plasma disappearance of intravenously injected cholyl[1-14C]glycine, 14CO2 in breath, and 14C in stools after oral administration of the same isotope. Mean serum fasting level of conjugated cholic acid was significantly reduced in hyperbilirubinemic patients (p less than 0.01) in comparison with the controls, while the postprandial elevation was similar. The cholyl[1-14C]glycine hepatic uptake was faster in the patients with Gilbert's syndrome, but no significant difference was found as far as 14CO2 in breath and 14C in stools were concerned. Additional in vitro studies showed that increasing bilirubin concentrations displace glycocholic acid and, to a lesser extent, glycochenodeoxycholic acid from their binding to albumin, the affinity constant of the latter bile acid being 30 times greater than that of the former one. This competition between bilirubin and bile acids explains the faster hepatic uptake of cholic acid conjugates and hence their lower serum levels in unconjugated hyperbilirubinemic conditions. In addition, low levels of cholic acid conjugates, together with normal serum chenodeoxycholic acid conjugate levels, discriminate Gilbert's syndrome from other causes of hyperbilirubinemia.
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10,000,384
Survey provides data on in-house planners and formalized planning.
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10,000,385
Product-oriented management helps hospital fight administrative problems.
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10,000,386
Adoptive parent program aids parents to be.
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10,000,387
Nurse-extern program eases "reality shock" for new staff nurses.
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10,000,388
Shared pharmacy arrangement benefits hospital and nearby convalescent center.
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10,000,389
Hospital trusteeship: liability and protection.
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10,000,390
No more business as usual.
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10,000,391
It's going to hurt for more than just a little while.
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10,000,392
Medical care prices rising faster than overall CPI.
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10,000,393
September expense rate is lowest in nine months.
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10,000,394
New 'employment line' is less costly, but effective tool for advertising hospital's job opportunities.
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10,000,395
Sharing work experiences helps ED nurses, paramedics improve communications.
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10,000,396
Gamble on food service technology pays off at United Hospitals.
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10,000,397
High school for health professions uses hospital for classrooms.
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10,000,398
Engineering department uses 'quick slip' to handle minor repairs in hospital.
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10,000,399
Vinyl graphics bring appeal, color to patient care areas.
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