Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of benazepril, metoprolol OROS and their combination was evaluated in 29 patients (42 to 74 years of age) with chronic stable angina and documented coronary artery disease in a placebo-controlled, double-blind, crossover trial using serial quantitated exercise testing and ambulatory electrocardiographic (ECG) monitoring. The mean (+/- SEM) exercise time was 8.5 +/- 0.7 min with placebo, 8.3 +/- 0.6 min (95% confidence interval [CI]-1.06 to 0.54) with benazepril, 9.4 +/- 0.5 min (95% CI -0.32 to 2.14) with metoprolol OROS and 9.6 +/- 0.5 min (95% CI -0.25 to 2.47) with the combination of benazepril and metoprolol OROS. The mean exercise time to the development of 1 mm ST segment depression was prolonged from 6.0 +/- 0.6 min with placebo to 6.3 +/- 0.6 min (95% CI -0.93 to 1.45) with benazepril, 7.9 +/- 0.5 min (95% CI 0.83 to 3.0) with metoprolol OROS and 8.1 +/- 0.6 min (95% CI 0.88 to 3.29) with the combination of benazepril and metoprolol OROS. Benazepril did not alter the rest or maximal heart rate, whereas metoprolol OROS alone and in combination significantly lowered the heart rate at rest and during maximal exercise. Systolic blood pressure at rest was nonsignificantly reduced, whereas diastolic blood pressure was lowered significantly by all treatments in comparison with placebo. At maximal exercise, only metoprolol OROS, whether given alone or in combination with benazepril, was able to blunt significantly systolic blood pressure and rate-pressure product.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of benazepril and metoprolol OROS alone and in combination on myocardial ischemia in patients with chronic stable angina. 221 77

To investigate the time course of restenosis, serial treadmill exercise testing was performed in the absence of medical therapy by 31 patients with single vessel coronary disease who underwent successful angioplasty. Exercise tests were performed before angioplasty and at 3 days and 1, 3 and 6 months after angioplasty; if the test was positive, it was repeated after administration of 10 mg of intravenous verapamil. At arteriography 6 months after coronary angioplasty, 17 patients (group 1) showed no restenosis but 14 patients (group 2) did. Before angioplasty all 31 patients had a positive exercise test with ST segment depression greater than or equal to 1 mm. At 3 days after angioplasty, three patients in group 1 had a positive exercise test compared with 11 patients in group 2 (p = 0.08). At 1, 3 and 6 months, 1 patient in group 1 had a positive exercise test compared with 14 patients in group 2 (p less than 0.01). The heart rate-blood pressure product (beats/min.mm Hg) calculated at 1 mm ST segment depression, or at peak exercise if the test was negative, was used as an index of the ischemic threshold. In group 1 (no restenosis) the ischemic threshold increased progressively from 14,840 +/- 1,075 (mean value +/- SEM) before angioplasty to 21,210 +/- 1,049 at 3 days and to 25,140 +/- 1,177 (p less than 0.001) at 6 months. In group 2 (restenosis) the ischemic threshold increased from 16,270 +/- 828 before angioplasty to 20,400 +/- 984 (p less than 0.0004) at 3 days but decreased to 16,090 +/- 1,298 (p less than 0.006) at 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Very early prediction of restenosis after successful coronary angioplasty: anatomic and functional assessment. 229 64

The effect of acutely elevated serum magnesium on the CNS and cardiac toxicity of bupivacaine was studied. Anesthesia was induced in mongrel dogs with thiopental, 25 mg/kg, and ventilation was controlled. Sedation was maintained with fentanyl (25 micrograms/kg bolus and 5 micrograms.kg-1h-1) and pancuronium (0.15 mg/kg bolus and 0.05 mg.kg-1h-1) provided paralysis. Two hours after the thiopental bolus, all animals received an intravenous (iv) infusion of bupivacaine (1 mg.kg-1 min-1). The control group (5 animals) received bupivacaine only. The Mg++ group (5 animals) received MgSO4 140 mg/kg iv and 80 mg.kg-1 h-1 15 min prior to beginning the bupivacaine infusion. Lead II ECG, cardiac hemodynamics, and two-channel EEG were continuously monitored. Serum magnesium concentrations in the Mg++ group rose from 0.67 mM (1.3 mEq/L) to 2.42 mM (4.8 mEq/L). The bupivacaine infusion caused PR and QRS interval prolongation in both groups, but QRS widening was greater in the control group. QT interval corrected for heart rate (QTIc) lengthened only in the control group. A depression of left ventricular stroke work index (LVSWI) occurred to an equal extent in both groups. The seizure dose of bupivacaine was not different between the two groups: 12.9 +/- 2.3 (SEM) mg/kg in the control group and 13.9 +/- 2.5 mg/kg in the Mg++ group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of magnesium sulfate administration on cerebral and cardiac toxicity of bupivacaine in dogs. 230 66

The steady state pharmacokinetics of propranolol was examined in 48 Saudi Arabian patients chronically treated with oral doses [mean (SEM) = 85.8 (5) mg] of this drug. The mean (SEM) of the steady state concentration (Css) per mg/kg daily dose was 21.8 (3.1) ng.ml-1/mg.kg-1. A 6-fold variability in Css was observed between patients treated with 40 mg every 8 hours and 14-fold between patients treated with 40 mg twice daily. The frequency distribution of the apparent oral clearance (TCLor) of propranolol was bimodal with 88% of the patients showing TCLor of 18 to 372 l.hr-1 while the remainder had TCLor of 471 to 749 l.hr-1. The mean (SEM) of the TCLor per kg body weight for all 48 patients was 3.16 (0.38) l.hr-1.kg-1. Both Css and TCLor obtained for Saudi Arabian patients are not significantly different from those reported for subjects from Western populations. While Css increased proportionally (P less than .001) with dosing, a near-significant (P less than .06), inverse, linear relationship was found between age and TCLor. No significant effect of sex, body weight, or disease state (i.e., heart diseases, hypertension, depression, migraine) on Css or TCLor was detected.
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PMID:Steady state pharmacokinetics of propranolol in Saudi Arabian patients and comparison with data for different populations. 231 65

Grey seal pups (Halichoerus grypus) were collected at the time of weaning (mid-October) and fasted for 52 days at thermoneutrality in separate cages. Body weight decreased exponentially, while metabolic rate dropped 45% from an average of 2.95 +/- 0.15 (SEM) W kg-1 at day 2 of fasting to a stable level of 1.62 +/- 0.06 (SEM) W kg-1 from day 10 to day 47 of fasting. Respiratory quotient was low, indicating extensive catabolism of triglycerides, while plasma cortisol was fairly stable at 110 +/- 8 (SEM) nmol l-1 throughout the fasting period. Daily urinary output decreased from 236 +/- 20 (SEM) ml day-1 at day 2 to a stable value of 87 +/- 6 (SEM) ml day-1 between days 8 and 50 of fasting. The urine was analysed for urea, uric acid, creatinine, ammonia, total nitrogen and osmolality. Urea was always the principal excretory end-product, amounting to between 70 and 80% of the total excreted nitrogen. The urine was moderately concentrated (range 770-1300 mosmol kg-1). Total excreted urinary nitrogen decreased by 68% from 3.7 +/- 0.7 (SEM) g day-1 to 1.2 +/- 0.4 (SEM) g day-1 between days 2 and 50. The urinary nitrogen was used to calculate the daily amount of protein being oxidized and its energy content was compared with the measured basal metabolic rate of individual animals. Approximately 6% of the energy expended by grey seal pups during the post-weaning fast is derived from oxidation of protein. It is concluded that a rapid depression of basal metabolic rate and extensive blubber catabolism enable grey seal pups to endure prolonged periods of fasting without any apparent signs of discomfort or stress.
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PMID:Depressed metabolism and low protein catabolism in fasting grey seal pups. 236 22

The ability of d-fenfluramine, a drug that releases brain serotonin and blocks its reuptake, to relieve premenstrual depression and excessive calorie and carbohydrate intakes was examined in 17 women with premenstrual syndrome. Subjects received d-fenfluramine (15 mg twice daily) or placebo, in random order, during the luteal phases of six menstrual cycles; ie, for three control and three treatment cycles each. Behavior was assessed with the Hamilton Rating Scale for Depression and its Addendum, and intakes of calories and nutrients were measured by allowing subjects unlimited access to isocaloric meal and snack foods rich in carbohydrates or protein. Pre-treatment follicular scores using the Hamilton Rating Scale for Depression and its Addendum were 2.0 +/- 0.5 and 0.5 +/- 0.5 (mean +/- SEM), respectively; corresponding luteal scores were 21.2 +/- 0.8 and 10.2 +/- 0.6 (P less than .0001). Luteal phase intakes of kilocalories, carbohydrates, and fats were also increased above follicular levels (P less than .01). d-Fenfluramine decreased premenstrual Hamilton Rating Scale for Depression and Addendum scores by 62% (P less than .001) and 60% (P less than .001), respectively; placebo reduced them by only 28% (P less than .02) and 30% (P less than .02). d-Fenfluramine also fully suppressed the premenstrual rise in kilocalorie, carbohydrate, and fat intakes (P less than .01).
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PMID:d-Fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression. 237 Oct 34

We developed a two-compartment model to simulate neuromuscular function and heart rate following the administration of four nondepolarizing neuromuscular blocking agents (atracurium, vecuronium, pancuronium, and d-tubocurarine), three neuromuscular block reversal agents (edrophonium, neostigmine, and pyridostigmine), and two anticholinergic agents (atropine and glycopyrrolate). Twitch depression, train-of-four ratio, and heart rate were modeled during fentanyl, halothane, enflurane, or isoflurane anesthesia, optionally supplemented with nitrous oxide. Simulation results, compared with published values for each drug, fell within the clinical accuracy range (onset time 6.1 +/- 3.9% [mean +/- SEM]; duration, 1.7 +/- 3.5%, 50% effective dose, 0.5 +/- 5.7%; and 95% effective dose, 2.1 +/- 1.1%). The simulation graphically demonstrates the pharmacokinetics, pharmacodynamics, and interactions between neuromuscular blocking agents, reversal agents, and anticholinergic agents. During a simulation, the need for frequent monitoring and repeated delivery of a neuromuscular blocking agent to keep neuromuscular blockade stable becomes apparent, especially with the intermediate-acting neuromuscular blocking agents. When inhalational agents are given concomitantly, the task becomes even more difficult, since potentiation changes with anesthetic uptake. Recurarization, tachycardia, or bradycardia may be seen with the simulation if an improper drug regimen is followed. Concurrent simulation of two identical patients allows comparison of different modes of administration, choice of anesthetic agents, and drug doses.
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PMID:A simulation of neuromuscular function and heart rate during induction, maintenance, and reversal of neuromuscular blockade. 240 85

To clarify the role of coronary responses to nitroglycerin (NTG) in relieving myocardial ischemia, we examined the effects of NTG in canine models of dynamic and fixed coronary stenoses. Application of coronary stenosis in the proximal left circumflex artery decreased resting coronary blood flow by approximately 40% and caused a significant depression of left ventricular (LV) dP/dt. During fixed coronary stenosis created with an externally applied constrictor device, intravenous NTG, 5 micrograms/kg, reduced mean aortic pressure by 12 +/- 1.1 mm Hg (mean +/- SEM, p less than 0.01) and coronary blood flow by 9 +/- 1.0% (p less than 0.01) but did not affect stenosis resistance and LV dP/dt. During dynamic coronary stenosis produced with an intraluminal microballoon occluder, intravenous NTG caused a marked increase in coronary blood flow by 40 +/- 8.3% (p less than 0.01) and a decrease in stenosis resistance by 62 +/- 9.3% (p less than 0.01), as compared with postocclusion values, concomitant with a significant improvement in LV dP/dt. Intracoronary infusion of NTG, 1.0 microgram/kg/min, had few systemic and coronary hemodynamic effects during fixed coronary stenosis, whereas intracoronary NTG increased coronary blood flow and reduced stenosis resistance, depending on its dose, during dynamic coronary stenosis. These results indicate that NTG is capable of increasing coronary blood flow and alleviating myocardial ischemia due to direct stenosis-dilating effects related to the vasomobility of the coronary stenosis.
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PMID:Dilatation of coronary stenosis as the salutary effect of nitroglycerin in relief of myocardial ischemia in the dog. 241 Jun 91

To assess whether an virus-specific immune defect may be associated with multiple sclerosis (MS), we have examined the ability to generate measles virus-and influenza virus-specific cytotoxic T cells (CTL) in patients with MS, normal individuals, and other disease controls (ODC). The mean (+/- SEM) measles virus-specific CTL response for normal individuals and ODC was 26.9 +/- 2.9% (N = 17) and 26.7 +/- 2.8% (N = 13) specific lysis, respectively. In contrast, the capacity of MS patients to generate measles virus-specific CTL was markedly diminished. Peripheral blood lymphocytes from MS patients stimulated with measles virus lysed their measles virus-infected autologous B cell line at a group mean level of 6.0 +/- 1.4% (N = 16) specific lysis. MS patients had significantly lower measles virus-specific CTL responses than normal individuals (p less than 0.00001) or ODC (p less than 0.0001). Importantly, this lowered response did not reflect a generalized depressed cytolytic activity of MS patients, since influenza virus-specific CTL and NK activity from these patients were comparable to normals and ODC. Thus, in MS there is a significant depression of measles virus-specific CTL which suggests that this virus-specific immune dysfunction may play a role in the pathogenesis of this disorder.
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PMID:Impaired measles virus-specific cytotoxic T cell responses in multiple sclerosis. 241 41

We have investigated the effects of OPC-8212, a new positive inotropic agent, and dobutamine, a known cardioselective inotropic agent, on global left ventricular (LV) and ischemic regional functions in 14 excised canine hearts with a flow-limiting stenosis of the left circumflex coronary artery (LCX) (i.e., 20-25% of control flow). OPC-8212 infusion (n = 7) under LCX stenosis improved cardiac depression [i.e., peak LV dP/dt increased from 1,295 +/- 143 mm Hg/s to 2,669 +/- 266 mm Hg/s (mean +/- SEM) (p less than 0.001)], while myocardial ischemic injury, assessed by myocardial CO2-tension and electrocardiogram (ECG)-ST changes, improved (i.e., delta CO2-tension and ECG-ST deviation decreased from 21.1 +/- 3.6 mm Hg and 3.8 +/- 0.6 mV to 13.3 +/- 2.8 mm Hg (p less than 0.01) and 2.0 +/- 0.7 mV (p less than 0.05), respectively). On the other hand, dobutamine infusion (n = 7) further increased myocardial CO2-tension and ECG-ST deviation [i.e., delta CO2-tension and ECG-ST deviation increased from 14.4 +/- 4.2 mm Hg and 2.5 +/- 1.2 mV to 29.0 +/- 6.0 mm Hg (p less than 0.01) and 4.9 +/- 1.0 mV (p less than 0.01), respectively]. At the same time, peak LV dP/dt clearly improved, but to a lesser degree; from 1,425 +/- 153 mm Hg/s to 2,393 +/- 245 mm Hg/s (p less than 0.001). There was also an increase in percent systolic segment shortening of each corresponding area as with OPC-8212.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of OPC-8212, a new positive inotropic agent, and dobutamine on left ventricular global and ischemic regional functions and coronary hemodynamics under coronary artery stenosis. 241 80


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