PubMed Health⌕ Search

Biomedical subjects

J D Lazar

Publications and source records attributed to J D Lazar.

At least 19 recordsLinked to original sources
PubMed1997

Internal and external distraction in the control of cold-pressor pain as a function of hypnotizability.

The effectiveness of different pain-distraction tasks was compared as a function of level of hypnotizability, using the cold-pressor pain-testing procedure. Selected high, medium, or low hypnotizable participants first underwent a 1-minute baseline immersion of a hand in ice water, with periodic pain ratings. Independent groups were then given 4-minute test immersions under one of five conditions. Analgesia suggestion and guided imagery were conceived to be internal distractors, whereas word memory and pursuit-rotor tasks were external distractors. Placebo-control groups were given permission to let their minds wander. All four experimental treatments reduced pain significantly for highly hypnotizable participants, compared to the control group, whereas none of the experimental treatments were effective for low hypnotizables. The different treatment instructions did not produce different preimmersion anxiety state ratings, so the treatment effects on pain ratings could not be explained in terms of their effects on anxiety. It appears that high hypnotizables are more effective than low hypnotizables at diverting attention to control pain, regardless of whether internal or external distractor tasks are used. Treatment effects on pain ratings did not change between 1 and 4 minutes of test immersion.

Adolescent↗
PubMed1992

Sertraline does not alter steady-state concentrations or renal clearance of lithium in healthy volunteers.

An open-label, placebo-controlled study was conducted to determine the effects of sertraline on the steady-state levels and renal clearance of lithium in 20 healthy volunteers. Subjects received 600 mg of lithium twice daily for 9 days. On the evening of day 8, subjects received orally either placebo or 100 mg of sertraline; these were administered twice, 8 hours apart, beginning 2 hours after the evening dose of lithium. In a comparison of day 8 with day 9 (before administration of the morning doses of lithium), sertraline was associated with only a 0.01 mEq/L (1.4%) decrease in steady-state levels and a 0.11 L/hour (6.9%) increase in the renal clearance of lithium. Neither change was statistically significant relative to placebo. Four subjects were excluded from analysis because of protocol violations or laboratory abnormalities unrelated to sertraline. Seven subjects who received lithium plus sertraline experienced side effects, mainly tremors, possibly related to treatment, whereas none of those administered lithium plus placebo experienced side effects. No sertraline-related laboratory abnormalities were observed.

1-Naphthylamine↗
PubMed1991

Induction of fluconazole metabolism by rifampin: in vivo study in humans.

The effects of rifampin on the pharmacokinetics of fluconazole were analyzed in an open-label, placebo-controlled, parallel study. Sixteen healthy male volunteers, randomized into two groups, received 200 mg of oral fluconazole on days 1 and 22. On days 8 through 27, group I received oral rifampin, 600 mg/d, and group II received placebo. Fluconazole in serum was analyzed by HPLC. On days 1 and 22, respectively, the AUC (micrograms.hr/mL) (mean +/- SD) was 160.5 +/- 19.5 and 124 +/- 22.2 in group I, 152 +/- 25 and 152.8 +/- 33.9 in group II; the Kel (hr-1) was .0211 +/- .0030 and .0264 +/- .0040 in group I, .0219 +/- .0036 and .0216 +/- .0053 in group II. Cmax and Tmax did not change significantly in either group. Urinary 6 beta-hydroxycortisol/cortisol increased from 3.47 +/- 1.04 to 15.2 +/- 5.07 in group I, but was unchanged (3.54 +/- 1.33-4.26 +/- 2.36) in group II on days 1 and 22, respectively. The findings in this study indicate that rifampin induces the metabolism of fluconazole.

Administration, Oral↗
PubMed1991

Pharmacokinetics of the penem CP-65,207 and its separate stereoisomers in humans.

CP-65,207 is a new broad-spectrum penem antimicrobial agent that is a 1:1 mixture of two stereoisomers. Five minutes after a 10-min intravenous infusion of 1 g of CP-65,207 to volunteers, mean concentrations in serum were 33 micrograms of the R isomer per ml and 29 micrograms of the S isomer per ml. Following rapid distribution, half-lives of the isomers were 53 and 55 min, respectively. Concentrations in urine exceeded 800 micrograms of each isomer per ml. Recovery of the S isomer in urine (46%) was much greater than recovery of the R isomer (26%). The serum kinetics of the S isomer (volume of distribution, 319 ml/kg; total clearance, 315 ml/min; elimination rate constant, 0.80 h-1 were similar when it was given alone and when it was contained in CP-65,207, demonstrating that the presence of the R isomer has little effect on the serum kinetics of the S isomer. However, when the S isomer was given alone, the urinary recovery of intact S isomer (36%) was substantially lower than that when it was given with the R isomer as CP-65,207 (57%). Administration of the S isomer alone did not produce the unpleasant sulfurous odor in urine that was observed following administration of CP-65,207. Oral doses of a prodrug, which contained 1 g of CP-65,207, produced peak concentrations in serum of 1.6 micrograms of the R isomer per ml and 1.8 micrograms of the S isomer per ml. Approximately 36% of the S-isomer component was absorbed, and 20% of this isomer was recovered in urine. A 1-g oral dose of the prodrug of the single S isomer provides concentrations in serum above 1.0 microgram/ml (the MIC for 90% of over 1,000 hospital pathogens) for 3.5 h, suggesting that the drug given orally will prove to be efficacious against many infections.

Adult↗
PubMed1990

The clinical pharmacology of fluconazole.

The pharmacokinetic profile of fluconazole clearly distinguishes it from other antifungal agents; oral bioavailability is more than 90%, and plasma protein binding is 12%. The volume of distribution approximates that of total body water. Both peak and minimum plasma concentrations are linearly proportional to dose over a range of 50 to 400 mg. Fluconazole is metabolically stable. Renal clearance is the predominant route of elimination, with only 11% of a single dose excreted as metabolites. The mean elimination half-life is approximately 30 hours. Consequently, dosage requirements in the presence of renal insufficiency are predictable from and dependent on renal function. Fluconazole has been extensively studied regarding drug interactions that may occur during concomitant therapy with cimetidine, rifampin, warfarin, oral hypoglycemics, phenytoin, and cyclosporin A. Results indicate that fluconazole can be safely administered with these drugs, as well as a number of other commonly used drugs.

Female↗
PubMed1988

Doxazosin in patients with hypertension.

The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mmHg in the supine and 13/18 mmHg in the standing position. Adverse effects were generally mild and of brief duration.

Adult↗
PubMed1985

A free lignocaine index as a guide to unbound drug concentration.

A free lignocaine index was developed on the basis of measurements of plasma lignocaine and its principle binding protein, alpha 1-acid glycoprotein (AAG) in 80 samples from 16 patients admitted to the coronary care unit and given prophylactic lignocaine therapy. The free drug fraction, fu, of lignocaine was determined by equilibrium dialysis and its relationship to AAG and total lignocaine concentration (T) defined by multiple linear regression analysis as l/fu = 1.45 + 0.023 (AAG) -0.129 (T) (multiple r = 0.872, P less than 0.001). This relationship was used to calculate the 'free lignocaine index' as fu X T and compared with the observed value obtained by equilibrium dialysis of 178 samples from 41 separate subjects who received lignocaine after suspected myocardial infarction. There was a highly significant relationship (r = 0.933, n = 178, P less than 0.001) between the observed and predicted values. We conclude that the free drug index may be useful in rapidly assessing the unbound (free) concentration of lignocaine in plasma.

Humans↗
PubMed1985

The effects of eicosanoid synthesis inhibitors on normoxic and hypoxic pulmonary vascular tone in dogs.

Prostaglandins have been implicated as possible modulators of normoxic and hypoxic pulmonary tone partly because of studies using cyclooxygenase inhibitors, but these drugs may exert effects that are independent of prostaglandin cyclooxygenase. We evaluated the hemodynamic effects of the acute intravenous administration of 3 cyclooxygenase inhibitor drugs in doses that inhibit prostaglandin synthesis in intact anesthetized dogs: indomethacin 5 mg/kg, meclofenamate 5 mg/kg, and ibuprofen 12.5 mg/kg. During room air ventilation, the administration of indomethacin produced an increase in mean pulmonary arterial pressure (8.0 +/- 1.27 to 13.1 +/- 1.52 mmHg, p less than 0.01) and pulmonary vascular resistance (1.2 +/- 0.23 to 2.7 +/- 0.39, p less than 0.01), whereas meclofenamate and ibuprofen had no effect. Indomethacin given during hypoxic ventilation slightly but insignificantly increased pulmonary artery pressure and pulmonary vascular resistance when compared with hypoxia alone and with the administration of vehicle or meclofenamate. Treatment with indomethacin methacin or meclofenamate 5 mg/kg given subcutaneously twice daily for 2 days had no effect on normoxic or hypoxic pulmonary tone. The combined cyclooxygenase-lipoxygenase inhibitor BW 755C in doses of 25 mg/kg given intravenously did not inhibit hypoxic pulmonary vasoconstriction. We conclude that prostaglandins do not appear to play a major physiologic role in modulating normoxic or hypoxic pulmonary vasomotor tone in intact anesthetized dogs, and that the indomethacin-induced increases in pressure and resistance are independent of inhibition of prostaglandin cyclooxygenase.

Animals↗
PubMed1983

Nonadrenergic effects of isoproterenol in dogs with hypoxic pulmonary vasoconstriction. Possible role of prostaglandins.

To determine whether the pulmonary vasodilation produced by isoproterenol is mediated solely by its beta adrenergic effects, we studied the hemodynamic responses to isoproterenol in three groups of dogs with pulmonary vasoconstriction produced by continuous ventilation with 10% oxygen: (a) hypoxia alone, (b) hypoxia and propranolol 0.3 mg/kg i.v. bolus followed by an infusion of 5 micrograms/kg per min, and (c) hypoxia after pretreatment with an inhibitor of cyclooxygenase, either indomethacin or meclofenamate 5 mg/kg s.c. twice daily for 2 d prior to study. All groups had similar values for mean pulmonary artery pressure (PAPm) and pulmonary vascular resistance (PVR) during room air and hypoxic ventilation. Isoproterenol in doses of 0.0025, 0.005, and 0.05 micrograms/kg per min produced a dose-related decline in PAPm and PVR during hypoxia in group 1. Despite beta-blockade with propranolol (group 2), isoproterenol at all three doses significantly reduced PAPm and PVR. The responses to isoproterenol were comparable in the presence or absence of propranolol; at 0.05 micrograms/kg per min the effects of isoproterenol were blunted, but not abolished, by propranolol. Similar results were observed even when five times the dose of propranolol was given. Isoproterenol at all three doses had no effect, however, on PAPm and PVR in the cyclooxygenase inhibitor-pretreated group. These data suggest that the pulmonary vasodilator effects of isoproterenol are not mediated solely by pulmonary vascular beta adrenergic receptors, and that vasodilator prostaglandins may play a role in the responses to this drug.

Animals↗
PubMed1983

Effects of chronic arachidonate on blood pressure of spontaneously hypertensive rats.

Three weeks of treatment with arachidonic acid (250 mg/kg/day, s.c.) produced an antihypertensive effect in 16 week-old spontaneously hypertensive rats (SHR) as compared with vehicle treated rats. Indomethacin (4 mg/kg, s.c. B.I.D.), given concurrently with arachidonate, abolished the antihypertensive effect. Plasma catecholamines were not altered by the arachidonate treatment, but blood pressure increments after spinal cord stimulation or after intravenous administration of norepinephrine and angiotensin II in the pithed rat were diminished. Increments in plasma catecholamines in response to spinal cord stimulation were similar in both groups of pithed rats. These data demonstrate the antihypertensive effect of arachidonic acid in SHR with established hypertension. This beneficial effect seems to be mediated through cyclooxygenase metabolites, and might be related to reduced responsiveness of peripheral blood vessels to pressor stimuli.

Angiotensin II↗
PubMed1981

Improved fitting of radioimmunoassay data by Scatchard analysis.

We present a model of radioligand binding, based on the approach of Scatchard, that improves the fit of the data to the standard curve by allowing for the presence of radioactivity with cannot be bound by the antibody and using this non-specific binding as an additional fitting parameter. Further, it accounts for the specific activity (mass contribution) of the radioligand. Our procedures aim to: (1) minimize the squared error of the fit rather than to maximize the correlation coefficient; (2) provide assistance in the design and debugging of routine radioimmunoassay data; and (3) help assure the quality of results produced by established assay systems.

Binding Sites, Antibody↗
PubMed1981

Prostaglandins and renin release: III. Effects of PGE1, E2 F2 alpha and D2 on renin release from rabbit renal cortical slices.

We have investigated the direct effects of prostaglandins E1, E2, F2 alpha and D2 on renin release from rabbit renal cortical slices. Prostaglandin E1 (PGE1) was the most potent stimulant of renin release, while PGE2 was 20-30 fold less active. PGF2 alpha was found not to be an inhibitor of renin release as reported by others, but rather a weak agonist. PGD2 up to a concentration of 10 microgram/ml had no activity in this system. That the stimulation of renin release by PGE1 is a direct effect is supported by the finding that PGE1-induced release is not blocked by L-propranolol or by delta 5,8,11,14-eicosatetraynoic acid (ETYA), a prostaglandin synthesis inhibitor. The fatty acid precursor of PGE1, delta 8,11,14-eicosatrienoic acid, also stimulated renin release, an effect which was blocked by ETYA. In addition to the above findings, ethanol, a compound frequently used to dissolve prostaglandins, was shown to inhibit renin release.

8,11,14-Eicosatrienoic Acid↗
PubMed1981

Influence of prostaglandin synthesis inhibitors on pulmonary vasodilatory effects of hydralazine in dogs with hypoxic pulmonary vasoconstriction.

TO DETERMINE WHETHER HYDRALAZINE, A SYSTEMIC VASODILATOR, EXERTED A SIMILAR EFFECT ON THE PULMONARY CIRCULATION, WE STUDIED THE CIRCULATORY CHANGES IN DOGS DURING THREE INTERVENTIONS: (a) the control state during room air ventilation; (b) during continuous hypoxic ventilation with 10% oxygen, and maintaining continuous hypoxic ventilation; and (c) after 1 mg/kg hydralazine intravenously. Ventilation with 10% oxygen caused the mean pulmonary artery pressure to increase from 10+/-1.2 to 23+/-2.4 mm Hg (P < 0.01) and the pulmonary arteriolar resistance to increase from 1.51+/-0.19 to 5.87+/-1.10 U (P < 0.01). Hydralazine significantly lowered the pulmonary artery pressure (23.0+/-2.4 to 14.3+/-1.5 mm Hg, P < 0.01) and the pulmonary arteriolar resistance (5.87+/-1.10 to 2.87+/-0.52 U, P < 0.01). Femoral artery pressure, pulmonary artery wedge pressure, heart rate, and cardiac output remained unchanged throughout. To ascertain the contribution of the prostaglandin system to the pulmonary vasodilator effects of hydralazine, we pretreated a group of dogs with the prostaglandin synthetase inhibitor, indomethacin, 5 mg/kg s.c., twice daily for 2 d. These animals then underwent identical studies.The pretreated dogs had comparable base-line and hypoxia hemodynamic data. However, hydralazine had no effect on pulmonary artery pressure (23.3+/-1.6 vs. 21.7+/-2.3 mm Hg, NS) or pulmonary arteriolar resistance (8.03+/-1.09 vs. 7.14+/-1.42, NS) during continuous hypoxic ventilation in the indomethacin-pretreated group. Pretreatment with indomethacin did not, however, block the pulmonary vasodilator effects of intravenous prostacyclin (PGI(2)). Pretreatment with meclofenamate, a cyclo-oxygenase inhibitor structurally unrelated to indomethacin, also blocked the effects of hydralazine during hypoxic ventilation. These data suggest that hydralazine exerts a pulmonary vasodilatory effect during hypoxia-induced pulmonary vasoconstriction, and that this vasodilator effect may be mediated by prostaglandins.

Animals↗