Advances in and Limitations of Up-and-down Methodology

2007 ◽  
Vol 107 (1) ◽  
pp. 144-152 ◽  
Author(s):  
Nathan L. Pace ◽  
Mario P. Stylianou ◽  
David C. Warltier
Keyword(s):  
Statistical Methods ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Binary Response ◽  
Target Dose ◽  
Anesthesia Research ◽  
Tolerance Distribution ◽  
Probability Of Response

Abstract Sequential design methods for binary response variables exist for determination of the concentration or dose associated with the 50% point along the dose–response curve; the up-and-down method of Dixon and Mood is now commonly used in anesthesia research. There have been important developments in statistical methods that (1) allow the design of experiments for the measurement of the response at any point (quantile) along the dose–response curve, (2) demonstrate the risk of certain statistical methods commonly used in literature reports, (3) allow the estimation of the concentration or dose—the target dose—associated with the chosen quantile without the assumption of the symmetry of the tolerance distribution, and (4) set bounds on the probability of response at this target dose. This article details these developments, briefly surveys current use of the up-and-down method in anesthesia research, reanalyzes published reports using the up-and-down method for the study of the epidural relief of pain during labor, and discusses appropriate inferences from up-and-down method studies.

Evaluation of cinnamamide as an avian repellent: Determination of a dose-response curve

1995 ◽  
Vol 44 (4) ◽  
pp. 335-340 ◽  
Author(s):  
Richard W. Watkins ◽  
Elaine L. Gill ◽  
Julie D. Bishop
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve

A Screening Procedure for Substances Which Inhibit Dextran Edema in the Rat

1958 ◽  
Vol 193 (2) ◽  
pp. 275-282 ◽  
Author(s):  
Jacob C. Stucki ◽  
Charles R. Thompson
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Intraperitoneal Administration ◽  
Dose Response Curve ◽  
Screening Procedure ◽  
Adrenergic Agents ◽  
Adrenergic Drugs ◽  
Before And After ◽  
Quantitative Bioassay

Determination of foot volume by mercury displacement before and after the intraperitoneal administration of dextran to rats demonstrated that pronounced edema occurs one-half to three-fourths of an hour after dextran, reaches a maximum in 1 1/2 hours, and gradually subsides over the next several hours. Inhibiting substances prevent the edema entirely, reduce its severity or delay its appearance. A method was presented for screening compounds for ability to inhibit dextran edema. A dose-response curve developed for chlorpromazine suggests that the technique might also be suitable for quantitative bioassay. It was found that strongly vasoconstrictor adrenergic agents inhibited edema while adrenergic drugs with other predominating activities did not. Atropine, Dibenamine, morphine, reserpine, hydroxyzine and meprobamate were inactive. Chlorpromazine, the antihistaminics and anesthetic doses of phenobarbital were active. Cortisone and phenylbutazine were inactive but the salicylates were moderately active.

Determination of a Dose-Response Curve for Intrathecal Sufentanil in Labor

1994 ◽  
Vol 81 (SUPPLEMENT) ◽  
pp. A1149 ◽  
Author(s):  
T. Van Decar ◽  
R. Callicot ◽  
R. Jones ◽  
N. Herman
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve

OVARIAN ASCORBIC ACID DEPLETION TEST FOR LUTEINIZING HORMONE

1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger
Keyword(s):  
Ascorbic Acid ◽  
Luteinizing Hormone ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Human Origin ◽  
Response Curves ◽  
Significant Difference ◽  
The Mean ◽  
Different Levels

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.

HYPERTROPHIC ADRENALS AND THEIR RESPONSE TO STRESS AFTER LESIONS IN THE MEDIAN EMINENCE OF TOTALLY HYPOPHYSECTOMIZED PIGEONS

1961 ◽  
Vol 37 (4) ◽  
pp. 565-576 ◽  
Author(s):  
Richard A. Miller
Keyword(s):  
Dose Response ◽  
Median Eminence ◽  
Response Curve ◽  
Liver Parenchyma ◽  
Dose Response Curve ◽  
Pars Distalis ◽  
Adrenal Enlargement ◽  
Response To Stress ◽  
Lethal Doses ◽  
Chromaffin Tissue

ABSTRACT Four per cent formaldehyde, insulin, or epinephrine in oil was injected for 5 days into pigeons subjected to varying degrees of hypophysectomy alone or together with large lesions in the median eminence and hypothalamus. Adrenals atrophied after the removal of the pars distalis alone or together with the neurohypophysis in untreated pigeons but showed markedly hypertrophic interrenal tissue (cortex in mammals) after treatment with formaldehyde or insulin. The slope of the dose-response curve was similar in operated and unoperated pigeons. The accumulation of bile in the liver parenchyma, which may occur after removal of the pars distalis, is an endogenous stress which was associated regularly with adrenal hypertrophy. After very large lesions of the median eminence and ventral hypothalamus in addition to total hypophysectomy, adrenals hypertrophied rather than atrophied, and the response to formaldehyde paralleled that in intact and »hypohysectomized« pigeons. Interrenal tissue was stimulated regularly; chromaffin tissue was partially degranulated, sometimes showed hyperplasia with colchicine, but only occasionally appeared hypertrophied. Epinephrine in nearly lethal doses caused only minimal adrenal enlargement. After adrenal denervation followed by hypophysectomy, the adrenals were still stimulated by formaldehyde. It appears that the interrenal tissue of the pigeon responds to a humoral stimulus not of hypophyseal origin in the absence of the hypophyseal-hypothalamic system.

ANTI-OVULATORY ACTIVITY OF STEROIDS ADMINISTERED BY GAVAGE IN THE ADULT OESTRUS RABBIT

1963 ◽  
Vol 42 (2_Suppl) ◽  
pp. S17-S30
Author(s):  
Fred A. Kind ◽  
Ralph I. Dorfman
Keyword(s):  
Dose Response ◽  
Active Compound ◽  
Subcutaneous Injection ◽  
Response Curve ◽  
Parent Compound ◽  
Dose Response Curve ◽  
Relative Potency ◽  
Reference Standard ◽  
Highly Active ◽  
Dose Levels

ABSTRACT Thirty-seven steroids have been studied as orally effective inhibitors of ovulation in the mated oestrus rabbit. Norethisterone served as the reference standard and a dose response curve was established between the 0.31 and 1.25 mg dose levels. Nine highly active anti-ovulatory compounds are described listed in a decreasing order of potency with norethisterone having the arbitrary value of one: 6-chloro-Δ6-dehydro-17α-acetoxyprogesterone (35), 6α-methyl-Δ1-dehydro-17α-acetoxyprogesterone (≥ 10), 6-fluoro-Δ6-dehydro-17α-acetoxyprogesterone(9), 6-methyl-Δ6-dehydro-17α-acetoxyprogesterone (5), Δ6-dehydro-17α-acetoxyprogesterone (≥ 3), 6α-methyl-17α-acetoxyprogesterone (2.6), 6-chloro-Δ1,6-bisdehydro-17α-acetoxyprogesterone (≥ 2), 2-hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one (≥ 2), and 6α-fluoro-16α-methyl-17α-acetoxyprogesterone (≥ 1.25). The anti-ovulatory activity of a compound was not related necessarily to the progestational activity of a compound nor to the anti-gonadotrophic activity as measured in parabiotic rats. 6-Chloro-Δ60dehydro-17-acetoxyprogesterone was as effective by gavage as previously shown by subcutaneous injection. 2-Hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one was at least 2.5 times more active by gavage than by injection. While 17α-acetoxyprogesterone was a very weak anti-ovulatory steroid, modifications of the structure by addition of methyl or halogen at the 6α position with or without unsaturation greatly increased the activity. 6-Chloro-Δ6-dehydro-27α-acetoxyprogesterone was the most active compound in this series showing a relative potency of 3500 times that of the parent compound 17α-acetoxyprogesterone.

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