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Biomedical subjects

J Pearl

Publications and source records attributed to J Pearl.

At least 37 records · Page 2Linked to original sources
PubMed1989

Surgical options for complex transposition of the great arteries.

Between September 1976 and November 1987, 53 patients underwent surgical treatment by the same surgeon for "complex transposition of the great arteries" with ventricular septal defect or severe left ventricular outflow tract obstruction, or both. Six patients with transposition and left ventricular outflow tract obstruction underwent atrial rerouting and direct relief of the left ventricular outflow tract obstruction. Twenty-two patients presented with transposition plus ventricular septal defect; 15 of these patients underwent atrial rerouting and ventricular septal defect closure and 7 underwent an arterial switch procedure. Twenty-five patients presented with transposition plus ventricular septal defect and left ventricular outflow tract obstruction, 23 of whom underwent a Rastelli procedure. There were one early death (mortality rate 1.9%; 90% confidence limits 0-7%) and three late deaths (mortality rate 5.8%) during a mean follow-up period of 42 months (range 2 to 124). These results show that 1) atrial rerouting is an appropriate surgical procedure for transposition of the great arteries with left ventricular outflow tract obstruction; 2) the arterial switch procedure provides excellent early correction of transposition with ventricular septal defect and is currently the preferred procedure for this lesion; and 3) the Rastelli procedure can be performed with a low early mortality rate and excellent long-term results for transposition with ventricular septal defect and left ventricular outflow tract obstruction.

Adolescent↗
PubMed1987

Differential modification of morphine and methadone dependence by interferon alpha.

Subcutaneous implantation of a pellet of methadone was presented as a novel method for the establishment of physical dependence upon this agent and it was compared to (1) the state of physical dependence induced by multiple injections of methadone, administered over several days, and (2) the dependence established by injections of morphine and the implantation of a morphine pellet. Comparable signs of drug dependence were observed in rats treated with both morphine and methadone following the administration of the opiate antagonist naloxone. The administration of interferon-alpha significantly attenuated the severity of the withdrawal syndrome in dependent rats after chronic exposure to morphine and to a lesser extent after morphine and methadone in combination. In contrast, alpha interferon did not affect 6 of the 7 abstinence signs in animals dependent upon methadone alone. The observations suggest that the states of physical dependence upon morphine and methadone may be separate phenomena that involve different physiological mechanisms. Thus, interferon may be a useful adjunct in the treatment of subjects dependent upon morphine but not in those dependent on methadone.

Animals↗
PubMed1985

3,4-Diphenyl-1H-pyrazole-1-propanamine antidepressants.

A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. Compounds were synthesized by Michael addition of acrylonitrile to diphenylpyrazole followed by reductive alkylation of the resultant diphenylpyrazolepropionitriles. Compound 3 was equipotent with imipramine in standard antidepressant assays in animals but showed no significant anticholinergic action and did not antagonize the antihypertensive effects of clonidine and guanethidine.

Animals↗
PubMed1983

Parasympatholytic (anticholinergic) esters of the isomeric 2-tropanols. 2. Non-glycolates.

The 19 esters in Table I were prepared from (+)-2 alpha-tropanol, (-)-2 beta-tropanol, (+/-)-3-quinuclidinol, and a variety of non-glycolic acids in order to compare their central and peripheral activities with those of the glycolates reported in the previous paper. The results (Table II) showed that esters 6 and 17 were approximately equivalent to one another and to atropine, that 8 was equal in both central and peripheral activity to reference glycolates, that 9 and 19 were less active than 8 but 9 had a substantially reduced central activity, and that 10 and 11 were more active than the methoxy analogue reported earlier.

Animals↗
PubMed1978

(exo, exo)-2-Aryltropane-3-carboxylic esters, hypoglycemic agents with accompanying analgesic activity.

(exo, exo)-2-Aryltropane-3-carboxylic esters of types 6, 7, and 10 lower circulating blood glucose levels by 60--80%. This activity is accompanied by an analgesic activity roughly equal to that of codeine. Both of these activities reside in the 1R enantiomer and extensive structure-activity studies failed to separate them. The specific opioid antagonist nalorphine blocks the analgesic activity but does not diminish the hypoglycemic action. Conformational integrity afforded by the ethylene bridge is neccessary for the observed activities.

Administration, Oral↗
PubMed1977

3-Aminotetrahydrocarbazoles as a new series of central nervous system agents.

3-Dimethylamino-1,2,3,4-tetrahydrocarbazole, a structurally modified tryptamine, prevented amphetamine-induced stereotyped behavior in rats and prevented reserpine-induced ptosis in mice. Further study of this compound and a number of substituted derivatives indicated that either imipramine-like or chlorpromazine-like profiles were obtainable by changing substituents and their positions.

Amphetamine↗
PubMed1977

Parasympatholytic (anticholinergic) esters of the isomeric 2-tropanols. 1. Glycolates.

The 38 esters in Table I were prepared from the four isomeric 2-tropanols and a variety of racemic glycolic acids and their optical isomers. Anticholinergic activity in mice was measured in the peripheral nervous system (mydriasis) and in the central nervous system (anti-tremorine) and compared with that of atropine, scopolamine, and racemic 2-quinuclidinyl benzilate. The results (Table III) showed that several esters (such as 8, 12, 14, and 21) had significantly greater activity in both the peripheral and central nervous systems than did the reference compounds. Esters of (+)-2alpha-tropanol were more potent than those of either its epimer (-)-2beta-tropanol or its optical isomer(-)-2alpha-tropanol. Esters derived from (-)-glycolic acids were uniformly more potent than those from the (+)-glycolic acids. Esters of (+)-2alpha-notropanol and five of its N-substituted derivatives had markedly decreased activity. Peripheral/central activity ratios and time-activity profiles for five active compounds are discussed and compared with those of the reference compounds.

Animals↗
PubMed1976

Anticholinergic activity of antipsychotic drugs in relation to their extrapyramidal effects.

Antipsychotic drugs were evaluated with two indices of anticholinergic activity, mydriasis in mice in vivo and antagonism of carbamylcholine-induced contractions of guinea-pig tracheal strips in vitro. The drugs from most to least potent as oral mydriatic agents were mepazine, clozapine, thioridazine, promazine and chlorpromazine. Trifluoperazine, pimozide and haloperidol were inactive. These results were consistent with the hypothesis that anticholinergic activity of antipsychotic drugs is inversely related to their propensity to produce extrapyramidal effects in man. In vitro results appeared to predict the incidence of extraphyramidal effects less accurately than in vivo results.

Animals↗
PubMed1976

Boredom and arousal: comparison of tasks differing in visual complexity.

This experiment was designed to examine the relationship of boredom to arousal. 32 male subjects participated, with 16 subjects performing a low-visual-complexity task and the remainder performing a task high in visual complexity. Both physiological and subjective measures were obtained. Responses to subjective questionnaires showed significant increases in boredom for both groups. Physiological measures indicated a mixed pattern of change. These results suggest a complex response pattern for the construct of boredom which cannot be described as clearly showing either increasing or decreasing arousal.

Adolescent↗
PubMed1969

Effects of opiates and opiate antagonists on the Straub tail reaction in mice.

1. Subcutaneous injections of opiates produced the Straub tail reaction in mice. The potencies of the opiates in mice were consistent with previous estimates of the analgesic potencies in animals and in man.2. The potencies of sixteen antagonists in counteracting the reaction were consistent with those previously obtained with the rat tail-flick test.3. The (-) isomers of four benzomorphan derivatives were much more potent in counteracting the reaction than their (+) isomers and about twice as potent as their racemates. The activity of the isomers seemed to follow Pfeiffer's rule: the lower the effective dose of a drug, the greater the difference in the pharmacological effects of the optical isomers. One of the trans isomers acted like an opiate, while its cis isomer acted like an antagonist.4. Naloxone and nalorphine fulfilled conventional criteria for competitive antagonism, whereas atropine and the (-) and the (+) isomers of pentazocine and of cyclazocine did not do so.5. The Straub tail test seems to be useful for studying structure-activity relations among opiates and opiate antagonists.

Analgesics↗