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Biomedical subjects

R J Katz

Publications and source records attributed to R J Katz.

At least 19 recordsLinked to original sources

The Cardiac Arrhythmia Suppression Trial: first CAST ... then CAST-II.

The Cardiac Arrhythmia Suppression Trial (CAST) was a study designed to test the hypothesis that suppression of ventricular premature complexes after a myocardial infarction would improve survival. Preliminary results showed that suppression of ventricular premature complexes with encainide and flecainide worsened survival, and the CAST continued as the CAST-II with moricizine compared with its placebo. The protocol for the CAST-II was changed to attempt to enroll patients more likely to experience serious arrhythmias. The enrollment time was narrowed to 4 to 90 days after myocardial infarction; the qualifying ejection fraction was lowered to less than or equal to 0.40; a higher dose of moricizine could be used; early titration itself was double-blind with a placebo, and the definition of disqualifying ventricular tachycardia was changed to allow patients with more serious arrhythmias to be entered into the trial. The Cardiac Arrhythmia Suppression Trial-II was subsequently terminated prematurely because 1) patients treated with moricizine had an excessive cardiac mortality rate during the 1st 2 weeks of exposure to the drug, and 2) there appeared to be little chance of showing a long-term survival benefit from treatment with moricizine. This report outlines the rationale behind the Cardiac Arrhythmia Suppression Trial and the reasons for selection of the drugs used in the CAST and CAST-II.

Anti-Arrhythmia Agents

Inhibition-mediating dopamine receptors and the control of intracranial reward.

A receptor selective agonist and antagonist of inhibition-mediating dopamine receptors (type II receptors) produced significant and dose-related alterations in bar-pressing for intracranial reward. Receptor inhibition by piribedil increased responding for reward while receptor activation by 3,4-dihydroxyphenylamino-2-imidazoline reduced responding. Inhibition-mediating receptors may therefore play a role opposite to classic excitation-mediating receptors in controlling reward.

Animals

ACTH4--10 antagonism of morphine-induced behavioral activation in the mouse.

The 4--10 fragment of adrenocorticotrophic hormone (ACTH4--10; Met-Glu-His-Phe-Arg-Trp-Gly) was administered intracerebroventricularly to C57Bl mice with and without concurrent systemic injection of a standard dose of morphine sulfate. Morphine produced stereotyped behavioral activation (running, environmental oblivion, Straub tail) which was antagonized in a dose related fashion by the ACTH fragment. This extends the range of opiate--ACTH4--10 interactions to a novel species and behavioral model, and is consistent with previous findings.

Adrenocorticotropic Hormone

Facilitation of opiate- and enkephalin-induced motor activity in the mouse by phenytoin sodium and carbamazepine.

In the first experiment, adult male Swiss-Webster mice were systemically injected with a standard dose of morphine. Compared to the influence of vehicle, the motor activity of morphine-injected mice was increased. Neither phenytoin sodium nor carbamazepine alone facilitated motor activity, but pretreatment with both drugs further facilitated the increased motor activity produced by morphine. In a second experiment, mice were injected centrally with a long-acting analog of leu-enkephalin. It also increased motor activity in comparison with vehicle. Again, both phenytoin sodium and carbamazepine further facilitated this response. Both experiments suggest a facilitatory interaction between some aspects of these anticonvulsants and opiate-induced motor activity.

Animals

Noninvasive diagnosis of left ventricular pseudoaneurysm: role of two dimensional echocardiography and radionuclide gated pool imaging.

This report describes a case of left ventricular pseudoaneurysm diagnosed with two dimensional real time echocardiography. The two dimensional echocardiogram identified not only the pseudoaneurysmal sac but also the site of left ventricular rupture. When supplemented with radioisotope gated cardiac blood pool scanning, the noninvasive studies demonstrated combined true and false left ventricular aneurysms. Left ventricular pseudoaneurysm can be diagnosed using two dimensional echocardiography and nuclear imaging, permitting early operative intervention before fatal rupture.

Aged

A rapid and inexpensive technique for assessing the reinforcing effects of opiate drugs.

Adult male Sprague-Dawley rats were placed in an apparatus consisting of 2 distinctive interconnected chambers. Choice preferences developed and stabilized over three 30 min exposures. Central injection of morphine or an enkephalin analogue in conjunction with placement upon the nonpreferred side caused a preference shift which was not evident in control subjects. Classical conditioning of opiate effects to distinctive environments may offer a novel means of assessing the hedonic effects of these compounds.

Animals

Stress, behavioral arousal, and open field activity--a reexamination of emotionality in the rat.

The effects of stress upon emotionality, and of emotionality upon the open field activity of rats have now been studied for over four decades. Controversy remains however regarding the degree to which stress alters behavior, and the direction of that change. One reason for this is the absence of an adequate behavioral definition of stress. The present series of experiments demonstrates a standard relatively nontraumatic stress induction procedure which may be used in conjunction with open field testing. Pre-exposure to moderately intense light and white noise facilitated open field activity as measured by initial activity, lowered defecation scores, and supplementary measures (rearing, grooming, center field penetration). Further parametric, psychoendocrine, and pharmacological studies characterized the nature of the facilitation, its time course, and its modification by other manipulations. Our results suggest the initial behavioral response to stress in an open field is activation. Previous studies may have differed in their results relating stress and behavior because of subtle procedural distinctions, some of which may be identified using the present technique.

Adrenal Glands

Stress induced grooming in the rat--an endorphin mediated syndrome.

Exposure of adult male Sprague--Dawley rats to a non-traumatic noise-light stress procedure subsequently increased grooming behavior in a novel environment. The grooming syndrome was marginally facilitated by adrenalectomy and by hypophysectomy. Opiate blockade by naltrexone returned grooming to basal levels. This suggests that stress induced grooming is not dependent upon pituitary-adrenal integrity for its expression, although it may be modulated by the latter. On the other hand this form of grooming may depend upon an endogenous opiate system.

Adrenalectomy

Stress induced Straub tail elevation. Further behavioral evidence in rats for the involvement of endorphins in stress.

Adult male Sprague-Dawley rats briefly immersed in cold water and forced to swim showed Straub tail elevation, a typical sign of opiate stimulation, upon removal. The presence of Straub tail was a function of degree of immersion and was reversed by naloxone. This suggests the Straub tail response may be a novel behavioral index of stress-induced endorphin release.

Animals

A reexamination of apomorphine induced stereotypy in the rat in light of self administration experiments.

1. Apomorphine is known to both elicit stereotypy and to support behavioral self administration. The present report examined a possible contribution of stereotypy to self administration. 2. Non-contingent intraperitoneal injection of apomorphine in adult male Sprague-Dawley rats immediately prior to their placement in an experimental chamber significantly elevated barpressing above operant rates. 3. This indicates a novel dopamine induced behavior which may play a role in determining self administration behavior. 4. The data suggest three interpretations of previous self administration experiments.

Animals

Enkephalin-dopamine interactions in behavioral arousal.

1. Central injection of a long lasting enkephalin analog (D-Ala2-leu-enkephalin-amide) produced a syndrome of stereotyped motor activity. 2. This activation syndrome was significantly reduced by two dopamine (DA) blockers (pimozide, fluspririlene) and by an agonist of inhibition-mediating DA receptors [(3,4-dihydroxyphenylamino)-2-imidazoline]. 3. Intact DA functioning is necessary for the occurrence of this enkephalin-mediated behavioral syndrome.

Animals

Serotonergic mediation of reward within the medial raphe nucleus: some persistent problems in interpretation.

Adult male Sprague Dawley rats were implanted with unipolar stimulating electrodes aimed at the medial forebrain bundle (MFB) or the medial raphe nucleus (MR). All MFB implanted subjects self-stimulated at high stable rates for at least three weeks. Only a minority (1/3) of MR rats self-stimulated at all. Rates for the MR group were considerably more variable, and could not be maintained for more than two weeks. Treatment with methysergide increased MFB self-stimulation but decreased MR self-stimulation. While this result suggests serotonergic mediation of self-stimulation this conclusion must be interpreted cautiously since parachlorophenylalanine (PCPA) reinstated self-stimulation in raphe animals which had spontaneously ceased responding.

Animals