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Biomedical subjects

K M Kumor

Publications and source records attributed to K M Kumor.

At least 19 recordsLinked to original sources
PubMed1997

A basic compositional requirement of agents having heparin-like cell-modulating activities.

Heparin has been recognized as possessing a large variety of cell-modulating activities. Using compositionally simple, structurally rigid, and low molecular weight saccharide molecules (cyclodextrins), we demonstrated that these activities depend primarily on a single, gross compositional parameter: a minimum intramolecular density of neighboring anionic (sulfate) groups. This same critical parameter is shown to be involved in achieving cell-modulating behavior as diverse as angiogenesis, endothelial proliferation, inhibition of smooth muscle cell growth, and cell protection against virus invasion. Physical chemical evidence is presented that associates this property with multi-ionic complex formation between the clusters of anionic and cationic sites on the complexing partners. These observations revive early suggestions of the decisive role of electrostatic complexation capabilities of glycosaminoglycans like heparin; taken together with numerous observations on heparinoids and other agents reported in diverse specialized fields of cell biology and medicine, they provide evidence that molecular agents of critical anionic (sulfate) density (MACADs) represent a broad class of molecules that, in contrast to proteins, do not rely on structural detail for their cell biological activities, but function by ionic complexation with proteinic agents (e.g. growth factors), thereby modifying their structure-specific activities.

Alcian Blue↗
PubMed1994

Impulsiveness and subjective effects of intravenous cocaine administration in the laboratory.

Cardiovascular and subjective responses to placebo and 40-mg intravenous (iv) cocaine injections were measured in 29 male iv cocaine users: most subjects received each of these injections on two separate occasions. Most of the subjects also completed various measures of psychopathology and personality. Although the small sample size made any conclusions tentative, an expected significant association between impulsivity and subjective euphoria following 40-mg cocaine administration was obtained, whereas associations of personality measures with cardiovascular responses to cocaine administration were inconsistent.

Adult↗
PubMed1992

Test-retest stability of cardiovascular and subjective responses to intravenous cocaine in humans.

Sixteen male i.v. cocaine users were measured on their cardiovascular and subjective responses to placebo followed on a separate day by 40 mg i.v. cocaine injections. They were retested within 2 weeks, again receiving placebo and 40 mg i.v. cocaine injections in a random order on separate days. Significant increases in baseline (pre-injection) heart rates during the later sessions were interpreted as possibly reflecting conditioning effects. There were no significant differences in post-injection increases in cardiovascular or subjective responses between the initial and later 40 mg conditions, which might have been indicative of tolerance or sensitization development. Test-retest correlations, indicative of response stability, were moderate to high for any particular timepoint for blood pressure, heart rate, and subjective responses, but pre- vs. post-injection change scores were stable across testings on these measures only under placebo. With the possible exception of some subjective responses, there was little evidence of test-retest stability in responses (change scores) to the 40 mg cocaine injection.

Adult↗
PubMed1991

Effects of nifedipine pretreatment on subjective and cardiovascular responses to intravenous cocaine in humans.

The effects of oral nifedipine pretreatment on subjective and cardiovascular responses to intravenous cocaine infusions were studied in cocaine-using volunteers. Nifedipine, 10 mg or placebo, was administered 20-25 min before placebo, 20 mg, or 40 mg cocaine, using a repeated measures randomized double-blind design. The variables measured were self-reported subjective effects, general behavior rated by two observers, blood pressure and heart rate. Cocaine produced the expected dose-related effects on subjective and cardiovascular measures. Nifedipine pretreatment attenuated some subjective effects of cocaine. Nifedipine directly reduced blood pressure but did not antagonize the effects of cocaine on blood pressure. These findings suggest that dihydropyridine calcium channel modulators may be useful compounds in the clinical management of cocaine users.

Adult↗
PubMed1991

A pharmacokinetic-pharmacodynamic model of heart rate during cocaine administration in humans.

We developed a pharmacokinetic-pharmacodynamic model of the heart rate response to cocaine consisting of the sum of the baseline heart rate, a chronotropic drug effect, and a conditioned heart rate response. The conditioned response was modeled as having a monoexponential decline. Cocaine's chronotropic effect was modeled as obeying a maximum (Emax) drug-effect relationship without tachyphylaxis. The model was tested by fitting the kinetic and heart rate data from an earlier study. The data from five subjects in that study were well fit by the model: mean Emax, 64 beats/min, and mean drug concentration producing 50% of Emax, 838 ng cocaine/ml. The data from the other three subjects in that study were fit well, employing a linear rather than an Emax drug effect relationship: mean effect coefficient, 0.035 beats/min/ng cocaine/ml. The findings emphasize the importance of conditioning in the responses to psychoactive drugs.

Cocaine↗
PubMed1990

Multidimensional scaling of subjective judgements of drug similarities among ketocyclazocine, morphine, cyclazocine, naloxone and placebo.

Profiles of the subjective and physiologic effects of opioid drugs in man cannot be assigned with precision to specific opioid drug-receptor interactions. We administered a set of training doses of ketocyclazocine, morphine, cyclazocine, naloxone and placebo to 10 drug-using volunteers and obtained similarity judgements between each of 2 test doses of the drugs and a training dose. These data were submitted to multidimensional scaling analysis (INDSCAL) using both neighboring cells estimates and root mean square estimates to estimate missing cells in the data matrices. The results of these analyses are convergent, appear valid and indicate that there are three drug dimensions expressed in this data set: morphine versus placebo and naloxone; cyclazocine and ketocyclazocine versus placebo and naloxone; and ketocyclazocine versus cyclazocine. We interpret this result as supporting evidence that in the set of five drugs studied, three subjective states are induced.

Adult↗
PubMed1989

Cardiovascular responses to cocaine placebo in humans: a preliminary report.

Cardiovascular responses after placebo-cocaine injections were in the same direction as the effect of cocaine iv in 22 male volunteers. Subjects received iv placebo in a room where they had been given repeated doses of iv cocaine. The placebo response consisted of an increase from baseline values of systolic and diastolic blood pressure and pulse rate. The control group, 8 subjects, which was not exposed to a conditioning phase, showed a smaller increase in the pulse rate and systolic blood pressure after the placebo injection. The results, in accordance with animal literature, suggest the existence of cocaine-conditioned effects in humans.

Adult↗
PubMed1989

Placebo responses to cocaine administration in humans: effects of prior administrations and verbal instructions.

Subjective and physiological responses of eight male cocaine-using research volunteers were studied after a double-blind saline infusion (placebo) was given when subjects were instructed that a cocaine infusion might be given. Cardiovascular and subjective responses to placebo were similar in pattern and direction, though of lesser magnitude, than after a 40 mg cocaine infusion. These placebo responses were compared to responses after an earlier saline infusion condition in which subjects were instructed prior to the infusion that they would receive saline (instructed placebo). The design was thus meant to test for the effects of instructions on placebo responses to cocaine. Heart rates at baseline (pre-infusion) were significantly higher in the placebo than in the instructed placebo condition. Similar trends were found for elevated baseline placebo responses on two subjective effects measures. A comparison with an initial placebo session prior to the placebo and instructed placebo conditions described above provided evidence for conditioning of placebo responses on diastolic blood pressure and heart rate. The present results suggest that verbal instructions, as well as conditioning in the laboratory, could contribute to the observed placebo responses to cocaine infusions.

Adult↗
PubMed1989

Cocaine-induced cocaine craving.

In nine experienced users of cocaine, we examined the urge to use cocaine or other drugs following a 40 mg dose of intravenous (IV) cocaine with and without oral pretreatment with 2.5 mg bromocriptine. The urge to use cocaine was assessed with a questionnaire constructed to assess both "wanting" and "craving" for cocaine or other drugs. Fifteen minutes after the administration of cocaine (but not after placebo), subjects' ratings for both drug "wanting" and drug "craving" were significantly increased. Our results provide a laboratory demonstration of cocaine-induced increases in the urge to use drugs in humans. The findings, stressing the role of internal stimuli associated with drug administration, suggest the possibility of distinguishing among related, but perhaps distinct, components of the fluctuating levels of motivation to reuse drugs.

Adult↗
PubMed1989

Intravenous cocaine infusions in humans: dose responsivity and correlations of cardiovascular vs. subjective effects.

Eight experienced IV cocaine users were intravenously administered 0, 10, 20, and 40 mg of cocaine hydrochloride on separate days in a pseudo-randomized ascending dose series, such that the 20 mg dose always preceded the 40 mg dose. They were subsequently administered 0, 20, and 40 mg of cocaine in a fully randomized presentation order. Cardiovascular effects of cocaine were significantly different from placebo for the 20 mg, but not the 10 mg dose, in contrast to subjective responses which differed from placebo for the 10 mg dose. Cardiovascular and subjective effects of cocaine did not differ between the 20 and 40 mg dose conditions for the pseudo-randomized trials, but did differ in the fully randomized trials. This lack of difference in responsivity between the 20 and 40 mg dose in the earlier trials may possibly have been due to contrast effects. Cardiovascular responses were not consistently correlated with subjective responses, either within a cocaine dose condition or across doses.

Adult↗
PubMed1989

Subjective response during continuous infusion of cocaine.

The relationship between the subjective effects induced by IV cocaine injection(s) and cocaine plasma concentrations is complex and difficult to interpret. We designed a study in which bolus loading doses of cocaine followed by 4-hr placebo infusions were compared with the same bolus loading doses of cocaine followed by 4-hr infusions of cocaine calculated to maintain the peak plasma concentrations produced by the bolus. Seven cocaine-using volunteers were successfully studied using a randomized double-blind design, in which self- and observer-rating scales were used to measure drug effects. After the cocaine bolus loading doses, scores for most subjective measures remained elevated when the bolus was followed by a cocaine infusion. In contrast, the subjective responses returned to baseline when the bolus was followed by a placebo infusion. However, self-estimates of the intensity of the cocaine "rush" were not altered by the presence of active cocaine infusions and returned rapidly to baseline.

Adult↗
PubMed1989

Effects of intravenous cocaine are partially attenuated by haloperidol.

We examined the effect of the dopaminergic blocking agent, haloperidol, on the subjective and physiologic response to cocaine in cocaine-using volunteers. Five subjects received cocaine (40 mg) or placebo administered intravenously 20 min following pretreatment with haloperidol (8 mg) or placebo intramuscularly in a randomized double-blind study design. Haloperidol pretreatment attenuated cocaine-induced increases in systolic and diastolic blood pressure but not heart rate. Pretreatment with haloperidol reduced subject ratings of pleasant sensations but had no effect on drug "rush." Haloperidol (8 mg) has a small and limited effect on the subjective response to cocaine when given 20 min before cocaine.

Adult↗
PubMed1988

Suspiciousness induced by four-hour intravenous infusions of cocaine. Preliminary findings.

Cocaine hydrochloride was administered to experienced users as an intravenous (IV) loading dose of 40 to 80 mg, followed by four-hour continuous IV infusions of either cocaine or placebo. Rates of cocaine infusion were individualized to maintain steady-state cocaine concentrations for the duration of the infusion. During the infusions, subjects rated themselves on questions that assessed their suspiciousness and paranoia, and nurse-observers took descriptive notes on the subjects' behavior; these notes were later scored on a scale for guarded, suspicious, and paranoid behavior. Nurses observed and rated moderately suspicious behavior when cocaine IV bolus loading doses were followed by cocaine infusions, but not when loading doses were followed by saline solution infusions; subjects did not rate themselves as suspicious during any of the study conditions. Suspiciousness during low-dose cocaine infusions significantly correlated with the amount of cocaine previously administered to the subjects. Suspiciousness during infusions was not related to plasma cocaine concentrations, preadmission drug use, or psychiatric symptoms and history. Cocaine infusions may be a useful tool to pursue the biology of stimulant psychoses.

Adult↗
PubMed1988

The psychopharmacologic and prolactin response after large doses of naloxone in man.

Large doses of naloxone (150-300 mg), placebo, and morphine (15-30 mg) were given intramuscularly to human volunteers and compared using measures of subjective feeling states, physiological measures and discriminative features. Plasma prolactin responses after naloxone 210 mg and placebo were compared. The subjective measures and discriminative features of naloxone revealed that the drug is subtly psychoactive but the stimulus is vague and cannot be identified clearly as an opioid agonist or antagonist in nondependent opioid-using volunteers. The physiologic and prolactin responses closely resembled opiate agonist activity. We conclude that naloxone in this dose range may act as an opiate agonist in man.

Adult↗
PubMed1987

Unusual opioid withdrawal syndrome. A case-report.

In a patient with advanced cancer, neurosurgery relieved severe pain that had been uncontrolled by very high doses of opioids. On reduction of opioid dosage he had visual and auditory hallucinations and showed deterioration of consciousness progressing to coma. Naloxone worsened his mental state whereas morphine restored it to normal. This syndrome may be related to opioid withdrawal at receptors other than the mu receptors that have been linked to analgesia and drug abuse.

Aged↗
PubMed1986

Human psychopharmacology of ketocyclazocine as compared with cyclazocine, morphine and placebo.

The activity of ketocyclazocine, a putative kappa opioid receptor agonist, was studied and compared with that of morphine, a mu opioid receptor agonist, and cyclazocine, a putative kappa and sigma opioid receptor agonist, vs. placebo in 10 drug abusers. The measures included vital signs and pupil measurements, established and new observer- and subject-completed psychopharmacologic questionnaires and several methods of drug discrimination. The results indicate that ketocyclazocine is different from morphine-like agonists in that it produces only minimal miosis and lacks euphoriant action. It causes a dysphoric state and was clearly discriminated from morphine. The dysphoria and pattern of responses was similar to cyclazocine though ketocyclazocine was discriminated from cyclazocine. This is consistent with the concept that morphine and ketocyclazocine have separate modes of primary activity. The similarity between ketocyclazocine and cyclazocine obscures the assignment of particular drug effects to activity at the kappa receptor.

Adult↗