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D Malec

Publications and source records attributed to D Malec.

At least 19 recordsLinked to original sources

A closer look at combining data among a small number of binomial experiments.

In a regulatory environment, the regulators and the regulated may not be able to agree on the use of subjective prior information for a clinical trial. The use of a data-based prior offers a greater possibility for agreement, however, the degree of importance given to the prior data may still be contentious. The use of a hierarchical model to link the prior data and the current trial is shown to provide a relatively objective method for assigning weight to the prior data. Using a series of examples combining two binomial experiments, the effect of a hierarchical model on estimating rates, on the degree to which data is combined and on hypothesis testing is illustrated. In addition, the phenomenon in which combining data reduces the precision is explained. Simpler models based on finite mixtures of beta distributions are shown to work as well as the more computationally intensive, continuous mixtures. Lastly, an example combining three concurrent studies is illustrated. Published in 2001 by John Wiley & Sons, Ltd.

Bayes Theorem↗

Model-based small area estimates of overweight prevalence using sample selection adjustment.

Using a hierarchical model with an adjustment for sample selection, we estimate the overweight prevalence for adults, by states, using data from the Third National Health and Nutrition Examination Survey (NHANES III). A two-stage hierarchical model was selected to account for geographic variability of outcomes and to model possible overdispersion of estimates due to cluster sampling. We compare our model-based estimates with design-based estimates at the national level and obtain excellent agreement. We also provide a check of our model at the state level by comparing estimates with design-based and synthetic estimates.

Adult↗

Chemical and pharmacological properties of new tetrahydropyrimido-[2,1-f]-purines.

Following a research program on piperazinoalkyl-substituted tricyclic purines, a number of N-9-aryl(alkyl)-piperazinopropyl substituted tetrahydropyrimido-[2,1-f]-purines were synthesized and tested pharmacologically with respect to their influence on the central nervous system. Two of the new compounds induced hypothermia and decreased the spontaneous locomotor activity of mice.

Amphetamine↗

Bayesian predictive inference for units with small sample sizes. The case of binary random variables.

The National Health Interview Survey is designed to produce precise estimates for the entire United States but not for individual states. In this study, Bayesian predictive inference is used to provide point estimates and measures of variability for the desired finite population quantities. The investigation reported here concerns binary random variables such as the occurrence of at least one doctor visit within the past 12 months. The specification is hierarchic. First, for each cluster, there is a separate logistic regression relating a patient's probability of a doctor visit with his or her characteristics. Second, there is a multivariate linear regression linking the (cluster) regression parameters to covariates measured at the cluster level. A fully Bayesian analysis is carried out; this technique provides gains over synthetic estimation and conventional randomization-based analysis. The reported approach is potentially useful for any situation when the sample size associated with a unit of interest (e.g., a hospital or small geographic area) is too small to permit satisfactory inference using only the data from that unit.

Bayes Theorem↗

[Adenosine and its neuronal receptors].

The recent data about biosynthesis, localization, metabolism and biological activity of adenosine is presented. Presumable role of adenosine as a neuromodulator is also discussed.

Adenine Nucleotides↗

Cross-tolerance between morphine and ethanol and their antinociceptive effects.

Morphinization of mice (37.5 mg morphine) and rats (75 mg) with subcutaneously implanted pellets has resulted in tolerance to the antinociceptive effect of morphine, measured in the tail-immersion test. All animals also developed cross-tolerance to the analgesic effects of ethanol (2.8 g/kg intraperitoneally for mice, per os for rats). These results suggest a commonality between morphine and ethanol antinociceptive action.

Analgesics↗

The effect of antihistaminics on cataleptogenic action of analgesics and haloperidol.

We investigated the effect of benzhydramine, thenalidine, mepyramine (H1 receptor antagonists) and cimetidine (H2 receptor antagonist) on cataleptogenic action of morphine, codeine, fentanyl, and haloperidol. Benzhydramine antagonized the catalepsy induced by analgesics (particularly by codeine). The antagonistic effect of thenalidine was weaker (but also very prominent for codeine catalepsy). Mepyramine did not affect the catalepsy induced by analgesics. All three H1 receptor antagonists attenuated the catalepsy induced by haloperidol. Cimetidine, injected intraventricularly, did not affect the catalepsy induced either by analgesics or by haloperidol. It is suggested that the antagonistic action of benzhydramine and thenalidine against analgesic catalepsy is related rather to their antiserotonin properties, while the anticataleptic activity of all three H1 receptor antagonists against haloperidol catalepsy is caused by their anticholinergic and antiserotonin properties.

Analgesics↗

Cholinergic influences on opioids activity in rats.

The influence of cholinergic and anticholinergic agents on the catalepsy and antinociceptive action of morphine, codeine, fentanyl and pentazocine was studied in rats. Anticholinergic drugs scopolamine (3 and 6 mg/kg) and slightly atropine (1 mg/kg) enhanced morphine-induced catalepsy. Benztropine did not change this action of morphine. Cholinergic physostigmine (0.2 and 0.4 mg/kg) showed marked and dose-dependent antagonism toward morphine catalepsy, but pilocarpine, in doses of 2 and 4 mg/kg, failed to influence it. Catalepsy induced by codeine and fentanyl was nearly not influenced by cholinergic and anticholinergic agents. In the hot plate test, cholinergic influences on antinociceptive activity of analgesics are slight, but sometimes it may be observed the similar interaction as in morphine catalepsy: anticholinergic agents enhance, and cholinergic agents antagonize these effects. Present results indicate that some cholinergic and anticholinergic agents influence morphine catalepsy, and this influence is opposite to that observed in neuroleptic-induced catalepsy. Failure of the cholinergic influences on fentanyl- and codeine-induced catalepsy suggests that the mechanisms of cataleptogenic activity of morphine and other analgesics are not the same.

Analgesia↗

Central action of narcotic analgesics. VIII. The effect of dopaminergic stimulants on the action of analgesics in rats.

We investigated the influence of apomorphine, amphetamine, amantadine, dimethylaminoadamantane, nomifensine, ergometrine and beta-phenylethylamine on cataleptogenic and antinociceptive action of analgesics in rats. Nomifensine, apomorphine, beta-phenylethylamine, amantadine and ergometrine antagonized the catalepsy induced by morphine and codeine. Catalepsy induced by fentanyl was depressed only by nomifensine and apomorphine. Amphetamine only slightly antagonized the analgesic-induced catalepsy and the effects were not dose-dependent. Dimethylaminoadamantane did not antagonize catalepsy at all. Antinociceptive action of morphine and codeine was antagonized by apomorphine and amphetamine. Ergometrine counteracted the action of morphine, and beta-phenylethylamine decreased the action of pentazocine. The results suggest that: 1. There are differences in the mechanism of cataleptogenic action of the opiates (morphine and codeine) and fentanyl; 2. Catalepsy after analgesia differs from the catalepsy produced by neuroleptics in respect of interaction with such drugs as amphetamine, apomorphine or dimethylaminoadamantane. Analgesic-induced catalepsy seems to depend on the presynaptic inhibition of dopaminergic neurotransmission; 3. Stimulation of the central dopaminergic system in rat brain either does not change or weakly antagonizes the action of analgesics in the hot plate test.

Amphetamine↗

The influence of 5-HT receptor blocking agents on the behavioral effects of analgesics in rats.

The influence of methergoline, methysergide, mianserine, cyproheptadine, and pizotifen on catalepsy induced by morphine, codeine, and fentanyl, and antinociception induced by these three drugs and by pentazocine was studied in rats. Methergoline dose-dependently reduced catalepsy induced by these three drugs. Methysergide abolished only morphine catalepsy, while mianserine significantly reduced the effect of morphine and codeine. Cyprohepatide and pizotifen did not modify the cataleptic effect of the three analgesics used. Antinociceptive action of morphine, codeine, fentanyl, and pentazocine, measured by the hot plate method, was not influenced or changed differentially by any serotonin receptor blocking compounds. One may conclude that catalepsy induced by morphine is, in general, antagonized by serotonin receptor blockade, but this does not concern all narcotic analgesics. In the antinociceptive effects of drugs used, the serotonergic influence seems to play a less important role than in catalepsy.

Analgesics↗

The role of serotonin in ephedrine-induced stereotypy and hypermotility.

The influence of serotonin agents on stereotypy and hypermotility induced with ephedrine was studied. P-Chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, had no influence on stereotypy. In reserpinized animals, this reaction was intensified only after high doses of ephedrine (100 and 120 mg/kg), but the precursor of 5-HT synthesis, tryptophan, strongly antagonized stereotypy. Ephedrine-induced hypermotility in mice and rats was potentiated by PCPA. It is suggested that serotonin ephedrine-induced effects, similarly to previous observations with amphetamine.

Animals↗

The role of 5-HT in the mechanism of amphetamine action.

AM stereotypy-inducing action was potentiated in rats in proportion to the previously administered doses of pCPA (3 X 100, 3 X 150 or 3 X 200 mg/kg); however, the dose of 3 X 300 mg/kg pCPA brought about the decrease in stereotypy. Reserpinized rats exhibited also increased AM stereotypy but of shorter duration. AM hyperactivity in mice was potentiated also by the pretreatment with pCPA but this action occurred within a further phase of observation (30 min after the injection). It seems then that 5-HT may be a factor suppressing the stimulating action of AM.

Amphetamine↗