Information-seeking behaviors of medical students: a classification of questions asked of librarians and physicians.

To solve a problem, a person often asks questions of someone with more expertise. This paper reports on a study of the types of questions asked and how the experts are chosen. In the study, sixty-three first-year medical students responded to clinical scenarios, each describing a patient affected by a toxin and asking questions concerning the identity of the toxin and its characteristics. After answering those questions, the students were asked to imagine that they had access to a medical reference librarian and an internist specializing in toxicology. The students then generated two questions for each expert about each clinical scenario. Each question was categorized according to the type of information requested, and the frequency of each type of question was calculated. The study found that students most often asked for the identification of the toxin(s), references about the scenario, or the effects of the toxin; an explanation of the patient's symptoms; or a description of the appropriate treatment. Students were more likely to address questions on the identity of the toxin and references to the hypothetical librarian; they were more likely to ask the internist for explanations of the symptoms and descriptions of the treatment. The implications of these results for the design of information and educational systems are discussed.

Preparing for the twenty-first century: report of the TOX-90's Commission. Planning Committee.

A clear consensus developed that toxicology will be driven by advances in related fields. New technology and knowledge developed by all relevant disciplines, therefore, must be integrated into toxicology; progress in toxicology demands that the discipline must increasingly address good science and the scientific method. Issues of critical importance to the field, such as risk estimation of the health effects of chemical and physical agents and the education of toxicologists, can only be addressed by meeting these objectives.

Dose-related alterations in growth and mineral disposition by chronic oral cadmium administration in the male rat.

The effect of cadmium (1, 10, or 100 ppm) administered to male rats in drinking water for 13 weeks on body weight and mineral disposition (Cd, Mg, P and Zn) in several body tissues was examined. Most alterations observed in these parameters occurred only at the 100 ppm dose of Cd. Terminal body weight was decreased by 10% in rats ingesting Cd at 100 ppm resulting from decreased food intake since weight gain/food consumption ratio was the same for all treatment groups. In serum, cadmium ingestion resulted in an inhibition of alkaline phosphatase activity at all concentrations and phosphorous was elevated only in animals receiving 100 ppm Cd. No changes were observed in Ca in urea. In bone, Cd decreased zinc content, increased Ca content, but did not influence bone ash, Mg or P and roentgenographic examination revealed no bone abnormalities. In both liver and kidney, cadmium ingestion did not influence intestinal absorption of Ca, Mg, P, or Zn or the renal excretion of Ca, P, or urea. The results of this study indicate that alterations in body weight and tissue mineral disposition resulting from chronic Cd ingestion are dose-related.

Effect of acute and chronic cadmium treatment on hepatic drug metabolism in male rats.

The effect of acute and chronic cadmium administration on hepatic drug metabolism was investigated in the male rat. 3 days after the acute administration of cadmium by either the intraperitoneal (0.84 mg Cd/kg) or the oral (greater than 80 mg Cd/kg) route, there was a significant potentiation in duration of hexobarbital hypnosis and inhibition of hepatic microsomal metabolism of hexobarbital and aniline. Administration of cadmium in the drinking water at levels of 100 or 200 ppm Cd for periods of 2--12 weeks or at levels of 5 or 20 ppm Cd for 50 weeks did not produce alterations in either drug response or hepatitic drug metabolism. Significant levels of metallothionein, a cadmium binding protein, found in the liver of the rats receiving cadmium chronically may offer an explanation for the observed differences in drug metabolism between the acute and chronic administration of cadmium. In additional studies, pretreatment of the rats with subthreshold doses of cadmium (0.21 or 0.42 mg Cd/kg) intraperitoneally produced a tolerance to the alterations in drug metabolism induced by the previous cadmium dose (0.84 mg Cd/kg, i.p.). However, chronic cadmium treatment (5 or 20 ppm Cd for 50 weeks) did not impart any such tolerance to subsequently administered Cd (0.84 mg/kg) by the intraperitoneal route. The hepatic levels of metallothionein induced by the chronic cadmium treatment were only 30--60% of those induced by the subthreshold cadmium and thus may not have bound enough of the large challenge cadmium dose to produce the tolerance phenomenon.

Tolerance development to cadmium-induced alteration of drug action.

Cadmium administration potentiates the duration of hexobarbital-induced hypnosis and inhibits the rate of hepatic microsomal metabolism of this drug in the male rat. The threshold dose of cadmium required to produce these alterations in drug action is 0.84 mg Ck/kg. If subthreshold doses of cadmium (0.21 or 0.42 mg Cd/kg) are administered prior to the 0.84 mg Cd/kg dose, the cadmium-induced alterations in drug action are no longer observed.

Some steric factors affecting smooth muscle relaxation by cAMP analogs.

The inhibitory potency of equimolar concentrations of cyclic adenosine monophosphate (cAMP) and three of its butyrylated derivatives; N6, O2'-dibutyryl cAMP (DBcAMP), N6-monobutyryl cAMP (N6MBcAMP) and O2' monobutyryl cAMP (O2' MBcAMP) was determined in isolated guinea pig ileal and aortic smooth muscle. Substitution in the N6 position did not markedly alter the inhibitory action of cAMP in these smooth muscles. However, an increase in the effectiveness of low concentrations of epinephrine in aorta was noted in the presence of the N6 substituted derivatives (0.1 mM). Addition of a butyryl group to the O2' position greatly decreased the activity of cAMP in both intestinal and vascular smooth muscle. The character of smooth muscle relaxation shown by cAMP and its analogs is very similar to that shown by adenosine and its analogs. These substances all appear to be acting in the same manner to relax intestinal and aortic smooth muscle.

Circadian rhythms in drug action and drug metabolism in the mouse.

The relationship between circadian rhythms in the pharmacological actions of meperidine and hexobarbital and similar rhythms in the hepatic metabolism of these drugs was examined in mice under a variety of environmental alterations to determine whether such rhythms may be causally related. The rate of metabolism of p-nitroanisole and hexobarbital by hepatic 9000 X g supernatant fractions was found to be higher at 2400 hours (middark phase) compared to 1200 hours (midlight phase). The rhythms in in vitro hexobarbital and in vivo merperidine metabolism were inversely related in time with similar rhythms in duration of hexobarbital sleep time and meperidine analgesia. Exposure of mice to continuous lighting abolished the rhythms in metabolism and response to meperidine and hexobarbital. Reversal of the usual lighting cycle inverted the rhythm in hexobarbital metablism while abolishing the rhythm in pharmacological response to hexobarbital; meperidine was similarly affected. Adrenalectomy abolished the rhythm in hexobarbital metabolism, diminished the amplitude of the circadian variation in meperidine metabolism and abolished the rhythm in hexobarbital hypnosis and meperidine analgesia. These results indicate that circadian rhythms in the action of hexobarbital and meperidine are well correlated with similar rhythms in the disposition of these drugs.