Verifying the curriculum of a family medicine clerkship.

The learning experience during a medical school clinical rotation is largely shaped by students' patient encounters. This paper reports on how a log system for recording these encounters can be used for course planning and evaluation. Over the past 5 years, 960 third-year students completed log forms based on their clinical encounters during a required 4-week family medicine clerkship at UT Southwestern. These forms were then optically scanned and the information entered into a computerized database. Log form data revealed that the most common medical problems encountered by students in their ambulatory settings were similar to those reported in the general family practice literature. There was a great deal of consistency in the types of encounters from year to year. The data also showed some differences among clerkship sites in terms of patient demographics and the most frequently reported diagnoses. Information generated from student log forms has been used by the clerkship faculty to determine required readings, prioritize didactic topics and other teaching, adjust curriculum content, prepare support materials and develop examinations. Given the utility of the information obtained and the ease of use of optical mark encounter sheets, we recommend this system for other clerkships.

Computerized performance support systems: applications in a family practice clerkship.

This article describes a computerized performance support system, the Clerkship Learning Expert and Resource Consultant (CLERC), developed to improve the quality and consistency of learning available to medical students in a third-year family practice clerkship. CLERC is an integrated computer system with an interactive knowledge base, software applications, literature search capabilities, and clinical diagnostic software programs. Medical students enrolled in a third-year family practice clerkship use CLERC to access up-to-date clinical information and to complete clerkship assignments.

Developing a support system for teaching and assessing clinical competence.

Primary care medical school faculty, in partnership with the faculty and staff of a Department of Biomedical Communications (Office of Medical Education) developed a teaching and logistical support system using standardized patients. The patients are used to teach history and physical examination skills to students in an introductory clinical medicine course. Having both clinical assessment team members, who are skilled biomedical communicators, and designated clinic rooms for standardized patients provides the foundation necessary for this growing area in medical education. Improved student performance, as measured by an Objective Structured Clinical Examination (OSCE), and students' positive ratings and comments in the evaluation of the course demonstrated the efficacy of using standardized patients in teaching and assessing clinical performance.

Local anesthetic effects of cocaine and several extracts of the coca leaf (E. coca).

Cocaine and a number of different fractions of a crude ethanol extract of the coca leaf (E. coca) were subjected to a local anesthetic screen using rat tail withdrawal from electric shock. Following an intradermal injection of 0.1 ml of a 2.0% (w.v) solution of cocaine HCl, an immediate response was observed. Two of the coca fractions also produced some local anesthesia. An alkaloidal fraction, containing an equivalent amount of cocaine, produced a maximum effect that was approximately 20% less than that observed with cocaine. The only other fraction producing any effect, a water soluble cocaine-free fraction, showed a maximum response that was approximately 30% of that observed with cocaine.

The effects of several anorexigenics on monkey social behavior.

The effects of fenfluramine HCl, diethylpropion HCl, and methylphenidate HCl on social behavior were studied in a heterosexual group of stumptailed monkeys (M. arctoides). Subjects were treated concurrently (i.e., every monkey received the same treatment on a given day). The range of doses studied was: fenfluramine (1.0-10 mg/kg), methylphenidate (1.0-5.0 mg/kg), and diethylpropion (2.0-20 mg/kg). In general most drug/dose combinations produced decreases in social interactions. However, there was one notable exception; presenting was dramatically increased following dosing with methylphenidate and diethylpropion. Some of the solitary behaviors recorded were also observed to increase, notably, vocalization and self-grooming, which at the higher doses of diethylpropion and methylphenidate took the form of intensely idiosyncratic stereotypies. Finally, food consumption was observed to decrease in some subjects (more dominant) and increase in others (less dominant) indicating that social variables may interact with pharmacological variables.

Metabolism and distribution of primaquine in monkeys.

Rhesus monkeys were administered primaquine diphosphate (6.0 to 10.5 mg/kg, I.V.), and plasma samples were analyzed by high performance liquid chromatography for the presence of the unchanged drug and the major metabolite , 8-(3-carboxy-l-methylpropylamino)-6-methoxyquinoline (II). Primaquine had an unusually high affinity for tissue compartments which produced a rapid initial drop in plasma concentration. Within 15 minutes, the plasma concentration of II far exceeded that of primaquine. 35 to 83 % of the primaquine dose was converted to II; moreover, metabolite II possessed much lower affinity for the tissue compartments than primaquine itself.

Pharmacological manipulation of sincalide (CCK-8)-induced suppression of feeding.

The current study involves an investigation of the possible neurotransmitter systems involved in the ability of exogenously administered sincalide (cholecystokinin octapeptide, CCK-8) to suppress feeding. Male rats previously trained to obtain food either during a daily 3-hr session, or conditioned to obtain food pellets on a fixed-ratio or fixed-interval schedule of reinforcement, were treated IP with CCK-8, following pretreatment with representative drugs of several pharmacological classes. Pretreatment with phenoxybenzamine, tolazoline, yohimbine, morphine, haloperidol or picrotoxin reduced the efficacy of CCK-8. However, pretreatment with naloxone or clonidine potentiated the suppressant action of CCK-8 on feeding. Propranolol, diphenhydramine, cimetidine, atropine, d-amphetamine, fenfluramine or diazepam pretreatment either had no effect or no consistent action in altering the activity of CCK-8. The ability of CCK-8 to suppress feeding was not altered by subacute treatment with the anorectics, d-amphetamine or fenfluramine, using a regimen known to induce tolerance. These data indicate that CCK-8 exerts a different mechanism of action than that of fenfluramine or d-amphetamine, and furthermore, that noradrenergic, dopaminergic, GABAergic or endogenous opioid systems either mediate or can modify the effect of CCK-8 on feeding.

Comparative lethality of coca and cocaine.

The 24 hour lethal effects of cocaine were compared to those of a crude ethanol extract of the coca leaf (Erthroxylon coca) in male, Swiss mice. Various doses of cocaine HCl and coca leaf extracts suspended in a Tween 60, Arlacel 83, and distilled water vehicle were injected IP into groups of 10 mice. The LD50 for cocaine was 95.1 mg/kg. The LD50 for the coca extract was 3450 mg/kg. The LD50 of the extract based on its cocaine content was 31.4 mg/kg. The results clearly indicate that the coca leaf contains constituents other than cocaine that can contribute to a toxic effect of the plant.

Comparative stimulus properties of two fractions of the coca leaf (E. coca).

Male and female Wistar rats were trained to discriminate 5.0 mg/kg cocaine from 2.0 ml/kg saline using a two-bar food reinforcement (FR 30) drug discrimination paradigm. Once discrimination behavior had stabilized the subjects were tested (in extinction) with several doses of two different fractions of the coca leaf and four doses of cocaine HCl (1.0, 2.5, 7.5, 10 mg/kg). The fractions were prepared by extracting powdered coca leaves with 95% ethanol and then partitioning the residue between chloroform and water. Two doses of the water fractions (480, 960 mg/kg) and five doses of the chloroform fraction (7.5, 15, 30, 60 120 mg/kg) were tested. The water fractions was devoid of cocaine while the five doses of the chloroform fraction contained cocaine equivalent to 0.4, 0.83, 1.65, 3.3 and 6.6 mg/kg, respectively, as determined by gas chromatographic analysis. The 2.5, 7.5, and 10.0 mg/kg cocaine doses generalized to cocaine. The 1.0 mg/kg dose of cocaine generalized to saline. The water fraction at 480 mg/kg generalized to saline; however following pretreatment with the 960 mg/kg dose of this fraction, the animals failed to respond. The two largest doses of the chloroform fraction (60 and 120 mg/kg) generalized to cocaine while the other three doses did not. The 7.5 mg/kg generalized to saline; the 15 and 30 mg/kg doses engendered an intermediate level of responding on both the cocaine and saline lever.

Determination of cannabidiol in plasma by electron-capture gas chromatography.

A procedure was developed for the analysis of cannabidiol (CBD) in blood plasma. Tetrahydrocannabidiol was used as an internal standard and was added prior to extraction. The plasma extracts were derivatized with pentafluorobenzyl bromide and the produce purified on a mini-column of Florisil. The pentafluorobenzyl derivatives were then analyzed by gas chromatography on a 5% OV-225 column using an electron-capture detector. A detection limit of 50 ng CBD per ml of plasma was observed. The procedure was used to study the plasma level of CBD after its oral and intravenous administration to monkeys.

Discriminative stimulus properties of cocaine, norcocaine, and N-allylnorcocaine.

A discriminative stimulus paradigm was employed to train eight male and female Wistar rats to discriminate 5.0 mg/kg cocaine HCl from 2.0 ml/kg saline. Subjects responded in a two bar operant chamber on an FR 30 schedule for food reinforcement. All sessions followed a 10 minute pretreatment with either saline, the training dose of cocaine, four probe doses of cocaine HCl (1.0, 2.5, 7.5, 10 mg/kg), four probe doses of norcocaine (1.0, 2.5, 5.0, 7.5 mg/kg) or four probe doses of N-allylnorcocaine (5.0, 7.5, 10, 20 mg/kg). All probe doses were treated using an extinction procedure. The three highest doses of cocaine generalized to cocaine while the 1.0 mg/kg dose of cocaine generalized to saline. The two highest doses of norcocaine generalized to cocaine while the 2.5 mg/kg dose of norcocaine resulted in 57% responding on the cocaine lever with the 1.0 mg/kg dose generalizing to saline. Only the highest dose of N-allylnorcocaine was found to generalize to cocaine with the intermediate doses resulting in an intermediate level of responding occurring on the cocaine lever. The 5.0 mg/kg dose of N-allylnorcocaine generalized to saline.

The anorexic and actometric effects of cocaine and two coca extracts.

The effects of cocaine and two extracts of the coca leaf were compared using locomotor activity and limited access food consumption paradigms. The three treatments were tested using both IP and PO routes of administration. The extracts were prepared by first extracting the powdered leaves with 95% ethanol, evaporating the ethanol and then partitioning the residue between water and chloroform. The doses of the extracts studied were 60, 120, 240, and 480 mg/kg. The doses of cocaine studied were 3.45, 6.9, 13.8 and 27.6 mg/kg. These doses corresponded to the amount of cocaine contained in the four doses of the chloroform layer. Cocaine and the chloroform layer (via both routes) produced dose related increases in locomotor activity and dose related decreases in food consumption. The water layer (containing only trace amounts of cocaine) produced no changes in locomotor activity; however, the highest IP dose did significantly reduce food consumption. Furthermore two of the doses (one IP, one PO) of the chloroform layer produced significantly greater effects than an equivalent amount of cocaine. These data suggest that plant constitutents other than cocaine may contribute to the overall effect achieved by chewing the leaf.

Sociopharmacology of d-amphetamine in Macaca arctoides.

This study was designed to assess the effects of acute d-amphetamine pretreatment on the social behavior of a heterosexual group of adult M. arctoides. The dominance status had been previously determined by use of daily group food competition tests. Prior to some sessions amphetamine was administered to a single group member; whereas on other occasions all subjects were drug treated. The effects of both the individual and concurrent pretreatments were compared to those produced by saline. Furthermore, the effects of individual treatment were compared to those following concurrent dosing. The behavior of the group was monitored for one hour after a fifteen minute pretreatment time. Although generally qualitatively similar, the effects of concurrent and individual treatment were in many instances quantitatively different. d-Amphetamine increased vocalization, self-grooming, playing (low doses), social grooming (low doses), and aggression (low doses). At higher doses most forms of social interaction (playing, social grooming) were greatly decreased. Presenting behavior was increased by all doses under both treatment conditions. Mounting was increased to a much lesser extent and only after concurrent dosing. The increased presenting and mounting may be a result of sexual stimulation or perhaps more likely, an indication of increased submissive behavior directed toward more dominant animals.

Effects of d-amphetamine and diazepam on paired and grouped primate food competition.

Two male and two female rhesus monkeys (Macaca mulatta) were the subjects of an experiment designed to assess the effect of d-amphetamine (DA; 0.125, 0.5 and 2.0 mg/kg, IM) and diazepam (DZP; 0.5 and 2.5 mg/kg, IM) on food-getting behavior in paired and group competition. Paired competition results show that in some cases submissive animals, that had previously failed to obtain apple pieces, were successful in obtaining some apple pieces when either the dominant animal of the pair or both subjects were given 0.5 mg/kg DA or 2.5 mg/kg DZP. Results revealed the same effect when all animals (group competition) were given 0.125 and 2.0 mg/kg DA and 2.5 mg/kg DZP. These results appear to indicate that the effect of drugs on food-getting behavior in competitive situations is in some manner influenced by the social status of the animal.

Comparative behavioral profile of cocaine and norcocaine in rats and monkeys.

The effects of cocaine and norcocaine were compared using locomotor activity, fixed-ratio 100 (FR 100) and fixed-interval 4 min (FI 4 min) food reinforcement and free feeding paradigms in rat and intravenous self-administration tests in rhesus monkeys. Cocaine was shown to significantly increase locomotor activity at doses of 20 and 40 mg/kg, while norcocaine had no effect at these doses and produced convulsions and death at 60 and 80 mg/kg. Both compounds significantly reduced food consumption at one or more of the doses tested. Cocaine and norcocaine at doses of 20 and 40 mg/kg, produced decreases in FR responding. Cocaine at doses of 10, 20, and 40 mg/kg, produced increases in FI responding; norcocaine had no effect following 10 mg/kg and decreased responding at 20 and 40 mg/kg. Cocaine (0.2 mg/kg/inj) and norcocaine (0.5, 0.2, 0.8 mg/kg/inj) maintained intravenous self-administration in all three monkeys tested. The data indicate that norcocaine is a pharmacologically active metabolite of cocaine which could account for some of the activity heretofore attributed to cocaine. However, the lack of any stimulatory effect of norcocaine or locomotor activity and the lack of increased responding produced by norcocaine on fixed-interval behavior suggest that norcocaine differs qualitatively from cocaine.

Cocaine reinforced progressive ratio performance in the rhesus monkey.

A series of experiments were conducted to determine the effectiveness of a progressive ratio (PR) procedure in measuring the relative reinforcing efficacy of several intravenous doses of cocaine. In Experiment 1, utilizing much smaller increases in the ratio requirement than previously reported, the animals generally displayed increases in breaking point with increases in the cocaine unit dose up to 0.4 mg/kg/inj. The highest dose studied (0.8 mg/kg/inj.) engendered breaking points lower than the 0.4 mg/kg dose but higher than the remaining lower doses. Experiment 2 was conducted utilizing the same reinforcement schedule as in Experiment 1 but with liquid Tang as the reward. The results demonstrated that this procedure would function to discriminate reinforcing strength with a more traditional reward. Experiment 3 examined a more expedient procedure to see if results similar to those seen in Experiment 1 could be obtained in a shorter period of time. However, the shorter procedure engendered excessive intrasubject variability, suggesting that some intermediate level of baseline experience between the 5-7 days used in Experiment 1 and the 50 reinforced responses used in Experiment 3 would be necessary to obtain consistent breaking point-unit dose functions.

Brief communication. Comparative pharmacology of norcocaine in M. mulatta and M. fascicularis.

Norcocaine was administered intravenously (0.05, 0.5, 5.0 mg/kg) to three chaired unanesthetized male rhesus monkeys and to three chaired male cynomolgus monkeys. Respiration rate, heart rate and rectal temperature were monitored. In the rhesus monkeys tachycardia and hyperventilation resulted. However, similar qualitative and quantitative changes were not observed in the cynomolgus species. There was a statistically significant difference in the response to norcocaine across species. These results indicate that cynomolgus monkeys are either less sensitive or respond differently than rhesus monkeys to some of the pharmacological effects of norcocaine. Furthermore, these data confirm that norcocaine is an active derivative of cocaine in both rhesus and cynomolgus monkeys.