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Biomedical subjects

L Fields

Publications and source records attributed to L Fields.

At least 55 records · Page 3Linked to original sources
PubMed1995

Activity of melphalan in combination with the glutathione transferase inhibitor sulfasalazine.

Glutathione (GSH) transferases (GST), a family of detoxification enzyme proteins, are suggested to play an important role in tumor cell resistance to melphalan. The GST-activity inhibitor ethacrynic acid has been shown to increase the antitumor activity of melphalan in vitro as well as in vivo. In this study we determined the activity and toxicity of melphalan in combination with another GST-activity inhibitor, sulfasalazine, an agent used to treat ulcerative colitis. We entered 37 previously treated patients with advanced cancer of different histologies on sulfasalazine given at the individually calculated maximum tolerated dose (MTD) and melphalan given at doses beginning at 20 mg/m2. The main toxicity arising from this combination was nausea and vomiting, whereas increased myelosuppression was not observed. A partial response was seen in 2/4 of the ovarian cancer patients only. Plasma sulfasalazine levels varied between 2.5 and 47.1 micrograms/ml. Although reductions in GSH/GST levels were observed in peripheral mononuclear cells of certain patients following sulfasalazine treatment, there was no correlation between the extent of reduction and the plasma sulfasalazine level. A larger patient population must be studied to determine the usefulness of this combination.

Drug Administration Schedule↗
PubMed1995

Hemolytic disease of the newborn due to the Scianna antibody, anti-Sc2.

BACKGROUND: Alloantibodies to the low-frequency antigen Scianna 2 (Sc2) are uncommon and not previously reported to cause immune hemolysis. CASE REPORT: A group B, Rh-negative infant born to a group B, Rh-positive mother had a 2+ direct antiglobulin test, as well as modest hyperbilirubinemia and a hematocrit of 45 percent. Ongoing immune hemolysis led to a hematocrit of 17.3 percent on Day 20 of life, and the infant required hospitalization and red cell transfusions. The routine maternal antibody screen was negative, but anti-Sc2 was detected during work-up for a low-frequency red cell antigen, and the father's red cells typed as Sc:1,2. CONCLUSION: Anti-Sc2 can cause clinically significant hemolytic disease of the newborn. Although the antibody is uncommon, its frequency and hemolytic potential may be underappreciated, in part because investigations often are not carried out in the infant whose red cells are ABO-incompatible with maternal blood.

Adult↗
PubMed1995

Association of postprandial triglyceride and retinyl palmitate responses with newly diagnosed exercise-induced myocardial ischemia in middle-aged men and women.

Although strong evidence exists linking fasting plasma levels of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) to risk for development of coronary artery disease (CAD), the data in support of an independent role for fasting triglyceride (TG) concentrations are weak. Humans are in the postprandial state most of the day, however, and results from both basic and clinical studies suggest that postprandial TG levels may be atherogenic. Previous studies have not, however, attempted to determine if postprandial TG levels are associated with CAD independent of other traditional risk factors or plasma lipid levels, particularly fasting plasma concentrations of TG and HDL-C. Ninety-two men and 113 women (mean age, 51.6 and 53.6 years, respectively) were recruited from populations undergoing diagnostic exercise electrocardiographic or thallium stress tests at our medical centers. Twenty-six men and 24 women had positive tests. We chose exercise-induced myocardial ischemia (EIM) as the criterion for defining case and control subjects because we wanted participants who did not have a prior diagnosis of CAD. Blood samples were obtained for measurement of plasma TG, TG-rich lipoprotein TG, and retinyl palmitate (RP) levels 2, 3.5, 5, and 8 hours after the subjects had consumed a fatty test meal. Logistic regression models were developed to test for associations between each variable and case-control status. Among men but not women postprandial TG and RP responses were associated with EIMI independent of age, race, and smoking status. In the male group, the odds ratio (OR) for an increase in postprandial TG response of approximately 1 SD was 1.69 (P = .007); the OR for an increase in RP response of 1 SD was 2.47 (P = .011). However, when fasting TG was added to the model, the OR for postprandial TG area in the men was reduced to 1.44 (P = .17); the OR postprandial RP area in the men was reduced to 1.88 (P = .12). There was no effect of adding other risk factors, including LDL-C and HDL-C, to the model. Significant effect modification by body mass index (BMI) on the relationship between postprandial responses and case-control status was observed. In men with BMI < 30, the OR was 1.83 for postprandial TG (P = .041) and 2.77 for postprandial RP (P = .032) in models that included fasting TG, LDL-C, and hypertension.

Age Factors↗
PubMed1995

Maintained nodal-distance effects in equivalence classes.

Twelve subjects were trained to select one of two stimuli from a pair (the B pair) when presented with one of two stimuli from another pair (the A pair), thus establishing two AB relations, A1-B1 and A2-B2. In a similar fashion, additional stimuli were used to establish BC, CD, and DE relations. Trials used to train all relations occurred in each session. Once performances were established, probe trials were introduced that tested for the emergence of untrained relations (e.g., B1-D1 or A1-E1). These emergent relations were categorized according to nodal distance (i.e., the number of stimuli across which transitivity would have to hold in order for the relation to emerge). For example, a test for A2-C2 crosses one node (B2), whereas a test for A1-E1 crosses three nodes (B1, C1, and D1). Only 2 of the subjects formed equivalence classes. The evocation of class-appropriate responding by each emergent-relation probe was an inverse function of nodal distance for all 12 subjects. In addition, performance on the originally trained relations was disrupted by the introduction of probes. The 2 subjects who exhibited equivalence classes were then trained to make different numbers of key presses in the presence of each of the four A and E stimuli. In a response-transfer test, the B, C, and D stimuli evoked the responses trained to the A and E stimuli in the same equivalence class. Likelihood of class-appropriate responses was an inverse function of nodal distance, and this pattern persisted across testing. Reaction times in the transfer test were an inverted U-shaped function of nodal distance. Because training of the baseline relations occurred concurrently and the B, C, and D stimuli were presented an equal number of times before the transfer test, the test performances illustrate effects of nodal distance that were not confounded by order or amount of experience with the stimuli. The results imply that ordered, sequential exposure to individual stimulus relations may facilitate the development of equivalence classes and that the relatedness of stimuli within an equivalence class is a relatively permanent inverse function of nodal distance.

Journal Article↗
PubMed1994

An examination of current and proposed drug-testing policies at US colleges and universities.

Administrators at 400 colleges and universities were surveyed for information regarding their schools' current or proposed policies for the urine drug testing of faculty, nonfaculty employees, and students. Three hundred seven schools (77%) responded regarding their testing policies for employees and applicants for employment, including faculty and nonfaculty; 332 (83%) responded with respect to students. Twenty-five schools reported testing one or more of these groups. None of the schools reported randomly testing applicants for either faculty or nonfaculty positions, and none tested all applicants for all positions. Fewer than 7% of the colleges and universities surveyed reported that they tested urine of employees and applicants for employment to detect drug use. In those institutions that carried out tests, the tests were most often directed toward particular types of workers. Student testing was limited to approximately 2% of the 332 responding institutions.

Adult↗
PubMed1994

A national survey of drug testing policies for college athletes.

This study examined current and proposed drug testing policies from a stratified random sample of colleges and universities in the United States. Two-hundred forty-five of the 288 athletic directors surveyed responded, and 29% reported drug testing of their student athletes. Testing was most commonly conducted on a random basis, with cocaine and amphetamines the most frequently screened drugs, 85% and 83%, respectively. Only 56% tested for other specific performance-enhancing drugs such as steroids. Referral for treatment was the most common consequence of testing positive. Among schools conducting testing, the majority of students supported the program, whereas in schools without a testing program, it was anticipated that the majority of students would be opposed. It is suspected that more schools will initiate testing over the short term.

Attitude↗
PubMed1993

The use of concentration measurements of parent drug and metabolites during clinical trials.

The need for well-designed pharmacokinetic (PK) and pharmacodynamic (PD) studies early in the development of new drugs is described. In this review we illustrate the application and cost-effectiveness of optimal sampling theory in PK study design for ongoing clinical trial studies of ethyol, a chemoprotector drug. The importance of careful selection of the appropriate biological fluid in which to measure drug concentration at the earliest possible stage of new drug development is described in the context of the development of new immunosuppressive drugs. We focus on the requirement for well-validated analytical methodology in PK-PD studies, described in a discussion of the analytical methodology in use in clinical trials of two immunosuppressive agents, cyclosporin G and RS-61443 (mycophenolate mofetil).

Clinical Trials as Topic↗
PubMed1992

Interactions among emergent relations during equivalence class formation.

The interactions among symmetry, transitivity, and equivalence tests during the formation of 3-member equivalence classes were studied with 14 college students. After training AB and BC, a test with BA, CB, AC, and CA was conducted concurrently. Failure led to serial testing with probes for CA equivalence, BA symmetry, CA equivalence, CB symmetry, CA equivalence, AC transitivity, and CA equivalence. For five subjects, equivalence tests were passed immediately once BA and CB symmetry as well as AC transitivity had been induced. Thus, symmetry and transitivity were precursors for successful performance on equivalence tests. The conjoint function of symmetry and transitivity was assessed with the equivalence probes. As the equivalence probes were passed immediately, the presence of symmetry alone and transitivity alone were sufficient for their conjoint function without additional intervention. For different subjects, transitivity alone and symmetry were induced either directly with BA, CB, or AC probes or indirectly with equivalence probes. Equivalence probes can also induce various combinations of symmetry and transitivity. Thus, different subjects formed classes in various patterns at different rates.

Adolescent↗
PubMed1991

Stimulus generalization and equivalence classes: a model for natural categories.

Two three-member classes were formed by training AB and BC using a conditional discrimination procedure. The A and B stimuli were nonsense syllables, and the C stimuli were sets of "short" or "long" lines. To test for equivalence, C1 or C2 was presented as a sample with A1 and A2 as comparisons. Once the class-related comparison was chosen consistently, different line lengths were substituted for the training lines in the CA tests. In general, the likelihood of choosing a given comparison was an inverse function of the difference in the length of the test line from the training line. Stimuli in an equivalence class became functionally related not only to each other but also to novel stimuli that resembled a member of the equivalence class. The combination of primary generalization and equivalence class formation, then, can serve as a model to account for the development of naturally occurring categories.

Adult↗
PubMed1990

The effects of nodality on the formation of equivalence classes.

A four-member equivalence class (A----B----C----D) can be formed by training AB, BC, and CD. The nodal stimuli, B and C, mediate all of the derivative (transitive and equivalence) relations in the class. The derivative relations AC, CA, BD, and DB are separated by one node, whereas AD and DA are separated by two nodes. How do the number of nodes that separate the stimuli in a derivative relation influence the induction of stimulus control exerted by that relation? Seven college students learned two four-member classes made up of nonsense syllables. After training, all derivative relations were presented repeatedly without informative feedback. Stimulus control exerted by each derivative relation was assessed concurrently. For the 7 subjects, control exerted by the derivative relations increased gradually with repeated presentations. With 6 of the 7 subjects, the one-node relations exerted more control than the two-node relations during the process. However, the disparity between the one- and two-node relations decreased with repeated presentations. Eventually, all derivative relations exerted complete control. The control exerted by derivative relations during induction was inversely related to the number of nodes separating the terms in the derivative relations. These results demonstrate that nodal distance is a determinant of the relatedness of stimuli in equivalence classes. The findings are discussed in terms of remote association, semantic memory networks, and the study of transitive inference.

Adult↗
PubMed1987

Exoneration of the mentally ill.

Mental illness may be manifested in the impairment of understanding or of volitional control. Impairment of understanding may be manifested in delusions. Impairment of volitional control is shown when a person is unable to act in accordance with good reasons that he himself accepts. In order for an impairment of understanding or of self-control to exculpate, the offence must be causally connected with the impairment in question. The rationale of exculpation in general, which applies also to the case of mental illness, is that the offence does not indicate a morally bad attitude in the offender. A consequence of this rationale is that Kenny is wrong to hold that no injustice would result from the elimination of the legal defence of diminished responsibility.

Delusions↗
PubMed1987

The structure of equivalence classes.

THE STRUCTURE OF EQUIVALENCE CLASSES CAN BE COMPLETELY DESCRIBED BY FOUR PARAMETERS: class size, number of nodes, the distribution of "singles" among nodes, and directionality of training. Class size refers to the number of stimuli in a class. Nodes are stimuli linked by training to at least two other stimuli. Singles are stimuli linked by training to only one other stimulus. The distribution of singles refers to the number of singles linked by training to each node. Directionality of training refers to the use of stimuli as samples and as comparison stimuli in training. These four parameters define the different ways in which the stimuli in a class can be organized, and thus provide a basis for systematically characterizing the properties of stimuli in a given equivalence class. The four parameters can also be used to account for the development of individual differences that are commonly characterized in terms of "understanding" and connotative meaning.Methods are described for generating all possible combinations of parameter values, and a formula is introduced which specifies all of the parameter values for an equivalence class. Its utility for interrelating experimental procedures is demonstrated by analyzing a number of representative experiments that have addressed equivalence-class formation.

Journal Article↗
PubMed1985

Reinforcement of probe responses and acquisition of stimulus control in fading procedures.

Stimulus control of pigeons' key pecking was transferred from colors to lines by the method of stimulus fading. Fading was conducted with the addition of probes consisting of the line stimuli presented alone at each fading level. Probe responding was used to measure stimulus-control acquisition by the lines. Effects of reinforcement and nonreinforcement of probe responding upon acquisition of stimulus control were assessed using a single-organism repeated-acquisition design in which three fades were conducted serially. Probe responding was not reinforced in the first and third fade but was in the second. Reinforcement of probe responding substantially reduced the number of fading levels needed to complete fading. The outcome of a control experiment ruled out the possibility of accounting for these results in terms of the specific stimuli used in each fade or in terms of the sequential exposure to the three discriminations. Although probes permitted measurement of stimulus-control acquisition in fading, a measurement/acquisition interaction was also present.

Journal Article↗
PubMed1985

Factors affecting the binding of disopyramide to serum proteins.

We investigated the influence of the following factors on the binding of disopyramide to serum proteins: method of drug quantification [enzyme immunoassay (EMIT) compared with liquid chromatography (HPLC)], separation technique (ultrafiltration vs equilibrium dialysis), temperature, pH, and total concentration of disopyramide. EMIT and HPLC measurements of disopyramide in ultrafiltrates prepared from 50 sera agreed well: EMIT = 1.046 HPLC + 0.042, (r = 0.928, SEE = 0.04 mg/L). Free disopyramide concentrations in ultrafiltrates of dialyzed sera were similar to those measured in the corresponding dialysates by the EMIT method for 30 patients' sera: ultrafiltrate of serum retentate = 1.053 dialysate + 0.042. Concentrations of free [14C]disopyramide were little affected by temperature. The concentration of free disopyramide decreased as the pH was increased from 7.0 to 7.8. The concentration of free disopyramide, as determined by ultrafiltration, is strongly and directly related to total drug concentration. In the sera of 50 cardiac patients receiving chronic therapy with disopyramide and with total disopyramide concentrations of 0.5 to 5.8 mg/L, the proportion of free disopyramide ranged from 16 to 54%.

Blood Proteins↗
PubMed1984

Stimulus equivalence and transitive associations: A methodological analysis.

When a number of two-stimulus relations are established through training within a set of stimuli, other two-stimulus relations often emerge in the same set without direct training. These, termed "transitive stimulus relations," have been demonstrated with a variety of visual and auditory stimuli. The phenomenon has served as a behavioral model for explaining the emergence of rudimentary comprehension and reading skills, and the development of generative syntactic repertoires. This article considers the range of relations that can arise between a given number of stimuli in a class, the number of directly established two-stimulus relations necessary for the emergence of transitive relations, the forms that training sets of stimuli can take, and the number of transitive two-stimulus relations that can be induced without direct training. The procedures needed to establish and assess transitive stimulus control, the possible interactions between the training and testing procedures, and the constrainst these interactions place upon the analysis of transitive stimulus control are also examined. The present analysis indicates that in a transitivity test, choice among such stimuli may be controlled by (1) the relation between the sample and the positive comparison stimulus (transitive stimulus control), (2) the relation between the sample and the negative comparison stimulus (S- rule control), and (3) possible discriminative properties that may inadvertently be established in the positive and negative comparison stimuli (valence control). Methods are described for distinguishing these three forms of stimulus control.

Journal Article↗
PubMed1983

Response rate, latency, and resistance to change.

Pigeons were trained on a multiple variable-interval/variable-interval schedule with pacing contingencies that generated high response rates in one component and low response rates in the other. Timeout periods separated the schedule components. During resistance-to-change tests, response-independent food was presented during the timeout periods, and the duration of that food presentation was varied among test sessions. Response rates in the schedule components decreased and latencies to the first response increased as a function of the duration of food presentations during the timeout. Both dependent measures changed about the same amount relative to their own baseline levels. The conclusions are that baseline response rates controlled by pacing contingencies are equally resistant to change, given equal reinforcement densities, and latency is a sensitive measure of resistance to change.

Journal Article↗
PubMed1982

Factors influencing theophylline serum protein binding.

We studied a number of influences on theophylline binding to serum proteins using equilibrium dialysis (37 degrees), a modified Krebs-Ringer bicarbonate buffer (pH 7.4), and 8-14C-theophylline with unlabeled theophylline (30 microgram/ml) added to sera from healthy subjects. Theophylline protein binding rose by 18.6% as pH rose from 7.0 to 7.8 (percent theophylline bound = 28.2 +/- 4.3 at pH 7.0 and 46.8 +/- 4.9 at pH 7.8, n = 5). Average theophylline binding to the proteins at 37 degrees in serum samples from 10 normal adults was 39.3 +/- 3.44%, which is 89.9% lower than the average of 48.2 +/- 3.74% for the same samples at 26 degrees. Theophylline binding was 6.1% higher with 0.1 mole/l phosphate buffer, pH 7.4, than with a modified Krebs-Ringer bicarbonate buffer, pH 7.4. Of the 19 drugs and metabolites tested for competition with theophylline for binding sites on serum proteins, 10 induced decreases in binding ranging from 6.8% in the case of furosemide to 18.3% for sodium salicylate. The latter was the only drug that induced a decrease in theophylline binding at concentrations that would be achieved in the therapy of same patients (i.e., patients on long-term salicylate therapy). All the other drugs that decreased theophylline binding did so at much greater concentrations than their usual therapeutic levels. The mean +/- SD of theophylline bound in 51 fresh serum samples from healthy adults was 48.6 +/- 10.2%; the pH of these specimens varied from 7.6 to 8.7. After adjusting pH to 7.4, theophylline binding was lowered to 37.6 +/- 4.5% and intersubject variability decreased. We recommend that the pH of serum specimens be adjusted to 7.4, or to the original pH of the blood specimen if it differs significantly from 7.4 (i.e., in acidotic or alkalotic patients). The wide range of reported values for theophylline binding to serum proteins in normal and asthmatic adults at least partly results from differences in the conditions used for the separation of free from bound drug.

Blood Proteins↗