Search

Los videojuegos son una nueva forma de entretenimiento masivo que cada vez más personas encuadran dentro de una nueva forma de deporte. En esta revisión se trata de dilucidar cuál es el estado de debate acerca de la relación entre uso de videojuegos violentos, violencia y variables relacionadas. Para ello se revisaron las bases de datos MEDLINE complete, Psychology and Behavioral Science Collection, Psychoinfo y Sportdiscuss. El volumen total de referencias fue de 2.000 documentos publicados desde el año 2013 al 2019, de los que se seleccionaron 20 trabajos representativos sobre la temática. Los resultados de estas investigaciones señalaron que las consecuencias violentas o similares de los jugadores se deben a variables personales (ira rasgo y edad, principalmente en etapa de adolescencia y joven adultez) y contextuales (competición) que median entre el videojuego y la conducta problema. Se concluye que son estos moderadores los que explican la relación entre video juegos violentos, violencia y variables relacionadas, y no el contenido de los videojuegos.

The article discusses the pharmacokinetics of intravascular itraconazole in the American horseshoe crab (Limulus polyphemus). It features a pilot study to establish a dose and sampling for itraconazole in American horseshoe crab. Drug administration were tested on cardiac sinus. The results are discussed.

Gemcitabine is a relatively new chemotherapeutic compound used to treat a variety of cancers in dogs. Previous work presented in a companion paper explored the plasma kinetics of gemcitabine and its inactive metabolite, 2′,2′-difluorodeoxyuridine (dFdU), in dogs after an intravenous bolus gemcitabine dose and demonstrated the saturation of intracellular dFdCTP (2′,2′-difluorodeoxycytidine 5′-triphosphate) occurs in vitro with increasing extracellular gemcitabine exposure in canine melanoma cells. In this study, the plasma pharmacokinetics (PKs) of gemcitabine and dFdU are further explored after gemcitabine doses of 10, 30, and 60 mg/kg administered by intravenous infusion with a loading dose. Gemcitabine displayed linear PKs, while the kinetics of dFdU were not dose proportional. The overall clearance, volume of distribution at steady-state, and terminal elimination half-life ( t1/2) for gemcitabine were 0.421 L/h·kg, 0.822 L/kg, and 1.49 h, respectively. Plasma concentrations of dFdU peaked at approximately 2 h postdosing and had a t1/2 of 14.9 h. [ABSTRACT FROM AUTHOR]

An interspecies pharmacokinetic model for gentamicin was developed using the mixed effects modeling approach and serum disposition data obtained from the Food Animal Residue Avoidance Databank (FARAD). Data that met a priori quality criteria was obtained from the database and analysed using the traditional double logarithmic analysis and the mixed effects modeling approach. Body weight, brain weight and fever were the covariates of interest in our study. Population pharmacokinetic models across species were developed and validated with swine data. The parameter volume of distribution was modeled as a function of body weight. The total clearance was initially modeled as a function of body weight. The predictability performance of the model improved dramatically when the parameter brain weight was included in the covariate model for clearance. This was a surprising finding worthy of further study. The covariate fever seemed to influence the magnitude of the volume of distribution, although the scarcity of data pertaining to diseased animals makes this finding uncertain. We conclude that the pharmacokinetic characteristics of drugs such as gentamicin, can be predicted across species using a population pharmacokinetics modeling approach, and that clinical features that affect species in a similar manner can be also explored in this fashion. [ABSTRACT FROM AUTHOR]

Antimicrobial efficacy can be predicted based on infection site exposure to the antimicrobial agent relative to the in vitro susceptibility of the pathogen to that agent. When infections occur in soft tissues (e.g., muscle, blood, and ligaments), exposure at the infection site is generally assumed to reflect an equilibrium between the unbound concentrations in plasma and that in the interstitial fluids. In contrast, for sporadic urinary tract infections (UTIs) in dogs and uncomplicated UTIs in humans, the primary site of infection is the bladder wall. Infection develops when bacteria invade the host bladder urothelium (specifically, the umbrella cells that form the urine-contacting layer of the stratified uroepithelium) within which these bacteria can avoid exposure to host defenses and antimicrobial agents. Traditionally, pathogen susceptibility has been estimated using standardized in vitro tests that measure the minimal concentration that will inhibit pathogen growth (MIC). When using exposure-response relationships during drug development to explore dose optimization, these relationships can either be based upon an assessment of a correlation between clinical outcome, drug exposure at the infection site, and pathogen MIC, or upon benchmark exposure-response relationships (i.e., pharmacokinetic/pharmacodynamic indices) typically used for the various drug classes. When using the latter approach, it is essential that the unbound concentrations at the infection site be considered relative to the MIC within the biological matrix to which the pathogen will be exposed. For soft tissue infections, this typically is the unbound plasma concentrations versus MICs determined in standardized media such as cation-adjusted Mueller Hinton broth, which is how many indices were originally established. However, for UTIs, it is the unbound drug concentrations within the urine versus the MICs in the actual urine biophase that needs to be considered. The importance of these relationships and how they are influenced by drug resistance, resilience, and inoculum are discussed in this review using fluoroquinolones and beta-lactams as examples., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) that has been used orally and intramuscularly in numerous avian species, but not studied to date, in African penguins ( Spheniscus demersus). The study describes the pharmacokinetic parameters of meloxicam after oral and intramuscular administration to African penguins. Several pilot studies were conducted initially where meloxicam (1, 0.5, and 0.25 mg/kg) was given intramuscularly to 4 birds, and orally (1 mg/kg) to 2 birds. Based on pilot study results, one group of 8 penguins was given meloxicam 0.5 mg/kg intramuscularly and one group of 8 penguins was given 1 mg/kg orally. Blood samples were collected at baseline and at 11 time intervals per group after administration of meloxicam. Meloxicam time to maximum plasma concentration (T max ), maximum concentration (C max ), and half-life (t 1/2 ) after intramuscular administration were 1.00 hour, 8.03 μg/mL, and 31.87 hours, respectively, while oral administration produced a T max , C max , and t 1/2 of 12.00 hours, 10.84 μg/mL, and 28.59 hours, respectively. Based on plasma meloxicam concentrations found to be therapeutic in other bird species and humans, the recommended dosage and frequency for African penguins is 1 mg/kg orally every 48 hours and 0.5 mg/kg intramuscularly every 24 hours. Further studies are needed to determine the multiple-dose pharmacokinetics of meloxicam in African penguins.

The purpose of this study was to evaluate the pharmacokinetics of moxidectin in alpacas after single subcutaneous injection of a non-aqueous formulation or oral administration of an aqueous drench at 0.2 mg∗kg(-1). Plasma moxidectin concentrations were measured with reverse phase HPLC, and data analyzed using non-compartmental methods. Half-life was longer (p=0.02) after subcutaneous administration than oral (292+/-170 vs 33+/-39 h). The area under the concentration-time curve was greater (p=0.04) following subcutaneous administration (1484.8+/-1049.5 h∗ng∗ml(-1)) than oral (157.6+/-85.9 h∗ng∗ml(-1)). The peak concentration (Cmax) was higher and the after subcutaneous administration, but the difference was not statistically significant (p=0.18). The relative bioavailability of the oral moxidectin to the subcutaneous moxidectin was 11%. The data suggest a higher relative bioavailability following subcutaneous compared to oral administration. Further studies are needed to determine the therapeutic concentrations of moxidectin in alpacas., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Neuropathic pain is a manifestation of chronic pain that arises with damage to the somatosensory system. Pharmacologic treatment recommendations for alleviation of neuropathic pain are often multimodal, and the few reports communicating treatment of suspected neuropathic pain in avian patients describe the use of gabapentin as part of the therapeutic regimen. To determine the pharmacokinetics of gabapentin in Hispaniolan Amazon parrots ( Amazona ventralis ), compounded gabapentin suspensions were administered at 30 mg/kg IV to 2 birds, 10 mg/kg PO to 3 birds, and 30 mg/kg PO to 3 birds. Blood samples were collected immediately before and at 9 different time points after drug administration. Plasma samples were analyzed for gabapentin concentration, and pharmacokinetic parameters were calculated with both a nonlinear mixed-effect approach and a noncompartmental analysis. The best compartmental, oral model was used to simulate the concentration-time profiles resulting from different dosing scenarios. Mild sedation was observed in both study birds after intravenous injection. Computer simulation of different dosing scenarios with the mean parameter estimates showed that 15 mg/kg every 8 hours would be a starting point for oral dosing in Hispaniolan Amazon parrots based on effective plasma concentrations reported for human patients; however, additional studies need to be performed to establish a therapeutic dose.

Tulathromycin is the first and only member of the triamilide sub-class of macrolides that is used therapeutically and has been registered in more than 30 countries across America, Europe, Oceania and Asia. The discovery of tulathromycin and its registration in multiple countries has been important for the food animal industry as it has been used successfully to treat economically important conditions such as bovine and porcine respiratory disease, infectious bovine keratoconjunctivitis and interdigital necrobacillosis. Since it was first registered about 8 years ago, considerable information has been generated to help define tulathromycin's role in veterinary medicine as well as setting the basis for new treatment strategies and for the discovery of new macrolides with further applications in veterinary and human medicine. This article reviews this information and examines more recent findings particularly the effects of tulathromycin on the immune response, its pharmacokinetics and pharmacodynamics, its pattern of susceptibility and the identification of genes that may be associated with resistance to the drug., (Copyright © 2013. Published by Elsevier Ltd.)

SHetA2 is a heteroarotinoid that has shown selective inhibition of cancer cell growth and an induction of apoptosis without activation of nuclear retinoic acid receptors. In the rat study, SHetA2 was administered in 1% aqueous methylcellulose/0.2% Tween 80 by oral gavage at 0, 100, 500, and 2,000 mg/kg/day for 28 days. The high-dose administration induced decreased activity in male rats, decreased body-weight gains and food consumption, and changes in organ weights. The major metabolite of SHetA2 in rat plasma was monohydroxy SHetA2, which was considerably higher than the parent compound after oral and intravenous administration. Pharmacokinetic analysis showed extremely low (<1%) systemic bioavailability of SHetA2 for all doses tested. The dose of 2,000 mg/kg/day was considered as the lowest observed adverse effect level. The no observed adverse effect level (NOAEL) was 500 mg/kg/day. In the dog study, no toxicity of SHetA2 in 30% aqueous Solutol(®) HS 15 was observed in any tested dose groups (0, 100, 400, and 1,500 mg/kg/day). The major metabolite of SHetA2 in dog plasma was also monohydroxy SHetA2, which was equal to or lower than the parent compound after oral administration. SHetA2 levels in dog plasma were notably higher, when compared to levels in rat plasma. However, exposure was not dose proportional, as exemplified by a lack of proportional increase in maximum concentration or area under the plasma concentration-time curve with increasing dose. The NOAEL was not established and was considered to be above 1,500 mg/kg/day.

Objective: To determine the pharmacokinetics of a long-acting formulation of ceftiofur, ceftiofur crystalline-free acid (CCFA), following SC injection to Asian elephants (Elephas maximus)., Animals: 11 adult Asian elephants., Procedures: Each elephant received CCFA (6.6 mg/kg, SC) in the area caudoventral to the base of an ear. Blood samples were collected from an ear vein immediately prior to and at 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after CCFA administration. Plasma concentrations of desfuroylceftiofur acetamide (the acetamide derivative of ceftiofur) were measured via ultrahigh-pressure liquid chromatography-tandem mass spectrometry. Data were analyzed via a noncompartmental pharmacokinetics approach., Results: The mean ± SD maximum plasma concentration of desfuroylceftiofur acetamide was 1.36 ± 0.74 μg/mL and was detected at 4718 ± 31.30 hours. The mean ± SD area under the curve from time 0 to infinity was 2278 ± 55.8 μg•h/mL, and the mean residence time from time 0 to infinity was 158.2 ± 90.2 hours. The terminal elimination half-life associated with the slope of the terminal phase had a harmonic mean ± pseudo-SD of 83.36 ± 30.01 hours., Conclusions and Clinical Relevance: Elephants tolerated CCFA at a dose of 6.6 mg/kg, SC, well. Dosing recommendations will depend on the mean inhibitory concentration of ceftiofur for each bacterial pathogen. Desfuroylceftiofur acetamide concentrations remained > 0.25 μg/mL for the entire 168-hour study period, which suggested CCFA would provide clinically relevant antimicrobial activity against certain pathogens for 7 to 10 days.

The objective of this study was to determine the pharmacokinetics of a long-acting formulation of ceftiofur crystalline-free acid (CCFA) following intramuscular injection in ball pythons (Python regius). Six adult ball pythons received an injection of CCFA (15 mg/kg) in the epaxial muscles. Blood samples were collected by cardiocentesis immediately prior to and at 0.5, 1, 2, 4, 8, 12, 18, 24, 48, 72, 96, 144, 192, 240, 288, 384, 480, 576, 720, and 864 hr after CCFA administration. Plasma ceftiofur concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was applied to the data. Maximum plasma concentration (Cmax) was 7.096 +/- 1.95 microg/ml and occurred at (Tmax) 2.17 +/- 0.98 hr. The area under the curve (0 to infinity) for ceftiofur was 74.59 +/- 13.05 microg x h/ml and the elimination half-life associated with the terminal slope of the concentration-time curve was 64.31 +/- 14.2 hr. Mean residence time (0 to infinity) was 46.85 +/- 13.53 hr. CCFA at 15 mg/kg was well tolerated in all the pythons. Minimum inhibitory concentration (MIC) data for bacterial isolates from snakes are not well established. For MIC values of < or =0.1 microg/ml, a single dose of CCFA (15 mg/kg) provides adequate plasma concentrations for at least 5 days in the ball python. For MICs > or =0.5 microg/ml, more frequent dosing or a higher dosage may be required.

9-cis-UAB30 is a potential chemopreventative agent that has been shown to be effective on many different types of tumors. The safety and toxicity of 9-cis-UAB30 had not been previously established. These studies were conducted to evaluate the potential toxicity and pharmacokinetics in a rodent and a nonrodent species for the purpose of investigational new drug submission. Oral gavage administration of 9-cis-UAB30 at the doses 0, 3, 15, and 100 mg/kg/day to CD® rats for 28 days showed a dose-dependent (although not dose-proportional) increase in plasma drug levels in week 4. The liver was the target organ for toxicity of 9-cis-UAB30. Hepatomegaly along with increases in serum aspartate-aminotransferase and alkaline-phosphatase levels were seen in rats. Moderate hypoalbuminemia and hyperglobulinemia resulted in a decreased albumin/globulin ratio. Histopathology revealed hepatocellular change consistent with hepatic glycogen deposition. Toxicity studies in dogs did not show treatment-related toxicity at doses as high as 100 mg/kg/day (highest dose tested) administered by capsules for 28 days. No effects on the central nervous system (functional observational battery in rats) or cardiovascular function (safety pharmacology study in telemeterized dogs) were seen. The no observed adverse effect level (NOAEL) in the rat studies was 3 mg/kg/day; however, the adverse effects seen in rats receiving 15 mg/kg/day (the least observed adverse effect level) was a slight, but statistically significant, elevation in fibrinogen and decrease in prothrombin time, which may be a sign of some tendency for increased blood coagulation. The NOAEL in the dog study was at least 100 mg/kg/day.

Methimazole (thiamazole) is an antithyroid drug commonly used to treat feline hyperthyroidism. It is routinely given twice daily. Carbimazole is a methimazole derivative that is rapidly metabolized to methimazole in vivo. A controlled-release tablet for once-daily carbimazole therapy has recently been developed in an attempt to improve compliance during medical management of feline hyperthyroidism. The results of a crossover study in six cats suggest that the pharmacokinetics of methimazole with a single dose of this controlled-release tablet may be similar to those with a single dose of a sugar-coated methimazole tablet when the two drugs are given at an equimolar dose. The mean half-lives were nearly identical (3.12 hours, sugar-coated methimazole tablets; 3.28 hours, controlled-release carbimazole tablets). The serum concentrations of methimazole at 24 hours were 21.7 ± 28.9 ng/mL in the cats treated with 5-mg sugar-coated methimazole tablets and 28.7 ± 37 ng/mL in the cats treated with 10-mg carbimazole tablets (which provide approximately 25% more methimazole after conversion to the active metabolite).

Carboplatin is an antineoplastic drug administered to treat different tumoral conditions in canine oncology. The objective of this study was to validate a high-performance chromatographic (HPLC) method which could be applied in canine pharmacokinetic studies. Following ultrafiltration using a Centrifree device, standards, quality controls and plasma samples were separated by isocratic reversed-phase HPLC on an Inertsil ODS-2 (250 x 4.6 mm i.d.) analytical column and quantified using UV detection at 220 nm. The mobile phase was potassium phosphate (pH 4.5), with a flow-rate of 1.0 mL/min. The procedure produced a linear curve (r(2) > 0.999) over the concentration range 1-200 microg/mL. The lower limit of quantification was 1 microg/mL. The intra-assay and inter-assay precision was approximately 90%. The overall recovery was approximately 90%. The method was illustrated with a preliminary pharmacokinetic analysis on nine dogs treated with carboplatin at our hospital. Carboplatin disposition followed a monocompartmental structure in dogs and was characterized by a short half-life (50 min).

The extralabel use of drugs can be defined as the use of drugs in a manner inconsistent with their FDA-approved labeling. The passage of the Animal Medicinal Drug Use Clarification Act (AMDUCA) in 1994 and its implementation by the FDA-Center for Veterinary Medicine in 1996 has allowed food animal veterinarians to use drugs legally in an extralabel manner, as long as an appropriate withdrawal period is established. The present study introduces and validates with simulated and experimental data the Extrapolated Withdrawal-Period Estimator (EWE) Algorithm, a procedure aimed at predicting extralabel withdrawal intervals (WDIs) based on the label and pharmacokinetic literature data contained in the Food Animal Residue Avoidance Databank (FARAD). This is the initial and first attempt at consistently obtaining WDI estimates that encompass a reasonable degree of statistical soundness. Data on the determination of withdrawal times after the extralabel use of the antibiotic oxytetracycline were obtained both with simulated disposition data and from the literature. A withdrawal interval was computed using the EWE Algorithm for an extralabel dose of 25 mg/kg (simulation study) and for a dose of 40 mg/kg (literature data). These estimates were compared with the withdrawal times computed with the simulated data and with the literature data, respectively. The EWE estimates of WDP for a simulated extralabel dose of 25 mg/kg was 39 days. The withdrawal time (WDT) obtained for this dose on a tissue depletion study was 39 days. The EWE estimate of WDP for an extralabel intramuscular dose of 40 mg/kg in cattle, based on the kinetic data contained in the FARAD database, was 48 days. The withdrawal time experimentally obtained for similar use of this drug was 49 days. The EWE Algorithm can obtain WDI estimates that encompass the same degree of statistical soundness as the WDT estimates, provided that the assumptions of the approved dosage regimen hold for the extralabel dosage regimen. Population models could be fitted to fragmentary data to predict residue concentrations in tissues, validate the EWE estimates, and obtain WDI estimates.

Differences in the disposition of certain drugs across mammalian species often arise because of their diverse physiology and anatomical characteristics. Factors such as body mass, brain weight, and maximum lifespan are related to the way that different species of mammals handle drugs. Drug disposition data can be scaled across species when chronological time is substituted by the appropriate measure of pharmacokinetic time. In this study, we developed allometric scaling models for oxytetracycline, using serum disposition data obtained from the Food Animal Residue Avoidance Databank. The data were modeled using the mixed-effects modeling approach. The models obtained were validated using disposition data on swine. Oxytetracycline scaled across species based on body weight and the best interspecies model adequately predicted the value of the pharmacokinetic parameters across species. The population approach allows one to estimate the allometric coefficients and exponents of the pharmacokinetic parameters to obtain a model that best fits the multi-species pooled concentration-time data. Furthermore, this approach allows decisions to be made based on the statistical significance of the parameter estimates and the adequacy of the models that are not possible with traditional approaches., (Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:331-341, 2002)

An interspecies pharmacokinetic model for gentamicin was developed using the mixed effects modeling approach and serum disposition data obtained from the Food Animal Residue Avoidance Databank (FARAD). Data that met a priori quality criteria was obtained from the database and analysed using the traditional double logarithmic analysis and the mixed effects modeling approach. Body weight, brain weight and fever were the covariates of interest in our study. Population pharmacokinetic models across species were developed and validated with swine data. The parameter volume of distribution was modeled as a function of body weight. The total clearance was initially modeled as a function of body weight. The predictability performance of the model improved dramatically when the parameter brain weight was included in the covariate model for clearance. This was a surprising finding worthy of further study. The covariate fever seemed to influence the magnitude of the volume of distribution, although the scarcity of data pertaining to diseased animals makes this finding uncertain. We conclude that the pharmacokinetic characteristics of drugs such as gentamicin, can be predicted across species using a population pharmacokinetics modeling approach, and that clinical features that affect species in a similar manner can be also explored in this fashion.

In 1996, the United States Congress passed legislation (Animal Medicinal Drug Use Clarification Act, AMDUCA), which allows some veterinary or human drugs to be used off label in food-producing animals. In order to implement this Act and protect the U.S. consumer, tolerances or safe concentrations are required before a withdrawal time can be estimated for extralabel drug use. Use of foreign MRLs to satisfy these data needs may not be applicable because of differences in safety standards between the U.S. and other countries. This paper presents strategies that can be used to derive equivalent safe concentrations, referred to as provisional acceptable residues (PARs), that may then be used to estimate drug withdrawal times. Health-based methods are proposed for calculating a PAR for a tissue. Procedure A partitions 50% of the acceptable daily intake (ADI) to edible tissues and reserves the remainder for milk. Procedure B equally partitions the ADI into all edible tissues. Procedure C partitions 50% of the ADI to milk and equally partitions the remaining 50% ADI into edible tissues. Simulations were performed for florfenicol, tetracycline, dexamethasone, azaperone, ivermectin, eprinomectin, and doramectin. In general, these simulations resulted in derivation of conservative PARs, which did not result in daily intakes of residues greater than the health-based ADI. These simulations demonstrated that provided the safe concentrations or equivalent PARs are based on rigorous toxicology safety data (e.g., NOELs, ADIs), the safety of food animal products will not be compromised. It is proposed that these PARs can be used for estimating withdrawal times after extralabel drug use or inadvertent exposure to an environmental contaminant where no approved withdrawal time exists. Finally, implementing similar transparent methods could have a positive impact on international harmonization and trade., (Copyright 1999 Academic Press.)

Objective: To develop and validate a population pharmacokinetic model for gentamicin in horses, using retrospective clinical data., Animals: 62 horses that had been treated IV with multiple doses of gentamicin at our veterinary teaching hospital between 1987 and 1996. Procedure-46 horses were assigned to the study group, and 16 to the validation group. Detailed history of dosage, sample collection times, and selected pathophysiologic variables were recorded for each patient. Samples were analyzed by use of a fluorescence polarization immunoassay method. Pharmacostatistical analysis was conducted, using computer software. The predictive model correlates pharmacokinetic parameters to concomitant pathophysiologic variables and estimates the inter- and intraindividual variability in disposition., Results: A two-compartment model best described the data. Clearance (CI) was linearly correlated to body weight and serum creatinine concentration. Volume of the central compartment (Vd(c)) was linearly related to body weight. Interindividual coefficients of variability for CI and Vd(c) were 24 and 16%, respectively. The residual variability (intraindividual) was 13%; mean prediction error percent (bias) was 2%; and mean absolute prediction error percent (precision) was 29%., Conclusions: Population pharmacokinetic analysis allows study of the basic features of gentamicin disposition in horses with sparse data per individual. A considerable proportion of the pharmacokinetic variability of gentamicin in our study population was explained by differences in body weight and serum creatinine concentration., Clinical Relevance: Population pharmacokinetics can be used to design first-dosage regimens according to the clinical characteristics of individual animals. Population pharmacokinetic models could also be included in Bayesian forecasting strategies to improve plasma concentration predictions in individual patients.

Population pharmacokinetics can be defined as a study of the basic features of drug disposition in a population, accounting for the influence of diverse pathophysiological factors on pharmacokinetics, and explicitly estimating the magnitude of the interindividual and intraindividual variability. It is used to identify subpopulations of individuals that may present with differences in drug kinetics or in kinetic/dynamic responses. Rooted in procedures used in engineering systems, population pharmacokinetics methods were conceived as a means to determine the pharmacokinetic profile in populations in which a sparse number of samples were obtained per individual, such as those in late stage human clinical trials. This is the situation commonly encountered in all aspects of veterinary medicine. The exploratory nature of this technique allows one to probe relationships between clinical factors (such as age, gender, renal function, etc.) and drug disposition and/or effect. Similarly, the utilization of these techniques in the clinical research phases of drug development optimize the determination of efficacy and safety of drugs. Given the observational nature of most studies published so far, statistical methods to validate the population models are necessary. Simulation studies may be conducted to explore data collection designs that maximize information yield with a minimum expenditure of resources. The breadth of this approach has allowed population studies to be more commonly employed in all areas of drug therapy and clinical research. Finally, in veterinary medicine, there is an additional field in which population studies are potentially ideally suited: the application of this methodology to the study of tissue drug depletion and drug residues in production animals, and the establishment of withdrawal times tailored to the clinical or production conditions of populations or individuals. Such application would provide a major step toward assuring a safe food supply under a wide variety of dose and off-label clinical uses. Population pharmacokinetics is an ideal method for generating data in support of the implementation of flexible labelling policies and extralabel drug use recently approved under AMDUCA (Animal Medicinal Drug Use Clarification Act. 21 CFR Part 530).

Most radiological signs are of low specificity for predicting malignancy in patients with a solitary pulmonary nodule (SPN), making clinical management difficult. Only certain calcification patterns in SPN or the absence of growth over a period two years assures that the nodule is benign. The clinical and radiological characteristics of 31 patients with SPN were studied. Twenty-two were cases bronchopulmonary carcinoma and 9 were pulmonary tuberculoma. Accuracy in the prediction of malignancy was assessed using Bayes' theorem, which is based on degrees of likelihood of various radiological and clinical characteristics. Patients with carcinoma (mean age 65 +/- 9 years) were significantly older than those with tuberculoma (38 +/- 19 years) (p < 0.05). The proportion of smokers was significantly higher among patients with carcinoma (91%) than those with tuberculoma (44%) (p < 0.05). In 50% of the patients with SPN due to bronchopulmonary carcinoma (11 patients), the nodule was in the upper right lobe; in 55% of those with tuberculomas (5 patients) the nodule was found in the upper left lobe. There were no significant differences in the characteristics of the computerized tomography images for the two groups. Mean likelihood of malignancy for patients with carcinoma, by Bayes' theorem, was 83.7%, a rate that was significantly higher than that of tuberculoma patients (46%) (p < 0.05). The application of Bayes' probability theorem for a set of clinical and radiological characteristics can orient the physician as to whether an SPN is likely to be malignant or not, thereby providing guidance on the advisability of performing invasive diagnostic procedures to determine etiology.

A 79-year old female patient with antecedents of headache and fever, was admitted because of fatigue, anorexia, anemia and elevated ESR. After admission she presented with rheumatic polymyalgia and synovial effusion in the knee. A first biopsy of the temporal artery was normal. After dismissing other possible causes a second biopsy of the contralateral temporal artery was bone and confirmed giant cell arteritis. Diagnostic value of a second temporal artery biopsy is discussed and justified by: a) a confirmed diagnosis is necessary for prolonged treatment with corticosteroids, b) if it is decided to treat the rheumatic polymyalgia with lower doses of corticosteroids than for temporal arteritis the certainty that no temporal arteritis is present and c) shortening the hospital stay and lowering the cost and number of diagnostic procedures. The frequency of arthritis and synovial effusion in temporal arteritis are also discussed.

A 75 year-old male presented with hyperkalemia unexplained by a moderate renal insufficiency, low basal levels of aldosterone and renin with a subnormal response to walking and saline depletion, and normal glucocorticoid function. The hyperkalemia was corrected by fluorocortisone administration. The concept of hypoaldosteronism is reviewed, defining it as an isolated aldosterone deficiency and thus excluding the combined deficiency of cortisol and aldosterone and the suprarenal enzyme deficits that simultaneously involve mineralocorticoid and glucocorticoid synthesis. Depending on the presence or absence of alterations of the renin-angiotensin axis, this infrequent syndrome can be pathophysiologically classified as low, normal or high renin hypoaldosteronism. The characteristic features of each type are described, and emphasis is made on the need for a high index of suspicion when unexplained hyperkalemia is present in order to perform the appropriate tests to confirm or rule out hypoaldosteronism.