The pharmacokinetics of cytarabine administered subcutaneously, combined with prednisone, in dogs with meningoencephalomyelitis of unknown etiology.

The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m2 as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5-2 mg kg-1 day-1 ). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 µg/ml. The population estimate (CV%) for elimination half-life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 µg/ml at the 30-, 60-, 90-, and 120-min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m2 SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs.

Association between ABCB1 genotype and seizure outcome in Collies with epilepsy.

BACKGROUND: Medically refractory seizures are an important problem in both humans and dogs with epilepsy. Altered expression of ABCB1, the gene encoding for p-glycoprotein (PGP), has been proposed to play a role in drug-resistant epilepsy. HYPOTHESIS: Heterogeneity of the ABCB1 gene is associated with seizure outcome in dogs with epilepsy. ANIMALS: Twenty-nine Collies with epilepsy being treated with antiepileptic drugs (AEDs). METHODS: Prospective and retrospective cohort study. Dogs were classified as having a good outcome (≤ 1 seizure/month, no cluster seizures) or a poor outcome (>1 seizure/month, with or without cluster seizures) based on owner-completed questionnaire. Serum AED concentrations were measured, and ABCB1 genotyping was performed on buccal tissue samples. Association analyses were performed for genotype and seizure outcome, number of AEDs administered, serum AED concentrations, and incidence of adverse effects. RESULTS: Fourteen dogs of 29 (48%) were homozygous for the ABCB1-1∆ mutation (M/M), 11 dogs (38%) were heterozygous (M/N), and 4 dogs (14%) had the wild-type genotype (N/N). Dogs with the M/M genotype were significantly more likely to have fewer seizures and have less AED-related sedation than M/N or N/N dogs (P = .003 and P = .001, respectively). Serum phenobarbital and bromide concentrations did not differ between groups, but the M/N and N/N groups received a larger number of AEDs than the M/M group (P = .014). CONCLUSIONS AND CLINICAL IMPORTANCE: ABCB1 genotype is associated with seizure outcome in Collies with epilepsy. This cannot be attributed to differences in PGP function, but might be because of intrinsic variations in seizure severity among phenotypes.

Obsessive-compulsive disorder in children.

Childhood OCD is a chronic and commonly disabling disorder with a lifetime prevalence of 2% to 3%. Traditionally OCD was a neglected diagnosis, but renewed research interest over the past decade has led to significant advances in the understanding of the disorder in young people. OCD is relatively consistent across the age span in terms of prevalence, phenomenology, etiology, and response to treatment. Comorbidity, especially depression and other anxiety disorders, is common in children with OCD and may exert a negative influence on treatment response and long-term outcome. Nevertheless, CBT and SSRI therapy have been shown to be effective and well-tolerated therapies for children with OCD.

Verbalization and imagery during worry activity.

This study examined a model of worry as verbal activity that suppresses imagery and autonomic fear. The effects of emotional imagery vs. verbalization upon worry and fearfulness of an impending public speaking situation were assessed in 54 public speaking anxious participants who were categorized as worriers. Randomly assigned groups that processed the impending public speaking task either verbally or imaginally were compared to a group that received no processing instructions. Subjective distress was measured throughout the study. Results revealed partial support for the hypotheses that proportions of verbal thought and imagery shift upon threat presentation and a mitigation of fear habituation with verbalization. However, interpretation of between-group differences was complicated because the groups did not report consistent or complete adherence to cognitive processing instructions. Methodological and design implications for future investigations in this area are discussed.

Quantum leaps. A look at the health care delivery system in twenty years.

What will the health care delivery system of the future look like? Though 20 years from now may seem like a long way off for some people, health care experts are already seeing the seeds of future realities begin to sprout. But the new era of delivery also will involve many features now just barely imaginable, including wearable PCs, gene therapy, a diffusion of hospital services across a broad geographical area, and computer-based diagnoses.

Short-term stability of task-generated, interactional patterns in families of schizophrenic patients.

Both researchers and therapists who study schizophrenia make inferences about enduring family roles from observed patterns of interactional talking behavior within families. Evidence regarding the stability of these patterns is rarely investigated. The present study examined the short-term stability of intrafamilial speech patterns (who talks to whom) across two consecutive discussions. The sample was composed of families containing a recent-onset, adult schizophrenic patient. All discussions involved two biological parents and a young adult patient (N = 28). Families were classified into one of three interactional role-structure categories based on the intrafamilial speech patterns in two 10-minute discussions obtained in the same session. In addition, the affective style (Doane, West, Goldstein, et al., 1981) of the content of the discussions was coded. The results indicated that intrafamilial speech patterns were relatively stable across two discussions despite variations in the focus of the problem discussed. Further, when one parent was predominant in the discussion, a higher rate of negative affective statements was observed than when both parents were equal participants. The results provide further support for the use of discussion tasks in generating meaningful family interaction data.

A national survey of attitudes and practices of primary-care physicians relating to nutrition: strategies for enhancing the use of clinical nutrition in medical practice.

A nationwide mail survey was used to determine the degree to which primary-care physicians indicated that they practice the "core competencies" in clinical nutrition identified by Young et al (Am J Clin Nutr 1983;38:800-10). We also surveyed the nutrition-related attitudes of these physicians. Although the 3416 physicians who responded to the survey tended to report favorable attitudes toward using nutrition in their practice, these favorable attitudes were not consistent with their own reports of clinical performance. Neither the positive- or negative-attitude score correlated highly with the reported behavior-practice score. The clinical practices reported by those surveyed are well below the minimum level defined by the Young et al essential core competencies in clinical nutrition. The attitudes, practices, and demographic characteristics associated with the clinical performance variables suggest educational strategies for improving the competence of primary-care physicians and medical students in clinical nutrition.

Medication may be required for the development of automatic information processing in schizophrenia.

Medicated and unmedicated schizophrenic patients and normal subjects (n's = 4) were examined on the extent to which their information-processing performance became automated over time, as reflected by increased competence in dual task performance. The central task was a computerized version of the Continuous Performance Test, and the secondary task was a word-list shadowing task. Normal subjects and medicated schizophrenic patients became much more efficient at performing both tasks simultaneously with practice, with unmedicated patients showing no improvement over time.

Eye tracking, schizophrenic symptoms, and schizotypal personality disorder.

Schizophrenic patients and patients with schizotypal personality disorder were significantly more likely than normal controls to demonstrate impaired eye tracking performance. Fifteen of 27 schizophrenics and 15 of 27 schizotypals had impaired eye tracking, compared with 11 of 39 normal controls. In the schizophrenic group, including 10 out-patients in a stable state of relative remission, impaired eye tracking was associated with more severe formal thought disorder and more time spent in psychiatric hospitals. Among stable schizophrenic out-patients, poor eye tracking was related to more severe formal thought disorder and greater overall psychopathology. This pattern of results suggests a possible relation between eye tracking impairment and more severe enduring symptoms across the spectrum of schizophrenic and schizophrenia-related disorders.