Cerebral accumulation of Tc-99m ethyl cysteinate dimer (ECD) in severe, transient hypothyroidism.

Thyroid dysfunction is a well-known contributor to psychiatric morbidity. To investigate the mechanism(s) by which thyroid hormone availability affects cerebral activity, a group of thyroidectomized individuals were studied at two points in time: when markedly hypothyroid in preparation for a thyroid cancer metastatic survey and when clinically and/or biochemically euthyroid. The analysis consisted of single photon emission computed tomography (SPECT) using a lipophilic radiopharmaceutical, technetium-99m (Tc-99m) ethyl cysteinate dimer (ECD), and measurement of mood, anxiety, and psychomotor function, at both points in time. Both increases and decreases in regional cerebral radiotracer activity were found in the hypothyroid condition relative to the euthyroid condition, and the neuropsychological assessment demonstrated significantly greater depression, anxiety, and psychomotor slowing during the hypothyroid state. Increased radiotracer activity was seen in frontal and temporal regions, posterior cingulate gyrus, thalamus, and putamen. Decreased activity was seen in the occipital cortex, and the pre- and postcentral gyri. This distribution pattern is partially consistent with findings in persons with depression and anxiety unrelated to thyroid disease, supporting the link between the symptoms observed in our subjects and their marked hypothyroidism. Finally, these results support the need to consider the effect of the thyroid state on cellular mechanisms of uptake and retention of cerebral blood flow radiopharmaceuticals when studying 'noneuthyroid' individuals.     

A model for sustainable short-term international medical trips.

The health status of many people in developing countries is often dismal compared with the norms in industrialized countries. Increasingly, medical practitioners in the United States and other industrialized countries have become interested in global health issues, an interest that often takes the form of short-term international medical trips. We discuss several ethical issues associated with participation in such trips and use our experiences in developing the Children's Health International Medical Project of Seattle (CHIMPS) to outline and illustrate a set of 7 guiding principles for making these trips. CHIMPS is a resident-run, faculty-supported international medical program founded in 2002 by pediatric residents at the University of Washington in Seattle. Members of CHIMPS work with a rural community in El Salvador to support ongoing public health interventions there and provide sustainable medical care in collaboration with the community and a local nongovernmental organization. The 7 principles developed as a result of this work-mission, collaboration, education, service, teamwork, sustainability, and evaluation-can be used as a model for health practitioners as they develop or select international medical trips. The importance of partnering with the community and working within the existing medical and public health infrastructure is emphasized. Many of the challenges of doing international medical work can be overcome when efforts are guided by a few specific principles, such as those we have outlined.     

Region-specific constitutive gene expression in the adult porcine meniscus.

The knee meniscus exhibits extensive spatial variations in native healing capacity, biochemical composition, and cell morphology that suggest the existence of distinct phenotypes for meniscus cells. Constitutive gene expression levels of appropriate extracellular matrix proteins may serve as useful molecular markers of cellular phenotypes; however, relatively little is known of variations in the gene expression for meniscus cells of different regions of the tissue. The objective of the present study was to evaluate constitutive differences between radial inner and outer regions in gene expression for extracellular matrix proteins relevant to the meniscus. A secondary objective was to determine if these region-specific differences in gene expression are maintained after periods of monolayer culture. The innermost regions of the meniscus were found to constitutively express higher mRNA levels for proteins highly expressed in articular cartilage, including aggrecan, type II collagen, and NOS2. In contrast, the outer meniscus was found to contain higher gene expression for proteins associated with fibrous tissues including type I collagen, and the proteases MMP2 and MMP3. Isolated inner and outer meniscus cells maintained these region-specific gene expression patterns for collagens and proteoglycans during short-term monolayer culture. The results provide new information that suggests the utility of constitutive gene expression levels as molecular markers to distinguish tissue and cells of the inner and outer meniscus.     

Acute marijuana effects on human risk taking.

Previous studies have established a relationship between marijuana use and risky behavior in natural settings. A limited number of laboratory investigations of marijuana effects on human risk taking have been conducted. The present study was designed to examine the acute effects of smoked marijuana on human risk taking, and to identify behavioral mechanisms that may be involved in drug-induced changes in the probability of risky behavior. Using a laboratory measure of risk taking designed to address acute drug effects, 10 adults were administered placebo cigarettes and three doses of active marijuana cigarettes (half placebo and half 1.77%; 1.77%; and 3.58% Delta9-THC) in a within-subject repeated-measures experimental design. The risk-taking task presented subjects with a choice between two response options operationally defined as risky and nonrisky. Data analyses examined cardiovascular and subjective effects, response rates, distribution of choices between the risky and nonrisky option, and first-order transition probabilities of trial-by-trial data. The 3.58% THC dose increased selection of the risky response option, and uniquely shifted response probabilities following both winning and losing outcomes following selection of the risky option. Acute marijuana administration thereby produced measurable changes in risky decision making under laboratory conditions. Consistent with previous risk-taking studies, shifts in trial-by-trial response probabilities at the highest dose suggested a change in sensitivity to both reinforced and losing risky outcomes. Altered sensitivity to consequences may be a mechanism in drug-induced changes in risk taking. Possible neurobiological sites of action related to THC are discussed.     

Inappropriate Vancomycin Prescribing Based on Criteria from the Centers for Disease Control and Prevention

Increasing reports of vancomycin resistance have raised concerns about the future effectiveness of this drug in treatment of critically ill patients with gram-positive infections. Due to these concerns the Centers for Disease Control and Prevention (CDC) recently published criteria that delineate the prudent use of vancomycin. Using these criteria, we attempted to determine the appropriateness of vancomycin prescribing patterns at our institution. A retrospective chart review was performed for 135 hospitalized patients treated between May 1993 and April 1994. Inappropriate empiric vancomycin use was documented in 81 (60%) of these patients. When culture results were available, 28 (21%) patients inappropriately received the drug. Results of this study are similar to those of other studies of vancomycin use in hospitals based on non-CDC criteria. If CDC criteria are to have a positive impact on physicians' vancomycin prescribing patterns, significant educational efforts will be required.     

An Integrated Psychotherapy Approach to the Management of Self-Destructive Behavior in Eating Disorder Patients with Borderline Personality Disorder

The management of self-destructive behavior in eating disorder patients with borderline personality is a genuine therapeutic challenge. We present an integrated psychotherapy appproach that we utilize in the context of an extended therapeutic milieu. This treatment model enables coordinated intervention to occur in three different arenas: individual psychotherapy, group psychotherapy, and consultation intervention. The paper closes with a discussion of the limitations of this approach.     

Randomized clinical trial of tacrolimus- vs cyclosporine-based immunosuppression in pediatric heart transplantation: preliminary results at 15-month follow-up.

BACKGROUND: While Tacrolimus (Tac) and Cyclosporine (Cya) immunosuppression are used after cardiac transplantation (tx), few studies have evaluated their use in pediatric patients. METHODS: We randomized 26 heart transplant recipients (pts) in a prospective, open-label trial to Tac (n = 14) or Cya (n = 12) to compare their efficacy and side-effects. Mean age at tx was 4.2 years for Tac and 5.8 years for Cya. Mean follow-up was 26 months (range: 11-39 months) for Tac and 24 months for Cya (range: 33-13 months). RESULTS: Our data suggest that both regimens are efficacious in the pediatric population. Conversion from Cya to Tac was useful for dealing with persistent rejection, although this sample did not suggest lower incidence of acute cellular rejection in the Tac group. CONCLUSIONS: Further studies are required to establish pharmacokinetic parameters to enhance therapeutic monitoring of these patients to minimize side effects and enhance outcomes.     

Alterations in the mechanical behavior of the human lumbar nucleus pulposus with degeneration and aging

This study tested the hypothesis that changes in the morphology and composition of the nucleus pulposus with age and degeneration have associated changes in its mechanical properties. A torsional shear experiment was used to determine viscoelastic shear properties of cylindrical samples of human nucleus pulposus with large ranges of grades of morphological degeneration (normal to severely degenerated) and ages (range: 16–88 years; average: 57 ± 21.5 years). Viscoclastic shear properties were determined from stress-relaxation and dynamic sinusoidal tests. A linear viscoelastic law with a variable-amplitude relaxation spectrum was used to model experimental behaviors of nucleus pulposus specimens. A statistically significant increase in the instantaneous and dynamic shear moduli was found with increasing age and grade of degeneration; the values for moduli ranged from 5.0 to 60 kPa. A significant decrease in tanδ was also detected; the values ranged from 0.43 to 0.33, indicating a decreased capacity for the nucleus pulposus to dissipate energy. The dynamic modulus and tanδ were also significantly affected by frequency. It was generally concluded that the nucleus pulposus undergoes a transition from “fluid-like” behavior to more “solid-like” behavior with aging and degeneration.     

Brief report: Does fenfluramine treatment enhance the cognitive and communicative functioning of autistic children?

This project was supported by two separate research grants from the Trust Fund Board, Washington Association for Retarded Citizens to Richard Neel and Truman E. Coggins. The research was also supported by a training grant to the University of Washington entitled Comprehensive Training in Mental Retardation and Other Handicapping Conditions (MCH-000913, Clifford J. Sells, M.D., Principal investigator); and, a training grant to the University of Arizona entitled Doctoral and Post-Doctoral Leadership Training and Clinical Research, Teaching and Administration: Clinical Language Research Center (G008630088, Linda Swisher, Ph.D., principal investigator). We are indeed grateful to the parents of our five subjects for their patience, understanding, and commitment. Finally, we express our appreciation to Arelene Chaussee for her technical expertise and untiring spirit.     

Family functioning in school-age children with cystic fibrosis: an observational assessment of family interactions in the mealtime environment

OBJECTIVE: To examine, using direct observation methodology, differences in family functioning at mealtime between families of school-age children with cystic fibrosis (CF) and families of school-age children without a chronic illness. METHOD: Family functioning was rated using the McMaster Mealtime Interaction Coding System (MICS) during a videotaped dinner among 28 families of children with CF and 27 families of non-ill, age-matched peers. Families were rated on overall family functioning and on six dimensions of the MICS: task accomplishment, communication, affect management, interpersonal involvement, behavior control, and role allocation. RESULTS: Ratings for families of a child with CF were significantly lower than they were for comparison families on overall family functioning and on four of the six MICS dimensions: communication, affect management, interpersonal involvement, and behavioral control. Moreover, a significantly greater percentage of families of children with CF were rated in the unhealthy range on overall family functioning and on five of six MICS dimensions. There was no relationship between family functioning and child weight status for children with CF. CONCLUSIONS: The current study suggests that for families of school-age children with CF, the family system is negatively affected during mealtime. Dietary interventions need to address family-centered, as well as child-centered, interventions to help families manage challenges presented during the family meal.