Child psychiatric disorders: prevalence and perspectives

This article provides a review of child psychiatric epidemiology, particularly as it applies to community prevalence surveys. By way of introduction, the administrative and scientific uses of epidemiology are outlined. Major issues in the field are discussed including prevalence versus incidence, definition of deviance and correlates, psychometric properties of instruments, sampling, sources of data, general maladjustment versus specific disorder, and comparability and generalizability of results. Current findings presented include a review of prevalence estimates for general maladjustment, conduct disorder, neurotic disorder, hyperactivity, and depressive disorder. Information is presented on the correlates of sex, age, social class, family factors, and school influences. The clinical implications of the correlate data are discussed and include the importance of utilizing multiple sources of data during the assessment phase and basing a treatment plan on a comprehensive assessment in which interventions are aimed at specific risk factors and strengths. Last, future directions of the field are suggested including the importance of gaining data on the correlates of the duration rather than the occurrence of disorders and the need for randomized clinical trials in which innovative prevention and treatment programs are launched and carefully evaluated.     

Differential effects of two citrus flavanones on bone quality in senescent male rats in relation to their bioavailability and metabolism

The effect of hesperidin (Hp) and naringin (Nar), two major citrus flavanones, on the regulation of bone metabolism was examined in male senescent rats. Twenty -month -old gonad-intact male Wistar rats received a casein-based diet supplemented with or without either 0.5% hesperidin (Hp), 0.5% naringin (Nar) or a mix of both flavanones (Hp+Nar, 0.25% each). After 3 months, daily Hp intake significantly improved femoral bone integrity as reflected by improvements in total and regional bone mineral densities (BMD) (9.7%-12.3% improvements, p<0.05) and trabecular bone volume fraction (24.3% improvement, p<0.05) at the femur compared with control group. In contrast, naringin exerted site-specific effects on BMD (10.2% improvement at the distal metaphyseal area, p<0.05) and no further benefit to bone mass was observed with the mix of flavanones. Bone resorption (DPD) was significantly attenuated by Hp and Nar given alone (40.3% and 26.8% lower compared to control, p<0.05, respectively) but not by the mixture of the two. All treatments significantly reduced expression of inflammatory markers to a similar extent (IL-6, 81.0-87.9% reduction; NO, 34.7-39.5% reduction) compared to control. Bone formation did not appear to be strongly affected by any of the treatments (no effect on osteocalcin levels, modest modulation of tibial BMP-2 mRNA). However, as previously reported, plasma lipid-lowering effects were observed with Hp and Nar alone (34.1%-45.1% lower for total cholesterol and triglycerides compared to control, p<0.05) or together (46% lower for triglycerides, p<0.05). Surprisingly the plasma circulating level of naringin (8.15μM) was >5-fold higher than that of hesperidin (1.44μM) at equivalent doses (0.5%) and a linear reduction in plasma levels was observed upon co-administration (0.25% each) indicating absence of competition for their intestinal absorption sites and metabolism. The higher efficacy of Hp at a lower plasma concentration than naringin, as well as the identification of the major circulating metabolite of hesperidin (hesperetin-7-O-glucuronide) underlines the importance of flavanone bioavailability and metabolism in their biological efficacy and suggests a structure-function relationship in the mechanism of action of the active metabolites.     

Validation of the revised Self-Administered Alcohol Screening Test (SAAST-R)

This study examined the sensitivity and specificity of the revised Self-Administered Alcohol Screening Test (SAAST-R)1 among adult outpatients evaluated at community addictions and psychiatry and psychology clinics. A total of 417 adults (mean +/- SD age of 41.4 +/- 15.0 years, 52% female, 91% Caucasian) completed the 36-item SAAST-R prior to their evaluation. Based on the clinician's documentation of the patient's alcohol use, two criterion groups were established: one composed of subjects classified as having no alcohol problems (n = 214), and one with alcohol problems (n = 203). The SAAST-R was found to have high internal consistency reliability (Cronbach's alpha = 0.96), sensitivity (90%), and specificity (82%) for differentiating outpatients with and without alcohol problems, respectively, using a cut point of >or=4 to indicate risk for alcohol-related problems. The SAAST-R was found to have good sensitivity and specificity among both males and females.     

Chemokine analogues show suitable stability for development as microbicides

New prevention strategies are urgently needed to slow the spread of the HIV/AIDS pandemic, and in the absence of an effective vaccine, there is hope that "microbicides"-HIV inhibitors applied to mucosal surfaces before sexual intercourse-may be able to make an impact. Because developing countries are at the center of the epidemic, affordability and stability during storage are key criteria for candidate microbicides. Furthermore, because formulation strategies that provide long-duration protection after a single dose may enhance acceptability and compliance, stability in the vaginal environment and in the presence of semen should also be considered. PSC-RANTES, a human chemokine analog, has shown promise as a candidate microbicide, but because it contains nonnatural structures that necessitate chemical synthesis steps, it is not suitable for production at a feasible cost and scale for general distribution in developing countries. We have recently developed 2 new fully recombinant chemokine analogs, 5P12-RANTES and 6P4-RANTES, which show equivalent anti-HIV activity to PSC-RANTES. In this study, we tested the stability of these molecules under conditions related to use as microbicides. Our results suggest that stability issues will not present a major obstacle to the further development of these promising molecules as microbicides.     

Dynamics of melanoma tumor therapy with vesicular stomatitis virus: explaining the variability in outcomes using mathematical modeling

Tumor selective, replication competent viruses are being tested for cancer gene therapy. This approach introduces a new therapeutic paradigm due to potential replication of the therapeutic agent and induction of a tumor-specific immune response. However, the experimental outcomes are quite variable, even when studies utilize highly inbred strains of mice and the same cell line and virus. Recognizing that virotherapy is an exercise in population dynamics, we utilize mathematical modeling to understand the variable outcomes observed when B16ova malignant melanoma tumors are treated with vesicular stomatitis virus in syngeneic, fully immunocompetent mice. We show how variability in the initial tumor size and the actual amount of virus delivered to the tumor have critical roles on the outcome of therapy. Virotherapy works best when tumors are small, and a robust innate immune response can lead to superior tumor control. Strategies that reduce tumor burden without suppressing the immune response and methods that maximize the amount of virus delivered to the tumor should optimize tumor control in this model system.     

Treatment of asthma with nebulized lidocaine: a randomized, placebo-controlled study

BACKGROUND: In 2 prior uncontrolled studies, nebulized lidocaine reduced oral glucocorticoid use in patients with severe glucocorticoid-dependent asthma. OBJECTIVE: We tested the safety and efficacy of nebulized lidocaine in a randomized, placebo-controlled study in patients with mild-to-moderate asthma. METHODS: We recruited 50 subjects (25 receiving lidocaine and 25 receiving placebo); all had a prebronchodilator FEV(1) of 64% to 125% of predicted normal value and were treated with daily inhaled glucocorticoids (but not systemic glucocorticoids) and bronchodilators for at least 2 months. Before treatment, subjects monitored their symptoms and peak flow values and maintained their medications for 2 weeks. At initiation, subjects inhaled either nebulized placebo (saline) or lidocaine (4%, 100 mg) 4 times daily. All subjects were instructed to reduce their inhaled glucocorticoid dosage by one half each week for 3 weeks and to discontinue glucocorticoid treatment at week 4. The subjects continued the nebulized lidocaine or placebo for a total of 8 weeks, monitored their symptoms, and used bronchodilators to control symptoms. RESULTS: Indicators of asthma severity showed benefit for the lidocaine-treated group: changes in FEV(1) (P < or =.001), nighttime awakenings (P < or =.02), symptoms (P < or =.010), bronchodilator use (P < or =.010), and blood eosinophil counts (P < or =.020). Subjects in both groups reduced use of inhaled glucocorticoids comparably. Subjects receiving nebulized placebo showed increases in their symptom scores, bronchodilator use (P < or =.05 for both), and blood eosinophil counts (P < or =.01) and decreases in FEV(1) (P < or =.001). CONCLUSION: Nebulized lidocaine provided effective and safe therapy in subjects with mild-to-moderate asthma.     

Role of epithelial interleukin-8 (IL-8) and neutrophil IL-8 receptor A in Escherichia coli-induced transuroepithelial neutrophil migration.

Escherichia coli stimulates neutrophil migration across human uroepithelial cell layers. This study investigated the role of the neutrophil chemokine interleukin-8 (IL-8) in this process. E. coli and IL-1alpha stimulated urinary tract epithelial layers to secrete IL-8 and induced transepithelial neutrophil migration. Anti-IL-8 antibody reduced neutrophil migration across epithelial cell layers, indicating a central role for this chemokine in the migration process. Furthermore, addition of recombinant IL-8 to unstimulated cell layers was sufficient to induce migration. The IL-8 dependence of neutrophil migration was maintained after removal of soluble IL-8 by washing of the cell layers. Flow cytometry analysis with fluorescein isothiocyanate-labelled IL-8 confirmed IL-8's ability to bind to the epithelial cell surface. Indirect immunofluorescence with confocal laser scanning microscopy showed that IL-8 associated with the epithelial cell layers. Prior incubation of neutrophils with antibodies to IL-8 receptor A (IL-8RA) reduced neutrophil migration. Anti-IL-8 RB antibody had no effect on neutrophil migration. These results demonstrate that IL-8 plays a key role in E. coli- or IL-1alpha-induced transuroepithelial migration and suggest that epithelial cell-produced IL-8 interacts with IL-8RA on the neutrophil surface.     

Development and feasibility of a parental support intervention for adolescent smokers

The aim of this investigation was to develop and evaluate the feasibility and acceptability of a parental support intervention. A new measure of perceived parental support for stopping smoking was also developed. The sample included 59 adolescent-parent pairs recruited from a mid-sized Midwestern town during 2000-2003. The mean +/- SD age of the participants (32 males, 27 females) was 16.3 +/- 0.9 (range 14-18) years and 86% were Caucasian, 7% American Indian, 5% African American, and 2% Hispanic. Participants were randomized to parental support or minimum behavioral intervention. Severity of nicotine dependence was evaluated using the Fagerstr?m Tolerance Questionnaire, and perceived social support was evaluated using the Family Environment Scale and the new measure of perceived parent support for stopping smoking that was developed as part of this investigation. Treatment attendance, adherence, and acceptability were also evaluated. The parental support intervention was feasible but not superior to the minimum behavioral intervention with respect to attendance, retention, or change in support. This study expands on the knowledge of treating adolescent smokers and presents a new assessment measure. The study's limitations are noted. This investigation was funded by NICHHD.