Reported distress associated with concern about a cigarette smoker

It is well documented that concerned others of alcohol abusers report distress associated with the substance user's behavior. No previous study has examined distress associated with concern for someone who smokes cigarettes. To investigate this association, college students, ages 18-24 (N=1719), completed a survey assessing whether or not they were close to someone who smokes whom they thought should quit and the level of distress they experienced regarding this person's smoking. 827 (48.1%) respondents endorsed knowing a smoker whom they thought should quit and 60% reported experiencing at least some distress regarding this person's smoking. From multivariate analysis, the presence of distress (any vs. none) was associated with female gender (OR=1.8, 95% C.I. 1.2, 2.5, p=0.001), never tobacco user (OR=2.0, 95% C.I. 1.4, 2.9, p<0.001), and elevated Perceived Stress Scale score (OR=1.05, 95% C.I. 1.02, 1.08, p<0.001, per 1 unit increase in PSS score). These findings contribute to our understanding of how smoking impacts the psychological well being of another and is intended to stimulate future research investigating the potential for distressed individuals to serve as change agents in tobacco control efforts.     

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.     

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.     

Candidate microbicides block HIV-1 infection of human immature Langerhans cells within epithelial tissue explants

Initial biologic events that underlie sexual transmission of HIV-1 are poorly understood. To model these events, we exposed human immature Langerhans cells (LCs) within epithelial tissue explants to two primary and two laboratory-adapted HIV-1 isolates. We detected HIV-1(Ba-L) infection in single LCs that spontaneously emigrated from explants by flow cytometry (median of infected LCs = 0.52%, range = 0.08-4.77%). HIV-1-infected LCs downregulated surface CD4 and CD83, whereas MHC class II, CD80, and CD86 were unchanged. For all HIV-1 strains tested, emigrated LCs were critical in establishing high levels of infection (0.1-1 microg HIV-1 p24 per milliliter) in cocultured autologous or allogeneic T cells. HIV-1(Ba-L) (an R5 HIV-1 strain) more efficiently infected LC-T cell cocultures when compared with HIV-1(IIIB) (an X4 HIV-1 strain). Interestingly, pretreatment of explants with either aminooxypentane-RANTES (regulated upon activation, normal T cell expressed and secreted) or cellulose acetate phthalate (potential microbicides) blocked HIV-1 infection of LCs and subsequent T cell infection in a dose-dependent manner. In summary, we document HIV-1 infection in single LCs after exposure to virus within epithelial tissue, demonstrate that relatively low numbers of these cells are capable of inducing high levels of infection in cocultured T cells, and provide a useful explant model for testing of agents designed to block sexual transmission of HIV-1.     

Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden

Patients with inflammatory bowel disease have an increased frequency of thromboembolism, and microvascular thrombosis has been proposed as a contributory pathogenic factor. The mechanism of enhanced procoagulant activity is not understood. We examined the clinical setting of thromboembolic events in 52 patients with Crohn's disease or ulcerative colitis, and assessed the procoagulant laboratory profile, including Factor V Leiden, in a subset of 20 patients to identify procoagulant risk factors. Patients who developed thrombosis tended to be young; 60% of thrombotic events occurred in patients under 50 years. Multiple thromboembolic episodes occurred in 13% and unusual sites of thrombosis (e.g. intracardiac, cerebral, inominate veins) in 11%. No risk factor was identifiable in 52% of cases and two-thirds of thromboses occurred in an out-patient setting. The mortality rate was 8%. Evidence for inflammatory disease activity was found in only 45% of patients with ulcerative colitis at the time of the thromboembolic event, in contrast to 89% of those with Crohn's disease. Assays for specific coagulation defects were negative in all cases tested (protein S, C were normal in 17/17; anti-thrombin III, anti-phospholipid antibodies and activated protein C resistance were negative in 20/20, and only 1/20 patients was found to be heterozygous for Factor V leiden. Thrombosis in inflammatory bowel disease is important because it occurs in a young population, often in unusual sites, and has a high mortality. The development of thrombosis is related to active inflammatory disease in most patients with Crohn's disease but apparently not in those with ulcerative colitis. Since approximately half of the patients had no other identifiable risk factor, there remains a substantial group of patients with IBD who develop thrombosis for unknown reasons.      

Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4- one iron chelators in overloaded and nonoverloaded mice

Five orally effective iron chelators of the 3-hydroxypyridin-4-one series have been administered intraperitoneally to iron-overloaded and nonoverloaded male mice at a dose of 200 mg/kg/24 h for a total of 60 days to investigate the effect on iron loading and toxicity. There was a significant reduction in hepatic iron at the end of the study in the iron-overloaded mice with all compounds studied using chemical iron quantitation (P less than .001) and with Perls' stain (P less than .01). Liver iron removal with the hydroxypyridinones ranged from 37% with CP20 to 63% with CP51, compared with 46% removal for desferrioxamine (DFO). There was no significant reduction in splenic or cardiac iron with any chelator. There were no deaths in iron-overloaded animals receiving any of the hydroxypyridin-4-ones, but significantly more deaths in the nonoverloaded groups as a whole (P less than .03). No weight loss was observed with any chelator. Significant reductions in hemoglobin and white cell count were observed with CP20(L1). No histologic abnormalities of kidney, spleen, bone marrow, or stifle joints were observed. Intracytoplasmic inclusion bodies were observed in the centrilobular hepatocytes of animals administered each of the hydroxypyridin-4-ones, while the DFO-treated and control groups showed no such changes.