Implementation,generalization and long-term results of the "choosing well" diabetes self-management intervention

Prerequisites for translating intervention research findings into practice are maintenance of results, generalization of effects and consistency of implementation. This report presents 12 months follow-up information on a randomized 2x2 factorial trial evaluating the incremental effects of adding (1) telephone follow-up or (2) a community resources utilization component to a basic touchscreen computer-assisted dietary goal-setting intervention for 320 type 2 diabetes patients. All conditions evidenced significant improvement from baseline to the 12 months follow-up across behavioral, biological and psychosocial measures. There were few consistent differences between conditions, but results were robust across interventionists and clinics. The telephone follow-up component appeared to enhance long-term results on some measures. When considered along with earlier results from a randomized trial that included a control condition without goal setting, it is concluded that this basic goal-setting intervention can be consistently implemented by a variety of interventionists and produce lasting improvements.     

Respiratory syncytial virus infection does not increase allergen-induced type 2 cytokine production, yet increases airway hyperresponsiveness in mice

Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined murine models of allergen-sensitization and RSV infection to explore the interaction of allergic and virus-induced airway inflammation and its impact on airway hyperresponsiveness (AHR). We found that RSV infection during ova-sensitization (OVA/RSV) increased and prolonged AHR compared to mice only RSV-infected (RSV) or ova-sensitized (OVA). AHR is known to be associated with an increase in Type 2 cytokines (IL-4, IL-5, and IL-13) in allergen-sensitized mice. Therefore, we hypothesized that RSV-induced enhancement of AHR was a result of potentiating the Type 2 cytokine profile promoted by ova-sensitization. Surprisingly, we found that Type 2 cytokines induced by ova-sensitization were not increased by RSV infection despite the increase in AHR, and in some cases were diminished. RNAse protection assay revealed no difference in IL-4 and IL-5 mRNA levels between the OVA and OVA/RSV groups, and IL-13 mRNA was significantly decreased in the OVA/RSV mice compared to the OVA group. Flow cytometric analysis of Type 2 cytokines demonstrated the same frequency of IL-4 and IL-5 production in lung-derived T lymphocytes from the OVA/RSV and OVA groups. Direct cytokine ELISA measurements of lung supernatant showed the level of IL-13 was significantly decreased in the OVA/RSV group compared to OVA mice, while there was no difference in either IL-4 or IL-5 between these two groups. These data indicate that the enhanced and prolonged AHR caused by the interaction of allergic airway inflammation and virus-induced immune responses is a complex process that can not be explained simply by augmented production of Type 2 cytokines.     

Measurement of total bile acids in gastric juice

An established method for the assay of total bile acids was validated for use in fasting and post-prandial gastric juice samples. Fasting and post-prandial intragastric bile acid concentrations were measured in 29 healthy volunteers, 15 patients after vagotomy and gastrojejunostomy (V and GJ) and 15 patients after vagotomy and pyloroplasty (V and P). Healthy female volunteers had higher post-prandial bile acid concentrations than age matched healthy males (p less than 0.02). Patients with V and GJ had higher fasting and post-prandial bile acid concentrations than age and sex matched control subjects (p less than 0.01). Patients with V and P had higher bile acid concentrations than control subjects only in post-prandial samples (p less than 0.05).     

Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells.

Interleukin-8 (IL-8) is a neutrophil chemotactic factor expressed in many cell types, including human airway epithelial cells (HAEC). Inhaled corticosteroids are now used increasingly early in the treatment of airway inflammation such as in asthma, and directly interact with HAEC at relatively high concentrations. We have investigated the effect of dexamethasone on IL-8 expression in primary cultured HAEC obtained from transplantation donors. Northern blot analysis was used to measure IL-8 mRNA levels in HAEC, and radioimmunoassay was used to measure IL-8 protein in culture supernatant fluids. We demonstrated that IL-8 was expressed by primary cultured HAEC and that this was enhanced by IL-1 beta and tumour necrosis factor-alpha stimulation, but not by IL-6 or lipopolysaccharide. Dexamethasone suppressed IL-8 mRNA expression and protein synthesis dose-dependently in both resting and stimulated HAEC. The half-life of IL-8 mRNA determined in the presence of actinomycin D was less than 1 hr, and dexamethasone preincubation had no effect on mRNA stability. These results support the view that HAEC may play an important role in the pathogenesis of airway inflammatory diseases, and that glucocorticosteroids may exert their anti-inflammatory effects by blocking IL-8 gene expression and generation in these cells.     

Risk and protective factors for suicidal behavior in abused African American women

This study examined risk and protective factors that differentiate low-income, abused African American women (N = 200) who attempted suicide from those who had never made a suicide attempt. Results from multivariate analyses revealed that numerous and/or severe negative life events, a history of child maltreatment, high levels of psychological distress and depression, hopelessness about the future, and alcohol and drug problems were factors associated with attempter status. Protective factors associated with nonattempter status included hopefulness, self-efficacy, coping skills, social support, and effectiveness in obtaining material resources. Culturally competent intervention approaches for abused women should target increasing their protective factors and reducing their risk factors to decrease the likelihood that these women engage in suicidal behavior.     

Study of T-lymphocyte subsets of healthy and Mycobacterium avium subsp. paratuberculosis-infected cattle.

The relative contributions of T-lymphocyte subsets to host defense in cattle infected with Mycobacterium avium subsp. paratuberculosis is reported. The subsets were purified with appropriate monoclonal antibodies and a magnetic bead column separation system, and their purity was verified by flow cytometry. Biological activity of each subset, expressed as lymphoproliferation and gamma interferon (IFN-gamma) production, was measured in response to phytohemagglutinin (PHA) and an M. avium antigen preparation (A-PPD). IFN-gamma was measured by antibody capture enzyme-linked immunosorbent assay. The results showed a correlation between proliferation and IFN-gamma production in response to A-PPD but not to PHA. In response to PHA, CD4+ lymphocytes were the most prolific producers of IFN-gamma. CD8+ lymphocytes produced IFN-gamma to a lesser extent, whereas gammadelta+ T lymphocytes produced little or no IFN-gamma. Differences observed between the amount of IFN-gamma produced by CD4+ versus CD8+ cells and CD4+ versus gammadelta+ cells were significant (P < 0.01), but those between peripheral blood mononuclear cells (PBMC) and CD4+ T cells were not. Similar responses to A-PPD were observed except that PBMC produced higher levels of IFN-gamma than did CD4+ T cells. These data for cattle are similar to observations made for other animal species, where CD4+ cells are the major type of T lymphocytes producing IFN-gamma. They further suggest that whatever the role gammadelta+ T cells may play in paratuberculosis, it is not likely to be mediated by IFN-gamma production.     

Population-based case control study of seroprevalence of Mycobacterium paratuberculosis in patients with Crohn's disease and ulcerative colitis

There is renewed enthusiasm for exploring the possibility that Mycobacterium paratuberculosis may be causative in Crohn's disease (CD). We aimed to determine whether CD subjects are more likely to be M. paratuberculosis seropositive than controls. Using our population-based University of Manitoba Inflammatory Bowel Disease Research Registry, we recruited CD and ulcerative colitis (UC) subjects between 18 and 50 years of age for a study involving detailed questionnaires and venipuncture. We accessed the population-based databases of Manitoba Health (single provincial health insurer) to get age-, gender-, and geography-matched controls to our inflammatory bowel disease (IBD) population. We asked enrolling IBD subjects for potential nonaffected sibling controls. We used an enzyme-linked immunosorbent assay (ELISA) for serum antibodies to M. paratuberculosis initially developed for cattle but adapted for human use. The rate of positive ELISA results, based on previously published interpretation criteria, was significantly higher for all study groups. There was no difference in M. paratuberculosis seropositivity rate among CD patients (37.8%; n = 283), UC patients (34.7%; n = 144), healthy controls (33.6%; n = 402), and nonaffected siblings (34.1%; n = 138). For siblings, there was no correlation between M. paratuberculosis serological status and that of the corresponding IBD affected sibling. None of the demographic or questionnaire variables studied were predictive of M. paratuberculosis status. Subjects with CD and UC were less likely to have ingested unpasteurized milk and less likely to have had a non-tap water source as a primary water source. In conclusion, in this population-based case control study, the M. paratuberculosis seropositivity rate was approximately 35% for all groups and there was no difference in rates between CD patients, UC patients, healthy controls, or nonaffected siblings. The much higher rate of seropositivity for subjects from Manitoba, Canada, than for those from Denmark or Wisconsin cannot be obviously explained. While these data seem to refute any association of CD with M. paratuberculosis, the high seroprevalence in Manitobans raises the possibility that the high rates of CD in Manitoba could be related to high exposure rates for M. paratuberculosis. Hence, the possibility of an association between M. paratuberculosis and CD remains inconclusive.     

Physiological response and childhood anxiety: association with symptoms of anxiety disorders and cognitive bias.

This study examined the physiological response (skin conductance and heart rate [HR]) of youth exposed to a mildly phobic stimulus (video of a large dog) and its relation to child- and parent-reported anxiety symptoms and cognitive bias in a community-recruited sample of youth (n = 49). The results of this study indicated that HR and skin-conductance response were associated with youth report but not parent report of their child's symptoms of anxiety disorders and that HR response was more strongly associated with anxiety symptoms than skin-conductance response. Physiological response was uniquely associated with youth-reported symptoms of anxiety rather than youth-reported depression. Finally, HR response interacted with cognitive bias in predicting childhood anxiety disorder symptoms in a manner consistent with theories of the etiology of anxiety disorders.     

An observational study of variation in GPs' out-of-hours emergency referrals.

Out-of-hours organisations are responsible for the care of patients 70% of the time, and their GPs act as gatekeepers to secondary care services. This observational study identifies the variations in GPs' out-of-hours referral rates to secondary care and factors that could explain these variations. One hundred and forty-nine GPs who worked in one UK general practice out-of-hours cooperative which served 19 practices with 167 000 registered patients. Data on patients who accessed the out-of-hours service over 3 years (2001-2004) were examined. Factors thought to be predictors of variation in referral rates were investigated using logistic regression analysis. There was a fivefold difference in referral rates between the lowest and highest referring quartiles of GPs (OR [odds ratio] = 4.56, CI [confidence interval] = 3.86 to 5.38). The sex (female) of the clinician, the time of the consultation (11 pm to 7 am), and the place of the consultation (home visit) accounted for some, but not all, of the increased referral rates. A doctor working out-of-hours disproportionately influences the fate of the patient, the number of hospital admissions, and extra costs to the health service. There is a need for follow-up studies to investigate the factors associated with referral behaviour, and how the variation relates to patient factors and the resources available. These findings could be used when planning the staffing of out-of-hours services to optimise appropriate care and minimise patients' exposure to unnecessary intrusive and expensive hospital care.