Predicting moderate improvement and decline in pediatric asthma quality of life over 24 months

Objective  

To determine factors associated with 24-month change in quality of life in children with asthma and their parents during the Childhood Asthma Management Program (CAMP).     

Follow-up of abnormal screening mammograms among low-income ethnically diverse women: findings from a qualitative study

OBJECTIVE: To understand factors that women feel facilitate or hinder their receipt of diagnostic services following an abnormal screening mammogram. METHODS: This qualitative study used a purposive sampling strategy to identify low-income, ethnically diverse women aged 40 or over who had a recent abnormal mammogram. Working with a community health center, breast evaluation center, and mobile mammography van, 64 women were interviewed to identify salient themes that differentiated women who received timely follow-up from those who did not. RESULTS: Prominent themes among women who delayed follow-up included dissatisfaction with communication of results; perceived disrespect on the part of providers and clinic staff; logistical barriers to access of diagnostic services; anxiety and fear about a possible cancer diagnosis; and a lack of information about breast cancer screening and symptoms. Women who received timely care more often reported an appreciation of efforts by providers and clinic staff to support their prompt follow-up; availability of social support that facilitated appointment-keeping; confidence in their ability to advocate for their health; and a high priority placed on self-care. CONCLUSION: A comprehensive approach to improving timely diagnostic follow-up among underserved groups must address patient beliefs and attitudes, provider practices and communication, and practices at the health care systems level. PRACTICE IMPLICATIONS: Implications and strategies for improving patient education, patient-provider communication, and organizational practices are discussed.     

Flow cytometric determination of peripheral blood lymphocyte subpopulations and haematological values in the neonatal calf

Non-vaccinated Holstein female calves, 3–31 days old (n=106) were examined in order to determine peripheral blood lymphocyte subpopulations and haematological values. The relative populations of lymphocytes were determined using flow cytometry. Monoclonal antibodies were used to identify BoCD2⁺, BoCD4⁺, BoCD8⁺, B-cells,/ T-cells, and monocytes/neutrophils, respectively. Complete blood counts were also determined. Calves were stratified into four groups by age (days): group A = 3–7 days, group B = 8–14 days, group C = 15–21 days and group D = 22–31 days. Group A calves had 30%–70% lower numbers of all lymphocyte subtypes compared to older calves. Group B calves had significantly lower numbers of B-cells than calves in group D, but were not different from group C. Calves in groups B and C had significantly lower/ T-cell counts than calves in group D. All other group comparisons of lymphocyte subtypes and the ratios of BoCD4⁺ to BoCD8⁺ T-cells were not significantly different.Calves in group A had significantly lower white blood cell counts than older calves and had significantly lower lymphocyte numbers than group C and D calves. Calves in group D had significantly higher lymphocyte counts than younger calves. Groups A and B had significantly higher neutrophil to lymphocyte ratios than groups C and D. Absolute numbers of monocytes, eosinophils and basophils were not different among any of the groups. Group A calves had significantly lower red blood cell counts than older calves. Calves in groups A and B had significantly higher mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) values than calves in group C. Group C calves also had significantly higher MCH and MCV values than calves in group D. Significant differences in haemoglobin, haematocrit and mean corpuscular haemoglobin concentration values were not apparent among any of the four groups. In this cross-sectional study we observed that older calves consistently had higher numbers of all subtypes of peripheral blood lymphocytes, compared to younger calves.     

Age-related changes in brain proDynorphin gene expression in the rat

Dynorphin has a well-established role in feeding and gustation. Alterations in taste perception and feeding behavior are common with age. We hypothesized that proDynorphin gene expression in brain areas involved in taste and feeding declines with age. Male Sprague-Dawley rats were housed individually with ad libitum access to food and water. Brain punches of the selected regions were dissected out in groups of rats aged 4–6, 12–14 and 18–21 months. ProDynorphin mRNA (measured using a cDNA probe) decreased significantly with age in arcuate nucleus and amygdala; increased significantly with age in hippocampus; and was not significantly affected in nucleus of the solitary tract, cortex, caudate putamen or hypothalamic paraventricular nucleus. These data suggest an age-related decrease in the synthesis of dynorphin in two brain regions strongly associated with feeding behavior, and an increase in dynorphin synthesis in a brain region associated with learning and memory.     

Analysis of Vascular Endothelial Growth Factor (VEGF) and a receptor subtype (KDR/flk-1) in the liver of rats exposed to riddelliine: a potential role in the development of hemangiosarcoma

Riddelliine alters hepatocellular and endothelial cell kinetics and function including stimulating an increase in hepatocytic vascular endothelial growth factor (VEGF) in the absence of increased serological levels of VEGF (Nyska etal. 2002). The objective of this study was to further assess hepatic VEGF and KDR/flk-1 synthesis and expression by hepatic cells under riddelliine treatment conditions. Forty-two male F344/N rats were dosed by gavage with riddelliine (0, 1.0, and 2.5 mg/kg/day) for 6 weeks. Seven animals/group were sacrificed after 8 consecutive daily doses; remaining rats were terminated after 30 daily doses, excluding weekends. Hepatic tissues were evaluated by immunohistochemistry and in situ hybridization. The results showed that VEGF mRNA expression was observed in control and treated animals; however, qualitative differences were noted. Treated animals exhibited VEGF mRNA in clustered, focal hepatocytes and bile duct epithelium, whereas VEGF mRNA in hepatocytes from vehicle control rats was distributed evenly across all hepatocytes. Results evaluating the distribution of the VEGF cognate receptor, KDR/flk-1 showed that randomly distributed, rare sinusoidal endothelium, including those demonstrating karyomegaly and cytomegaly expressed KDR/flk-1. Phosphorylation of KDR/flk-1 at pTyr996 and pTyr1054/1059, but not pTyr951, was also detected, evidence that endothelial cell KDR/flk-1 was activated. These results suggest that both hepatocytes and endothelial cells are targets of riddelliine-induced injury. We speculate that damage to both populations of cells may lead to dysregulated VEGF synthesis by hepatocytes and activation of KDR/flk-1 by endothelium leading to the induction of sustained endothelial cell proliferation, culminating in the development of hepatic hemangiosarcoma.     

Current advances in HIV vaccines

Development of a safe and preventive HIV-1 vaccine is a high priority. Recent advances in HIV vaccine development include an improved understanding of HIV envelope structure, development of techniques that enable a detailed analysis of vaccine-induced immune responses in humans, expansion of the pipeline of promising candidate vaccines, and completion of the first vaccine efficacy trials. A common feature of several preventive vaccine strategies in early clinical trials is their ability to attenuate clinical disease rather than completely prevent HIV infection in nonhuman primates. One or more candidate vaccines will likely advance into efficacy trials within the next few years, while efforts to identify new designs that induce broadly neutralizing antibodies continue with incremental success.     

Identification and molecular characterization of EatA, an autotransporter protein of enterotoxigenic Escherichia coli

Enterotoxigenic Escherichia coli (ETEC) strains remain a formidable cause of diarrheal disease. To identify novel surface proteins of ETEC, we performed TnphoA mutagenesis of prototype ETEC strain H10407 and discovered a secreted protein not previously recognized in ETEC. DNA sequencing of the interrupted locus in mutant TnphoA.977 revealed a candidate 4,095-bp open reading frame without significant homology to commensal E. coli K-12 genomic DNA. Translation of this sequence revealed that it encoded a predicted peptide of 147.7 kDa that bears significant homology to members of the autotransporter family of bacterial virulence factors, particularly the serine protease autotransporters of the Enterobacteriaceae proteins. The gene identified in H10407, eatA (ETEC autotransporter A), encodes a potential serine protease motif (GDSGSP) in the secreted amino-terminal domain, and the predicted peptide shows more than 80% homology with SepA, a virulence protein secreted by Shigella flexneri. DNA hybridization and PCR demonstrated that eatA resides on the 92-kDa pCS1 virulence plasmid of H10407 and that it is present in multiple clinical ETEC strains. Immunoblots with antisera directed against a recombinant EatA passenger protein fragment identified a 110-kDa protein in supernatants purified from H10407 but not from the TnphoA.977 mutant or H10407-P, which lacks pCS1. EatA possesses serine protease activity that is abolished by mutations within a serine protease catalytic triad formed by residues H(134), D(162), and S(267). Finally, interruption of the eatA gene retarded fluid accumulation in the rabbit ileal loop model, suggesting that this autotransporter contributes to the virulence of ETEC.     

Implementation of HaemScreen, a workplace-based genetic screening program for hemochromatosis

There is debate as to whether community genetic screening for the mutation(s) causing hereditary hemochromatosis (HH) should be implemented, due to issues including disease penetrance, health economic outcomes, and concerns about community acceptance. Hemochromatosis is a common preventable iron overload disease, due in over 90% of cases to C282Y homozygosity in the HFE gene. We are, therefore, piloting C282Y screening to assess understanding of genetic information and screening acceptability in the workplace setting. In this program, HaemScreen, education was by oral or video presentation in a group setting. C282Y status was assessed by polymerase chain reaction (PCR) and melt-curve analysis on DNA obtained by cheek-brush sampling. Of eligible participants, 5.8% (1.5-15.8%) attended information and screening sessions, of whom 97.7% (5571 individuals) chose to be tested. Twenty-two C282Y (1 : 253) homozygotes were identified and offered clinical follow-up. There were 638 heterozygotes (1 : 8.7). The determinants for participation have been analyzed in terms of the principles outlined in the Health Belief Model. Widespread screening for HH is readily accepted in a workplace setting, and a one-to-many education program is effective. The level of participation varies greatly and the advertizing and session logistics should be adapted to the specific features of each workplace.     

Interleukin-1 receptor antagonist attenuates airway hyperresponsiveness following exposure to ozone

The role of an interleukin (IL)-1 receptor antagonist (IL-1Ra) on the development of airway hyperresponsiveness (AHR) and airway inflammation following acute O(3) exposure in mice was investigated. Exposure of C57/BL6 mice to O(3) at a concentration of 2.0 ppm or filtered air for 3 h resulted in increases in airway responsiveness to inhaled methacholine (MCh) 8 and 16 h after the exposure, and an increase in neutrophils in the bronchoalveolar lavage (BAL) fluid. IL-1beta expression, assessed by gene microarray, was increased 2-fold 4 h after O(3) exposure, and returned to baseline levels by 24 h. Levels of IL-1beta in lung homogenates were also increased 8 h after O(3) exposure. Administration of (human) IL-1Ra before and after O(3) exposure prevented development of AHR and decreased BAL fluid neutrophilia. Increases in chemokine levels in lung homogenates, tumor necrosis factor-alpha, MIP-2, and keratinocyte chemoattractant following O(3) exposure were prevented by IL-1Ra. Inhalation of dexamethasone, an inhibitor of IL-1 production, blocked the development of AHR, BAL fluid neutrophilia, and decreased levels of IL-1 following O(3) exposure. In summary, acute exposure to O(3) induces AHR, neutrophilic inflammation, epithelial damage, and IL-1. An IL-1Ra effectively prevents the development of altered airway function, inflammation, and structural damage.