Chronic hyperplastic eosinophilic sinusitis as a predictor of aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a disease of intense eosinophilic inflammation that can produce fibrosis, hyperplasia, and remodeling. OBJECTIVE: To investigate the usefulness of quantifying severity of chronic hyperplastic eosinophilic sinusitis in predicting the presence of AERD. METHODS: Data were compared between asthmatic patients who reported exacerbations after aspirin ingestion and those who did not. The primary outcome measure was severity of sinusitis using a validated computed tomography (CT) scan-based scoring system. Indices of lower airway remodeling and other markers of inflammation were also evaluated. RESULTS: Twenty-one patients with AERD were compared with 19 patients with aspirin-tolerant asthma (ATA). Patients were well matched for asthma severity as shown by their similar lung function as measured by postbronchodilator forced expiratory volume in 1 second. Patients with AERD were distinguished by their sinus CT scores (AERD patients: 16.9; 95% confidence interval [CI], 13.4-21.3; ATA patients: 6.2; 95% CI, 4.2-9.1; P < .001), and they were considerably more likely to have nasal polyps (AERD patients: 90%; ATA patients: 26%; P < .001). In addition, AERD patients demonstrated increased total lung capacity (AERD patients: 107.9%; 95% CI, 99.9%-117.6%; ATA patients: 98.0%; 95% CI, 93.7%-102.5%; P = .05), reflecting a trend toward increased air trapping. No significant differences occurred in diffusing capacity, exhaled nitric oxide, eosinophilia, or exhaled breath condensate pH. CONCLUSIONS: AERD can be distinguished from ATA by the extent of hyperplasia on CT scan and the presence of nasal polyps. We hypothesize that AERD represents a remodeling process that affects both the upper and lower airways.     

p75(NTR) gene and suicide attempts in young adults with a history of childhood-onset mood disorder.

Recently, evidence has accumulated for the role of neurotrophic processes in mood disorders. Neurotrophins operate on receptors, one of which is the p75 neurotrophin receptor (p75(NTR)). We examined three p75(NTR) markers at the p75(NTR) gene, including a missense polymorphism that changes serine to leucine (S205L), for association with suicide attempt (SA) in 203 childhood-onset mood disorder (COMD) cases. There was no difference between COMD suicide attempters and COMD non-attempters with logistic regression models for any of the three markers. We also compared the three polymorphisms between 192 COMD cases and 192 matched healthy controls and found no significant differences between COMD and healthy controls. Our results do not support an association of the p75(NTR) S205L polymorphism with risk for COMD or SA in COMD.     

Effect of lithium carbonate therapy on thyroid immune status in manic depressive patients: a prospective study

Serum thyroid autoantibodies to thyroglobulin (TG) and thyroid microsomes (M) were measured by ELISA prospectively in 37 manic depressive patients prior to receiving lithium carbonate and during therapy with this drug for a mean of 16.2 months. They were also measured once in 27 normal subjects and several times in five psychiatric patients not receiving lithium. Sixteen patients (43%) had either thyroglobulin, microsomal antibodies or both before receiving lithium therapy. During therapy significant fluctuations in antibody titre, both upwards and downwards were observed in ten out of 12 patients with M antibodies and in nine out of 11 with TG antibodies. The fluctuations in antibody titre are consistent with an immunomodulatory effect of lithium as has been shown in animal studies. It is suggested that psychiatric patients should have thyroid antibodies measured routinely before and during lithium therapy.     

Factor structure and validity of the parenting scale.

Confirmatory factor analyses based on the scoring derived from 5 prior studies of the Parenting Scale were conducted using a representatively recruited sample of 453 couples parenting 3-to 7-year-old children. Comparative analyses favored the Reitman et al. (2001) 2-factor scoring system as well as a 3-factor solution, including Lax, Overreactive, and Hostile discipline. This 3-factor solution demonstrated good fit across parent gender and child age and gender. Mothers rated themselves as more overreactive than fathers. The factor scores correlated significantly with several validity measures, including child behavior problems. The Hostile factor contributed significantly to the prediction of child behavior problems after controlling for Lax and Overreactive discipline. Both parents reported using more dysfunctional discipline than they thought they should.     

Using path analysis to understand executive function organization in preschool children

There continues to be no consensus definition of executive functions. One way to understand different executive function components is to study abilities at their emergence, that is, early in development, and use advanced statistical methods to understand the interrelations among executive processes. However, to fully determine the constructs of interest, these methods often require complete data on a large battery of tasks, which are difficult to obtain with young children. Path analysis is an alternative statistical technique that requires only a single measure of each construct, yet still allows researchers to investigate complex relations among measures, to compare nested models, and to compare model fit across groups. Therefore, 117 preschool children (ages 2 years 8 months to 6 years 0 months) completed several executive function tasks. Path analysis was used to determine the relations between complex problem solving and working memory, inhibition, and set shifting processes. The best-fitting model included paths from working memory and inhibition to problem solving, and a correlation between working memory and inhibition. Interestingly, in younger children, inhibition was the strongest predictor of problem solving, whereas working memory contributed more strongly in older children. Suggestions for useful statistical methods to investigate the relations among executive functions in children are discussed.     

Disseminated toxoplasmosis in cardiac transplantation.

The first case of disseminated toxoplasmosis following cardiac transplantation in the UK is described, with details of Toxoplasma antibody tests made on other cardiac transplant patients. Sixteen of 40 (39%) of recipients had Toxoplasma antibody before operation. Eleven of 30 (37%) of donors had Toxoplasma antibody. The were four occasions when a negative recipient received a heart from a positive donor. Three survived the immediate postoperative period and two became infected with toxoplasmosis. The implications of this are discussed. Disseminated toxoplasmosis appears much more often when heart muscle from a dye test positive donor is given to a dye test negative recipient. Antibiotic therapy is limited by the fact that the antitoxoplasma drugs available are static in their effect, and need to be given for prolonged periods postoperatively.     

Recombinant Helicobacter bilis Protein P167 for Mouse Serodiagnosis in a Multiplex Microbead Assay

Infection of mice with Helicobacter bilis is widespread in research and commercial mouse colonies. Therefore, sensitive, specific, and high-throughput assays are needed for rapid and accurate testing of mice in large numbers. This report describes a novel multiplex assay, based on fluorescent microbeads, for serodetection of H. bilis infection. The assay requires only a few microliters of serum to perform and is amenable to a high-throughput format. Individual microbead sets were conjugated to purified, H. bilis-specific, recombinant proteins P167C and P167D and bacterial membrane extracts from H. bilis and Helicobacter hepaticus. For detecting H. bilis infection in the microbead multiplex assay, P167C and P167D provided significantly higher sensitivities (94 and 100%, respectively) and specificities (100 and 95%, respectively) than membrane extract (78% sensitivity and 65% specificity). Microbead multiplex assay results were validated by enzyme-linked immunosorbent assay. Purified recombinant proteins showed low batch-to-batch variation; this feature allows for ease of quality control, assay robustness, and affordability. Thus, recombinant antigens are highly suitable in the multiplex microbead assay format for serodetection of H. bilis infection.     

Cytokine gene polymorphism in human disease: on-line databases

The pathologies of many infectious, autoimmune and malignant diseases are influenced by the profiles of cytokine production in pro-inflammatory (TH1) and anti-inflammatory (TH2) T cells. Interindividual differences in cytokine profiles appear to be due, at least in part, to allelic polymorphism within regulatory regions of cytokine gene. Many studies have examined the relationship between cytokine gene polymorphism, cytokine gene expression in vitro, and the susceptibility to and clinical severity of diseases. A review of the findings of these studies is presented. An on-line version featuring appropriate updates is accessible from the World Wide Web site, http://www.pam.bris.ac.uk/services/GAI/cytokine4.htm.