Wegener's granulomatosis: a challenging disease for otorhinolaryngologists

Diagnosis of Wegener's granulomatosis (WG) can be delayed because of its aspecific presenting symptoms. Detection of serum circulating antineutrophil cytoplasm antibodies (c-ANCAs), in combination with histology, permits one to identify WG at an early stage and to implement stage-adapted therapy. c-ANCA levels may also help to evaluate the response to medical therapy. Recently, the quality of life of WG patients has been improved by administering cotrimoxazole in order to prevent infections and recurrent diseases during the remission period.WG is of special significance to the otorhinolaryngologist because it is often initially limited to the upper respiratory tract before becoming systemic. The aim of this paper was to describe a series of WG patients and underline the difficulties involved in diagnosing and treating this challenging disease.This was a prospective study in 23 consecutive patients with head and neck manifestations of WG (17 systemic, 6 limited). Diagnosis was performed by means of both c-ANCAs detection using indirect immunofluorescence and histology in biopsy specimens. Treatment consisted of daily cyclophosphamide (CYC; 2 mg/kg/day) and glucocorticoids (prednisone; 1 mg/kg/day). If an improvement or toxic events occurred, CYC was discontinued and methotrexate was started. If, during remission of the disease, low serum c-ANCAs levels were detected, CYC was suspended and cotrimoxazole (1 g/day) was introduced.Serum c-ANCAs detection was positive for all patients. Biopsy was diagnostic from the beginning in 19/23 cases. The six patients with limited WG did not show a progression to systemic disease. Only 3 patients with a diagnosis of delayed systemic WG died, whereas 19/23 patients were alive with good control of relapses.     

A large outbreak of scombroid fish poisoning associated with eating escolar fish (Lepidocybium flavobrunneum)

In August 2003, an outbreak of scombroid fish poisoning occurred at a retreat centre in California, USA. In a retrospective cohort study, 42 (75%) of the 56 dinner attendees who ate escolar fish (Lepidocybium flavobrunneum) met the case definition. Individuals who ate at least 2 oz of fish were 1.5 times more likely to develop symptoms than those who ate less (relative risk 1.5, 95% confidence interval 0.9-2.6), and to develop more symptoms (median 7 vs. 3 symptoms, P = 0.03). Patients who took medicine had a longer duration of symptoms than those who did not (median 4 vs. 1.5 h, P = 0.05), and experienced a greater number of symptoms (median 8 vs. 3 symptoms, P = 0.0002). Samples of fish contained markedly elevated histamine levels (from 2000 to 3800 ppm). This is one of the largest reported outbreaks of scombroid fish poisoning in the United States and was associated with a rare vehicle for scombroid fish poisoning, escolar.     

Mental health and hostility as predictors of temporary employment: evidence from two prospective studies

We used two studies to examine whether mental health and hostility predicted temporary employment. Study 1 involved a cohort of 970 Finnish hospital employees (102 men, 868 women) who had temporary job contracts at baseline. After adjustment for demographics, organisational tenure and part-time work status, doctor-diagnosed psychiatric disorder predicted continuing in temporary employment instead of receiving a permanent job by the end of the 2-year follow-up. A higher level of hostility was also associated with temporary employment, but only among employees in low socioeconomic positions. In Study 2, anxiety and aggressive behaviour were measured in a cohort of 226 Finnish school children (116 boys, 110 girls) at 8 years of age. Anxiety in childhood predicted temporary employment at age 42. Aggressive behaviour in childhood was related to ongoing temporary employment status in adulthood among individuals in low socioeconomic positions. Our findings suggest that selection by individual characteristics operates between the temporary and permanent workforces. Mental health problems, a part of which are already seen in childhood, seem to restrict individuals' possibilities to gain secure labour market positions. Hostility and aggressiveness seem to be related to labour market prospects only among individuals in low socioeconomic positions.     

Case-mix adjusted odds ratios as an alternative way to compare hospital performances

The purpose of this study was to compare two different methods to describe C-section variability among hospital units: case-mix adjusted ORs and case-mix adjusted rates.About 41,755 deliveries without previous C-section occurred in 60 hospitals in 2001 were analysed. Logistic regression was used to produce both adjusted rates and ORs by maternity unit. The two methods showed similar rankings, however ORs estimates were more precise and proved to be a useful tool to describe C-section variability across hospitals.The revised version was published online in July 2005 with corrections in the title.     

Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure

Substituted 3-(phenylamino)-1H-pyrrole-2,5-diones were identified from a high throughput screen as inducers of human ATP binding cassette transporter A1 expression. Mechanism of action studies led to the identification of GSK3987 as an LXR ligand. GSK3987 recruits the steroid receptor coactivator-1 to human LXRalpha and LXRbeta with EC(50)s of 40 nM, profiles as an LXR agonist in functional assays, and activates LXR though a mechanism that is similar to first generation LXR agonists.     

The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura

Background  

The C677T variant in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased levels of circulating homocysteine and is a mild risk factor for vascular disease. Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that may also be affected by genetically influenced hyperhomocysteinaemia. To determine whether the C677T variant in the MTHFR gene is associated with migraine susceptibility we utilised unrelated and family-based case-control study designs.     

P16 as a molecular biomarker of cervical adenocarcinoma

OBJECTIVE: Cervical adenocarcinomas are increasing in incidence each year. The aim of this study was to identify a molecular biomarker to improve early detection. STUDY DESIGN: Fifty-five in situ and invasive cervical adenocarcinomas were compared with 5 normal endocervical controls by immunohistochemical analysis of p16, p21, p27, cyclin D1, cyclin E, p53, and Ki-67. Expression was scored from 0 to 8 by using an automated imaging system. Western blotting and polymerase chain reaction-based human papillomavirus (HPV) testing were performed on 16 of the invasive cases having fresh-frozen tissue. RESULTS: P16 exhibited a higher mean expression score for in situ (7.4; P<.0001) and invasive cervical adenocarcinoma (6.6; P<.0001) versus controls (2.0). A cutoff p16 expression score of 5 had a sensitivity of 94.5% and a specificity of 100%. Western blotting confirmed p16 protein expression. Fourteen (88%) of 16 invasive cervical adenocarcinomas were HPV-positive. CONCLUSION: P16 is a putative molecular biomarker of cervical adenocarcinoma. Overexpression appears to primarily reflect HPV-induced cell cycle dysregulation.