Genetic association studies of interleukin-13 receptor alpha1 subunit gene polymorphisms in asthma and atopy.

Interleukin (IL)-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13 receptor alpha1 subunit (IL-13Ralpha1) and IL-4Ralpha. The genetic diversity at the IL-13Ralpha1 gene (IL13RA1) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with asthma and atopy phenotypes examined. The promoter and coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects. Genetic association was determined using case-control and transmission disequilibrium test analyses. Two common polymorphisms were identified, a newly found thymidine (T) to guanine (G) transition of nucleotide -281 (-281T>G) single nucleotide polymorphism in the IL13RA1 promoter and the previously described 1365A>G variant in the IL13RA1 proximal 3' untranslated region. No significant association of either -281T>G or 1365A>G with risk of asthma or atopy phenotypes was found, apart from a suggestive association between the IL13RA1 -281T/1365A haplotype and raised total serum immunoglobulin E levels in adult female asthmatics. These findings indicate that the interleukin-13 receptor alpha1 subunit gene -281T>G and 1365A>G polymorphisms do not contribute to asthma susceptibility or severity, although the interleukin-13 receptor alpha1 subunit gene locus might be involved in the control of immunoglobulin E production.     

Developmental expression of aldehyde dehydrogenase in rat: a comparison of liver and lung development.

Metabolism is one of the major determinants for age-related changes in susceptibility to chemicals. Aldehydes are highly reactive molecules present in the environment that also can be produced during biotransformation of xenobiotics and endogenous metabolism. Although the lung is a major target for aldehyde toxicity, early development of aldehyde dehydrogenases (ALDHs) in lung has been poorly studied. The expression of ALDH in liver and lung across ages (postnatal day 1, 8, 22, and 60) was investigated in Wistar-Han rats. In adult, the majority of hepatic ALDH activity was found in mitochondria, while cytosolic ALDH activity was the highest contributor in lung. Total aldehyde oxidation capability in liver increases with age, but stays constant in lung. These overall developmental profiles of ALDH expression in a tissue appear to be determined by the different composition of ALDH isoforms within the tissue and their independent temporal and tissue-specific development. ALDH2 showed the most notable tissue-specific development. Hepatic ALDH2 was increased with age, while the pulmonary form did not. ALDH1 was at its maximum value at postnatal day 1 (PND1) and decreased thereafter both in liver and lung. ALDH3 increased with age in liver and lung, although ALDH3A1 was only detectible in lung. Collectively, the present study indicates that, in the case of aldehyde exposure, the in vivo responses would be tissue and age dependent.     

Suppurative corneal ulceration in Bangladesh

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.     

Psychiatric mental health nursing: challenge and change

. We invited Dr Peplau to provide a personal reflection on the recent history of psychiatric nursing and her thoughts on immediate challenges facing the profession. The paper is an individual scholar's commentary on the way that psychiatry has waxed and waned over the years, in relation to nursing. This historical review discovers and reports a challenge to current practice. Dr Peplau describes a professional shift that is pulling nurses toward the subordinate role observed earlier this century. The paper draws attention to how contemporary practice can be positively influenced, e.g., by giving a structure to the allocation and conduct of nurse–patient time.     

Red blood cell methotrexate and folate levels in children with acute lymphoblastic leukemia undergoing therapy: a Pediatric Oncology Group pilot study

Summary We enrolled children with acute lymphoblastic leukemia (ALL) in a Pediatric Oncology Group (POG) pilot study to monitor erythrocyte (RBC) methotrexate (MTX) and folate (F) levels before and during treatment. The mean value for RBCF at diagnosis was 0.86±0.46 nmol/ml RBC in the 214 patients who achieved remission and 1.21±0.74 nmol/ml RBC in the 10 patients who did not (P=0.020). Folate levels tended to increase during remission induction, but they dropped following an intensive consolidation with methotrexate to levels that were sustained throughout chemotherapy treatment. Methotrexate levels reached mean values of approximately 0.15 nmol/ml RBC at the end of an intensive methotrexate consolidation, then fell to levels that were sustained throughout maintenance therapy. There was a weak correlation between improved event-free survival and higher RBCMTX levels after consolidation, but no correlation was found between improved survival and the level of RBCMTX or RBCF during maintenance therapy. A larger study with more complete data is needed to determine whether RBCMTX or RBCF might be useful in predicting event-free survival in patients with ALL.This work was supported in part by grants from the National Cancer Institute and the National Institute of Health (CA-30969, CA-28476, CA29139, CA-159-89, and CA-33587)