Placebo-controlled study of inhaled budesonide on indices of airway inflammation in bronchoalveolar lavage fluid and bronchial biopsies in cross-country skiers

BACKGROUND: Asthma-like symptoms, methacholine hyperresponsiveness, use of inhaled steroids, airway inflammation, and increased tenascin expression in the reticular basement membrane have been reported in competitive cross-country skiers. OBJECTIVE: To investigate the effect of inhaled budesonide, 400 mug twice daily, on indices of airway inflammation in 'ski asthma', defined as asthma-like symptoms within the previous year and bronchial hyperresponsiveness to methacholine. METHODS: A randomised double-blind placebo-controlled parallel-group bronchial biopsy and bronchoalveolar lavage (BAL) study of 25 (19 male) competitive cross-country skiers (mean age 18 (16-20) years for a mean (range) treatment period of 22 (10-32) weeks over the competitive season. RESULTS: No changes were seen regarding cellular inflammation in the bronchial mucosa or tenascin expression. In the BAL fluid, both groups had a significant decrease in activated T-suppressor (CD8) lymphocytes and an increase in macrophages, with no differences across the groups. Within the budesonide group, there was a decrease in IL2 receptor-activated T-helper lymphocytes and an improvement in FEV(1). Asthma-like symptoms were unchanged in 17 (68%) skiers. Methacholine provocation test was negative in 15 subjects, and remained positive in 5 subjects in each group. The improvement in bronchial responsiveness occurred in both groups and was not accompanied by a decrease in cellular inflammation. CONCLUSIONS: We were unable to show any clear beneficial effect of budesonide in 'ski asthma'. As changes in training intensity probably accounted for the spontaneous improvement in bronchial responsiveness, more attention should be directed at reducing environmental stress to the airways than at attempting pharmacological modulation of induced inflammatory changes.     

Radioimmunotherapy with 90Y-Labeled Monoclonal Antibodies in a Nude Mouse Ovarian Cancer Model

Tumor stroma contains much fibrin, and so monoclonal antifibrin antibody can accumulate in tumors. We treated nude mice bearing human ovarian carcinoma xenografts with ⁹⁰Y-labeled monoclonal antifibrin antibody Fab fragments administered intratumorally. The survival time vs. a control group was significantly prolonged and tumor growth rate was decreased. Another group of animals was treated with ⁹⁰Y-labeled OC 125-monoclonal antibody; these mice received the antibodies intratumorally, intraperitoneally or intravenously. The survival time was longest in the intratumorally treated group. There was no significant difference in survival between ⁹⁰Y-labeled OC 125 and antifibrin in the intratumorally treated animal groups. The tissue activity distribution studies revealed that bone marrow is the critical organ. Intratumorally injected monoclonal ⁹⁰Y-antifibrin antibodies were retained at least 36h (up to 50% of injected activity per gram tumor tissue) in the xenograft after one treatment, causing cell death. Beta-camera imaging and immunohistochemistry were performed for studies of the correlation between ⁹⁰Y activity and fibrin distribution in tumor specimens. These results were in concordance. In conclusion, intratumoral administration seems suitable for radioimmunotherapy, with an antibody that targets stromal structures. The accumulation can be successfully monitored by a beta-camera.     

Tolerability and Kinetics of a Solvent-Detergent-Treated Intravenous Immunoglobulin Preparation in Hypogammaglobulinaemia Patients

The tolerability and kinetics of a solvent-detergent-treated 6% intravenous immunoglobulin (IVIG) preparation were studied in 15 hypogammaglobulinaemia patients during 3–4 regular substitution infusions of 9–18 g, the mean dose being 359 mg/kg. The infusions were well tolerated, and the trough serum IgG levels achieved were comparable to two commercial IVIG preparations. The stepwise increase of the infusion rate up to 5 mg/kg/min and the use of this IVIG as a 12% solution were possible without serious adverse events in all the 6 studied hypogammaglobulinaemia patients. This greatly reduced the time needed for the infusions.     

Immunoglobulin G antibodies to herpes simplex type 1 virus detected by radioimmunoassay in serum and cerebrospinal fluid of patients with schizophrenia.

Serum and CSF specimens from 16 schizophrenic patients and 18 nonpsychiatric controls were tested by radioimmunoassay for immunoglobulin G antibody of capsid, envelope and excreted antigens of herpes simplex type 1 virus. There were no significant differences in the antibody levels between the schizophrenic patients and the controls. The etiological role of viruses and virus-like agents in schizophrenia and some methodological aspects are discussed.     

Characterization of breast milk received by infants with gross blood in stools

OBJECTIVE: The aim of this study was to ascertain factors that might be protective of the appearance of gross blood in the stools of breast-fed infants. METHODS: Logistic regression models were formed to search for variables possibly explaining the condition. In addition to the analyzed breast milk factors, mother's allergic disease was introduced into the models to control for its possible confounding effect. The breast milk samples, collected from mothers of infants with gross blood in stools (n = 23) and from mothers of healthy age-matched infants (n = 71), were analyzed for concentrations of transforming growth factor-beta2, tumor necrosis factor-alpha, interleukin (IL)-4, IL-10, prostaglandin (PG)E2, cysteinyl leukotrienes (Cys-LTs) and fatty acid composition. RESULTS AND CONCLUSIONS: Increase in the concentrations of PGE2 and Cys-LTs in the breast milk together with mother's allergic disease reduced the likelihood of gross blood in stools in the breast-fed infant. The results suggest that no single factor, but a combination of immunomodulatory factors may protect the child from gross blood in the stools of breast-fed infants. Allergic disease was not a risk factor as mother's allergic disease appeared to counterbalance the gross blood in stools. Due to the preliminary nature of the study, the results need to be verified in a larger setting. The challenge for the future lies in identifying of such active compounds for dietary modification to enforce particularly the properties of the breast milk which are immunoprotective for the infant and to reduce the likelihood of intestinal disorders in at risk infants.     

Novel approaches to the nutritional management of the allergic infant

The increased prevalence of atopic diseases, i.e. atopic eczema, allergic rhinitis and asthma, has been described as the epidemic of the 21st century in Western societies. New approaches in the fight against allergic diseases are clearly called for, the target being the persistence of the allergic responder pattern beyond infancy. The advantage afforded by elimination diets lies in the silencing of specific allergic inflammation induced by an offending food. Novel nutritional approaches, beyond the treatment of food allergies, have recently attracted research interest subsequent to the identification of the immunomodulatory potential of specific dietary compounds. Dietary lipids as immunomodulators may prevent allergic sensitization by down-regulating inflammatory response whilst protecting the epithelial barrier. Probiotic bacteria have been shown to reinforce the different lines of gut defence: immune exclusion, immune elimination and immune regulation. On this basis, the strategy against allergic disease proposed here is based on the administration of tolerogenic gut-processed peptide fragments of a specific protein, in addition to the use of specific dietary compounds such as fatty acids and antioxidants, and introducing a microbial stimulus for the immature immune system by means of cultures of beneficial live micro-organisms characteristic of the healthy infant gut microbiota.     

Body mass index and weight change from adolescence into adulthood, waist-to-hip ratio and perceived work ability among young adults

OBJECTIVES: To study how body mass index (BMI, kg/m2) at 14 and 31 years (y) changes in BMI between 14 and 31 y, and waist-to-hip ratio (WHR) at 31 y are associated with poor perceived working ability at 31 y. DESIGN AND SUBJECTS: A population-based cohort, originally 11637 people, born in Northern Finland in 1966 was resurveyed at 14 and 31 y. MEASUREMENTS: Perceived work ability (measured by modified work ability index, WAI), BMI, WHR, alcohol intake, smoking, basic education and work history were recorded at 31 y and BMI also at 14 y. RESULTS: Low WAI (15% of lowest values) at 31 y showed a U-shaped association with BMI at 14 y, and also with BMI at 31 y, except in obese males. Low WAI similarly had a U-shaped association with WHR, but in males only, while in females, the probability of low WAI increased almost linearly with WHR. Low WAI was more common among smokers and people with a low level of education. The pattern for alcohol intake was more equivocal, with a nonsignificant finding in males and an almost linear decrease of low WAI with increasing alcohol intake in females. CONCLUSIONS: Work ability, health habits and anthropometric measures should be evaluated regularly in young workers, and preventive measures against diseases leading to premature retirement should be taken in time, for example by the occupational health-care service.