Effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a multinational randomized, controlled birth-cohort study – 24 months results of the Study of Prevention of Allergy in Children in Europe

BACKGROUND: Sensitization to house dust mite (HDM) is an important risk factor for the development of asthma and allergic disease in childhood. Higher levels of HDM allergen are linked to increased sensitization to HDM. OBJECTIVE: To study the effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a newborn cohort. METHODS: Six hundred and ninety-six newborns at high risk of developing allergies were enrolled in three European countries (Germany, Austria, UK) in a prospective, randomized, controlled birth-cohort study. Children were randomly assigned to an intervention and control group. Intervention measures included the use of mite-impermeable mattress encasings for the child's bed and a simple educational package on allergen avoidance. The control group received basic information about allergies. Children were followed up at age 6, 12, 18 and 24 months. RESULTS: 80.9% of the children were followed up to the age of 24 months. No difference in the prevalence of sensitization to HDM (control vs. intervention group: 8.4% vs. 6.1%, P=0.33) or the development of symptoms (recurrent wheezing 10.3% vs. 10.7%, nocturnal cough 12.5% vs. 12.5%) or allergic diseases (asthma 3.5% vs. 5.1%, eczema 20.0% vs. 19.6%, rhinitis 28.9% vs. 25.8%) could be found between the control and intervention group. CONCLUSION: In this study, HDM avoidance did not show a protective effect on the development of sensitization to HDM or symptomatic allergy in children at age 24 months.     

Rectus muscle flap for repair of refractory bladder fistula following renal transplantation: a case report

We report a case of refractory bladder fistula in a diabetic renal allograft recipient that recurred shortly after conventional operative repair without any detectable external cause. After reoperation and use of a vascularized rectus muscle flap the fistula closed and the patient has retained excellent graft function. It is suggested that this technique should be considered as the primary repair modality for bladder fistulas in diabetic recipients, when wound healing is impaired seriously as a consequence of the combined effects of diabetic microangiopathy and steroid therapy.     

Urinary leukotriene E(4), eosinophil protein X, and nasal eosinophil cationic protein are not associated with respiratory symptoms in 1-year-old children

BACKGROUND: Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation. METHODS: We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis. RESULTS: One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1). CONCLUSIONS: At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in characterizing the phenotype of a single patient.     

Accumulation of atopic disorders within families: a sibling effect only in the offspring of atopic fathers

BACKGROUND: Several studies have reported an association between a child's risk of atopic disorders and family size. However, the inverse association might not be the same in populations with a different genetic disposition for atopic disorders. OBJECTIVE: This longitudinal study was designed to assess risk factors of atopy. METHODS: Lifetime prevalence of asthma, hay fever and eczema of 1440 families including 3165 offspring was ascertained by means of standardized questionnaires. RESULTS: After possible confounders had been controlled for, an inverse association between atopic disorders and the number of older siblings was found only in the offspring of atopic fathers (trend for older siblings: chi2 = 13.38, degrees of freedom [d.f.] = 1, P= 0.0002; odds ratio 'no older sibling'= 2.87 (95% confidence interval 2.18-3.78); '1 older sibling' = 2.11 [1.52-2.92], '2 older siblings' = 1.29 [0.74-2.23]; '3 or more older siblings' = 0. 15 [0.02-0.981). No such relationship was found for children without a history of paternal atopy (trend for older siblings: chi2 = 1.5 1, d.f. = 1, P = 0.22; odds ratio 'no older sibling' = 1 [reference]; '1 older sibling' =0.82 [0.63-1.06]; '2 older siblings' = 0.97 [0.67-1.40]; '3 or more older siblings' = 0.64 [0.31-1.33]). The trend for older siblings in the case of paternal atopy was significantly different from the trend for older siblings without a history of paternal atopy (chi2 = 8.68, d.f. = 1, P = 0.003). The number of younger siblings was not related to child's risk of atopy (trend for younger siblings: chi2 = 0.001, d.f. = 1, P = 0.97). CONCLUSIONS: Data from this study suggest a protective effect of sibship size only in children with a history of paternal atopy and if older siblings are present. The reason for this combined effect remains unclear. Thus, further investigations are needed to interpret the biological cause of the so called 'sibling effect'.     

Asthma und asthmatypische Beschwerden bei Schulkindern: Vergleich von Gebieten in Deutschland und Osterreich

Conclusion

Geographical differences in morbidity of asthma and asthmalike complaints were ascertained and remained stable after adjustment for potential confounders. However, the choice of the way of presentation (relative risk versus deviation from the weighted mean of the prevalences) can provoke different suggestive effects.     

Medicine misuse or drug abuse? A critical appraisal of current issues and research in the UK

During the last decade consumption of licit medications and illicit drugs has risen substantially. It is estimated that the 100 000–200 000 severely dependent drug misusers in the UK generate social costs of 3–4 billion annually, while the cost of prescribed medicines for the entire population is currently 5 billion. Although attitudes and behaviours have been extensively researched, they remain complex and often contradictory. In particular, little is known of how perceptions of the benefits and risks of chemical substances influence behaviour. At an epidemiological level, new methods such as capture–recapture are being used to delineate forms of drug abuse which have previously not been detected in household surveys. There are few current data on the extent of inappropriate medicine prescribing, although there are various initiatives to promote rational and cost-effective prescribing. Reasons for inappropriate medicine use include patient expectations, prescribers' perceptions of patients and drug company marketing. Advances in basic science are revealing hitherto unsuspected consequences of both licit and illicit drug use. Examples include (1) the role of analgesics in causing severe headache and (2) suppression of immune functioning due to Ecstasy. One illustration of changing attitudes, as a result of public and medical pressure, is the growing call for the licensing of cannabis for medicinal use, particularly for intractable conditions such as multiple sclerosis. With the recently announced drug strategy promising a shift towards evidence-based decision-making, innovative research is required to improve the currently fragmentary view of the general population's attitudes and behaviour in relation to medicines and drugs.     

Vascular endothelial growth factor receptor-2 inhibition in experimental murine colitis

Background

In the setting of inflammatory bowel disease, inflammation is associated with a simultaneous increase in angiogenesis; moreover, elevated vascular endothelial growth factor (VEGF) levels implicate angiogenesis as a pathologic contributor to disease severity. We hypothesize that selectively inhibiting vascular endothelial growth factor receptor-2 (VEGFR2) in a model of murine colitis will reduce angiogenesis, resulting in decreased inflammation and disease severity, providing mechanistic insight into the role of pathologic angiogenesis in IBD.

Materials and methods

In a dextran sodium sulfate model of murine colitis, anti-VEGFR2 monoclonal antibody (DC101) or placebo was administered. Clinical assessments followed by histologic and molecular tissue analysis were performed to quantify inflammation, microvessel density (MVD), VEGF and VEGFR2 gene expression, and phosphorylated mitogen-activated protein kinase protein expression.

Results

Weight loss began after d 6 with the treatment group demonstrating a more favorable percent weight change. Inflammation and MVD were similar between cohorts, both increasing in parallel toward a plateau. VEGF and VEGFR2 messenger RNA expression were not significantly different, but phosphorylated mitogen-activated protein kinase was elevated in the DC101 cohort (P = 0.03).

Conclusions

Despite a more favorable weight change profile in the treated group, no difference was observed between cohorts regarding clinical disease severity. However, a parallel rise in inflammation and MVD was observed coinciding with weight loss, suggesting their relationship in IBD. VEGFR2 downstream signaling was significantly elevated in the treated cohort, possibly by VEGF-independent signal transduction. Early and effective inhibition of angiogenesis by limiting downstream VEGF signaling or targeting multiple angiogenic pathways may block angiogenesis, thereby reducing disease severity and provide evidence toward the mechanism and clinical benefit of antiangiogenics in the setting of IBD.