Prognostic values of specific respiratory sounds for asthma in adolescents

Childhood wheezing is a common condition associated with asthma, but the term is often misapplied. The present study aimed to investigate the prognostic values of specific respiratory sounds for asthma onset in adolescence. In a prospective study, six specific respiratory sounds were evaluated for their prediction of asthma. Parents were asked for respiratory sounds of their initially asthma-free children and to describe them in specified terms. Self-reported doctor-diagnosed asthma of 1,569 children aged 5 to 14 years from Germany was assessed at baseline and at follow-up for up to 12 years later. Except for ‘ronchus’ (17%), reported ‘gasp’ and ‘whimper’ had the highest positive predictive values of 15% and 11%, respectively. These sounds also showed the greatest increase in asthma incidence (odds ratio = 3.18; 95%CI, 1.46–6.94 and odds ratio = 2.09; 95%CI, 1.00–4.37). It could be shown that from six respiratory sounds, ‘gasp’ and ‘whimper’ were the expressions with the best prediction for asthma onset. This study suggests that parents can sensibly distinguish between respiratory sounds and that it is important to specify breathing sounds, as not all are good predictors for asthma.     

Individual outcome prediction for myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia from MDS after allogeneic hematopoietic cell transplantation

We integrated molecular data with available prognostic factors in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) from MDS to evaluate their impact on prognosis. Three hundred four patients were sequenced for mutations in 54 genes. We used a Cox multivariate model and competing risk analysis with internal and cross validation to identify factors prognostic of overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). In multivariate analysis, mutated NRAS, U2AF1, IDH2, and TP53 and/or a complex karyotype were significant prognostic markers for OS besides age above 60 years, remission status, IPSS-R cytogenetic risk, HCT-CI > 2 and female donor sex. Mutated NRAS, IDH1, EZH2, and TP53 and/or a complex karyotype were genetic aberrations with prognostic impact on CIR. No molecular markers were associated with the risk of NRM. The inclusion of molecular information results in better risk prediction models for OS and CIR when assessed by the Akaike information criterion. Internal cross validation confirmed the robustness of our comprehensive risk model. In summary, we propose to combine molecular, cytogenetic, and patient- and transplantation-associated risk factors into a comprehensive risk model to provide personalized predictions of outcome after alloHCT.     

Altered Cardiac Repolarization in Association with Air Pollution and Air Temperature among Myocardial Infarction Survivors

Background

Epidemiological studies have shown that ambient particulate matter (PM) and changes in air temperature are associated with increased cardiopulmonary events.

Objective

We hypothesized that patients with previous myocardial infarction (MI) experience changes in heart rate (HR) and repolarization parameters, such as Bazett-corrected QT interval (QTc), and T-wave amplitude (Tamp), in association with increases in air pollution and temperature changes.

Methods

Between May 2003 and February 2004, 67 MI survivors from the Augsburg KORA-MI registry repeatedly sent 16 sec electrocardiograms (ECGs) with a personal transmitter (Viapac) via telephone to the Philips Monitoring Center, where ECG parameters were immediately analyzed. Meteorological data and air pollutants were acquired from fixed monitoring sites on an hourly basis. Additive mixed models were used for analysis. Effect modification by patient characteristics was investigated.

Results

The analysis of the 1,745 ECGs revealed an increased HR associated with interquartile range (IQR) increases in PM levels among participants not using beta-adrenergic receptor blockers and among those with body mass index ≥ 30 kg/m². We observed a 24- to 47-hr lagged QTc prolongation [0.5% change (95% confidence interval, 0.0–1.0%)] in association with IQR increases in levels of PM ≤ 2.5 μm in aerodynamic diameter, especially in patients with one [0.6% (0.1–1.0%)] or two [1.2% (0.4–2.1%)] minor alleles of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) single-nucleotide polymorphism rs2364725. Positive immediate (0–23 hr) and inverse delayed (48–71 hr up to 96–119 hr) associations were evident between PM and Tamp. We detected an inverse U-shaped association between temperature and Tamp, with a maximum Tamp at 5°C.

Conclusions

Increased air pollution levels and temperature changes may lead to changes in HR and repolarization parameters that may be precursors of cardiac problems.     

Laparoscopic partial myectomy

BACKGROUND: A number of different surgical procedures have been described for the treatment of gastroesophageal reflux disease. Moreover, modifications and completely new techniques are being introduced on a regular basis. Nonetheless, in most cases of novel laparoscopic techniques profound experimental data have not been collected prior to their clinical introduction. Due to the lack of an animal model of inadequate esophageal sphincter function, most experimental studies on antireflux procedures were done on normally functioning esophageal sphincters. METHODS: It is well-known that myotomy alone cannot induce sphincter insufficiency in animal models. In addition, complete myectomy is associated with severe mortality and, therefore, is not useful as an experimental model. This study introduces a new model of laparoscopic partial in vivo myectomy. The procedure described here forms a myectomy of the esophagus using scissors and a sponge on the side of the greater gastric curvature. The size of the myectomy is approximately 6 x 1.5 cm and was successfully performed in a consecutive series of eight experimental animals (male German house pigs). RESULTS: Following an intensive team training on dead animals, the procedure was performed with success via the laparoscope in all study animals (n = 8). The sphincter pressure as determined by manometry was significantly reduced from 7.7 mmHg (range, 4.5-9.1; preoperative values) to 2.2 mmHg (range, 0-6.8; early postoperative values) and 2.3 mmHg (range, 0-3.7) at 8 weeks after surgery (p < 0.001). In addition, the length of the lower esophageal sphincter as well as the sphincter pressure vector volume were significantly reduced early as well as at 8 weeks after laparoscopic myectomy. Furthermore, endoscopy and reflux testing were pathologic compared with control animals. CONCLUSIONS: Laparoscopic partial myectomy results in complete sphincter insufficiency with only little procedure-related morbidity. This procedure allows for the experimental evaluation of surgical procedures on the gastroesophageal junction. Future modifications of surgical antireflux procedures can therefore be evaluated in an experimental setting prior to their clinical introduction.     

Mutation analysis of the MCHR1 gene in human obesity

OBJECTIVE: The importance of the melanin-concentrating hormone (MCH) system for regulation of energy homeostasis and body weight has been demonstrated in rodents. We analysed the human MCH receptor 1 gene (MCHR1) with respect to human obesity. DESIGN: This consisted of genomic screening of 13.4 kb encompassing the MCHR1 in extremely obese German children and adolescents and association analyses for two coding single nucleotide polymorphisms (SNPs). To confirm initial positive association results, additional association studies and transmission disequilibrium tests in further German, Danish, French and American samples were conducted. Selected SNPs were investigated using functional in vitro studies and reporter gene assays. METHODS: Single-stranded conformation polymorphism analysis, re-sequencing, PCR-restriction fragment length polymorphism analyses, tetra-primer amplification refractory mutation systems, matrix-assisted laser desorption/ionization time of flight mass spectrometry and reporter gene assays were carried out as well as measuring inositol phosphate formation, inhibition of cAMP formation and activation of p42/44 MAP kinase. RESULTS: We identified 11 infrequent variations and two SNPs in the MCHR1 coding sequence and 18 SNPs (eight novel) in the flanking sequence. Association and transmission disequilibrium with obesity were detected for several SNPs in independent study groups of German obese children and adolescents and controls. In two German samples, encompassing 4056 and 295 individuals, trends towards association with obesity were detected. Findings in a second epidemiological German sample and in Danish, French and American samples were negative. Functional in vitro studies as well as reporter gene assays revealed no significant results. CONCLUSION: Our initial association of MCHR1 alleles/haplotype detected might be related to juvenile-onset obesity, conditional on a particular genetic and/or environmental background. Alternatively, we could not exclude the possibility that the initially detected association represented a false positive finding.     

The prevalence of contact allergy differed between population-based and clinic-based data

OBJECTIVE: Epidemiologic evidence on contact allergy (CA) largely relies on clinical studies. However, the effects of the selection process until consultation as patient are largely unclear. STUDY DESIGN AND SETTING: Prevalences of contact allergy to important allergens estimated from the population-based nested case-control study "KORA Allergy Study" in Augsburg, Germany (a subsample from the third MONICA survey in 1997/1998, n=1141), were compared with proportions found in the Department of Dermatology of the Augsburg Municipal Hospital in patients of similar age patch tested between 1997 and 2000 (n=555). Prevalences were standardized for sex, age, and atopic dermatitis as potential confounders. RESULTS: Among the 25 substances tested, the fragrance mix (MONICA, estimated from the KORA Allergy Study: 11.4%, hospital: 12.9%) and nickel (MONICA: 9.9%, hospital: 12.9%) were the most common allergens. Larger differences between prevalences were noted particularly with ingredients of topicals used to treat varicose ulcers-a speciality of the Augsburg department, which is also reflected by comparing the department with the whole Information Network of (n =40) Departments of Dermatology (IVDK). CONCLUSION: This locally matched comparison illustrates the differential effect of selection until presentation in dermatological departments.     

Two dimensions of measurement error: classical and Berkson error in residential radon exposure assessment

Measurement error in exposure assessment is unavoidable. Statistical methods to correct for such errors rely upon a valid error model, particularly regarding the classification of classical and Berkson error, the structure and the size of the error. We provide a detailed list of sources of error in residential radon exposure assessment, stressing the importance of (a) the differentiation between classical and Berkson error and (b) the clear definitions of predictors and operationally defined predictors using the example of two German case-control studies on lung cancer and residential radon exposure. We give intuitive measures of error size and present evidence on both the error size and the multiplicative structure of the error from three data sets with repeated measurements of radon concentration. We conclude that modern exposure assessment should not only aim to be as accurate and precise as possible, but should also provide a model of the remaining measurement errors with clear differentiation of classical and Berkson components.