Comparison of lactase persistence polymorphism in ancient and present-day Hungarian populations.

The prevalence of adult-type hypolactasia varies ethnically and geographically among populations. A C/T-13910 single nucleotide polymorphism (SNP) upstream of the lactase gene is known to be associated with lactase non-persistence in Europeans. The aim of this study was to determine the prevalence of lactase persistent and non-persistent genotypes in current Hungarian-speaking populations and in ancient bone samples of classical conquerors and commoners from the 10th-11th centuries from the Carpathian basin; 181 present-day Hungarian, 65 present-day Sekler, and 23 ancient samples were successfully genotyped for the C/T-13910 SNP by the dCAPS PCR-RFLP method. Additional mitochondrial DNA testing was also carried out. In ancient Hungarians, the T-13910 allele was present only in 11% of the population, and exclusively in commoners of European mitochondrial haplogroups who may have been of pre-Hungarian indigenous ancestry. This is despite animal domestication and dairy products having been introduced into the Carpathian basin early in the Neolithic Age. This anomaly may be explained by the Hungarian use of fermented milk products, their greater consumption of ruminant meat than milk, cultural differences, or by their having other lactase-regulating genetic polymorphisms than C/T-13910. The low prevalence of lactase persistence provides additional information on the Asian origin of Hungarians. Present-day Hungarians have been assimilated with the surrounding European populations, since they do not differ significantly from the neighboring populations in their possession of mtDNA and C/T-13910 variants.

Skin wipe test: A simple, inexpensive, and fast approach in the diagnosis of cystic fibrosis.

OBJECTIVE: To assess the performance of a newly developed skin wipe test (SWT) for the diagnosis of cystic fibrosis (CF). STUDY DESIGN: Spontaneously formed sweat from the forearm was wiped by a cotton swab moistened with 100 µL of deionized (DI) water and extracted into 400 µL of DI water (SWT). The conventional Macroduct sweat test (ST) was performed simultaneously. SWT samples of 114 CF patients, 76 healthy carriers, and 58 controls were analyzed by capillary electrophoresis with contactless conductivity detection and Cl- /K+ and (Cl- + Na+ )/K+ ion ratios were evaluated. Chloride concentrations from Macroduct ST were analyzed coulometrically. RESULTS: Analysis of 248 SWT samples and simultaneous Macroduct ST samples showed comparable method performance. Two ion ratios, Cl- /K+ and (Cl- + Na+ )/K+ , from the SWT samples and Cl- values from the ST samples were evaluated to diagnose CF. Sensitivity of the SWT method using the Cl- /K+ ratio (cutoff value 3.9) was 93.9%, compared to 99.1% when using the (Cl- + Na+ )/K+ ratio (cutoff value 5.0) and 98.3% in using Macroduct Cl- (cutoff value higher or equal to 60 mmol/L). The methods' specificities were 97.8%, 94.0%, and 100.0%, respectively. CONCLUSIONS: The developed SWT method with capillary electrophoretic analysis for CF diagnosis performs comparably to the conventional Macroduct ST. The SWT method is simple, fast, inexpensive, and completely noninvasive. Use of an ion ratio in obtained SWT samples is proposed as a new diagnostic parameter that shows significant promise in CF diagnostics.

Human Epididymis Protein 4: A Novel Serum Inflammatory Biomarker in Cystic Fibrosis.

BACKGROUND: Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF. METHODS: Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR. RESULTS: Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P < .0001). This observation was replicated in adults with CF (115.7 [77.8-148.7] pmol/L; P < .0001). In contrast, abnormal but lower HE4 concentrations were found in cases of severe bronchitis, asthma, pneumonia, and bronchiectasis. In patients with CF, the concentrations of HE4 were positively correlated with overall disease severity and C-reactive protein concentrations, whereas a significant inverse relationship was found between HE4 and the spirometric FEV1 value. Relative HE4 mRNA levels were significantly upregulated (P = .011) with a decreased miR-140-5p expression (P = .020) in the CF vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator/bronchial epithelial cells compared with wild-type cells. CONCLUSIONS: HE4 serum levels positively correlate with the overall severity of CF and the degree of pulmonary dysfunction. HE4 may thus be used as a novel inflammatory biomarker and possibly also as a measure of treatment efficacy in CF lung disease.

Urinary magnesium excretion in asthmatic children receiving magnesium supplementation: a randomized, placebo-controlled, double-blind study.

The aims of this study were to establish whether a magnesium (Mg) deficit indicated by a decreased urinary excretion exists and to determine whether 12-week oral Mg supplementation affects the Mg status and bronchodilator use in children with stable bronchial asthma. The effects of long-lasting Mg supplementation were investigated in 89 children 4 to 16 years of age with mild or moderate persistent bronchial asthma in a randomized, double-blind, placebo-controlled, prospective study. Each subject received one capsule of Mg citrate per day (= 7 years: 200 mg, > 7 years: 290 mg) or one capsule of placebo containing 260 mg glucose during 12 weeks. Evaluation was performed at 4-week intervals. Venous blood serum total and free Mg and urine Mg levels were determined at the beginning and end of the 12-week period. Parents recorded the number of bronchodilator doses twice daily. A urinary Mg loss (6.81 +/- 3.9 versus 2.79 +/- 1.39 mmol/day, p = 0.01) was observed in the placebo-treated persistent moderate asthmatics. Bronchodilator use was significantly higher after 8 and 12 weeks in the placebo-treated than in the Mg-treated patients with moderate asthma (31.1 +/- 1.8 versus 29.5 +/- 1.2 puffs per patient/4 weeks, p < 0.05, and 31.0 +/- 2.3 versus 29.3 +/- 0.9 puffs per patient/4 weeks, p < 0.05, respectively). Long-lasting Mg supplementation is clearly of benefit in mildly to moderately asthmatic children and is recommended as a concomitant drug in stable asthma.

The 8.1 ancestral MHC haplotype is associated with delayed onset of colonization in cystic fibrosis.

Major cause of death in patients with cystic fibrosis (CF) is colonization with Staphylococcus aureus and Pseudomonas aeruginosa. The wide phenotypic variation in CF patients suggests that genes other than the cystic fibrosis transmembrane conductance regulator (CFTR) gene modify the disease. The 8.1 ancestral haplotype (8.1AH) in main histocompatibility complex is associated with alterations of the immune response. To study the influence of carriage of 8.1AH on frequency and onset of colonization in CF patients, DNA samples of 72 CF patients (39 homozygous and 33 heterozygous for DeltaF508) were genotyped for member alleles of the 8.1AH: HLA-DQB1*0201, HLA-DRB1*0301, receptor for advanced glycation end products (AGER) -429C, HSP70-2 -1267G (HSP70-2G) and tumor necrosis factor-alpha (TNF-alpha) -308A (TNF2). Colonization was verified by regular clinical and bacteriological screening. Frequency of colonization was significantly (P = 0.012) lower in the 8.1AH carriers; age, gender and DeltaF508 genotype-adjusted odds ratio to be colonized of the carriers versus non-carriers was 0.112 (0.024-0.520). According to survival analysis, patients with 8.1AH had significantly (P < 0.0001) longer colonization-free period compared with non-carriers. Our novel observations demonstrate that the 8.1AH is associated with delayed onset of colonization in CF, presumably by influencing defense mechanisms against infections.

Pulmonary capillary haemangiomatosis in children and adolescents: report of a new case and a review of the literature.

Pulmonary capillary haemangiomatosis (PCH) in childhood is a rarity, characterised by the uncontrolled proliferation of pulmonary microvessels which may invade pulmonary, bronchial and vascular structures, resulting in diffuse alveolar haemorrhage, manifesting clinically in haemoptysis, dyspnoea and symptoms of pulmonary hypertension (PH). A 14-year-old boy with some particular features (pericardial effusion and thrombocytopenia) is presented and 14 paediatric/adolescent cases from the literature are surveyed. The diagnostic problems and difficulties are discussed, including the importance of imaging (high-resolution CT) and histopathological studies, with the aim of providing a clear-cut distinction of PCH from other conditions such as primary PH (PPH). The literature data can be regarded as ambiguous: both similarities and relatively sharp distinctions between PCH and PPH are to be found. New developments in the field of genetics are also discussed. The early coexistence of PCH and other (vascular) disorders and associations, involving focal or diffuse, disseminated forms is summarised briefly. Conclusion. The diagnosis of this progressive disorder may lead to effective therapy. Treatment possibilities include the rapidly evolving field of anti-angiogenic therapy, but at present lung transplantation is universally accepted as the final definitive treatment for pulmonary capillary haemangiomatosis.