Nutritional supplements and plasma antioxidants in childhood asthma.

OBJECTIVE: This study investigated the relationship of plasma antioxidants to airway inflammation and systemic oxidative stress in children suffering from atopic asthma with consideration of the intake of nutritional supplements. SUBJECTS AND RESEARCH METHODS: A total of 35 asthmatic children (AG) and 21 healthy controls (CG) participated in this study. Plasma levels of vitamins A and E, ß-carotene, coenzyme Q10 and malondialdehyde (MDA) were analyzed with high-performance liquid chromatography (HPLC); the total antioxidant capacity (TAC) was measured photometrically, and selenium was determined by atomic absorption spectroscopy (AAS). The volume of fractionated exhaled nitric oxide (FeNO) was measured with the NIOX nitric oxide monitoring system. RESULTS: The plasma antioxidants vitamins A and E, selenium, and coenzyme Q10 but not ß-carotene were significantly (p < 0.05) lower in asthmatics than in controls. Further, asthmatic children had significantly reduced plasma concentrations of TAC (p < 0.01), significantly enhanced levels of MDA (p < 0.001), and exhaled a significantly (p < 0.001) higher mean volume of FENO than healthy children. Regular intake of supplements had a significant positive influence on plasma vitamin E (p < 0.01), selenium (p < 0.01), TAC (p < 0.05), MDA (p < 0.01), and FENO (p < 0.01) in asthmatics but not in controls. Additionally, significant negative associations of vitamin E and MDA (AG: p < 0.01; CG: p < 0.05), and vitamin E and FENO (AG: p < 0.05; CG: p > 0.05) were identified. CONCLUSION: These results indicate that nutritional supplements beneficially modulate plasma antioxidants and thus might have a positive influence on systemic redox balance and subsequently, pulmonary inflammation in asthmatic children.

Activities of antioxidant enzymes in relation to oxidative and nitrosative challenges in childhood asthma.

BACKGROUND: This study aimed to investigate the relationship between antioxidant enzyme activities, extent of airway inflammation, and systemic oxidative stress in children suffering from atopic asthma. METHODS: A total of 35 asthmatic (AG) and 21 healthy children (CG) participated in this study. The volume of fractionated exhaled NO (Fe(no)) was measured with the NIOX test system. The activities of the erythrocyte antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and the total antioxidant capacity (TAC) were determined photometrically. Plasma interleukin (IL)-6 was measured using ELISA; malondialdehyde (MDA) levels were analyzed using HPLC. RESULTS: Compared to healthy controls, asthmatic children exhaled a significantly (p < .001) higher mean volume of Fe(no), had significantly reduced plasma concentrations of TAC (p = .006), and significantly enhanced levels of MDA (p < .001) and IL-6 (p = .012). SOD (p = .027), CAT (p < .001), and GSH-Px (p = .005) were significantly less active in the asthma group and significantly negatively associated with Fe(no) (SOD/Fe(no): p = .017; CAT/Fe(no): p = .008; GSH-Px/Fe(no): p = .001); the oxidative stress marker MDA showed such correlations in both investigated groups (SOD/MDA: AG: p = .001, CG: p = .381; CAT/MDA: AG: p = .003, CG: p = .020; GSH-Px/MDA: AG: p = .006, CG: p = .011). Furthermore, there was a significant (p< .01) positive correlation between MDA/Fe(no) and MDA/IL-6 observed in both groups. CONCLUSIONS: These results indicate that inflammation of the bronchial tree, reflected by increased NO formation in the airways and enhanced systemic oxidative stress, is related to an alteration of antioxidant enzyme activities in childhood asthma. Modulating the activity of antioxidant enzymes may therefore have beneficial effects on pulmonary and systemic antioxidant defense mechanisms and could reduce airway inflammation and oxidative stress in asthmatics.

A single-dose influenza A (H5N1) vaccine safe and immunogenic in adult and elderly patients: an approach to pandemic vaccine development.

With the ongoing pandemic of influenza A (H1N1) virus infection and the threat of high fatality rates for recent human cases of infection with highly pathogenic H5N1 strains, there has been considerable interest in developing pandemic vaccines. Here we report a randomized multicenter dose-finding clinical trial of a whole-virion, inactivated, adjuvanted H5N1 vaccine in adult and elderly volunteers. Four hundred eighty patients were randomly assigned to receive one or two doses of 3.5 microg of the vaccine or one dose of 6 or 12 microg. The subjects were monitored for safety analysis, and serum samples were obtained to assess immunogenicity by hemagglutination inhibition and microneutralization tests. The subjects developed antibody responses against the influenza A (H5N1) virus. Single doses of > or = 6 microg fulfilled EU and U.S. licensing criteria for interpandemic and pandemic influenza vaccines. Except for occasional injection site pain, malaise, and fever, no adverse events were observed. We found that the present vaccine is safe and immunogenic in healthy adult and elderly subjects and requires low doses and, unlike any other H5N1 vaccines, only one injection to trigger immune responses which comply with licensing criteria. A vaccine using the same methods as those described in this report, but based on a wild-type swine-origin 2009 (H1N1) influenza A virus isolate from the United States (supplied by the CDC), has been developed and is currently being tested by our group.

Safety and immunogenicity of a prepandemic influenza A (H5N1) vaccine in children.

BACKGROUND: The avian influenza A (H5N1) virus is considered to be a potential cause of the next influenza pandemic. Children may be particularly vulnerable to the pandemic virus, and they may react differently than adults to vaccines. We report the results of the first clinical trial of an H5N1 vaccine in children. METHODS: Twelve healthy children (mean age +/- SD: 12.73 +/- 2.77 years) received a single dose of 6 microg of the inactivated whole virus vaccine Fluval. Twenty-one days after vaccination, immunogenicity was assessed by hemagglutination inhibition and microneutralization assays. Safety information was collected for 180 days. RESULTS: No side-effects were observed, and the vaccine fulfilled all applicable U.S. and European immunogenicity criteria for licensure. The post/prevaccination geometric mean titer ratio was 16.95, the rate of seroconversion was 75% and the rate of seroprotection was also 75% 21 days after vaccination. CONCLUSIONS: We confirmed our earlier findings of the present vaccine in adults showing encouraging safety and immunogenicity properties in children. Studies with the present vaccine in elderly subjects are underway.

Yearly licensing studies from 1997 to 2007 of the inactivated whole virus seasonal influenza vaccine fluval--a useful approach to pandemic vaccine development even in less well developed countries?

OBJECTIVE: Seasonal vaccination has been consistently shown to significantly reduce morbidity and mortality because of influenza epidemics, even in healthy, working adults. Here we report the results of the yearly licensing studies of the past 11 influenza seasons (1997-2007) with a trivalent, inactivated whole virus vaccine with an aluminum phosphate adjuvant system. METHODS: Sixty healthy volunteers per age group (18-60 years and 60 years and older) were enrolled to receive vaccination each year, thus, a total of 1080 subjects were studied. Serum antibody titers were measured by hemagglutination inhibition (HI). RESULTS: The vaccine met the criteria for licensing each year, meaning seroprotection (achievement of an HI titer of >1:40 in >70% of subjects); seroconversion, i.e. a >4-fold increase in HI antibody titer, or reaching a titer of >1:40, in >40% of subjects; and an increase in geometric mean titers by >2.5-fold. Side effects were rare and mild. The same method was used to produce a pre-pandemic vaccine against influenza A (H5N1), which has been shown to be safe and immunogenic in humans. CONCLUSIONS: We conclude that the method presented is safe, effective and may serve as a useful approach to seasonal and pandemic vaccine production even in less well-developed countries by means of technological transfer.

Prevalence of atopic dermatitis among children under 19 in an East-Hungarian agricultural county.

The prevalence of atopic dermatitis has significantly increased in developed countries during the past several decades. Surveys performed in Hungary also show a growing number of atopic dermatitis (AD) cases, although, a carefully designed case-controlled studies have not been performed. Therefore, we investigated the prevalence of AD in individuals under 19 years of age within the agricultural area of East-Hungary. Combined data obtained with Schultz-Larsen questionnaire on 1158 children were analyzed, and 25% of the index persons were examined by dermatologist. The mean prevalence of AD determined by questionnaires appeared to be 17.5% in the entire study population. Result of dermatological examination verified the validity and sensitivity of the questionnaire. A negative correlation was found between the severity of the disease and the length of breast feeding period. (Spearman's correlation coefficient = - 0.2247, p = 0.034). The prevalence of AD in an East-Hungarian agricultural area is nearly as high as that reported for populations residing in industrially developed countries, with a higher prevalence during childhood. Data suggest that premature abruption of breast feeding maybe one of the major factors among other environmental factors that is contributing to the development of AD.

Echocardiographic findings in patients with Williams-Beuren syndrome.

BACKGROUND: Williams-Beuren syndrome is a multisystem developmental disorder caused by a microdeletion at chromosome 7q11.23. In its classic form it includes dysmorphic facial features, joint contractures, retardation of growth and mental development, gregarious personality, visuospatial cognitive deficits, hypercalcemia, primary or secondary hypertension and cardiovascular disorders. AIM: Clinical diagnosis of Williams-Beuren syndrome can be a challenge in young patients if none of the characteristic cardiovascular features, i.e. supravalvular aortic stenosis or pulmonary artery stenosis, are present. Our aim was to demonstrate the changes in cardiovascular lesions during the postnatal development of Williams-Beuren patients and to follow all cardiovascular findings beyond the most common ones. METHODS: The cardiovascular status of 29 patients with Williams-Beuren syndrome (mean age 12.8 years) was recorded in correlation with age. RESULTS: Cardiovascular diagnoses changed in the majority (72.4%) of patients. Interestingly, 44.8% of the patients had periods with no reported cardiovascular disease. Furthermore, 65.5% of the patients experienced periods when none of the typical cardiovascular lesions, i.e. diffuse or localized supravalvular aortic stenosis and/or pulmonary artery stenosis, were detected. Spontaneous regression and progression of both supravalvular aortic stenosis and pulmonary artery stenosis were observed. An unexpectedly high frequency (41%) of mitral valve disorders was found. CONCLUSIONS: Our study showed that temporary absence of and changes in cardiovascular findings are frequent in Williams-Beuren syndrome. These results could contribute to the refinement of diagnostic criteria and recommendations for cardiovascular follow-up of patients with this syndrome.

Uterine leiomyosarcoma with osteoclast like giant cells and long standing systemic symptoms.

INTRODUCTION: The leiomyomatous type of uterine sarcoma with osteoclast-type giant cell component is a rare variant of uterine tumors with poor prognosis. The histological diagnosis of these rare tumors can be problematic and only five such tumors have been published previously. CASE REPORT: A 54-year-old woman presented with fever and weight loss for 7 months and laboratory findings suggestive of inflammation. After extensive clinical investigation, a uterine tumor was found, which was considered to be an incidental finding and was thought to be unlikely to explain the symptoms. After hysterectomy, the patient had a surprising and quick recovery with the complete relief of systemic symptoms and normalization of laboratory changes. The tumor was a dedifferentiated leiomyosarcoma with osteoclast-like giant cells and contained extensive necrosis. The patient continues to do well and is tumor-free 1 year after the operation. DISCUSSION: To our knowledge, this is the first report of a patient being alive and disease-free 12 months after surgery with a dedifferentiated uterine leiomyosarcoma with osteoclast-like giant cells.

An improved technique for repeated bronchoalveolar lavage and lung mechanics measurements in individual rats.

Lung function and bronchoalveolar lavage (BAL) fluid are commonly analyzed to assess the severity of lung disease in sacrificed animals. The input impedance of the respiratory system (Z(rs)) was measured and BAL fluid was collected in intubated, anesthetized, mechanically ventilated rats on three occasions 1 week apart. Measurements were performed in control animals (group C), while lung injury was induced in the other group (group LPS) by i.p. injection of lipopolysaccharide (LPS) before the second measurement. The airway resistance (R(aw)), tissue damping (G) and elastance (H) were determined from the Z(rs) spectra. The total cell counts (TC) from 0.3- to 0.4-ml BAL fluid were also determined. R(aw) exhibited no significant change in either group C (-6.7+/-3.6[S.E.]%) or LPS (-0.9+/-3.7%). Reproducible G and H values were obtained in group C (2.5+/-5.3%, -7.0+/-4.4%), while G and H increased in group LPS (18.4+/-6.5%, 14.9+/-13.8%, p<0.05). The changes in TC followed a similar pattern to those observed in G, with no change in group C (-7.9+/-30%), but with a marked increase in group LPS (580+/-456%, p<0.05). The method devised for repeated BAL measurements in another group of rats without intubation and muscle relaxant resulted in similar results in BAL profile. We conclude that longitudinal follow-up of the airway and tissue mechanics and inflammatory cells in the BAL fluid are feasible in rats. The current method allows an early detection of lung injury, even in a relatively mild form.

[Effect of the leukotriene receptor antagonist montelukast therapy on asthma in childhood]. / A leukotriénreceptor-antagonista montelukast-kezelés hatása a gyermekkori asthma bronchialeban.

The authors have summed up the survey results for children with asthma below 14 years of age participating in the Hunair II. surveillance program. This program proves the efficiency of montelucast 5mg treatment in cases of childhood asthma bronchiale. The 255 patients participating in the survey have received 5 mg montelucast therapy for 8 weeks. During the surveillance period they have used questionnaires to record the change of day and night symptoms, decrease of different restrictions and the quantity change of long- and short-acting beta agonists and inhaled steroids. The use of short-acting agonists decreased from 5 inhalations to 1 in 4 weeks. During the leukotriene antagonist montelucast treatment according to symptom scores 61% of the patients have experienced improvements after the 4th week, 80% after the 8th week. To sum up all the survey results--after the 8th week of treatment the daytime restrictions in the everyday lives of children with asthma have decreased by 88.1%, nighttime restrictions by 80.1%. After the 2nd month of the HUNAIR II. surveillance program it could be deduced that montelucast 5 mg therapy used in child populations less then 14 years of age with asthma has proven useful.