Serum tryptase level is a better predictor of systemic side effects than prostaglandin D2 metabolites during venom immunotherapy in children.

OBJECTIVES: We performed a prospective study to analyze mast cell mediators as predictors of systemic adverse reactions during rush venom-specific immunotherapy (VIT) in children. PATIENTS AND METHODS: Nineteen children aged 5-17 years received VIT with Venomenhal (HALAllergy). We analyzed serum tryptase (CAP, Phadia), plasma prostaglandin (PG) D2 metabolites (9alpha, 11beta-PGF2), and urine PGD2 metabolites (9alpha, 11beta-PGF2, tetranor-PGD-M) using gas chromatography mass spectrometry before and after the rush protocol. RESULTS: Three boys with high baseline serum tryptase values (>7.76 g/L) (P < .001) and low 9alpha, 11beta-PGF2 concentrations developed grade III systemic adverse reactions during VIT. Baseline serum tryptase was lowest in children who had a Mueller grade II reaction (1.93 [0.36]) before VIT and highest in children with a Mueller grade III reaction (6.31 [4.80]) (P = .029). Repeated measures analysis of variance confirmed that, in children who developed systemic adverse reactions during VIT, serum tryptase was higher both before and after desensitization and increased significantly following the procedure. Analysis of PGD2 metabolites in the prediction of systemic adverse reactions during VIT was inadequate (sensitivity 67% and specificity 0.53%), whilst prediction based on serum tryptase was accurate. CONCLUSIONS: In children with severe systemic adverse reactions to Hymenoptera sting, the evaluation of baseline tryptase levels should be a standard procedure. Children with Apis mellifera venom allergy and baseline tryptase levels higher than 7.75 g/L are at risk of anaphylaxis during buildup. Lower baseline values of plasma and urinary PGD2 metabolite concentration in patients with systemic adverse reaction during VIT suggest that prostaglandin catabolism is altered.

Comparative analysis of zinc status, food products' frequency intake and food habits of 11-year-old healthy children.

Children are particularly vulnerable to zinc (Zn) deficiency during periods of rapid growth and development such as infancy and adolescence. The aim was to find the relationship between food frequency, intake, food habits and zinc status in 11-year-old healthy children from southern Poland. The study group comprised children (n = 157) in the age range 11.0 +/- 0.4 years. The level of Zn in serum, erythrocytes and hair samples was measured using atomic absorption spectrophotometry. The parents of children examined completed a special food frequency questionnaire. The Zn concentration in hair (boys 182.98 +/- 65.63 microg x g(-1), n = 78; girls 203.82 +/- 39.80 microg x g(-1), n = 79; p = 0.0171), erythrocytes (8.60 +/- 2.76 mg x l(-1), n = 50) and blood serum (0.79 +/- 0.15 mg x l(-1)) correlated significantly (p < 0.05) with frequency intake of different products (hair: meat, rolls, fruit juices without additives, brawn, pate, barley, black pudding, fish canned, chips, margarine used for cooking, bacon; erythrocytes: fruits, matured cheese, dishes of meal, white cottage cheese, fruit juices without additives, cakes and cakes with cream, margarine used for bread spread; blood serum: bread, fruits, milk, kefir, yoghurt). The relationship of the Zn amount in food products, food frequency intake and the concentration in different healthy children tissues is influenced by many internal and external factors.

[Molecular studies in a population of children with bronchial asthma. I. Polymorphism in the promotor region of gene CD14]. / Badania molekularne w populacji dzieci chorych na astme oskrzelowa. Cz. I. Polimorfizm regionu promotorowego genu CD14.

UNLABELLED: Allergic asthma is associated with the recruitment of the inflammatory cells into the bronchial mucosa. Surface expression of CD14, a marker of activation and differentiation of macrophages/monocytes, was suggested to protect against Th-2 response. OBJECTIVE: To investigate clinical effects of genetic polymorphism of CD14 promoter in asthmatic children. METHODS: In ISAAC survey, 50 children with asthma were identified (wheezing in the last year, serum IgE level > 150 kIU/l, positive bronchial challenge test with aerolized hypertonic saline) and 73 children without the above signs. Age range of surveyed children was 13-14 years. Genotypic pattern of CD14 promoter -159 C to T transition was assessed by RFLP method. RESULTS: There was no difference in the allelic (0.36 vs. 0.38 for -159T) or genotype frequencies (0.12 vs. 0.15 for -159TT) of CD14 polymorphism between allergic asthmatics and controls. Moreover, there was no relationship between CD14 genotype and serum IgE level or bronchial hyper-responsiveness. CONCLUSION: Our results do not confirm the association of CD14 polymorphism (promoter -159 C to T transition) with asthma in Polish children.

The influence of lead and cadmium environmental pollution on anthropometric health factors in children.

THE AIM: The aim of the study was to examine the relationship between environment pollution (lead and cadmium) and selected anthropological factors. MATERIAL AND METHODS: The study group comprised 267 children, aged 11 +/- 0.4. Blood sampling and anthropological measurements were carried out in Kraków (polluted area) and in the Krosno region (low polluted area) in 1995. The lead and cadmium concentrations in the whole blood were determined using atomic absorption spectrometry with a graphite furnace and automatic dosage. The anthropometric measurements were made at the same time as the blood collection. RESULTS: The blood lead content in boys and girls was: 5.89 +/- 2.54, 5.01 +/- 1.62 micrograms/dl respectively, and the cadmium blood content was: 0.65 +/- 0.30, 0.68 +/- 0.47 microgram/l. Body mass and height did not correlate with lead and cadmium concentrations in the children's blood. Smaller head circumferences, independently of gender, were associated with a higher cadmium level. The values of four skin-folds (on the arm: biceps, triceps, under scapular bone and above iliac crest), as well as the percentage of fat content in the organism (PFDWB) calculated by the Slaughter-Lohman equation was higher in girls than in boys. CONCLUSIONS: 1. The relationships between cadmium and lead blood levels in children on the one hand and the degree of environmental pollution with these metals, and the gender of the children on the other were observed. The boys accumulated more lead, whereas the girls absorbed more cadmium. 2. Anthropometric analysis did not show a significant influence exerted by the polluted environment on the basic auxological parameters. In the group of children examined, the only differences observed were related to gender, head circumferences and indicators of obesity.

[Genetic background of retinoblastoma]. / Genetyczne podloze siatkówczaka plodowego.

Retinoblastoma is a malignant tumour of the eye ball, which develops as a result of the mutation of both alleles of RB-1 gene. Molecular mechanisms and their implications in clinical diagnosis and genetic counselling in retinoblastoma families are discussed.

[Chromosome aberrations in patients with papillary thyroid cancer and other neoplasms]. / Aberracje chromosomalne u chorych z rakiem brodawkowatym tarczycy i innymi nowotworami.

Cancer is essentially a genetic disease resulting from congenital or acquired alterations in some cells of the patient. Such changes may occur in particular oncogens and are responsible for the tumour phenotype of the affected population of cells. In contrast, unaltered tumour-suppressor genes are responsible for suppressing the neoplastic phenotype, and their inactivation by deletion or mutation permits cancerous development in the affected cells. The genetic model of carcinogenesis is based on the idea mutations at the DNA level, what creates a functional imbalance between the oncogenes and the tumour-suppressor genes, resulting in uncontrolled clonal proliferation. The ret/PTC oncogene is unique to papillary thyroid cancer. The paper presents a correlation analysis between chromosomal changes in papillary thyroid cancer and abnormalities of chromosomes in patients with breast cancer and chronic lymphocytic leukemia.

[Neural tube defects (NTD)--assessment from the perspective of 25 years of studies]. / Wady cewy nerwowej (WCN)--ocena z perspektywy 25 lat badan.

The present paper illustrates the authors 25-year experience in step by step approach to the definition of environmental and genetic background of neural tube defects. Based on the birth defects registry, a complete ascertainment of all deliveries was performed in Southern Poland during two period: 1970-1972, and 1979-1981. The birth prevalence of neural tube defects (NTD), as well as other CNS malformations was determined. The empiric recurrence risk was calculated as 3.2% +/- 1.6. Based on this figure, the relative risk (RR = 37.6 p < 0.001) and heritability (h2 = 74.7 +/- 6.7) were estimated. Our own modification of Morton's complex segregation analysis was applied. Three Mendelian (dominant, additive and recessive) and one multifactorial model were tested. The results did not provide a clear cut discrimination between different models; however the lowest 2 value was obtained for additive inheritance with 61% of penetrance and the frequency of sporadic cases equaled 55%. A search for genetic markers did not support the hypothesis that HLA-A,B,C loci are equivalents of T/t like locus in mice. The results of the study on transcobalamine levels in amniotic fluid may suggests that different transcobalamine metabolism reflects phenotypic expression of genetic susceptibility to NTD development. Current research and future perspectives on genetic and environmental background of NTD are also presented.

Response-dose ratio as an index of bronchial responsiveness to hypertonic saline challenge in an epidemiological survey of asthma in Polish children.

This epidemiological survey was done to evaluate the bronchial responsiveness (BHR) to a 4.5% hypertonic saline (HS) challenge in 13-14 year-old schoolchildren. BHR was measured by the response-dose ratio in which the response was estimated by the decline of FEV1 index of BHR (IxFEV1). Validity of the HS challenge test as a screening test for confirmation of reported asthma symptoms and the diagnosis of asthma was assessed. With a cutoff of 90th percentile of IxFEV1 in controls, the test sensitivity and specificity for asthma symptoms in the last 12 months was 44% and 90%, respectively. For the diagnosis of asthma the test sensitivity was 67% and specificity 90%. The mean log transform of IxFEV1 was significantly higher in children with more than three episodes of wheezing in the last 12 months and a diagnosis of asthma than in controls. Moreover, in the group with more than three episodes of asthma in the last 12 months the mean IxFEV1 was higher in girls than in boys. There was no gender difference in other groups of asthmatic children and controls. In Polish schoolchildren the prevalence of BHR to HS was 12.5% when adjusted to the prevalence of wheezing in the last 12 months. By multiple linear regression analysis, factors associated with BHR were serum levels of total IgE in children and of maternal IgE, as well as children's peripheral blood eosinophil counts. Also, the size of skin reaction to mite and dog allergens correlated with BHR.

[Gene therapy--hopes and fears]. / Terapia genowa--nadzieje i obawy.

Gene therapy assumes the correction of a genetic defect by the delivery of a correct DNA sequence to the target cells. Depending on the target cells two types gene therapy have been defined: somatic and germinal. By July 1998, 351 protocols of somatic therapy were approved by the Recombinant DNA Advisory Committee. The majority of protocols focus on cancer therapy and monogenic diseases. By now, still there is more unfulfilled expectation than clinically sound achievements, since no effective prevention or successful treatment for genetic diseases or cancer have been developed. Germline genetic modification is considered as the treatment of choice for such a diseases like retinoblastoma. Tay-Sachs, Lesch-Nyhan and metachromatic leuko-dystrophy. This approach which is still illegal or prohibited by rules in many European countries, is gathering more and more advocates. Once we learn how to control gene expression the perspectives for clinical application of gene therapy might be enormous. The safety of genetic modification of gametes or embryonal stem cells remains to be properly addressed and successfully solved. The ethical issues of germinal gene therapy are still the subject of controversial opinions among the scientists, lawyers and philosophers.

Familial four breakpoint complex chromosomal rearrangement as a cause of monosomy 9p22-->pter and trisomy 10p11.2-->pter and 11q21 analysed by dual and triple colour FISH.

A familial four breakpoint complex chromosomal rearrangement involving chromosomes 9, 10, and 11 was ascertained through a child with dysmorphic features, hypertrophic cardiomyopathy, and hypotonia. A cryptic insertion, invisible in G banded chromosomes was identified by fluorescence in situ hybridisation (FISH) using chromosome specific libraries. Possible mechanisms of its formation as well as karyotype-phenotype correlation are discussed.

A search for environmental and genetic background for neural tube defects: twenty-five years of experience.

The present paper illustrates the author's 25-year experience in a step by step approach to the definition of environmental and genetic background of neural tube defects. Based on the birth defects registry, a complete ascertainment of all deliveries was performed in Southern Poland during two periods: 1970-1972, and 1979-1981. The birth prevalence of neural tube defects (NTD), as well as other CNS malformations was determined. The empiric recurrence risk was calculated as 3.2% +/- 1.6. Based on this figure, the relative risk (RR = 37.6 p < 0.001) and heritability (h2 = 74.7 +/- 6.7) were estimated. Our own modification of Morton's complex segregation analysis was applied. Three Mendelian (dominant, additive and recessive) and one multifactorial model were tested. The results did not provide a clear cut discrimination between different models; however the lowest x2 value was obtained for additive inheritance with 61% of penetrance and the frequency of sporadic cases equaled 55%. A search for genetic markers did not support the hypothesis that HLA-A,B,C loci are equivalents of T/t like locus in mice. The results of the study on transcobalamine levels in amniotic fluid may suggests that different transcobalamine metabolism reflects phenotypic expression of genetic susceptibility to NTD development. Current research status and future perspectives on genetic and environmental background of NTD are also presented.

[Evaluation of hyperresponsiveness to the exercise challenge test in school children]. / Ocena nadreaktywnosci oskrzeli w tescie wysilkowym u dzieci szkolnych.

Bronchial hyperresponsiveness (BHR) to the exercise challenge test was measured in 161 pupils randomly chosen from the epidemiologic survey of 2967 schoolchildren (13 to 14 yr of age). In the study group there were 73 pupils who were identified as "ever wheezers" by the ISAAC questionnaires, and 88 ones as the control group. BHR was measured as the percentage drops in FEV, FEF50, FEF25-75 from the baseline (% delta FEV1, % delta FEV50%, % delta FEF25-75%). The % delta FEV1 was significantly higher in the "ever wheezers" comparing to the control group, and this parameter was also significantly higher for the "wheezers in the last 12 mo" in comparison to "ever wheezers", who had no symptoms in the last year. The "ever wheezers" group had higher % delta FEF50%, % delta FEF25-75% but the value was not significant when compared to the control group. In the epidemiologic survey, the sensitivity and specificity for the exercise challenge test as a screening test (level %FEV1 > 11%) to identify "wheezers in the last 12mo" were 39% and 81%, respectively, and to identify the "diagnosed asthma" group were 40% and 76%. The BHR was modified by atopy (measured with the allergic skin tests) and the diagnosis of asthma.

[Bronchial asthma: do boys or girls have the highest incidence?]. / Astma oskrzelowa: kto czesciej choruje dziewczeta czy chlopcy?.

The aim of the study was to assess the gender related prevalence of asthma and asthma symptoms in schoolchildren. The survey was performed using standardized ISAAC questionnaire in two age groups: 6-7 yr. (n = 2281; girls 49.7%) and 13-14 yr. (n = 4849; girls 49.8%). It was revealed that in older group the prevalence of ever diagnosed asthma was lower in girls than in boys (2.0% versus 3.3%; odds ratio [OR] = 0.58; p = 0.004). But the prevalence of symptoms: wheeze ever (OR = 1.16; p = 0.056), current wheeze (last 12 mo) (OR = 1.26; p = 0.029), current exercise wheeze (OR = 1.40; p = 0.0008), current night cough (OR = 1.67; p = 0.0001) were higher in girls than in boys. However, in younger group of schoolchildren the prevalence of ever diagnosed asthma and asthma symptoms were higher in boys (5.1% male versus 3.5% female). The girls in comparison to boys revealed lower risk of ever asthma diagnosis (OR = 0.66; p = 0.056) and symptoms: wheeze ever (OR = 0.63; p = 0.0001), current wheeze (OR = 0.69; p = 0.003), current exercise wheeze (OR = 0.59; p = 0.008) and current night cough (OR = 0.70; p = 0.0003).

[Diagnostic value of selected eosinophil activity parameters in children with hay fever]. / Wartosc diagnostyczna wybranych parametrów aktywnosci granulocytów kwasochlonnych u dzieci z alergia pylkowa.

Seventy three children aged 5-15 years were involved in the survey. Thirteen children suffered from seasonal allergic rhinitis (SAR), fourty four children suffered from seasonal allergic rhinitis and bronchial asthma (SAR-A), sixteen patients with no allergic symptoms were treated as a control group (CG). All the patients were examined twice: in July--during the highest pollen season and in December--period free of pollen. During each examination samples were collected to measure the following parameters: blood eosinophilia, serum eosinophil cationic protein (ECP) and eosinophil percentage in the nasal mucosal smears (nasal eosinophilia). In statistical analysis values of all parameters in pollen and free of pollen seasons were compared the groups of patients as well as within the groups. In winter values of: blood eosinophilia, ECP and nasal eosinophilia were statistically higher in SAR-A group in comparison to SAR group and CG, simultaneously there was no statistical difference in blood eosinophilia and ECP between SAR group and CG. In the pollen season the highest values of all parameters were observed in SAR-A group. SAR group values were higher in comparison to control group. The difference between groups was significant. Both groups of allergic patients (SAR, SAR-A) revealed statistically higher values of all measured parameters in pollen season in comparison to winter. In CG only level of ECP was significantly higher in July than in December.

[Pollen allergy. I. Pathophysiology and clinic]. / Alergia pylkowa. Czesc I: Patofizjologia i klinika.

Pollen allergy constitutes about 1/3 of allergic disorders in people. Clinical manifestation of the disease depends on the natural allergen exposure. Main clinical symptoms are dealing with conjunctivitis, allergic rhinitis, bronchial asthma. Permanent increase in number of pollen sensitive patients observed during last years, depends on atopic genetic background, as well as natural allergen exposure and other environmental factors. Better understanding of pathophysiological mechanisms underlying the disease and opportunity to monitor the degree of allergen exposure seems to play the vital role in current treatment and prophylaxis. The allergic reaction takes place in two phases--the first one--early response (EAR) depends on IgE receptors binding which results in mast cell and basophils activation, in the second one--the late response (LAR), adhesive molecules, eosinophils, lymphocytes and their products, as well as neuropeptides are engaged. Also homeostasis of respiratory tract mucous membrane plays an important role at this stage.

[Pollen allergy. II. Diagnosis and treatment]. / Alergia pylkowa. Czesc II: Diagnostyka i leczenie.

Pollen allergy--one of the most frequent allergies in people is diagnosed by combined data, derived from patient's history together with in vitro and in vivo examinations. Basic in vivo examinations consist of skin prick tests with chosen allergens, functional tests of upper and lower respiratory tract, specific as well as non-specific nasal and bronchial challenge tests. The major role among in vitro examinations is played by those tests, which confirm atopic background of the disease (total and specific IgE). Other tests, like those for T-cell function and tests for effector cells activation, have secondary importance. Patients who are asymptomatic but endangered by the possibility of symptoms occurrence, are treated by primary prevention. Complex therapeutical approach consists of causal treatment (identification of allergens, specific immunotherapy), secondary prevention and symptomatic pharmacology.

[The effect of air pollution on the prevalence of asthma in schoolchildren from Krakow]. / Wplyw zanieczyszczenia powietrza na wystepowanie astmy oskrzelowej u dzieci szkolnych z Krakowa.

The aim of the study was to assess the relationship between asthma, wheezing prevalence and the rate of air pollution in Kraków. In the survey of 6696 schoolchildren aged 12-14 year, ISAAC questionnaires were performed. According to the distribution of the mean annual concentration of dust particles (PM10) and sulfur dioxide, four classes of these compounds were established. In the similar way, the lead concentration in garden soil and lettuce was categorized into three classes, which were surrogates of the automobile exhaust. Children's passive smoking was established by questionnaire. The study revealed a significant association and a positive correlation between the prevalence of asthma diagnosis and the soil and lettuce lead concentrations. Wheezing history (past and current) was significantly correlated with soil lead classes and the classes of dust particles (PM10). Maternal smoking was significantly associated with the asthma diagnosis and past or current wheezing. A significant relationship was found between paternal smoking and wheezing during and/or post exercise.

[Prevalence of allergic diseases in schoolchildren in Krakow and Poznan (based on a standardized ISAAC questionnaire)]. / Wystepowanie chorób alergicznych u dzieci szkolnych w Krakowie i Poznaniu (na podstawie badan ankietowych ISAAC).

The study population included children aged 6-7 and 13-14 years from primary schools in Kraków (2302 and 2967 children respectively) and Poznan (3132 and 4069 children respectively). The prevalence was assessed using ISAAC questionnaire. In younger age group the number of children with diagnosed asthma and presenting asthma symptoms was significantly higher in Kraków than in Poznan. In older age group higher percentage was observed in Kraków in relation to wheeze ever and nocturnal cough during last year. Pupils from Kraków had symptoms of allergic rhinitis and were diagnosed as allergic rhinitis more frequently than from Poznan. Symptoms suggestive for skin allergy were more often observed in Kraków, but the differences were significant in relation to symptoms during last year in both age groups and in relation to symptoms ever in older age group. Our study revealed discrepancy between the prevalence of symptoms of asthma and allergic rhinitis and the prevalence of established diagnosis.

[Genetic background of atopy]. / Genetyczne podloze atopii.

The paper presents contemporary views on atopic inheritance patterns. Results of molecular studies are presented which map genes linked with disturbances in IgE to chromosomes 5 and 11. The role of HLA antigens in atopic reaction mechanisms is also discussed.