Testing children for allergies: why, how, who and when: an updated statement of the European Academy of Allergy and Clinical Immunology (EAACI) Section on Pediatrics and the EAACI-Clemens von Pirquet Foundation.

Allergic diseases are common in childhood and can cause a significant morbidity and impaired quality-of-life of the children and their families. Adequate allergy testing is the prerequisite for optimal care, including allergen avoidance, pharmacotherapy and immunotherapy. Children with persisting or recurrent or severe symptoms suggestive for allergy should undergo an appropriate diagnostic work-up, irrespective of their age. Adequate allergy testing may also allow defining allergic trigger in common symptoms. We provide here evidence-based guidance on when and how to test for allergy in children based on common presenting symptoms suggestive of allergic diseases.

Age- and sex-determined differences in the establishment of tetanus antitoxin production in guinea-pigs.

For lack of relevant data of the literature, the tetanus immunisation results obtained in the two sexes were compared in an animal model. Complete immunisation series of weaned, adult and aged guinea-pigs (20-25 animals/group) were performed with aluminium phosphate (AlPO4) adsorbed purified tetanus toxoid (PTAP) as well as with typhoid-tetanus vaccine (TY-TE) containing lipopolysaccharide (LPS). Both vaccines contained 5.0 Lf (limes flocculans, Ramon) per single dose of tetanus toxoid, purity degree: 1500 Lf/mg protein nitrogen (PN). Tetanus antitoxin titres (TAT) were measured after the first shot, and subsequently before and after booster. Compared to TAT of male animals, significantly lower titres were found in female animals after basic immunisation with PTAP in all the three age groups: 1.03 vs. 0.57, 8.75 vs. 5.64, and 0.27 vs. 0.15 IU (international units, related to the Copenhagen International Standard) per ml (sex-chromosome-dependent differences?), as well as in adult animals immunised with TY-TE, before booster: 0.07 vs. 0.02 IU/ml (hormone-dependent differences?). In the latter case the TAT results after booster were 14.49 vs. 12.89 IU/ml. Thus, the lower female prebooster titres were counterbalanced by a quick and effective increase of titres following booster. These results are in accordance with our previous observations in humans (Réthy and Réthy, 1986). From our observations with tetanus immunisation series on guinea-pigs it can be concluded that TAT may be influenced by the effects of sex chromosomes as well as of sexual hormones. During active anti-tetanus immunisation with LPS-containing vaccine (TY-TE) the lower adult female prebooster titres are presumably counterbalanced by the better functionality of the female immune memory.

Growth regulation, acid sphingomyelinase gene and genomic imprinting: lessons from an experiment of nature.

The author investigated the possible role of acid sphingomyelinase (ASM) gene (SMPD1) in the regulation of growth, in connection with an experiment of nature. The association of a decreased ASM activity and an overgrowth disorder, Beckwith-Wiedemann Syndrome (BWS) with hemihypertrophy has been described at a 23 months old boy in a recent case report (Réthy et al, in this issue). ASM catalyses the production of ceramide, a key molecule of apoptosis, from sphingomyelin. Based on these data it is suggested that the ASM gene (SMPD1) can suppress/counterbalance the anti-apoptotic effects of BWSrelated growth-promoters, like IGF-II, under normal circumstances. Recent literary data support this view. ASM deficient lymphoblasts derived from patients with Niemann-Pick disease (NPD) fail to undergo apoptosis in response to external signals and Fas cross-linking. BWS-related genes are considered to be regulated by genomic imprinting. Therefore the author compared some characteristics of both SMPD1 and imprinted genes. The analyzed features of SMPD1 gene (few and small introns, Alu 1 repeat element, CC-rich regulatory region, alternative splicing) are characteristic to imprinted genes. Hemihypertrophy, mentioned in the referred BWS-case, is distinctive to the involvement of the maternal allele of the second BWS chromosomal region (BWSCR2) at 11p15.3. The SMPDI gene has been localized just distal to the B05 breakpoint of BWSCR2. Furthermore, in BWS-associated tumors, the loss of heterozygosity (LOH) found on 11p15 was always maternal. Thus, in the case referred to with ASM deficiency the maternal allele has certainly been effected. These conclusions are in accordance with the 'cluster-model of imprinting' as well as with the conflict theory of imprinting. Taken together, the above mentioned clinical and experimental data suggest that SMPD1, most likely at 11p15.4, is an imprinted, maternally expressed, BWS- and apoptosis-related growth suppressor gene. Further studies are necessary to prove this hypothesis.

[Detection of delta F508 mutation in cystic fibrosis]. / A delta F508 mutáció kimutatása cystikus fibrosisban.

The common major mutation (delta F508) resulting in the removal of a phenylalanine residue of the cystic fibrosis gene product has been identified in patients with cystic fibrosis in several European countries. The frequency of this mutation was analyzed in 39 Hungarian patients with cystic fibrosis and in some of their relatives. In 43 out of the total 65 persons involved in the study (66.15%), and in 50% of cystic fibrosis chromosomes the delta F508 mutation could be detected. 56.4% of the patients were homozygous for the mutation. The frequency of the delta F508 mutation in these Hungarian patients resembles the values found in Middle Europe. Pulmonary and enteral symptoms were more severe in cystic fibrosis patients with delta F508 mutation. Although the number of patients is relatively low, missing or mild lung involvement characterized the cases with non-delta F508 mutation.

[Comparative immunochemical study of the antigenic makeup of native tetanus toxin from sporulating and nonsporulating C1. tetani strains]. / Sravnitel'noe immunokhimicheskoe izuchenie antigennogo sostava nativnogo stolbniachnogo toksina sporovogo i nesporovogo shtammov C1. tetani

Crude tetanus toxin of nonspore-bearing strain Harward had a complicated antigenic composition; 8 fractions were revealed in disc electrophoresis in polyacrylamide gel, and 8-10 precipitation bands in immunoelectrophoresis. All the antigenic components of the crude toxin of nonspore-bearing strains detected in diffuse precipitation test and immunoelectrophoresis were identical to the corresponding antigens of the spore-bearing strain Kolle 154. However, the filtrate of the culture fluid of the spore-bearing strain contained at least two antigenic components absent in the culture fluid of the nonspore-bearing strain. Identity of the amin antigenic component--tetanospamin--was demonstrated in nonspore-bearing and spore-bearing industrial C1. tetani strains in experiments of immunoelectrophoresis with the use of antibodies against tetanospasmin.

The effect of enhancing factor on the immunity of mice against tetanus.

Enhancing factor was prepared from spleens of mice primed and reinjected with tetanus toxoid. The culture supernatant was separated by gel chromatography on Sephadex G-150, the resulted fractions were ultrafiltered and their enhancing activity was tested in vivo. The 1st fraction separated by gel chromatography proved to be active.

Comparison of the shock-inducing effect of anti-mouse anti-thymocyte horse serum and normal horse serum. I. Experiments with three-week-old mice.

Sera administered intravenously to mice hypersensitized with normal horse serum and with horse serum of anti-lymphocytic activity, produce reactions that differ considerably in mice treated in different ways. The experiments of the authors indicate that the anaphylactogenic effect of ATS is substantially stronger than that or normal horse serum. The paper discusses the clinical and theoretical conclusions to be drawn from this phenomenon observed in the experiments.