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Background: the heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. Methods: following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. Results: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87–0.92, specificity 0.73–0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10 −6–1.23 × 10 −3). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. Conclusion: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

Background:It is not well-understood why symptom severity varies between patients with peanut allergy (PA).Objective:To gain insight into the clinical profile of subjects with mild-to-moderate and severe PA, and investigate individual and collective predictive accuracy of clinical background and IgE to peanut extract and components for PA severity.Methods:Data on demographics, patient history and sensitization at extract and component level of 393 patients with probable PA (symptoms ≤ 2 h + IgE sensitization) from 12 EuroPrevall centers were analyzed. Univariable and penalized multivariable regression analyses were used to evaluate risk factors and biomarkers for severity.Results:Female sex, age at onset of PA, symptoms elicited by skin contact with peanut, family atopy, atopic dermatitis, house dust mite and latex allergy were independently associated with severe PA; birch pollen allergy with mild-to-moderate PA. The cross-validated AUC of all clinical background determinants combined (0.74) was significantly larger than the AUC of tests for sensitization to extract (0.63) or peanut components (0.54–0.64). Although larger skin prick test wheal size, and higher IgE to peanut extract, Ara h 1 and Ara h 2/6, were associated with severe PA, and higher IgE to Ara h 8 with mild-to-moderate PA, addition of these measurements of sensitization to the clinical background model did not significantly improve the AUC.Conclusions:Models combining clinical characteristics and IgE sensitization patterns can help establish the risk of severe reactions for peanut allergic patients, but clinical background determinants are most valuable for predicting severity of probable PA in an individual patient.

BACKGROUND: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce.OBJECTIVES: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy.METHODS: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity.RESULTS: Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89).CONCLUSIONS: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy.

BACKGROUND: Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. AIM: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. METHODS: Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double-blind placebo-controlled food challenge [DBPCFC]) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (ORs) and areas under receiver-operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value. RESULTS: Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. CONCLUSION: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.

BACKGROUND: We tested the hypothesis that specific molecular sensitization patterns correlate with the clinical data/manifestation in a European peanut allergic population characterized under a common protocol. METHODS: 68 peanut allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom-eliciting-dose were established by double-blind placebo-controlled food-challenge in all but anaphylactic subjects. Information of early or late (before or after 14 years of age) onset of peanut allergy was obtained from standardized questionnaires. IgE to peanut allergens rAra h 1-3, 6, 8-9, profilin and CCD were determined using ImmunoCAP. RESULTS: 78% of peanut allergics were sensitised to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut allergic population. Geographic differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitisation to rAra h 1 and 2 were exclusively observed in early onset peanut allergy. Peanut tolerant subjects were frequently sensitised to rAra h 8 or 9 but not to storage proteins. Sensitisation to Ara h 2 ≥1.0 kUA /L conferred a 97% probability for a systemic reaction (p=0.0002). Logistic regression revealed a significant influence of peanut extract sensitization and region on the occurrence of systemic reactions (p=0.0185 and p=0.0436 respectively). CONCLUSION: Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood. IgE to Ara h 2 ≥1.0 kUA /L is significantly associated with the development of systemic reactions to peanut. This article is protected by copyright. All rights reserved.

Kiwifruit is a common cause of food allergy. Symptoms range from mild to anaphylactic reactions. We sought to elucidate geographic differences across Europe regarding clinical patterns and sensitization to kiwifruit allergens. Factors associated with the severity of kiwifruit allergy were identified, and the diagnostic performance of specific kiwifruit allergens was investigated. This study was part of EuroPrevall, a multicenter European study investigating several aspects of food allergy. Three hundred eleven patients with kiwifruit allergy from 12 countries representing 4 climatic regions were included. Specific IgE to 6 allergens (Act d 1, Act d 2, Act d 5, Act d 8, Act d 9, and Act d 10) and kiwifruit extract were tested by using ImmunoCAP. Patients from Iceland were mainly sensitized to Act d 1 (32%), those from western/central and eastern Europe were mainly sensitized to Act d 8 (pathogenesis-related class 10 protein, 58% and 44%, respectively), and those from southern Europe were mainly sensitized to Act d 9 (profilin, 31%) and Act d 10 (nonspecific lipid transfer protein, 22%). Sensitization to Act d 1 and living in Iceland were independently and significantly associated with severe kiwifruit allergy (odds ratio, 3.98 [P = .003] and 5.60 [P < .001], respectively). Using a panel of 6 kiwifruit allergens in ImmunoCAP increased the diagnostic sensitivity to 65% compared with 20% for skin prick tests and 46% ImmunoCAP using kiwi extract. Kiwifruit allergen sensitization patterns differ across Europe. The use of specific kiwifruit allergens improved the diagnostic performance compared with kiwifruit extract. Sensitization to Act d 1 and living in Iceland are strong risk factors for severe kiwifruit allergy

BACKGROUND: Fish allergens represent one of the most common causes of adverse reactions to food worldwide. Double-blind placebo-controlled food challenges (DBPCFC) are the gold standard for food allergy diagnosis. However, no standardised recipes are available for common food allergens such as fish, and a well trained dietitian is essential for creating and standardising them. The present study aimed to create and standardise recipes for use in DBPCFCs to fish. METHODS: Three recipes were prepared. Employing a standardised procedure, a total of 35 panelists evaluated the different matrices using an evaluation form. A paired comparison test was used to estimate total evaluation's outcome. Fish allergic patients were challenged with different fish species blinded with the selected matrix and evaluated the recipe using the same form. RESULTS: From a base recipe and step-by-step modifications, a low fat recipe was selected among other recipes tested, which proved to be appropriate for fish blinding, in terms of taste, odour, appearance and blinding. Patients challenged with the final matrix found it acceptable, no matter which fish type was used. CONCLUSIONS: In this pilot study, a recipe with satisfactory organoleptic characteristics was developed and validated for DBPCFC to fish.

Background The EuroPrevall project aimed to develop effective management strategies in food allergy through a suite of interconnected studies and a multidisciplinary integrated approach. To address some of the gaps in food allergy diagnosis, allergen risk management and socio-economic impact and to complement the EuroPrevall population-based surveys, a cross-sectional study in 12 outpatient clinics across Europe was conducted. We describe the study protocol. Methods Patients referred for immediate food adverse reactions underwent a consistent and standardized allergy work-up that comprised collection of medical history; assessment of sensitization to 24 foods, 14 inhalant allergens and 55 allergenic molecules; and confirmation of clinical reactivity and food thresholds by standardized double-blind placebo-controlled food challenges (DBPCFCs) to milk, egg, fish, shrimp, peanut, hazelnut, celeriac, apple and peach. Results A standardized methodology for a comprehensive evaluation of food allergy was developed and implemented in 12 outpatient clinics across Europe. A total of 2121 patients (22.6%

Background Sensitization to hazelnut allergens vary depending on the geographic origin and age of the patients. The objective of this study was to further investigate the allergenic activity of hazelnut allergens using sera from patients recruited in various European regions and presenting different sensitization patterns to hazelnut proteins. Methods Natural Cor a 11 and Cor a 9 were purified from hazelnut whereas Cor a 1 and Cor a 8 were produced as recombinant proteins (rCor a 1.04 and rCor a 8). Sera from hazelnut allergic patients were collected in France (n = 5), Switzerland (n = 2), Greece (n = 11) and Spain (n = 3), within the Europrevall project. Total and allergen-specific IgE were quantified by enzyme allergosorbent test and IgE immunoblot were performed using pooled sera from birch-pollen endemic region or from Greece. Histamine Release (HR) assays were performed with stripped basophils passively sensitized with individual sera and challenged by a hazelnut extract or the different hazelnut allergens. Results As previously described, hazelnut allergic patients from Mediterranean countries are mainly sensitized to the nsLTP Cor a 8 whereas patients from France and Switzerland are sensitized to pollen-related allergens. Interestingly, an intermediate profile was evidenced in patients from Madrid. Hazelnut 7S globulin (Cor a 11) and 11S globulin (Cor a 9) were found to be minor allergens, recognized only by patients from Mediterranean countries. The biologic activity of the 4 tested allergens, analysed by HR assay, further confirmed the sensitization patterns, but also demonstrated the very high elicitation potency of Cor a 8. Conclusions This work, extending previously published researches, represents a step towards the better understanding of the complexity of hazelnut allergy and provides new data on the biological activity of hazelnut allergens and extracts. Electronic supplementary material The online version of this article (doi:10.1186/s13601-015-0066-7) contains supplementary material, which is available to authorized users.

Allergy to banana fruit appears to have become an important cause of fruit allergy in Europe. Among five allergens that have been found, beta-1,3-glucanase denoted as Mus a 5 was identified as a candidate allergen for the component-resolved allergy diagnosis of banana allergy. Because of the variations in protein levels in banana fruit, in this study Mus a 5 was produced as a fusion protein with glutathione-S-transferase in Escherichia coli. The recombinant Mus a 5 was purified under native conditions by a combination of affinity, ion-exchange, and reversed phase chromatography. N-terminal sequence was confirmed by Edman degradation and 55 % of the primary structure was identified by mass fingerprint, while the secondary structure was assessed by circular dichroism spectroscopy. IgG reactivity of recombinant protein was shown in 2-D immunoblot with anti-Mus a 5 antibodies, while IgG and IgE binding to natural Mus a 5 was inhibited with the recombinant Mus a 5 in immunoblot inhibition test. IgE reactivity of recombinant Mus a 5 was shown in ELISA within a group of ten persons sensitized to banana fruit. Recombinant Mus a 5 is a novel reagent suitable for the component-resolved allergy diagnosis of banana allergy.

We prospectively examined the epidemiology of invasive Haemophilus influenzae type b (Hib) infections among children under 5 y of age in the Greater Athens area before the introduction of immunization. The annual incidence of systemic Hib infections was 12/100000. Meningitis was the most common clinical entity and accounted for 69% of the cases. In the prevaccine era, the incidence of systemic Hib disease, particularly that of meningitis, was much lower in Greece compared to rates reported from Northern and Central Europe.

Scope Banana fruit has become an important cause of fruit allergy in the recent years. Among the five registered IUIS allergens, Mus a 1 and Mus a 2 have been characterized in detail. In this study, molecular characterization and evaluation of the allergenic properties of beta-1,3-glucanase from banana (Musa acuminata), denoted as Mus a 5, were performed Methods and results: The gene of Mus a 5 was cloned and sequenced. The obtained cDNA revealed a novel Mus a 5 isoform with an open reading frame encoding a protein of 340 amino acids comprising a putative signal peptide of 28 amino acid residues. By MALDI-TOF analysis Mus a 5 isolated from banana fruit revealed a molecular mass of 33 451 +/- 67 Da. Two Mus a 5 isoforms (pI 7.7 and 8.0) were detected by 2D immunoblot with an identical N-terminal sequence. By mass fingerprint, 76 and 83% of the primary structure was confirmed for the two mature Mus a 5 isoforms, respectively. IgE reactivity to Mus a 5 was found in 74% of patients sensitized to banana fruit. Upregulation of basophil activation markers CD63 and CD203c was achieved with Mus a 5 in a concentration-dependent manner. Conclusion: Mus a 5 is a functional allergen and a candidate for the component-resolved allergy diagnosis of banana allergy.

The aim of the study was to evaluate whether the timing of performing a voiding cystourethrography (VCUG) following a first urinary tract infection (UTI) in infants is related to the presence or the severity of vesicoureteral reflux (VUR). A total of 411 children (male 230, female 181) with a first-recognised UTI between ages 15 days and 12 months (median 3 months) underwent a VCUG within 4–81 days (median 9 days) following diagnosis. The presence and the grade of the VUR were compared in two groups: an “early” group in which the VCUG was performed during the first week of the start of treatment and a “late” group in which the examination was performed during the second week or thereafter. The prevalence of VUR in the study cohort was 23.3% (96/411 infants). A VUR was diagnosed in 44 infants in the early group (28%) and in 52 in the late group (21%). Reflux of grade III or higher was seen in 25/44 (57%) of the infants in the early group and in 27/52 (52%) infants in the late group. These differences were not significant. Our results suggest that neither the presence nor the grade of VUR in infants is influenced by the timing of the examination following diagnosis. We therefore recommend that it is better to perform VCUG as soon as possible, provided the inflammation has subsided.

Ketotifen was administered orally, for 3 months, to 40 children aged 3-14 years with chronic extrinsic asthma of moderate severity in a double-blind placebo-controlled study. A significant clinical improvement with concomitant reduction of antiasthmatic drugs was found in the group receiving the active drug compared with the placebo group (p less than 0.05). The continued administration of ketotifen in an open study to a group of 21 children comprised of patients belonging to both groups (active-placebo) for a period of 15-18 months resulted in disappearance of symptoms in 10 children (47.6%) and moderate improvement in 7 (33.3%).

OBJECTIVE. Therapeutic delay has been suggested as the most important factor that is likely to have an effect on the development of scarring after acute pyelonephritis. However, this opinion has not been supported by prospective studies, so we tested it. METHODS. In a prospective clinical study, we evaluated whether the time interval between the onset of the renal infection and the start of therapy correlates with the development of acute inflammatory changes and the subsequent development of renal scars, documented by dimercaptosuccinic acid scintigraphy. A total of 278 infants (153 male and 125 female) aged 0.5 to 12.0 months with their first urinary tract infection were enrolled in the study. RESULTS. The median time between the onset of infection and the institution of therapy was 2 days (range: 1–8 days). Renal inflammatory changes were documented in 57% of the infants. Renal defects were recorded in 41% of the patients treated within the first 24 hours since the onset of fever versus 75% of those treated on day 4 and onward. Renal scarring was developed in 51% of the infants with an abnormal scan in the acute phase of infection. The frequency of scarring in infants treated early and in those whose treatment was delayed did not differ, suggesting that once acute pyelonephritis has occurred, ultimate renal scarring is independent of the timing of therapy. Acute inflammatory changes and subsequent scarring were more frequent in the presence of vesicoureteral reflux, especially that which is high grade. However, the difference was not significant, which suggests that renal damage may be independent of the presence of reflux. CONCLUSIONS. Early and appropriate treatment of urinary tract infection, especially during the first 24 hours after the onset of symptoms, diminishes the likelihood of renal involvement during the acute phase of the infection but does not prevent scar formation.

Community-acquired pneumonia remains a common and serious illness, which affects children of all age groups. The spectrum of causative organisms is wide and it differs according to the age of the patients. With the advent of new and improved diagnostic techniques our understanding of the aetiology of the disease has been improved considerably. Viruses have been shown to cause up to 90% of pneumonias, especially in the first year of life, with the respiratory syncytial virus to be the most important pathogen and this percentage decreases to approximately 50% by school age. Viral pneumonias frequently are complicated by bacterial infections and mixed infections are identified in 30% of the cases. The precise role of viruses and bacteria in these cases, remains to be clarified.

Rotor syndrome is an inheritable disorder of bilirubin metabolism characterized by a chronic, benign, nonhemolytic jaundice, due to raised, predominantly direct bilirubin. It is considered a pathophysiologic entity primarily involving the storage of organic anions leading to increased reflux of bilirubin from the hepatocytes back to the plasma, resulting in decreased net hepatic uptake. This concept is further supported by scintigraphic findings (i.e., prolonged visualization of the cardiac blood pool with concomitant delayed and markedly decreased uptake of the radionuclide by the liver cells). Furthermore, this scintigraphic pattern differentiates Rotor syndrome from Dubin-Johnson syndrome, extrahepatic biliary obstruction, or advanced hepatocellular disease.

Component resolved diagnosis in relation to severity of hazelnut allergy across Europe MR Datema, L Zuidmeer, C Garino, J Marsh, A Lovegrove, M Clausen, D Gislason, R Dubakiene, I Reig, L Barreales, AC Knulst, T-M Le, ML Kowalski, M Jedvzejczak, J Lidholm, T Kralimarkova, T Popov, R Asero, S Seneviratne, N Sinaniotis, N Papadopoulos, A Purohit, F de Blay, P Bures, S Vieths, M Fernandez-Rivas, K Hoffmann-Sommergruber, R van Ree, B Ballmer-Weber

We present a study of a mentally retarded and mildly dysmorphic female in whom initial cytogenetic studies identified the karyotype 46,X, + mar. Further characterisation of the structurally abnormal chromosome by fluorescence in situ hybridisation (FISH) showed that it is composed of both X and Y chromosome material with a centromere originating from the Y chromosome. The presence of the DMD gene and the absence of the XIST gene was shown by FISH using locus specific probes. The Y segment included the SRY and ZFY genes. Based on these findings, the karyotype was defined as 46, X,der(Y)t(X;Y) (p21.1;q11). This case illustrates male to female sex reversal owing to a partial duplication of the short arm of the X chromosome in the presence of SRY.

A boy, 4 years, 9 months of age, presented with acute hemiplegia, lethargy, ataxia, and dysarthria 24 hours prior to the eruption of typical varicella exanthem. Magnetic resonance imaging findings were typical of multiple cerebral ischemic infarcts. It is suggested that during the period of secondary viremia varicella zoster virus invaded the cerebral blood vessels causing vasculopathy and cerebrovascular infarcts.

The C-band heterochromatin polymorphisms of chromosomes 1, 9, and 16 were studied on peripheral lymphocytes of 67 children with acute lymphoblastic leukemia (ALL) and 50 control individuals. A statistically significant difference between patients and controls was found for large heterochromatin regions (level 3) of chromosomes 1 and 9 (P < 0.001) and for small heterochromatin regions (level 1) of chromosome 16 (P < 0.001). The patients also showed a significant increase in chromosomes 1 and 9 heteromorphism with respect to controls (P < 0.001).

A study was undertaken to determine whether blue fluorescent light might affect the sister chromatid exchange (SCE) frequency of peripheral lymphocytes in icteric newborns undergoing continuous phototherapy treatment (72 h). Also, the potential preventive effect of vitamin E on SCE frequency was studied in a subgroup of 11 preterm and 9 fullterm newborns after daily administration of vitamin E (46.44 mumol/kg/d, im). The results revealed that only the preterm icteric newborns showed an increase in mean SCE frequency of peripheral lymphocytes after phototherapy (9%, p = 0.02), but in no case did the highest SCEs/cell ratio exceed the normal values. No correlation was found between the average SCE rate and birth weight, gestational age or bilirubin levels. Also, no difference in SCEs was observed between newborns treated or untreated with vitamin E.

Community-acquired pneumonia remains a common and serious illness, which affects children of all age groups. The spectrum of causative organisms is wide and it differs according to the age of patients. Therefore, age is a good predictor of the cause of pneumonia. Because of the nonspecificity, of clinical and radiological findings and the limitations of diagnostic tests for identifying the etiologic pathogen, initial therapy is inevitably empiric.

A case of congenital nephrotic syndrome with diffuse mesangial sclerosis and bilateral cataract without other ocular anomalies is presented. This association, to our knowledge, has not been reported before.

Nowadays, clinicians rely greatly on Renal Ultrasound (RU) as a screening examination. RU seems to be less sensitive than Fluoroscopic Voiding Cystourethrography (FVCU) for the detection of Vesicoureteral Reflux (VUR), but relevant percentages in large numbers of patients with Urinary Tract Infection (UTI) are scanty. This study evaluates the potential reliability of RU as a means to detect VUR in children with UTI. The population under study consisted of 288 infants and children (101 boys and 187 girls, median age 3.8 years) with UTI. RU and FVCU were performed within the same day. For data analysis both kidneys were considered separately for a total of 576 kidneys. Of 576 kidneys, VUR documented on FVCU in 116 (20%). In 85 of these refluxing kidneys (73%), the RU was normal and in 31 (27%) was abnormal. Of 517 normal kidneys on RU 85 (16%) had VUR on FVCU. In the remaining 59 kidneys with an abnormal RU (dublex system, dilatation, pyelonephritis, small scarred kidney), VUR was documented on FVCU in 31 (53%). This study oonfirms, that RU does not reliably diagnose VUR, since only 27% of the refluxing kidneys were identified on RU. On the other hand, patients with an abnormal RU would alert the clinician and radiologist to the increased possibility of VUR (53%). It is concluded, that a) RU is not an adequate substitute for the FVCU, if the clinical question is VUR in children with UTI, b)RU should be performed prior to FVCU.

Night and day rhythms of HGH secretion were measured in 5 children before any treatment, 10 days after prednisone administration, and 3 days after ACTH treatment. Corticosteroids and corticotrophin were found to have a pronounced effect on the spontaneous level of HGH with the almost complete disappearance of the normally observed peaks during the 24 hours in the pretreatment study. It is postulated that this disappearance of the spontaneous peaks might explain in part the growth retardation noticed in children on long-term treatment with corticosteroids or corticotrophin.

Fifty-four patients aged between 21 and 50 years with typical symptoms of chronic prostatitis and 10 healthy men serving as control group had prostatic-fluid cultures according to the Meares-Stamey technique. Prostatic-fluid LDH levels were also estimated by agar gel electrophoresis. Eight patients were found to have bacterial prostatitis and significantly elevated LDH5/LDH1 isoenzymes ratio, 24 patients fulfilled the criteria for nonbacterial prostatitis and 22 patients were classified as suffering from prostatodynia. The LDH5/LDH1 isoenzymes ratio was found to decrease gradually as the inflammatory elements of the prostatic fluid reduced with the lowest value detected in the control group.

The pharmacokinetic properties of amikacin sulfate in infants and children aged from three weeks to 6 years were studied during treatment with doses of 7.5 mg/kg every 12 hours using standard assay methods and technique of two compartment open model kinetic analysis. Peak serum concentrations of amikacin were measured 30 or 60 min after the first intramuscular injection. These ranged from 11.8 microgram/ml to 23 microgram/ml in infants and from 9.0 microgram/ml to 29 microgram/ml in children. Five minutes after the first intravenous bolous injection they varied from 16 microgram/ml to 29.8 microgram/ml in infants and from 34 microgram/ml to 42 microgram/ml in children. Twelve hours after injection serum concentrations were less than 0.8 microgram/ml in all patients. Mean serum half-lives of amikacin in infants and children were 2.1 hours and 2.0 hours after intramuscular, and 2.2 and 2.0 hours after intravenous administration respectively. No evidence of accumulation was observed after four days treatment. The amount of antibiotic recovered within 12 hours from the urine in all patients ranged from 34.5 to 65% of an intramuscular dose, and from 45.8 to 63.3% of an intravenous dose. The dosage regime of 7.5 mg/kg body weight given every 12 hours should be safe and effective for the treatment of infections in the age groups studied.

Archives of Disease in Childhood

This study was undertaken in order to evaluate the cytogenetic and immunological responses to the effective, harmless and world-wide used vaccines of I. rubella and II. Measles–mumps–rubella (M-M-RII). In one group (A) of five girls vaccinated against rubella and in another group (B) of four boys and two girls vaccinated against measles–mumps–rubella, the following parameters were studied before and repeatedly after vaccination: (a) SCE frequency, in peripheral lymphocytes, (b) DNA-synthesis, in peripheral mononuclear cells, and (c) antibody titres. The mononuclear cell proliferation rate was elevated between the 3rd and 7th day, preceeding the humoral immunological reactions, which began after the 25th day (group A) and the 28th day (group B). The latter findings coincided with a significant increase of SCE frequency in group A (one child) and in group B (all six children); in no case did the highest SCE/cell ratio exceed the normal value.

Cefotaxime is a new cephalosporin with a spectrum of activity which may make it appropriate for use in pediatric patients. In 33 infants and children, administration of cefotaxime resulted in cure or improvement in 97% of patients, with eradication of 94% of isolated pathogens. Toxicity was minimal. The disposition of cefotaxime in this age group was similar to that reported for adults, with an elimination half-life of approximately 1.5 h, a volume of distribution of 1 liter/kg, a total serum clearance of 10 ml/min per kg, and a renal clearance of 6 ml/min per kg.

The incidence of INH-associated liver injury was evaluated in 239 children aged between 9 and 14 years, who were receiving 300 mg INH/day for tuberculosis prophylaxis. Serum SGOT and SGPT levels were determined before INH administration and at 4-weekly intervals thereafter. Levels of both enzymes were raised during the first 3 months of treatment in 18 (7.5%) children, while in 23 (9.6%) children either SGOT or SGPT exceeded normal levels (SGOT greater than 40 units, SGPT greater than 30 units). Only 2 (0.8%) children showed SGOT and SGPT values above 100 units and in them treatment with INH had to be discontinued. In all other children transaminases returned to normal during uninterrupted INH administration. It was noted also that transaminase values in children who did not exhibit a rise above normal, still had significantly higher levels during treatment compared with before. The findings of this study suggest that liver injury in children receiving INH for prophylaxis occurs more often than it had hitherto been believed but that it is usually mild and transient.

Background Hazelnut allergy is birch pollen–driven in Northern/Western Europe and lipid transfer protein–driven in Spain and Italy. Little is known about other regions and other allergens. Objective Establishing a molecular map of hazelnut allergy across Europe. Methods In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP. Results Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen–driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium , plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen. Conclusions In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established.

An 11-year-old boy was admitted to the hospital because of fever and enlargement of the liver and spleen. During examination of the patient, lymphography of the lower limbs was performed in order to exclude the possibility of Hodgkin's disease. For this purpose 10 ml. of iodized oil (Lipiodol) containing 480 rag. of iodine per milliliter was administered. Three weeks'later a goiter was noticed, which gradually increased in size. A lalI test, performed in another laboratOry, revealed a thyroid uptake of 35 per cent after 3 hours, 7 per cent after 24 hours, and 2 per cent after 48 hourS. The protein-bound radioiodine value 48 hours after administration of the tracer dose was 0.19 per

Night and day growth hormone levels during daily or alternate-day therapy with corticosteroids