Chemokine levels in serum of children with atopic dermatitis with regard to severity and sensitization status.

BACKGROUND: Many infants with atopic dermatitis (AD) are sensitized against food or airborne allergens. The severity of AD, using the SCORAD, seems to correlate with elevated serum levels of TARC/CCL17. Other chemokines, such as CCL20 or CCL25, have been described in the context of allergic inflammation. The aim of this study was to analyze whether chemokine serum levels differ within a cohort of infants suffering from varying severities of AD with or without allergic sensitization. METHODS: Chemokine serum levels (CCL8, CCL17, CCL20, CCL25) as well as food and airborne allergen-specific IgE were analyzed in infants with AD. RESULTS: About 60.9% (78/128) infants with AD (median age 8.8 months, 49 (38%) girls and 79 (62%) boys) showed a positive screening test to common food allergens and 26.6% to common airborne allergens. There was a strong correlation between serum levels of CCL17 and SCORAD in food-sensitized infants (r(s) = 0.646, p = <1e-04) and airborne-sensitized infants (r(s) = 0.587, p = 0.00065) in contrast to non-sensitized ones. Moreover, food-sensitized infants showed significantly higher levels of CCL25 compared to non-food-sensitized ones (p = 0.007). CONCLUSION: The strong correlation between TARC/CCL17 and SCORAD in infants with specific sensitizations may be accounted for by the impaired skin barrier. As TARC/CCL17 has been found mainly in the (inflamed) skin but not in the gut, the detection of significantly higher levels of CCL25, ligand of CCR9, localized primarily in the gastrointestinal tract, suggests its impact on food allergen-induced inflammation processes in food-sensitized infants.

Changes in cerebral oxygenation during early postnatal adaptation in newborns delivered by vacuum extraction measured by near-infrared spectroscopy.

BACKGROUND: Newborns delivered by vacuum extraction quite often show clinical signs of a hemodynamic compromise, which is difficult to assess in terms of severity. The conventional means to measure the hemodynamic status are not sensitive enough to appreciate the severity of general, and more specifically of cerebral circulatory imbalance. The aim was to study cerebral tissue oxygenation during postnatal adaptation in these infants using near-infrared spectroscopy. METHODS: The tissue hemoglobin index (THI), tissue oxygenation index (TOI), arterial oxygen saturation (pre-ductal SaO2) and heart rate (HR) were recorded immediately after birth, and again after 12-24 hours of life in 15 newborns delivered by vacuum extraction due to fetal distress. A comparison with 19 healthy newborns delivered by elective cesarean section was performed. RESULTS: Newborns delivered by vacuum extraction had significantly higher THI 10 to 15 minutes after birth. TOI and HR were significantly higher in the first 5 min and SaO2 in the first 10 minutes but then did not differ from those after cesarean section. CONCLUSION: Infants delivered by vacuum extraction following fetal distress show transient deviations in cerebral oxygenation and perfusion after birth which were not detectable after 24 hours.

Molecular sIgE profile in infants and young children with peanut sensitization and eczema.

BACKGROUND: Many children develop a sensitization to peanut in early infancy, even before peanut is introduced in their diet. Sensitization is particularly common in young children with eczema. There have been scant data available to date on the sensitization pattern for specific peanut allergens in this patient group. The aim of this study was to investigate the allergen profile of infants and young children with peanut sensitization and eczema. METHODS: Sera from 53 children aged ≤ 20 months with eczema and sensitization to peanut but who had not yet consumed products containing peanuts were included in the analysis. Sera were analyzed using microarray immunoassay (ImmunoCAP ISAC). RESULTS: In total, 63 % of peanut-sensitized children showed specific immunoglobulin E (sIgE) against at least one peanut allergen on the microarray. Specific IgE to the 7S globulin Ara h 1 was detected in 40 % of the children, to the 2S albumin Ara h 2 in 30 % and to the 11S globulin Ara h 3 in 23 %. Only one child had sIgE to Arah 8, the homologoue of Bet-v-1. Data on clinical relevance were available for 24 of 53 children: 14 of 24 patients had objective allergic reactions to peanut, while 10 children were peanut-tolerant. The seed storage protein Ara h 2 was not detected on microarray in 43 % (6 of 14) of children with peanut allergy. Two of these six children were mono-sensitized to Ara h 1 and two to Ara h 3, while in three children none of these seed storage proteins was detected. DISCUSSION: It could be shown that infants and young children with eczema and sensitization to peanut recognize predominantly seed storage proteins from peanut, even before the introduction of peanut into their diet. Sensitization to pollen-related food allergens seems to be rare at this age. At this age not only Ara h 2, but also Ara h 1 seems to be related to clinical relevance.

The value of specific IgE to peanut and its component Ara h 2 in the diagnosis of peanut allergy.

BACKGROUND: To avoid unnecessary oral food challenges, which are time consuming, stressful, and risky, improved in vitro diagnostic methods for food allergy such as component resolved diagnostics are still under investigation. OBJECTIVE: To investigate the role of whole peanut- and peanut-component (Ara h 1, Ara h 2, Ara h 3, Ara h 6 and Ara h 8)-specific IgE levels in the diagnostic procedure of peanut allergy as well as the diagnostic properties of peanut-specific IgG and IgG4. METHODS: Sixty-one children underwent oral peanut challenge tests for diagnostic purposes irrespective of their peanut-specific IgE levels. Peanut-specific serum IgE, IgG, and IgG4 levels were determined by ImmunoCAP FEIA and specific IgE against individual peanut proteins by Immuno Solid-phase Allergen Chip. RESULTS: Thirty-four of 61 patients (56%) had a peanut allergy. No significant difference was observed for peanut-specific IgG or peanut-specific IgG4 levels between patients who were allergic and tolerant patients, whereas peanut-specific IgE was significant higher in patients who were allergic than in tolerant patients (P < .005). Twenty-five of 61 children had peanut-specific IgE above a previously proposed cutoff level of 15 kUA/L; however, 7 of these 25 children (28%) were clinically tolerant. Ara h 2-specific IgE was significantly lower in tolerant than in patients with allergies (P < .0001). Interestingly, 94% of the patients with peanut allergies showed IgE-binding to Ara h 2. Unfortunately, 26% of the sensitized but tolerant patients have shown IgE binding to Ara h 2 too. CONCLUSIONS: Neither the level of specific IgE to peanut nor to Ara h 2 was able to clearly distinguish patients with clinical relevant peanut allergy from those who were clinical tolerant in our population. As expected, peanut-specific IgG and IgG4 did not improve the diagnostic procedure.

Near-infrared spectroscopy measurements of cerebral oxygenation in newborns during immediate postnatal adaptation.

OBJECTIVE: In view of growing concerns regarding the optimal supplementation of oxygen at birth, we measured cerebral oxygenation during the first minutes of life. STUDY DESIGN: Using near-infrared spectroscopy, changes in cerebral oxygenated hemoglobin (O(2)Hb), dexoxygenated hemoglobin (HHb), and tissue oxygenation index (TOI) were measured during the first 15 minutes of life in 20 healthy newborn infants delivered at term by elective cesarean section. RESULTS: O(2)Hb and TOI increased rapidly within the first minutes of life (median slope for O(2)Hb, 3.4 micromol/L/min; range, 1.4 to 20.6 micromol/L/min; median slope for TOI, 4.2 %/min; range, -0.4 to 27.3%/min), and cerebral HHb decreased (median slope, -4.8 micromol/L/min; range, -0.2 to -20.6 micromol/L/min). O(2)Hb, TOI, and HHb all reached a plateau within 8 minutes. CONCLUSIONS: A significant increase in cerebral O(2)Hb and TOI and a significant decrease in HHb occur during immediate adaptation in healthy term newborns, reaching a steady plateau at around 8 minutes after birth.

Can the use of HEPA cleaners in homes of asthmatic children and adolescents sensitized to cat and dog allergens decrease bronchial hyperresponsiveness and allergen contents in solid dust?

BACKGROUND: Exposure and sensitization to pet allergens are associated with allergic asthma in children. Conflicting data have emerged regarding the potential benefit of air cleaners with respect to a reduction of indoor pet allergens and bronchial hyperresponsiveness (BHR). METHODS: In a randomized controlled trial 36 asthmatic children with sensitization to cat and/or dog and significant exposure to cat and/or dog allergen (Fel d 1 and/or Can f 1 >500 ng/g of carpet dust) were included in order to study the effect of high-efficiency particulate arresting (HEPA) air cleaners placed in the living room and bedroom compared with the effect of sham air cleaners. Patients were allocated to two groups: group 1 exposed to active filters and group 2 exposed to sham filters. At month 0, after 6 months and after 12 months, pulmonary function testing and cold air challenge were performed, serum eosinophil cationic protein (ECP) and specific IgE to seven aeroallergens were determined, and carpet dust samples and filters were collected. Major pet allergen concentrations (Fel d 1, Can f 1) were determined in filters and bulk dust samples. RESULTS: Thirty patients completed the study. After 6 and 12 months, there was no significant change in delta FEV(1) after cold air challenge, or in the use of medication and serum ECP levels. However, there was a trend in the active group towards an improvement of bronchial hyperresponsiveness, whereas the sham filter group showed a deterioration of BHR. CONCLUSION: Although HEPA air cleaners retained airborne pet allergens, no effect on disease activity or allergen concentrations in bulk dust samples was observed in this study.

Use of Phadiatop Infant in diagnosis of specific sensitization in young children with wheeze or eczema.

Wheezing and eczema are common symptoms in young children and it is important to disclose sensitization for correct management. The objective of this study was to assess the diagnostic values of Phadiatop Infant, an in vitro test for graded determination of immunoglobulin E (IgE) antibodies to food and inhalant allergens. One-hundred and forty-nine children (median age 1.4 yr) with symptoms of wheezing (51%) eczema (28%) or a combination of both (21%) were classified as atopic or non-atopic based on case history, atopic history, physical examination and determination of IgE antibodies. The clinical performance of Phadiatop Infant was evaluated for 145 children against this classification in a blinded manner to the allergist. Fifty-one children were classified as atopic of which Phadiatop Infant identified 49. Ninety-four were non-atopic of which the test identified 90. This resulted in a sensitivity of 96%, a specificity of 96%, a positive and a negative predictive value of 94% and 98%, respectively. Logistic regression showed that probability had to be assessed as atopic increased with increasing Phadiatop Infant values. These results suggest that Phadiatop Infant can be recommended as an adjunct to the clinical information in the differential diagnosis on IgE-mediated allergy in young children. The test thus provides an opportunity for early correct diagnosis and identification of subjects at risk for whom intervention may be necessary.

Reproducibility of cerebral oxygenation measurement in neonates and infants in the clinical setting using the NIRO 300 oximeter.

OBJECTIVE: To study reproducibility of cerebral tissue oxygenation index (cTOI) values in neonates and infants in a clinical setting using the NIRO 300 oximeter (Hamamatsu Photonics, Hamamatsu City, Japan). DESIGN: Clinical, observational study. SETTING: University hospital, pediatric intensive care unit. PATIENTS: Twenty neonatal and pediatric intensive care patients (age 0-190 days; median 4.5 days). INTERVENTIONS: Reproducibility of cTOI was measured at the lateral forehead of the patients. MEASUREMENTS AND MAIN RESULTS: Sensor exchange experiments were performed by removing the sensor and reapplying another sensor (sensor 1 vs. sensor 2) at the same position. Simultaneous measurements, comparing cTOI values from the right and left forehead, were performed using both sensors. Corresponding sensor exchange experiments were performed within 10 mins. All tests were done under stable, steady-state cardiorespiratory conditions. Data were compared using Bland-Altman bias analysis and paired, two-sided Student's t-test (p < .05). Sensor exchange experiments and simultaneous left-to-right forehead measurements revealed only small mean differences (<5%) and no significant differences between corresponding values (p = .953/.164). However, Bland-Altman bias analysis revealed poor agreement with large 95% limits of agreement in particular for sensor exchange experiments (-17.8% to 17.6%) and less for simultaneous left and right measurements (-14.4% to 10.4%). CONCLUSIONS: The present study shows that cTOI measurements using the NIRO 300 oximeter at the lateral forehead of neonates and infants are not well reproducible under clinical conditions. This raises the question whether generally valid normal values can be defined with the used approach and makes it difficult to determine a normal range of cerebral oxygenation.

Near-infrared spectroscopic cerebral oxygenation reading in neonates and infants is associated with central venous oxygen saturation.

BACKGROUND: The aim of the study was to elucidate easily determinable laboratory and vital parameters in clinical practice to explain variability of near-infrared spectroscopic cerebral oxygenation readings in critically ill newborns and infants using the NIRO 300 spectrometer. METHODS: Near-infrared spectroscopy (NIRS) cerebral tissue oxygenation index (cTOI) was measured on the forehead of critically ill neonates and infants with existing arterial and/or central venous access. We recorded patient characteristics and simultaneously determined sedation state, hemodynamic, respiratory and laboratory data, such as arterial blood gas analysis, electrolytes, hemoglobin and arterial lactate concentration, blood glucose and central venous oxygen saturation. Data were compared using linear, multiple and forward stepwise regression analysis (P < 0.05). RESULTS: A total of 155 neonates and infants aged from 0 to 365 days (median 12 days) were studied. cerebral tissue oxygenation index (cTOI) values ranged from 32.1 to 91.0% (60.5 +/- 11.5%). Simple linear regression analysis revealed significant associations between cTOI and arterial oxygen saturation (r = 0.254, P = 0.001), transcutaneously measured arterial oxygen saturation (r = 0.320, P < or = 0.0001), central venous oxygen saturation (r = 0.489, P < 0.0001), arteriovenous oxygen extraction (r = 0.445, P < 0.0001) and presence of a cardiac shunt (r = 0.250, P = 0.024). Multiple regression analysis and forward stepwise regression revealed two independent, significant predictors for cTOI, namely SvO2 (P < 0.0001) and presence or absence of a cardiac shunt (P = 0.003). SvO2 alone explained 23.9% of the variability of cTOI. The addition of the variable 'cardiac shunt' improved the model to 33%. CONCLUSIONS: Based on our study results cerebral tissue oxygenation readings by the NIRO 300 near-infrared spectrometer is influenced by central venous oxygen saturation, which partially explains intersubject variability of NIRS cerebral oxygenation readings.

Tissue oxygenation monitoring during major pediatric surgery using transcutaneous liver near infrared spectroscopy.

BACKGROUND: The aim of the study was to compare liver tissue oxygenation determined by near infrared spectroscopy (NIRS) with central venous oxygen saturation (SvO(2)) and intestinal perfusion as measured by gastric intramucosal pH (pHi) in pediatric surgical patients. METHODS: Twenty children undergoing craniofacial surgery with expected major intraoperative blood loss were studied. NIRS tissue oxygenation index (TOI(Liver)) and pHi values were recorded. Arterial blood gas analysis and SvO(2) were assessed from periodically taken blood samples. Data are presented as ranges (median) and were compared using linear regression analysis. Sensitivity and specificity of the intra-individual changes in TOI(Liver) to predict falling SvO(2) or pHi values were calculated. RESULTS: Patients age ranged from 0.79 to 8.27 years (1.92 years). TOI(Liver) ranged from 41.5 to 77.4% (61.5%), gastric pHi from 7.13 to 7.60 (7.37) and SvO(2) from 51 to 86% (74%). Among patients only moderate correlation was found between TOI(Liver) and SvO(2) (r = 0.594, P < 0.0001) and gastric pH(i) (r = 0.502, P < 0.0001). Intra-individual measured TOI(Liver) values, however, demonstrated close correlation with SvO(2) values (r = 0.680 to 0.976) but a varying correlation with gastric pHi values (r = 0.055 to 0.972). Sensitivity/specificity of TOI(Liver) to predict decreasing SvO(2) or gastric pHi values were 76.4/73.4% and 67.4/62.7% respectively. CONCLUSIONS: TOI(Liver) provided a better trend monitor of central venous oxygen saturation than gastric intramucosal pH. Because of its limited sensitivity and specificity to indicate deterioration of SvO(2), liver tissue oxygenation measured by transcutaneous NIRS does not provide additional practical information for clinical management.

Slow blood sampling from an umbilical artery catheter prevents a decrease in cerebral oxygenation in the preterm newborn.

OBJECTIVE: Blood sampling from an umbilical artery catheter (UAC) placed in a high position (thoracal 6-9) has the potential to produce clinically significant changes in cerebral blood flow and, thereby, in cerebral oxygenation. This may contribute to cerebral impairment in preterm newborn infants. Therefore, we set up a study to determine the effects of different sampling speeds through a UAC on cerebral oxygenation in preterm infants. METHODS: Thirty pairs of measurements were conducted on 20 preterm infants (median gestational age: 30.14 weeks; median birth weight: 1170 g). For each infant, 2 blood samplings (both 2.3 mL, including flush volume) through the UAC in high position were taken at 2 different speeds (20 and 40 seconds) in alternating sequence. Cerebral oxygenation was measured noninvasively by near-infrared spectroscopy. Concentration changes in cerebral oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb), along with the tissue oxygenation index (TOI; O2Hb/[O2Hb + HHb] x 100), were recorded while blood was withdrawn and subsequently reinfused. RESULTS: A significant decrease in O2Hb and TOI occurred during blood sampling within 20 seconds (median DeltaO2Hb: -1.5 micromol/L; range: -4.1-2.3; median DeltaTOI: -0.6%; range: -6.3-2.3), whereas HHb increased (median DeltaHHb: 0.4 micromol/L, range: -1.1-3.9). No significant change was found in O2Hb, HHb, and TOI when sampling time was extended to 40 seconds. CONCLUSION: Our results show that blood withdrawal over 20 seconds from a UAC in high position significantly decreases cerebral O2Hb and TOI in preterm infants. Prolonging sampling time to 40 seconds can prevent this phenomenon.

Transcutaneously measured near-infrared spectroscopic liver tissue oxygenation does not correlate with hepatic venous oxygenation in children.

PURPOSE: To compare transcutaneous near-infrared spectroscopic (NIRS) measured liver tissue oxygenation with hepatic vein oxygen saturation (SvhO2) in children undergoing cardiac catheterization. METHODS: A NIRS optode (containing an emitter and a receiver of near-infrared light) was placed directly below the right costal arch above the palpable liver in 40 children aged 0.02 to 7.28 yr (median: 1.8 yr). Spatially resolved spectroscopic measured tissue oxygenation index (TOI) was recorded using the NIRO-300. Paired blood samples from the hepatic vein were taken under radiological control for determination of SvhO2 in a co-oxymeter. TOI values were compared with hepatic vein oxygenation, with simultaneously obtained arterial oxygen saturation (SaO2), inferior vena cava SO2 and hemoglobin concentration using simple linear and multi-regression analysis. RESULTS: TOI values ranged from 35% to 73% (58.6 +/- 8.4%); SvhO2 from 32% to 80% (58.4 +/- 14.4%), and arterial SO2 from 54% to 100% (90.0 +/- 11.4%). TOI and hepatic vein oxygen saturation failed to correlate (r = 0.052/P = 0.752). A regression model containing arterial saturation (Delta R2 = 0.177) and the ratio of pulmonary to systemic resistance (Delta R2 = 0.095) explained 27.3% of the observed variance in TOI. In this model, hepatic vein oxygen saturation was no longer significant; explaining only 3.4% of the variance. No other variable retained a significant association. CONCLUSION: Transcutaneously measured NIRS tissue oxygenation with an optode placed over the palpable liver does not correlate with SvhO2. The value is dominated by non-hepatic variables such as arterial saturation and vascular resistances.

Placebo-controlled study of the mite allergen-reducing effect of tannic acid plus benzyl benzoate on carpets in homes of children with house dust mite sensitization and asthma.

We studied the effect of a spray containing 1% benzyl benzoate, an acaricide, and 1% tannic acid ('Lowal'; a protein-denaturing substance), on concentrations of major allergens from house dust mite (HDM) species Dermatophagoides pteronyssinus and D. farinae (Der p 1 and Der f 1, respectively) in carpets. In a double-blind, placebo-controlled study with crossover design, 30 homes of children with HDM sensitization and asthma were included. All houses showed > or = 400 ng/g of Der p 1 + Der f 1 in carpet dust. The first treatment was performed on day 0 (group 1 active treatment, n = 15; group 2 placebo treatment, n = 15). After 2 and 8 weeks, dust samples were collected for quantification of mite allergens. After a 2-week washout period, the second treatment was performed (group 1 placebo treatment; group 2 active treatment). Again, carpet dust was collected after 2 and 8 weeks. Twenty-two of 30 families completed the trial: 14/15 in group 1 and eight of 15 in group 2. On day 0, there was no significant difference in mite allergen exposure between group 1 and group 2 (1,498 vs. 2,239 ng/g of Der p 1 + Der f 1, respectively). In group 1, the geometric mean for the difference of mite allergen concentration comparing day 0 and week 6 was 196 ng/g (95% CI: -7,161 and 8,401) for the first treatment (active) and 15 ng/g (95% CI: -1,079 and 1,292) for the second treatment (control). In group 2, the difference was 66 ng/g (95% CI: -398 and 1,515) for the first treatment (control) and 609 ng/g (95% CI: 186 and 9,264) for the second treatment (active). Comparing placebo and active treatment in total, there was a significant decrease following placebo treatment after 14 days (p = 0.026). After 8 weeks, active treatment was superior to placebo treatment (p = 0.049), but the allergen reduction achieved was < 20% (median 1,500 ng/g on day 0 vs. 1,250 ng/g after 8 weeks). We conclude that the slight mite allergen reduction on carpets achieved by the treatment with 'Lowal' is unlikely to achieve worthwhile clinical benefit either in the treatment of mite-sensitive patients or in primary or secondary prophylaxis.

Liver tissue oxygenation as measured by near-infrared spectroscopy in the critically ill child in correlation with central venous oxygen saturation.

OBJECTIVE: To evaluate the clinical usefulness of near-infrared spatially resolved spectroscopic quantitative assessment of liver tissue oxygenation for simple, non-invasive estimation of global tissue oxygenation in critically ill neonates and children. DESIGN: Prospective observational clinical study. SETTING: A tertiary multidisciplinary neonatal and paediatric intensive care unit (23 beds). PATIENTS: One hundred neonates and children consecutively admitted to the paediatric intensive care unit. MEASUREMENTS AND RESULTS: Near-infrared spectroscopic single-point assessment of liver tissue oxygenation index (TOI(Liver)) was compared with global tissue oxygenation as measured by central venous oxygen saturation (SvO(2)) and derived haemodynamic parameters. Data were compared using linear and multiple regression analysis. Overall correlation between TOI(Liver)and SvO(2) was good ( r=0.72, p<0.0001). Multivariable regression revealed that SvO(2) alone explained 51% of the observed variance of TOI(Liver). However, our data demonstrated large inter-individual differences between SvO(2) and TOI(Liver) values. CONCLUSION: Near-infrared spatially resolved spectroscopic quantitative measurement of liver tissue oxygenation correlates well with SvO(2) in critically ill neonates and children. Large inter-individual SvO(2) to TOI(Liver) differences may prevent its use for non-invasive single-point estimation of global tissue oxygenation. Further clinical studies are required to validate the method with other regional and global haemodynamic parameters and to evaluate its clinical use for continuous non-invasive haemodynamic monitoring.

The atokous-epitokous border is determined before the onset of heteronereid development in Platynereis dumerilii (Annelida, Polychaeta).

In most nereids sexual maturation is accompanied by a dramatic reorganization of the body that enables swarming of the formerly benthic worms. However, a border exists between unchanged anterior (atokous) and metamorphosed posterior (epitokous) segments. The site of this atokous-epitokous border (a/e border) is different in sexually mature males and females of Platynereis dumerilii. There is no correlation between the total number of setigerous segments of a specimen and the location of the a/e border. The location of the a/e border and sexual development are affected neither by cutting off caudal segments of juveniles (including the prospective a/e border) nor by transecting the ventral nerve cord. When parapodia are transplanted from prospective epitokous regions to prospective atokous regions and vice versa, they maintain their original character during metamorphosis. The results presented here suggest that prospective atokous as well as epitokous characters are determined at or only very shortly after formation of the respective segments. Thus the a/e border is established well in advance of the onset of epitokous metamorphosis.