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Jolanta Wasilewska, Mark Klukowski Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, Bialystok, Poland Abstract: Autism spectrum disorder (ASD) is a genetically determined neurodevelopmental brain disorder presenting with restricted, repetitive patterns of behaviors, interests, and activities, or persistent deficits in social communication and social interaction. ASD is characterized by many different clinical endophenotypes and is potentially linked with certain comorbidities. According to current recommendations, children with ASD are at risk of having alimentary tract disorders – mainly, they are at a greater risk of general gastrointestinal (GI) concerns, constipation, diarrhea, and abdominal pain. GI symptoms may overlap with ASD core symptoms through different mechanisms. These mechanisms include multilevel pathways in the gut–brain axis contributing to alterations in behavior and cognition. Shared pathogenetic factors and pathophysiological mechanisms possibly linking ASD and GI disturbances, as shown by most recent studies, include intestinal inflammation with or without autoimmunity, immunoglobulin E-mediated and/or cell-mediated GI food allergies as well as gluten-related disorders (celiac disease, wheat allergy, non-celiac gluten sensitivity), visceral hypersensitivity linked with functional abdominal pain, and dysautonomia linked with GI dysmotility and gastroesophageal reflux. Dysregulation of the gut microbiome has also been shown to be involved in modulating GI functions with the ability to affect intestinal permeability, mucosal immune function, and intestinal motility and sensitivity. Metabolic activity of the microbiome and dietary components are currently suspected to be associated with alterations in behavior and cognition also in patients with other neurodegenerative diseases. All the above-listed GI factors may contribute to brain dysfunction and neuroinflammation depending upon an individual patient’s genetic vulnerability. Due to a possible clinical endophenotype presenting as comorbidity of ASD and GI disorders, we propose treating this situation as an “overlap syndrome”. Practical use of the concept of an overlap syndrome of ASD and GI disorders may help in identifying those children with ASD who suffer from an alimentary tract disease. Unexplained worsening of nonverbal behaviors (agitation, anxiety, aggression, self-injury, sleep deprivation) should alert professionals about this possibility. This may shorten the time to diagnosis and treatment commencement, and thereby alleviate both GI and ASD symptoms through reducing pain, stress, or discomfort. Furthermore, this may also protect children against unnecessary dietary experiments and restrictions that have no medical indications. A personalized approach to each patient is necessary. Our understanding of ASDs has come a long way, but further studies and more systematic research are warranted. Keywords: epigenetics, dysautonomia, food allergy, gluten-related disorders, gut-brain axis, microbiome

Hypersomnia is a significant problem in about 5% of the general population. We discussed clinical aspects in 3 patients with hypersomnia diagnosed in our sleep laboratory. All of the patients, both obese and non-obese, presented abnormal oral glucose tolerance test (OGTT) and plasma insulin level. (1) A 17-year-old girl (BMI=20.3) with a two-year history of daytime sleep attacks (e.g. on the bus, in a classroom, while reading or eating), followed by refreshed feeling. The first symptoms appeared 2 years after spine injury (L2-L3). Total sleep time was >98 perc. The diagnosis of narcolepsy was confirmed by sleep-onset REM periods in 3 of 4 daytime naps (positive Multiple Sleep Latency Tests) and HLA-DQB1 (alleles *0201,*0602). (2) A 16-year-old girl (BMI=32.4) with a history of increased sleepiness (Epworth Sleepiness Scale score=13), not refreshing naps, along with BMI increase, since the age of 13. The metabolic syndrome was diagnosed based on the presence of obesity, hypercholesterolemia (CH=240 mg/dl, HDL-CH=49 mg/dl) and insulin resistance (HOMA index =6.75, hyperinsulinemia -- 367 µU/mL at 30'after OGTT). (3) A 6-year-old boy (BMI=16.0) with a 10-month history of daytime sleep attacks and postprandial sleepiness; nocturnal enuresis, high simple carbohydrate diet, low plasma insulin level after OGTT. Diagnosis of food-related hypersomnia and obstructive sleep apnea was confirmed when the boy recovered after his nutrition habits had been changed, which resulted in decreased respiratory disturbance index (RDI) from 17.7/h in October 2005 to 2.9/h in October 2006. Within that time his parents did not observe any episodes of daytime sleepiness, irritability or nocturnal enuresis. [ABSTRACT FROM AUTHOR]

Purpose: Commonly described multiorgan manifestation of acid GER: primary and secondary to cow's milk allergy and/or other food (CMA/FA) sometimes coexists with ALTE (Apparent Life Threatening Events) syndrome symptoms. Among these symptoms are apnea, cyanosis, pallor, hypotonia, non-epileptic seizures, consciousness disorders and bradycardia. Materials and methods: 264 children aged: 4-102 months (x=20.78±17.23 months) of both sexes, with symptoms suggestive of GER were enrolled into study. 8 children (4.8%) aged up to 2 years (x=10.00±2.78 months) of both sexes with symptoms suggestive of ALTE were selected from the group. 24-hour esophageal pH monitoring was used for acid GER diagnosis in these children. X-ray of esophagus with barium swallow was performed in order to evaluate the height of GER in infants. Immunoallergologic tests were performed in order to differentiate acid GER: primary and secondary to food allergy in these children. Aims: 1. Assessment of the prevalence of acid GER in children with symptoms suggestive of ALTE, 2. Clinical evaluation of symptoms in children with ALTE and acid GER, 3. Assessment of efficacy of conservative treatment in children with reflux and ALTE symptoms, 4. Natural regression of the disease in children with ALTE Results: From among 264 examined children who underwent 24-hour esophageal pH monitoring acid GER was confirmed in 170 (64.4%), and ALTE in 8 (4.8%). The causative role of primary acid GER in children with ALTE regarded to 4 children (50.0%) and GER secondary concerned 4 remaining children (50.0%). Mean number of ALTE episodes that appeared before admission to the hospital was similar in both study groups. The presence of typical reflux symptoms in 5 (62.5%) out of 8 children with ALTE symptoms on the basis of primary or secondary acid GER is significant. Mean value of total acid GER index in a subgroup of children with primary GER constituted x=11.13±1.45 and was not statistically significant in comparison with mean value x=12.13±1.30 of a parameter measured in a subgroup of children with secondary GER. The most common clinical manifestation was apnea and it was of identical prevalence in both study subgroups. Analysis of clinical differentiation of the course of ALTE in children with primary and secondary acid GER under conservative therapy was performed. Under this therapy, gradual regression of ALTE symptoms was achieved in all (8/100.0%) patients, with a tendency to longer time of improvement in children with secondary GER. Typical and atypical symptoms of GER receded in a subgroup with primary GER and were alleviated in a subgroup with secondary GER. In the second half year of clinical observation aggravation of reflux and ALTE symptoms was observed in subgroups. In the second year of clinical observation various typical and atypical symptoms of GER were observed in both subgroups. All these malaises during this period coexisted with ALTE symptoms. In the third year of clinical observation in both subgroups ALTE symptoms connected with acid GER were not observed. Conclusion: Primary and secondary GER were defined as the causative factors of ALTE in 8 (4.8%) examined infants. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is a problem frequently occurring among physically and intellectually disabled individuals. In this group of patients GERD is often overlooked, since the symptoms are usually non-specific. We present two cases of disabled children, who developed complications of GERD in the form of Barrett's esophagus, Barrett's ulceration and bleeding, the life-threatening events which were not preceded by typical GERD complaints. [ABSTRACT FROM AUTHOR]

Subfertility is a global health issue, and as many as 30% of cases are attributed to unexplained reasons. A hypercaloric, high-fat diet stimulates the expansion of pro-inflammatory gut microbiota with a consequent rise in circulating lipopolysaccharides. Adverse gut microbiota remodeling can exacerbate insulin resistance, while sex and thyroid hormones may influence the variability in gut microbiota. This cross-sectional study included 150 participants and was designed to determine a biochemical, nutritional-related pattern that may distinguish subfertile from fertile individuals and couples. A panel of 28 biomarkers was assessed. Four biochemical phenotypes of unexplained subfertility were found, including two metabolic and two immune, when assessed using binary logistic regression models. Two phenotypes were distinguished in women: cardio-metabolic with atherogenic dyslipidemia ( Low HDL-cholesterol: OR = 10.9; p < 0.05) and autoimmune thyroid disorder ( High anti-thyroid-peroxidase: OR = 5.5; p < 0.05) and two in men: hepato-metabolic with elevated liver injury enzymes ( High HOMA-IR: OR = 6.1; p < 0.05) and immune type-2 response ( High IgE: OR = 6.4; p < 0.05). The chances of a couple's subfertility rose with the number of laboratory components of metabolic syndrome in the couple (OR = 1.7; p < 0.05) and if at least one partner had an elevated total IgE level (>100 kU/L) (OR = 6.5; p < 0.05). This study found that unexplained subfertility may be accompanied by mutually overlapping immune and metabolic dysregulations in individuals and couples. We propose one-time laboratory diagnostics taking into account the lipid profile, insulin resistance, anti-thyroid-peroxidase, and total IgE in both males and females with unexplained subfertility. This may allow for a one-time assessment of targeted medical and nutritional interventions and help optimize patients' health. The gut-organ axes related to subfertility are discussed in the context of the obtained results.

Introduction: The long-term observation of the incidence of IgE-dependent sensitization to environmental allergens (food and airborne allergens) of a specific population plays an important role in epidemiological studies., Aim: Retrospective, comparative assessment of IgE-dependent sensitization to food and airborne allergens in the group of patients from the north-eastern region of Poland, in selected years (1998, 2003, 2008, 2012). Long-term assessment of the incidence of IgE-dependent sensitization depending on the age of the patients (1998-2012)., Material and Methods: A group of 6577 children and adolescents aged up to 18 years with a suspicion of an allergic process, diagnosed in 1998-2012. Skin prick tests (SPT) with selected food allergens and airborne allergens were used to evaluate the sensitization process of patients., Results: A significant increase in the percentage of patients sensitized was found, comparing 1998 vs. 2012: to at least one allergen (35.3% vs. 40.4%); only to food allergens (5.1% vs. 13.1%), and to at least one food allergen (10.5% vs. 20.1%). There were no significant changes in the percentage of children and adolescents sensitized to airborne allergens (22.7% vs. 20.3%). The percentage of sensitization to at least one allergen was lowest in 2-year-old children (30.2%), and highest in 15-year-old children (46.8%). The percentage of patients sensitized to airborne allergens increased statistically significantly with their age: 6.3% in infants, 43.7% in adolescents., Conclusions: During the 14-year-period of the study the authors observed an upward trend in the frequency of sensitization to food allergens. The frequency of sensitization to airborne allergens was similar at the beginning and the completion of the study., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

Introduction: Tyrosine kinase inhibitors (TKIs) have greatly improved the treatment outcome for most patients with chronic myeloid leukemia (CML). Ponatinib is a new pan-inhibitor of TK active in resistant CML. This study aimed to evaluate the efficacy and safety of ponatinib in patients suffering from CML., Patients and Methods: This multicenter, non-randomized, observational, retrospective study evaluated the efficacy and safety of ponatinib administered in adult CML patients in any disease phase, including those with a detected ABL T315I mutation, which were resistant or intolerant to previous-generation TKIs. The study comprised 43 patients benefiting from the ponatinib donation program who were treated in 16 Polish centers., Results: For patients who started treatment with ponatinib in chronic phase (CP) (n = 23) and in accelerated phase (AP) (n = 3) the median time on ponatinib was 19.5 months (range: 1.0-35.4), and 31.7 months (range: 31.0-34.1), respectively. All these patients were in CP after 1 month of treatment and at the end of observation - none of them progressed to AP or blastic phase (BP) during the study, meaning that progression-free survival was 100% at the end of observation (35.4 months). The estimated 2-year survival in this group of patients was 84%. For all 43 patients, median survival was not reached (lower quartile 6.3 months), and estimated 2-year survival was 60%., Conclusion: Our analysis confirmed ponatinib efficacy in a significant proportion of patients heavily pre-treated with TKIs achieving durable responses in both CP and AP/BP CML groups., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: A small number of studies concern trophoallergens and aeroallergens sensitization in the developmental age population in Poland. Only a few studies describe the role of selected factors determining the frequency and type of IgE-dependent sensitization in this population., Aim: To assess the rate of sensitization to chosen tropho- and aeroallergens in the group of sensitized patients living in the north-eastern region of Poland with regard to age, sex and birth season., Material and Methods: Skin prick testing (SPT) with selected food allergens (trophoallergens) and airborne allergens was used to evaluate the sensitization process of patients recruited to this study between 1998 and 2012. A positive result of sensitization was defined when the patient had at least one positive skin prick test with the allergen studied. The skin prick tests were done after written consent had been obtained from the parents., Results: Significant results were as follows: sensitization was more common in boys (41.9%) than in girls (35.7%); the highest percentage of sensitized patients was observed in the group of children aged 13-18 years (45.0%) as compared to the group of children up to 3 years old (the lowest 33.1%). The highest percentage of sensitized patients was observed among children born during winter (41.3%), the lowest among children born in autumn (36.8%)., Conclusions: The assessment of sensitization to chosen trophoallergens and airborne allergens should include the role of age, sex and birth season of the diagnosed patient., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia Sp. z o. o.)

Introduction: Good evidence has been provided over the last three to four decades that the prevalence of allergic diseases has been increasing in many developed countries worldwide. Recent data suggest that this increase may now be levelling off., Aim: Retrospective analysis of the prevalence of IgE-dependent sensitization and changes in selected environmental allergens in the population of children and adolescents in the north-eastern region of Poland in the years 1998-2012., Material and Methods: Skin prick testing (SPT) with selected food allergens (trophoallergens) and airborne allergens was used to evaluate the sensitization process of patients recruited to the study in the years 1998-2012. A positive result of sensitization was defined when the patient had at least one positive skin prick test with the allergen studied. The skin prick tests were done after written consent had been obtained from the parents., Results: The retrospective study included children and adolescents aged up to 18 years with a suspicion of an allergic disease, referred to the regional tertiary medical centre for further diagnosis. A total of 6577 patients were studied, including 1556 (23.7%) in 1998, 1473 (22.4%) in 2003, 1690 (25.7%) in 2008, and 1858 (28.2%) in 2012. Sensitization to at least one allergen was observed in 39.0% of the examined children (regardless of the allergen type), of which 8.1% were sensitized to food allergens only, 23.9% to airborne allergens only, and 7.0% simultaneously to food and airborne allergens. During the 14-year study period, an increase was noted in the percentage of the sensitized children from 35.3% at baseline to 40.4% when the study was completed. The percentage of those sensitized to food allergens increased from 10.5% (1998) to 20.1% (2012). The percentage of children sensitized to airborne allergens remained unchanged at the level of 28.2% in 1998 and 27.2% in 2012., Conclusions: Measurement of skin prick test reactivity to different allergens is a useful and commonly used method in epidemiological studies for the assessment of allergic sensitization and changes in selected populations. The obtained results confirmed the need for systematic epidemiological research into allergic sensitization and allergic diseases among children and adolescents in Poland., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia.)

Autism spectrum disorder (ASD), a neurodevelopmental disorder with a prevalence of 1 in 68 children, commonly presents with comorbid conditions which include sleep disorders. Sleep disorders reported in ASD include, among others, increased bedtime resistance, insomnia, parasomnia, sleep disordered breathing, morning rise problems, and daytime sleepiness. Polysomnography studies show that children with ASD have altered sleep architecture including shorter total sleep time and longer sleep latency than typically developing peers. Sleep-related problems have been shown to affect overall autism scores, social skills decits, stereotypic behavior, and cognitive performance. Additionally, problematic sleep in children with ASD has been associated with higher levels of parental stress. Underlying causes specically related to sleep disorders are not fully known. Gastrointestinal (GI) disorders are commonly associated with sleep problems in these patients. Children with ASD and GI symptoms have been found to have a higher prevalence of sleep disturbances compared with typically developing peers who do not have GI symptoms. Treatment approaches to children with sleep disorders are varied and range from lifestyle modications and behavioral interventions to drug therapies and surgical interventions. Physicians should take into account GI disorders as possible underlying causes of sleep-related problems in children with ASD. Therapeutic interventions should begin with less invasive methods before progressing to more invasive options such as pharmacotherapy and should be based on medical indications in order to provide effective care while minimizing potential adverse health effects. Evidence-based studies concerning GI and sleep disorders in children with ASD are limited and further studies are warranted.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with population prevalence of approximately 60-70 per 10,000. Data shows that both opioid system function enhancement and opiate administration can result in autistic-like symptoms. Cow milk opioid peptides, including β-casomorphin-7 (BCM7, Tyr-Pro-Phe-Pro-Gly-Pro-Ile), affect the μ-opioid receptor (MOR) and are subjected to degradation resulting from the proline dipeptidyl peptidase IV (DPPIV, EC 3.4.14.5) enzyme activity. The presence of MOR and DPPIV activity are crucial factors determining biological activity of BCM7 in the human body. Our study examined the effect of β-casomorphin-7 on the MOR and DPPIV genes expression according to specific point mutations in these genes. In addition, we investigated frequency of A118G SNP in the MOR gene and rs7608798 of the DPPIV (A/G) gene in healthy and autistic children. Our research indicated correlation in DPPIV gene expression under the influence of BCM7 and hydrolyzed milk between healthy and ASD-affected children with genotype GG (P<0.0001). We also observed increased MOR gene expression in healthy children with genotype AG at polymorphic site A118G under influence of BCM7 and hydrolyzed milk. The G allele frequency was 0.09 in MOR gene and 0.68 in the DPPIV gene. But our results suggest no association between presence of the alleles G and A at position rs7608798 in DPPIV gene nor alleles A and G at position A118G of the MOR and increased incidence of ASD. Our studies emphasize the compulsion for genetic analysis in correlation with genetic factors affecting development and enhancement of autism symptoms., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Although autistic spectrum disorders (ASD) are a strongly genetic condition certain metabolic disturbances may contribute to clinical features. Metabolism of oxalate in children with ASD has not yet been studied., Aim: The objective was to determine oxalate levels in plasma and urine in autistic children in relation to other urinary parameters., Method: In this cross-sectional study, plasma oxalate (using enzymatic method with oxalate oxidase) and spontaneous urinary calcium oxalate (CaOx) crystallization (based on the Bonn-Risk-Index, BRI) were determined in 36 children and adolescents with ASD (26 boys, 10 girls) aged 2-18 years and compared with 60 healthy non-autistic children matched by age, gender and anthropometric traits., Results: Children with ASD demonstrated 3-fold greater plasma oxalate levels [5.60 (5th-95th percentile: 3.47-7.51)] compared with reference [(1.84 (5th-95th percentile: 0.50-4.70) μmol/L (p < 0.05)] and 2.5-fold greater urinary oxalate concentrations (p < 0.05). No differences between the two groups were found in urinary pH, citraturia, calciuria or adjusted CaOx crystallization rates based on BRI. Despite significant hyperoxaluria no evidence of kidney stone disease or lithogenic risk was observed in these individuals., Conclusions: Hyperoxalemia and hyperoxaluria may be involved in the pathogenesis of ASD in children. Whether this is a result of impaired renal excretion or an extensive intestinal absorption, or both, or whether Ox may cross the blood brain barrier and disturb CNS function in the autistic children remains unclear. This appears to be the first report of plasma and urinary oxalate in childhood autism., (Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Objective: Evaluation of the respiratory response to proton pump inhibitors (PPI) in children with obstructive sleep apnea syndrome (OSAS) and gastroesophageal reflux disease (GERD)., Methods: Of 131 children diagnosed with OSAS (Apnea Hypopnea Index, AHI >1/h), 37 children (6.9 years; 28.24%) with GERD symptoms (>3 times/week) were included. Overnight polysomnography with 24h pH-metry was performed before and after 4-8 weeks of PPI treatment (omeprazole once a day, 1mg/kg)., Results: Of 37 children, 21 were diagnosed with acid GERD where pre- and post-treatment reflux indexes were 14.09±1.47 vs. 7.73±1.36; (p<0.001). The number of obstructive apneas and hypopneas decreased after PPI treatment, resulting in an AHI reduction from 13.08±3.11/h to 8.22±2.52/h; (p<0.01). Respiratory response to PPI ranged from complete resolution of OSA (three children with mild OSA; AHI<5/h; 10.31years; 14.29%) to lack of significant AHI change (six children with severe OSA; AHI>10/h; 3.62 years; 28.57%). Post-treatment AHI was predicted by pre-treatment reflux index (adjusted R(2)=0.487; p<0.001)., Conclusions: Reduction of obstructive respiratory events following short-term PPI treatment in children with both GERD and OSAS may suggest a causal relationship between apnea and reflux in some children. Questionnaire screening for GERD in children with OSAS may be of benefit., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: Immune system dysfunction is considered to be one of many medical disorders found in children with autism. The primary objective of the study was to assess if blood tests reflecting humoral immunity (IgA, IgG, IgM, IgE) are useful in identifying children with regressive autism. The secondary objective was to evaluate a part of the cellular arm of immunity (CD4/CD25 Tregs, CD4/CD23 cells) in those children., Material and Methods: Using a clinical case-control design, the systemic levels of immunoglobulins and lymphocyte subpopulations analysed by flow cytometry were compared in children aged 3-6 years old with a new diagnosis of regressive autism (n = 24; mean age: 4.25 ±1.70 years; male 23/24) and in sex- and age-matched healthy children (n = 24; aged 4.25 ±2.20 years; male 23/24)., Results: The humoral immunity profile, described by three binary variables, IgA < 0.97 g/l, IgE > 36 IU/ml, and IgG > 6.3 g/l, with a sensitivity of 79% and a specificity of 83% (p < 0.0001), was able to identify children with autism. The highest risk of autism diagnosis was associated with IgA < 0.97g/l (OR - 23.0; p < 0.001). A higher number of CD19/CD23 was found in children diagnosed with autism than in the control group (36.82 ±6.72% vs. 18.20 ±3.95%; p < 0.02). No correlation between the number of CD23-positive cells and serum IgE levels was observed., Conclusions: A subtle shift of serum immunoglobulins consisting of low-normal IgA and B cell activation expressed by an increase of CD23-positive cells may characterize children with regressive autism aged 3-6 years old.

Casein-derived peptides have been suggested to play a role in sudden infant death syndrome (SIDS). In this study, we have determined the content of bovine β-casomorphin-7 (bBCM-7) and the activity of dipeptidyl peptidase-IV (DPPIV) in sera of infants with apparent life threatening events (ALTE syndromes, 'near miss SIDS'). We have found that the sera of some infants after an apnoea event contained more β-casomorphin-7 than that of the healthy infants in the same age. In all the children after an apnoea event, however, a lowered DPPIV was detected. We suspect that the low activity of that peptidase may be responsible for opioid-induced respiratory depression, induced by bBCM-7 in the general circulation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: The mechanism of persisting obstructive sleep apnea (OSA) after adenotonsillectomy is not fully explained. The purpose of this study was to evaluate factors associated with residual OSA. The primary outcome measures were metabolic tests and polysomnographic respiratory indices in children with residual disease compared with children who were diagnosed with OSA but were untreated. Secondary outcome measures were acid gastroesophageal reflux indices recorded parallel to the sleep study., Methods: In the one-year study consecutive series of patients with sleep disordered breathing hospitalized in a tertiary pediatric center were evaluated. Following the study protocol a sleep interview, physical examination, metabolic blood tests (serum leptin and the homeostasis model assessment index for insulin resistance, HOMA-IR) and an overnight polysomnography with pH-metry recording were performed. Children diagnosed with OSA were analyzed in two groups: I - residual OSA (after surgery), II - non-residual OSA (newly diagnosed). Logistic regression analysis was applied to obtain significant risk factors for prediction of OSA., Results: Fifty-seven children (mean age ± SE, 6.9 ± 0.5 years; 66.7% boys) met the inclusion criteria and were enrolled in the study as residual (n=19) or non-residual OSA (n=38). The groups differed significantly in mean oxygen saturation, SpO₂ (94.3% vs. 96.2%; p=0.018 respectively), in the Apnea Hypopnea Index, (20.6/h vs. 9.1/h; p<0.03), the number of respiratory arousals with desaturation (2.2/h vs. 0.8/h; p<0.03); mean intraluminal esophageal pH (5.36 vs. 5.86; p=0.007) and the Reflux Index (9.61% vs. 4.35%; p=0.003). The groups did not differ in total sleep time, tonsil size, BMI z-score and blood metabolic indices. Logistic regression analysis showed that residual OSA was significantly predicted by two polygraphic findings: the obstructive hypopnea index (OR 1.15; 95% CI 1.02-1.28; p=0.014) and by the Reflux Index (OR 1.01; 95% CI 1.00-1.34; p=0.042)., Conclusions: 1. Obstructive hypopneas, rather than obstructive apneas, persist after adenotonsillar surgery resulting in residual OSA. 2. Children with residual OSA are at higher risk of acid gastroesophageal reflux and should be evaluated for gastroesophageal reflux disease., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Unrecognized gastrointestinal disorders may contribute to the behavioral problems in non-verbal patients, but they are often overlooked since the clinical symptoms are nonspecific. Eosinophilic esophagitis (EE) is a chronic inflammatory disorder manifesting itself predominantly in reflux-type symptoms that do not respond to standard anti-reflux pharmacotherapy. Here we report the first case of EE in an autistic patient with feeding difficulties caused by exacerbated EE symptoms.

Ascariasis is the most common soil-transmitted helminth infection in the world. The objective of this study was to analyze the clinical symptoms and selected hematological indices of ascariasis in hospitalized children from the northeastern region of Poland. Patients in the Pediatric Ward hospitalized in the Regional Hospital in Dabrowa Białostocka in the period of 2005-2007 were included in this retrospective study. The intestinal stage of ascariasis was diagnosed on the basis of positive coprological survey performed using the decantation technique. A total of 938 patients were included in the study, 1801 stool samples were evaluated, and A. lumbricoides-positive tests were obtained from 252 children. Ascaris-positive young children (< or = 3 yrs) accounted for 3.0% of all hospitalized children, Ascaris-positive preschool-aged children (4-7 yrs) accounted for 8.1% and school-aged children (8-18 yrs) for 15.8%. Seasonal patterns were observed in the prevalence of A. lumbricoides (maximum in August-December). There was no relationship between BMI z-score, hemoglobin levels and prevalence of infection with Ascaris lumbricoides. Significant predictors of intestinal stage ascariasis in a multivariate logistic regression model were: abdominal pain as a reason for hospital admission (OR-2.19; 95% CI 1.62-2.95; p < 0.001) and age from 4 to 7 years (OR-2.0; 95% CI 1.41-2.80; p < 0.001). The prevalence rate of ascariasis was not higher in the group of patients with atopic diseases (bronchial asthma, allergic rhinitis, atopic dermatitis) and co-existing ascariasis did not affect the eosinophil counts in the peripheral blood. Ascariasis is still a current pediatric clinical problem characterized by non-specific clinical manifestations, which should be taken into consideration in the differential diagnosis of children's diseases.

Obstructive sleep apnea is a sleep respiratory disorder characterized by cessation or reduction in air flow through the nose and mouth, leading to a drop in oxygen saturation in the arterial blood, increased respiratory muscle work, arousals and sleep fragmentation. Pathophysiology of the syndrome is multifactorial, with the major role of addenotonsillar hypertrophy and obesity. The frequency of obstructive sleep apnea (OSA) in children grows, which is partly a secondary phenomenon to the rise in the frequency of obesity. The clinical picture is characterized by numerous symptoms that occur during night sleep and at daytime. Apart from difficulties in breathing, snoring and apnea events, the nocturnal symptoms are non-characteristic and can be easily overlooked, especially when a child sleeps alone in a room. In the clinical picture, daytime symptoms may predominate, their intensity being proportional to the degree of airway obstruction (strictures or collapse) and hypoxia. In the morning, the child wakes up tired, with blocked nose, breathes through the mouth, gets tired easily, have concentration problems, is irritated, demonstrates locomotor hyperactivity, which may resemble ADHD symptoms. Long-term disease leads to exacerbation of all-systemic symptoms, results in cardiovascular complications, induces developmental inhibition and cognitive dysfunction, and is responsible for school/social failures and reduced life quality. Most of these symptoms are reversible (partly or completely) after adenotonsilectomy, which is the therapeutic intervention of choice.

The autistic spectrum disorder (ASD) is a neurodevelopmental disorder characterized by socially aloof behavior and impairment of language and social interaction. This paper is a review of literature on gastrointestinal problems in children with ASD. Gastrointestinal symptoms are described in 9-54% of autistic children, among which most common are: constipation, diarrhea and abdominal distension. The gastro-intestinal abnormalities reported in autism include: inflammation (esophagitis, gastritis, duodenitis, enterocolitis) with or without autoimmunity, lymphoid nodular hyperplasia, increased intestinal permeability, low activities of disaccharidase enzymes, impairment of detoxification (e.g. defective sulfation of ingested phenolic amines), dysbiosis with bacterial overgrowth, food intolerance or exorphin intoxication (by opioid derived from casein and gluten). A beneficial effect of dietary intervention on behavior and cognition of some autistic children indicates a functional relationship between the alimentary tract and the central nervous system. There are no epidemiologic data concerning the incidence or prevalence of gastrointestinal problems within the population of children with ASD in comparison to the population of non-ASD children.

Unlabelled: Allergic diseases have a significant impact on the quality of life. The aim of the study was to compare sleep parameters of allergic and non-allergic children., Material and Methods: Pediatric Sleep Questionnaire was used to asses sleep quality in 202 participants in a 3-year prospective study: in 122 hospitalized (mean age 7.9 +/- 4.7) (F/M 75/47) due to allergic (n = 70) or non-allergic disease (n = 52), and in 80 healthy children (mean age 6.3 +/- 5.0) (F/M 36/44). Of 70 allergic participants, 26 had atopic dermatitis (SCORAD > or = 20); 25 were with bronchial asthma (GINA' criteria) and 19 with IgE-dependent food allergy confirmed by oral food challenge. Of 52 non-allergic patients, 31 children had gastro-esophageal reflux disease and 21 children had recurrent respiratory infection., Results: The group of patients needed significantly more time to fall asleep than controls (17.9 +/- 13.7 vs 12.8 +/- 8.5 min; p < 0.004). Children with food allergy and atopic dermatitis had greatest problems with falling asleep (21.4 +/- 13.8 vs 12.8 +/- 8.5 min; p < 0.006) and 20.4 +/- 14.9 vs 12.8 +/- 8.5 min; p < 0.024). The number of nights of sound sleep without waking up was lower in the study group than in controls (3.5 +/- 2.6 vs 5.0 +/- 2.7; p < 0.0002). Atopic dermatitis and food allergy were found to predispose to sleep disruption most. Snoring history was revealed in 43.4% of patients and in 6.4% of controls (p < 0.0001), being significantly more common in children with bronchial asthma and recurrent respiratory tract infections. Allergic disease was a risk factor for snoring (OR--2.94; 95%CI--1.72-5.05; p < 0.001). As many as 91% of parents did not inform doctors about poor sleep of their children., Conclusions: 1. Allergic diseases are accompanied by different sleep disorders included dyssomnias and parasomnias, e.g. bedtime resistance, disrupted sleep or sleep-disordered breathing. 2. Physicians should pay particular attention to sleep quality in children with allergic diseases irrespective of which body system is affected i.e. the skin (atopic dermatitis), the respiratory tract (bronchial asthma) or the alimentary system (food allergy).

Sudden Infant Death Syndrome (SIDS) is a subgroup of unexpected infant deaths that occur during the postneonatal period with relatively consistent clinical, epidemiological, and pathological features. SIDS remains the major cause of death in infants aged between 1 week and 1 year in western countries. While many SIDS risk factors have been and continue to be identified, the diagnosis remains one of exclusion--the definition of SIDS requires a negative history as well as a negative autopsy result. Epidemiological studies have led to the definition of populations with an increased risk for SIDS: prematurely born infants with perinatal risk factors, subsequent siblings of SIDS victims, ALTE infants (10%). Avoidable risk factors such as those associated with inappropriate infants' sleeping position, type of bedding used and sleeping arrangements strongly suggest a basis for further substantial reductions in SIDS incidence rates. The current guidelines for reducing the risk of SIDS are presented.

Unlabelled: Patchy villous atrophy of duodenal mucosa has been described in young children with cow's milk allergy (CMA). Cow's milk protein-sensitive enteropathy may persist in older children and shows characteristic histological features. The advent of magnification endoscopy may allow the macroscopic detection of unrecognised villous atrophy in these patients., Aim: the aim of the study was to evaluate the duodenum mucosa in older children with CM A in infancy using chromoendoscopy and magnification endoscopy., Methods: the study involved 15 children (mean age 15 years; range 12-18) with CM A diagnosed and treated in infancy, currently on normal diet, referred to our department due to abdominal pain. The control group consisted of 8 children with abdominal pain without any evidence of allergy (mean age 15 years, range 13-18). In all patients magnification endoscopy and chromoendoscopy was performed under general anaesthesia (GIFQ 160Z, Olympus). The bulb and the descending portion of the duodenum were examined. 1% methylene blue was used for staining. Each endoscopy was recorded on DVD. Patients with celiac disease, after surgery or treated for other disorders were excluded from this part of the investigation., Results: seven of 15 patients with CM A in infancy had focal villous atrophy of the descending part of the duodenum. In the control group, the villous atrophy was seen in one case., Conclusions: 1. Magnification endoscopy and chromoendoscopy are a valuable method of detecting focal villous atrophy in patients with suspected food allergy. 2. Focal villous atrophy may indicate the presence of food hypersensitivity of persisting from infancy process.

Background: Food allergy is an abnormal response of the immunological system, especially of mucosal immunological system on antigens supplied per os. There are very complicated and still unexplained immunological mechanisms, which lead to hypersensitivity reaction. Most often food hypersensitivity is identified as the effect of atopy, which is connected with humoral response (specific IgE antibody). On the other hand cell immunological response are less investigated, however they can be very important, especially as a significant factor to initiate pathological allergic processes., Aim: To investigate, the usefulness of flow cytometry for estimation of specific sensitization of subpopulation of lymphocytes on food allergens in the allergy diagnosis., Patients and Methods: The investigations were performed on 60 children from 6 months to 5 years old: 20 children with CM A IgE dependent, 20 with CM A IgE independent and 20 healthy children. IgE total, sIgE, IgG, IgA, IgM, basic immunological panel, CD 23, CD25, CD26, CD30, CD69, PCNA were measured., Results: We noticed decrease of expression of CD4+CD30+ between I and II examination (p=0.029), between I and III (p=0.009); decrease of expression of CD8+CD26+ between I and III test (p=0.038); decrease of expression of CD19+CD23+ between I and II examination (p=0.012) in I type of hypersensitivity. We observed a decrease of expression of CD4+CD25+ between I and III examine (p=0.026) and decrease of expression of CD4+ CD26+ between I and III examination (p=0.036) in IV type of hypersensitivity. Expression of CD69 was decreased after diet in IgE dependent allergy. Values of expression of PCNA are similar in I and IV type of hypersensitivity in children with CM A. Decrease of expression of PCNA in II examination was observed in both cases. Reintroduced allergen caused increase of expression of PCNA in both types of allergy (p=0.048 and p=0.041)., Conclusions: Our recent research confirms changes of the expression of T lymphocytes activation markers. It is connected with in vivo stimulation to allergen or with allergen elimination. The study of expression of activation markers using flow cytometry in food allergy in children can be helpful in observation of the dynamic progress process, but it cannot be used as a single diagnosis test.

Gastroesophageal reflux disease (GERD) is a problem frequently occurring among physically and intellectually disabled individuals. In this group of patients GERD is often overlooked, since the symptoms are usually non-specific. We present two cases of disabled children, who developed complications of GERD in the form of Barrett's esophagus, Barrett's ulceration and bleeding, the life-threatening events which were not preceded by typical GERD complaints.

Purpose: Atopic eczema/dermatitis syndrome (AEDS) is often the first manifestation of atopic disease in children. Food hypersensitivity should be considered in approximately 40% of these patients. AEDS children with cow's milk allergy are commonly prescribed a hydrolyzed formulas or amino acid-based formulas for an alternative protein source. The aim of this study was to investigate hypersensitivity to extensive hydrolyzed casein and whey proteins in AEDS children with cow's milk protein allergy (CMA)., Material and Methods: The study included 67 hospitalized children with AEDS (m/f--43/24), aged 1-28 months (mean 11.34 +/- 8.52) and CMA confirmed by oral food challenge. All patients were treated with extensively hydrolyzed formulas: 48/67 children with casein hydrolysates and 19/67 children with whey hydrolysates., Results: In most of studied children we recognized severe AEDS (SCORAD Index: mean 55.41 +/- 17.4; 95% CI 51.17-59.66) with elevated total IgE (mean 432.98 +/- 1030.46; 95% CI 181.63-684.33). In 22/67 children (32.8%) we established diagnosis of hypersensitivities to hydrolyzed formula (HHF): in 17/22 to casein hydrolysates, in 4/22 to whey hydrolysates and in 1/22 to amino-acid based formula. Children with HHF did not differ in the severity of AEDS evaluated by SCORAD (57.18 +/- 16.59 vs 54.56 +/- 17.90), the serum level of total IgE (603.9 +/- 1253 vs 349.4 +/- 906.1) and the time of breast-feeding (4.4 +/- 4.0 months vs 6.8 +/- 7.28). They differ in the number of plasma eosinophils and positive correlation between number of eosinophils and serum level of total IgE (p<0.05, r=0.46 vs r=0.07)., Conclusions: Children with moderate or severe atopic eczema/dermatitis syndrome can demonstrate hypersensitivity to hydrolyzed formula recommended for therapeutic indications.

Bartter syndrome is an uncommon tubular disorder inherited as an autosomal recessive entity. It is associated with hypokalemic metabolic alkalosis with high renin and aldosterone plasma concentration with low or normal blood pressure. Recent studies have demonstrated genetic heterogeneity in Bartter syndrome. Mutations of two genes encoding the Na/K/2Cl cotransporter and potassium channel ROMK are responsible for clinical features of neonatal Bartter syndrome. Mutations of gen encoding the chloride channel ClC-Kb is identified as being causative for the classic Bartter syndrome. And dysfunction of Na/Cl cotransporter in the distal convoluted renal tubule is described as Gitelman syndrome.

The authors present the case of 4-month-old girl, who was admitted to our hospital with hypokalemia, metabolic alkalosis, hyperaldosteronism, hyperreninism with normal blood pressure and high urine concentration of PGE2. All the clinical and biochemical features have led to the diagnosis of Bartter syndrome. Treatment consisted of 15% KCI, spironolacton and indometacin.

Purpose: Coincidence of gastroesophageal reflux disease with obstructive sleep apnea/hypopnea syndrome has been discussed in recent years. Treatment with nasal continuous positive airway pressure (nCPAP) reduces gastroesophageal reflux (GER) in adult patients with obstructive sleep apnea (OSA). Moreover, treatment of gastroesophageal reflux with omeprazole can reduce the severity of obstructive sleep in selected individuals. The aim of the study was to test the hypothesis that gastroesophageal reflux does not influence sleep quality and breathing pattern during sleep in children., Material and Methods: 24 children (14 boys, 10 girls, aged 2 months-3 years) with sleep disturbances indicating GER were studied. Standard polysomnography with parallel recording of 24-h oesophageal monitoring was performed. Apnea/hypopnea index (AHI) in active/REM sleep and quiet/NREM sleep was compared between nocturnal acid GER children (13 children; 7 boys, 6 girls; aged 1.28 +/- 0.95y; FRT-18.63 +/- 11.83%) and nocturnal acid GER-free controls (11 children; 7 boys, 4 girls; aged 1.64 +/- 0.97y; FRT-2.93 +/- 2.08%). Exclusion criteria were: 1. laboratory signs of infection (increasing OB, increasing CRP, increasing alpha2-globulin); 2. clinical symptoms of infection in the respiratory tract, the alimentary tract or in the urinary tract., Results: In children with nocturnal GER higher incidence of obstructive apnea/hypopnea during REM sleep was found: AHI = 23.35/h +/- 19.1; (CI 95%11.81-34.89) vs AHI = 4.99/h +/- 3.12 in children without nocturnal GER. We found no differences between the groups in saturation < 90% time during sleep., Conclusions: The study confirms coincidence of nocturnal gastroesophageal reflux and sleep-related breathing disorders in children. Higher number of apnea/hypopnea during REM sleep was found in children with nocturnal gastroesophageal reflux.

Alkaptonuria is a rare metabolic condition caused by congenital homogentisate oxidase deficiency of recessive inheritance. Homogentisate polymers are accumulated and cause urine darkening, brown pigmentation of connective tissue, articular cartilage pathology. The authors present clinical picture, pathogenesis, diagnostic and therapeutic possibilities in patients with alkaptonuria. Two siblings with alkaptonuria are described.