The Childrens Memorial Health Institute
The Childrens Memorial Health Institute
Pronicka E.,The Childrens Memorial Health Institute
Medical Hypotheses | Year: 2017
Leigh syndrome (LS) is a neurogenetic disorder of children caused by mutations in at least 75 genes which impair mitochondrial bioenergetics. The changes have typical localization in basal ganglia and brainstem, and typical histological picture of spongiform appearance, vascular proliferation and gliosis. ATP deprivation, free radicals and lactate accumulation are suspected to be the causes. Hypocapnic hypothesis proposed in the paper questions the energy deprivation as the mechanism of LS. We assume that the primary harmful factor is hypocapnia (decrease in pCO2) and respiratory alkalosis (increase in pH) due to hyperventilation, permanent or in response to stress. Inside mitochondria, the pH signal of high pH/low bicarbonate ion (HCO− 3) is transmitted by soluble adenyl cyclase (sAC) through cAMP dependent manner. The process can initiate brain lesions (necrosis, apoptosis, hypervascularity) in OXPHOS deficient cells residing at the LS area of the brain. The major message of the article is that it is not the ATP depletion but intracellular alkalization (and/or hyperoxia?) which seem to be the cause of LS. The paper includes suggestions concerning the methodology for further research on the LS mechanism and for therapeutic strategy. © 2017 The Author
Kolodziejczyk E.,The Childrens Memorial Health Institute
Pancreas | Year: 2016
OBJECTIVES: To evaluate the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) in the detection of chronic pancreatitis (CP)–specific changes in the pediatric population. METHODS: The study included 48 children with pancreatic disorders subjected to both endoscopic retrograde cholangiopancreatography (ERCP) and MRCP within a 1- to 4-month interval. The sensitivity, specificity, positive predictive value, and negative predictive value of MRCP in the detection of CP-specific changes were determined using ERCP as a diagnostic standard. RESULTS: Diagnostic ERCP pancreatograms were obtained in 41 (85.4%) of 48 patients and diagnostic MRCP images in all 48 children. The sensitivity and positive predictive value of MRCP were 77.1% and 90%, respectively, and its specificity and negative predictive value amounted to 50% and 27.3%, respectively. The patients with consistent results of MRCP and ERCP (ie, true-positive and true-negative cases) and individuals with incompatible results of the tests (ie, false-positive and false-negative cases) differed in terms of their median age at MRCP (14.17 vs 10.33 years) and median CP stage according to the Cambridge Scale (4 vs 2). CONCLUSIONS: Magnetic resonance cholangiopancreatography provides diagnostic information equivalent to ERCP in a large percentage of pediatric patients with CP and should be used as the imaging method of choice, especially if the likelihood of therapeutic intervention is low. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Grenda R.,The Childrens Memorial Health Institute
Pediatric Nephrology | Year: 2016
Delayed graft function (DGF) is commonly defined as the requirement for dialysis within the first 7 days following renal transplantation. The major underlying mechanism is related to ischaemia/reperfusion injury, which includes microvascular inflammation and cell death and apoptosis, and to the regeneration processes. Several clinical factors related to donor, recipient and organ procurement/transplantation procedures may increase the risk of DGF, including donor cardiovascular instability, older donor age, donor creatinine concentration, long cold ischaemia time and marked body mass index of both the donor and recipient. Some of these parameters have been used in specific predictive formulas created to assess the risk of DGF. A variety of other pre-, intra- and post-transplant clinical factors may also increase the risk of DGF, such as potential drug nephrotoxicity, surgical problems and/or hyperimmunization of the recipient. DGF may decrease the long-term graft function, but data on this effect are inconsistent, partially due to the many different types of organ donation. Relevant management strategies may be classified into the classic clinical approach, which has the aim of minimizing the individual risk factors of DGF, and specific pharmacologic strategies, which are designed to prevent or treat ischaemia/reperfusion injury. Both strategies are currently being evaluated in clinical trials. © 2016 IPNA
Niemirska A.,The Childrens Memorial Health Institute
Hypertension | Year: 2013
Primary hypertension is associated with disturbed activity of the sympathetic nervous system and altered blood pressure rhythmicity. We analyzed changes in cardiovascular rhythmicity and its relation with target organ damage during 12 months of antihypertensive treatment in 50 boys with hypertension (median, 15.0 years). The following parameters were obtained before and after 12 months of antihypertensive treatment: 24-hour ambulatory blood pressure, left ventricular mass, carotid intima-media thickness, and MRI for visceral and subcutaneous adipose tissue. Amplitudes and acrophases of mean arterial pressure and heart rate rhythms were obtained for 24-, 12-, and 8-hour periods. After 1 year of treatment, 68% of patients were normotensive, and left ventricular mass and carotid intima-media thickness decreased in 60% and 62% of patients, respectively. Blood pressure and heart rate rhythmicity patterns did not change. Changes in blood pressure amplitude correlated with the decrease of waist circumference (P=0.035). Moreover, the decrease of visceral fat correlated with the decrease of 24-hour mean arterial pressure and heart rate acrophases (both P<0.05). There were no differences in changes of blood pressure and heart rate rhythms between patients who achieved or did not achieve normotension and regression of left ventricular mass and carotid intima-media thickness. It was concluded that abnormal cardiovascular rhythmicity persists in children with primary hypertension despite effective antihypertensive treatment, which suggests that it may be the primary abnormality. The correlation between changes in cardiovascular rhythmicity and visceral obesity may indicate that the visceral fat plays an important role in the sympathetic activity of adolescents with hypertension.
Chrzanowska K.H.,The Childrens Memorial Health Institute
Orphanet journal of rare diseases | Year: 2012
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to malignancies. Due to a founder mutation in the underlying NBN gene (c.657_661del5) the disease is encountered most frequently among Slavic populations. The principal clinical manifestations of the syndrome are: microcephaly, present at birth and progressive with age, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism. Combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections, a strong predisposition to develop malignancies (predominantly of lymphoid origin) and radiosensitivity are other integral manifestations of the syndrome. The NBN gene codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear role wherever double-stranded DNA ends occur, either physiologically or as a result of mutagenic exposure. Laboratory findings include: (1) spontaneous chromosomal breakage in peripheral T lymphocytes with rearrangements preferentially involving chromosomes 7 and 14, (2) sensitivity to ionizing radiation or radiomimetics as demonstrated in vitro by cytogenetic methods or by colony survival assay, (3) radioresistant DNA synthesis, (4) biallelic hypomorphic mutations in the NBN gene, and (5) absence of full-length nibrin protein. Microcephaly and immunodeficiency are common to DNA ligase IV deficiency (LIG4 syndrome) and severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation due to NHEJ1 deficiency (NHEJ1 syndrome). In fact, NBS was most commonly confused with Fanconi anaemia and LIG4 syndrome. Genetic counselling should inform parents of an affected child of the 25% risk for further children to be affected. Prenatal molecular genetic diagnosis is possible if disease-causing mutations in both alleles of the NBN gene are known. No specific therapy is available for NBS, however, hematopoietic stem cell transplantation may be one option for some patients. Prognosis is generally poor due to the extremely high rate of malignancies.
Grajda A.,The Childrens Memorial Health Institute
Medycyna wieku rozwojowego | Year: 2011
The aim of the study was to compare the prevalence of overweight, obesity, and underweight in children and adolescents from different provinces in Poland. Data from the recent, large, population-representative sample of school-aged children and adolescents (N=17573) OLAF study: "Elaboration of the reference range of arterial blood pressure for the population of children and adolescents in Poland" - PL0080 OLAF were used in the analysis. The survey was conducted in all provinces of Poland (N=16). Data were analyzed using SAS 9.2, EpiInfo 3.5.1 and LMSgrowth software packages. The frequency of overweight, obesity, and underweight were determined. For overweight and obesity (jointly) and underweight the odds ratio (OR) was calculated for gender and voivodship of residence. The body mass index (BMI) was standardized and expressed as a z-score. The statistical significance of differences between BMI z-scores depending on voivodship of residence was assessed by the t-test. Significant differences were found in the occurrence of overweight and obesity among the analysed regions, and voivodships with a lower (małopolskie, świetokrzyskie, lubelskie, and podkarpackie) and higher (mazowieckie) risk of overweight and obesity were identified. In case of underweight, łódzkie and podkarpackie (<0.040) provinces were higher risk areas, while mazowieckie (<0.001) had lower risk. The prevalence of overweight (including obesity) was higher compared to the prevalence of underweight in the majority of provinces (15 out of 16). Analysis of regional differences in the prevalence of obesity, overweight and underweight in children and adolescents may point to the direction in which nationwide and local efforts should be made to reduce the inequalities stemming from nutritional status.
Wejnarska K.,The Childrens Memorial Health Institute
Journal of Pediatric Gastroenterology and Nutrition | Year: 2016
OBJECTIVES:: The etiological factors of chronic pancreatitis (CP) in children differ from those in adults. To date, no study has assessed the clinical course of CP in young children. The aim of our study was to evaluate the etiology and the clinical presentation of the disease in children with disease onset before 5 years of age in comparison to later-onset of CP. METHODS:: A total of 276 children with CP, hospitalised from 1988 to 2015, were enrolled in the study. Data on presentation, diagnostic findings and treatment were reviewed. Two-hundred sixty patients were screened for the most frequent mutations in major pancreatitis-associated genes, such as cationic trypsinogen /serine protease gene (PRSS1), serine protease inhibitor, Kazal type 1 gene (SPINK1), cystic fibrosis transmembrane conductance regulator gene (CFTR). RESULTS:: The disease onset before the age of 5 years occurred in 51 patients (group 1), the later onset in 225 patients (group 2). We found no significant discrepancies in distribution of the etiological factors between groups. The youngest patients (group 1) had more pancreatitis episodes (median 5.0 vs. 3.00;p?0.05) and underwent surgeries more frequently (25.5% vs. 8.9%;p?0.05). It could be associated with significantly longer follow-up in early onset group (median 6 yrs vs. 4 yrs;p?0.05). There were no differences in nutritional status or exocrine and endocrine pancreatic function. CONCLUSIONS:: Early- and later-onset pancreatitis have similar etiological factors with predominance of gene mutations. The most frequent mutation found was p.Asn34Ser (N34S) in SPINK1 gene. The clinical presentation differed in number of pancreatitis episodes and frequency of surgeries. © 2016 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
Lipka B.,The Childrens Memorial Health Institute
Wiadomości parazytologiczne | Year: 2011
The study objective was to determine plasma concentration of pyrimethamine in 24 infants aged 1-5 months, treated for congenital toxoplasmosis. Pyrimethamine was used in a single daily dose at an amount of 0.35-0.98 mg/kg daily, with sulfadiazine (50-100 mg/kg/day) in divided doses 2-3 times a day, and folinic acid given twice a week (7.5 mg). This regimen was continued for 2-6 months, then Fansidar was administered. Pyrimethamine concentration in plasma was measured using high-performance liquid chromatography method (HPLC). A total of 70 tests were performed. Concentration of pyrimethamine ranged from 0.01 to 1.2 microg/ml. In 14 children (58 tests) the concentration of pyrimethamine achieved therapeutic value. In 7 patients (8 tests) the concentration was below therapeutic level, and in 3 patients (4 tests) above therapeutic level. In 11/24 (46%) children transient moderate neutropenia was observed. Modification of therapy was necessary in 12 patients. Monitoring of pyrimethamine concentration in plasma improves safety and effectiveness of the therapy and is useful in obtaining correct individual dose of the drug. Neutropenia is the most common side-effect of pyrimethamine observed even when using the recommended dose.
Grenda R.,The Childrens Memorial Health Institute
Pediatric Nephrology | Year: 2015
The biologics used in transplantation clinical practice include several monoclonal and polyclonal antibodies aimed at specific cellular receptors. The effect of their mechanisms of action includes depleting or blocking specific cell subpopulations, complement system, or removing circulating preformed antibodies and blocking their production. They are used in induction, desensitization ABO-incompatible renal transplantation, rescue therapy of steroid-resistant acute rejection, treatment of posttransplant recurrence of primary disease such as nephrotic syndrome or atypical hemolytic–uremic syndrome, and in late humoral rejection. There are various indications for the use of biologic agents before and early or late after renal transplantation in both high- and low-risk recipients. In the latter situation, the biologics-based induction is used to further minimize immunosuppression maintenance. The targets of several biologic agents are present across a variety of cells, and manipulation of the immune system with biologics may be associated with significant risk of acute and late-onset adverse events; therefore, clinical risk-versus-benefit ratio must be carefully balanced in every case. Several trials on novel biologics are reported in adults but not in the pediatric population. © 2014, The Author(s).
Jurecka A.,The Childrens Memorial Health Institute
Journal of inherited metabolic disease | Year: 2010
This report describes the clinical, biochemical and molecular data of a 78-year-old patient with xanthine dehydrogenase deficiency presenting as rheumatoid arthritis. Xanthinuria type I is a rare disorder of purine metabolism caused by xanthine dehydrogenase (XDH) deficiency; fewer than 150 cases have been described in the literature so far. We describe the clinical history and urine and serum findings of a 78-year-old patient with isolated XDH deficiency presenting as rheumatoid arthritis. The diagnosis was confirmed by mutation analysis. The patient suffered from arthral symptoms and nephrocalcinosis. Very low concentrations of uric acid were observed in her serum and urine. The allopurinol loading test indicated her xanthinuria to be type I. Analysis of genomic DNA revealed novel heterozygous deletion in exon 8 (g.27073delC, p.214QfsX4) and previously published heterozygous nucleotide missense transition in exon 25 (g.64772-C>T, p.T910M). Hereditary xanthinuria is a rare disorder, but it also needs to be considered in patients not originating from Mediterranean countries or the Near or Middle East. Urate concentration in serum and urine may provide an initial indication of XDH deficiency before high-performance liquid chromatography (HPLC) analysis is performed. The key to identifying the disorder is a greater awareness of XDH deficiency amongst primary care physicians, nephrologists, and urologists, but also rheumatologists. The diagnosis and therapeutic management requires a multidisciplinary approach.