Burton B.K.,Childrens Memorial Hospital |
Nowacka M.,Instytut Matki I Dziecka |
Hennermann J.B.,Charité - Medical University of Berlin |
Lipson M.,Kaiser Permanente |
And 8 more authors.
Molecular Genetics and Metabolism | Year: 2011
Background: Phenylketonuria (PKU) results from impaired breakdown of phenylalanine (Phe) due to deficient phenylalanine hydroxylase (PAH) activity. Sapropterin dihydrochloride (sapropterin, Kuvan®) is the only US- and EU-approved pharmaceutical version of naturally occurring 6R-BH 4, the cofactor required for PAH activity. Sapropterin enhances residual PAH activity in sapropterin-responsive PKU patients and, in conjunction with dietary management, helps reduce blood Phe concentrations for optimal control. Approval was based on the positive safety and efficacy results of four international clinical studies, the longest of which was 22weeks in duration. Objective: To evaluate the safety of long-term treatment with sapropterin in PKU subjects who participated in previous Phase 3 sapropterin trials. Methods: PKU-008 was designed as a Phase 3b, multicenter, multinational, open-label, 3-year extension trial to evaluate the long-term safety of sapropterin in patients with PKU who were classified as sapropterin responders and participated in prior Phase 3 sapropterin studies: 111 subjects aged 4-50. years completed prior studies and were subsequently enrolled in study PKU-008. Routine safety monitoring was performed at 3-month intervals and included adverse event reporting, blood Phe monitoring, clinical laboratory evaluations, physical examinations and vital sign measurements. Results: Average exposure during PKU-008 was 658.7 ± 221.3 days (range, 56-953; median, 595). The average total duration of participation in multiple studies (PKU-001, PKU-003, PKU-004, and PKU-008; or PKU-006 and PKU-008) was 799.0 ± 237.5 days (range, 135-1151). The mean sapropterin dose was 16.2 ± 4.7. mg/kg/day. Most adverse events were considered unrelated to treatment, were mild or moderate in severity, and were consistent with prior studies of sapropterin. No age-specific differences were observed in adverse event reporting. Three subjects discontinued treatment due to adverse events that were considered possibly or probably related to study treatment (one each of difficulty concentrating, decreased platelet count, and intermittent diarrhea). No deaths were reported. Of seven reported serious adverse events, one was considered possibly related to study treatment (gastroesophageal reflux). There were no laboratory or physical examination abnormalities requiring medical interventions. For most subjects, blood Phe concentrations were consistently within target range, confirming the durability of response in subjects undergoing extended treatment with sapropterin. Conclusion: Sapropterin treatment was found to be safe and well tolerated at doses of 5 to 20. mg/kg/day for an average exposure of 659. days. This study supports the safety and tolerability of sapropterin as long-term treatment for patients with PKU. © 2011 Elsevier Inc.
Witek J.,Instytut Matki I Dziecka |
Witek P.,Klinika Endokrynologii Centrum Medyczne Ksztalcenia Podyplomowego |
Pankowska E.,Instytut Matki I Dziecka
Pediatric Endocrinology, Diabetes and Metabolism | Year: 2011
Insulin resistance is characterized by decreased tissue sensitivity to insulin. The hallmark of insulin resistance is decreased tissue glucose uptake despite normal or elevated insulin concentration. There has been an upward trend in the incidence of insulin resistance in developed countries, although in pediatric population it is difficult to assess. Both genetic and environmental factors play an important role in the etiology of insulin resistance, namely increased diet caloricity and decreased physical activity. Gradually, this leads to adipose tissue build-up. The role of visceral adipose tissue is of particular importance, mainly due to its significant endocrine activity, leading to adverse metabolic effects. The most important consequences of insulin resistance in children include increased incidence of type 2 diabetes, atherogenic dyslipidemia and arterial hypertension, which lead to increased cardiovascular risk. Children with insulin resistance can develop non-alcoholic steatohepatitis and sleep apnea syndrome. In case of female pediatric patients a higher incidence of polycystic ovary syndrome (PCOS) is observed. Furthermore, the authors reviewed opinions on risk factors for insulin resistance, as well as direct and indirect insulin resistance assessment methods. The article presents the principles of primary and secondary prevention of insulin resistance in children, with particular allowance for dietary recommendations and recommendations to increase physical activity, and, in selected cases, current guidelines on pharmacological treatment.
Kanieska A.,Instytut Matki i Dziecka |
Hozyasz K.K.,Instytut Matki i Dziecka
Pediatria Polska | Year: 2014
The concept of paleolithic diet is based on an assumption that modern human is not evolutionarily adapted to contemporary nutrition, which may result in high frequency of diseases considered as civilization-related such as ischemic heart disease, arterial hypertension, obesity, diabetes, cancer and other. In the article, reconstruction of the diet is presented and it is compared to modern nutrition guidelines. In addition, the most common objections against the paleodiet are quoted. The subject of the paleodiet remains an open research concept whose development can influence nutrition recommendations. © 2014 Polish Pediatric Society. Published by Elsevier Urban & Partner Sp. z o.o. All.
Wolkowicz A.,Instytut Matki i Dziecka |
Hozyasz K.K.,Instytut Matki i Dziecka
Pediatria Polska | Year: 2014
Galactosemia, rare inherited metabolic disease, causes 1-3% of all cases of congenital cataract. Lens opacity occurs even in 68% of patients with classic galactosemia and in almost all galactokinase deficiencies. Decreased enzymatic activity results in overproduction and accumulation of galactitol in eye lens, which leads to lens opacity due to osmotic swelling of lens cells. Such dysfunction of galactose metabolic pathway enzymes can also lead to presenile cataract formation. Early diagnosis and dietary intervention, in most cases, lead to regression or delay of cataract formation. Unfortunately, surgical treatment is needed in some patients, especially those with insufficient dietary compliance. © 2013 Polish Pediatric Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
Rowicka G.,Instytut Matki i Dziecka
Medycyna wieku rozwojowego | Year: 2012
Children treated with a dairy-free diet are in a group of those at risk of nutritional deficiencies, including vitamin D deficiency.THE AIM of this study was to evaluate the vitamin D status in children with cow's milk allergy (CMA) treated with a dairy-free diet. The study involved 66 children with CMA, aged 2-5 years (mean age 3.9±1.9 yrs). The children were treated with a milk-free diet (high degree of protein hydrolysates or soy formulas/soy products) and remained under the care of the medical and nutritional team. The majority of the children lived in urban areas and their parents have mainly secondary or higher education. The supply of vitamin D in children's daily food rations was evaluated and related to Adequate Intake (AI) as well as the recommendations contained in the Medical Standard (2009) for the prophylaxis of vitamin D deficiency. Fifteen (22.7%) children in the autumn-winter season used vitamin D containing supplements. The serum 25-hydroxyvitamin D [25(OH)D] concentration was measured and related to the recommended levels from Medical Standard (2009). Taking into consideration the possibility of seasonal differences in vitamin D status, blood samples for the 25(OH)D assay were collected from April to September (spring-summer season) in 34 (51.5%) children and from October to March (autumn-winter season) in 32 (48.5%) children. The mean supply of vitamin D in the diets of the children with CMA was 5.9±3.7 μg/d. The mean supply of vitamin D in supplements in the group of children receiving them was 143.6±132.9 IU/d [3.6±3.3 μg/d]. The mean 25 (OH)D serum concentration among the children without taking into account the season for blood withdrawal was 28.7±9.9 ng/ml. Taking into account the season of blood sample collection, the mean 25(OH)D serum concentration in children in spring-summer was 30.1±7.8 ng/ml, while in autumn-winter 27.5±11.2 ng/ml, p>0,05. A positive correlation between the supply of vitamin D in the children's diets and 25(OH)D serum concentration (Spearman correlation coefficient r=0.46, p<0,01) was found. The mean supply of vitamin D in the children's diets and the mean 25(OH)D serum concentration did not differ significantly depending on the place of living and the parents' education. 1. Vitamin D supplied by the diets of the children with CMA remaining under our care was compliant with the Adequate Intake, but lower than the recommendations contained in the Medical Standard. 2. The serum 25(OH) D concentration in these children in the spring-summer as well as autumn-winter season indicated the optimal vitamin D status. 3. Being under constant medical and nutritional care is one of the conditions for an appropriate vitamin D supply in children with CMA.
Zielinska M.,Instytut Matki i Dziecka |
Hozyasz K.K.,Instytut Matki i Dziecka
Pediatria Polska | Year: 2012
Trehalose is a naturally found disaccharide that is a key element for anhydrobiosis, the capability of surviving complete dryness, in some organisms. The protective effect of trehalose is not well understood at the molecular level. Trehalose is used in the cryopreservation of human cells and as ingredient in processed food stuffs. Low trehalase activity causes maldigestion of trehalose. Trehalose has been shown to be effective in preventing the aggregation of numerous proteins, inhibiting this process might be effective in treating neurodegenerative disorders, for example Alzheimer's disease, Parkinson's disease. Trehalose solution is an effective and safe eye drop for the treatment of dry eye syndrome.
[Evaluation of selected parameters of cellular immunity in children with osteosarcoma at diagnosis]. [Ocena stanu immunologicznego dzieci I mlodzinezy z miesakiem kosciopochodnym w momencie rozpoznania choroby.]
Markiewicz K.,Instytut Matki i Dziecka
Medycyna wieku rozwojowego | Year: 2012
The causes of osteosarcoma (OS) and effector mechanisms of the immune response against OS and other neoplastic diseases remain unknown. According to current knowledge, the major role is attributed to cytotoxic T lymphocytes, NK, NKT and Tǎä lymphocytes, which are engaged directly in the destruction of the tumour cells. Helper T lymphocytes (CD4+) and indirectly B lymphocytes are of special importance. There is sparse data on the state and efficiency of the immune system in children with neoplastic disease, with bone tumours in particular. THE AIM OF THE STUDY was the evaluation of selected elements of cellular immunity in children with osteosarcoma at the time of diagnosis. The study was performed on a group of 44 children with osteosarcoma, aged from 6 to 20 years (median 15.0 years). The control group consisted of 22 children of the same age (median 14.5 years) without the diagnosis of neoplastic disease and active inflammatory state. T lymphocytes with their subpopulations, activated T lymphocytes (CD3+/HLA-DR+), B lymphocytes, NK and NKT cells were analyzed in peripheral blood using the flow cytometry method. Examinations were performed before the therapy - in the diagnostic period. A lower number of peripheral blood lymphocyte population in children with osteosarcoma at diagnosis, compared to the control group was observed. The differences concerned T lymphocytes CD3+(1609.0 vs 3038.0 kom/μl, p<0.001) CD4+(598.0 vs 1071.0 kom/l; p<0.001) and their cytotoxic subpopulation CD8+ (386.0 vs. 866.0 cells/μL; p<0.001), activated T lymphocytes CD3+/HLA-DR+(39.0 vs. 81.0 cells/μL; p<0.025), B lymphocytes CD19+(205.0 vs. 381.0 cells/μL; p<0.025) and NK cells (161.0 vs. 339.0 cells/μL; p<0.005). The number and percentage of peripheral blood lymphocytes in children and youth with osteosarcoma at diagnosis is over 50% lower compared to the patients without neoplastic disease. 1. The general analysis of peripheral blood without differentiating lymphocyte subpopulations is insufficient to determine disturbances which are forming in the immune system of patients developing the neoplastic disease. 2. The course of the neoplastic disease (osteosarcoma) in patients of developmental age is very diverse, and associated with individual biological variation. 3. The evaluation of the immunologic status in patients with osteosarcoma may have prognostic meaning for the further course of the disease, may prevent the formation of unfavourable clinical changes, and be the basis for correcting the administration of cytostatic agents.
Kowalewska-Kantecka B.,Instytut Matki I Dziecka
Pediatria i Medycyna Rodzinna | Year: 2011
Breastfeeding is a gold standard of feeding newborn and infants that brings optimal somatic- psychomotor development and cognitive ability. Mother milk is species specific for human infants and also their irreplaceable, optimal food. Every child has natural right for his mother milk. The act of breastfeeding itself, as a mode of mother-infants interaction, may favour cognitive development. Taking milk directly from the breast has profound effects on both mother and her child. According to WHO and AAP recommendations breastfeeding should be the only food during first 6 months of life, and after introduction of complementary, solid food, this should be prolonged up to 12 months or longer. Unique value of mother milk depends on many specific bioactive agents that create requirement for optimal somatic and mental development. It is the most optimal food for brain development. Breastfeeding is irreplaceable source of immunoglobulins, bioactive growth promoters and anti-inflammatory agents, live activated leukocytes and immunomodulatory agents as well. Longchain polyunsaturated fatty acids (LCPUFAs) in human milk have an effect on the chemical composition of the brain and enhance retinal and cortical function. This immunological properties are not to reconstruct on the formula. Specific properties of mother milk could significantly prevent or reducing the death rate of children under five. In this article short survey of breastfeeding concerning papers and the most important WHO, UNICEF worldwide recommendations, programs, declarations and strategies on the promotion, protection and support of breastfeeding and International Code of Marketing of Breast-milk Substitutes are presented. © Pediatr Med Rodz 2011.
Cudzilo D.,Instytut Matki i Dziecka
Medycyna wieku rozwojowego | Year: 2012
As publications on craniofacial anomalies, malocclusions and dental complications recognised in patients suffering from Moebius syndrome are scarce, the authors of this paper decided to discuss the above aspects in broader terms along with the possibilities offered by orthodontic treatment. The etiology of Moebius syndrome has not hitherto been discovered, however the opinion prevails that it is brought on by multiple factors and conditions. In the analysed case, Moebius syndrome was diagnosed only when the patient was 6 years old. Based on the clinical examination, typical characteristics of the syndrome were observed: craniofacial dysmorphism as well as foot development disorder in the form of talipes equinovarus (club foot). Moreover, Type II Angle's classification of malocclusion was detected - crowded teeth in the mandible and maxilla and hypoplastic enamel. Cephalometric analysis identified retruded position of the mandible against the cranial base, protruded position of the maxilla, shortening of posterior face height, protrusion of incisors in the maxilla. The orthopantomogram showed the presence of all permanent teeth. At the beginning of the orthodontic treatment removable appliances were used, but despite good cooperation on the part of the patient, only a slight improvement was observed. Further orthodontic treatment envisaged extraction of permanent teeth and use of fixed appliances while waiting for the improvement of occlusion.
PubMed | Instytut Matki i Dziecka
Type: Journal Article | Journal: Developmental period medicine | Year: 2014
The aim of the paper is to present the psychological situation of the family of a child with a craniofacial condition, as well as to describe the role of the psychologist in the therapeutic process. The perspective of the paper is based on both the authors clinical experience and a review of the literature. The paper adopted the parents perspective and is therefore focused on their experiences concerning the diagnosis of the congenital craniofacial malformation. The author made an attempt to define what comprises a problem for parents and identify how their difficulties may influence the childs psychological development. Attention was devoted to challenges stemming from the unknown etiology of the malformation, difficulties in accepting and conducting the multistage treatment, changes in the look of the face, and the broadly considered imperfection. In the review of the literature, particular attention was drawn to identifying the risk factors for psychological development disorders associated with the cleft condition, as well as factors concerning the risk of the disorder influencing the parent-child relationship. It was concluded that the quality of that relationship may be influenced by the psychological state of the parents. Relying upon both the literature and own research results, it was established that the parents psychological situation can be classified as atrauma. Its significance for the parent-child relationship was identified - especially in reference to parental sensitivity to the childs needs and their ability to support the child. The parent-child relationship may be meaningful for the childs psychological development - especially his or her emotions, self-esteem, and perception of the world. The basic idea was that the parents experience a period of mourning over the imagined ideal child, going through which is crucial for them to adapt to their role of parenting a disfigured one. Adjusting to the requirements of the situation, i.e. involvement in treatment, is also among the key challenges. Developing some coping strategies in the parents, as well as introducing certain therapeutic interventions, is of high importance in this process of adjustment. Some fields of psychological work - which are most useful for the parents sense of competence are also pointed out in the article.