Safety assessment during initiation and maintenance of propranolol therapy for infantile hemangiomas.

BACKGROUND: Propranolol is an effective method of treatment for infantile hemangiomas (IH). A recent concern is a shift of the therapy into outpatient settings. OBJECTIVES: The aim of the study was to evaluate the safety of initiating and maintaining propranolol therapy for IH. MATERIAL AND METHODS: The study involved 55 consecutive children with IH being treated with propranolol. The patients were assessed in the hospital at the initiation of the therapy and later in outpatient settings during and after the therapy. Each time, the following monitoring methods were used: physical examination, cardiac ultrasound (ECHO), electrocardiography (ECG), blood pressure (BP), heart rate (HR), and biochemical parameters: blood count, blood glucose, aspartate transaminase (AST), alanine transaminase (ALT), and ionogram. The therapeutic dose of propranolol was 2.0 mg/kg/day divided into 2 doses. RESULTS: Four children were excluded during the qualification or the initiation of propranolol; a total of 51 patients were subject to the final analysis. All the children presented clinical improvement. There was a significant reduction in the mean HR values only at the initiation of propranolol. There were no changes in HR during the course of the therapy. Blood pressure values were within normal limits. Both systolic and diastolic values decreased in the first 3 months. Bradycardia and hypotension were observed sporadically, and they were asymptomatic. Electrocardiography did not show significant deviations. The pathological findings of the ECHO scans were not a contraindication to continuing the therapy. There were no changes in biochemical parameters. Apart from 1 symptomatic case of hypoglycemia, other low glucose episodes were asymptomatic and sporadic. The observed adverse effects were mild and the propranolol dose had to be adjusted in only 6 cases. CONCLUSIONS: Propranolol is effective, safe and well-tolerated by children with IH. The positive results of the safety assessment support the strategy of initiating propranolol in outpatient settings. Future studies are needed to assess the benefits of the therapy in ambulatory conditions.

Association of genetic variation in the natriuretic peptide system and left ventricular mass and blood pressure in newborns.

BACKGROUND: The natriuretic peptides play a key role in the modulation of left ventricular mass (LVM) and blood pressure (BP). We hypothesised that NPPA (natriuretic peptide precursor A gene), NPPB (natriuretic peptide precursor B gene), and NPPC (natriuretic peptide precursor C gene) are candidate genes possibly involved in the development or modulation of LVM at early life. AIM: To assess the relationship between NPPA, NPPB, and NPPC gene polymorphisms with LVM and BP in newborns. METHODS: A total of 206 healthy newborns were studied by two-dimensional M-mode echocardiography. The polymorphisms NPPA rs5065, NPPB rs198389, and NPPC rs5268 were characterised. RESULTS: Newborns carrying the C allele of the NPPB polymorphism had significantly lower LVM/body surface area (BSA) and LVM/body weight (BW) values when compared with newborns' homozygotes for the T allele (41.76 g/m2 vs. 48.31 g/m2, p adjusted = 0.044 and 2.78 g/kg vs. 3.26 g/kg, p adjusted = 0.031, respectively). An association was observed between NPPA genotype and systolic BP, diastolic BP, and mean arterial pressure ≥ 90th percentile (p = 0.029, p = 0.0048, p = 0.004, respectively). Also an association was observed for systolic BP ≥ 90th percentile for NPPB (p = 0.016). CONCLUSIONS: The present study shows that the NPPB gene polymorphism is associated with modulation of LVM in newborns. The NPPA and NPPB gene polymorphisms are associated with BP.

Evaluation of final height prediction and selected parameters in Polish patients with severe and partial growth hormone deficiency.

OBJECTIVES: The main goal of growth hormone therapy is to reach the height in the population ranges. The aim of the study was the comparison of selected methods for predicting final height in Polish patients with severe (sGHD) and partial (pGHD) growth hormone deficiency. METHODS: 149 children with growth hormone deficiency treated with rhGH in the Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology Developmental Age, PUM, in Szczecin, in 2000-2010 have been evaluated. Patient were divided into two groups: sGHD and pGHD. Two methods of final height prediction have been used: Roche-Weiner-Thissen (RWT) and target height (TH), results were compared to the final height (FH). 117 children finished therapy in the analysed period and reached final height. RESULTS: The mean FH was similar in both groups. There was no significant difference between the accuracy of prediction methods of TH and RWT between groups of pGHD v. sGHD. Further analysis revealed, that in the group of boys with sGHD the prediction error of RWT was significantly lower than of the TH method (p < 0.05). CONCLUSIONS: It seems that in the group of boys with sGHD RWT is a more accurate method than TH.

Association of genetic variation in calmodulin and left ventricular mass in full-term newborns.

Calmodulin II (CALM2) gene polymorphism might be responsible for the variation in the left ventricular mass amongst healthy individuals. The aim was to evaluate the correlation between left ventricular mass (LVM) and g.474955027G>A (rs7565161) polymorphism adjacent to the CALM2 gene. Healthy Polish newborns (n = 206) were recruited. Two-dimensional M-mode echocardiography was used to assess LVM. Polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism and sequencing analyses. The carriers of the G allele of the CALM2 polymorphism had significantly higher left ventricular mass/weight (LVM/BW) values, when compared with newborns homozygous for the A allele (3.1 g/m(2) versus 2.5 g/m(2), P adjusted = 0.036). The AG genotype of CALM2 was associated with the highest values of LVM/BW, exhibiting a pattern of overdominance (2.9 g/kg versus 3.1 g/kg versus 2.5 g/kg, P adjusted = 0.037). The results of this study suggest that G>A CALM2 polymorphism may account for subtle variation in LVM at birth.

Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease.

INTRODUCTION: CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy. MATERIAL AND METHODS: The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic parameters in Caucasian patients with early onset coronary artery disease. The study group comprised 100 patients. Electrocardiography and echocardiography were performed in all patients. Amplicons of exons 4 to 6 including fragments of introns were studied using the denaturing high-performance liquid chromatography technique. RESULTS: IVS3-6TC (rs3173798) heterozygotes had impaired left ventricle diastolic function. 573GA heterozygotes (rs5956) had higher frequency of pseudonormal left ventricular diastolic function and it was confirmed by the increase in wave A' in the tissue Doppler. 591AT genotype was associated with borderline higher posterior wall end-diastolic thickness and lower E/A ratio. These results are consistent with electrocardiography parameters which could reflect left ventricular hypertrophy (higher RV5(6) and RV5(6) + SV1(2) parameters, depressed ST segments and tendency to longer Qtc II interval) in 591AT heterozygotes. CONCLUSIONS: Detected variant alleles of CD36 may be associated with features of left ventricular hypertrophy and impaired diastolic function.

An insertion/deletion ACE polymorphism and kidney size in Polish full-term newborns.

The number of nephrons is a multifactorial trait controlled by the interaction of environmental factors and genetic variants that influence the extent of branching nephrogenesis during foetal life. A correlation between renal mass and nephron number in newborns allows the use of the total kidney volume at birth as a surrogate for congenital nephron number. Since the renin-angiotensin system plays an important role in renal development we hypothesized that the common, functional insertion/deletion (I/D) polymorphism in the ACE gene might be responsible for the variation in kidney size amongst healthy individuals. We recruited 210 healthy Polish full-term newborns born to healthy women with uncomplicated pregnancies. The kidney volume was measured sonographically. Total kidney volume (TKV) was calculated as the sum of left kidney volume and right kidney volume. TKV was normalized to body surface area (TKV/BSA). The I and D alleles were identified using polymerase chain reaction. TKV/BSA in newborns carrying at least one insertion ACE allele was significantly reduced by approximately 8% as compared with homozygous newborns for the D allele (DD genotype) (105.1±23.6 vs. 114.2±28.2 cm(3)/m(2), p<0.05). The results of this study suggest that I/D ACE polymorphism may account for subtle variation in kidney size at birth, which reflects congenital nephron endowment.

Genetics of the renin-angiotensin system with respect to cardiac and blood pressure phenotypes in healthy newborn infants.

INTRODUCTION: Left ventricular mass (LVM) is a strong predictor of various heart diseases. We examine the association between the G(-6)A AGT, I/D ACE, A1166C AGTR1, T(-344)C CYP 11ß2, A538G MR and A10631G REN polymorphisms and LVM and blood pressure in newborn infants. MATERIAL AND METHODS: The study included 211 healthy newborn infants. Two-dimensional M-mode echocardiography was used to assess LVM between days 3-4 after birth. Polymorphisms were determined by polymerase chain reaction - restriction fragment length polymorphism (PCR-RLFP). RESULTS: AGTR1 genotype was significantly associated with neonatal systolic blood pressure (≥90 percentile). LVM indexes (LVMIs) were tested for association with genotypes in multivariate analysis. The carriers of the A allele of the AGT polymorphism had significantly higher LVM/body length (BL) values when compared with newborn infants homozygous for the G allele (p adjusted=0.03). The higher LVM/BL values were seen in the carriers of the A alleles of the AGTR1 polymorphism (p adjusted=0.046). All examined indexes (LVM/body surface area (BSA), LVM/BL, LVM/bodyweight (BW)) were associated with CYP11B polymorphism. The newborn infants homozygous for the T allele had significantly higher values of LVM/BSA, LVM/BL, and LVB/BW compared to non-TT-homozygous neonates (p adjusted=0.003; p adjusted=0.003; p adjusted=0.004 respectively). CONCLUSION: The AGT, AGTR1, CYP11ß polymorphisms are associated with increased LVMIs in newborns. This observation indicates that genetic factors may be modulating LVM at birth.

Association of 1936A > G in AKAP10 (A-kinase anchoring protein 10) and blood pressure in Polish full-term newborns.

OBJECTIVE: The 1936G AKAP10 allele is associated with increased adult basal heart rate (HR) and decreased variability, markers of low cholinergic/vagus sensitivity associated with hypertension. Blood pressure (BP) values in newborns are important measurable markers of cardiovascular risk later in life. The question was whether decreased vagal function-related 1936A > G AKAP10 is associated with newborn BP. STUDY DESIGN: 114 healthy Polish newborns born after 37th gestational week to healthy women with uncomplicated pregnancies. At birth, newborn cord blood obtained for isolation of genomic DNA. BP and HR measured on days 1 and 3 after delivery. RESULTS: Diastolic BP on day 3 and absolute and relative differences between diastolic BP values, as well as between mean BP values on day 3 and on day 1 after birth, in carriers of 1936G AKAP10 allele, were significantly higher as compared with wild-type homozygotes. CONCLUSION: Results demonstrate possible association between 1936G AKAP10 variant and BP in Polish newborns.

Common genetic variants of the BMP4, BMPR1A, BMPR1B, and ACVR1 genes, left ventricular mass, and other parameters of the heart in newborns.

The members of the family of bone morphogenetic proteins (BMPs) are important regulators in cardiac development. The present study was designed to evaluate the effect of common genetic variants of BMP-4 and its receptors BMPR1A, BMPR1B, and ACVR1 on left ventricular mass (LVM) and other parameters of the heart and blood pressure in newborns. The study included 210 healthy newborns. Two-dimensional M-mode echocardiography was used to assess LVM between days 3 and 4 after birth. Polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism technique. We found lack of associations between LVM, values of blood pressure, and the BMP4, BMPR1A, BMPR1B, and ACVR1 genotypes. A significant association was observed between the 455C allele of BMP4 and increased left ventricular internal diameter systolic (p=0.004) and between 1650T allele of BMPR1B and lower left atrium diameter (p=0.038). Presence of the 455C allele of BMP4 and the 8474T allele of ACVR1 gene was significantly associated with decreased left ventricular ejection fraction (LVEF) (p=0.0004 and p=0.046, respectively). The 455C allele of BMP4 and the 8474T allele of ACVR1 may play a role as significant predictors for decreased LVEF in newborns.

Familial distal monosomy 3p26.3-pter with trisomy 4q32.2-qter, presenting with progressive ataxia, intellectual disability, and dysmorphic features.

We present a boy diagnosed with partial 3p monosomy and partial 4q trisomy. The patient was 9 years of age with intellectual disability, dysmorphic features, and ataxia. A family history and medical evaluation showed that the father manifested similar facial dysmorphic features, intellectual disability, quadriparesis, and progressive cerebrospinal ataxia. The chromosomal aberration found in the proband was inherited from his father who was found to have a balanced reciprocal translocation of chromosomes 3p and 4q, which was in turn inherited from the paternal grandfather. The final cytogenetic diagnosis according to microarray was 46,XY,der(3)t(3;4)(p26.1;q32.2)arr 3p26.1(39,066-5,363,502)x1,4q32.2q35.2(162,555,236-191,173,881)x3. We describe the cytogenetic investigations that led to the identification of the breakpoints. In addition, we present an overview of the clinical features found in patients with partial 3p monosomies and partial 4q trisomies as reported in the literature.

[The "heart-hand" syndrome in a 8-year-old-boy with short stature]. / Zespól "serce-reka" u 8-letniego chlopca z niskorosloscia.

"Heart-hand" syndrome is a broad category of diseases. The most common form is Holt-Oram syndrome (HOS) that occurs in approximately 1:100 000 live births. It is characterized by upper limb defects (carpal bone defects, triphalangeal thumbs, hypoplasia or absence of the thumb and the radial ray) and cardiac septal defects (atrial septal defects or ventricular septal defects). There are three main types of "heart-hand" syndromes. "Heart-hand" syndrome type I--HOS is characterised by atrial septal defect and thumb anomaly, type II (Tabatznik syndrome) by short distal phalanx of the thumb, upper limb abnormalities and cardiac arrhythmias, type III by cardiac conduction diseases and shortening of the middle phalanges. The aim of this report is to present a new case of the "heart-hand" syndrome in the family. This diagnosis was established on the base of clinical examination, radiological findings, and echocardiography. Our patient demonstrates congenital bilateral absence of a radial bone and thumbs, dextrocardia and patent foramen ovale.

A fetal dilated and hypertrophic cardiomyopathy associated with maternal gestational diabetes--a case report.

There is an increased risk of a hypertrophic cardiomyopathy and congenital heart defects among newborns of diabetic mothers. We report a case of hypertrophic cardiomyopathy preceded with dilated cardiomyopathy in a fetus of a diabetic mother. The fetal echocardiography at the 23rd week of gestation revealed signs of dilated cardiomyopathy with signs of cardiac failure. Under the echocardiographic monitoring the successful treatment was performed. In spite of poor prognosis, the child was born at the 39th gestation week in a good condition.

The role of magnetic resonance imaging in early prediction of cerebral palsy.

This work was undertaken to assess the usefulness of magnetic resonance imaging (MRI) of the brain for early prognosis of cerebral palsy. The study group included 47 neonates (24 term and 23 preterm) with symptoms of perinatal asphyxia. MRI examinations in term neonates were performed during the first month of life but not before the second week of life, while in preterm neonates MRI data were acquired between 38 and 40 weeks from conception. MRI of the brain demonstrated hypoxic-ischemic findings in all neonates born with perinatal asphyxia who later progressed to cerebral palsy. These results support the hypothesis that MRI performed in the neonatal period plays an essential role in predicting cerebral palsy in both term and preterm neonates, regardless of their gestational age.

[Diabetes in pregnancy: cord blond insulin level and neonatal outcome in relation to maternal glycated haemoglobin A1c in last trimester of pregnancy]. / Cukrzyca ciezarnych: stezenie insuliny we krwi pepowinowej, stan noworodka po urodzeniu a odsetek HbA1c u matki w trzecim trymestrze ciazy.

AIM OF THE STUDY: The pattern of the complications observed in the foetus and newborn of diabetic mothers has been changed owing to improvement of care and treatment. Due to the introduction of the Saint Vincent Declaration goals, the improvement in prognosis of diabetic mothers has been noted. The goals are being pursued in our country. The aim of the study was to evaluate whether there is an association between maternal glycated haemoglobin, cord blood insulin level and general condition in infants of diabetic mothers. MATERIAL AND METHODS: In the study 158 newborns of diabetic mothers (86 G1, 56 G2, 16 P) and 171 newborns of the healthy mothers were evaluated. In the newborns of diabetic mothers venous cord blood samples were collected at delivery and analyzed for insulin and fructosamine level in relation to the maternal glycated haemoglobin. RESULTS: The mean birth weight was significantly different between the control group 2885 +/- 905 g and the diabetic group 3199 +/- 617 g. The positive correlation between cord blood insulin level and birth weight in the diabetic group was observed; that indicates the higher fetal insulinemia influence on increased birth weight. Neither the correlation between birth weight and fructosamine nor birth weight and glycated haemoglobin were found. The mean glycated hemoglobin level was 5.17% (G1 5.15%, G2 5.18%, P 5.30%). CONCLUSIONS: There is an association between cord blood insulin level in infants of diabetic mothers and birth weight. Increased insulin level is correlated with hypoglycemia. The incidence of cesarean section, macrosomia, hypoglycemia, hyperbilirubinemia in the study group was not different in comparison to control subject.

[An abdominal inflammatory pseudotumor in a 9-year-old girl with newly diagnosed diabetes mellitus type 1--a case report]. / Guz zapalny jamy brzusznej u 9-letniej pacjentki ze swiezo ujawniona cukrzyca typu 1--opis przypadku.

An inflammatory tumor is a rare, benign pathology with a variable natural course. The hypotheses of the etiology of the inflammatory tumor are associated with trauma, infections or the immune mechanisms. To our knowledge, in the literature are described some single cases of solid omental and peritoneal masses as an uncommon cause of abdominal lump in children. We describe a case of a 9-year-old girl with clinical symptoms at onset of type 1 diabetes and accidentally diagnosed omental and peritoneal tumor.

[Hypoparathyroidism with calcifications in the central nervous system in an 8-year-old boy--case report]. / Niedoczynnosc przytarczyc z ogniskami zwapnien w obrebie osrodkowego ukladu nerwowego u 8-letniego chlopca--opis przypadku.

Hypoparathyroidism is a cause of the tetany in children. Except from the signs of generalized neuromuscular irritability it can also present with less characteristic signs of psychomotor development retardation, calcifications in the soft tissues, including CNS. In our report we describe a case of 8-year-old boy in whom hypoparathyroidism revealed for the first time as an episode of seizures and calcifications of the basal ganglia.

Relation of low-grade inflammation and endothelial activation to blood pressure in obese children and adolescents.

OBJECTIVE: To determine the role of low-grade, systemic inflammation and endothelial activation in the modulation of blood pressure (BP) independently of other traditional risk factors in obese children and adolescents. DESIGN: We surveyed 281 obese subjects, aged 6-18 years to investigate the relationship of serum inflammation and endothelial activation markers and blood pressure. MEASUREMENTS: Clinical variables, indices of obesity, ambulatory 24-h blood pressure and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), glucose and insulin. HOMA IR was used as a marker of insulin resistance (IR). RESULTS: CRP, IL-6, IL-1 beta, and ICAM-1 correlated significantly with mean 24-h systolic BP, whereas CRP and IL-6 was positively correlated with mean 24-h diastolic BP. Multiple regression analysis showed that serum IL-6 (P < .001) concentration, HOMA IR (P < .01), and waist to hip ratio (P < .05) were the significant determinants of systolic BP, whereas CRP (P < .05) level was the only predictor of diastolic BP. There were no significant associations of cell adhesion molecules with BP. CONCLUSIONS: These results indicate that low-grade inflammation may play a role in the modulation of arterial BP relatively early in life.

[Secundum atrial septal defect in newborns of diabetic mothers]. / Ubytek przegrody miedzyprzedsionkowej typu II u noworodków matek chorych na cukrzyce.

AIM: To evaluate in own material the incidence of secundum atrial septal defect type fossa ovalis (ASD II) with signs of cardio-respiratory maladaptation in infants of diabetic mothers (IDM) during the first 48 hours of life, and subsequent echocardiography follow-up of babies with ASD II during the first year of life. MATERIAL AND METHODS: In the period from September 2002 to March 2003 a total of 502 neonates were born and 62 number them were from diabetic mothers. Echocardiography scanning was performed in a group of 49 neonates (42 IDM and 7 full-term infants of healthy mothers) with signs of cardio-respiratory maladaptation during the first 48 hours of life. Six neonates were born from pregestational diabetes mothers and 36 from gestational diabetes mothers (G1-17, G2-19), Birth weight of the newborns were in the range from 1370 to 4450 g, and gestational age was in the range between 30 to 41, mean 38.6 weeks. Apgar score was > 7 in 91.8% of neonates. In the whole study besides laboratory tests in direction of early onset infection, brain ultrasound and echocardiography scanning were performed. M-mode, 2-D presentation and Doppler blood flow velocity were done 4 times during the first year of life (in 2nd, 4th and 12th month). RESULTS: ASD II with 2 to 9 mm diameter was diagnosed in 20 (40.8%) of the examined neonates. Among them 16 were IDM and 4 from healthy mothers. There was no statistically significant difference in the frequency of ASD II recognition in accordance with type of maternal diabetes. During subsequent echocardiography scanning, spontaneous closure of ASD II was found in 11 (55.0%) babies at the age of 12 months. In the remaining 9 (45.0%) infants a decrease in ASD II was notices in 6 (30.0%) cases and the same diameter of arterial defect was left in 3 (15.0%). CONCLUSION: In 38.1% of neonates born to diabetic mothers, cardio-respiratory disturbances during the first 48 hours of life were accompanied by secundum atrial septal defect. During 12 months follow-up with echocardiography evaluation, decrease in diameter or spontaneous closure o ASD II occurred in most of our patients.