Cytidine 5'-diphosphocholine ameliorates hyperoxic lung injury in a neonatal rat model.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is an important cause of morbidity. The aim of this study was to evaluate the preventive effect of cytidine 5'-diphosphocholine (CDP-choline) treatment on hyperoxic lung injury in a neonatal rat model. METHODS: A total of 30 newborn pups were divided into control, hyperoxia, and hyperoxia + CDP-choline groups. After birth, pups in the control group were kept in room air and received saline injections, whereas those in hyperoxia and hyperoxia + CDP-choline groups were exposed to 95% O2 and received daily injections of saline and CDP-choline throughout postnatal day 10, respectively. Histopathological scoring, radial alveolar count, lamellar body membrane protein expression, fibrosis, proinflammatory cytokine levels, lung tissue and bronchoalveolar lavage (BAL) fluid phospholipid content, and apoptosis were evaluated. RESULTS: Hyperoxia-induced severe lung damage was reduced significantly by CDP-choline treatment. Radial alveolar count and lamellar body membrane protein expression were significantly recovered, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells, active caspase-3 expression, and tissue proinflammatory cytokine levels were decreased by CDP-choline administration. Lung tissue and BAL phospholipid contents showed significant increases after CDP-choline administration. CONCLUSION: These data show that CDP-choline ameliorates hyperoxic lung injury in a neonatal rat model. It may therefore be suggested that CDP-choline may be a novel therapeutic option for the prevention of BPD.

CDP-choline reduces severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis.

BACKGROUND: Cytidine 5'-diphosphocholine (CDP-choline) is an endogenous intermediate in the biosynthesis of phosphatidylcholine, a contributor to the mucosal defense of the intestine. The aim of this study was to evaluate the possible cytoprotective effect of CDP-choline treatment on intestinal cell damage, membrane phospholipid content, inflammation, and apoptosis in a neonatal rat model of necrotizing enterocolitis (NEC). METHODS: We divided a total of 30 newborn pups into three groups: control, NEC, and NEC + CDP-choline. We induced NEC by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. We administered CDP-choline intraperitoneally at 300 mg/kg/d for 3 d starting from the first day of life. We evaluated apoptosis macroscopically and histopathologically in combination with proinflammatory cytokines in the gut samples. Moreover, we determined membrane phospholipid levels as well as activities of xanthine oxidase, superoxide dismutase, glutathione peroxidase, and myeloperoxidase enzymes and the malondialdehyde content of intestinal tissue. RESULTS: Mean clinical sickness score, macroscopic gut assessment score, and intestinal injury score were significantly improved, whereas mean apoptosis score and caspase-3 levels were significantly reduced in pups in the NEC + CDP-choline group compared with the NEC group. Tissue proinflammatory cytokine (interleukin-1ß, interleukin-6, and tumor necrosis factor-α) levels as well as tissue malondialdehyde content and myeloperoxidase activities were reduced, whereas glutathione peroxidase and superoxide dismutase activities were preserved in the NEC + CDP-choline group. In addition, NEC damage reduced intestinal tissue membrane phospholipids, whereas CDP-choline significantly enhanced total phospholipid and phosphatidylcholine levels. Long-term follow-up in additional experiments revealed increased body weight, decreased clinical sickness scores, and enhanced survival in CDP-choline-receiving versus saline-receiving pups with NEC lesions. CONCLUSIONS: Our study reports, for the first time, beneficial effects of CDP-choline treatment on intestinal injury in a neonatal rat model of NEC. Our data suggest that CDP-choline may be used as an effective therapeutic agent to prevent NEC.

Risk factor analysis for long-term unfavorable ocular outcomes in children treated for retinopathy of prematurity.

The aim in this study was to report long-term ocular outcomes of neonates treated for retinopathy of prematurity (ROP) and potential risk factors for unfavorable ocular outcomes. The study consisted of neonates treated for ROP between March 1999 and November 2009. Data relating baseline characteristics and late structural, functional and refractive ocular outcomes were recorded. The association between the unfavorable ocular outcomes and ROP-related risk factors was evaluated by regression analysis. Forty-eight children were included for assessment. Average chronological age at the time of followup was 3.11±0.73 years. The rates of unfavorable structural and functional outcomes were 12% and 15.3%, respectively. Ocular deviation was common (27.1%), and mostly esotropic (12/13). A clear myopic tendency was observed (51.2%), and the mean spherical equivalent per eye was -0.72±2.9 diopters. Regression analyses for unfavorable ocular outcomes revealed intraventricular hemorrhage as a core independent risk factor. In conclusion, ROP treatment has shown promising results in both structure and function. Because of the high risk of developing an unfavorable outcome, a more intense follow-up is required in neonates with a history of intraventricular hemorrhage in the neonatal period. Further studies from other centers are needed to develop a national database, which may validate this observation.

Increased fecal calprotectin in preterm infants with necrotizing enterocolitis.

BACKGROUND: Necrotizing entrocolitis (NEC) remains a potentially fatal disease in premature infants despite the recent advances in neonatal care. It is a disease with a multifactorial etiology leading to the one common final pathway of necrosis and inflammmation of the neonatal intestine. METHODS: Calprotectin is a calcium and zinc-binding protein in human neutrophils. Its concentration rises in various organic bowel diseases in adults and is resistant to degradation and has been proposed as a useful, simple, and rapid diagnostic method of inflammatory bowel disease that shows gastrointestinal inflammation in children and adults. RESULTS: We found that infants with necrotizing enterocolitis had increased fecal calprotectin concentrations, and there was a correlation between calprotectin concentrations and severity of NEC. CONCLUSIONS: We concluded that fecal calprotectin is a useful marker for diagnosis and severity of NEC in preterm infants.

Neurodevelopmental status of preterm newborns at infancy, born at a tertiary care center in Turkey.

Our objective was to determine the incidence of early neonatal problems and the neurodevelopmental status and probable risk factors associated with neurodevelopmental abnormality in preterm infants of < or = 32 weeks of gestation. Preterm newborns of < or = 32 weeks of gestation followed at the neonatal intensive care unit of the Department of Pediatrics of Gülhane Military Medical Academy, Ankara, Turkey, were evaluated with a complete neurological examination and the Bayley Scales of Infant Development at a mean age of 25.85 + or - 11.79 months (range, 10 to 42 months). Multivariate logistic regression analyses were performed to determine the probable risk factors associated with neurodevelopmental abnormalities. Regarding the results of the neurological examination in a total of 169 preterms included in the study, 28 (16.6%) and 14 (8.3%) patients were determined to have mild neurological dysfunction or cerebral palsy, respectively. The rate of psychomotor abnormality according to a low Bayley Psychomotor Development Index (PDI) score was 24.8%, and the rate of mental/cognitive abnormality on the basis of a low Bayley Mental Development Index (MDI) score was 25.4%. In the subgroup of infants with < or = 29 weeks of gestational age (n = 55); 22 (40%) patients had an abnormal neurological examination, and 24 (43.6%) and 23 (41.8%) patients had low Bayley PDI and MDI scores, respectively. In the study group, logistic regression analysis revealed the significant predictors of an abnormal neurological examination to be the duration of mechanical ventilation (odds ratio [OR], 1.133; 95% confidence interval [CI], 1.062 to 1.208) and necrotizing enterocolitis (OR, 6.697; 95% CI, 1.776 to 25.252). One of the major conclusions of the present study is the risk of neurodevelopmental sequelae in one of every four preterm infants with <32 weeks of gestation and the need for follow-up in this group. Measures in neonatal care and treatment, such as the use of less traumatic modes of mechanical ventilation with as short duration as possible as well as increasing perinatal/antenatal care, should be taken to overcome these risk factors.

Investigation of the relationship between cord clamping time and risk of hyperbilirubinemia.

BACKGROUND: Although the relationship between umbilical cord clamping time and various parameters such as hemoglobin (Hb) levels, iron deficiency, and risk of neonatal jaundice has previously been studied, to the best of our knowleadge there have been no studies investigating the relationship between cord clamping time and the risk of significant hyperbilirubinemia. We aimed to investigate the relationship between the time of umbilical cord clamping and transcutaneous bilirubin (TcB) measurements made on various postnatal hours, Hb and serum total bilirubin (STB) levels measured on postnatal 4th day, and the risk of development of significant hyperbilirubinemia requiring phototherapy treatment. METHODS: Eligible newborns were divided into two groups on the basis of the time of cord clamping: those clamped late (60 seconds or more; Group I) and those clamped early (less than 60 seconds; Group II). Groups were compared with respect to the parameters of cord Hb, postnatal TcB measurements at 6th, 48th, 96th and 168th hours, and 96th hour Hb, STB and direct bilirubin levels. RESULTS: TcB levels at the 96th and 168th hour were significantly higher in Group I when compared to Group II (p < 0.001 and p < 0.001, respectively). The 96th hour STB level was significantly higher in Group I when compared to Group II (p < 0.001). The need of phototherapy requirement was higher in Group I when compared to Group II (p=0.001). Increase in cord blood Hb for each 1 gr/dl caused a 3.94-fold increased risk in the requirement of phototherapy treatment. Cord clamping time showed statistically significant positive correlations with both cord blood and 96th hour venous Hb levels, with both 96th hour and 168th hour TcB levels, and with 96th hour STB levels. CONCLUSIONS: Newborns whose cords are clamped late should be followed up closely with respect to high postnatal bilirubin levels and other risks associated with significant hyperbilirubinemia requiring phototherapy treatment.

Congenital cytomegalovirus infection associated with severe lung involvement in a preterm neonate: a causal relationship?

We report a preterm neonate with congenital cytomegalovirus (CMV) infection associated with severe lung involvement progressing to early chronic lung disease (CLD) and death. The present case represents the earliest and the most severe lung involvement depending on recurrent maternal CMV infection reported in the literature. Neonatal mortality and progression to early CLD should be considered in the list of possible neonatal sequelae resulting from recurrent maternal CMV infection.

Screening for retinopathy of prematurity in a tertiary care newborn unit in Turkey: frequency, outcomes, and risk factor analysis.

PURPOSE: To report the frequency, risk factors, and outcomes of screening for retinopathy of prematurity (ROP). METHODS: Data of neonates with a gestational age of 34 weeks or less were analyzed and the predictors on the development of ROP were determined by using logistic regression analysis. RESULTS: Of the 318 neonates, the frequency of ROP was 37.1% for any stage and 7.2% for stage 3 or greater. Treatment was needed in 16.1% of neonates with ROP. No treatment was required in neonates with a gestational age of greater than 32 weeks. Oxygen therapy, sepsis, gestational age of 32 weeks or less, and birth weight of less than 1,250 g were determined as the independent risk factors. CONCLUSIONS: Although frequency of ROP in Turkey is similar to that in the United States, the rate of severe ROP necessitating treatment seems to be higher in Turkey. Neonates with a gestational age of 32 weeks or less, a birth weight of less than 1,250 g, sepsis, and oxygen therapy may have a greater risk of developing ROP and screening should be intensified in the presence of these risk factors.

Neutrophil hypersegmentation in children receiving angiotensin converting enzyme inhibitors.

Captopril and enalapril are the most commonly used angiotensin converting enzyme inhibitors in several cardiac diseases in children. On the other hand, the intrinsic renin-angiotensin system in the bone marrow might affect the growth of hematopoietic colonies and cellular production, proliferation and differentiation in physiological and pathological states. Starting with the hypothesis that inhibition of the renin-angiotensin system may have some effects on the hematopoietic system, including morphological changes within the granulocytes, we thus aimed to investigate prospectively whether the use of angiotensin converting enzyme inhibitors has any effect on the morphology, and especially segmentation, of neutrophils in peripheral blood. A total of 40 children with various heart diseases receiving either of two angiotensin converting enzyme inhibitors (captopril or enalapril) aged between 2 to 16 years were enrolled, and 40 healthy age- and sex-matched children were enrolled as controls. Complete blood count, peripheral blood smear, liver and renal function tests, and measurement of serum alkaline phosphatase, ferritin, vitamin B12 and folate levels were performed in all cases. Peripheral blood smears were viewed by two pediatric hematologists in a blinded manner. Neutrophil hypersegmentation was described as presence of five or more neutrophils with five well-separated lobes or at least one neutrophil with six or more lobes among 100 segmented neutrophils. The number of patients with neutrophil hypersegmentation in the study group was significantly higher than in the control group, and the mean lobe count in the study group was significantly higher than in the control group. Neutrophil hypersegmentation, as detected in patients using angiotensin converting enzyme inhibitors in the present study, has not been reported previously. Further studies aiming to explain the pathophysiological mechanism(s) underlying neutrophil hypersegmentation in patients receiving angiotensin converting enzyme inhibitors are needed.

Self-application of complementary and alternative medicine by patients with gynecologic cancer.

OBJECTIVES: In this study we aimed to determine the epidemiology and demographic data on complementary and alternative medicine (CAM) use along with the medical/surgical treatment modalities in patients with gynecologic cancers in Turkey. MATERIALS AND METHODS: A cross-sectional study was designed to determine demographic data on CAM use of patients with gynecologic cancers who had medical and/or surgical treatments. Semistructured questionnaires were used for collecting data from 126 patients. RESULTS: When the CAM use ratio of patients was evaluated with respect to demographic characteristics, patients using any type of CAM were younger and more educated, and there were no significant differences between the patients who used and who did not use any type of CAM with respect to geographical region. There were no significant correlations between the use of CAM and the type of malignancy, treatment modality and time period after diagnosis. CONCLUSION: There is critical concern about the probable serious risks associated with non-educated CAM practitioners. Therefore, informed and educated healthcare professionals should inform and help in relieving patients in a more professional and multidisciplinary way.

Genetic factors in neonatal hyperbilirubinemia and kernicterus.

Although the relationship between hyperbilirubinemia and genetic factors has long been questioned, the role of genetic factors in the development of severe hyperbilirubinemia and kernicterus has been investigated in detail in the last decade with the rapid progression in molecular medicine. Although the first historical data gathered about genetical tendency to neonatal hyperbilirubinemia dates back to description of the Crigler-Najjar syndrome in 1952, a substantial interest is currently focused on coding and promoter region mutations of uridine diphosphoglucuronate glucuronosyltransferase 1A1 gene. In this article, the role of uridine diphosphoglucuronate glucuronosyltransferase gene mutations in neonatal significant hyperbilirubinemia and kernicterus is reviewed together with the clinical presentations of the most common syndromes of bilirubin conjugation, such as Gilbert and Crigler-Najjar syndromes. Genetic counseling and investigation may be useful and necessary in newborns presenting with severe, unexplained familial hyperbilirubinemia. In these various syndromes where enzymatic and genetic deficiencies are present, studies about treatment with gene replacement, though currently experimental, are ongoing, especially in type 1 Crigler-Najjar.

Hyperbilirubinemia due to minor blood group (anti-E) incompatibility in a newborn: a case report.

In addition to Rh and ABO incompatibilities subgroup incompatibilities may rarely play a role among the causes of hemolytic anemia and indirect hyperbilirubinemia in newborns. The most common minor blood group antigens that cause blood incompatibility between the mother and baby are C, c, E, e, Kell, Duffy, Diego, Kidd and MNSs antigens. In this article, a newborn in whom hyperbilirubinemia due to anti-E minor blood group incompatibility developed and was treated with phototherapy succesfully is presented and minor blood group incompatibilities due to anti-E are reviewed.

Association Between Early Idiopathic Neonatal Jaundice and Urinary Tract Infections.

BACKGROUND AND PURPOSE: Etiologic role, incidence, demographic, and response-to-treatment characteristics of urinary tract infection (UTI) among neonates, its relationship with significant neonatal hyperbilirubinemia, and abnormalities of the urinary system were studied in a prospective investigation in early (⩽10 days) idiopathic neonatal jaundice in which all other etiologic factors of neonatal hyperbilirubinemia were ruled out. PATIENTS AND METHODS: Urine samples for microscopic and bacteriologic examination were obtained with bladder catheterization from 155 newborns with early neonatal jaundice. Newborns with a negative urine culture and with a positive urine culture were defined as group I and group II, respectively, and the 2 groups were compared with each other. RESULTS: The incidence of UTI in whole of the study group was 16.7%. Serum total and direct bilirubin levels were statistically significantly higher in group II when compared with group I (P = .005 and P = .001, respectively). Decrease in serum total bilirubin level at the 24th hour of phototherapy was statistically significantly higher in group I compared with group II (P = .022). CONCLUSIONS: Urinary tract infection should be investigated in the etiologic evaluation of newborns with significant hyperbilirubinemia. The possibility of UTI should be considered in jaundiced newborns who do not respond to phototherapy well or have a prolonged duration of phototherapy treatment.

Effects of iron deficiency versus iron deficiency anemia on brainstem auditory evoked potentials in infancy.

There has been little or no evidence of brainstem auditory evoked potentials (BAEPs) among infants with iron deficiency (ID) that is not severe enough to cause anemia. To our knowledge, the effect of ID on auditory functions and/or potentials has not been investigated previously, though it seems reasonable that it should be associated with BAEP measures intermediate between those observed in iron deficiency anemia (IDA) and in iron sufficiency, considering the role of iron in myelin formation and maintenance. We therefore aimed in this study to investigate the effect of ID on BAEPs by comparing three groups of infants with ID, IDA and iron sufficiency (control) both before and after iron treatment (in iron-deficient groups). Three groups of infants (IDA, n = 25; ID, n = 24; Control, n = 44) were compared on the basis of hematological laboratory parameters and BAEP measurements both at entry into and after (12 weeks treatment with oral iron in IDA and ID groups) the study. BAEP measurements recorded at 85 dB both at entry into and after the study were not significantly different among the groups, although a sufficient response to iron treatment was achieved in iron-deficient groups (Group I and Group II). The only positive finding determined in our study was a slight decrease in latencies obtained at the end of the study when compared to the pre-study values in all three groups of the study in accordance with the expected age-dependent developmental changes. Although no negative electrophysiological effect of ID on brainstem auditory functions was found in the present study, further longer term (late childhood or adult) studies are necessary to elucidate the relationships among anemia (maybe other than IDA), ID and auditory functions, and clinical implications of hearing loss (if any) should be questioned.

Permanent neonatal diabetes caused by glucokinase deficiency: inborn error of the glucose-insulin signaling pathway.

Neonatal diabetes can be either permanent or transient. We have recently shown that permanent neonatal diabetes can result from complete deficiency of glucokinase activity. Here we report three new cases of glucokinase-related permanent neonatal diabetes. The probands had intrauterine growth retardation (birth weight <1,900 g) and insulin-treated diabetes from birth (diagnosis within the first week of life). One of the subjects was homozygous for the missense mutation Ala378Val (A378V), which is an inactivating mutation with an activity index of only 0.2% of wild-type glucokinase activity. The second subject was homozygous for a mutation in the splice donor site of exon 8 (intervening sequence 8 [IVS8] + 2T-->G), which is predicted to lead to the synthesis of an inactive protein. The third subject (second cousin of subject 2) was a compound heterozygote with one allele having the splice-site mutation IVS8 + 2T-->G and the other the missense mutation Gly264Ser (G264S), a mutation with an activity index of 86% of normal activity. The five subjects with permanent neonatal diabetes due to glucokinase deficiency identified to date are characterized by intrauterine growth retardation, permanent insulin-requiring diabetes from the first day of life, and hyperglycemia in both parents. Autosomal recessive inheritance and enzyme deficiency are features typical for an inborn error of metabolism, which occurred in the glucose-insulin signaling pathway in these subjects.

Bone mass toxicity associated with inhalation exposure to toluene.

The inhalation of a wide range of organic solvents has become popular among young adults. Toluene is one of the most commonly used solvents in industry; it is easily available and convenient to use. Many toxicologic effects on biological systems secondary to deliberate inhalation of toluene have been reported, but investigations on adverse effects associated with bone morbidity is limited. The purpose of this study is to determine bone mineralization and investigate the adverse effects of toluene on bone. The bone mineral density and content of the femoral neck of mice exposed to toluene at 300 ppm for 8 wk were measured by dual X-ray absorptiometry and found significantly reduced compared to the control group. Chronic exposure to toluene was found to affect bone metabolism, and toluene-induced changes could contribute to bone resorption and inhibition of bone formation. Toluene seems to be the responsible component for the demineralizating effects of commonly abused substances, and medical doctors must promote their education about the health hazards in those who abuse solvents especially in areas where inhalant abuse is endemic.

Evaluation of visual evoked potentials in children with headache.

Headache is a common problem in childhood. Visual evoked potential (VEP) P100 latencies were recorded in children with headache. Sixty-four patients, aged 10.7 +/- 1.2 years, met the criteria of the International Headache Society for the diagnosis of migraine. Fifty-eight patients, aged 10.2 +/- 1.3 years, with tension headache and 56 healthy subjects, aged 10.3 +/- 1.3 years, as the control group were also studied. Patients with migraine had slightly longer P100 latencies than the other two groups. We conclude that VEP latency recording is a valuable test in the diagnosis of migraine, and can be safely used in children.

The triad of nesidioblastosis, congenital neuroblastoma and glomerulocystic disease of the newborn: a case report.

Neuroblastoma is the most common malignant tumor of the newborn, comprising 20% of all malignancies encountered during the neonatal period. We herein report a newborn who was born after 29 weeks' gestation and died unexpectedly at the 12th hour of life with no response to vigorous cardiopulmonary resuscitation. Autopsy findings revealed a right pararenal mass; microscopic examination showed neuroblastoma. Although the pancreas was grossly normal, its microscopic sections revealed a reduced number of islets of Langerhans and dispersion of the islet cells throughout the exocrine cells of the pancreas, and immunocytochemistry for the pancreatic hormones confirmed the dispersion of the islet cells. Final pathologic interpretation thus concluded the presence of nesidioblastosis. Furthermore, microscopic examination of the kidney showed glomerulocystic disease. Although the association of congenital neuroblastoma and nesidioblastosis has recently been defined as a new complex, neurocristopathy, the triad of congenital neuroblastoma, nesidioblastosis and glomerulocystic disease of the newborn has not been reported previously. To our knowledge, our case is the first reported newborn presenting with this triad. In conclusion, the association of nesidioblastosis and/or renal glomerulocystic disease should be kept in mind when encountering a case of congenital neuroblastoma. However, whether the presence of glomerulocystic disease in association with those other neurocristopathic pathologies is a coincidental finding or shares a common pathophysiological mechanism remains to be determined.

Selenium and zinc levels in volatile substance abusers.

Plasma and erythrocyte levels of selenium (Se) and zinc (Zn) have not been investigated in volatile (inhalant) substance abusers previously, although changes in the activities of antioxidant enzymes resulting from oxidative damage caused by various constituents of volatile substances have been shown in a few animal and human studies. Concentrations of these two elements in erythrocytes and plasma of 37 adolescents with inhalant abuse were measured by atomic absorption spectrophotometry and compared with those of 37 age-matched healthy controls. Erythrocyte and plasma levels of Se and plasma level of Zn were significantly lower in the study group when compared to the control group. Chronic inhalation of volatile substances can decrease the plasma levels of Se and Zn and, thus, may lead to a decrease in the activity of antioxidant enzyme systems in adolescent abusers. The role of Se and Zn supplementation in children with inhalant abuse remains to be determined considering the reduced antioxidant activity resulting from deficiency of these trace elements.