Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival.

Effects of Inhaled Corticosteroids on the Growth Plates of Infant Rats.

The most significant adverse effect of inhaled steroid administration in children is suppression of hypothalamic-pituitary-adrenal axis responsiveness and suppression of growth. This study evaluates the effects of inhaled corticosteroids on the growth plates in infant rats. Rats aged 10 days were divided into five groups. Low and high doses of budesonide and fluticasone propionate (50-200-250 mcg/day) were applied with a modified spacer for 10 days. The rat's tibias were then removed and the effects of the steroids on the growth plates were compared. Growth cartilage chondrocyte proliferation and apoptosis rates; IGF-1 and glucocorticoid receptor levels; and resting, proliferative, hypertrophic, and total zone (TZ) measurements were compared using immunohistochemical-staining methods. With high doses of fluticasone, growth plates were affected much more than with high doses of budesonide (p = 0.01). Fluticasone, particularly at a dose of 250 mcg, inhibited the growth plate with an intensive negative impact on all parameters.

High serum 25-hydroxyvitamin D levels are associated with pediatric sepsis.

Despite major advances in intensive care, sepsis continues to be a major cause of morbidity and mortality. Vitamin D is involved in various physiologic functions, including cellular responses during infection and inflammation. The aim of this study was to evaluate diagnostic value of 25-hydroxyvitamin D in childhood sepsis because it can be fatal if diagnosis delayed. The study included 40 children with sepsis and 20 children without sepsis (control group). We included only the patients with high probable sepsis, judged by clinical and laboratory findings, including positive blood culture. Blood samples were collected from patients with sepsis before treatment (pre-treatment group) and 48-72 hours later (post-treatment group). Treatment varied from ampicillin-sulbactam to cephalosporin. Blood samples were collected from control group once on admission. Serum 25-hydroxyvitamin D levels were significantly higher in sepsis (pre-treatment group) than control group (74 ± 8 ng/ml vs. 28 ± 12 ng/ml, p = 0.01) and the serum 25-hydroxyvitamin D levels were decreased to 44 ± 5 ng/ml (p = 0.01) after treatment. Moreover, we found significant positive correlation between 25-hydroxyvitamin D and each of well-know sepsis markers, C-reactive protein, tumor necrosis factor-α and interleukin-6. A cut-off point of 20 ng/mL for serum 25-hydroxyvitamin D showed 84% sensitivity and 76% specificity for sepsis diagnosis. This is the first study evaluating the diagnostic role of vitamin D in pediatric sepsis, thereby suggesting that serum 25-hydroxyvitamin D level can be used as a diagnostic marker for sepsis with high sensitivity and specificity.

Comparison between daily supplementation doses of 200 versus 400 IU of vitamin D in infants.

The daily supplementation of vitamin D is mandatory for infants. However, there are still conflicting opinions about the exact daily dose. Thus, we aimed to evaluate a daily supplementation dose of 200 IU is sufficient and compared the supplementation doses of 200 and 400 IU per day. One hundred and sixty-nine infants were randomly assigned to two groups (group 1, 200 IU/day; group 2, 400 IU/day) and there were 75 infants in group 1 and 64 were in group 2 with a total number of 139. The median levels of 25-hydroxyvitamin D3 were significantly increased in group 2 at the age of 4 months (group 1, 39.60 mcg/L; group 2, 56.55 mcg/L; p < 0.0001). We clearly demonstrated that at the age of 4 months, none of the infants on the group 2 had a serum level of 25-hydroxyvitamin D3 less than 30 mcg/L. However, 21.3% of the infants in group 1 had a level below 30 mcg/L. Thus, in order to avoid vitamin D deficiency and rickets, we recommend supplementation dose of vitamin D at 400 IU/day as a safe and effective dose.

[Investigation of a nosocomial outbreak caused by ESBL positive Klebsiella pneumoniae in neonatal intensive care unit by AP-PCR]. / Yenidogan Yogun Bakim Ünitesinde Ortaya Çikan GSBL Pozitif Klebsiella pneumoniae Nedenli Nozokomiyal Bir Salginin AP-PCR ile Arastirilmasi

In the present study, we describe an outbreak caused by extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae in the neonatal intensive care unit (NICU) of a tertiary-care hospital. Nosocomial blood-stream infections were detected in three patients hospitalized in NICU. Two of the cases were transferred to NICU due to premature birth and the other due to the presence of cleft palate and retrognathia. K.pneumoniae was isolated on the 5th day of hospitalization of the first patient from umbilical swab and blood culture; on the 15th day of hospitalization of the second patient from blood culture and on the 7th day of hospitalization of the third patient from blood culture. The isolates were identified by automated API Rapid ID 32 Staph (BioMerieux, France) system in addition to conventional laboratory methods. Antibiotic susceptibilities of the isolates were determined by using Kirby-Bauer disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI) criteria. The same antibiotic susceptibility patterns were detected in all isolates. Active surveillance cultures included environmental sampling from surfaces of NICU, laryngoscopes, ventilators and connections of ventilators, stethoscopes, nebulizers, aspiration tubings, disinfectant solutions, couveuse and couveuse distilled water. Two ESBL producing K.pneumoniae strains, presenting the same antibiotic susceptibility pattern with the clinical strains, were isolated from one couveuse distilled water sample and one aspiration tubing. All of the K.pneumoniae isolates were resistant to amoxycillin-clavulonic acid, cefazolin, cefepime, ceftriaxone, ceftazidime, cefuroxime, aztreonam and trimetoprim-sulphametoxazole and susceptible to cefoxitin, imipenem, meropenem, gentamicin, tobramycin, amikacin, netilmisin, tetracycline, ciprofloxacin and chloramphenicol. Arbitrarily primed polymerase chain reaction (AP-PCR) analysis done with M13 primer revealed the same genotype for the patient and environmental K.pneumoniae isolates. It was concluded that AP-PCR which is a simple, rapid and cheap method for the determination of genetic relatedness between isolates, can be applied for the detailed evaluation of nosocomial outbreaks to detect the source of infection and control the dissemination of the outbreak.

Bilateral renal hypoplasia and cystic dysplasia: a new phenotype of Thomas syndrome or a new syndrome?

Thomas syndrome is a rare syndrome including Potter sequence, renal anomalies, heart defects, cleft palate with other oropharyngeal anomalies. Here, we report a newborn with Potter sequence, bilateral renal hypoplasia and cystic dysplasia, multiple cardiovascular malformations, long large ears, frontal bossing, small lips, partial simple toe syndactyly, and cleft palate. To our best knowledge, this patient may be considered as a new variant of Thomas syndrome or a new syndrome.

Renal zinc clearance/glomerular filtration rate ratio as an indicator of marginal zinc deficiency associated with iron deficiency in childhood.

OBJECTIVE: To evaluate the usefulness of renal zinc clearance/glomerular filtration rate ratio (R(ClZn)/GFR) as an indicator of marginal zinc deficiency that is generally associated with iron deficiency in childhood. METHODS: Zinc status was evaluated in 36 iron-deficient children (22 boys and 14 girls) who ranged in age from 1 to 10 years using serum zinc concentration and U(Zn/Cr) and R(ClZn)/GFR ratios. The results were compared with the zinc status of 36 similar-aged healthy children (24 boys and 12 girls). RESULTS: Serum zinc concentrations were 96.72 +/- 2.13 microg/dL and 93.93 +/- 1.95 microg/dL in iron-deficient and healthy subjects, respectively (p > 0.05). U(Zn/Cr) ratios were 0.54 +/- 0.04 microg/mg and 0.88 +/- 0.04 microg/mg (p < 0.0001); R(ClZn)/GFR ratios were 2.27 x 10(-3) +/- 0.20 and 3.32 x 10(-3) +/- 0.20 (p < 0.001) in iron-deficient and healthy subjects, respectively. Individual values of R(ClZn)/GFR and U(Zn/Cr) ratios correlated with hemoglobin (Hb) concentrations (r = 0.34, p < 0.01 and r = 0.26, p < 0.05). Data grouped according to the ranges of Hb concentrations and R(ClZn)/GFR and U(Zn/Cr) ratios fit the following equations: The statistically significant difference in U(Zn/Cr) and R(ClZn)/GFR ratios between groups indicates decreased urinary estimation of marginal zinc deficiency, whereas no change was observed in serum zinc concentrations. According to the regression equation, it can be postulated that the R(ClZn)/GFR ratio is a linear function of Hb concentration and the U(Zn/Cr) ratio. CONCLUSION: R(ClZn)/GFR ratio was a reliable indicator for reduction in urinary zinc excretion; it estimated the marginal zinc deficiency associated with iron deficiency. The R(ClZn)/GFR ratio can be calculated using one sample of blood and urine; thus it could serve as an alternative indicator of marginal zinc deficiency, especially in routine health care.

Elevated plasma levels of apelin in children with type 1 diabetes mellitus.

BACKGROUND: Apelin is a novel adipocytokine produced by white adipose tissue that binds the APJ receptor with high affinity. Insulin may have a role in regulation of apelin synthesis and secretion from the adipose tissue. OBJECTIVE: To investigate blood apelin concentrations in children with type 1 diabetes mellitus (T1DM) and display association of apelin with adiponectin, body mass index (BMI), lipids and insulin sensitivity. METHODS: Thirty patients with T1DM and 45 healthy controls were enrolled. Apelin levels were measured along with BMI, lipids, fasting plasma glucose, HbA1c and adiponectin levels. RESULTS: Plasma apelin and adiponectin levels were significantly higher in the diabetic group when compared to controls. No correlation was found between the apelin blood concentrations and adiponectin, BMI, lipids and insulin sensitivity. CONCLUSIONS: Children with T1DM have significantly increased circulating apelin levels when compared to healthy controls. However, no significant relation was found between the apelin and BMI, glucose, lipids and adiponectin levels, and also insulin sensitivity.

Evaluation of neuropsychological development of children diagnosed with primary monosymptomatic nocturnal enuresis: A pilot study.

OBJECTIVE: Studies on primary monosymptomatic nocturnal enuresis have supported neuromotor development delay. This study aims to examine the neuropsychological development of children with primary monosymptomatic nocturnal enuresis. MATERIAL AND METHODS: This study included 30 children diagnosed with primary monosymptomatic nocturnal enuresis and 30 healthy children. Both groups were analyzed by pediatric psychologists using the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Bender Gestalt Visual Motor Detection test. The WISC-R test is an intelligence test that includes six verbal subscales (information, similarities, arithmetic, vocabulary, judgment, and digit span) and six performance subscales (picture completion, picture arrangement, block design, object assembly, coding, and labyrinths). The Bender Gestalt test is a psychological assessment instrument used to evaluate visuomotor functioning, visuospatial functions, spatial memory, visuomotor integration skills, and visual perception skills. RESULTS: There were no differences in age (7.66±0.9 versus 8±1.07 years, p>0.05) or sex (20 females versus 20 males, p>0.05) between the groups. Picture completion (p=0.024), picture arrangement (p=0.001), and object assembly test (p=0.000) performance was found to be worse in subjects with primary monosymptomatic nocturnal enuresis. Similarity (p=0.021) and judgment tests (p=0.048) of the verbal subtests were also found to be delayed in the nocturnal enuresis cases. CONCLUSION: Our results suggest that children with nocturnal enuresis have lower performance compared with the control group in terms of abstract thinking, correct expression of thought, cause-result relation, short-term memory, and problem-solving ability. These children should be routinely tested by neurodevelopment tests and receive support in areas in which they are delayed.

A rare case in childhood: Pott's puffy tumor developing secondary to frontal sinus osteoma.

Pott's puffy tumor is a rare and serious complication of frontal sinusitis, characterized by the development of osteomyelitis and subperiostal abscess in the frontal bone. Paranasal sinus osteomas are benign osteoblastic tumors, usually seen in the 3rd and 4th decades of life. In this report, we present a case of Pott's puffy tumor due to frontal sinus osteoma in an adolescent male patient. In the literature, we found no similar case in the pediatric age group and we wanted to emphasize the development of Pott's tumor as a rare complication of chronic or recurrent sinusitis and draw attention to the fact that paranasal sinus osteomas may be the underlying cause.

A case of cerebello-oculo-renal syndrome with situs inversus totalis: a new phenotype.

Cerebello-oculo-renal syndromes are rare, autosomal recessive syndromes with uncertain nosology. Cerebello-oculo-renal syndromes involve many congenital malformations and may be associated with other disorders. The authors present a case of cerebello-oculo-renal syndrome with situs inversus totalis from a consanguineous family. The patient had cerebellar vermis hypoplasia, ocular abnormalities (Leber congenital amaurosis with retinal dystrophy, abnormal eye movements), developmental delay, growth deficiency, severe renal failure, and severe anemia. Imaging studies showed molar tooth sign, which was compatible with cerebello-oculo-renal syndromes and situs inversus totalis.

Parvovirus B19 associated papular-purpuric gloves-and-socks syndrome.

The papular-purpuric gloves-and-socks syndrome (PPGSS) is a disease characterized by an itching erythema and edema of the hands and feet, oral mucosal lesions and fever. It may be caused by various agents. Parvovirus B19 has been implicated as the etiological factor in most cases. Here we report a case of PPGSS in a nine-year-old previously healthy girl with papular and petechial lesions on her peroral area and trunk, and primarily on the dorsal areas of her hands and feet. Serologic study confirmed the acute infection by parvovirus B19. We believe that our case is worthy of particular attention because of the rarity of the disease in the pediatric age group and because it is the first documented case of PPGSS in Turkey.

The effect of the pre-pregnancy weight of the mother and the gestational weight gain on the bilirubin level of term newborn.

OBJECTIVE: Jaundice is a problem in newborns. There are many maternal and infant-related factors affecting neonatal jaundice. The maternal pre-pregnancy weight, maternal body mass index (BMI) and gestational weight gain may have an effect on the newborn bilirubin levels. We research the effect of the maternal pre-pregnancy weight and gestational weight gain on the bilirubin levels of the newborn infants in the first 2 weeks prospectively. METHODS: Term and healthy infants who were born between 38 and 42 weeks in our clinic were included in the study. Maternal pre-pregnancy BMIs were calculated. Babies were divided into three groups according to their mothers' advised amount of gestational weight gain. Total serum bilirubin (TSB) values of the newborns were measured in the 2nd, 5th and 15th postnatal days. RESULTS: In our study, the 5th and 15th day capillary bilirubin level of the babies with mothers who gained more weight than the advised amount during pregnancy were found statistically significant higher compared to the other two groups (p < 0.05). Similarly, the hematocrit level of the babies with mothers who gained more weight than the advised amount were found statistically significant higher compared to the other two groups (p < 0.05). CONCLUSIONS: We conclude that the babies with mothers who gained more weight than the advised amount were under risk for newborn jaundice. Therefore, these babies should be monitored more closely for neonatal jaundice and prolonged jaundice.

Urinary Netrin-1: A New Biomarker for the Early Diagnosis of Renal Damage in Obese Children.

OBJECTIVE: Urinary netrin-1 is a new marker to demonstrate early tubular damage. The aim of this study was to determine whether urinary netrin-1 is increased in obese children. METHODS: A total of 68 normoalbuminuric and normotensive obese patients and 65 controls were included in the study. Urine samples were collected for assessment of urinary phosphorus, sodium, potassium, creatinine, albumin, and netrin-1. Blood samples were collected for measurements of fasting glucose, insulin, lipid, phosphorus, sodium, potassium, and creatinine levels. Homeostatic model assessment insulin resistance index was calculated. RESULTS: Gender and age were similar between obese and control groups (12.01±3.03 vs. 11.7±3.2 years, p=0.568 and 33 vs. 35 girls, p=0.543, respectively). Obese patients had significantly higher netrin-1 excretion than the controls (841.68±673.17 vs. 228.94±137.25 pg/mg creatinine, p=0.000). Urinary netrin-1 level was significantly higher in obese subjects with insulin resistance compared to those without insulin resistance (1142±1181 vs. 604.9±589.91 pg/mg creatinine, p=0.001). CONCLUSION: In normotensive and normoalbuminuric obese children, urinary netrin-1 level can increase before onset of albuminuria. Urinary netrin-1 excretion appears to be affected predominantly by insulin resistance and hyperinsulinemia. Urinary netrin-1 may be a new biomarker for determining early tubular injury in obese children.

The Association between Serum 25-Hydroxy Vitamin D Level and Urine Cathelicidin in Children with a Urinary Tract Infection.

OBJECTIVE: Cathelicidin is an important antimicrobial peptide in the urinary tract. Cathelicidin expression is strongly stimulated by 1,25-dihydroxy vitamin D in epithelial cells, macrophages/monocytes, and neutrophils. Vitamin D and cathelicidin status in children with urinary tract infection (UTI) caused by Escherichia coli is unknown. To establish the relationship between serum vitamin D and urine cathelicidin levels in children with a UTI caused by Escherichia coli. METHODS: Serum 25-hydroxy vitamin D and urine cathelicidin levels were measured in 36 patients with UTI (mean age 6.8±3.6 years, range: 0.25-12.6 years) and 38 controls (mean age 6.3±2.8 years, range: 0.42-13 years). RESULTS: There were no significant differences in urine cathelicidin levels between the study and control groups (p>0.05). Eight (22.2%) patients in the study group and 21 (58.3%) children in the control group were found to have sufficient vitamin D (≥20 ng/mL). Patients with sufficient vitamin D had higher urine cathelicidin levels than the controls with sufficient vitamin D (respectively 262.5±41.1 vs. 168±31.6 ng/mL, p=0.001). There were no significant differences between the patients and controls with insufficient vitamin D (p>0.05). CONCLUSION: The children with vitamin D insufficiency may not be able to increase their urine cathelicidin level during UTI caused by Escherichia coli. There is a need of prospective studies in order to prove a beneficial effect of vitamin D supplementation for the restoration of cathelicidin stimulation and consequently for prevention of UTI recurrence.

Efficacy of interferon alpha-2b and lamivudine therapy for chronic hepatitis B in children.

OBJECTIVE: To evaluate the efficacy of interferon (IFN) alpha-2b and lamivudine therapy in children with chronic hepatitis B virus (HBV) infection. METHOD: Ten children who developed chronic hepatitis B infection received IFN alpha-2b 10 million international units (IU)/m(2) body surface area, subcutaneously three times a week for six months. IFN + lamivudine therapy began to be used in the cases who were unresponsive to IFN treatment. RESULTS: Among 27 HBsAg (+) subjects in this study, interferon treatment was given to 11 subjects who developed chronic hepatitis. One case was excluded from the study due to detection of Herpes type 1 encephalitis. At the end of six months of follow-up, complete response was obtained in three (30%) patients and partial response in four (40%) patients, whereas no response was detected in three (30%) patients. Fifty percent of the cases experienced serological response, 70% biochemical response, and all (100%) had histological response. In three cases started concomitant IFN + lamivudine therapy, HBV-DNA became negative at the second month of treatment. CONCLUSIONS: IFN-alpha and lamivudine can be used for the treatment of chronic hepatitis B infection in children.

[Treatment of chronic hepatitis B in children]. / Die Behandlung der chronischen Hepatitis B bei Kindern.

Hepatitis B virus (HBV) infection is an important health problem. It's believed that there are now at least 400 million carriers of HBV in the world. Infants born to HBeAg-positive carrier mothers have a 60% to 90% chance of contracting chronic hepatitis B infection and of possible subsequent progression to cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis B is aimed at sustained suppression of HBV replication and remission of liver disease. Treatment with interferon alpha has a 36% to 45% remission rate after a four-month course of treatment in selected patients. The criteria of good response for the treatment include elevated aminotranspherase levels, the presence of HBV DNA but a level of less than 200 pg/mL, and a liver biopsy suggesting moderate or severe inflammatory activity. Interferon can be used alone or concurrently with lamivudine in chronic hepatitis patients. Although there were hopeful data about the efficacy of lamivudine therapy, the combination of more than one antiviral agent needs to be assessed to improve the actual response rate obtained with interferon-alpha. Preliminary reports suggest that 73% to 86% of patients remained HBeAg-negative after HBeAg seroconversion in clinical trials, but some responders who had early relapse were not included in these follow-up studies, so these results may be overly optimistic.

Correlation between cord blood apelin and IGF-1 levels in retinopathy of prematurity.

AIM: We hypothesized that circulating apelin concentrations in preterm babies might be linked with retinopathy of prematurity (ROP), similar to IGF-1 levels. PATIENTS & METHODS: A total of 97 infants born with a gestational age before 32 weeks in 2007-2009 were screened for ROP at the Gata Haydarpasa Hospital (Turkey). Fourteen of them with classified ROP stage 3-5 comprised our study group. RESULTS: The non-ROP group had higher apelin and IGF-1 levels than ROP neonates at birth. After 4-6 weeks, postnatal ROP subjects had lower apelin and IGF-1 levels than non-ROP controls. At the end of the study, the change in apelin levels was positively correlated with the change in IGF-1 levels (r = 0.852; p = 0.01). CONCLUSION: We suggested that the pathogenesis of ROP, which is regarded as a neovascular retinal disorder, includes variations in the levels of apelin and IGF-1.