M. Mansur Tatli

Mesenchymal Stem Cell Therapy in Necrotizing Enterocolitis: A Rat Study

We evaluated the potential therapeutic use of exogenous human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in an experimental rat model of necrotizing enterocolitis (NEC). Thirty-six newborn Sprague-Dawley rats were randomly divided into three groups: NEC, NEC + hBM-MSC, and a control (control and control + hBM-MSC). NEC was induced by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. After NEC was induced, iron-labeled hBM-MSCs were administered by intraperitoneal injection. All pups were killed on the fourth day following injection, and the terminal ileum was excised for a histopathological and immunohistochemical evaluation. The pups in the NEC + hBM-MSC group showed significant weight gains and improvements in their clinical sickness scores (p < 0.01). Bowel damage severity observed in the histopathological evaluation was significantly lower in the NEC + hBM-MSC group than that in the NEC group (p = 0.012). The number of MSCs homing to the bowel was significantly higher in the NEC + hBM-MSC group than that in the control + hBM-MSC group. In conclusion, this is the first study that has evaluated the effectiveness of hBM-MSCs in a neonatal rat NEC model. MSCs reduced histopathological damage significantly.

A chromosomal-effect study of intensive phototherapy versus conventional phototherapy in newborns with jaundice

In this study, we aimed to make a comparison between chromosomal effects caused by conventional phototherapy and intensive phototherapy in jaundiced newborns. The study group included 83 newborns with gestation age of > or =35 weeks, and on days 3-10 after birth. Newborns were divided into four groups on the basis of total serum bilirubin (TSB) levels upon admission and need for phototherapy. The intensive group (n=19) consisted of newborns who received light-emitting diode (LED) phototherapy, the conventional group (n=23) consisted of newborns who received conventional phototherapy, the jaundiced control group (n=21) consisted of newborns whose TSB levels were higher than 10mg/dL (average = 13.7 + /-1.5 mg/dL) on admission and who did not receive phototherapy, and the non-jaundiced control group (n=20) consisted of newborns whose TSB levels were less than 5 mg/dl (average = 3.6 +/- 0.8 mg/dL). TSB level of the intensive group at admission was 20.2 +/- 1.3 mg/dL, whereas the level of conventional group was 19.6 +/- 1.5 mg/dL. Blood samples were taken from all infants on admission to determine sister chromatid exchange (SCE1) frequency. Blood sampling was repeated on discharge (SCE2) of infants who had received phototherapy. Demographic information, hospitalization details and the rate of decline in TSB were recorded, and frequencies of SCE1 and SCE2 were compared. There was no difference in demographic information among the four groups. SCE1 frequencies in 50 metaphases were evaluated in the intensive, conventional, jaundiced control and non-jaundiced control groups, and the SCE1 frequency was determined as 9.37/cell, 9.54/cell, 9.23/cell and 6.17/cell, respectively. The SCE1 frequency of the jaundiced groups (intensive, conventional and newborns-with-jaundice control group) was significantly higher than that in the non-jaundiced control group (p = 0.001). There was no significant difference between the intensive group and the conventional group in SCE2 frequency (13.5/cell vs. 13.55/cell, p = 0.39). SCE2 frequency was higher than SCE1 frequency in both the intensive and conventional groups (p = 0.001). A strong correlation was found between admission TSB and SCE1 frequency (p = 0.001; r = 0.79). The rate of decline in TSB was higher in the intensive group compared with the conventional group (0.26mg/(dLh) vs. 0.14 mg/(dLh); p = 0.001). We found that intensive and conventional phototherapies similarly increase SCE frequency in newborns. There was a strong, positive correlation between the TSB-on-admission level and SCE1 frequency. In the light of this study, we may conclude that intensive and conventional phototherapies may have an effect on chromosomes in jaundiced newborns. TSB levels higher than 10mg/dL are, too, reported hazardous on chromosomes. Further studies are warranted to elucidate this relationship.

Moderate hypernatremic dehydration in newborn infants: Retrospective evaluation of 64 cases

Objectives. This study was carried out to assess the incidence, presenting complaints, risk factors, and methods for prevention of hypernatremic dehydration among term and near-term breastfeeding infants. Methods. We retrospectively evaluated term and near-term (≥35 weeks of gestation) neonates admitted to our neonatology department, during a four-year period with serum sodium concentrations of ≥146 mEq/L. A detailed maternal and infant history and examination including presenting complaints, risk factors, feeding problems, and weight loss, if present, were registered. Results. Among 1150 neonates admitted to our unit, 64 (5.6%) had serum sodium concentrations of >145 mEq/L, in whom 43 of them had sodium concentrations of >149 mEq/L. The most common presenting complaint was jaundice in 30 patients (48%). Forty-one (95%) of the 43 patients described a more than 7% weight loss and there was a positive correlation between serum sodium and urea and creatinine concentrations, and a negative correlation between serum sodium and glucose concentrations in these patients (p < 0.05). There was no difference between patients with sodium >149 mEq/L and <149 mEq/L with respect to maternal age, parity, educational level, hospital stay, type of delivery, and anesthesia and also with respect to seasons (p > 0.05). Conclusions. Weight loss in an infant of greater than 7% from birth weight increases the risk of hypernatremia, a weight loss limit that is lower than the previously reported 10%. This indicates possible breastfeeding problems and requires more intensive evaluation of breastfeeding and possible interventions to correct problems and improve milk production and transfer.

N-acetylcysteine may prevent severe intestinal damage in necrotizing enterocolitis

OBJECTIVE The aim of this study was to evaluate the preventive effect of N-acetylcysteine (NAC) on the development of necrotizing enterocolitis (NEC) in an experimental rat model. MATERIAL AND METHODS Thirty newborn Sprague-Dawley rats were randomly divided into 3 groups: NEC, NEC + NAC, and control. Necrotizing enterocolitis was induced by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. Pups in the NEC + NAC group were administered NAC at a dose of 150 mg/kg daily by intraperitoneal route from the first day until the last day of the study. All pups were killed on the fifth day. Proximal colon and ileum were excised for histopathologic, immunohistochemical (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling and caspase-3, caspase-8, caspase-9), and biochemical evaluation, including xanthine oxidase, total antioxidant status, total oxidant status, malondialdehyde, and myeloperoxidase activities. RESULTS The pups in the NEC + NAC group had better clinical sickness scores compared with those in the NEC group (P < .05). In histopathologic and apoptosis evaluations (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling and immunohistochemical evaluation for caspase-3 and caspase-9), the severity of bowel damage was significantly less in the NEC + NAC group compared with the NEC group (P < .01). Tissue malondialdehyde, myeloperoxidase, xanthine oxidase levels, and total oxidant status were significantly decreased in the NEC + NAC group, whereas total antioxidant status (TAS) was significantly increased in the NEC + NAC group (P < .01). CONCLUSION N-acetylcysteine therapy significantly reduced the severity of intestinal damage in NEC.

Surfactant treatment for neonatal respiratory disorders other than respiratory distress syndrome

Abstract Background: It is suggested that there may be expanded use of surfactant replacement for the neonatal diseases such as meconium aspiration syndrome (MAS), pneumonia and possibly bronchopulmonary dysplasia (BPD). Objective: To evaluate the characteristics and short-term outcome of the neonates given exogenous surfactant because of the diseases other than respiratory disease syndrome (RDS). Methods: This retrospective study included 35 neonates admitted to the neonatal intensive care unit from January 2012 to December 2012 for an expanded use of surfactant. Data related to gestational age, birth weight, gender and perinatal risk factors were obtained from the patients’ records. The short-term prognosis was also noted. Results: The diagnosis was sepsis in 16 patients, eight MAS, seven transient tachypnea of the newborns (TTN) and four BPD. Mean gestational age was 35.6 ± 4.5 weeks and mean birth weight was 2661 ± 981 g. Of overall cases, 65% were boys and 35% girls. The mortality rate was 17%. Of six fatal cases, three was with BPD, two with sepsis and one with MAS. Conclusion: We think that surfactant replacement may be life saver in the neonatal diseases other than RDS such as BPD, MAS and sepsis by rapidly improving oxygenation. Further investigation is necessary to validate the significance of expanded use of surfactant.

Is bicarbonate solution tolerated better than Shohl’s solution in neonatal renal tubular acidosis?

Sirs, Distal renal tubular acidosis (dRTA) was first recognized by Albright et al. as a distinct entity in 1946 [1]. The clinical syndrome described hypokalemia, hyperchloremic metabolic acidosis, inability to lower urine pH below 5.5, nephrocalcinosis, nephrolithiasis and potassium depletion. Additional features included osteomalacia or rickets. The syndrome was designated as “distal renal tubular acidosis” because the establishment of a large pH gradient between urine and blood is the function of the distal nephron. Distal RTA is almost always observed in children as a primary entity inherited in both autosomal dominant and recessive patterns [2]. If detected early in life, therapeutic correction of the acidosis by continuous alkali administration may induce resumption of normal growth, arrest of nephrocalcinosis, and preservation of renal function [2]. We describe the case of a 20-day-old girl with dRTA associated with hypokalemia, metabolic acidosis and dehydration. The girl was born at 40 weeks of gestation, weighing 3,250 g. Her parents described a sister diagnosed with dRTA and treated with Shohl’s (potassium or sodium citrate) solution in the neonatal period. The sister could not tolerate the solution and suffered persistent vomiting and diarrhea, which resulted in death at 4 months. At 20 days of age, the patient was admitted to our outpatient clinic for weight loss (body weight loss 110 g), dehydration, and generalized weakness. Laboratory examination on admission revealed severe acidemia (pH 7.27, PCO2 27 mmHg, plasma bicarbonate 12 mmol/l, base excess −12.4 mmol/l) and a high urine pH (pH=8). Serum analysis revealed sodium 138 mmol/l, chloride 118 mmol/l, total calcium 11.6 mmol/l, ionized calcium 1,26 mmol/l, phosphorus 6.4 mmol/l, urea 58 mg/dl, creatinine 0.6 mg/dl, glucose 83 mg/dl and serum alkaline phosphatase 537 IU/l. Pyuria was noted. However, urine cultures on two occasions showed no growth. No significant protein, glucose, or amino acid was detected in the urine. The urine anion gap (Na + K Cl) was +86 mmol/l [normal range: −10 to +10 mmol/l]. The urinary calcium/creatinine ratio was 0.52 (normal values for infants are below 0.6). Renal ultrasonography was normal. A diagnosis of distal RTA was made, and treatment with sodium bicarbonate infusion was initiated. Two days after admission, infusion was stopped. Shohl’s solution was initiated at a dose of 2 mEq kg day and increased to 16 mEq kg day. Oral potassium citrate, about 2 mEq body weight per day, was added to treat hypokalemia. Vomiting and diarrhea were observed under treatment with Shohl’s solution. Plasma bicarbonate concentrations decreased from 17 to 9 mmol/l and serum pH was 7.1. Metabolic acidosis was treated with bicarbonate infusion and thereafter per oral 2 mmol kg day sodium bicarbonate was initiated. Under sodium bicarbonate and potassium citrate therapies, pH increased to 7.44, PCO2 to 40 mmHg, plasma bicarbonate to 27 mmol/l, base excess to +3.2 mmol/l and potassium to 3.7 mmol/l. No vomiting or diarrhea was observed. In the second month her body weight was 4,450 g, pH 7.42, PCO2 40 mmHg, plasma bicarbonate 28 mmol/l, base excess +3 and potassium 4 mmol/l. Pediatr Nephrol (2007) 22:152–153 DOI 10.1007/s00467-006-0249-5

Multiply the weight of a low-birthweight newborn by six; find out how necessary the phototherapy is: A new Esperanto?

Sir,Hyperbilirubinaemia in premature infants is moreprevalent, more severe, and its course more protractedthan in term neonates as a result of exaggerated levelsof neonatal red cell, hepatic and gastrointestinalimmaturity [1]. In spite of its importance, studiesand nomograms regarding hyperbilirubinaemia inlow-birthweight infants are limited. Guidelines pub-lished by the American Academy of Pediatrics (AAP)in 2004 are concerned with hyperbilirubinaemia interm and near-term babies [2].There are two important studies in the literatureabout the levels for beginning phototherapy inlow-birthweight (LBW) infants. Maisels reportedlimits for phototherapy of 85 120 mmol/l (5 8 mg/dl) in B