Keisuke Nose

Glutamine Prevents Total Parenteral Nutrition-Associated Changes to Intraepithelial Lymphocyte Phenotype and Function: A Potential Mechanism for the Preservation of Epithelial Barrier Function

Total parenteral nutrition (TPN) results in a number of derangements to the intestinal epithelium, including a loss of epithelial barrier function (EBF). As TPN supplemented with glutamine has been thought to prevent this loss, this article further defined the impact of glutamine on EBF, and investigated potential mechanisms that contributed to the preservation of EBF. C57BL/6J male mice were randomized to enteral nutrition (control), TPN, or TPN supplemented with glutamine (TPN+GLN). Changes in intraepithelial lymphocyte (IEL)-derived cytokine expression were measured, and EBF was assessed with electrophysiologic methods and assessment of junctional protein expression. TPN resulted in a significant decline in EBF, and this loss of EBF was significantly prevented in the TPN+GLN group. Coincident with these changes was a loss of intraepithelial lymphocyte (IEL, mucosal lymphocyte)-derived IL-10 and increase in interferon-gamma (IFN-gamma) expression, and a decline in IEL numbers in the TPN group. A prevention in the increase in IFN-gamma and decline in IL-10 expression was seen in the TPN+GLN group. To determine the mechanism responsible for these glutamine-associated cytokine changes, we tested whether blockade of the IL-7 signaling pathway between epithelial cells (EC) and IEL would prevent these changes; however, blockade failed to influence IEL-derived cytokine changes. Glutamine-supplemented TPN leads to a specific IEL-derived cytokine profile, which may account for the preservation of EBF; and such action may be due to a direct action of glutamine on the IEL.

Sensitivity enhancement of fiber-laser-based stimulated Raman scattering microscopy by collinear balanced detection technique

We propose the collinear balanced detection (CBD) technique for noise suppression in fiber laser (FL)-based stimulated Raman scattering (SRS) microscopy. This technique reduces the effect of laser intensity noise at a specific frequency by means of pulse splitting and recombination with a time delay difference. We experimentally confirm that CBD can suppress the intensity noise of second harmonic (SH) of Er-FL pulses by 13 dB.The measured noise level including the thermal noise is higher by only ~1.4 dB than the shot noise limit. To demonstrate SRS imaging, we use 4-ps SH pulses and 3-ps Yb-FL pulses, which are synchronized subharmonically with a jitter of 227 fs. The effectiveness of the CBD technique is confirmed through SRS imaging of a cultured HeLa cell.

Should fundoplication be added at the time of gastrostomy placement in patients who are neurologically impaired

BACKGROUND/PURPOSE Patients who have advanced neurologic impairment (NI) and require gastrostomy placement (GP) frequently have symptomatic gastroesophageal reflux. We investigated the outcomes of GP without fundoplication in patients who had NI. METHODS This was a retrospective review of 54 patients with NI (median, 7 years; range, 1-18 years) undergoing GP alone. The operative criteria included medically controllable or no reflux symptoms. The patients were divided into 2 groups based on the percentage of total esophageal time with a pH less than 4.0 (reflux index, or RI): group I (GI, n = 33), RI less than 5.0% (median age, 6 years; range, 2-15 years); group II (GII, n = 21), RI 5.0% or greater (median age, 10 years; range, 1-18 years). Data are expressed as medians and ranges. RESULTS Nutritional management was successfully conducted after GP with or without the administration of lansoprazole, famotidine, or rikkunshito in all but 2 patients. One GI patient with alpha-thalassemia required fundoplication, and one GII patient with Cockayne syndrome required gastrojejunal tube feeding. The RI increased significantly in GI patients (2.1% [0%-4.8%] vs 4.5% [0.2%-11.4%], P = .004), whereas it decreased significantly in GII patients (11.2% [5.9%-41.6%] vs 9.8% [1.05-26.6%], P = .04). CONCLUSION Gastroesophageal reflux and related symptoms rarely deteriorate to require additional treatment after GP in patients with NI. Gastrostomy placement is a less invasive and effective procedure for improving the quality of life in those patients.

Reliability of the lung to thorax transverse area ratio as a predictive parameter in fetuses with congenital diaphragmatic hernia

PurposeAn accurate prenatal assessment of the patients’ severity is essential for the optimal treatment of individuals with congenital diaphragmatic hernia (CDH). The purpose of this study was to clarify the reliability of the lung to thorax transverse area ratio (L/T) as a prenatal predictive parameter.MethodsA multicenter retrospective cohort study was conducted on 114 isolated CDH fetuses with a prenatal diagnosis during the period between 2002 and 2007 at five participating centers in Japan. The relationship between the gestational age and the L/T was analyzed. The most powerful measurement point and accurate cutoff value of the L/T was determined by an analysis of a receiver operating characteristic curve, which was verified by comparing the patients’ severity.ResultsThere was a negative correlation between the gestational age and the L/T in the non-survivors, and no correlation in the survivors. There were significant differences in the parameters which represented the patients’ severity including the respiratory and circulatory status, the surgical findings, and the final outcomes between the groups divided at 0.080 in the minimum value of the L/T during gestation.ConclusionThe L/T was not strongly influenced by the gestational age, and it was found to be a reliable prenatal predictive parameter in fetuses with isolated CDH.

Physiological and clinical characteristics of gastroesophageal reflux after congenital diaphragmatic hernia repair

BACKGROUND/PURPOSE Gastroesophageal reflux (GER) is an important sequela of congenital diaphragmatic hernia (CDH) repair. This study investigated the physiological and clinical characteristics of GER in CDH survivors. METHODS A total of 52 CDH survivors were investigated retrospectively. Esophageal acid exposure was evaluated with 24-h esophageal pH monitoring in all patients, and esophageal anatomical and motor functional abnormalities were examined with videomanometry in 16 patients. RESULTS Fundoplication was necessary in 1 patient. Medical treatment with acid suppression or rikkunshito, a traditional Japanese medicine, was successful in nine patients, and the reflux symptoms were ameliorated at the age of 3 years. The percentage of total time the esophageal pH was below 4.0 (reflux index: RI) ranged from 0.1 to 44.3%. No patient with an RI < 10% had reflux symptoms requiring treatment. The basal lower esophageal sphincter (LES) tone ranged from 15 to 35 mmHg (median 25 mmHg). Esophageal peristalsis was preserved in all of the patients examined, except one who had failed peristalsis and poor clearance in the dilated esophagus. CONCLUSION The motor function of the esophageal body and LES is usually preserved in CDH survivors despite the wide range of esophageal acid exposure in early infancy. Those with symptomatic GER outgrow it, unless associated with advanced respiratory distress or neurological impairment.

Psychosocial and cognitive consequences of major neonatal surgery

PURPOSE To evaluate the long-term quality of life (QOL) of patients who had undergone major neonatal surgery, the psychosocial and cognitive consequences of neonatal surgical stress were assessed when the patients reached school age. MATERIALS AND METHODS Seventy-two patients who had undergone major neonatal surgery were enrolled in this study. Their primary diseases were anorectal malformation (ARM) in 27 cases, esophageal atresia (EA) in 23, and congenital diaphragmatic hernia (CDH) in 22. Intelligence tests using Wechsler Intelligence Scale for Children III (WISC-III) or a developmental test and the Child Behavior Checklist were conducted through questionnaires and interviews with clinical psychologists. RESULTS Mental retardation (MR) was apparent in 25% of EA, 20% of ARM, and 18% of CDH, significantly higher than the 2% to 3% commonly found in the general population. The clinical range (CR) of the Child Behavior Checklist was seen in 35% of EA, 59% of ARM, and 38% of CDH, which is also significantly higher than the 25% typically seen in the general population. No significant differences in MR and CR were seen among the primary diseases. The most important factors influencing MR and CR remain to be identified. CONCLUSIONS To ensure true quality of life after neonatal surgical stress, pediatric surgeons must consider not only physical assessments but also cognitive, emotional, and psychosocial assessments.

Extralobar pulmonary sequestration with venous drainage to the portal vein: a case report.

Abstract Venous drainage to the portal vein in pulmonary sequestration is rare. A 7-month-old girl was referred to our hospital following surgery for ventricular septal defect because of a left upper abdominal mass with a large feeding artery from the abdominal aorta and venous drainage to the portal vein. She had had frequent pulmonary infections and was growth retarded. MRI demonstrated that the mass was above the left diaphragm, suggesting extralobar sequestration. An extralobar sequestered lung was resected at thoracotomy. Diagnostic problems and clinical features are presented.

Prenatal risk stratification for isolated congenital diaphragmatic hernia: results of a Japanese multicenter study

BACKGROUND/PURPOSE The aim of this study was to establish a prenatal prognostic classification system for risk-stratified management in fetuses with isolated congenital diaphragmatic hernia (CDH). METHODS A multi-institutional retrospective cohort study of isolated CDH, diagnosed prenatally in fetuses delivered during the 2002 to 2007 period at 5 participating institutions in Japan, was conducted. The risk stratification system was formulated based on the odds ratios of prenatal parameters for mortality at 90 days. The clinical severity in CDH infants were compared among the stratified risk groups. RESULTS Patients were classified into the 3 risk groups: group A (n = 48) consisted of infants showing liver-down with contralateral lung-to-thorax transverse area ratio (L/T) ratio ≥0.08; group B of infants showing liver-down with L/T ratio <0.08 or liver-up with L/T ratio ≥0.08 (n = 35), and group C of infants showing liver-up with L/T ratio <0.08 (n = 20). The mortality at 90 days in groups A, B, and C were 0.0%, 20.0%, and 65.0%, respectively. The intact discharge rates were 95.8%, 60.0%, and 5.0%, respectively. This system also accurately reflected the clinical severity in CDH infants. CONCLUSIONS Our prenatal risk stratification system, which demonstrated a significant difference in postnatal status and final outcome, would allow for accurate estimation of the severity of disease in fetuses with isolated CDH, although it needs prospective validation in a different population.

Influence of thoracoscopic esophageal atresia repair on esophageal motor function and gastroesophageal reflux.

BACKGROUND/PURPOSE Thoracoscopic repair has recently been attempted in newborns with esophageal atresia (EA), but it remains unclear whether thoracoscopic dissection reduces pathological gastroesophageal reflux. We investigated the influence of a thoracoscopic approach on esophageal motor function in patients with EA. METHODS Clinical and gastrointestinal data of 10 patients with EA with open repair (group A) and 7 with thoracoscopic repair (group B) were analyzed retrospectively. Videomanometry was conducted to investigate esophageal motor patterns. Esophageal acid exposure was evaluated with 24-hour esophageal pH monitoring. Data are expressed as medians and ranges. RESULTS Contractions in the distal esophagus were conspicuously absent in 1 and 3 patients in groups A and B, respectively (P = .26). There were no significant differences in esophageal acid exposure (5.5% [0.7%-24.6%] vs 3.7% [0.3%-56.8%]; P = .71) or mean esophageal acid reflux time (0.5 minutes [0.1-1.4 minutes] vs 0.5 minutes [0.1-1.3 minutes]; P = .87) between the 2 groups. Fundoplication was conducted in 2 patients in each group (P = .60), all of whom had conspicuously absent distal esophageal contractions. Those contractions were preserved in the remaining patients with the exception of 1 group B patient. CONCLUSION There are unlikely to be benefits from thoracoscopic repair of EA in terms of postoperative esophageal motor function.

Clinical significance of the lung/thorax transverse-area ratio in fetuses with cystic lung disease

Abstract We examined the clinical significance of the lung-thorax transverse-area ratio (L/T) in fetuses with cystic lung disease (CLD). The transverse section of the thorax was analyzed at the level of the 4-chamber view of the heart. L/T was calculated as the bilateral normal lung area divided by the thoracic area. Within a 9-year period, ultrasonography was performed in 15 fetuses with CLD, 13 of which were histologically diagnosed: congenital cystic adenomatoid malformation of the lung (CAM; n = 8), pulmonary sequestration (n = 4), and bronchial atresia (n = 1). Although the initial L/T measurement (29.6 ± 4.2 weeks) showed significantly lower values than in the controls, the final measurement (36.4 ± 1.6 weeks) indicated that the L/T in CLD excluding CAM was significantly higher than that in CAM. Six patients with a final L/T of less than 0.21 required mechanical ventilation immediately after birth. Two of these patients died, and the autopsy findings indicated pulmonary hypoplasia. In these cases, a significant correlation was observed between the maximal value of L/T and preductal alveolar-arterial oxygen difference (A-aDO2), although the final L/T was not correlated to A-aDO2. These results indicate that serial measurements of L/T may be useful in the diagnosis of CLD and may help to predict postnatal respiratory conditions.