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We investigated whether multiple food allergies could be safely prevented by simultaneously administering very small amounts of multiple foods.Infants 3-4 months old with atopic dermatitis from 14 primary care pediatric clinics in Japan were enrolled in this randomized, placebo-controlled trial. The infants were administered either mixed allergenic food powder (MP) containing egg, milk, wheat, soybean, buckwheat, and peanuts, or placebo powder (PP). The amount of powder was increased in a stepwise manner on weeks 2 and 4, and continued until week 12. The occurrence of food allergy episodes after powder intervention was assessed at 18 months old. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000027837).A total of 163 participants were randomly allocated to either the MP group (n = 83) or the PP group (n = 80). The incidence of food allergy episodes by 18 months was significantly different between the MP and PP groups (7/83 vs. 19/80, respectively; risk ratio 0.301 [95% CI 0.116-0.784]; P = 0.0066). Egg allergies were reduced in the MP group. In addition, food allergy episodes from any of the other five foods were significantly reduced, although the reductions in those due to individual foods were not significant.Gradually increasing the intake of very small amounts of multiple foods in early infancy can safely reduce the incidence of egg allergies. Other foods may also suppress food allergies, but no definitive conclusions could be reached.

Background: There is controversy regarding the efficacy and side effects of proactive administration of allergenic foods in early infancy to prevent food allergies. This is the first trial involving the gradual introduction of trace amounts of multiple foods to infants. Methods: Infants under 4 months old with atopic dermatitis from 14 primary care pediatric clinics in Japan were enrolled in this randomized, double-blind, placebo-controlled trial. The infants were administered either mixed allergenic food powder (MP) containing eggs, milk, wheat, soybeans, buckwheat, and peanuts, or placebo powder (PP). The amount of powder was increased in a stepwise manner on weeks 2 and 4 and continued until week 12. Weaning food was started subsequently according to the Japanese guidelines for nursing/bottle feeding, and for baby food. The occurrence of food allergy episodes after powder intervention was assessed at 18 months old by the physician responsible for each participant. Findings: A total of 163 participants were randomly allocated to either the MP group (n = 83, 50.9%) or the PP group (n = 80, 49.1%). There was a significant difference in the incidence of food allergy episodes by 18 months between the MP and PP groups (7/83 vs. 19/80, respectively; risk ratio 0.301 [95% CI 0.116 – 0.784]; P = 0.008). No serious adverse events attributable to MP were observed. Interpretation: Gradually increasing the intake of trace amounts of multiple foods in early infancy can safely reduce the incidence of food allergies. Clinical Trial Registration Details: UMIN000027837. The protocol for this study and the subsequent changes are available on the UMIN-CTR Trial website. Funding Information: This study was self-funded and did not receive any other support. Declaration of Interests: The authors declare that no conflicts of interest exist. Ethics Approval Statement: Written informed consent was obtained from the parents of the participants at the time of enrollment. The study was approved by the institutional review board of Umezu Clinic.

To establish a strategy for congenital cytomegalovirus (cCMV) screening and to establish confirmatory assays approved as in vitro diagnostics by the regulatory authorities, we evaluated the clinical risks and performance of diagnostic assays developed by commercial companies, since cCMV infection has significant clinical consequences.Newborns with clinical manifestations considered to be consequences of cCMV infection (n = 575) were screened for the presence of cytomegalovirus (CMV) DNA in urine specimens collected onto filter paper placed in their diapers using the polymerase chain reaction-based assay reported previously. Liquid urine specimens were obtained from all of 20 CMV-positive newborns and 107 of the CMV-negative newborns identified in the screening. We used these 127 specimens, as well as 12 from cCMV cases identified in a previous study and 41 from healthy newborns, to compare the performance of 2 commercial assays and 1 in-house assay.The risk-based screening allowed the identification of cCMV cases at least 10-fold more efficiently than our previous universal screening, although there appears to be a limit to the identification of asymptomatically infected newborns. Although CMV-specific IgM during pregnancy was found frequently in mothers of cCMV newborns, CMV-IgM alone is not an effective diagnostic marker. The urine-filter-based assay and the 3 diagnostic assays yielded identical results.Although risk-based and universal newborn screening strategies for cCMV infection each have their respective advantages and disadvantages, urine-filter-based assay followed by confirmatory in vitro diagnostics assays is able to identify cCMV cases efficiently.

Infants with Down Syndrome (DS) are at risk of developing a transient abnormal myelopoiesis (TAM). TAM is characterised by increased circulating blast cells but usually self-limiting. DS patients with TAM sometimes show fetal hydrops and effusion in body cavities, but the mechanism remains unclear. We report here a case of infant with DS who had pericardial effusion, TAM, and eosinophilia. In her pericardial effusion, white blood cell count was 6.0 × 103/µL, 41% of which were eosinophils. After administration of prednisolone, pericardial effusion gradually decreased, and TAM and eosinophilia improved. In order to elucidate the immunological mechanism, we measured the levels of 17 cytokines in her pericardial effusion fluid and serum. In her pericardial fluid, there were high levels of 12 cytokines, and they were higher than those in her serum. In particular, IL-6 (44,573 pg/mL), IL-8 (4,865 pg/mL), and IL-13 (579.41 pg/mL) were at extremely high levels in her pericardial fluid. After administration of prednisolone, the levels of 8 of the 12 elevated cytokines in her pericardial fluid decreased and all of the elevated cytokines decreased in her serum. Corticosteroids can be effective to reduce cytokine levels and the amount of effusion in patients with DS. It is presumed that effusion seen in DS with TAM could be related to an abnormal production of cytokines at the effusion site.

Neonatal or infantile uterine prolapse is a quite rare condition and is usually managed with conservative treatment. There is no standard surgical treatment for infantile uterine prolapse, and to the best of our knowledge, only 2 out of 30 patients suffering from it have been reported to undergo surgical repair in English literature since 1961. We here report the first successful case of laparoscopic repair for uterine prolapse in an infant. The patient was a 2-month old girl who had sacral myelomeningocele and Chiari type 2 malformation. She had undergone closure of myelomeningocele and ventriculoperitoneal shunting within 6 weeks after birth. At 7 weeks of age, the rectum and the uterus prolapsed, and the prolapse gradually deteriorated. Conservative treatments including repeated digital reduction, use of ointment and glycerin enema, and placement of a Foley catheter into the vagina were not effective. At the age of 100 days, she underwent laparoscopic hysteropexy and rectopexy. Three ports were placed on the umbilicus and the bilateral abdomen, and the bilateral mesovaria were sutured to the anterior abdominal wall to improve the visualization of the pelvis. The rectum and the uterine body were directly sutured to the sacral promontory with 2 non-absorbable braided sutures each, not using mesh prosthesis. The postoperative course was uneventful and neither uterine nor rectal prolapse has recurred for 2.5 years. We plan to follow up the patient for a long period since the long-term prognosis is not known.

Background Preterm infants are at significant risk of reduced bone mineral content and subsequent bone disease (metabolic bone disease of prematurity, MBDP). MBDP is frequently found in very low-birthweight (VLBW) infants, but long-term height prognosis is not well known. Methods VLBW infants from two major neonatal intensive care units were studied. Medical records were reviewed. A total of 143 subjects were analyzed after excluding subjects who died, or who had severe complications that could affect linear growth, Silver–Russell syndrome, severe cholestasis, and/or chromosomal abnormality. The relationship between MBDP and height at age 3 was investigated. Results Height standard deviation score (SDS) at age 3 negatively correlated with peak serum alkaline phosphatase (ALP) activity in early life (r = −0.30, P = 0.0003) and positively correlated with serum phosphorus (P) at peak ALP (r = 0.33, P = 0.0002). In addition, serum P independently affected height SDS at 3 years of age (β = 0.19, P = 0.018), and was significantly different between infants with and without catch-up growth in height (difference: 0.23 mmol/L, 95%CI: 0.09–0.36, P = 0.0010). Conclusions MBDP, particularly hypophosphatemia in the early period of life, is associated with linear growth until 3 years of age in VLBW infants.

Embedded systems that realize specific functions are usually hardware constrained systems running dedicated software. These embedded systems rarely take into account the possibility to change functions after their release. As a result, it would be difficult to change some function from outside an embedded system in its operational environment. In order to keep up with the need of quickly reacting to changes affecting requirements and environments, it is paramount to find a way to update the functions of these systems. We constructed a programming framework for updating functions based on the MAPE loop mechanism, which is generally used to develop self-adaptive systems. We regard MAPE loop as a set of independent components that make it easy to separate the updating functions from other functions. We apply our framework to a web application and an embedded system. The proposed framework is independent of the target embedded system and makes it possible to easily inject new functions into it.

A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants.

Herein is described a case of neonatal neuroblastoma with cyclic blood pressure fluctuation and elevated catecholamines. The fluctuations stabilized after treatment with α-adrenergic blocker and the perioperative course was uneventful. The possibility of catecholamine-related symptoms including hypertension, heart failure, and blood pressure fluctuations should be considered in the treatment for neuroblastoma; if they are present, treatment with α-blockers is effective.

Neonatal subgaleal hemorrhage (SGH) is a serious adverse event that is often underestimated and sometimes goes unrecognized. It can cause bleeding complications and jeopardize the patient's life. Early diagnosis and prompt treatment are important in optimizing the outcome in neonates with SGH. Herein we describe the case of a newborn who developed severe SGH and died. We report unenhanced computed tomography (CT) of ongoing SGH, which showed a low-density region in the surrounding area of the head. The density could be explained by unclotted active bleeding and low hematocrit. Even if a patient with clinically suspected SGH has a low-density region on CT, the presence of SGH should not be excluded.

A violet divalent europium-doped strontium aluminate (Sr–Al–O:Eu2+) phosphor particle was synthesized from a metal-ethylenediaminetetraacetic acid (EDTA) solution of Sr, Al, Eu, and particulate alumina via spray drying and sintering in a reducing atmosphere. The emission properties, crystal structures, cross-sectional emissions, and elemental distributions of the obtained Sr–Al–O:Eu2+ phosphor particles were investigated. The product was determined to be secondary SrAl12O19:Eu2+ particles with an average diameter of 20 μm. The violet SrAl12O19:Eu2+ emission phase was found in a 1-μm-thick coating of the particles where elemental Al diffusion occurred. These particles are anticipated to find commercial applications such as paints.

To determine whether skin and subcutaneous blood flow measurements using a novel laser Doppler flow meter are useful for evaluating the cardiovascular status of very low birth weight (VLBW) infants during the early postnatal period.In eight VLBW infants and eight non-VLBW infants born at Tokyo University Hospital between May 2007 and April 2008, forehead and lower limb skin blood flows were measured continuously for 72 h. Data were averaged every 8 h, and the t-test was used for analysis.In VLBW infants, forehead blood flow started to increase from the start of measurement to 32 h (16.6 +/- 3.9 ml/min vs. 24.1 +/- 2.1 ml/min; p = 0.002 compared with 8 h) and remained constant thereafter. Lower limb blood flow increased rapidly after 24 h (22.2 +/- 5.5 ml/min vs. 29.5 +/- 5.0 ml/min; p = 0.002 compared with 8 h) and continued increasing thereafter. In contrast, blood flows remained constant in non-VLBW infants.The results showed that skin and subcutaneous perfusion in VLBW infants increased spontaneously at around 24 h. Differences in blood flow changes between VLBW and non-VLBW infants demonstrate that these parameters successfully identified physiological changes in tissue perfusion in VLBW infants.

Complete urorectal septum malformation sequence (URSMS) is usually a lethal anomaly that is characterized by urethral obstruction, imperforate anus, ambiguous genitalia, renal agenesis or dysplasia, and mullerian duct maldevelopment. This anomaly is thought to be caused by the cessation of urorectal septum migration toward the caudal cloacal membrane. Teratogenic factors or a genetic abnormality is postulated as the etiology. To date, only 4 patients with URSMS have survived the neonatal period; however, 2 of these infants died before the age of 1 year. We report the survival in a case with complete URSMS who had moderate pulmonary hypoplasia and preserved left renal function. The cloacal remnant wasdilated more than expected because the wall of the muscle layer was torn, perhaps in early fetal life, and timely placement of vesico-amniotic shunts prevented severe pulmonary hypoplasia caused by oligohydramnios.

Mutations in ACTN1, the gene encoding the actin-crosslinking protein α-actinin-1, cause autosomal dominant macrothrombocytopenia. α-Actinin-1 exists as antiparallel dimers, composed of an N-terminal actin-binding domain (ABD), four spectrin-like repeats (SLRs), which form the spacer rod, and a C-terminal calmodulin-like (CaM) domain. All of the previously reported ACTN1 mutations associated with macrothrombocytopenia reside within the ABD and the CaM domain and not within the SLR domain. In this report, we describe a mutation in SLR2 of α-actinin-1 (p.Leu395Gln) associated with familial macrothrombocytopenia. A 3-year-old boy and his mother both had this mutation. They showed a mild form of thrombocytopenia without severe bleeding, accompanied by an elevated mean platelet volume. Consistent with the previous reports of mutations that reside in the ABD or the CaM domain, immunofluorescence examination revealed disorganization of the actin cytoskeleton in Gln395 mutant-transduced Chinese hamster ovary cells. Our findings suggest a novel mechanism for the pathogenesis of ACTN1-related macrothrombocytopenia that does not involve functional domain mutations.

Many authors have suggested that the mechanism by which atelectasis contributes to injury is through the repetitive opening and closing of distal airways in lung regions that are atelectatic. However, neither the topographic nor mechanistic relationships between atelectasis and distribution of lung injury are known.To investigate how atelectasis contributes to ventilator-induced lung injury.Surfactant depletion was performed in anesthetized rats that were then allocated to noninjurious or injurious ventilation for 90 min.Lung injury was quantified by gas exchange, compliance, histology, wet-to-dry weight, and cytokine expression, and its distribution by histology, stereology, cytokine mRNA expression, in situ hybridization, and immunohistochemistry. Functional residual capacity, percent atelectasis, and injury-induced lung water accumulation were measured using gravimetric and volumetric techniques.Atelectasis occurred in the dependent lung regions. Injurious ventilation was associated with alveolar and distal airway injury, while noninjurious ventilation was not. With injurious ventilation, alveolar injury (i.e., histology, myeloperoxidase protein expression, quantification, and localization of cytokine mRNA expression) was maximal in nondependent regions, whereas distal airway injury was equivalent in atelectatic and nonatelectatic regions.These data support the notion that lung injury associated with atelectasis involves trauma to the distal airways. We provide topographic and biochemical evidence that such distal airway injury is not localized solely to atelectatic areas, but is instead generalized in both atelectatic and nonatelectatic lung regions. In contrast, alveolar injury associated with atelectasis does not occur in those areas that are atelectatic but occurs instead in remote nonatelectatic alveoli.

Reduction of perivascular pH in acidemia produces hyporesponsiveness of vascular bed to vasoconstrictors. In the present study, we examined the effects of modest acidification on dilatory responses of isolated rat thoracic aorta. Acetylcholine produced endothelium-dependent relaxation in phenylephrine-precontracted aorta, which was markedly enhanced by acidification of Krebs-Henseleit solution from pH 7.4 to 7.0. A similar augmentation was observed in the relaxing responses to NO donors (SNP, SIN-1, SNAP), 8-Br-cGMP and NS-1619 (a putative K(Ca) channel opener and/or Ca channel inhibitor) in endothelium-denuded, phenylephrine-contracted aorta. However, papaverine-induced relaxation was not affected by the change in pH. At pH 7.4, the relaxing responses to acetylcholine and SNP were partially inhibited by charybdotoxin (K(Ca) channel inhibitor) but not glibenclamide (K(ATP) channel inhibitor), while at pH 7.0 the relaxation induced by either drug was not affected by K(+) channel inhibitors. Relaxation induced by 8-Br-cGMP or NS-1619 was not inhibited by charybdotoxin or glibenclamide. Acidification to pH 7.0 increased the cGMP production in response to acetylcholine in endothelium-intact aorta and to SNP in endothelium-denuded aorta. These results show that modest acidification augments NO-mediated relaxation in rat aorta, probably due to an enhancement of cGMP-dependent but K(+) channel-unrelated relaxation mechanisms.

A theoretical expression for a range of the d/P0 ratio in which two distinct states exist in the equilibrium condition has been derived as a function of Asa0d/K, where Asa0 is the azimuthal anchoring energy, K the elastic constant and d the cell thickness. An expression for the lower limit of azimuthal anchoring energy exhibiting two distinct states has been derived. Theoretical calculations have been performed on the bi-stable energy curve which has two minimal energy levels corresponding to bi-stable states. It has been shown that the energy barrier between the two states mainly originates from the azimuthal anchoring energy and the height of the energy barrier is affected by the d/P0 ratio and cell thickness.

Preterm infants are at significant risk of reduced bone mineral content and subsequent bone disease (metabolic bone disease of prematurity, MBDP). MBDP is frequently found in very low-birthweight (VLBW) infants, but long-term height prognosis is not well known.VLBW infants from two major neonatal intensive care units were studied. Medical records were reviewed. A total of 143 subjects were analyzed after excluding subjects who died, or who had severe complications that could affect linear growth, Silver-Russell syndrome, severe cholestasis, and/or chromosomal abnormality. The relationship between MBDP and height at age 3 was investigated.Height standard deviation score (SDS) at age 3 negatively correlated with peak serum alkaline phosphatase (ALP) activity in early life (r = -0.30, P = 0.0003) and positively correlated with serum phosphorus (P) at peak ALP (r = 0.33, P = 0.0002). In addition, serum P independently affected height SDS at 3 years of age (β = 0.19, P = 0.018), and was significantly different between infants with and without catch-up growth in height (difference: 0.23 mmol/L, 95%CI: 0.09-0.36, P = 0.0010).MBDP, particularly hypophosphatemia in the early period of life, is associated with linear growth until 3 years of age in VLBW infants.

Potent antihypertrophic effect of the bradykinin B2 receptor system on the renal vasculature. Background Angiotensin type 1 (AT1) receptor-deficient mice ( Agtr1 -/-), which selectively lack both AT1A and AT1B receptor genes, are characterized by marked intrarenal vascular thickening. In the present study, we explored the possible involvement of the kinin-kallikrein system in the development of this renal vascular hypertrophy. Methods Wild-type and Agtr1 -/- mice were examined for the developmental regulation pattern of the kinin-kallikrein system and treated with aprotinin (a kallikrein inhibitor), AcLys [D-b Nal 7 , Ile 8 ] des-Arg 9 -bradykinin (a bradykinin B1 receptor antagonist), or Hoe-140 (a bradykinin B2 receptor antagonist) from 3 to 14 days of age. Results The normal postnatal up-regulation of kininase II was organ-specifically suppressed in Agtr1 -/- kidneys at 2 and 3 weeks of age. Immunohistochemical staining in Agtr1 -/- mice revealed tissue kallikrein staining along the nephron from connecting tubules to cortical collecting tubules in proximity to the hypertrophic vasculature, whereas tissue kallikrein staining was confined to connecting tubules in wild-type mice. Aprotinin and Hoe-140 accelerated the vascular hypertrophy significantly as determined by wall thickness ratio, whereas B1 receptor antagonism had no effect. Conclusion The kinin-kallikrein system in the Agtr1 -/- mouse kidney is functionally activated by local suppression of kininase II and extensive redistribution of kallikrein to perivascular areas. This activation, specific to the kidney, serves to dampen a development of the marked vascular hypertrophy. These results demonstrate, to our knowledge for the first time, the antihypertrophic effect of the bradykinin B2 receptor system on the renal vasculature in vivo.

The embryonic development of mammalian kidneys is completed during the perinatal period with a dramatic increase in urine production, as the burden of eliminating nitrogenous metabolic waste shifts from the placenta to the kidney. This urine is normally removed by peristaltic contraction of the renal pelvis, a smooth muscle structure unique to placental mammals. Mutant mice completely lacking angiotensin type 1 receptor genes do not develop a renal pelvis, resulting in the buildup of urine and progressive kidney damage. In mutants the ureteral smooth muscle layer is hypoplastic and lacks peristaltic movements. We show that angiotensin can induce the ureteral smooth muscles in organ cultures of wild-type, but not mutant, ureteral tissues and that, in wild-type mice, expression of both renal angiotensin and the receptor are transiently upregulated at the renal outlet at birth. These results reveal a new role for angiotensin in the unique cellular adaptations of the mammalian kidney to the physiological stresses of postnatal life.

It was experimentally observed that the number of spike-like noise was increased as the anode approached the emitter, under bad vacuum conditions of 10 −6 Torr. The duration of the stable emission also decreased upon approaching the anode to the emitter. It is numerically solved that the number of generated gas molecules and ions by electron-stimulated desorption on the anode surface come to the emitter surface. Under UHV (ultra-high vacuum), the number was not much affected by the distance. On the other hand, under bad vacuum conditions, the number was increased largely as the anode approached the emitter. It suggests that the gas molecules and/or ions generated at the anode surface hitting the emitting area on the emitter is affected by the emitter to anode distance.

We null mutated the mouse angiotensin type 1B (AT1B) receptor gene (Agtr1b) by gene targeting. To identify the specific cell types carrying high Agtr1b gene transcriptional activities, the AT1B coding exon was replaced with a reporter gene, lacZ. In 6- to 8-wk-old Agtr1b -/- mice, high AT1B transcriptional activity was observed in adrenal zona glomerulosa cells and the testis, including mature and immature spermatic cells, whereas low activity was detected homogeneously in anterior pituitary cells and choroidal plexus vessel walls. A similar pattern was observed in Agtr1b +/- mice with less intensity. Microscopically, the anterior pituitary, heart, adrenal, zona glomerulosa, kidney, and the testis of Agtr1b -/- mice were intact and were indistinguishable from those of Agtr1b +/+ mice. Systemic blood pressure was comparable in Agtr1b -/- and Agtr1b +/+ mice. Moreover, plasma aldosterone level was comparable between the two mouse groups. No compensatory enhancement of AT1A mRNA was found in the kidney and adrenal gland of Agtr1b -/- mice. The observed absence of the abnormal phenotypes in Agtr1b -/- mice, which have been described for homozygous angiotensinogen null mutant mice, indicates that 1) AT1A receptors can take over the role of AT1B receptors in Agtr1b -/- mice or 2) functionally significant non-AT1, non-AT2 receptor(s) may exist for the action of angiotensin.

We measured urinary nitrite/nitrate (NOx − ) excretion, an index of endogenous nitric oxide formation, in term and preterm infants aged 1 week and 1, 4, 7 months. In normal term infants, urinary NOx − excretion increased from 1 week to 1 month and then decreased until 4 months where it stabilized thereafter. Urinary NOx − excretion in preterm infants was significantly higher compared with term infants at 1 week of age. This finding suggests that the nitric oxide pathway in preterm infants may be activated compared with term infants in early life. With the reference values obtained in this study, this urinary marker can now be used for identifying infants with abnormal nitric oxide production.

骨格系の代謝の基本は破骨細胞による骨吸収と骨芽細胞による骨形成の繰り返しである。これらの細胞は全身性因子の統御の下，様々な局所因子を分泌しauto-crine/paracrine 的に互いの機能調整を行っている。 本稿では，その広範な生理的役割が注目されている一酸化窒素 (NO) が骨組織における強力な局所メディエータであることを支持する最近の研究成果を紹介した。とくに，成長期ラットの骨発育においてinducible型のNO合成酵素活性が重要な役割を果たすことを証明したわれわれの研究について詳述した。最後に，NOの骨代謝調節機構を対象とする研究の将来の方向性に触れた。

Neonatal subgaleal hemorrhage (SGH) is a serious adverse event that is often underestimated and sometimes goes unrecognized. It can cause bleeding complications and jeopardize the patient's life. Early diagnosis and prompt treatment are important in optimizing the outcome in neonates with SGH. Herein we describe the case of a newborn who developed severe SGH and died. We report unenhanced computed tomography (CT) of ongoing SGH, which showed a low-density region in the surrounding area of the head. The density could be explained by unclotted active bleeding and low hematocrit. Even if a patient with clinically suspected SGH has a low-density region on CT, the presence of SGH should not be excluded.

We examined the effects of chronic nitric oxide (NO) blockade on bone mineral status in growing rats. Oral administration of NG-nitro-L-arginine methyl ester (L-NAME) for 4 wk caused hypertension and a significant reduction in urinary NO2- and NO3- excretion. Four-week oral aminoguanidine (AG, 400 mg/dl of drinking water) did not alter blood pressure but caused a significant decrease in urinary NO2- and NO3-. Rats treated with L-NAME at doses of 20 and 50 mg/dl had normal bone mineral mass in the lumbar spine, but the highest dose (80 mg/dl) caused a slight decrease in bone mass. Chronic AG induced a significant spine osteopenia. This effect of AG was abolished by the simultaneous administration of L-arginine (2.0 g/dl). AG-induced osteopenia was associated with a significant increase in urine excretion of collagen cross-links with normal serum osteocalcin. These findings indicate that chronic AG administration can cause an imbalance between bone resorption and formation, resulting in a decrease in bone mass in growing rats, and suggest that NO produced by inducible NO synthase plays an important role in basal osteoclast bone degradation activity in vivo.

Near-infrared spectroscopy (NIRS) imaging studies have revealed the functional development of the human brain in early infancy. By measuring spontaneous fluctuations in cerebral blood oxygenation with NIRS, we can examine the developmental status of the functional connectivity of networks in the cortex. However, it has not been clarified whether premature delivery and/or chromosomal abnormalities affect the development of the functional connectivity of the cortex. In the current study, we investigated the spontaneous brain activity of sleeping infants who were admitted to a neonatal intensive care unit at term age. We classified them into the 3 following infant groups: (i) term-or-late-preterm, (ii) early-preterm, and (iii) Down's syndrome (DS). We used multichannel NIRS to measure the spontaneous changes in oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) at 10 measurement channels, which covered the frontal, temporal, and occipital regions. In order to reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of the time-course signals among all of the pairs of measurement channels. The functional connectivity was classified into the 4 following types: (i) short-range, (ii) contralateral-transverse, (iii) ipsilateral-longitudinal, and (iv) control. In order to examine whether the local properties of hemodynamics reflected any pathological conditions, we calculated the phase differences between the oxy- and deoxy-Hb time-course signals in the 3 groups. The statistical analyses of the functional connectivity data showed main effects of group and the types of connectivity. For the group effect, the mean functional connectivity of the infants in the term-or-late-preterm group did not differ from that in the early-preterm group, and the mean functional connectivity of the infants in the DS group was lower than that in the other 2 groups. For the effect of types of connectivity, short-range connectivity was highest compared to any of the other types of connectivity, and the second highest connectivity was the contralateral-transverse one. The phase differences between the oxy- and deoxy-Hb changes showed that there were significant differences between the DS group and the other 2 groups. Our findings suggested that the development of the functional connectivity of cortical networks did not differ between term-or-late-preterm infants and early-preterm infants around term-equivalent ages, while DS infants had alterations in their functional connectivity development and local hemodynamics at term age. The highest short-range connectivity and the second highest contralateral-transverse connectivity suggested that the precursors for the basic cortical networks of functional connectivity were present at term age.

Several quantitative methods of urine microscopic examination for bacteriuria and pyuria on a blood cell counting-chamber have been found reliable for the diagnosis of urinary tract infection (UTI). However, no one technique has become popular or widely used because of laborious procedures associated with the method. We investigated the usefulness of microscopic examination of uncentrifuged urine on disposable counting-chambers. A total of 89 urine samples were obtained from 53 children (24 male and 29 female). Urine samples were examined for bacteriuria and pyuria using a disposable counting chamber and its reliability was analyzed in predicting significant bacteriuria defined by routine urine culture. Significant bacteriuria was diagnosed in 23 of 89 urine samples by urine culture. Microscopic urine examination on disposable counting-chambers was very easy without the need to set up or wash chambers and provided immediate information. Urine bacterial concentration determined by the counting-chamber method was closely correlated to that determined by bacterial culture. The counting-chamber method identified bacteriuria correctly in 21 of 23 urine samples diagnosed as significant bacteriuria (sensitivity = 91%) and also gave a correct diagnosis of 64 of 66 urine samples with non-significant bacteriuria (specificity = 98%). Nineteen of the 23 urine samples with significant bacteriuria also had pyuria. The positive predictive value of concomitant bacteriuria and pyuria was 100%. When neither bacteriuria nor pyuria was found, the negative predictive value was 100%. It was concluded that urine microscopy using disposable counting chambers was very easy, inexpensive, quick and reliable and thus an extremely useful method for diagnosing UTI.

Urinary albumin and beta 2-microglobulin (B2M) were measured during the neonatal period. Urinary albumin decreased postnatally in term neonates, while it remained almost constant in preterm neonates. Urinary B2M showed a peak level on day 7 both in term and preterm neonates. There was some trend towards higher levels of albumin and B2M with decreasing gestation, showing that glomerular permeability increases and proximal tubular protein reabsorption decreases with increasing degrees of prematurity. In sick preterms who were depressed at birth and had respiratory failure, both parameters were elevated during the first 2 weeks, indicating the presence of glomerular and tubular damage in this period. The changes in B2M with gestation or clinical condition were more pronounced than those in albumin.

Objective The increasingly younger age of onset of allergic rhinitis (AR) has recently become a problem. This study examined the prevalence of inhaled antigen sensitization and nasal eosinophils in children younger than two years old, with measurement of the serum concentrations of aeroallergen-specific IgE antibodies to house dust mites, cat fur, and Japanese cedar pollen, measurement of nasal eosinophil counts, and a questionnaire administered to the children's parents. Methods The subjects were a group of healthy children undergoing 18-month infant health checks provided by the local government, and sick children younger than two years old at the pediatric hospital. Results Among 408 healthy infants, 44 (10.7%) had antigen-specific IgE antibodies, 29 (7.1%) had nasal eosinophils, and eight (2.0%) had both specific IgE antibodies and nasal eosinophils. Nasal assessment revealed that 125 children had rhinorrhea. Of the infants who showed both sensitization to antigens and nasal eosinophils, six (1.5%) had confirmed rhinorrhea. Among 186 sick children younger than two years old at the pediatric hospital, aeroallergen-specific IgE antibodies were detected in five (2.6%). The presence of nasal eosinophils was confirmed in six children (3.2%), which percentage was smaller than that of the healthy group. No infant had either sensitization to antigens or nasal eosinophils. Conclusion The findings described above indicate that the minimum prevalence of AR might be 1.5% in 18-month-old children and that around 10% of affected children have aeroallergen-specific IgE antibodies in Japan. The incidence of AR in young children might increase further.

We measured urinary growth hormone (U-GH), β2-microglobulin (U-B2) and serum growth hormone (S-GH) in preterm neonates on days 1 4, 7, 14 and 28 of age. U-GH as well as U-B2 were high, particularly in the more premature and sick neonates with respiratory failure requiring mechanical ventilation. U-GH showed significant positive correlations with U-B2 throughout the study but with S-GH only on day 7. Therefore, we conclude that in preterm neonates, U-GH mainly reflects the degree of renal proximal tubular function, which is determined by the degree of renal maturation of the subject and of tubular injury due to disease states such as respiratory failure.

We tested the hypothesis that inhibition of cyclooxygenase (COX) attenuates in vivo ventilator-induced lung injury (VILI) in a prospective, randomized laboratory investigation in a university-affiliated laboratory. Adult male rats were anesthetized and randomized with or without nonselective COX inhibition (ibuprofen) and were subjected to injurious mechanical ventilation (positive end-expiratory pressure = 0; peak inspiratory pressure = 21 mm Hg).We investigated the profile of VILI (respiratory mechanics, cytokines, eicosanoids), expression of COX enzymes, and activation of nuclear factor (NF)-κB in ibuprofen- versus vehicle-treated animals. Injurious ventilation caused lung injury (i.e., decrement in compliance, tissue edema, and elevated inflammatory cytokines, eicosanoids, and COX-2).Pretreatment with ibuprofen that effectively inhibited eicosanoid synthesis and COX-2 activity increased survival and attenuated lung edema and decrement in respiratory mechanics. Ibuprofen had no modulatory effect on ventilator-induced activation of NF-κB or inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, GRO/KC [growth-related oncogene/keratinocyte chemoattractant]). COX activity seems important in the pathogenesis of VILI in the in vivo rat. Inhibition of COX provides significant protection (i.e., survival, pulmonary function) in VILI, but without affecting levels of important mediators (tumor necrosis factor-α, IL-1β, IL-6, GRO/KC) or activation of NF-κB.These data confirm that nonselective COX inhibition provides partial protection against VILI and that the NF-κB signaling pathway is not exclusively eicosanoid dependent. Studies of COX inhibition in ventilator-associated lung injury might benefit from multimodal targeting that includes a comprehensive focus on inflammatory cytokines and NF-κB.

We describe an 11-month-old boy who presented clinically with hyperkalemic renal tubular acidosis due to hyporeninemic hypoaldosteronism. Persistent hyperchloremic acidosis and mild azotemia were present. All abnormal laboratory values were corrected by the administration of fludrocortisone. Renal biopsy showed prominent medial hypertrophy of renal arterioles and interstitial fibrosis, which closely resemble those of the gene-targeted mice with disruption of the renin angiotensin system. This is the first case report raising the possibility that a defective renin angiotensin system in infancy may lead to tubulointerstitial damage with medial hypertrophy of intrarenal arterioles.

Clinical and experimental studies have clearly established that mechanical ventilation with large tidal volumes is harmful to the lung. However, there is uncertainty about the micromechanics of injured lungs as well as many unanswered questions about the optimal levels of PEEP and tidal volume in individual patients. In this chapter we focus on the mechanical and molecular mechanisms of ventilator-induced lung injury, the characteristics of bronchopulmonary dysplasia and the eventual feasibility of selective targeted therapy for these conditions.

The effectiveness of intermittent low-dose trimethoprim-sulfamethoxazole (TMP-SMZ) for the prophylaxis of recurrent urinary infection is well established in adults. The present study assessed the effectiveness and safety of intermittent low-dose TMP-SMZ in 35 children (24 boys, 11 girls, aged 1 month to 9 years, median age 5 months) with vesicoureteral reflux; 18 children had bilateral reflux. A total of 53 refluxing ureters were graded as I in 2, II in 16, III in 19, IV in 14, and V in 2 cases. The children were given 1 mg/kg body weight of trimethoprim together with 5 mg/kg of sulfamethoxazole at bedtime every other day for 6-50 months (mean +/- SD, 22.9 +/- 11.7 months). None of the boys had a recurrence of urinary infection, while 2 of the 11 girls had a total of 7 recurrences during the prophylaxis period, with a recurrence rate of 0.027 per patient month in girls. Both girls were over 3 years and had a mildly unstable bladder. Transient neutropenia (1,000/microliter) developed in 2 infants during the prophylaxis period, but disappeared spontaneously. Intermittent low-dose TMP-SMZ seemed very effective for the prevention of recurrent urinary infection in children with ureteral reflux even of higher grades.