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Objective: The aim of this study was to determine the prenatal causes of slight lateral ventricular enlargement in infants treated in a neonatal intensive care unit., Methods: We examined 318 infants with a gestational age of at least 28 weeks who were treated in a neonatal intensive care unit. We investigated the relationships between slight lateral ventricular enlargement and prenatal factors. Also, we investigated the relationships between the laterality of lateral ventricular enlargement and arm growth to verify our proposed mechanism of lateral ventricular enlargement., Results: Slight lateral ventricular enlargement was observed in 97 (30.5%) infants. Slight lateral ventricular enlargement was related to gestational age ( p  < .001), maternal anemia ( p  = .025), diabetes mellitus ( p  = .048), threatened premature labor ( p  = .027), and premature rupture of the membrane ( p  = .049). In 97 infants with ventricular enlargement, the numbers of infants with left-side dominant, equivalent, and right-side dominant laterality were 60 (61.9%), 27 (27.8%), and 10 (10.3%), respectively. Maternal anemia and diabetes mellitus were related to left-side dominant ventricular enlargement. Threatened premature labor and premature rupture of the membrane were related to right-side dominance. The laterality of lateral ventricular enlargement was not relate to that of the arm growth., Conclusions: We propose that the main cause of slight lateral ventricular enlargement may not be malnutrition but instead may be hypoxic stress in utero .

Objective: The efficacy of routine brain MRI for term infants admitted to a neonatal intensive care unit (NICU) has not been well studied. This study aimed to investigate the types and frequencies of abnormal findings on routine brain MRI and the predictors of abnormality for term infants in an NICU setting., Methods: We examined the results of routine brain MRI of 239 term infants who were hospitalized in the NICU. Data on the perinatal factors were also collected, and the association with MRI abnormalities was assessed., Results: Of the 239 MRI scans, we found abnormal findings in 52 (21.8%) patients. Intracranial hemorrhage accounted for 74% of the abnormal findings, including subdural, intraparenchymal, cerebellar, and subependymal hemorrhages. Twenty-six percent of these were ischemic lesions, including cerebral infarction, white matter abnormal intensities, and cystic periventricular leukomalacia (PVL). Five (2.1%) MRI scans required detailed examination or were known to be associated with a poor neurological prognosis. No patient needed treatment for the findings. An Apgar score ≤7 points at 5 min was identified as a perinatal factor significantly associated with abnormal MRI findings (adjusted OR = 3.034, 95% CI: 1.107-8.315, p  = .031)., Conclusion: The efficacy of routine brain MRI for term infants admitted to the NICU was limited. Routine brain MRI is not recommended for this population.

Objective: The aim of this study was to determine the prenatal causes of slight lateral ventricular enlargement in healthy infants., Methods: We examined 1089 healthy infants who weighed at least 2000 g and were born at a gestational age of at least 36 weeks. We assessed the presence of ventricular enlargement when an apparent space was observed in the frontal horn or body of the lateral ventricle of the brain by a transfontanel ultrasound scan. We investigated the relationships between slight lateral ventricular enlargement and various prenatal factors., Results: Slight lateral ventricular enlargement was observed in 497 (45.6%) infants. Slight lateral ventricular enlargement was related to maternal anemia ( p  = .004; odds ratio = 1.630; 95% CI: 1.168-2.276), threatened premature labor ( p  = .010; odds ratio = 1.441; 95% CI: 1.093-1.900), and diabetes mellitus ( p  = .022; odds ratio = 2.020; 95% CI: 1.109-3.682) using multiple logistic regression analysis. The birth weight of the infants with slight lateral ventricular enlargement was heavier than that of those without ventricular enlargement at 36-40 weeks of gestation. Forty infants with ventricular enlargement had head circumferences greater than the 90th percentile, while only one infant without ventricular enlargement did ( p  < .001). In addition, 22 infants with ventricular enlargement had head circumferences less than the 10th percentile, while only 4 infants without ventricular enlargement did ( p  < .001). In 497 infants with ventricular enlargement, the numbers of infants with left side dominant, equivalent, and right side dominant ventricular enlargement were 289 (58.1%), 110 (22.1), and 98 (19.7%), respectively., Conclusions: Slight lateral ventricular enlargement could be caused by several pathological conditions in utero , including brain atrophy, ventricular enlargement, the influence of blood flow in the brain, and various pathological changes in different brain regions.

Objective: The goal of this study was to investigate the prognosis of infants with neonatal respiratory inhibition syndrome (NRIS). Methods: Infants with a gestational age of at least 36 weeks and a birth weight of at least 2000 g who were born at Nara Prefecture General Medical Center, in Nara, Japan, between March 2013 and June 2016 were screened for NRIS using our established method. NRIS was defined as severe hypoxemia caused by respiratory inhibition immediately after crying (RIAC) or gastroesophageal reflux (RIGER) or as a respiratory pause during feeding (feeding hypoxemia), accompanied clinically by central cyanosis and a decrease in SpO 2 to less than 70%. All infants were monitored using pulse oximetry immediately after birth. Diagnosis of RIAC, feeding hypoxemia, and RIGER are based on observation by both parents and medical staff as well as on on-screen computer analysis using specific software. All infants were examined at a one-month check-up. Parents of the infants who experienced one or more episodes of NRIS accompanied by a decrease in SpO 2 to less than 70% for more than approximately 60 s received a questionnaire by mail about their child's development. We conducted a logistic regression analysis with developmental problems as the dependent variable. Results: NRIS was observed in 362 (28.5%) infants; 216 (17.0%) infants showed RIAC, 254 (20.0%) infants showed feeding hypoxemia, and 54 (4.2%) infants showed RIGER. Although all infants were monitored in the maternity ward nursery, 184 (85.2%) infants with RIAC and 111 (43.7%) infants with feeding hypoxemia were overlooked. All infants with NRIS were found to have successfully recovered at one month after birth. Sixty-two cases were examined in the follow-up study by the mailed questionnaire. The median age of the subjects at time of study was 22 months. Fourteen cases (22.6%) exhibited developmental problems including delayed speech development, stereotyped interests and behaviors, sensory disturbance, hyperactivity, delayed motor development, and short stature. Developmental problems tended to relate to shorter gestational age (odds ratio, 0.622; p  = .068; 95% CI, 0.373-1.036), smaller birth weight (odds ratio, 0.998; p  = .069; 95% CI, 0.997-1.000), and maximum duration of SpO 2 to less than 70% by RIAC (odds ratio, 1.009; p  = .086; 95% CI, 0.999-1.020). All cases had experienced severe hypoxemia accompanied by a decrease in SpO 2 to less than 60%. Seven cases had experienced prolonged hypoxemia accompanied by a decrease in SpO 2 to less than 70% for at least 2 min. Among the subjects, 19 infants were examined closely, and their natural course of NRIS was observed in the neonatal intensive care unit. No cases demonstrated abnormal findings with blood examinations, chest-abdominal X-ray, echocardiogram, laryngoendoscopy, hearing loss screening, or mass screening. Only one case had a small intracranial hemorrhage as evidenced in a magnetic resonance imaging of the head. Conclusions: The infants with severe NRIS tended to have developmental problems. Spreading knowledge about NRIS worldwide is thought to be very important.

Objective: In our previous studies, we documented that threatened premature labor and asymmetrical intrauterine growth restriction were risk factors for respiratory inhibition. The goal of this study was to determine the cause of respiratory inhibition by considering perinatal risk factors., Methods: We examined 1497 infants with a gestational age of 36 weeks or greater. All infants were monitored using pulse oximetry and examined via cranial sonography. Respiratory inhibition was defined as severe hypoxemia caused by respiratory inhibition immediately after crying or gastroesophageal reflux or as a respiratory pause during feeding. We examined the relationships between respiratory inhibition and perinatal factors and speculated on the cause of respiratory inhibition., Results: The median gestational age, birth weight, Apgar score at 1 min, and Apgar score at 5 min of the subjects were 38.9 weeks, 2930 g, 8.0 points, and 9.0 points, respectively. Respiratory inhibition was observed in 422 infants. Lateral ventricle enlargement and increased echogenicity in the ganglionic eminence were observed in 417 and 516 infants, respectively. Respiratory inhibition was significantly correlated with shorter gestational periods, twin pregnancies, lateral ventricle enlargement, and increased echogenicity in the ganglionic eminence., Conclusions: We speculate that umbilical cord compression is a major cause of respiratory inhibition.

Objective: Calcineurin inhibitors are highly effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with calcineurin inhibitors fails, adalimumab can be considered to avoid colectomy. The efficacy and safety of this sequential alternative salvage therapy remain unknown. Therefore, the present study was performed to investigate the short- and long-term efficacy and safety of adalimumab after failure of calcineurin inhibitors in corticosteroid-refractory UC., Materials and Methods: Patients with a corticosteroid-refractory flare of UC who did not respond to calcineurin inhibitors and received continuing salvage therapy with adalimumab were included in this retrospective, observational, single-centre study. The cumulative rates of colectomy were calculated using the Kaplan-Meier method. Clinical remission and response were evaluated based on the Rachmilewitz index. The cumulative rates of colectomy were calculated. Predictive factors for clinical remission and colectomy were identified. In the safety evaluation, any adverse event occurring after the administration of adalimumab was considered., Results: Forty-one patients were enrolled; 78% had extensive colitis and 87% had moderate to severe colitis. Seventeen patients (41%) underwent colectomy during the follow-up period. At week 8, 26, and 52 after adalimumab injection, 27%, 39%, and 32% of patients achieved clinical remission, respectively. The adverse event rate was 17%, including one case of tuberculosis., Conclusions: The efficacy of adalimumab for calcineurin inhibitor-refractory UC was examined for the first time. Treatment with adalimumab avoided the need for colectomy in two-thirds of patients with corticosteroid-refractory UC in whom calcineurin inhibitors had failed. However, attention is needed to avoid adverse events, especially infection.

Objective: The aim of this study was to determine the clinical significance of slightly lateral ventricular enlargement., Methods: We examined 1151 infants with a gestational age of 36 weeks or greater. We assessed for the presence of ventricular enlargement when apparent space was observed in the frontal horn or body of lateral ventricle by a transfontanel ultrasound scan., Results: Two hundred and forty-eight infants had ventricular enlargement. The atrial widths in most infants were less than 10 mm. Ventricular enlargement correlated with Cesarean delivery, gestational age, birth weight, respiratory disturbance at delivery and respiratory inhibition after crying (RIAC). Ventricular enlargement could be divided into three types by ultrasound findings. Forty-five infants showed only enlargement of the anterior horn (Type A), 97 infants showed enlargement from the body to the posterior horn (Type B), and 108 infants showed whole enlargement from the anterior to the posterior horn (Type C). The infants with Type A correlated with intrauterine growth restriction, placenta previa, male gender and birth weight. The infants with Type B correlated with cesarean delivery. The infants with Type C correlated with diabetes mellitus, respiratory disturbance at delivery, RIAC and feeding hypoxemia., Conclusions: Slightly lateral ventricular enlargement should be considered clinically significant.

Objective: To determine the relationships between gastroesophageal reflux (GER) and both respiratory inhibition after crying (RIAC) and feeding hypoxemia in infants., Methods: We screened for RIAC and feeding hypoxemia among infants with a gestational age of 36 weeks or greater using pulse oximetry. We investigated the infants who showed hypoxemia with a decrease in SpO2 to less than 70% and bradycardia with a heart rate of less than 100 beats per minute caused by GER. We then evaluated the relationships between these events and both RIAC and feeding hypoxemia., Results: We examined 250 infants in the present study. RIAC and feeding hypoxemia were observed in 35 (14.0%), and 30 (12.0%) infants, respectively. Ten infants showed hypoxemia and bradycardia caused by GER. These events were correlated with RIAC (p = 0.006) and feeding hypoxemia (p = 0.031)., Conclusions: In the infants with RIAC and feeding hypoxemia, some show severe hypoxemia and bradycardia caused by GER. Medical staff caring for infants should note the presence of RIAC and feeding hypoxemia.

Objective: We investigated whether intrauterine growth restriction (IUGR) correlated with respiratory inhibition after crying (RIAC) and feeding hypoxemia., Methods: We screened for RIAC among 1248 infants with a gestational age ≥36 weeks using our established method with cranial ultrasound, SpO2 monitoring, and polygraphy. We classified the infants into three groups: symmetric IUGR, asymmetric IUGR, and control. We compared the perinatal factors with the incidence of RIAC and feeding hypoxemia among the three groups., Results: Overall, 26 infants had symmetric IUGR, 143 infants had asymmetric IUGR, and 1079 infants were in the control group. RIAC was observed in 10 (6.9%) infants in the asymmetric IUGR group and in 37 (3.4%) infants in the control group. Feeding hypoxemia was observed in 15 (10.5%) infants in the asymmetric IUGR group and in 52 (4.8%) infants in the control group. The incidence of RIAC and feeding hypoxemia in the asymmetric IUGR group was significantly more than that in the control group. None of the infants with symmetric IUGR exhibited RIAC or feeding hypoxemia., Conclusions: The results indicate that asymmetric IUGR is a risk factor for RIAC and feeding hypoxemia. These infants should be aggressively screened for RIAC.

Objective: To determine the incidence, risk factors and natural history of respiratory inhibition after crying (RIAC) and feeding hypoxemia., Methods: We screened for RIAC and feeding hypoxemia among 393 infants with a gestational age ≥ 36 weeks using pulse oximetry. Twenty-seven infants were treated in the neonatal intensive care unit., Results: RIAC and feeding hypoxemia were observed in 95 (24.2%) and 124 (31.6%) infants, respectively. RIAC correlated with feeding hypoxemia (p < 0.001), grade II increased echogenicity in the ganglionic eminence (p = 0.005), dilation of the lateral ventricle (p = 0.044), threatened premature labor (p = 0.033) and twin gestation (p = 0.089). Feeding hypoxemia correlated with RIAC (p < 0.001), abnormal cranial ultrasound findings (p < 0.001), maternal smoking during pregnancy (p = 0.083), asymmetric intrauterine growth restriction (p = 0.012) and twin gestation (p = 0.067). All infants recovered from RIAC in an average of 4.5 (2.0-7.0) d. Fifteen infants recovered from feeding hypoxemia, but 10 infants needed additional assistance and monitoring by nursing until the day of discharge. The day of discharge was day 8.0 (5.0-12.4)., Conclusions: RIAC and feeding hypoxemia are observed among healthy infants, and these infants experience repeated events of prolonged hypoxemia.

Objective: To report the polygraphic findings of infants with respiratory inhibition after crying (RIAC)., Methods: We screened for RIAC among infants with a gestational age ≥36 weeks using our established method with cranial ultrasonography, SpO(2) monitoring and polygraphy. RIAC is defined as central apnea that occurred immediately after crying with a decrease in SpO(2) to <60%, followed by repeated irregular respiration and apnea as the respiration gradually recovered. The subjects were infants with RIAC for whom we could study the polygraphic findings in detail., Results: Forty-seven RIAC cases were included in the present analysis. The frequency of RIAC was 2.1 (1.2-7.0) times per 24 h. The maximum duration of respiratory inhibition was 78.0 (52.6-109.0) s. The maximum duration of SpO(2) <60% during RIAC was 39.0 (9.8-93.2) s. The minimum SpO(2) value during RIAC was 53.0% (42.2-58.0%). The minimum heart rate during RIAC was 103.0 (79.1-127.1) bpm., Conclusions: RIAC is observed among healthy infants, and they experience repeated prolonged hypoxemia.

The effects of blue light emitter diode (LED) light exposure on retinal pigment epithelial cells (RPE cells) were examined to detect cellular damage or change and to clarify its mechanisms. The RPE cells were cultured and exposed by blue (470 nm) LED at 4.8 mW/cm(2). The cellular viability was determined by XTT assay and cellular injury was determined by the lactate dehydrogenase activity in medium. Intracellular reactive oxygen species (ROS) generation was determined by confocal laser microscope image analysis using dihydrorhodamine 123 and lipid peroxidation was determined by 4-hydroxy-2-nonenal protein-adducts immunofluorescent staining (HNE). At 24 h after 50 J/cm(2) exposures, cellular viability was significantly decreased to 74% and cellular injury was significantly increased to 365% of control. Immediately after the light exposure, ROS generation was significantly increased to 154%, 177%, and 395% of control and HNE intensity was increased to 211%, 359%, and 746% of control by 1, 10, and 50 J/cm(2), respectively. These results suggest, at least in part, that oxidative stress is an early step leading to cellular damage by blue LED exposure and cellular oxidative damage would be caused by the blue light exposure at even lower dose (1, 10 J/cm(2)).

Life expectancy in Japan is highest in the world. Cancer is the leading cause of mortality in Japan, accounting for about 30 percent of all deaths. Many Japanese cancer patients experience severe pain although they and their families hope to be pain free at the end of their lives. Toward that end, the consumption of morphine in Japan has increased markedly since 1989. The amount of morphine hydrochloride and morphine sulfate consumed in 2001 was 6.1 times that used in Japan in 1989. However, the amount of morphine consumed in Japan is still less than in other developed nations, and was only one-sixth of the amount used in Australia in 2001. As a result, many Japanese cancer patients experience potentially manageable cancer pain, largely because the amount of the drug used by doctors is insufficient for pain control. An increasing number of Japanese doctors now understand that their patients' quality of life is most important in end-of-life care and how to use the three step analgesic ladder of the World Health Organization (WHO). However, other doctors do not understand these issues sufficiently causing some patients to die without good pain control. Both the general population and some medical professionals misunderstand and have prejudice against the use of morphine. Patients often do not participate in decision making about medical treatment because of remaining paternalism in the relationship between Japanese doctors and patients. Thus, cancer pain management in Japan is not as effective as it can be and not all Japanese cancer patients receive appropriate management for their cancer pain. To improve outcomes for Japanese patients, it is necessary for health professional and social work students and practicing professionals to receive contemporary education including an introduction to palliative care and ethics.

Purpose: We identified the temporal expression of activator protein-1 (AP-1) and matrix metalloproteinases (MMPs) after linoleic acid hydroperoxide (LHP) induction of retinal neovascularization., Methods: After injection of LHP into the vitreous of rabbits, samples were collected for AP-1 binding activity and mRNA for MMP-9 and MMPs activity. AP-1 binding activity was measured by electrophoretic mobility shift assay. MMP-9 activity was measured by zymography and mRNA by quantitative RT-PCR., Results: AP-1 binding activity was increased at 1-3 hr. MMP-9 mRNA levels were increased at 3 hr in the neural retina and by 12 hr in the retinal pigment epithelium (RPE) layer. MMP-9 proteolytic activity was elevated within the neural retina and within the vitreous and in the RPE-interphotoreceptor matrix (IPM) at 12 hr and peaked at 24 hr or 4 days., Conclusions: LHP increases the transcription factor AP-1 which in turn may regulate retinal MMP-9 synthesis during neovascularization.

Purpose: To compare the effect of hyperglycemia on corneal neovascularization (NV) induced by linoleic acid hydroperoxide (LHP) in a rabbit model., Methods: Male New Zealand rabbits received 80 mg/kg alloxan i.v. and subsequently developed hyperglycemia. Four weeks later, 10 microl of LHP (40 mM) was injected into corneal stroma 5 mm from the superior limbus with a 30 gauge needle. Vessel growth area from the limbal vasculature was measured over a period of 2 weeks and was correlated with plasma levels of insulin, HbA(1c), and corneal vascular endothelial growth factor (VEGF)., Results: Two days after alloxan, blood glucose was increased from 97 +/- 4 mg/dl in the untreated control group to 413 +/- 3 mg/dl. At 24 and 72 hours after LHP injection, VEGF in cornea of hyperglycemic rabbits was elevated 2 to 4 times above that of normoglycemic rabbits. At 14 days after LHP injection, the normoglycemic rabbits vessel growth area measured 2.42 +/- 0.31 mm(2), but in the hyperglycemic group, vessel growth area was significantly increased to 7.96 +/- 2.26 mm(2) (p < 0.05). At the end of the experimental period, HbA(1c) was elevated from 3.9 +/- 0.8 % to 8.4 +/- 0.6 % and insulin was decreased from 440 +/- 123.9 pg/ml to 24 +/- 11.0 pg/ml., Conclusions: These data suggest that hyperglycemia may sensitize corneal and vascular endothelial cells, perhaps by glucose derived radicals, which enhance production of additional LHP through endogenous propagation reactions, and raise in turn the concentration of VEGF levels to induce an enhanced, sustained NV response.

1. Caucasian liver samples were used in this study. N-demethylation of trimethadione (TMO) to dimethadione (DMO) was monitored in the presence of chemical inhibitors of CYPs, such as fluconazole, quinidine, dimethyl-nitrosamine, acetaminophen, phenacetin, chlorzoxazone and mephenytoin. Trimethadione N-demethylation was selectively inhibited by dimethylnitrosamine and chlorzoxazone (> 50%) and weakly inhibited by tolbutamide (12%) and fluconazole (22%), whereas other inhibitors showed no effect. This result suggested that TMO metabolism to DMO is mainly mediated by CYP2E1 and marginally by CYP2C and CYP3A4. 2. Fifteen human livers were screened and interindividual variability of TMO N-demethylation activity was 3-fold. Chlorzoxazone 6-hydroxylation activity was also measured and both activities were significantly correlated (r=0.735, p < 0.01). 3. DMO production by human cDNA expressed CYP enzymes was observed mainly for CYP2E1 (10.8 nmol/tube), marginally for CYP2C8 (0.22 nmol/tube) and not detectable for other CYP enzymes. 4. These results indicate that TMO metabolism is primarily catalysed by CYP2E1 and that trimethadione would be a suitable selective probe drug for the estimation of human CYP2E1 activity in vivo.

1. Prediction of hepatic injury from changes in blood concentrations of caffeine (CA) and its three primary metabolites (theobromine: TB; paraxanthine: PX; theophylline; TP) after CA administration has been studied in carbon tetrachloride (CCl4)-intoxicated rats. 2. The plasma half-life (t1/2) of CA (10 mg/kg, oral) was increased, and total body clearance (CL) decreased, in CCl4-treated rats; the apparent volume of distribution (Vd) was relatively unchanged. 3. The ratios of CA to the three metabolites (TB/CA, PX/CA, TP/CA) were significantly decreased compared to those of controls. 4. There were good correlations between the ratios of TB/CA, PX/CA, and TP/CA and CL of CA (TB/CA; r = 0.944 at 1 h, r = 0.942 at 2 h: PX/CA; r = 0.974 at 1 h, r = 0.923 at 2 h: TP/CA; r = 0.866 at 1 h, r = 0.962 at 2 h). 5. Results indicate that it is possible to evaluate hepatic drug-oxidizing capacity by measuring the ratio of CA to its metabolites, using single blood sampling 1 or 2 h after CA administration in CCl4-intoxicated rats.