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The aim of this study is to evaluate the usefulness of T cell receptor excision circle (TREC) and/or kappa-deleting recombination excision circle (KREC) measurements integrated with diagnostic next-generation sequencing (NGS) analysis using a severe combined immunodeficiency (SCID) newborn screening (NBS) program.TREC and/or KREC values were measured in 137,484 newborns between April 2017 and December 2021 using EnLite TREC (n = 80,791) or TREC/KREC kits (n = 56,693). For newborns with positive screening results, diagnostic NGS analysis was performed with a 349-gene panel to detect genetic mutations associated with primary immunodeficiencies (PIDs).A total of 145 newborns (0.11%) had abnormal TREC and/or KREC values, and a genetic diagnosis was established in 2 patients with SCID (1 in 68,742 newborns) (IL2RG-SCID and reticular dysgenesis) and 10 with non-SCID PIDs with T and/or B cell deficiencies (1 in 13,748 newborns) using NGS analysis. Furthermore, TREC values of 2849 newborns were measured and confirmed the significant correlation between the results of both TREC and TREC/KREC kits (P 0.001) and naïve T cell counts.We performed the first large-scale TREC and TREC/KREC NBS programs in Japan. Our NBS programs followed by the diagnostic NGS analysis for newborns with abnormal TREC and/or KREC values are useful for the early identification and rapid molecular evaluation of not only SCID but also different non-SCID PIDs.

The incidence of pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) has not been investigated in regional cohorts. The aim of this study was to clarify the incidence of PH associated with BPD in all very low birthweight infants (VLBWIs) born during the study period in Aichi Prefecture, Japan.We conducted a retrospective observational cohort study of all VLBWIs born in Aichi Prefecture. The inclusion criteria were VLB, birth between 1 January 2015 and 31 December 2015, and admission to any neonatal intensive care unit in Aichi Prefecture. BPD28d and BPD36w were defined as the need for supplemental oxygen or any respiratory support at 28 days of age or 36 weeks of postmenstrual age (PMA). The primary outcome was the incidence of PH after 36 weeks' PMA (PH36w) in VLBWIs with BPD28d and BPD36w. The secondary outcomes were the clinical factors related to PH36w in BPD36w patients. Mann-Whitney U-test and Fisher's exact test were used for univariate analysis. Differences were considered statistically significant at P 0.05. Risk ratio (RR) and 95% confidence interval (CI) were also evaluated.A total of 441 patients were analyzed. A total of 217 and 131 patients met the definition of BPD28d and BPD36w, respectively. Nine patients were diagnosed with PH36w (4.2% and 6.9% of the BPD28d and BPD36w patients, respectively). The presence of oligohydramnios (RR, 2.71; 95% CI: 1.55-4.73, P = 0.014) and sepsis (RR, 3.62; 95% CI: 1.51-8.63, P = 0.025) was significant in the PH36w patients.The incidence of PH36w was 4.2% and 6.9% in the BPD28d and BPD36w patients, respectively. Oligohydramnios and sepsis were significantly associated with PH36w in VLBWIs.

U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential pre-mRNA splicing factor in an early step of splicing. Alternative splicing plays an important role in neuronal development, and disorders of RNA processing steps are implicated in neurological disorders. Recently, the large trio whole-exome sequencing study reported U2AF2 as a novel gene significantly associated with developmental disorders: however, the clinical details of patients with U2AF2 variants were not available. Here, we report an individual with a de novo U2AF2 variant (c.445C>T, p.(Arg149Trp)) using trio-based whole-exome sequencing. This residue was positioned in the RNA recognition motif 1 which recognizes a polypyrimidine-tract splice site signal. The patient showed global developmental delay, intellectual disability, epilepsy, short stature, microcephaly, facial dysmorphism, intermittent exotropia, bilateral ptosis, muscle hypotonia and thin corpus callosum, indicating that U2AF2-related disorder could include systemic dysmorphisms, epilepsy and brain malformation along with global developmental delay.

Respiratory syncytial virus (RSV) induces not only infantile recurrent wheezing but also potentially atopic asthma.To test the effect of RSV infection on development of subsequent atopic asthma, we evaluated whether palivizumab, an anti-RSV monoclonal antibody, by preventing severe RSV disease in the first year of life, could impact subsequent recurrent wheezing and atopic asthma at 6 years of age.During the 2007 to 2008 RSV season, the decision to administer palivizumab was made based on standard medical practice and an observational prospective multicenter (n = 52) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed from 0 to 3 years (preceding Committee on Recurrent Wheezing study). The 52 investigators at hospitals then followed these subjects until 6 years of age, reported here (Effects of Preventive Treatment for Respiratory Syncytial [RS] Virus Infection During Infancy on Later Atopic Asthma in Preterm Infants; Scientific Committee for Elucidation of Infantile Asthma). Parents of study subjects reported the infants' physicians' assessment of recurrent wheezing, using a report card and a novel mobile phone-based reporting system using the Internet. The primary endpoint was the incidence of atopic asthma.Of 444 preterm infants enrolled, 349 received palivizumab during the first year of life. At 6 years, atopic asthma was not different in the groups: 15.3 and 18.2% of infants in the treated and untreated groups, respectively (P = 0.57). On the other hand, physician-diagnosed recurrent wheezing was observed in 15.3 and 31.6% in the treated and untreated groups, respectively (P = 0.003).Palivizumab prophylaxis administered to preterm infants did not suppress the onset of atopic asthma but resulted in a significantly lower incidence of recurrent wheezing during the first 6 years. Clinical trial registered with www.clinicaltrials.gov (NCT 01545245).

Only the low-risk category of over-the-counter (OTC) drugs was permitted to be sold via the Internet, which was stipulated by the ordinance of the Minister of Health, Labour and Welfare under the Pharmaceutical Affairs Law in Japan. Two Japanese retailers of OTC drugs, who want to retail OTC drugs via the Internet, launched proceedings against the rule, and the Supreme Court gave a decision that the ministerial ordinance is illegal and invalid. The Ministry of Health, Labour and Welfare immediately started discussion to make rules for Internet retailing of OTC drugs. Finally, a bill designed to enable Internet retailing of OTC drugs was passed by the Diet on December 5, 2013, and the act was promulgated on December 13. The act was enforced on June 12, 2014. This article briefly touches on the decision process and also illustrates the key points of the new rules for Internet retailing.

Background Hydrops fetalis (HF) has low survival rate, particularly in cases of preterm birth. In addition, the severity index of HF has not been fully investigated yet. This study was aimed to clarify the prognostic factors of HF patients with pleural effusion. Methods All live-born HF patients with pleural effusion, except for chromosomal abnormality or complex congenital heart disease, born from 2009 to 2013 in Aichi Prefecture in Japan were included. The prenatal, perinatal, and postnatal information was obtained from their medical records and was retrospectively analyzed. Results Forty-one HF patients with pleural effusion were included, and twenty-eight patients (68%) survived. The multivariate logistic stepwise analysis revealed that the gestational birth week (OR 0.71, 95% CI 0.52–0.96, p = 0.027) and standard deviation (SD) score of the birth weight (OR 1.74, 95% CI 1.01–2.99, p = 0.045) were significant factors for postnatal death. All patients with both >32 gestational weeks and

Background Chorioamnionitis, or infiltration of the chorioamnion by neutrophils, is a risk factor associated with the development of bronchopulmonary dysplasia. Increased neutrophil elastase levels are observed in the tracheal aspirates of these patients. Aims To examine the effects of early administration of the selective neutrophil elastase inhibitor sivelestat, which is used to treat acute lung injury in adults, on bronchopulmonary dysplasia in extremely premature infants. Study design Retrospective cohort study. Subjects This study included extremely low-birth-weight infants born at a gestational age Outcome measures The primary outcome was the rate of bronchopulmonary dysplasia-free survival at a postmenstrual age of 36 weeks, and the secondary outcomes included various clinically significant factors of neonatal mortality and morbidity and adverse events. Results Of the 1031 included neonates, 124 (12.0%) were treated with sivelestat. Significant differences between the groups were noted for gestational age, delivery method, fetal number, the frequency of chorioamnionitis, immunoglobulin M levels, and WBC counts. No differences were identified concerning the bronchopulmonary dysplasia-free survival rate at a postmenstrual age of 36 weeks (adjusted odds ratio for sivelestat to control, 0.83; 95% confidence interval = 0.53–1.30). Secondary outcomes did not significantly differ between the groups. Conclusions In extremely premature infants, early sivelestat use was not associated with an improved rate of survival without bronchopulmonary dysplasia at a postmenstrual age of 36 weeks.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled activation of T cells and macrophages with overproduction of cytokines. Familial HLH type 2 (FHL2) is the most common form of primary HLH and is caused by mutations in PRF1. We have recently described a significant increase in the subpopulation of CD8+ T cells with clonal expansion and CD5 down-regulation in Epstein-Barr virus associated-HLH, which represented a valuable tool for its diagnosis. However, this unusual phenotype of CD8+ T cells has not been investigated fully in patients with FHL2. We performed immunophenotypic analysis of peripheral blood and measured serum pro-inflammatory cytokines in five patients with FHL2. All patients showed significantly increased subpopulations of activated CD8+ T cells with down-regulation of CD5, which were negligible among normal controls. Analysis of T-cell receptor Vβ repertoire suggested the reactive and oligoclonal expansion of these cells. The proportion of the subset declined after successful treatment concomitant with reduction in the serum levels of cytokines in all patients except one who continued to have a high proportion of the subset and died. These findings suggest that down-regulation of CD5 on activated CD8+ T cells may serve as a useful marker of dysregulated T cell activation and proliferation in FHL2. © 2013 American Society for Histocompatibility and Immunogenetics.

OBJECTIVE To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. STUDY DESIGN We included 58 004 infants born weighing

Newborn males are more sensitive to brain injury than newborn females are. The aim of the present study was to find an explanation for this. We used the neuron-specific enolase (NSE) levels in the cerebrospinal fluid (CSF) for the classification of 32 newborns (19 males and 13 females) on their fifth postnatal day. The NSE levels were higher than normal (8.4 +/- 1.6 ng/mL) in 10 newborn males and 6 females and were, respectively, considered asphyxiated male and female groups. The remaining newborns, 9 males and 7 females, had normal CSF levels of NSE and were considered normal newborn male and female groups. The CSF samples were measured for 12 cytokines, using a cytokine array kit, and for total hydroperoxide and biological antioxidant potentials (BAPs), using the free radical analytic system. Among the 12 cytokines measured, only interleukin 8 (IL-8) was properly detected. The CSF levels of IL-8 were higher in the asphyxiated newborn females than in the other three groups. The mean CSF levels of BAPs in the asphyxiated newborn females were higher compared with the other three groups, but significance was detected only in comparison with the BAP levels in the CSF samples of the normal newborn males. There were no differences in total hydroperoxide levels among the groups. There are sex-related differences in the CSF levels of IL-8 and antioxidants in asphyxiated newborns, with higher levels in newborn females; this might contribute in the sexual dimorphism regarding the fact that females have better protection from brain injury than the males.

A 29-year-old, primiparous woman was referred to our hospital at 21 weeks of gestation because of right pleural effusion in the fetus shown by routine ultrasonographic examination. Cytology revealed abundant lymphocytes, suggesting chylothorax. We removed the pleural effusion and injected OK-432 into the chest cavity at 24 and 25 weeks of gestation. Pleural effusion declined and an adhesion between the lung surface and the pleural membrane seemed to form. At 33 weeks of gestation, a female infant was born by cesarean section (1,090 g and Apgar score 6/8). Although she demonstrated slight retraction and tachypnea, management could be achieved by administration of oxygen alone without mechanical ventilation. Later, the baby was diagnosed as suffering from the Cornelia de Lange syndrome with characteristic features. OK-432 injections could thus prevent complications of chylothorax and hypoplastic lungs, without injury to either the baby or the mother.

Background: Persistent pulmonary hypertension of the newborn (PPHN) commonly appears as a complication of several pulmonary and non-pulmonary diseases. The hypoxia possibly inhibits Ca 2 + ′ dependent K + channels, thus resulting in membrane depolarization of pulmonary smooth muscle cells, which leads to the opening of Ca 2 + channels and Ca 2 + entry, resulting in contraction of the vascular smooth muscle. However, magnesium (Mg 2 + ) is an antagonist of Ca 2 + . We studied the effect of magnesium sulfate on the treatment of hypoxia-induced pulmonary hypertension and compared to the site of action of nitric oxide (NO). Methods: Zero-day-old piglets were used in each experiment. The effects of Mg 2 + were tested in each hypoxic, normoxic and hyperoxic states. Once the desired physical state was achieved, Mg 2 + was administered at a dose of 100 mg/kg approximately every 10 min. In order to determine the exact mechanism of the Mg 2 + , Nw-nitro-L-arginine (LNNA), a NO synthase-inhibitor, was administered simultaneously with Mg 2 + in some of the experiments. Results: There was a significant correlation between the percent reduction of the pulmonary arterial pressure (PAP) caused by magnesium and the level of oxygen (O 2 ) present in the pulmonary artery. The greatest amount of reduction was seen in the hypoxic condition where the least amount of O 2 is found. A further reduction in the PAP was seen when NO was given at the end of the Mg 2 + trials. There was no significant reduction seen in the systemic arterial pressure. Conclusion: Inhaled NO further reduced the PAP in piglets already treated with Mg 2 + .

We report a case of lissencephaly which could be diagnosed by detailed examination during pregnancy. We first found bilateral enlarged ventricles in the fetus by routine abdominal ultrasonography at mid-pregnancy. Fast scanning MRI subsequently allowed confirmation of a diagnosis of lissencephaly during pregnancy.

In order to evaluate the influence of maternal anti-HLA antibody on neonatal thrombocytopenia, clinical features and maternal anti-HLA antibody of three groups of infants (19 thrombocytopenic and low birth weight, 27 nonthrombocytopenic and low birth weight, and 80 healthy full-term) were investigated. The incidence of positive maternal anti-HLA antibodies in the three groups was 73.7%, 29.6% and 27.5%, respectively. Thrombocytopenia in small-for-gestational-age (SGA) infants was closely related to the presence of maternal anti-HLA antibodies. Among 20 SGA infants (11 thrombocytopenic, 9 non-thrombocytopenic), anti-HLA antibody was detected in 10 mothers (90.9%) of thrombocytopenic SGA infants, while it was positive in only one mother (11.1%) of nonthrombocytopenic SGA infants. Investigation of the SGA infants revealed that in those whose mothers were sensitized to HLA antigen, not only the platelet count but also the leukocyte and lymphocyte counts in the first week of life were significantly lower than in infants whose mothers were not sensitized. The results suggest that the presence of maternal anti-HLA antibody is a cause of neonatal thrombocytopenia especially in SGA infants.

Background: The sudden appearance of hypotension and oliguria without obvious cause following stable circulation and respiration in preterm infants is frequent in Japan. Such episodes are referred to as late-onset circulatory dysfunction of premature infants (LCD). Volume expanders and inotropic agents are often ineffective against this condition, whereas i.v. steroids are significantly effective. A major problem is that cystic periventricular leukomalacia (PVL) often develops a few weeks after an episode. The aim of the present study was to clarify the risk factors, including LCD, related to cystic PVL. Methods: A case–control study was performed for preterm infants who were delivered at

The incidence of late-onset circulatory dysfunction (LCD) of premature infants, which is characterized by sudden hypotension and oliguria, has recently increased in Japan. This condition suddenly occurs after several days of age without obvious causes in preterm infants with stable respiration and circulation. Intravenous steroids frequently improve the hypotension. The main problem with LCD is the subsequent and frequent onset of periventricular leukomalacia (PVL), and neurological development appears to be worse in PVL patients with LCD than those without LCD. The aim of this study was to determine whether the severity of magnetic resonance imaging (MRI) findings and neurological outcomes differ between infants who developed PVL after LCD and those who developed PVL without LCD. We retrospectively studied preterm infants who were delivered at less than 33 weeks of gestation between the years 2000 and 2003. During the study period, 10 and 26 infants developed PVL with and without LCD, respectively. The incidence of severe or moderate MRI findings was significantly higher in PVL patients with LCD (100%) than those without LCD (50%; p < 0.05). The incidence of severe cerebral palsy was 88% in PVL infants with LCD and 43% in PVL infants without LCD (p < 0.05). Moreover, the incidence of visual disorders was significantly higher in PVL infants with LCD (63%) than those without LCD (9%; p < 0.01). In conclusion, neurological outcomes are worse in preterm infants who develop PVL with LCD than those without LCD, which is well correlated to the severity judged by MRI findings.

Sepsis and its sequela remain a major source of morbidity and mortality in neonates despite advances in antimicrobials and aggressive supportive care. Many models of neonatal sepsis have been developed for investigating the pathophysiology of this disease and application of therapy, and a model with an infectious focus is closer to clinical reality. To establish an animal model that mimics the clinical characteristics of neonatal sepsis, the cecal devascularization and perforation procedure was implemented on 15 mixed-strain newborn piglets, which produced an infectious focus that acted as a continuous source of microorganisms to the peritoneal cavity. The mean survival time in animals with sepsis was 10.4 h (range 5.5-17.9 h), whereas all of the sham-operated control animals survived more than 24 h. Animals with sepsis showed a gradual significant decrease in the mean systemic blood pressure (mSBP; 71 +/- 3 mmHg in sepsis vs. 64 +/- 3 mmHg in control at 3 h, 38 +/- 7 mmHg in sepsis vs. 59 +/- 4 mmHg in control at 6 h, mean +/- SEM). They also showed an increase of serum levels of endotoxin (5.6 x 10 +/- 4.5 x 10 pg/mL in sepsis vs. 6.0 x 10 +/- 3.8 x 10 pg/mL in control at 6 h). Serum levels of TNF-alpha in the animals with sepsis became significantly higher than the control animals at 0 h (96 +/- 31 pg/mL in sepsis vs. 12 +/- 1 pg/mL in control) and remained significantly higher than all through the experiment. Serum levels of IL-6 in animals with sepsis showed a gradual increase (484 +/- 231 pg/mL in sepsis in its peak at 6 h vs. 24 +/- 5 pg/mL in control), however, there were no significant differences in serum IL-10 levels between the groups. Microorganisms detected in the blood of animals with sepsis were gram-negative enteric and anaerobic organisms. These results suggested that this model mimics the clinical state of neonatal sepsis and hence may have significant implications for the treatment of sepsis, including its use as a model in further investigations.

We investigated the relationship between the levels of granulocyte elastase alpha 1-proteinase inhibitor complex (E-alpha 1-PI) in plasma and severe intraventricular hemorrhage (IVH) in very low birthweight infants. The concentrations of E-alpha 1-PI and the ratio of the concentrations of E-alpha 1-PI to polymorphonuclear leucocyte counts within 24 h of birth in infants with severe IVH were significantly higher compared with those in infants without severe IVH. E-alpha 1-PI seems to be a useful indicator of IVH.

Norihisa Koyama,1 Masanori Kouwaki,1 Taihei Tanaka,2 Shigeru Ohki,3 Kazuhiro Iwase,4 Shunichi Terasawa,5 Masanao Miyaji,6 Toshimitsu Iwaki,7 Minoru Kokubo,8 Satoru Kobayashi,9 Haruo Mizuno,10 Shinji Fujimoto,10 Hajime Togari10 1Department of Pediatrics, Toyohashi Municipal Hospital, Toyohashi, 2Department of Pediatrics, Nagoya Daini Red Cross Hospital, Nagoya, 3Department of Pediatrics, Seirei Hamamatsu General Hospital, Hamamatsu, 4Department of Pediatrics, Nagoya City West Medical Center, Nagoya, 5Department of Pediatrics, Ichinomiya Municipal Hospital, Ichinomiya, 6Department of Pediatrics, Shizuoka Saiseikai General Hospital, Shizuoka, 7Department of Pediatrics, Gifu Prefectural Tajimi Hospital, Tajimi, 8Department of Pediatrics, Kainan Hospital Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Yatomi, 9Department of Pediatrics, Seirei Mikatabara General Hospital, Hamamatsu, 10Department of Pediatrics, Neonatology and Congenital Disorders, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Background: Sudden unpredictable hypotension during the post-transitional period, termed late-onset circulatory dysfunction (LCD) of premature infants, has been reported in low birth-weight infants who overcame major problems during the early neonatal period. We investigated the clinical features of LCD and factors associated with the occurrence of LCD. Methods: A multicenter retrospective case-control study. The clinical records of 1,004 children born at less than 32 weeks of gestation were reviewed. Patients with LCD were compared with age-matched non-LCD controls. Results: Of the 1,004 infants, 73 (7.3%) were diagnosed with LCD, with the incidence differing significantly among institutions (P

We investigated platelet-activating factor (PAF) in the tracheal aspirate from 3 intubated low birth weight infants with symptomatic patent ductus arteriosus (PDA). PAF increased with the onset of symptomatic PDA and decreased to the control range soon after the ductal closure. The concentration of PAF in 26 samples taken during symptomatic PDA (median 16 pg/micrograms lipid phosphorus, range 1.4-1,200 pg/micrograms lipid phosphorus) was significantly higher than that of 31 samples from the same three patients during the periods without symptomatic PDA (median 1.9 pg/micrograms lipid phosphorus, range 0-12 pg/micrograms lipid phosphorus; P0.001). All 3 infants later developed chronic lung disease. These results suggest that large shunting PDA provokes PAF release to the air way of the neonate and that PAF might play a role in chronic lung disease developing after symptomatic PDA.

A serial determination of pulmonary surfactant apoprotein-A (SP-A) was made on tracheal aspirates from seven intubated infants with different types of respiratory failure in the first week of life. A two-site immunoassay with monoclonal antibodies was adopted to determine the SP-A concentration. The concentrations of albumin in the same samples were also assayed, and these data were expressed as the ratio of SP-A to albumin (SP-A/albumin ratio), and evaluated against clinical data such as the arterial-alveolar oxygen tension ratio (a/APO2) or ventilatory index. In infants with respiratory distress syndrome, the SP-A/ albumin ratio was initially low, and increased gradually in the first few days of life with the improvement of a/APO2 and ventilatory index. The complication of pulmonary hemorrhage due to patent ductus arteriosus (PDA) resulted in a temporary decrease in the ratio. The infant with transient tachypnea of the newborn showed higher concentration from the first day of life and, in the course of PDA without pulmonary hemorrhage, the ratio did not decrease. The cases of congenital pneumonia showed the SP-A/albumin ratio remaining low while the infection was evident. These data suggest that the SP-A/albumin ratio of the tracheal aspirate can be used for the quantitative and qualitative evaluation of endogenous pulmonary surfactant in newborn infants with different respiratory disorders.

Recent advances suggest that mutations in nuclear DNA are involved in the etiology of autosomal dominant hypertrophic cardiomyopathy. Mitochondria have their own DNA, and mutations in mitochondrial DNA have been shown to contribute to the genesis of various diseases. In this study, we developed rapid sequencing methods with the use of a fluorescence-based sequencing system and analyzed total mitochondrial DNA of seven patients with nonautosomal dominant hypertrophic cardiomyopathy. Multiple point mutations were observed in all patients with hypertrophic cardiomyopathy, although some of them were common among the subjects examined and the others are unique to each subject. Point mutations in transfer RNA genes were observed in five of the seven patients, and point mutations that replaced conserved amino acids were also observed. These mutations may result in the impairment of mitochondrial function. According to these results, mutations in mitochondrial DNA may contribute to the genesis of some cases of nonautosomal dominant hypertrophic cardiomyopathy, and our methods may be useful for the detection of point mutations in mitochondrial DNA.

Human pulmonary surfactant contains four groups of apoproteins, SP-A, B, C and D. We determined the concentration of SP-A in the tracheal aspirate of newborn infants by a two-site simultaneous immunoassay with monoclonal antibodies, and used this assay to assess changes in surfactant in various clinical situations. SP-A concentrations were standardized per milligram of albumin in the aspirate. The ratio of SP-A/albumin (micrograms/mg) in tracheal aspirates of 18 preterm infants with respiratory distress syndrome (RDS), in which samples were obtained within 12 hours of birth, was significantly lower (0.2 +/- 0.1 microgram/mg, mean +/- S.D.) compared to a group of 20 non-RDS preterm infants of similar gestational age (15.8 +/- 7.4 micrograms/mg) (p less than 0.05). None of the RDS infants had a SP-A/albumin ratio above 1 microgram/mg within 12 hours of birth, but the ratio exceeded 5 micrograms/mg in all samples from non-RDS infants. The SP-A/albumin ratio significantly increased, however, at 48 to 72 hours after birth in infants with RDS (15.7 +/- 9.5 micrograms/mg). During the recovery phase of RDS, no difference was evident in the SP-A/albumin ratio in babies treated with artificial surfactant compared to those not treated.

Alterations in the electrical activity of the stomach were studied in 40 unanes-thetized dogs with intact vagal innervation, with selective proximal vagotomy (SPV) and with truncal vagotomy (TV) using a chronically implanted unipolar needle electrodes.The basic electrical rhythm (BER) of the normal canine stomach occurred regularly in the frequency of 4.5 to 5.5 cycles per minutes with a waxing and waning of initial and second potentials repeated in every 5 to 6 minutes. After SPV, irregular BER was observed occasionally within a few days postoperatively. After TV, irregularity of BER was more marked and frequent for the first 2 weeks. Subcutaneous administration of bethanechol chloride or histamine decreased the frequency of regular BER and increased the magnitude of second potentials equally in any dog of the control, SPV and TV groups. Similar changes were observed after feeding of the canned meat. Insulin-induced hypoglycemia increased the magnitude of antral second potentials in either control or SPV dogs. In contrast, TV dogs revealed repetition of initial potentials shortly after intravenous administration of insulin, but failed to show any changes relevant to hypoglycemia.