Cerebellar injury in preterm infants less than 28 weeks gestational age.

BACKGROUND: Cerebellar injury is one of the perinatal complications in preterm infants. Recent studies have highlighted the effect of perinatal complications on neurological morbidity. We investigated the perinatal risk factors and morbidity for cerebellar injury in extremely premature infants. METHODS: This retrospective cohort study included 285 infants born between April 2009 and December 2020 at gestational age <28 weeks at our institution. The infants were divided into two groups based on magnetic resonance imaging findings: those with and without cerebellar injury. We performed a statistical analysis of the perinatal background and short-term morbidity of the two groups. RESULTS: Significant differences (p < 0.05) were observed between the groups with respect to the perinatal background, especially gestational weeks, birthweight, and hemoglobin values at birth. In the short-term morbidity, significant differences (p < 0.05) were observed in the incidence of respiratory distress syndrome, chronic lung disease, hydrocephalus, severe intraventricular hemorrhage (IVH), and cerebellar hemorrhage. Extensive cerebellar lesions, such as cerebellar agenesis or global cerebellar hypoplasia, accounted for 11 of the 22 cases of cerebellar injury; seven of the 11 cases had severe IVH in addition to cerebellar hemorrhage. CONCLUSIONS: Gestational age was significantly lower in the cerebellar injury group. The combination of severe IVH and cerebellar hemorrhage may promote cerebellar injury.

[TWO CASES OF USING DUPILUMAB FOR REFRACTORY ATOPIC DERMATITIS WHO HAD HISTORIES OF BACTEREMIA AND UNDERLYING CONGENITAL HEART DISEASE].

Defects in the skin's barrier function are known to make it more likely for skin and soft tissue infection to occur in association with atopic dermatitis. These secondary infections sometimes develop into systemic infections such as bacteremia. Here, we report on our use of anti-IL-4/13 monoclonal antibody (dupilumab) on two cases with atopic dermatitis that was refractory to conventional management techniques and who had a history of serious infection (bacteremia and associated sternal osteomyelitis, infective endocarditis) caused by Staphylococcus aureus. Both cases had underlying congenital heart disease. The dermatological symptoms of both cases showed marked improvement at 16 weeks after the start of dupilumab use. The use of dupilumab on atopic dermatitis may lead to less risk of infection of skin and soft tissues deveroping serious infections due to an underlying congenital disease. When determining the treatment strategy, the cooperation of specialists in a variety of fields as well as the primary care physician was important.

Short- and Long-Term Outcomes of Extremely Preterm Infants in Japan According to Outborn/Inborn Birth Status.

OBJECTIVES: Outborn (born outside tertiary centers) infants, especially extremely preterm infants, are at an increased risk of mortality and morbidity in comparison to inborn (born in tertiary centers) infants. Extremely preterm infants require not only skilled neonatal healthcare providers but also highly specialized equipment and environment surroundings. Maternal transport at an appropriate timing must be done to avoid the delivery of extremely preterm infants in a facility without the necessary capabilities. Cases of unexpected deliveries at birth centers or level I maternity hospitals need to be attended emergently. We compared the differences in short- and long-term outcomes between outborn and inborn infants to improve our regional perinatal system. DESIGN: Retrospective cohort study. SETTING: Neonatal Research Network of Japan database. PATIENTS: Extremely preterm infants (gestational age between 22 + 0 and 27 + 6 wk) in the Neonatal Research Network of Japan database between 2003 and 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 12,164 extremely preterm infants, who were divided into outborn (n = 785, 6.5%) and inborn (n = 11,379, 93.5%) groups, were analyzed. Significant differences were observed in demographic and clinical factors between the two groups. Outborn infants had higher short-term odds of severe intraventricular hemorrhage (adjusted odds ratio, 1.49; 95% CI, 1.11-2.00; p < 0.01), necrotizing enterocolitis (adjusted odds ratio, 1.49; 95% CI, 1.11-2.00; p < 0.01), and focal intestinal perforation (adjusted odds ratio, 1.58; 95% CI, 1.09-2.30; p = 0.02). There were no significant differences in long-term outcomes between the two groups, except in the rate of cognitive impairment (adjusted odds ratio, 1.49; 95% CI, 1.01-2.20; p = 0.04). CONCLUSIONS: The frequency of severe intraventricular hemorrhage, necrotizing enterocolitis or focal intestinal perforation, and cognitive impairment was significantly higher in outborn infants. Thus, outborn/inborn birth status may play a role in short- and long-term outcomes of extremely preterm infants. However, more data and evaluation of improvement in the current perinatal environment are needed.

Application of the perfusion index in obstetric bleeding.

OBJECTIVE: We assessed the utility of the pulse oximeter perfusion index (PI) in maternal monitoring immediately after delivery. METHODS: We examined 30 pregnant women without any complications using the Rad7 device at delivery. The correlations between heart rate (HR), systolic blood pressure (BP), oxygen saturation SpO2, PI, Pleth variability index (PVI), shock index and blood loss were assessed. RESULTS: Blood loss at 20-min postpartum was not correlated with the difference in heart rate, systolic BP, SpO2, shock index or PVI taken immediately after delivery and at 20-min postpartum, but showed a strong negative correlation with the difference in the PI taken immediately after delivery and at 20-min postpartum (r = -0.70). CONCLUSION: PI changes were correlated with post-delivery blood loss and can be used for maternal monitoring at delivery.

Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

BACKGROUND: Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. METHOD: Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. RESULTS: Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. CONCLUSION: These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

Association of antenatal corticosteroids and the mode of delivery with the mortality and morbidity of infants weighing less than 1,500g at birth in Japan.

OBJECTIVE: This study aimed to re-evaluate the effectiveness of antenatal corticosteroids (ACS) and to analyze the association between ACS and the mode of delivery in the context of perinatal morbidity and mortality in very-low-birth-weight (VLBW) infants. STUDY DESIGN: This retrospective cohort study involved 15,765 VLBW infants born between 2003 and 2008 at less than 34 weeks of gestation and weighing less than 1,500 g at birth. Data were obtained from the Japanese neonatal research network database. Univariate and multivariate logistic regression analyses were performed to evaluate the impact of ACS and mode of delivery on the risk of infant mortality and morbidity. RESULTS: Administration of ACS was associated with decreases in mortality rate, intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP), and was not associated with the incidence of respiratory distress syndrome (RDS), periventricular leukomalacia or necrotizing enterocolitis (NEC). When the administration of ACS was analyzed in the context of different modes of delivery, the incidence of IVH and ROP tended to decrease with cesarean section deliveries, whereas the incidence of RDS tended to decrease and the incidence of NEC tended to increase for infants delivered vaginally. The incidence of chronic lung disease tended to increase in association with both delivery methods. CONCLUSIONS: This large cohort study reconfirms that ACS treatment is associated with decreases in infant mortality and severe morbidity. Furthermore, the delivery method may be associated with severe morbidity in VLBW infants exposed to ACS.

Retrospective review of thoracoamniotic shunting using a double-basket catheter for fetal chylothorax.

OBJECTIVE: From a single-center retrospective cohort with fetal chylothorax, we evaluated the factors related to the decision to use shunting, poor prognostic factors, and reported shunting outcomes with a new double basket-catheter device. METHODS: A retrospective single-center study was performed in 35 cases of fetal chylothorax. RESULTS: There were 35 cases of chylothorax: 23 with hydrops and 12 without hydrops. Twenty-one procedures were performed on 15 fetuses (11 with hydrops) with a single shunt in 11, two shunts in 3 and four shunts in 1. All 12 nonhydropic cases survived. In 23 hydropic cases, overall survival rates with and without thoracoamniotic shunting were 46 and 33%, respectively. The mortality rates of fetal hydropic cases with and without ascites were 93 and 11%, respectively. Fetal ascites, progression of fetal hydrops, and premature delivery at <33 weeks were significant risk factors for a poor prognosis. Progression of polyhydramnios after shunting was also associated with a poor prognosis. Obstruction of the catheter was observed in 38%. There were no direct fetal deaths associated with shunting. CONCLUSION: Thoracoamniotic shunting should be considered for pleural effusion before development of fetal hydrops, or at least before the appearance of fetal ascites. A double-basket catheter tends to be obstructive, but may be less invasive for fetuses.

Maternal outcome in pregnancy complicated with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH), including Eisenmenger syndrome, has a risk of mortality in pregnancy of 10-40%. The aim of this study was to investigate whether pulmonary artery blood pressure (PABP) is a prognostic factor for pregnancy outcome in patients with PAH. METHODS AND RESULTS: The subjects were 42 patients with PAH during pregnancy. Severe and mild cases were defined by PABP before and during the first 14 weeks of pregnancy, with severe cases having mean PABP >40 mmHg by catheterization or systolic PABP >50 mmHg on echocardiography. Eighteen women chose termination of pregnancy before 14 weeks, leaving 24 women (10 mild, 14 severe) for analysis. The women with severe PAH delivered earlier (35.4 vs. 31.5 weeks, P<0.05) and had higher rates of small-for-gestational-age infants (0/10 vs. 7/14, P<0.01). Among the women with severe PAH, the New York Heart Association class dropped by 1 in 9 cases, by 2 in 3 cases, and remained the same in 2 cases as pregnancy progressed, whereas among the women with mild PAH, the class dropped by 1 in 1 case and 9 women remained in the same class. Among the severe cases, 1 woman died and there was 1 fetal death; PABP markedly increased in later pregnancy from 54 to 74 mmHg (catheter measurement) and from 78 to 93 mmHg (echocardiography) (P<0.05). CONCLUSIONS: The level of PABP before or in the early stage of pregnancy is an important predictor of pregnancy outcome.

Thyroid regeneration: characterization of clear cells after partial thyroidectomy.

Although having the capacity to grow in response to a stimulus that perturbs the pituitary-thyroid axis, the thyroid gland is considered not a regenerative organ. In this study, partial thyroidectomy (PTx) was used to produce a condition for thyroid regeneration. In the intact thyroid gland, the central areas of both lobes served as the proliferative centers where microfollicles, and bromodeoxyuridine (BrdU)-positive and/or C cells, were localized. Two weeks after PTx, the number of BrdU-positive cells and cells with clear or faintly eosinophilic cytoplasm were markedly increased in the central area and continuous to the cut edge. Clear cells were scant in the cytoplasm, as determined by electron microscopy; some retained the characteristics of calcitonin-producing C cells by having neuroendocrine granules, whereas others retained follicular cell-specific features, such as the juxtaposition to a lumen with microvilli. Some cells were BrdU-positive and expressed Foxa2, the definitive endoderm lineage marker. Serum TSH levels drastically changed due to the thyroidectomy-induced acute reduction in T(4)-generating tissue, resulting in a goitrogenesis setting. Microarray followed by pathway analysis revealed that the expression of genes involved in embryonic development and cancer was affected by PTx. The results suggest that both C cells and follicular cells may be altered by PTx to become immature cells or immature cells that might be derived from stem/progenitor cells on their way to differentiation into C cells or follicular cells. These immature clear cells may participate in the repair and/or regeneration of the thyroid gland.

Outcome of pregnancy and effects on the right heart in women with repaired tetralogy of fallot.

BACKGROUND: Improved medical techniques have allowed most women with repaired tetralogy of Fallot (TOF) to reach childbearing age. The predictors of adverse events and the effects of pregnancy on cardiac function have not been clearly described in these patients. METHODS AND RESULTS: In the present study we retrospectively reviewed 40 deliveries in 25 patients with repaired TOF. There were 23 patients in New York Heart Association (NYHA) class I, and 2 in classes II-III before pregnancy. The mean age at delivery was 29.1 years and the mean gestational period was 37.8 weeks. Seven pregnancies (17.5%) in 7 patients were complicated with cardiac events such as a decline in NYHA class and arrhythmia. History of ablation and the baseline cardiothoracic ratio on chest radiography were predictors of adverse events. Peak plasma brain natriuretic peptide (BNP) level after the second trimester was higher in patients with cardiac events. Left ventricular size and contraction did not change from before to after pregnancy, but the right ventricle was enlarged at 6 months after delivery. CONCLUSIONS: Many of the pregnancies in women with repaired TOF were successful. However, careful management is required for some patients and the BNP level may be a useful marker to identify these patients. Because the right heart tended to be enlarged in the late postpartum period, pregnancy may also affect the long-term prognosis of patients with repaired TOF.

Pregnancy-associated aortic dilatation or dissection in Japanese women with Marfan syndrome.

BACKGROUND: Aortic dilatation and dissection are severe complications of pregnancy that may cause maternal death. The purpose of the present study was to investigate risk factors for aortic dilatation or dissection in pregnant Japanese women with Marfan syndrome. METHODS AND RESULTS: A total of 28 patients with Marfan syndrome were investigated retrospectively during pregnancy and after delivery at 1 institution. These patients were divided into 2 groups: those who experienced aortic dilatation or dissection (group D, n=11) and those who did not (group ND, n = 17). In group D, aortic dilatation or dissection occurred in 7 cases during pregnancy (2 in the 2(nd) trimester, 5 in the 3(rd) trimester) and 4 cases after birth. The 2 cases in the 2nd trimester involved aortic dilatation > 60mm and those patients underwent hemiarch replacement and a David operation, respectively. Delivery by cesarean section (64% vs. 18%, P < 0.05), sinus of Valsalva ≥ 40mm (86% vs. 21%, P < 0.05), aortic size index (size of sinus of Valsalva/body surface area) ≥ 25 mm/m² (7/7, 100% vs. 0/14, 0%, P < 0.0001), and faster growth of the sinus of the Valsalva (median, [interquartile range]: 0.41 mm/month [0.23-0.66 mm/month] vs. 0.05 mm/month [-0.13 to 0.22 mm/month]; P < 0.05) were significantly higher in group D than in group ND. CONCLUSIONS: A large sinus of Valsalva, increased aortic size index, and rapid growth of the sinus of Valsalva are risk factors for aortic dilatation or dissection in pregnant Japanese women with Marfan syndrome.

Axillary accessory breast associated with galactorrhea in an adolescent girl.

We present herein a case of right axillary accessory breast associated with galactorrhea in an adolescent girl. A 14-year-old Japanese girl presented with an 11-month history of a tender, subcutaneous lesion in the right axillary fossa. Seven months later, she experienced menarche. Subsequently, the patient noticed pressure-induced galactorrhea from both nipples. Physical examination revealed an elastic, firm and well-demarcated subcutaneous tumor 3 × 2 cm in size. A biopsy specimen showed proliferation of mammary gland tissue in the stroma located below the subcutaneous fat tissue. On the basis of these findings the patient was diagnosed with an accessory breast. Interestingly, the galactorrhea ceased after surgical removal of the accessory breast.

VIBE MRI for evaluating the normal and abnormal gastrointestinal tract in fetuses.

OBJECTIVE: The great potential of MRI for assessing gastrointestinal abnormalities in fetuses has been described. T1-weighted images may add additional information to T2-weighted images in diagnosing fetal gastrointestinal abnormalities. The objective of this study was to assess the performance of a 3D volumetric interpolated breath-hold sequence (VIBE) in evaluating the normal and abnormal fetal gastrointestinal tract. CONCLUSION: VIBE provides high-quality T1-weighted and 3D MR colonography images for the evaluation of the normal and abnormal gastrointestinal tract in fetuses, and 3D MR colonography provides excellent delineation of the meconium.

Polymorphic alleles of the human MEI1 gene are associated with human azoospermia by meiotic arrest.

Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Mouse meiotic mutant mei1 (meiosis defective 1) was isolated by a screening of infertile mice. Male mei1 mice have azoospermia due to meiotic arrest, and the mouse Mei1 gene is responsible for the mei1 phenotype. To investigate whether human MEI1 gene defects are associated with azoospermia by meiotic arrest, we isolated the human MEI1 cDNA based on the mouse Mei1 amino acid sequence. MEI1 is expressed specifically in the testis. Mutational analysis by direct sequencing of all MEI1 coding regions was performed in 27 men (13 European Americans, 13 Israeli and 1 Japanese) having azoospermia due to complete early meiotic arrest. This identified four novel, coding single-nucleotide-polymorphisms (cSNPs), i.e., SNP1 (T909G), SNP2 (A1582G), SNP3 (C1791A) and SNP4 (C2397T) in exons 4, 8, 9 and 14, respectively. Using these cSNPs, an association study was carried out between 26 non-Japanese patients with azoospermia and two sets of normal control men (61 normal European Americans and 60 Israelis). Consequently, SNP3 and SNP4 were shown to be associated with azoospermia among European Americans (P =0.0289 and P =0.0299 for genotype and allele frequencies at both the polymorphic sites, respectively), although no such association was observed among Israelis (P >0.05). Haplotype estimation revealed that the frequencies of SNP3-SNP4 (C-T), SNP3-SNP4 (A-C) and SNP3-SNP4 (A-T) were higher in the European American patients, and the frequency of SNP3-SNP4 (A-T) was also higher than in both control groups. These results suggest that MEI1 may play a role in meiosis during spermatogenesis, especially in European Americans.

Three-dimensional magnetic resonance imaging after ultrasonography for assessment of fetal gastroschisis.

A 24-year-old woman (Gravida I, Para I) at estimated 32 weeks of pregnancy was referred to our department for evaluation of a suspected fetal gastroschisis. Ultrasound scan revealed multiple loops of dilated bowel outside the fetal abdomen and absence of membrane surrounding the herniated loops of the intestines. Three-dimensional (3D) magnetic resonance imaging was performed to obtain more information on the bowel both outside and inside the abdomen. Images were constructed with T1-weighted fat-suppressed 3D fast low-angle shot sequences using a maximum intensity projection algorithm. The 3D images made possible the realization of fetal bowel conditions with greater definition and accuracy.

GATM, the human ortholog of the mouse imprinted Gatm gene, escapes genomic imprinting in placenta

The GATM gene encodes L-arginine:glycine amidinotransferase, which catalyzes the conversion of L-arginine into guanidinoacetate, the rate-limiting step in the synthesis of creatine. Since, deficiencies in creatine synthesis and transport lead to certain forms of mental retardation in human, the human GATM gene appears to be involved in brain development. Recently it has been demonstrated that the mouse Gatm is expressed during development and is imprinted with maternal expression in the placenta and yolk sac, but not in embryonic tissues. We investigated the imprinting status of the human GATM by analyzing its expression in four human placentas. GATM was biallelically expressed, thus suggesting that this gene escapes genomic imprinting in placentas, differently from what has been reported in mouse extra-embryonic tissues.

Isolation and expression analysis of the testis-specific gene, human OPPO1.

PURPOSE: To investigate human spermatogenesis, we isolated human testis-specific genes. METHODS: Using mouse amino acid sequences, we found the region including homology in amino acid level in the human genome sequences. The primers encompassing introns were made and RT-PCR and RACE were carried out. The resultant PCR products were sequenced. RESULTS: The full-length cDNA of human OPPO1 was isolated. It encodes 257 amino acid residues. The expression of the human OPPO1 was predominantly in the testis. On the other hand, partial cDNAs of ZNF8, GR194, GR219, GR093, GR046, GR163, and GR200 were expressed in the various tissues. CONCLUSIONS: Our data suggests that the human OPPO1 may play important roles in human spermatogenesis.

Counterclockwise barber-pole sign on prenatal three-dimensional power Doppler sonography in a case of duodenal obstruction without intestinal malrotation.

Three-dimensional (3D) power Doppler sonographic imaging provides a 3D view of the blood vessels. This technique reportedly has advantages over other forms of sonography in visualizing normal and abnormal fetal vascular anatomy. We report the case of a 36-year-old pregnant woman in whom 3D power Doppler sonography with simultaneous gray-scale imaging was performed at 32 weeks' gestational age to investigate an intestinal obstruction in the fetus that was suspected on the basis of 2-dimensional sonographic findings. The 3D sonograms revealed that the superior mesenteric artery and vein of the fetus were wound counterclockwise, forming the "barber-pole" sign. At 38 weeks' menstrual age, the female infant was delivered vaginally. Only duodenal atresia and annular pancreas, but not intestinal malrotation, were found postnatally. Surgical reconstruction of the duodenum was performed, with no major complications. Previous research suggests that the counterclockwise barber-pole sign is a normal finding. On the basis of our case, we believe that this "negative finding" might be used to exclude the diagnosis of midgut volvulus, a condition that would be expected to cause these vessels to wrap around in a clockwise direction.

The human transcript induced in spermatogenesis 50.

Background and Aims: Recently, a number of genes that are expressed specifically in the testis have been identified in rat and mouse. In 2002, 80 transcript induced in spermatogenesis (Tisp) genes with this specific expression were isolated in mice. In the human, however, the number of such genes isolated is much lower. The aim of this study therefore was the isolation of human genes specifically expressed in testis. Methods: We searched for human genome region with homology to the mouse Tisp gene family at the amino acid level using GenBank. The primers were made in human homologous regions, and polymerase chain reaction analysis was performed with templates using cDNA libraries of a range of human tissues. The cDNA specifically expressed in testis were isolated and detailed expression analysis was performed. Results: The 28 human TISP related genes were analyzed. Five of these genes were not expressed in testis and only three, TISP50, TISP15 and TISP43 related gene, were expressed specifically in testis. The cDNA of these three genes were isolated. Conclusion: Expression analysis demonstrated that there is some discrepancy between human and mouse for the TISP gene family. From expression patterns and amino acid sequences, it is suggested that the human TISP50, TISP15 and TISP43 related genes play some critical roles in spermatogenesis. (Reprod Med Biol 2004; 3: 237 - 243).