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Background The risk of ipsilateral breast tumor recurrence (IBTR) and the prognostic outcome of breast-conserving surgery (BCS) for germline BRCA1/2 pathogenic variant (BRCA1/2+) carriers remain controversial. We examined differences in IBTR and prognosis between BRCA1/2+ carriers and non-carriers following BCS for breast cancer. Methods Clinical and pathological data were collected by retrospectively reviewing charts of consecutive patients with stage 0-III breast cancer who underwent genetic testing for germline BRCA1/2 and BCS between 1996 and 2020. Patients with variants of breast cancer-associated genes other than BRCA1/2 were excluded. We compared the incidence of IBTR and prognosis, including overall survival (OS), breast cancer-specific survival (BCSS), and distant recurrence-free survival (DRFS), between BRCA1/2+ carriers and non-carriers. Results We analyzed 551 patients (587 breasts with cancer), including 30 BRCA1+ carriers (32 breasts) and 31 BRCA2+ carriers (32 breasts). The median follow-up was 5.8 years (7.2 and 5.3 years for carriers and non-carriers, respectively). The median age at breast cancer diagnosis was 43 and 46 years for carriers and non-carriers, respectively, indicating younger onset of cancer in carriers (age ≤ 40 years; 46.9% for carriers vs. 27.5% for non-carriers, p = 0.001). In carriers, breast cancer more frequently expressed estrogen receptor-negative (56.2% for BRCA1+ carriers and 15.6% for BRCA2+ carriers vs. 22.0% for non-carriers, p = 0.013), progesterone receptor-negative (62.5% for BRCA1+ carriers and 31.3% for BRCA2+ carriers vs. 29.5%, p = 0.005), nuclear grade III (45.3% for carriers vs. 29.5% for non-carriers, p = 0.010), or a higher Ki-67 index (Ki-67 index > 20) (89.5% vs. 61.8%, p = 0.001) than non-carriers. Moreover, carriers underwent chemotherapy more frequently than non-carriers (62.5% vs. 42.4%, p = 0.002). Cancer stage, tumor size, HER2 status, presence of lymphovascular invasion, and the rate of positive or close surgical margins did not statistically differ between the examined groups. No statistical differences were detected in the number of patients who underwent whole-breast radiotherapy following BCS: 59 breasts in carriers and 503 in non-carriers (92.2% vs. 96.4%). During follow-up, we noted that 9 breasts of BRCA1/2+ carriers (5 [15.6%] for BRCA1+ and 4 [12.5%] for BRCA2+) and 35 breasts (6.7%) of non-carriers developed IBTR (p = 0.035). In an analysis excluding patients who did not undergo radiotherapy, the rate of IBTR remained significantly higher in BRCA1/2+ carriers (p = 0.034) than that in non-carriers. The median time to IBTR was 10.2 years in carriers (10.2 years for BRCA1+ and 8.5 years for BRCA2+) and 3.5 years in non-carriers. Carriers were more likely than non-carriers to exhibit distinct subtypes of recurrent tumors in the ipsilateral breast (66.7% for carriers vs. 19.4% for non-carriers, p = 0.006), occurring in a different quadrant from the primary tumor (50.0% vs. 27.3%, p = 0.215). No significant differences in OS (p = 0.068), BCSS (p = 0.109), or DRFS (p = 0.359) were noted between carriers and non-carriers. Conclusion BRCA1/2+ carriers exhibited a higher risk of IBTR after BCS and a longer time to IBTR than non-carriers. One limitation of the present study is a longer follow-up period for carriers than for non-carriers, as carriers typically underwent long-term observation at our institution; hence, further data accumulation is warranted for validating these findings. Subtypes and quadrants of IBTR were frequently distinct in carriers, indicating the increased incidence of new primary breast cancer. Although the prognosis did not differ between carriers and non-carriers, our results suggest the necessity for long-term intensive breast surveillance of BRCA1/2+ carriers after BCS. Citation Format: Sakiko Kondo, Kumiko Kida, Misato Suzuki, Chika Fukano, Atsushi Yoshida, Naoki Hayashi, Junko Takei, Michiko Yamanaka, Hideko Yamauchi. Impact of BRCA1/2 pathogenic variants on ipsilateral breast tumor recurrence and prognosis following breast-conserving surgery [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-03.

Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1. This is the largest Asian case series and the first to apply an amplification-based next-generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys-Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non-Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in-frame deletions, and one (2.9%) had a multi-exon deletion, including two deceased patients analyzed with formalin-fixed and paraffin-embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples.

Umbilical cord rupture (UCR) in utero is a very rare and critical emergency that can cause fetal death within minutes. A 38-year-old nulliparous woman was admitted at 39 weeks in labour. Sudden watery vaginal discharge and bleeding with a rapid drop in the fetal heart rate to 60 beats/min necessitated an emergency caesarean section. A male infant weighing 2632 g was delivered 21 min after the onset of bradycardia; Apgar scores were 0 and 1 at 1 and 5 min, respectively. He was extremely pale; the umbilical arterial blood pH was 6.89 and haemoglobin was 9.0 g/dL. The umbilical cord had a velamentous insertion and was lacerated, with haemorrhage in the outer layer of an umbilical artery close to the placental end. The presentation was typical of UCR: vaginal bleeding following the rupture of membranes. Prompt diagnosis of UCR and termination of pregnancy are essential for fetal survival.

Inductively coupled plasma–tandem mass spectrometry (ICP-MS/MS) is a relatively new technique, with the first triple quadrupole ICP-MS (ICP-QQQ) being introduced commercially in 2012. However, the technique has quickly been accepted for a wide variety of applications in industries including, but not limited to, manufacturing, contract analysis, government, research, and academia. In this article, we explain the key steps to setting up an ICP-MS/MS method and address some of the common misconceptions surrounding the technique.

To evaluate the perinatal outcomes by gestational weight gain (GWG) range at 30 weeks of gestation among underweight pregnant women (pre-pregnancy body mass index ≤ 18.5 kg/mThis retrospective study was conducted at a hospital in Japan from 2003 to 2020. The underweight pregnant women (UPW; n = 3643) were divided into quartile groups based on the weight gain at 30 weeks of gestation: group Q1 ≤ 5.7 kg, 5.7 kg Q2 ≤ 7.2 kg, 7.2 kg Q3 ≤ 8.8 kg, and 8.8 kg Q4. Clinical characteristics and outcomes were compared using the t-test, chi-square test, and multivariable logistic regression analysis.The cumulative incidences of preterm births were 7.5% (n = 70), 5.0% (n = 45), 5.4% (n = 50), and 4.9% (n = 44), and the birth rates of small for gestational age (SGA) infants were 15.7% (n = 147), 9.6% (n = 87), 6.9% (n = 64), and 5.9% (n = 53) in Q1, Q2, Q3, and Q4, respectively. Multivariable analysis revealed that Q1 was significantly associated with preterm births (adjusted odds ratio [aOR] = 1.6; 95% confidence interval [CI] = 1.0-2.3), and Q1 and Q2 were significantly associated with SGA (adj. OR = 3.0; 95% CI = 2.2-4.3; adj. OR = 1.7; 95% CI = 1.2-2.5, respectively). None of the quartile groups were significantly associated with the incidence of primary cesarean sections, gestational diabetes mellitus, and macrosomia.In UPW, GWG at 30 weeks of ≤5.7 kg and ≤7.2 kg are associated with preterm birth and SGA rates, respectively.

In research enabling preclinical development and attaining a deeper understanding of the behavior of metallodrugs in cancer cells with acquired resistance, intracellular Pt accumulation could be considered an important biomarker and analytical focus. In this work, Pt accumulation patterns in terms of the number of cells and Pt mass in single cells were precisely defined by using inductively coupled plasma-mass spectrometry (ICP–MS) operating in a fast time-resolved analysis mode. This technique is otherwise known as single-cell (SC)–ICP–MS. By applying the nascent and validated SC–ICP–MS technique, comparisons across three Pt drugs (cisplatin, carboplatin, and oxaliplatin) in the A2780 and A2780cis ovarian cancer cell models could be made. Additional roles of transporters on top of passive diffusion and the drugs’ bioactivity could be postulated. The SC–ICP–MS-based observations also served as a cross-validation point to augment preexisting research findings on Pt-resistance mechanisms. Conjectures regarding S and Fe metabolism were also derived based on an additional and direct ICP–MS analysis of endogenous elements. Overall, our work not only confirms the utility of SC–ICP–MS in chemotherapeutic research, but also provided insights into further ICP–MS-based analytical capacities to be developed.

The elemental composition of a single yeast, green alga, or red blood cell (RBC) was precisely determined by using inductively coupled plasma-mass spectrometry (ICP-MS) operating in fast time-resolved analysis (TRA) mode. The technique is known as single-cell (SC)-ICP-MS. Phosphorus, sulfur, magnesium, zinc, and iron were detected in the three types of cell. The elemental composition of yeast and green alga obtained by SC-ICP-MS was consistent with results obtained from conventional ICP-MS measurements following acid digestion of the cells. Slight differences were found in the measured values between SC-ICP-MS and the conventional ICP-MS results for RBC. However, the SC-ICP-MS results for S and Fe in RBC were closer to the estimated values for these elements that were calculated from the level of hemoglobin in RBCs. The data suggest that SC-ICP-MS is suitable for the analysis of various cell types, namely, fungus, plant, and animal cells.

Background: A fast and sensitive method for the simultaneous analysis of iodine and bromine species in infant formula was developed using HPLC–inductively coupled plasma–MS (HPLC-ICP-MS). Method: To determine the four halogen species [iodide (I−), iodate (IO3−), bromide (Br−), and bromate (BrO3−)] in a milk-based Standard Reference Material and four commercially available infant formula products. Results: The four halogen species were baseline separated in less than 6.5 min using an anion exchange resin column and 5.0 mM NaH2PO4 / 15.0 mM Na2SO4 / 5.0 mM EDTA (pH 7.0) mobile phase. Following separation, the halogen species were detected by measuring m/z 79 for Br and m/z 127 for I using a triple quadrupole–ICP-MS. The instrument was operated in single quadrupole mode with helium cell gas. Excellent linearity (R = 0.9999 or better) was obtained for all four species with calibration standards ranging from 0 to 100 ppb. The LOD for I−, IO3−, Br−, and BrO3− were all less than 0.67 μg/kg. To test the suitability of the method for the accurate determination of low concentrations of the four species in infant formula samples, a spike recovery test was carried out at 20 and 40 μg/kg into the diluted infant formula samples. Conclusions: Total elemental determinations of iodine and bromine were also performed using the triple quadrupole–ICP-MS without HPLC.

The case was a male neonate born by emergent cesarean section due to non-reassuring fetal status at 30 weeks of gestation. His manifestations were consistent with those of Rodriguez syndrome. Molecular analysis revealed an SF3B4 mutation.

Background: The antenatal weight targets of gestational weight gain (GWG) (earlier than 40 weeks) among underweight pregnant women (UPW: pre-pregnancy body mass index≤18.5 kg/m2) that are useful for the management of weight during pregnancy have not been reported. It had been recently pointed out that firm GWG restrictions have led to an increase in the number of low-birth-weight infants in Japan. Thus, this study aimed to evaluate the perinatal outcomes by GWG at 30 weeks of gestation among UPW and to discuss the effects of GWG restrictions.Methods: This retrospective cohort study was conducted at a hospital in Japan from 2003 to 2020. The UPW (n=3,643) were divided into the four quartile groups based on the GWG at 30 weeks of gestation: group A ≤ 5.7 kg, 5.7 kg < group B ≤ 7.2 kg, 7.2 kg < group C ≤ 8.8 kg, and 8.8 kg < group D. Their clinical characteristics and outcomes were compared using t-test, chi-square test, and multivariate logistic regression analysis.Results: The incidence rates of preterm births were 7.5% (n=70), 5.0% (n=45), 5.4% (n=50), and 4.9% (n=44) and the birth rates of small-for-gestational age (SGA) infants were 15.7% (n=147), 9.6% (n=87), 6.9% (n=64), and 5.9% (n=53) in groups A, B, C, and D, respectively. Multivariate logistic regression analysis showed that group A was significantly associated with preterm births [adjusted odds ratio (Adj. OR) = 1.6; 95% confidence interval (CI) = 1.0–2.3; p = 0.018], and groups A and B were significantly associated with SGA [Adj. OR = 3.0; 95% CI = 2.2–4.2; p < 0.001] [Adj. OR = 1.7; 95% CI = 1.2–2.5; p = 0.002] . No significant differences were noted in the ratio of cesarean section (CS) (p = 0.344), hypertensive disorders of pregnancy (HDP) (p = 0.954), and macrosomia (p = 0.147) among the four groups.Conclusions: The GWG at 30 weeks of >5.7 kg for preterm birth and >7.2 kg for SGA is recommended. Firm weight restrictions for UPW may have led to an increase of adverse outcomes without reducing the risk of CS, HDP, and macrosomia.

Even though evaluating the metal content in asphaltenes is now a routine analysis, determining the nature of the metals present in asphaltenes has continued to be an elusive subject. In this work, we presented, for the first time, the application of single-particle inductively coupled plasma mass spectrometry (spICP–MS) in hydrocarbon media to determine the presence of metal-containing nanoparticles in asphaltene solutions. This method also offers the unique ability to differentiate between metal-containing nanoparticles and dissolved metals. The study of three asphaltene samples from different origins indicates that vanadium and nickel are entirely dissolved probably as part of soluble coordination complexes, such as porphyrins. In clear contrast, we found that molybdenum and iron are forming part of nanoparticles and report nanoparticle distributions. We found that nanoparticle distributions for molybdenum are very similar for the different asphaltenes, while for iron oxide, the size increases as the co...

A 24-year-old woman at 38 weeks of gestation with no past medical history was transferred to our hospital because of acute onset of severe dyspnea. Her conscious level was E4V2M5 on the Glasgow Coma Scale and she displayed stress cardiomyopathy (Takotsubo cardiomyopathy) with multiple organ failure. Intrauterine fetal death was confirmed. After immediate application of intubated ventilation, percutaneous cardiopulmonary support and hemodialysis, she was diagnosed with pheochromocytoma multisystem crisis. After multidisciplinary team discussion, surgical resection of the left pheochromocytoma was performed on the same day. However, the bleeding from retroperitoneal drainage did not decrease, therefore, on the fourth day of hospitalization, embolization of the left renal artery under angiography was performed. A 2774 g female infant was stillborn spontaneously on the seventh day of hospitalization. Percutaneous cardiopulmonary support was discontinued on the fifth day of hospitalization and the tracheal tube was extubated on the 11th day. The patient was discharged after 30 days.

Tools that provide absolute quantification of biomolecules, particularly of proteins and their post-translational modifications, without needing suitable specific standards, are urgently demanded nowadays. To this end, we have significantly improved the recently introduced strategy based on CH addition to the plasma for absolute quantification of biomolecules using HPLC-ICP-MS. Addition of CO has been optimized and finally selected as a safer, more efficient quantitative strategy that is able to provide constant (, The authors acknowledge financial support of Spanish Ministry of Economy and Competitiveness through CTQ2016-79412-P, and BES-2014-068032 and EEBB-I-17-12654 (F.C.C).

To investigate the pregnancy outcome of the fetuses with trisomy 18, we studied 123 cases of trisomy 18 who were born at our hospital from 1993 to 2009. Among them, 95.9% were diagnosed with trisomy 18 prenatally. Prenatal ultrasound findings showed fetal growth restriction in 77.2%, polyhydramnios in 63.4% and congenital heart defects in 95.1%. For 18 cases, cesarean section (C-section) was chosen, and for 75 cases, transvaginal delivery was chosen. Premature delivery occurred in 35.5%. Stillbirths occurred in 50 cases (40.7%). Fetal demise before onset of labor occurred in 30 cases and fetal demise during labor occurred in 20 cases which was 26.7% of vaginal deliveries. Among the 73 live-born infants, the survival rate for 24 h, 1 week, 1 month and 1 year were 63%, 43%, 33% and 3%. The median survival time was 3.5 days. There was no significant difference between the survival time of C-section and that of vaginal delivery. However, for the births involving breech presentation, the survival time of C-section was significantly longer than that of vaginal delivery. When the fetus is diagnosed with trisomy 18, the parents have to make many choices. These findings constitute critical information in prenatal counseling to the couples whose fetuses have been found to have trisomy 18, especially when they choose palliative approaches in the perinatal management.

Bent bone dysplasia-fibroblast growth factor receptor 2 type (BBD-FGFR2) is a recently identified skeletal dysplasia caused by specific FGFR2 mutations, characterized by craniosynostosis and prenatal bowing of the long bones. Only a few cases have been published. We report an affected fetus terminated at 21 weeks of gestation. The clinical and radiologic manifestations mostly recapitulate previous descriptions; however we suggest additional hallmarks of this disorder in early gestation. These hallmarks include distinctive short, thick clavicles and wavy ribs, as well as vertebral bodies that showed striking anteroposterior shortening. Femoral fractures were also present in our case. Although craniosynostosis is a hallmark of the disease, clinicians should be aware that craniosynostosis might not be readily apparent on plain films early in gestation.

To obtain basic data for improving genetic counseling, we focused on couples' decision-making with regard to having additional children after notification of their status as a carrier of a reciprocal balanced chromosomal translocation. Carrier status is typically determined after birth of a child with a birth defect derived from a chromosomal unbalanced translocation inherited from the parents' balanced translocation. From April 2004 to December 2004, 15 couples from Kanagawa prefecture of Japan were interviewed. Children of the couples had unbalanced translocations, and one member of each couple was diagnosed or hypothesized to be a carrier of a reciprocal translocation. Clinical and familial information was obtained by personal interviews in our hospital, and then statistically analyzed. Fifteen couples were interviewed in which the mean age of propositi, fathers, and mothers were 4.7, 31.2, and 31.1 years, respectively. The couples were divided into two groups according to their decision-making process. Each couple that did not want more children already had at least one healthy child before the birth of the propositus. Each couple that did not disclose their own carrier status had a propositus younger than 2 years old. Each couple that had at least one healthy child before the birth of the propositus carrying an unbalanced translocation showed reluctance towards another pregnancy. On the other hand, each couple that did not have healthy children before the birth of the propositus showed strong willingness for a future pregnancy. Each couple that had a propositus younger than 2 years old needed more time to accept the evidence of their carrier status.

Background Delay of umbilical cord clamping by at least 1 min is recommended for newborns not requiring resuscitation in the International Liaison Committee On Resuscitation–Consensus on Science with Treatment Recommendations (ILCOR-CoSTR) 2010 guidelines. The delay in clamping improves iron status through early infancy but may increase the likelihood of jaundice requiring phototherapy. The present study investigated the relationship between umbilical cord hemoglobin and the rate of jaundice requiring phototherapy in healthy Japanese newborns. Methods Cord hemoglobin was measured in healthy newborns and the rate of infants receiving phototherapy for jaundice and other data were obtained from medical records. Results Jaundice requiring phototherapy mostly occurred in association with high cord blood hemoglobin, which is increased by delayed cord clamping. Conclusions Higher cord hemoglobin may increase neonatal jaundice in newborns in Japan, therefore the present results support the Japan Resuscitation Council guideline 2010, which does not recommend delay of umbilical cord clamping by at least 1 min, in contrast to the ILCOR guidelines.

Familial congenital diaphragmatic hernia (CDH) is extremely rare; it comprises about 2% of all CDH cases. The empirical risk is about 2%, increasing to 10% in a family with two affected children. This report describes severe CDH in two siblings who had been diagnosed prenatally. The female newborn diagnosed with left CDH prenatally was born at 38 weeks of gestation. Despite surgical repair and intensive treatment, she died 10 days after birth. Her younger brother was born at 39 weeks of gestation after being diagnosed with bilateral CDH prenatally, and died 75 min after birth. Both infants had neither other congenital anomaly nor chromosomal abnormalities. Their parents are healthy without consanguinity. Their first daughter and the fourth child have no congenital anomalies.

Background Infants are at particular risk of iron-deficiency anemia. We investigated the changes in the blood count of mother and infant as well as the relationship between them and the relationship between an infant's nutrition method and infant anemia. Methods This retrospective cohort study included healthy neonates born between August 2011 and July 2014 in St. Luke's International Hospital, Tokyo, Japan. Data from blood samples of mothers obtained during late pregnancy and those of infants obtained at birth and at the age of 3, 6, and 9 months were analyzed. Using multivariate logistic regression, we investigated nutrition methods, maternal anemia, and other clinical relevant parameters that were potential risk factors for infant anemia. Results In total, data for 3472 infants and their mothers were analyzed. Nutrition method was the most significant risk factor for infant anemia, with risk of future anemia decreasing in the following order: exclusively breastfeeding, partially breastfeeding, and formula feeding. Furthermore, low umbilical cord blood hemoglobin lead to a tendency for the child to suffer from anemia Conclusion The method of infant nutrition was the most significant factor related to anemia in late infancy. Infants with low umbilical cord blood hemoglobin value are more likely to suffer from anemia in late infancy. This article is protected by copyright. All rights reserved.

Although recent studies in patients with paternal uniparental disomy 14 [upd(14)pat] and other conditions affecting the chromosome 14q32.2 imprinted region have successfully identified underlying epigenetic factors involved in the development of upd(14)pat phenotype, several matters, including regulatory mechanism(s) for RTL1 expression, imprinting status of DIO3 and placental histological characteristics, remain to be elucidated. We therefore performed molecular studies using fresh placental samples from two patients with upd(14)pat. We observed that RTL1 expression level was about five times higher in the placental samples of the two patients than in control placental samples, whereas DIO3 expression level was similar between the placental samples of the two patients and the control placental samples. We next performed histological studies using the above fresh placental samples and formalin-fixed and paraffin-embedded placental samples obtained from a patient with a maternally derived microdeletion involving DLK1, the-IG-DMR, the MEG3-DMR and MEG3. Terminal villi were associated with swollen vascular endothelial cells and hypertrophic pericytes, together with narrowed capillary lumens. DLK1, RTL1 and DIO3 proteins were specifically identified in vascular endothelial cells and pericytes, and the degree of protein staining was well correlated with the expression dosage of corresponding genes. These results suggest that RTL1as-encoded microRNA functions as a repressor of RTL1 expression, and argue against DIO3 being a paternally expressed gene. Furthermore, it is inferred that DLK1, DIO3 and, specially, RTL1 proteins, play a pivotal role in the development of vascular endothelial cells and pericytes.

Down syndrome is an autosomal chromosome disorder, characterized by intellectual disability and muscle hypotonia. Muscle hypotonia is observed from neonates to adulthood in Down syndrome patients, but muscle hypertonicity is extremely unusual in this syndrome. During a study period of nine years, we found three patients with severe spastic quadriplegia among 20 cases with Down syndrome and congenital duodenal stenosis/atresia (3/20). However, we could find no patient with spastic quadriplegia among 644 cases with Down syndrome without congenital duodenal stenosis/atresia during the same period (0/644, P

We report a female fetus with sirenomelia with 46,X,t(X;16)(p11.23;p12.3) de novo. Fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes were employed for narrowing down the breakpoint regions. On chromosome 16, the breakpoint was mapped in the region of RP11-453F10 (19 920 640-20 118 153 bp from 16pter). On chromosome X, the breakpoint was mapped in the region of RP11-794A15 (47 333 744-47 524 066 bp from Xpter). This is the first case report of sirenomelia associated with translocations. The abnormal phenotype, associated with a balanced translocation, was caused by deletion or breakage of dosage-sensitive genes of the breakpoint, disruption of an imprinted gene, or uniparental disomy. Although the parental origin of normal 16 and der(16) remained undetermined, this case will provide insight into the pathogenetic mechanism of sirenomelia.

Introduction: Unlike gastroschisis, congenital omphalocele is often associated with other anomalies and is frequently complicated by polyhydramnios. We examined the relationships between polyhydramnios, pregnancy outcome and fetal prognosis.Patients and Methods: Clinical data from cases diagnosed antenatally with congenital omphalocele from 1993 to 2006 were analyzed retrospectively. Results: Fifty-two cases were diagnosed antenatally with congenital omphalocele, and 38 of these pregnancies resulted in delivered infants. Of these 38 pregnancies, 55.3% were preterm births before 37 weeks of gestation. The mean birth weight was 2,148 g (n = 38). Associated anomalies were recognized in 29 cases (76.3%), including 13 cases (34.2%) of chromosomal aberrations. There were 2 cases of trisomy 13, 10 cases of trisomy 18 and 1 case of trisomy 21. Polyhydramnios was detected in 14 cases (36.8%), and other anomalies were present in all of these cases. Discussion: For antenatal evaluation in cases of congenital omphalocele, it is important to examine the fetus for associated anomalies or underlying disease, especially when polyhydramnios is detected.

Aim: We examined birth-related malpractice civil litigation cases in Japan to clarify the actual status related to the implementation of an obstetrical no-fault compensation system in 2009. Material & Methods: In this retrospective review, we analyzed legal and medical information from 64 cases with a delivery date after 1987 and a judgment date between April 1997 and March 2007. Results: The malpractice claim was accepted in 44 cases and rejected in 20 cases. The period from the delivery to the judgment date was lengthy (90.1 months overall). The average amount of damages awarded was ¥97 810 000 for cases of cerebral palsy (CP). Preterm births and less than 2500 g infants represented a higher incidence rate in the rejected cases. There were 32 cases (50.0%) with CP, 18 (28.1%) with infant death, 10 (15.6%) with neonatal death, and 4 (6.3%) with fetal death. Twenty-three of 44 accepted cases (52.3%) and 11/20 rejected cases (55.0%) had a gestational age of more than 33 weeks at birth and weighed more than 2000 g. Forced deliveries were performed in 45/64 cases (70.3%), and augmentation/induction of labor was performed in 28/64 cases (43.8%). There were 13/16 (81.3%) accepted cases that underwent vacuum and/or forceps extraction after labor augmentation/induction. Conclusions: More than half of our cases could be sufficient for a no-fault compensation system in Japan. Though the system is considered to have some problems that need to be solved, this finding suggests that many children and their families may benefit from the new system without having to file.

To evaluate whether the routinely collected data in birth defect registries could be used to assess association between medications and risk for congenital anomalies an "exposed case-only" design was performed.Twelve registries provided 18,131 cases exposed to a medication during the first trimester of pregnancy and with at least one major malformation. Odds ratios for malformations associated with maternal use of selected medications were computed.Among seven most commonly used medications very few significant associations with malformations were identified. Among fourteen potentially teratogenic medications several strong associations were found, including valproic acid with spina bifida, and insulin (as proxy for diabetes) with several types of cardiac defects.Finding known associations provides assurance on the validity of this approach, whereas identifying new associations provides a signal to be followed by confirmatory studies. Through this activity, international networks of birth defect registries can contribute with limited resources to post-marketing surveillance of the teratogenicity of medications. (C) 2010 Elsevier Inc. All rights reserved.

Aim: This study of pregnant women was undertaken to clarify their immune status for rubella and to evaluate the efficacy of, and adverse reaction to, post-partum rubella vaccination. Methods: We determined the levels of both rubella antibody by hemagglutination inhibition test and IgM antibody by enzyme-linked immunosorbent assay in the first gestational trimester and surveyed the positive rates for rubella antibody in pregnant women at our perinatal center; we recommended post-partum vaccination for women with poor immune status. We also evaluated the effectiveness of the vaccine and any adverse reaction. Results: Among 2741 pregnant women, 185 cases (6.7%) were seronegative for rubella virus. This rate was especially high (12.4%) in the population who had opted out of the vaccination because of a change in Japanese government policy. A total of 30 cases (1.1%) were positive or false-positive for IgM antibody, but no congenital rubella syndrome (CRS) developed. The seropositive rate was 93.3% in total, but this figure includes those who required post-partum vaccination (558 cases or 20.3%) because their titers were 16× or lower. Among 145 cases who received post-partum rubella vaccine, no severe adverse reaction was detected, and in all 37 cases with hemagglutination inhibition antibody titers of 8× or lower, the efficacy rate was 100%. Conclusions: It is necessary to appropriately evaluate the CRS risk. Also, we need to emphasize the importance and safety of post-partum rubella vaccination in Japan.

Introduction: Fetus-in-fetu is a rare congenital fetiform mass whose etiology is still controversial. We report two cases of fetus-in-fetu. Case 1: A fetal retroperitoneal cystic tumor including two masses was detected by ultrasonography at 26 gestational weeks. The masses showed distinctive structures resembling a vertebral axis and were prenatally diagnosed as fetus-in-fetu. A resected specimen revealed two fetiform masses. Case 2: An intracranial tumor with hydrocephalus was detected by ultrasonography at 19 gestational weeks. The pregnancy was terminated, and a postmortem examination revealed six fetiform masses with immature teratoma. Discussion: The tumors may possibly consist of parasitic monozygotic diamniotic twins or highly differentiated teratomas.

A series of bimetallic complexes composed of lanthanide metallocene and trimethylaluminum, Cp*2Ln[(μ-Me)AlMe2(μ-Me)]2LnCp*2 (Cp* = η5-C5Me5, Ln = Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Tm, Yb, Lu), were prepared, and the ability to catalyze polymerization of butadiene in the presence of cocatalysts, AlR3 (R = Me, iBu) and [Ph3C][B(C6F5)4], was studied as a function of the 11 different lanthanide metal species and the kind of alkylaluminum in the cocatalyst. Both catalytic activity and microstructure of polybutadiene depended strongly on the kind of lanthanide metal and the trialkylaluminum. The Gd complex in combination with AliBu3/[Ph3C][B(C6F5)4] was extremely active and gave perfectly 1,4-cis regulated polybutadiene at −40 °C. In contrast, the Ce complex with almost similar cocatalysts, AlMe3/[Ph3C][B(C6F5)4], yielded polybutadiene having a very high content of 1,4-trans microstructure (1,4-trans selectivity = 93.8%). With the Al/Ln ratio was 3−5, the polymerization systems, in which the alkylaluminum worked ...

A 6-month-old girl had multiple congenital anomalies, including dysmorphic face; tetralogy of Fallot, pulmonary atresia and patent ductus arteriosus; congenital cystic adenomatoid malformation of the right upper lung, and hemilateral kidney defect. Chromosome analysis as well as fluorescence in situ hybridization (FISH) and polymorphic marker analyses in the girl and her parents revealed a de novo large interstitial deletion of 17p13.1-p11.2 of the paternally derived chromosome 17. The deletion involved the Smith-Magenis chromosome region (SMCR). Lack of involvement of the Miller-Dieker syndrome region at 17p13.3 was confirmed by both FISH analysis and radiological examinations that showed no migrational abnormality. The girl died at age 7 months. This is the first report of a patient with a large interstitial deletion of 17p.

We present a boy and two girls with paternal uniparental disomy of chromosome 14q (patUPD14). One girl had a Robertsonian translocation, whereas two a normal karyotype. Based on the manifestations of these patients and four previously reported patients who all had translocated chromosome 14, The patUPD14 was thought to constitute a distinctive syndrome. The hallmarks included abdominal muscular defects, skeletal anomalies, and characteristic facies. The phenotype of patUPD14 was consistent with that of a previously reported mouse model, i.e., mouse embryos with paternal uniparental disomy of chromosome 12 that has a region orthologous to that of human chromosome 14. Dose effects of newly recognized imprinted genes on human chromosome 14q32, DLK1 and GTL2, could play an important role in the pathogenic mechanism of the distinctive malformation complex.

Our purpose is to prove that prolonged inflammation of the chorionic plate, which we have termed subacute chorioamnionitis (SCAM), is a distinctive entity and should be differentiated from acute chorioamnionitis (ACAM) because it is an excellent prognostic indicator of chronic lung disease (CLD), including Wilson-Mikity syndrome (WMS). Ninety singleton placentas with stage-3 chorioamnionitis were delivered at 23 to 32 weeks of gestation during 1993 to 1996, and the infants survived more than 28 days. There were 49 placentas with stage 3 SCAM, 33 placentas with stage 3 ACAM, and 8 placentas with subacute necrotizing funisitis (SNF) and without inflammation of the chorionic plate. Fifty-three of gestation- and birthweight-matched placentas without chorioamnionitis were selected as control. To determine the risk factors for CLD, 27 clinical and 6 histological variables were analyzed. Logistic regression analysis showed that amniotic necrosis (AN) (P =.0168) and low birthweight (P =.0341) were the major contributing risk factors for CLD. SNF was not significantly related to CLD. Patients with SCAM (AN+, SNF-) were highly susceptible to CLD. In conclusion, SCAM, especially when associated with AN, seems to be a unique prognostic indicator of CLD.

To investigate the pregnancy outcome of the fetuses with trisomy 18, we studied 123 cases of trisomy 18 who were born at our hospital from 1993 to 2009. Among them, 95.9% were diagnosed with trisomy 18 prenatally. Prenatal ultrasound findings showed fetal growth restriction in 77.2%, polyhydramnios in 63.4% and congenital heart defects in 95.1%. For 18 cases, cesarean section (C-section) was chosen, and for 75 cases, transvaginal delivery was chosen. Premature delivery occurred in 35.5%. Stillbirths occurred in 50 cases (40.7%). Fetal demise before onset of labor occurred in 30 cases and fetal demise during labor occurred in 20 cases which was 26.7% of vaginal deliveries. Among the 73 live-born infants, the survival rate for 24 h, 1 week, 1 month and 1 year were 63%, 43%, 33% and 3%. The median survival time was 3.5 days. There was no significant difference between the survival time of C-section and that of vaginal delivery. However, for the births involving breech presentation, the survival time of C-section was significantly longer than that of vaginal delivery. When the fetus is diagnosed with trisomy 18, the parents have to make many choices. These findings constitute critical information in prenatal counseling to the couples whose fetuses have been found to have trisomy 18, especially when they choose palliative approaches in the perinatal management.

Delay of umbilical cord clamping by at least 1 min is recommended for newborns not requiring resuscitation in the International Liaison Committee On Resuscitation-Consensus on Science with Treatment Recommendations (ILCOR-CoSTR) 2010 guidelines. The delay in clamping improves iron status through early infancy but may increase the likelihood of jaundice requiring phototherapy. The present study investigated the relationship between umbilical cord hemoglobin and the rate of jaundice requiring phototherapy in healthy Japanese newborns.Cord hemoglobin was measured in healthy newborns and the rate of infants receiving phototherapy for jaundice and other data were obtained from medical records.Jaundice requiring phototherapy mostly occurred in association with high cord blood hemoglobin, which is increased by delayed cord clamping.Higher cord hemoglobin may increase neonatal jaundice in newborns in Japan, therefore the present results support the Japan Resuscitation Council guideline 2010, which does not recommend delay of umbilical cord clamping by at least 1 min, in contrast to the ILCOR guidelines.

Objective: To evaluate the risk of recurrence of fetal chromosomal aberrations in women who had offspring with numeric chromosomal abnormalities. Subjects and Methods: This collaborative study consisted of 1,076 Japanese women with a history of offspring with trisomy-21, -18, -13, or 45,X. Second-trimester amniocenteses were performed, resulting in 1,248 fetal karyotypes that were analyzed with reference to prior offspring karyotypes and maternal age. Results: Of the 842 women with trisomy-21 offspring, 10 conceived another such fetus. In 2 women with 3 or more such offspring, parental mosaicism of trisomy-21 was suspected. The incidence of recurrence of trisomy-21 increased with age, and significantly exceeded the incidence of trisomy-21 fetuses in the general population. None of the 170 women with trisomy-18 offspring, and none of the 46 women with trisomy-13 offspring, had another such fetus. Of the 18 women with 45, X offspring, 1 with mos 45, X/46, XX had another such fetus. Conclusions: The risk of recurrence of trisomy-21 is affected by maternal age and parental germline mosaicism. The risk of recurrence of trisomy-18 or -13 appears to be much lower than that of trisomy-21. Women who give birth to more than 1 offspring with 45, X should be examined for mos 45, X/46, XX.

Trace metals in sea-water were determined by ion chromatography (IC)–inductively coupled plasma mass spectrometry (ICP-MS). A nitrilotriacetate (NTA)-type chelating resin was applied to the separation and enrichment of the analyte metal ions. Transition metals and rare earth elements except Mn were retained on the NTA resin column whereas alkali and alkaline earth metals were eluted from the column by elution with 0.5 mM nitric acid. The NTA resin can simplify the procedure for matrix elimination and enrichment of analyte metals since mineral acids can be used as eluents. A linear calibration and repeatability of the signal intensity of ICP-MS were obtained in the determination of trace metals at the

A specific determination for bromate, iodate and other halogen anions in drinking water by direct injection using ion chromatography (IC), with either inductively-coupled plasma mass spectrometry (ICP-MS) or postcolumn derivatization, is described. The advantages of ICP-MS as an element-selective detector was evaluated for bromate and iodate by considering the comparison with the postcolumn derivatization. Samples were directly injected into the IC column, and halogen anions were separated. The eluates were directly introduced into ICP-MS and detected at 79 and 127 u. The detection limit (S/N=3) for bromate and iodate with injection of 0.5 ml were 0.45 μg/l and 0.034 μg/l, respectively. IC combined with ICP-MS was applied to the simultaneous determination of bromate, bromide and other halogen anions in raw and ozonized water. Good agreement was obtained for the determined values by IC–ICP-MS and postcolumn derivatization. Furthermore, several bromine species different from bromate or bromide were detected by IC–ICP-MS.

Familial congenital diaphragmatic hernia (CDH) is extremely rare; it comprises about 2% of all CDH cases. The empirical risk is about 2%, increasing to 10% in a family with two affected children. This report describes severe CDH in two siblings who had been diagnosed prenatally. The female newborn diagnosed with left CDH prenatally was born at 38 weeks of gestation. Despite surgical repair and intensive treatment, she died 10 days after birth. Her younger brother was born at 39 weeks of gestation after being diagnosed with bilateral CDH prenatally, and died 75 min after birth. Both infants had neither other congenital anomaly nor chromosomal abnormalities. Their parents are healthy without consanguinity. Their first daughter and the fourth child have no congenital anomalies.

Tenascin (TN) is an extracellular matrix glycoprotein that seems to be involved in embryogenesis, carcinogenesis and wound healing. In order to clarify the biological significance of TN in the human endometrium, we investigated its expression in the normal as well as in the hyperplastic and neoplastic human endometrium, using immunohistochemistry. We also investigated the coexistence of TN with proliferating cell nuclear antigen (PCNA), a marker of cell proliferation, in endometrial carcinoma to further assess the involvement of TN in regulating cell proliferation. TN expression was observed in the stroma surrounding the endometrial gland in the proliferative phase, whereas it could not be found in the secretory phase. The localization of TN and PCNA coincided frequently, as the stromal portion where the expression of TN was observed always showed positive for PCNA. These results suggest that TN is involved in cell proliferation and carcinogenesis in the human endometrium.

A 29-year-old primigravida developed polyhydramnios at 24 weeks of gestation, requiring six serial amnioreductions. In addition, prenatal ultrasound examinations revealed a fetus with small stomach pouch, small thorax, slightly shortened limbs, and skin edema; paternal uniparental disomy 14(upd(14)pat) phenotype was suspected. At 37 weeks, the patient delivered a 2558 g female infant with characteristic facial features, webbed neck, thoracic deformity, abdominal wall defect, skin edema, overlapping fingers, placentomegaly, and small thorax with 'coat-hanger' appearance of the ribs on chest X-ray. A phenotype consistent with upd(14)pat was confirmed by DNA analysis. Although the infant's condition was initially stable, hepatoblastoma was subsequently detected and right hepatectomy was performed on day 224. On day 382, the infant was discharged with in-home respiratory management.

We report a female fetus with sirenomelia with 46,X,t(X;16)(p11.23;p12.3) de novo. Fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes were employed for narrowing down the breakpoint regions. On chromosome 16, the breakpoint was mapped in the region of RP11-453F10 (19 920 640-20 118 153 bp from 16pter). On chromosome X, the breakpoint was mapped in the region of RP11-794A15 (47 333 744-47 524 066 bp from Xpter). This is the first case report of sirenomelia associated with translocations. The abnormal phenotype, associated with a balanced translocation, was caused by deletion or breakage of dosage-sensitive genes of the breakpoint, disruption of an imprinted gene, or uniparental disomy. Although the parental origin of normal 16 and der(16) remained undetermined, this case will provide insight into the pathogenetic mechanism of sirenomelia.

Down syndrome is an autosomal chromosome disorder, characterized by intellectual disability and muscle hypotonia. Muscle hypotonia is observed from neonates to adulthood in Down syndrome patients, but muscle hypertonicity is extremely unusual in this syndrome. During a study period of nine years, we found three patients with severe spastic quadriplegia among 20 cases with Down syndrome and congenital duodenal stenosis/atresia (3/20). However, we could find no patient with spastic quadriplegia among 644 cases with Down syndrome without congenital duodenal stenosis/atresia during the same period (0/644, P 0.05). Further, we did not find any cases with spastic quadriplegia among 17 patients with congenital duodenal stenosis/atresia without Down syndrome admitted during the same period to use as a control group (0/17, P 0.05). Our results suggest that congenital duodenal stenosis/atresia is a potential risk factor for spastic quadriplegia in patients with Down syndrome. Long-term survival is improving, and the large majority of people with Down syndrome are expected to live well into adult life. Management and further study for the various problems, representing a low prevalence but serious and specific to patients with Down syndrome, are required to improve their quality of life.

Lobelia sessilifolia hairy roots (six clones: A-1 ∼4, and J-1 and 2), induced by Agrobacterium rhizogenes ATCC 15834 and A. rhizogenes MAFF 03-01724, grew well and produced some polyacetylenes (lobetyol, lobetyolin and lobetyolinin) in various hormone-free media. J-1 clone, transformed with A. rhizogenes MAFF 03-01724, produced the highest amount of lobetyolin (21.48 mg in 50 mi Murashige - Skoog liquid medium) under illumination. Cultured in Murashige - Skoog medium in the light, only the greenish hairy roots which produced chlorophylls a and b showed better growth and polyacetylene production.