Status epilepticus due to brain tumor during pregnancy.

There is no consensus on the timing of delivery of an infant with nonreassuring fetal status that is associated with maternal status epilepticus. We herein describe a case of status epilepticus due to brain tumor at 28 weeks of gestation.

Synovial plicae and temporomandibular joint disorders: surgical findings.

PURPOSE: Synovial plicae and their relation to pain and disability have been reported in the orthopedic literature in association with the knee and other extremity joints. However, the occurrence of synovial plicae in the temporomandibular joint (TMJ) have rarely been reported. This report describes the surgical appearance, distribution, and histologic findings of synovial plicae in patients with TMJ recurrent dislocation and internal derangement. MATERIALS AND METHODS: Twenty consecutive patients, 16 with recurrent dislocation and 4 with internal derangement, who underwent open TMJ surgery by the same surgeon from 2010 to 2013 were studied retrospectively. RESULTS: Synovial plicae were detected in 18 of 28 joints (64.3%). Synovial plicae were observed in 15 of 24 joints (62.5%) with recurrent dislocation and in 3 of 4 joints (75%) with internal derangement. Histologic findings of these plicae were consistent with dense fibrous or cartilaginous tissues, with some exhibiting a synovial lining. CONCLUSIONS: Although the role of synovial plicae in TMJ disorders is unknown and unstudied, consideration should be given to investigating the possible relation of these structures to the signs and symptoms of TMJ disorders.

Adverse pregnancy outcomes associated with adenomyosis with uterine enlargement.

AIM: The aim of this study was to elucidate the risk of poor pregnancy outcomes in women with adenomyosis by comparing their outcomes to those of women without uterine abnormalities. MATERIAL AND METHODS: The subjects were 36 women diagnosed with adenomyosis before pregnancy who were managed at a tertiary care center between January 2002 and December 2012. Our hospital database was retrospectively reviewed to identify pregnancy outcomes associated with adenomyosis. The control group consisted of 144 women without uterine abnormalities who gave birth during the same period and whose age at delivery was adjusted by applying propensity scores. Pregnancy outcomes were compared between the adenomyosis and control groups. The main outcomes were gestational age at delivery, preterm delivery, preterm premature rupture of membranes, fetal malpresentation, cesarean delivery, small-for-gestational age, 5-min Apgar score < 7, umbilical arterial pH < 7.1, and neonatal intensive care unit admission. The data are presented as medians (range) or frequencies (percentage). RESULTS: The adenomyosis group had significantly higher rates of preterm delivery (41.7% vs 12.5%), preterm premature rupture of membranes (19.4% vs 4.2%), small-for-gestational age (33.3% vs 10.4%), fetal malpresentation (27.8% vs 8.3%), and cesarean delivery (58.3% vs 24.3%), as compared with the control group. No significant differences were observed in 5-min Apgar score < 7 or umbilical arterial pH < 7.1 between the two groups. CONCLUSIONS: Pregnancies in women with adenomyosis were associated with a higher preterm delivery rate and more frequent occurrences of fetal growth restriction and fetal malpresentation, such that both pregnancy and delivery outcomes were poor.

Guidelines for obstetrical practice in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2014 edition.

The 'Clinical Guidelines for Obstetrical Practice, 2011 edition' were revised and published as a 2014 edition (in Japanese) in April 2014 by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction of burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. The number of Clinical Questions and Answers items increased from 87 in the 2011 edition to 104 in the 2014 edition. The Japanese 2014 version included a Discussion, a List of References, and some Tables and Figures following the Answers to the 104 Clinical Questions; these additional sections covered common problems and questions encountered in obstetrical practice, helping Japanese readers to achieve a comprehensive understanding. Each answer with a recommendation level of A, B or C was prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' was weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 104 Clinical Questions and Answers items, with the omission of the Discussion, List of References, and Tables and Figures, are presented herein to promote a better understanding among English readers of the current standard care practices for pregnant women in Japan.

A classification of congenital uterine anomalies predicting pregnancy outcomes.

OBJECTIVE: To evaluate pregnancy outcomes in women with uterine anomalies by applying a method for diagnosing and classifying congenital uterine malformations. DESIGN: Retrospective study. SETTING: Tertiary care center. POPULATION: Ninety-four women with uterine anomalies who delivered after 22 gestational weeks. METHODS: Excluding the 14 women with a history of surgery and seven with one endometrial cavity, 73 women with two endometrial cavities were subdivided into those with two external uterine orifices (2-OS subgroup) and those with one external uterine orifice (1-OS subgroup). MAIN OUTCOME MEASURES: Pregnancy outcomes, such as preterm birth, abnormal fetal presentation, cesarean delivery and placental abruption. RESULTS: The 2-OS subgroup comprised women with a didelphic or complete septate uterus who had a significantly higher rate of cesarean delivery (91% vs. 18%, p < 0.001) than the control group (normal uterine morphology; n = 5763). The 1-OS subgroup comprised women with a bicornuate or incomplete septate uterus who had significantly higher rates of preterm birth (27% vs. 5%, p < 0.001) and placental abruption (14% vs. 0.7%, p < 0.001) than the control group. CONCLUSIONS: Classification of uterine anomalies by the number of uterine endometrial cavities and external uterine orifices is an easy and reliable means of predicting pregnancy outcomes.

Generation of mouse models for type 1 diabetes by selective depletion of pancreatic beta cells using toxin receptor-mediated cell knockout.

By using the toxin receptor-mediated cell knockout (TRECK) method, we have generated two transgenic (Tg) murine lines that model type 1 (insulin-dependent) diabetes. The first strain, C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg, carries the diphtheria toxin receptor (hDTR) driven by the human insulin gene promoter, while the other strain, C57BL/6-ins2(BAC)-TRECK-Tg, expresses hDTR cDNA under the control of the mouse insulin II gene promoter. With regard to the C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg strain, only one of three Tg strains exhibited proper expression of hDTR in pancreatic ß cells. By contrast, hDTR was expressed in the pancreatic ß cells of all four of the generated C57BL/6-ins2(BAC)-TRECK-Tg strains. Hyperglycemia, severe ablation of pancreatic ß cells and depletion of serum insulin were observed within 3days after the administration of diphtheria toxin (DT) in these Tg mice. Subcutaneous injection of a suitable dosage of insulin was sufficient for recovery from hyperglycemia in all of the examined strains. Using the C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg model, we tried to perform regenerative therapeutic approaches: allogeneic transplantation of pancreatic islet cells from C57BL/6 and xenogeneic transplantation of CD34(+) human umbilical cord blood cells. Both approaches successfully rescued C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg mice from hyperglycemia caused by DT administration. The high specificity with which DT causes depletion in pancreatic ß cells of these Tg mice is highly useful for diabetogenic research.

Quality-assessments of characteristics of placental/umbilical cord blood associated with maternal age- and parity-related factor.

Umbilical cord blood (CB) has been widely used for unrelated allogeneic stem cell transplantation. It is important to determine the quality of CB units to avoid frequent problem of limited cell yields. However, no practical and/or optimum obstetric factors to predict them are yet available. This study analyzed the relationship between maternal/neonatal obstetric factors and the laboratory parameters of CB units to identify the optimum factors associated with a high yield of total nucleated cells (TNC). Primiparae in their early 30s may be one of the first selection criteria for CB donors to obtain higher yield of TNC.

Disrupted balance of angiogenic and antiangiogenic signalings in preeclampsia.

The placenta plays a central role in governing local circulatory system that mediates maternal condition and fetal growth. In early gestational phases, the placenta exerts properties of invasion and neovascularization for successful placentation. Extravillous invasive trophoblasts replace uterine endometrial vasculature and establish local blood pathway to obtain oxygen and nutrients from the mother. In later phases, the placenta promotes villous angiogenesis and vascular maturation that are finely controlled by angiogenic and antiangiogenic molecules. Among various molecules involved in placental neovascularization, vascular endothelial growth factor receptors (VEGFRs) and angiotensin II receptor type 1 (AT1) mediate important signaling pathways for maternal circulatory system and fetal growth. VEGFR1 and VEGFR2 are functional receptors for placental growth factor (PlGF) and VEGF, respectively, and PlGF-VEGFR1 and VEGF-VEGFR2 interactions are disturbed in many preeclamptic patients by excess amount of soluble form of VEGFR1 (also named sFlt1), a natural PlGF/VEGF antagonist. Recent studies have disclosed that excessive sFlt1 production in the placenta and aberrant AT1 signaling in the mother are closely associated with the pathology of preeclampsia and intrauterine growth restriction (IUGR). In this paper, neovascularization of the placenta and pathological events associated with disrupted balance between angiogenic and antiangiogenic signaling in preeclampsia are discussed.

Isolation and characterization of mesenchymal stem cells from human umbilical cord blood: reevaluation of critical factors for successful isolation and high ability to proliferate and differentiate to chondrocytes as compared to mesenchymal stem cells from bone marrow and adipose tissue.

Human umbilical cord blood (CB) is a potential source for mesenchymal stem cells (MSC) capable of forming specific tissues, for example, bone, cartilage, or muscle. However, difficulty isolating MSC from CB (CB-MSC) has impeded their clinical application. Using more than 450 CB units donated to two public CB banks, we found that successful cell recovery fits a hyper-exponential function of time since birth with very high fidelity. Additionally, significant improvement in the isolation of CB-MSC was achieved by selecting cord blood units having a volume ≥90 ml and time ≤2 h after donor's birth. This resulted in 90% success in isolation of CB-MSC by density gradient purification and without a requirement for immunoaffinity methods as previously reported. Using MSC isolated from bone marrow (BM-MSC) and adipose tissue (AT-MSC) as reference controls, we observed that CB-MSC exhibited a higher proliferation rate and expanded to the order of the 1 × 10(9) cells required for cell therapies. CB-MSC showed karyotype stability after prolonged expansion. Functionally, CB-MSC could be more readily induced to differentiate into chondrocytes than could BM-MSC and AT-MSC. CB-MSC showed immunosuppressive activity equal to that of BM-MSC and AT-MSC. Collectively, our data indicate that viable CB-MSC could be obtained consistently and that CB should be reconsidered as a practical source of MSC for cell therapy and regenerative medicine using the well established CB banking system.

Maternal and neonatal factors associated with the high yield of mononuclear low-density/CD34+ cells from placental/umbilical cord blood.

Placental/umbilical cord blood (CB) contains nucleated cells and hematopoietic stem/progenitor cells (CD34(+) cells). However it is difficult to predict the number of nucleated/CD34(+) cells in each CB before cell processing. Despite many previous studies from institutes affiliated with CB banks in metropolitan areas, little information is available regarding the characteristics of CB units from other medical facilities. The purpose of the present study was to analyze the maternal/neonatal factors on the yield of cells in CB units. A total of 176 CB units were obtained from single-birth and normal vaginal deliveries. Mononuclear low-density (LD) cells were separated using Ficoll-Paque within 24 hrs after CB collection and then processed for the purification of CD34(+) cells. A multiple linear regression analysis was performed to assess the correlations between the yield of cells and maternal/neonatal factors including maternal age, gravid status, duration of labor, gestational age, neonatal height and weight, cord length, and meconium in the amniotic fluid. The total LD cells per CB unit had a weak positive correlation with the maternal age of primigravidae. The total LD cells per CB unit from the primigravidae aged > or = 25 were significantly higher than those from the primigravidae aged < or = 24. The total CD34(+) cells per CB unit from the 1-gravidae were significantly higher than those from the 2-gravidae and 3-gravidae, respectively among all donors. These results indicate that the CB units from the primigravidae aged > or = 25 are more likely to contain higher yield of LD/CD34(+) cells.

Viability does not necessarily reflect the hematopoietic progenitor cell potency of a cord blood unit: results of an interlaboratory exercise.

BACKGROUND: Clinical transplant outcome with umbilical cord blood (UCB) as source of hematopoietic progenitor cells (HPCs) is, among other factors, determined by the total number of viable nucleated cells and/or CD34+ cells in the unit. Quantitative and qualitative losses by processing and cryopreservation and by thawing and washing before transfusion may occur, however. Another reason for a discrepancy between the number of cells in the unit released by the cord blood bank and found in the transplant center may be technical differences in cell counting methods between the two sites. STUDY DESIGN AND METHODS: With the collaborative group for Biomedical Excellence for Safer Transfusion (BEST), an interlaboratory exercise was conducted among nine sites for thawed UCB variables: total nucleated cells, CD34+ cells, viability, and HPC cultures. Three frozen UCB samples were shipped, with instructions for thawing, counting, and HPC plating. RESULTS: Unexpectedly samples arrived at all nine receiving centers without detectable hematopoietic progenitor colony-forming cells. Nevertheless, wide interlaboratory ranges for viability were obtained. The proportion of viable cells was found higher with manual methods, but all viability assays used in the study overestimated functional progenitor cells. CONCLUSIONS: The results underscore the complexity of evaluation of frozen-thawed cord blood cells and the need for standardization of assessment.

Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells.

Placental tissue draws great interest as a source of cells for regenerative medicine because of the phenotypic plasticity of many of the cell types isolated from this tissue. Furthermore, placenta, which is involved in maintaining fetal tolerance, contains cells that display immunomodulatory properties. These two features could prove useful for future cell therapy-based clinical applications. Placental tissue is readily available and easily procured without invasive procedures, and its use does not elicit ethical debate. Numerous reports describing stem cells from different parts of the placenta, using nearly as numerous isolation and characterization procedures, have been published. Considering the complexity of the placenta, an urgent need exists to define, as clearly as possible, the region of origin and methods of isolation of cells derived from this tissue. On March 23-24, 2007, the first international Workshop on Placenta Derived Stem Cells was held in Brescia, Italy. Most of the research published in this area focuses on mesenchymal stromal cells isolated from various parts of the placenta or epithelial cells isolated from amniotic membrane. The aim of this review is to summarize and provide the state of the art of research in this field, addressing aspects such as cell isolation protocols and characteristics of these cells, as well as providing preliminary indications of the possibilities for use of these cells in future clinical applications.

Morphometric analysis of the inferior alveolar nerve fails to demonstrate sexual dimorphism.

PURPOSE: With regard to the incidence of inferior alveolar nerve (IAN) damage after an IAN block or following oral and maxillofacial surgical procedures, there are reports of sexual dimorphism, no sexual dimorphism, and little sexual dimorphism. However, details of the morphology and sexual dimorphism in the characteristics of the IAN have not been available in textbooks. We morphometrically analyzed the human IAN and clarified these issues. MATERIALS AND METHODS: The materials were obtained from 22 cadavers (11 female and 11 male), aged 59 to 84 years (average age: 74.1 yr), and dentulous. The causes of death did not influence the nervous system, so the IANs were considered to be normal. Human IANs were resected at the mandibular foramen. We counted the myelinated axons and measured the transverse area, perimeter, and circularity ratio of the myelinated axons. RESULTS: We estimated the average total number of myelinated axons in the female IAN to be 25,230, with an average transverse area of 34.1 microm(2), an average perimeter of 21.8 microm, and an average circularity ratio of 0.86, with the same measurements in the male IAN being 20,278, 31.7 microm(2), 20.7 microm, and 0.87, respectively. Our data showed no significant difference between the female and male specimens in any measured item (P < .05). CONCLUSIONS: We assumed that the sex difference in the incidence of IAN damage was not affected by the morphometric findings. Our findings might partly explain why there is no significant sex difference in the incidence of IAN damage.

Clinical anatomical study of pedicled vascularised scapular bone graft using the angular branch.

This study is an anatomical investigation of the angular branch of thoracodorsal artery, and examines the possible range of clinical targets for pedicled vascularised scapular bone graft. Forty-six cadavers were studied. The blood vessel length was calculated, and the distance required to reach the distal humerus from the lower end of the articular surface of the humeral head as reference point was compared with bone length. The length from reference point was an average of 121.7 mm. It was thought that the maximum distance to arrive in reference point to the distal humerus was a total of blood vessel length and transplantation bone length, which was an average of 246.3 mm. This was longer than the average of 240.8 mm of bone length from reference point to humeral medial condyle. This study had confirmed that a pedicled vascularised scapular bone graft using the angular branch could be transplanted to the distal humerus.

Prospective study of intramuscular ergometrine compared with intramuscular oxytocin for prevention of postpartum hemorrhage.

AIM: To compare the efficacy and safety of intramuscular oxytocin with intramuscular ergometrine in the management of postpartum hemorrhage during the third stage of labor. METHODS: Women who had been pregnant for more than 35 weeks and delivered cephalic singletons vaginally without predelivery administration of oxytocics were included. The cases considered to be at high risk were excluded, such as those who had uterine fibroids, a previous cesarean section, previous postpartum hemorrhage, or severe anemia. Five units of oxytocin or 0.2 mg of methylergometrine were administered intramuscularly immediately after delivery of the baby. RESULTS: Compared with intramuscular ergometrine, the use of intramuscular oxytocin was associated with a significant reduction in mean total postpartum blood loss (288.16 g vs 354.42 g, P = 0.004), frequency of postpartum hemorrhage (> or=500 mL: 10.9% vs 20.32%, relative risk [RR] = 0.54, 95% confidence interval [CI] = 0.32-0.91), and need for therapeutic oxytocics (5.13% vs 12.3%, RR = 0.42, 95% CI = 0.19-0.91). There were no differences between the groups in terms of the mean duration of the third stage, the mean level of hemoglobin on the second postpartum day, and the frequency of postpartum hemorrhage (> or =1000 mL), or manual removal of placenta. Few side-effects were found, with no significant differences between the groups. CONCLUSIONS: The routine use of intramuscular oxytocin is more effective than the use of intramuscular ergometrine for prevention of postpartum hemorrhage in the third stage of labor.

Results of a phase I clinical study using dendritic cell vaccinations for thyroid cancer.

OBJECTIVE: We assessed the feasibility and efficacy of dendritic cell (DC) therapy for advanced thyroid papillary and follicular cancer. DESIGN: Six Japanese patients (2 men and 4 women; aged 46-72 years, mean 60 years), who were diagnosed as advanced thyroid cancer with refractory distant metastases (papillary, n=5; follicular, n=1), were enrolled. Patients were first vaccinated weekly for 4 weeks with 10(7) autologous tumor lysate-pulsed monocyte-derived mature DCs followed by fortnightly vaccinations for 8 weeks (total=8 vaccinations). Lowdose (350 KIU) interleukin-2 was also administered for 3 days at each vaccination. Clinical response, adverse effects, delayed-type hypersensitivity skin testing (DTH), and IFN-( ) production by peripheral CD3(+) lymphocytes were evaluated. MAIN OUTCOME: Of the 6 patients, disease was assessed as stable in 2 and as progressive in 4. No adverse events were observed. Results of DTH and IFN-( ) production in peripheral lymphocytes did not correlate to the clinical response. CONCLUSIONS: DC immunotherapy could be administered to patients with thyroid papillary or follicular cancer without substantial side effects.

Successful immortalization of mesenchymal progenitor cells derived from human placenta and the differentiation abilities of immortalized cells.

We reported previously that mesenchymal progenitor cells derived from chorionic villi of the human placenta could differentiate into osteoblasts, adipocytes, and chondrocytes under proper induction conditions and that these cells should be useful for allogeneic regenerative medicine, including cartilage tissue engineering. However, similar to human mesenchymal stem cells (hMSCs), though these placental cells can be isolated easily, they are difficult to study in detail because of their limited life span in vitro. To overcome this problem, we attempted to prolong the life span of human placenta-derived mesenchymal cells (hPDMCs) by modifying hTERT and Bmi-1, and investigated whether these modified hPDMCs retained their differentiation capability and multipotency. Our results indicated that the combination of hTERT and Bmi-1 was highly efficient in prolonging the life span of hPDMCs with differentiation capability to osteogenic, adipogenic, and chondrogenic cells in vitro. Clonal cell lines with directional differentiation ability were established from the immortalized parental hPDMC/hTERT+Bmi-1. Interestingly, hPDMC/Bmi-1 showed extended proliferation after long-term growth arrest and telomerase was activated in the immortal hPDMC/Bmi-1 cells. However, the differentiation potential was lost in these cells. This study reports a method to extend the life span of hPDMCs with hTERT and Bmi-1 that should become a useful tool for the study of mesenchymal stem cells.

Regeneration of megakaryocytopoiesis and thrombopoiesis in vitro from X-irradiated human hematopoietic stem cells.

In the present study, we investigated whether X-irradiated hematopoietic stem cells can be induced to undergo megakaryocytopoiesis and thrombopoiesis in vitro using cytokine combinations that have been demonstrated to be effective for conferring increased survival on irradiated human CD34(+) megakaryocytic progenitor cells (colony-forming unit megakaryocytes; CFU-Meg), such as thrombopoietin (TPO), interleukin 3 (IL3), stem cell factor and FLT3 ligand. Culture of nonirradiated CD34(+) cells in serum-free medium supplemented with multiple cytokine combinations led to an approximately 200- to 600-fold increase in the total cell numbers by day 14 of culture. In contrast, the growth of X-irradiated cells was observed to be one-sixth to one-tenth that of the nonirradiated cultures. Similarly, total megakaryocytes were increased by 50- to 130-fold, while culture of X-irradiated cells yielded one-fourth to one-eighth of the control numbers. At this time, CD41(+) particles, which appeared to be platelets, were produced in the medium harvested from nonirradiated and irradiated cultures. Although radiation suppressed cell growth and megakaryocytopoiesis, there were no significant differences in thrombopoiesis between the two types of culture. These results suggest that X-irradiated CD34(+) cells can be induced to undergo nearly normal terminal maturation through megakaryocytopoiesis and thrombopoiesis by stimulation with appropriate cytokine combinations.

Multiple-laboratory comparison of in vitro assays utilized to characterize hematopoietic cells in cord blood.

BACKGROUND: Understanding the variability in results obtained by multiple laboratories is important because cord blood units are distributed worldwide for transplantation. STUDY DESIGN AND METHODS: Four exercises were conducted by multiple laboratories to assess assay variability on nucleated cell (NC), mononuclear cell (MNC) by hematology analyzers [HAs], and CD34+ cell (flow cytometry) measurements. Exercise 1 was an intralaboratory exercise in which the reproducibility of cell measurements was determined. Exercises 2 and 3 involved the shipment of identical processed cord blood samples. In Exercise 2, laboratory-specific methods were utilized. In Exercise 3, two commercial CD34+ cell methods (Stem-Kit and TruCOUNT) were used. In Exercise 4, CD34+ cell levels were determined on repetitive regating of identical list-mode files. RESULTS: Intralaboratory reproducibility was highest for NC measurements and lowest for CD34+ cell measurements. In Exercise 2, all laboratories except one utilized HA with an impedance technology and determined comparable results for NC and MNC levels, whereas the other laboratory utilized a HA with an optical counting method. Substantial variation was observed on measuring CD34+ cells with ranges of 32 to 141, 32 to 66, and 25 to 116 CD34+ cells per microL for the three identical samples. In Exercise 3, on the use of one specific commercial assay, the ranges of CD34+ levels were 214 to 411 and 62 to 178 cells per microL for the two identical samples. Nearly all participating laboratories determined comparable CD34+ levels on the use of identical list-mode files. CONCLUSION: These studies indicate that substantial variability in CD34+ cell levels were determined with flow cytometry. The variability in NC and MNC levels was minimal with HA methodology.