BACKGROUND: Dexmedetomidine is a highly selective central α₂-agonist used as a sedative in pediatric intensive care unit (PICU). However, little is known about the relationship between dexmedetomidine dose and its plasma concentration during long-term infusion. We have previously demonstrated that the sedative plasma dexmedetomidine concentration is moderately correlated with the administered dose in adults (r = 0.653, P = 0.001). We hypothesized that there would be a similar relationship between the sedative dexmedetomidine concentration and administered dose in infants. METHODS: All patients admitted to the PICU at Nagoya City University Hospital, Japan, between November 2012 and March 2013 were eligible for inclusion in the study. Plasma dexmedetomidine concentration was measured by ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: We measured the plasma dexmedetomidine concentration in 203 samples from 45 patients. Of these, 96 samples collected from 27 patients < 2 years old were included in this study. All patients received dexmedetomidine at 0.12–1.40 µg/kg/h. The median administration duration was 87.6 hours (range: 6–540 hours). Plasma dexmedetomidine concentration ranged from 0.07 to 3.17 ng/ml. Plasma dexmedetomidine concentration was not correlated with the administered dose (r = 0.273, P = 0.007). The approximate linear equation was y = 0.690x + 0.423. CONCLUSIONS: In infants, plasma dexmedetomidine concentration did not exhibit any correlation with administered dose, which is not a reliable means of obtaining optimal plasma concentration.
Adult ; Chromatography, Liquid ; Cohort Studies* ; Critical Illness* ; Dexmedetomidine* ; Humans ; Infant* ; Intensive Care Units ; Japan ; Plasma* ; Prospective Studies* ; Tandem Mass Spectrometry

　　Placental abruption occurs suddenly and may cause maternal and fetal mortality. Forced delivery is the only way to improve perinatal outcome, but the aftereffects could be severe despite a high survival rate.　　Our hospital manages approximately 170 cases of maternal transport annually, including cases of severe placental abruption. Longer transport time can lead to undesirable maternal and fetal outcome. Hence this study, we compared the perinatal backgrounds and outcome of placental abruption retrospectively between the cases managed by maternal transport and by the local hospital (our hospital). The study included 54 cases of placental abruption during the period from January 2008 to December 2012, of which 27 cases were managed by our hospital, the other halves were managed by maternal transport. There were 6 intrauterine fetal deaths but not a single maternal death. There were no significant differences in the amount of blood lost and obstetric DIC (disseminated intravascular coagulopathy) score between two groups (p＝0.342, p＝0.649), and the number of cases that needed anti-DIC therapy and blood transfusion in each group was statistically similar (p＝0.807, p＝0.115). The time taken from the on-set of placental abruption to delivery was significantly shorter for the cases managed by our hospital (in-hospital management 143±133 minutes, maternal transport management 265±176 minutes, p‹0.05), while obstetric DIC score and Apgar score showed no significant differences (p＝0.336, p＝0.780) between the two groups. Thus, it could be said there were no correlations between the time taken from onset to delivery and perinatal outcome. It should be noted, however, maternal and fetal outcome of placental abruption could be fatal even with the rapid intervention, so quick diagnosis and management at the first contact are crucial. Thus, we concluded that forced delivery managed by the local hospitals is necessary for the potential better perinatal outcome, and an ideal system to manage maternal and/or neonate transport after the delivery should be established immediately.

  Twin pregnancy is increasing as infertility treatment is widely given nowadays using assisted reproductive technologies. Twin pregnancy is a risk factor for some complicated pregnancies and it may also cause a hard labor. Although cesarean delivery is frequently indicated in many hospitals in Japan for twin pregnancy in view of the risk of vaginal delivery of the second baby, we have tried vaginal delivery of twin pregnancy in a certain situation. We studied the methods of twin delivery, its outcomes and the early neonatal condition.
  We found 251 twin deliveries (4.6%) in a total of 5,464 deliveries after 22 weeks of pregnancy from January 2005 to December 2009 in the delivery record. Forty-six percent of women pregnant with twins delivered their babies after 33-36 weeks of pregnancy and 41% after 37 weeks of pregnancy. Sixty-five percent delivered by Cesarean section, 33% by vaginal delivery, and 2% vaginally for the first baby and by Cesarean section for the second baby. Fifty percent of the Cesarean deliveries were performed as patients so desired. Ninety women pregnant with twins chose vaginal delivery in which 92% (64/69) of vertex/vertex presentation and 86% (18/21) of vertex/ breech presentation succeeded in vaginal delivery. Neonatal outcome was assessed in 90 vaginally deliveried babies by use of the Apgar scoring system. One-minute Apgar scores of 0-3 (severe asphyxia) were given to 4.5% (8/180) of babies and scores of 4-6 (moderate asphyxia) to 3.3% (6/180) of babies. The incidence meant that a mother had 8.9% and 6.7% of high risk of severe and moderate asphyxia of her babies. But severe asphyxia decreased to 1.7% (3/180), moderate asphyxia to 1.1% (2/180) of babies on the assessment of 5-minute Apgar scores that reflected long-term neonatal outcome. Eleven cases were second babies of all 14 cases of asphyxia on the assessment of 1-minute Apgar scores. In the vaginal delivery group, 5 cases of umbilical cord prolapsed and 3 cases of placental abruption occurred in second babies. In conclusion, twin delivery should be attempted at the birth center where neonatologists and anesthesiologists are available 24 hours as extra-emergency Cesarean delivery can be performed because of the high incidence of emergency Cesarean delivery of second baby (5.6%) and asphyxia of neonates delivered vaginally.

  A 41-year-old woman, gravid 3, para 3, was admitted to the Department of Obstetrics and Gynecology at Tsuchiura Kyodo General Hospital, complaining of a tender, gradually enlarging mass in the right inguinal region during menses. Examination found the mass was about 2 cm in diameter, which protruded slightly (on lying position?). During menstrual periods, the mass enlarged and the pain intensified, but between menses, the mass decreased in size and the pain subsided. The case was diagnosed as inguinal endometriosis and then a preoperative GnRH analog therapy was given for six weeks to make a good operative local condition. Surgery was performed under general anesthesia and a mass about 4.0×3.0 cm in diameter near inguinal ligament was removed. The cut surface revealed small hemorrhagic areas or spaces. Microscopic examination of the dissected mass confirmed the diagnosis of inguinal endometriosis. It was found that the patient had a moderate inguinal swelling on the first visit to the hospital as an outpatient 7 days after operation, but the swelling disappeared shortly afterword. She has been receiving a post-operative GnRH analog therapy for 3 months to maintain a good local condition. The authors concluded thatthe appearance of a lump in the inguinal region and objective changes of the lesion in relation to the menstrual cycle should be considered as the symptoms of endometriosis.

  We report a case of new-onset depressive disorder in a patient with a history of rectal endometriosis treated with GnRH analog and no previous psychiatric history. This medical history allowed us to suspect the possibility of a link between GnRH analog and depression. It also highlighted the need to screen patients treated with GnRH analog for depression.
  The patient was 41-year-old woman who had been diagnosed with rectal endometriosis. She was referred to the Gynecology Department of Tsuchiura Kyodo General Hospital. The subjective symptoms included cyclic abdominal pains and rectal bleedings. The patient had undergone total abdominal hysterectomy and left salpingo-oophorectomy for endometriosis two years before. She was started by her first gynecologist on GnRH agonist (nafarelin acetate) and the symptoms disappeared soon. But several weeks after the initiation of the GnRH agonist treatment, she began to feel depressed and hopeless. She visited a psychiatric hospital and diagnosed as having depression. She was given anti-depressive drugs and inpatient treatment at the psychiatric hospital. Her clinical course was reviewed by her second gynecologist, and she was suspected to have developed depressive disorder by GnRH analog treatment. She stopped taking GnRH analog medication and started progestin (Dinagest) therapy. She became soon free of depressive disorder and then anti-depressive drugs with rectal endometriosis well controlled. This case also suggested Dinagest is a recommended drug for rectal endometriosis.

　　Catamenial pneumothorax (CP) is defined as a form of thoracic endometriosis syndrome (TES) and the clinical manifestations and management of this disease are not consensual. Successful treatment depends on how closely pulmonary specialists and gynecologists work together. Such being the circumstances, we reviewed our experience with CP in terms of treatment and follow-up. We treated surgically many patients with pneumothorax during the period from 1989 to 2014, of which eight cases had endometriosis on the diaphragm, lung or pleura histologically. The median age at the time of operation was 37 (range, 17 to 41). CP was right-sided in seven of the eight patients (87.5%). Six patients underwent an examination with diagnostic laparoscopy and five had positive findings. The median period of follow-up after surgery was 33.5 months (range, 4 to 129 months). Two patients had no recurrence without hormonal therapy. Six other patients experienced a recurrence of pneumothorax, although two patients received dienogest after surgery. The use of only dienogest or both GnRHa and dienogest prevented recurrence in all patients. CP is a critical condition that requires prompt action, so after surgical treatment, the choice of hormonal therapy with a high rate of patient compliance are needed. No recurrence occurred in young patients who had only surgical treatment, suggesting that there were some associations between age and recurrence. Since we succeeded in preventing recurrence after using GnRHa in all cases, we recommend GnRHa or dienogest following GnRHa for the first choice of hormonal therapy after surgery. However, treatment with only dienogest could achieve successful results with no recurrence, so more case studies need to be done to make the best treatment choice for each case.

　　Adhesion formation after abdominal surgery is a commonly recognized entity. Many studies have shown that women giving birth by cesarean section are at the risk of developing complications related to the postoperative formation of adhesions including ileus, bowel obstructions, impaired fertility, and chronic abdominal pain. Among several adhesion barriers, one that has been tested in randomized, controlled trials is the hyaluronic cid-carboxymethylcellulose (HA/CMC) membrane (Seprafilm®: Genzyme, Cambridge, MA, USA). This bioresorbable membrane serves as a mechanical barrier between surgically damaged tissues and resorbs afterwards. At our institution, we have used HA/CMC in cesarean sections. We report our experience with this patient population using placement of HA/CMC.　　This study enrolled 45 women who had undergone cesarean sections twice or more who had received HA/CMC during the previous cesarean section between January 2013 and November 2014. The incidence of adhesions to the area of abdominal wall incisions and uterine surface, intestinal obstructive symptoms, and adverse events were studied. The incidence of adhesions to midline incisions was 4.4% (n＝2). The filmy adhesion by major omentum was detected in these two cases. The incidence of adhesions to uterine surface was 2.2% (n＝1). The moderate thickness adhesion was detected at the left side of the vesico-uterine peritoneal incision by pelvic peritoneum which did not affect the operative procedure. No symptoms related to intestinal obstructions such as abdominal pains, nausea and vomiting were observed. No adverse events were observed. These three cases had fever which had nothing to do with HA/CMC applications but was attributable respectively to influenza infection, mastitis, phlebitis associated with a needle procedure.　　HA/CMC was considered a useful adhesion barrier membrane for use in cesarean sections as an adjunct intended to reduce the incidence of postoperative adhesions between the abdominal wall and the underlying viscera such as omentum, small bowel, and between the uterus and surrounding structures.

　　We have developed a new surgical procedure for uterine prolapse of round ligament suspension to the psoas minor tendon by the use of a laparoscope. Here, we describe the new technique and report the outcome of surgery in three cases.　　Operative procedure: The fundus of the uterus is lifted back up to its natural position by fixing the round ligament of the uterus to the psoas minor tendon after incising the peritoneum covering psoas. It is important to use the tendon as a stronger reattachment site in addition to the psoas major muscle. The round ligament is tacked to the tendon by a 2-0 nonabsorbable suture on bilateral sides. The second suture may be added if the uterus is not appropriately lifted up by the first suture. The retroperioneum is closed by a continuous 3-0 absorbable suture after fixation.　　Cases: Two patients with severe uterine prolapse and one patient with a mild condition went through the operation safely and have experienced no recurrence for 10 to 24 months. One severely ill patient complained about post -operative right inguinal pain early and another with the severe condition complained that something felt wrong with the right thigh.　　We propose the operation of laparoscopic round ligament psoas minor tendon-hitching as a safe and effective surgical treatment for uterine prolapse.

　　A 59-year-old woman, para 2, attended our hospital for an abdominal mass and atypical genital bleeding. Magnetic resonance imaging revealed a 30×25cm uterine myoma. A preoperative blood examination showed the following results: hemoglobin, 21g/dl; hematocrit, 71.5%; erythropoietin, 38.5mIU/ml; and estradiol, 29.9pg/ml. Abdominal total hysterectomy and bilateral salpingo-oophorectomy were performed, with an estimated blood loss of 1650ml. The weight of the uterus, including the myoma nodule, was 4740g, and the results of histology confirmed the diagnosis of leiomyoma. By postoperative day 28, her hemoglobin, erythropoietin, and estradiol levels had fallen to levels of 15.1g/dl, 6.0mIU/ml, and 5.8pg/ml, respectively, which are normal for a postmenopausal woman. The findings suggest that the leiomyoma secreted erythropoietin and induced erythrocytosis. Estradiol stimulates erythropoietin secretion and enlargement of the leiomyoma. Some studies have shown that erythropoietin is also a growth factor for leiomyoma. More than half of the erythropoietin-producing leiomyomas are detected after menopause. It was discovered that leiomyoma cells can produce aromatase, which transforms androstenedione into estradiol. Although estradiol secretion from the ovaries decreases in the postmenopausal period, the estradiol and erythropoietin autocrine/paracrine system in leiomyoma might promote its own growth after menopause.

　　We researched intrauterine fetal death (IUFD) after 22 weeks of gestation from 2009 to 2014 in our departments. During this period, there were 6236 childbirths and 35 cases (0.56%) resulted in IUFD. We researched the background and causes of IUFD in these 35 cases. The median age was 34 years and advanced maternal age accounted for 48.6% of cases, while elderly primipara accounted for 20%. There were 5 cases (14.3%) of pregnancy after fertility treatment. The median gestational age when IUFD was recognized was 30 weeks, but the gestational age in 4 cases was unclear because of lack of antenatal check-ups. The main risk factors for IUFD were maternal age over 35 (0.95% to 0.40%) and lack of antenatal check-ups (3.7% to 0.5%). The major causes of IUFD were umbilical cord abnormalities (n=10) and placental abruption (n=8), but IUFD of unknown etiology accounted for about 30% of cases. We should better inform mothers about the importance of antenatal check-ups and manage pregnancies carefully for those who have risk factors for IUFD. Furthermore, we should increase research into the causes of stillbirths.