Effect of urinary trypsin inhibitor on preterm labor with high granulocyte elastase concentration in cervical secretions.

AIMS: To explore whether intravaginal treatment with urinary trypsin inhibitor (UTI) prevents preterm delivery in patients in preterm labor with increased levels of granulocyte elastase in cervical secretions. METHODS: The subjects were patients in preterm labor with increased levels of granulocyte elastase in cervical secretions from 16 to 33 weeks gestation. Maternal and neonatal outcomes were compared between patients receiving UTI treatment (UTI group; n=33) and those not receiving UTI treatment (control group; n=40). RESULTS: In patients receiving UTI, the mean gestational age at delivery was greater than that in the control group (37.8 vs. 35.6 weeks, p=0.003), and the rates of premature delivery before 34 and 37 weeks gestation were lower (3% vs. 20%, p=0.028; and 18% vs. 47%, p=0.008, respectively). The percentage of neonates weighing more than 2,500 g was significantly higher in the UTI group, with no neonates weighing less than 1,500 g. The neonatal hospitalization rate was lower in the UTI group (9% vs. 42%, p=0.001). CONCLUSION: In patients in preterm labor with a high elastase concentration in cervical secretions, treatment with UTI reduced the risk of preterm delivery and improved neonatal outcomes.

Factors influencing the accuracy of digital examination for determining fetal head position during the first stage of labor.

OBJECTIVE: The objective of this study was to explore factors influencing the accuracy of transvaginal digital examination for determining fetal head position during the first stage of labor. MATERIALS AND METHODS: Fetal head position was assessed in 87 women in the first stage of labor at term with normal singleton cephalic presentation. Transvaginal digital examinations were performed by attending midwives and were followed immediately by transabdominal ultrasound assessments performed by a single sonographer. Accuracy was defined as agreement of the results of each examination. Multivariate logistic regression analysis was performed to determine the independent factors influencing accuracy. RESULTS: In only 40.3% of patients (n = 35) were transvaginal digital examinations consistent with ultrasound assessments. Multivariate logistic regression analysis showed that the accuracy of digital examinations was significantly associated with cervical dilatation more than 7 cm (odds ratio, 3.01; 95% confidence interval [CI], 1.03-9.4), birth weight less than 2,500 g (odds ratio, 8.68; 95% CI, 1.08-86.28), and the anterior occiput position group (odds ratio, 4.73; 95% CI, 1.76-13.49). CONCLUSIONS: The present study demonstrates that transvaginal digital examination is less accurate than ultrasonography for determining fetal head position during the first stage of labor. The results suggest that ultrasound assessments should be routinely performed in patients with a cervical dilatation less than 7 cm, an estimated fetal body weight more than 2,500 g, the occiput posterior position, or the occiput transverse position.

Clinical efficacy of Kampo medicine (Japanese traditional herbal medicine) in the treatment of primary dysmenorrhea.

OBJECTIVE: We intended to evaluate the clinical efficacy of Kampo medicine, a Japanese traditional herbal medicine, for primary dysmenorrhea which was prescribed according to the Kampo diagnosis, with classification of its severity. METHOD: A retrospective evaluation of Kampo treatment in 176 subjects with dysmenorrhea during the previous 12 years was performed. In order to minimize the subjective discretion of the severity of symptoms, classification of the severity level of abdominal pain during menstruation was applied by considering the requirement for non-steroidal anti-inflammatory drugs (NSAIDs) and disturbance of daily activities. The following severity levels were used: no abdominal pain (level 0), abdominal pain with no requirement of NSAIDs (level 1), abdominal pain with no daily activity disturbances with use of NSAIDs (level 2), and painful menstruation which required absenteeism even with use of NSAIDs (level 3). RESULTS: Severity levels before and after Kampo treatment were defined in 108 subjects. Distribution of the severity levels in 108 subjects was significantly changed by Kampo treatment; the numbers of cases in levels 0, 1, 2, and 3 changed from 0 (0%), 0 (0%), 47 (43.5%), and 61 (56.5%) to 5 (4.6%), 42 (38.9%), 51 (47.2%), and 10 (9.3%), respectively. (P<0.0001) There were 25 kinds of Kampo formulae prescribed in effective cases. CONCLUSION: Kampo medicine prescribed according to Kampo diagnosis reduced the severity of primary dysmenorrhea and is therefore suggested to be beneficial in improving quality of life.

Risk factors for peripartum blood transfusion in women with placenta previa: a retrospective analysis.

BACKGROUND: The incidence of placenta previa has been increasing. It is of a great importance to determine the clinical risk factors for peripartum blood transfusion in women with placenta previa in an effort to anticipate cases of severe hemorrhage. METHODS: A total of 129 consecutive cases of placenta previa (64 cases of complete placenta previa and 65 cases of marginal placenta previa), including 43 cases requiring blood transfusion, were retrospectively analyzed. Maternal and neonatal clinical data were examined with univariate and multivariate logistic regression analyses for potential risk factors for peripartum blood transfusion. RESULTS: The independent risk factors for blood transfusion were maternal age greater than 34 years (adjusted odds ratio [OR]=3.7; 95% confidence interval [CI]=1.5-7.5, p<0.05), history of having undergone dilatation and curettage more than once (adjusted OR=4.8; 95% CI=1.1-26.2, p<0.05), and complete placenta previa (adjusted OR=2.6, 95% CI=1.2-5.9, p<0.05). Body mass index, gravidity, parity, previous cesarean section, antepartum hemorrhage, use of tocolytic agents, gestational age at delivery, preoperative anemia, emergent surgery, birth weight, and Apgar score were not associated with the incidence of blood transfusion. CONCLUSION: Risk factors for blood transfusion in women with placenta previa are advanced maternal age, repeat dilatation and curettage, and complete placenta previa. Women with placenta previa who are at risk for blood transfusion should be carefully managed with sufficient preparation for blood transfusion.

Role of mitochondrial permeability transition in fetal brain damage in rats.

Recirculation after transient in utero ischemia has previously been found to be accompanied by delayed deterioration of cellular bioenergetic state and of mitochondrial function in the fetal rat brain. Our objective was to assess whether the delayed deterioration is a result of the activation of mitochondrial permeability transition which is observed ultrastructurally as mitochondrial swelling. The respiratory activities and ultrastructure of isolated mitochondria and the cellular bioenergetic state in fetal rat brain were examined at the end of 30 minutes of in utero ischemia and after 1, 2, 3 and 4 hours of recirculation. Cyclosporin A, a potent and virtually specific mitochondrial permeability transition blocker, or vehicle was administered 1 hour after recirculation. In the vehicle-treated animals, the transient ischemia was associated with a delayed deterioration of cellular bioenergetic state and mitochondrial activities at 4 hours of recirculation. The number of swollen mitochondria increased markedly after 4 hours of recirculation. The deterioration and the swelling were prevented by cyclosporin A. The present study indicates that cyclosporin A treatment improves recovery of fetal brain energy metabolism and inhibits the mitochondrial swelling after transient in utero ischemia. The results suggest that mitochondria and mitochondrial permeability transition may be involved in the development of ischemic brain damage in the immature rat.

Accuracy and reproducibility of ultrasound measurements in obstetric management.

OBJECTIVE: The aim of this study was to assess the potential of ultrasonography as a routine diagnostic tool in obstetric management. SUBJECTS AND METHODS: For the investigation on interobserver reproducibility, 2 sonologists independently measured the biparietal diameter (BPD), femur length (FL), amniotic fluid index (AFI), and resistance index (RI) of the umbilical and middle cerebral arteries in 20 healthy pregnant women between 28 and 36 weeks of gestation using color and pulsed Doppler ultrasound. A second group of 10 healthy pregnant women between 30 and 35 weeks of gestation were examined to assess the level of intraobserver reproducibility of the Doppler and ultrasound measurements by 2 sonologists. For each patient in this group, the flow waveform was measured three times in succession. Calculations of the intraclass correlation coefficient (Ri) were used to determine the levels of reproducibility. The agreement was considered acceptable only when the Ri value was > or = 6. RESULTS: The interobserver Ris for BPD, FL, AFI, and RI of the umbilical and middle cerebral arteries were 0.93, 0.8, 0.58, 0.49 and 0.56, respectively. The intraobserver Ris of the 2 sonologists in BPD, FL, and RI of umbilical artery were >0.6, whereas those in AFI and RI of middle cerebral artery were <0.6. CONCLUSIONS Both the interobserver and intraobserver reproducibilities of BPD and FL were clinically acceptable, but not in the AFI and RI of umbilical and middle cerebral arteries.

Vitamins ameliorate secondary mitochondrial failure in neonatal rat brain.

Recirculation after transient intrauterine ischemia has previously been found to be accompanied by secondary mitochondrial dysfunction in the immature rat brain. This study was performed to assess the efficacy of combined treatment with ascorbic acid and alpha-tocopherol in improving secondary brain damage. On the 17th day of gestation, transient intrauterine ischemia was induced by 30 minutes of uterine artery occlusion. Either vehicle, ascorbic acid, alpha-tocopherol, or combination of ascorbic acid and alpha-tocopherol was randomly administered to pregnant rats before and after occlusion. The pups were delivered by cesarean section at 21 days of gestation, and cerebral neocortical tissue was sampled. The mitochondrial respiration was measured polarographically in homogenates. In the ischemia uterine horn, mitochondrial activity of the vehicle treatment decreased significantly to 56% of nonischemic controls. Treatment with ascorbic acid or alpha-tocopherol alone demonstrated a moderate improvement of the secondary mitochondrial dysfunction to 64% and 62% of nonischemic controls, respectively. The combined treatment caused a normalization of mitochondrial activity to 91% of nonischemic controls. These results indicate that combined treatment with ascorbic acid and alpha-tocopherol has a more protective effect against secondary mitochondrial dysfunction after transient intrauterine ischemia compared with the administration of ascorbic acid or alpha-tocopherol alone.

Short therapeutic window for nifedipine in transient intrauterine ischemia in fetal rat brain.

The aim of this study was to explore whether nifedipine influences the secondary deterioration of cerebral mitochondrial function after transient intrauterine ischemia in fetal rats. Intrauterine ischemia was induced by a 30-min occlusion of the right uterine artery at 20 days of gestation in Wistar rats. Nifedipine (1 mg kg(-1)) or vehicle was injected subcutaneously before the onset of ischemia or 1 h after the start of recirculation. Fetuses were delivered by cesarean section at the end of ischemia (n=6 with vehicle; n=6 with nifedipine pretreatment) or at 4 h of recirculation (n=6 with vehicle; n=6 with nifedipine pretreatment; n=6 with nifedipine posttreatment), and the cerebral mitochondrial respiration was measured polarographically. Tissue oxygen tension was evaluated in placental and fetal cerebral tissues (n=5 with vehicle; n=5 with nifedipine pretreatment). The vehicle treated animals showed a significant decrease in mitochondrial activities at the end of ischemia and 4 h of recirculation. Nifedipine attenuates the secondary deterioration at 4 h of recirculation when given just prior to ischemia, but had no neuroprotective activity when given 1 h after the start of recirculation. Nifedipine pretreatment had no influence on oxygen delivery in placenta and fetal cerebrum during and after ischemia. Despite the short therapeutic window, the treatment of nifedipine attenuates the secondary deterioration of cerebral mitochondrial function after transient intrauterine ischemia in fetal rats when given just prior to ischemia.

Effect of dexamethasone on mitochondrial maturation in the fetal rat brain.

OBJECTIVE: The objective of the present study was to explore whether prenatal dexamethasone treatment influences mitochondrial maturation in the fetal rat brain. STUDY DESIGN: Mitochondrial respiration was measured polarographically with homogenates of fetal cerebral cortical tissues on day 16 (with saline solution, n = 8; with dexamethasone, n = 8), day 18 (with saline solution, n = 8; with dexamethasone, n = 8), and day 20 (with saline solution, n = 8; with dexamethasone,n = 8) of gestation. Four doses of dexamethasone (0.1 mg small middle dot kg) or vehicle (saline solution) were given, with an interval of 12 hours, until 12 hours before each measurement. RESULTS: In the vehicle-treated animals, mitochondrial respiratory activity was increased significantly after day 18 of gestation. Dexamethasone-treated animals showed a significant increase in mitochondrial activity at day 16 of gestation compared with vehicle-treated animals. CONCLUSION: The results indicate that prenatal dexamethasone treatment contributes to the precocious maturation of mitochondrial activity in the fetal rat brain. Because acceleration in cerebral mitochondrial activities is required immediately after birth to maintain high-energy phosphate levels, the precocious maturation may be crucial for the successful outcome of the preterm infant.

Doppler ultrasound measurement of cerebral blood flow in healthy pregnant women.

PURPOSE: To compare global cerebral blood supply in healthy pregnant women and nonpregnant women. MATERIALS AND METHODS: Flow volumes in the common, internal, and external carotid, arteries and the vertebral arteries were determined using color Doppler ultrasonography in 17 nonpregnant women, 55 healthy pregnant women at 10 to 40 weeks gestation, and 24 puerperal women within 1 week after spontaneous delivery. Global cerebral blood flow was defined as the sum of flow volumes in the bilateral internal carotid and vertebral arteries. RESULTS: In the nonpregnant group, mean flow volumes of the common, internal, and external carotid arteries and the vertebral arteries, and mean global cerebral blood flow volume were (mean±SD) 863±108 ml/min, 554 ±94 ml/min, 386±65 ml/min, 115±24 ml/min, and 669±104 ml/min, respectively. During the second trimester, flow volumes of the common and external carotid arteries increased significantly in the healthy pregnant women, to about 130 percent and 140 percent of the nonpregnant level, respectively. Global cerebral blood flow volume remained unchanged during pregnancy. CONCLUSION: During pregnancy, increase in flow volumes in the common carotid arteries were accompanied by elevated flow volumes of the external carotid arteries but not the internal carotid arteries. This distribution would tend to regulate the volume of global cerebral blood flow throughout the period of pregnancy.

Windows of therapeutic opportunity on fetal growth retardation induced by transient intrauterine ischemia in rats.

OBJECTIVE: To assess the windows of therapeutic opportunity for drugs with various chemical actions on fetal growth retardation induced by transient intrauterine ischemia in rats. METHODS: At 17 days of gestation, ischemia was induced by 30 min of right uterine artery occlusion. The administration of either alpha-phenyl-N-tert-butyl-nitrone (PBN), FK 506, nifedipine, or MK-801 to pregnant rats was randomly started before occlusion, 1 hour, 3 hours, or 24 hours after recirculation. All of the pups were delivered by cesarean section at 21 days of gestation and were weighed to determine the degree of fetal growth retardation. RESULTS: The vehicle-treated animals exposed to ischemia showed a significant decrease in fetal body weight compared with the normoxic control animals. The growth disturbances were prevented by nifedipine and MK-801 only when given just prior to ischemia. In contrast, PBN and FK 506 had a protective effect even when given 1 hour and 3 hours after the start of recirculation, respectively. CONCLUSIONS: The present results indicate that treatment with PBN and FK 506 gives relatively wide windows of therapeutic opportunity in fetal growth retardation induced by transient intrauterine ischemia in rats and suggest the possibility of therapeutic intervention after the start of recirculation.