Vascular endothelial growth factor in monochorionic twins with twin-twin transfusion syndrome.

OBJECTIVE: The purpose of this study was to determine vascular endothelial growth factor (VEGF) concentrations in the donor and the recipient in monochorionic twin pregnancies with twin-twin transfusion syndrome (TTTS) and single pregnancies in order to investigate the involvement of VEGF in the pathophysiology of TTTS. METHODS: Six twin pregnancies in 11 monochorionic twin pregnancies complicated with TTTS and 11 single control pregnancies were compared. Gestational age-matched fetal blood and placental samples were obtained at birth. Serum VEGF concentration in the umbilical vein was measured by an enzyme-linked immunoabsorbant assay. Tissue protein expression of VEGF was determined by using immunohistochemistry. Western blot analysis and scanning densitometry were used to quantify and compare the VEGF expression in the terminal villi. RESULTS: Serum VEGF concentrations in the umbilical vein in both donors and recipients tended to be higher than those in the controls. Immunolocalization of VEGF in terminal villous placenta samples in both donors and recipients was mainly observed in the syncytiotrophoblastic layer and vascular endothelial cells with less intense staining in stromal cells. The expression of VEGF in the donor placenta increased significantly (p=0.006) compared to that in the control placenta, but the expression of VEGF in the recipients tended to be higher than in the controls. CONCLUSION: Intrauterine circulatory imbalance may induce changes in VEGF expression and these alterations may be involved in both donor and recipient in the pathogenesis of TTTS, due to the maintenance of hemodynamic stability between the circulation of the twins.

Telomerase activity in pancreatic juice differentiates ductal carcinoma from adenoma and pancreatitis.

Telomerase activity was measured in pancreatic juice obtained by endoscopic retrograde pancreatography from 34 patients (12 with ductal carcinoma, 12 with pancreatic adenoma, and 10 with pancreatitis). The activity in pancreatic juice was expressed as the number of cells of a human pancreatic cancer cell line, MIA PaCa-2, that exhibit an activity equal to that expressed in 1 microg of protein from pancreatic juice. A telomerase ladder was detected in the pancreatic juice obtained from a majority of the patients with ductal adenocarcinoma. The median value of relative telomerase activity in the carcinoma samples was 9.38 (25th percentile, 3.14; 75th percentile, 95.8), a value significantly higher than that derived from patients with either pancreatitis or pancreatic adenoma (P < 0.0001). When a threshold value of relative telomerase activity of 3.00 was used, 75% (9 of 12) of the samples obtained from patients with ductal carcinoma were positive. We conclude that telomerase activity in pancreatic juice differentiates adenocarcinoma from adenoma and pancreatitis and may serve as a useful diagnostic tool.

Telomerase elevation in pancreatic ductal carcinoma compared to nonmalignant pathological states.

Telomerase activity was measured in surgically resected tissues of 20 human pancreatic ductal carcinomas, 12 adenomas, 5 pancreatitis tissues, 14 normal pancreatic ducts, and 13 normal pancreatic tissues (primarily made up of acinar cells) using a PCR-based telomerase assay. Relative telomerase activity was expressed as the equivalent telomerase intensity of the number of cells of a human pancreatic cancer cell line, MIA PaCa-2, per microgram of protein in the tissue samples. The median value (25th percentile, 75th percentile) of relative telomerase activity in pancreatic carcinomas was 13.2 (3.58, 244), which was significantly higher relative to normal tissues, normal ducts, pancreatitis tissues, and adenomas (P < 0.0001). When the cutoff value of relative telomerase activity was set at 1.00 and 3.00, the positivity rates of telomerase activity in pancreatic ductal carcinomas were 100 and 80%, respectively. Some of the adenoma samples displayed a weak telomerase ladder. However, when semiquantitatively analyzed, the relative telomerase activity of all adenoma tissues was less than 1.00 equivalent cells per microgram protein of the tissues, which was equivalent to the values encountered in normal ducts. Thus, our results indicate that reactivation of telomerase may occur at a late stage of pancreatic ductal carcinogenesis. Therefore, telomerase may be a specific marker for distinguishing pancreatic cancer from pancreatitis and adenomas.

Uterine artery Doppler velocimetry in relation to trophoblast migration into the myometrium of the placental bed.

OBJECTIVE: To test the hypothesis that an abnormally high resistance in the uterine artery indicates impaired trophoblast migration into the myometrium of the placental bed. METHODS: Doppler velocimetry in the uterine artery was carried out in 43 pregnant women within 7 days before cesarean delivery and placental bed biopsy. A pathologist evaluated the placental bed biopsies histologically. Trophoblast migration was absent in 28 cases (impaired migration group) and present in 15 (migration group). Clinical characteristics were compared between these two groups. RESULTS: There was no significant difference in the mean gestational ages at delivery in the two groups, but those with impaired migration included a higher incidence of small for gestational age infants (46.4 versus 6.7%, P < .01) and a lower mean (+/- standard deviation) birth weight (1622 +/- 528 versus 2287 +/- 748 g, P < .01). The systolic-diastolic ratio (S/D) in the uterine artery was higher in the impaired migration group (2.45 +/- 0.81 versus 1.92 +/- 0.34, P < .05). The absence of migration could be deduced from the S/D of the uterine artery, with a predictive value of 92.3% when we set the cutoff value of the ratio at 2.5. CONCLUSION: The results suggest that abnormal uterine artery flow velocity waveforms may indicate impaired trophoblast migration into the myometrium of the placental bed.

Prenatal detection of ischemic changes in the placenta of the growth-retarded fetus by Doppler flow velocimetry of the maternal uterine artery.

OBJECTIVE: To determine the relationships among the pregnancy outcomes of growth-retarded fetuses, Doppler flow velocimetry of the fetomaternal circulation, and pathologic changes in the placenta. METHODS: Forty-seven fetuses confirmed to be growth-retarded by ultrasonographic biometry were monitored during pregnancy in terms of the resistance indexes of the maternal uterine, fetal umbilical, and fetal middle cerebral arteries. After delivery, the placentas were examined for pathologic changes such as infarction and villous ischemia. RESULTS: Compared with 23 fetuses with nonischemic placentas, 24 growth-retarded fetuses whose placentas showed ischemic lesions were more frequently delivered preterm (P < .001) and by cesarean for fetal distress (P < .01), and they also had lower mean pH, higher carbon dioxide pressure, and lower oxygen pressure values (P < .05). Compared with the fetal umbilical and middle cerebral artery resistance indexes, the uterine artery resistance index showed the highest sensitivity (91.7%), specificity (78.3%), and positive predictive value (81.5%) for detecting placental ischemic changes. Linear discriminative analysis also showed that the uterine artery resistance index had the strongest correlation (P < .00001) with the placental ischemic changes. CONCLUSION: Ischemia of the placenta is associated with an adverse pregnancy outcome in growth-retarded fetuses. The placental ischemic changes can be detected using Doppler flow velocimetry. Measurement of the uterine artery resistance index might be useful for determining the clinical management of growth-retarded fetuses.

Analysis of carbohydrate-intolerant profiles of mothers with normal glucose tolerance tests and their large for gestational age neonates.

OBJECTIVE: To examine endocrine states of mothers with normal 75-g oral glucose tolerance tests (GTTs) who gave birth to large for gestational age (LGA) neonates (group I) and to examine those neonates. METHODS: We examined plasma glucose levels and serum immunoreactive insulin responses after the 75-g oral GTT was given to group I mothers (N = 34), mothers with an abnormal oral GTT who gave birth to LGA neonates (group II, N = 21), and those with normal oral GTTs having appropriate for gestational age neonates (group III, N = 173). We also examined the infants, checking neonatal birth weight, levels of immunoreactive insulin and C-peptide immunoreactivity in cord sera at birth and the lowest blood sugar level after birth to see if a correlation existed between them. RESULTS: Group I and II mothers showed higher titers in plasma glucose levels and remarkably enhanced ratios of 60- to 30-minute immunoreactive insulin values (immunoreactive insulin up-ratio) after load compared with those of group III mothers. Cord serum immunoreactive insulin and C-peptide immunoreactivity were significantly higher and the lowest blood sugar level was significantly reduced in group I and II neonates compared with those in group III. We observed a positive correlation between cord serum immunoreactive insulin, C-peptide immunoreactivity, and birth weight, but a negative correlation between cord serum immunoreactive insulin, birth weight, and the lowest blood sugar level in group I and II neonates (strongest tendency in group II), but not in group III neonates. CONCLUSION: All of the abnormal carbohydrate metabolic responses in group I mothers and neonates may result in the promotion of growth in LGA fetuses similar to group II, but to a lesser extent. Identification of group I mothers by the immunoreactive insulin up-ratio after oral GTT will help predict the occurrence of LGA neonates and their possible hypoglycemia.

Semi-quantitative analysis of telomerase in pancreatic ductal adenocarcinoma.

Using a polymerase chain reaction-based amplification assay, we measured telomerase activity in surgically resected pancreatic ductal carcinomas (n = 16 cases) and normal ducts (n = 6), comparing findings with the telomerase activity of a human pancreatic cancer cell line, MIA PaCa-2, as a standard, i.e., relative telomerase activity was determined. Telomerase activity was expressed as the equivalent telomerase intensity of the number of cells of MIA PaCa-2 per microgram protein of tissue samples. The median value for telomerase activity in normal pancreatic ducts was 0.13 and the 25th and 75th percentile were 0.01 and 0.76. The median value for telomerase activity in pancreatic ductal adenocarcinoma was 34.7 (25th percentile, 4.98; and 75th percentile, 296), significantly higher than that of normal ducts (P < 0.001). When the cut-off value was set at 1.0 and 3.0, the telomerase positivity rate of pancreatic ductal adenocarcinomas was 100% and 81.3%, respectively. Telomerase may be specific marker for pancreatic ductal carcinomas.

Usefulness of cord-blood harvesting for autologous transfusion in surgical newborns with antenatal diagnosis of congenital anomalies.

BACKGROUND/PURPOSE: The risks of homologous transfusion and the effectiveness of predeposit autologous transfusion have been described. The authors examined the clinical usefulness of cord-blood harvesting for autologous transfusion in newborns who had congenital anomalies antenatally diagnosed that would require surgical intervention at or near the time of delivery. METHODS: Of 112 cases of antenatal diagnosis of congenital anomalies, 50 mothers gave informed consent and enrolled in this study. Cord-blood was withdrawn immediately after clamping of the umbilical cord and was used for autologous transfusion in newborns within the first 3 days postpartum. RESULTS: A mean of 72 +/- 54 mL of cord-blood was harvested (27 +/- 18 mL/kg). While preserving cord-blood for 3 days at 4 degrees C, no signs of clot formation or hemolysis were observed. The harvested cord-blood included plasma-free Hb ranging from 1 to 68 (13 +/- 18) mg/dL and thrombin-antithrombin III complex ranging from 2 to 273 (18 +/- 50) ng/mL. Bacteriologic examination of the stored cord-blood showed negative cultures, except for samples from 3 newborns after vaginal delivery. A mean of 46 +/- 34 mL of cord-blood was used in 26 patients for autologous transfusion. No significant complications related to cord-blood transfusion were recognized clinically. CONCLUSIONS: Autologous cord-blood transfusion has the potential to be a useful alternative to homologous transfusion in newborns requiring surgery. Adequate collection and storage techniques for cord-blood must be developed. J Pediatr Surg 36:851-854.

Antenatal diagnosis of sacrococcygeal teratoma with hydrops fetalis; a case report.

Fetal sacrococcygeal teratoma (SCT) with hydrops fetalis is known to have a poor prognosis. We report a case of SCT with hydrops fetalis which was diagnosed antenatally at 30 weeks gestation. After delivery by cesarean section, the tumor was removed and the infant is alive one year after surgery with no sign of recurrence. However, he has profound brain damage, perhaps caused by hypoxia secondary to the perinatal hypovolemia. This case demonstrates that a 30 weeks' gestation, survival is possible in fetal cases of SCT with hydrops fetalis, and illustrates the importance of perinatal circulatory management.

[Extremely low birth-weight infant with hydrocephalus; management of hydrocephalus using a miniature Ommaya's reservoir].

Use of the miniature Ommaya's reservoir in the treatment of extremely low birth-infant (under 1,000 mg) with hydrocephalus was studied in a series of five patients. The reservoir has a small-caliber with a 3 cm ventricular catheter. For these infants, this miniature Ommaya's reservoir is extremely useful for protection of the cortical mantle until a definitive procedure can be carried out after increase of body weight. The clinical course in five cases are summarized.

[Antenatal detection of developing nervous system abnormalities and perinatal surgical management].

As the use of prenatal ultrasound sonographic study becomes more popular, it is likely that several fetal anomalies of the central nervous system will be diagnosed in utero more frequently and accurately. Obstetric sonogram correlates well with the results of postnatal CT scanning. Now, with improved diagnosis and support facilities for the newborn, neurosurgical intervention is being requested, as more concern is expressed for such fetus. We have experienced seven cases of fetal disorders of the central nervous system-meningocele, meningoencephalocele, myeloschisis, arachnoid cyst and maximal hydrocephalus. When diagnosed late in gestation (after the 2nd trimester), it may be reasonable to consider early delivery at the time of pulmonary maturity, and extrauterine management to decrease secondary damage to the developing central nervous system. The method of delivering a fetus must be tailored to suit each case. We present our program for the management of fetal hydrocephalus-placement of a subcutaneous low profile Ommaya's reservoir for neonate immediately after birth, and then subsequently conversion to a ventriculoperitoneal shunt three or four weeks later. As advances are made in antenatal diagnostic techniques and appropriate therapy, prognostic data on congenital abnormalities of the central nervous system will increase and become more pertinent.

[Perinatal neurosurgical care for one fetal hydrocephalus on twin gestation].

Twin gestations are responsible for a disproportionate amount of perinatal mortality and morbidity. Such gestations may impose greater demands on maternal and child physiologic systems than singleton pregnancies. The most common antenatal complications were preterm labor. The clinical record of myelomeningocele infant presenting with overt hydrocephalus in utero at 27 weeks of twin gestation and operated miniature Ommaya's reservoir placement early after birth and intentional delayed back closure for myelomeningocele was reported. Although perinatal neurosurgical care for one fetal hydrocephalus on twin gestation is clearly advantageous, it alone is relatively ineffective in reducing the incidence of the complication, preterm labor.

[Anesthesia for cesarean section in patients with fetal anomaly].

Twenty-two cases of Cesarean section due to fetal anomaly diagnosed prenatally were reviewed in terms of the anesthetic managements. In 6 cases, diazepam 0.3 mg.kg-1, which provides fetal anesthesia for surgery scheduled immediately after birth, was administered intravenously to the mothers with/without fentanyl (2 general anesthesia and 4 regional anesthesia). The diagnosis of their fetuses was congenital diaphragmatic hernia, congenital cystic adenomatoid malformation of the lung, gastroschisis or omphalocele. No fetal anesthesia was performed in the other 16 cases (15 spinal anesthesia and 1 general anesthesia). Seven of their fetuses were diagnosed as hydrops. Since the general condition of the diseased newborn is known to be deteriorated after receiving various stress and aerophagia, fetal anesthesia in Cesarean delivery has the advantage of stress reduction and prevention of aerophagia. When the newborn is considered to need immediate neonatal resuscitation or intensive care including surgery, fetal anesthesia may be a choice of anesthetic technique.

[Specific activation of telomerase in pancreatic cancer tissue and preoperative diagnosis of pancreatic cancer by telomerase in pancreatic juice].

Telomerase activity was measured in surgically resected tissues in various pancreatic diseases. Relative telomerase activity was expressed as the number of MIA PaCa-2 cells containing an equivalent activity in 1 microgram protein from samples. Telomerase activity in carcinomas was significantly higher than in the other nonmalignant pathologic states. Subsequently, telomerase activity was measured in pancreatic juice from patients with carcinoma, adenoma, and pancreatitis. Telomerase activity in carcinoma samples was significantly higher than that in either pancreatitis or adenoma samples as in tissue samples. High activity of telomerase in pancreatic juice indicates the existence of pancreatic cancer and may serve as a diagnostic tool.

Successful in utero treatment of fetal goitrous hypothyroidism: case report and review of the literature.

In this report, we present a case of fetal goiter with overdistended fetal neck and mild polyhydramnios. Amniocentesis and cordocentesis were conducted at 32 weeks' gestation and fetal goitrous hypothyroidism was diagnosed. Intra-amniotic injection of l-thyroxine (T4) was performed with a weekly dose of 150 microg four times between 33 and 36 weeks' gestation. In response to this in utero treatment, the goiter was reduced and polyhydramnios was improved. The mother gave birth to a healthy live male infant with normal thyroid function. From our case report and review of previous literature, we recommend that the amount of l-thyroxine start as low as 150 microg, and that repeat cordocentesis be avoided as long as other clinical and laboratory parameters indicate improvement of the fetal conditions.

[Clinical spectrum and congenital anomalies in trisomy 18].

Ultrasound sonography has become a major diagnostic tool in the detection of fetal trisomy 18. And, because understanding fetal trisomy 18 is important for us, we examined the variegated presentations of trisomy 18. Clinical observation of 16 cases and autopsy findings in 14 cases of 18 trisomy are presented. These patients were seen during the seven-year period 1981-1988. All patients died in the first 3 months of life. The mean maternal age was 31.8 years and other clinical observation coincided well with those of other reports well recognized. In 15 cases, typical features of 18 trisomy (intrauterine growth retardation, trisomy face, hand and foot deformities) were seen. However, one case presented an atypical phenotype. Holoprosencephaly was superimposed, and this combination is believed to be unique. Another abnormality of the central nervous system was cerebellar hypoplasia in 50% of the cases and this incidence was much higher than in Smith's textbook (less than 10%). And in this paper we also reported a rare anomaly of the coronary artery and described first an abnormality of aortic arch and calcification of the placental vein in this paper. Findings in the present study were compared to the literature.

A lethal osteochondrodysplasia with mesomelic brachymelia, round pelvis, and congenital hepatic fibrosis: two siblings born to consanguineous parents.

We report a hitherto unknown, lethal osteochondrodysplasia in two Japanese siblings born to consanguineous parents. The skeletal abnormalities are characterised by mesomelic brachymelia with bowed forearms, a round pelvis with shortened greater sciatic notches, an ossification defect of the pubic bones, and absence of ossification centers in the cervical vertebral bodies. The associated visceral anomalies comprised periportal fibrosis and cystic dysplasia of the intrahepatic bile ducts, pancreatic ductal ectasia, a simple renal cyst, microcephaly with multifocal laminar necrosis and ectopic gray matter, dysplastic tracheobronchial cartilage, abnormal lobulation of the lung, diaphragmatic hernia, and stenotic pulmonary valve. Thrombocytopenia was present but megakaryocytes were slightly increased in the bone marrow. The patients showed various dysmorphic features including aniridia, a long palpebral fissure, prominent nasal bridge, beaked nose, flat philtrum, low-set fleshy ears, micrognathia with submucosal cleft palate, and multiple joint contractures.

Hydatidiform mole in a triplet pregnancy following gonadotropin therapy.

A first case is reported of complete hydatidiform mole with two coexistent fetuses in a triple pregnancy following human menopausal gonadotropin human chorionic gonadotropin (hMG-hCG) therapy. The molar mass and two fetuses were delivered separately at 17 weeks of gestation. The fetuses were female (155 g) and male (160 g) with individual placentae (85 g, 90 g). The hydatidiform mole (650 g) had a normal 46,XX karyotype. The sexes of the two fetuses and the karyotype of the mole are consistent with previous reports that the chromosomes of fetuses and moles are derived from both parents and the father, respectively.