Gene Expression Profiles as Markers of Aggressive Disease-EGFR as a Factor

We previously reported that 43 (58%) of 75 head and neck squamous cell carcinoma (HNSCC) tumors harbor increased epidermal growth factor receptor (EGFR) gene copy numbers as determined by fluorescent in situ hybridization. In this study, an increased EGFR copy number was associated with decreased progression-free survival and overall survival of HNSCC patients. However, activated EGFR protein levels are difficult to quantify by immunohistochemistry and are subject to dynamic regulation, specifically receptor downregulation on ligand binding. Therefore, we generated an activated EGFR gene expression signature in an in vitro HaCaT keratinocyte model system to further study genes involved in the EGFR signaling pathway in HNSCC. The results from this model system have suggested that the activated EGFR signature might reflect the activated state of the EGFR pathway in human HNSCC tumors and that it is associated with the increased EGFR gene copy number by fluorescent in situ hybridization. Furthermore, the activated EGFR signature has provided additional leads, because they are related to co-regulated molecular pathways and associated gene products on activation of EGFR. These could be exploited to refine and optimize combination therapies to be used in conjunction with available EGFR inhibitors in individual HNSCC patients

Fetal blood sampling from the intrahepatic vein: analysis of safety and clinical experience with 214 procedures

Transabdominal fetal blood sampling under ultrasonic guidance was performed at the intrahepatic vein on 214 occasions in 177 fetuses. In 72 cases, an intravascular transfusion was also attempted at the same site. In 91.1% of the samplings, more than 1 mL of pure fetal blood was obtained, and in 89.9% of transfusions, fetal hematocrit or platelet concentration was raised to a satisfactory level. Fetal bradycardia and intraperitoneal bleeding occurred in 2.3% of the cases. Among fetuses at low risk, there was only one intrauterine death, which occurred 3 weeks after the procedure, and one spontaneous abortion in a patient with twin pregnancy. In fetuses with Rh/Kell alloimmunization or perinatal alloimmune thrombocytopenia, the survival rate was 86%. Four liver enzyme were assayed in the blood of 13 fetuses that underwent transfusions at the intrahepatic vein and 13 controls in whom the site of sampling was the umbilical vein at the placental cord insertion. No differences were found between the groups at the subsequent transfusion 2-5 weeks later. The intrahepatic vein is an alternate site of sampling/transfusion when access is difficult or failure occurs at the placental cord insertion. This approach minimizes the risks of fetal blood loss, fetomaternal hemorrhage, arterial vasospasm, and cord tamponade

Prenatal diagnosis of an ectopic intrathoracic kidney in right-sided congenital diaphragmatic hernia using color Doppler ultrasonography

The prenatal sonographic features of a fetus with right-sided congenital diaphragmatic hernia diagnosed at 33 weeks are presented. Color Doppler demonstrated an abnormal course of the right renal artery, arising from the aorta and feeding the intrathoracic right kidney. This case report stresses the role of color Doppler in defining which organs have herniated in fetuses with diaphragmatic hernia

Endocrine pancreatic function in growth-retarded fetuses

Maternal-fetal glucose gradient and fetal plasma glucose, insulin, and glucagon were measured in 63 fetuses: 34 controls and 29 with growth retardation (nine with and 20 without end-diastolic frequencies in the umbilical artery). Maternal-fetal glucose gradient and fetal glucagon levels were higher in the growth-retarded group than in controls (P < .001), whereas fetal insulin and glucose concentrations were lower (P < .001). Although maternal-fetal glucose gradient, fetal glucose, and insulin concentrations were similar among the growth-retarded fetuses, fetuses without end-diastolic frequencies in the umbilical artery had higher fetal glucagon levels (P = .01) than those with end-diastolic frequencies. In growth-retarded fetuses, the increase in fetal glucagon might reflect a compensatory response to hypoglycemia and appears to be a better index of fetal compromise than is glucose or insulin

Erythropoietic suppression in fetal anemia because of Kell alloimmunization

OBJECTIVE: Our purpose was to test the hypothesis that maternal anti-Kell alloimmunization produces fetal anemia by erythroid suppression

Fetal macrocytosis in association with chromosomal abnormalities

Mean red cell volume (MCV) was determined in 264 fetuses between 15-41 weeks. After exclusion of anemic, hypoxic, and chromosomally abnormal fetuses, the MCV in 208 umbilical venous samples was shown to decrease with gestation (r = 0.64; P < .001), and a normal range was constructed by linear regression analysis. An elevated MCV was found in both fetuses with triploidy, in four of five with monosomy X, and in four of ten with trisomies 18 or 21. The MCV was similarly raised in four of five fetuses with gross anomalies in whom cytogenetic cultures had failed. Significant correlations were found in chromosomally abnormal fetuses between the elevation in MCV and both the nucleated red cell (r = 0.69; P < .01) and reticulocyte counts (r = 0.57; P < .05). There was a similar correlation with nucleated red cells in 16 severely anemic fetuses with Rh disease, 12 of whom had a raised MCV. Elevation in MCV was unrelated to hypoxia. Macrocytosis had a sensitivity of 71% and a specificity of 95% in the second trimester for predicting an abnormal karyotype in nonanemic fetuses (kappa index 0.60). Fetal MCV may provide clinically useful information while one awaits culture results. We suggest that karyotyping be considered in fetuses undergoing blood sampling for other indications in whom the MCV is raised

Uterine peritoneal amniotic fluid leakage: an unusual complication of intrauterine shunting

Bilateral pleuroamniotic shunting was performed at 33 weeks' gestation in a fetus with bilateral hydrothorax, hydrops, and gross polyhydramnios. The procedure was successful, but acute amniotic fluid leakage into the maternal peritoneal cavity occurred soon after. This produced marked maternal discomfort and transient oligohydramnios, with consequent fetal distress. Expectant management was adopted in view of fetal lung immaturity. Resolution of maternal ascites occurred within 24 hours and the fetal heart rate normalized as amniotic fluid reaccumulated. The pregnancy progressed uneventfully thereafter

Diagnostic and therapeutic transabdominal amnioinfusion in oligohydramnios

We report our experience with 92 antenatal amnioinfusion procedures. In order to facilitate ultrasound visualization, a diagnostic infusion was attempted at a median of 22 weeks (range 16-36) in 61 pregnancies with oligohydramnios in the absence of ruptured membranes on clinical examination. The procedure was successful in 58 (95%). Infusion (mean volume 181 mL, range 40-64) significantly increased (P < .001) the deepest pool of amniotic fluid to a mean of 3.2 cm. Suspected fetal anomalies were then confirmed in 27 of 30 cases, whereas kidneys were clearly demonstrated in three fetuses suspected of renal agenesis. In addition, previously unsuspected anomalies were identified in five. Vaginal leakage indicating ruptured membranes occurred in 16 women. Leakage occurred in zero of 24 patients with, compared to 16 of 35 without, fetal urinary disorders (chi-2 = 15.1, P < .001), which does not support the recent suggestion that amnioinfusion causes rather than unmasks rupture of the membranes. Membranous detachment was observed by ultrasound in 13 patients, 11 of whom leaked vaginally. Information obtained at amnioinfusion led to a change of etiologic diagnosis in eight (13% of subjects). Forty serial infusions were performed in nine women as a pilot study to prevent oligohydramnios sequelae. There were no skeletal deformities; three neonates survived, and five of the six perinatal deaths had normal lung-body weight ratios. Overall, only two of 89 infusions (2.2%) were complicated by clinical amnionitis. Our findings support a role for amnioinfusion in oligohydramnios