Iliocaval arteriovenous fistula presenting with multiple organ failure.

Iliac arteriovenous fistulas are an uncommon condition, which may be spontaneous or traumatic in nature. Such fistulas classically present with a triad of high-output cardiac failure, pulsatile abdominal mass with a bruit and unilateral leg ischaemia or venous congestion. We describe a case of an iliocaval fistula secondary to rupture of a common iliac artery aneurysm, with an unusual presentation of multiple organ failure, masquerading as sepsis. We describe the CT findings of iliocaval fistula, which was the means of diagnosis in this study.

Eversion carotid endarterectomy.

BACKGROUND: Eversion carotid endarterectomy (ECEA) is a technique that obviates the need for traditional longitudinal arteriotomy and patch closure, with low stroke and restenosis rates. The aim of the present study was to report an Australian experience and technique of ECEA. METHODS: All patients who underwent ECEA by the investigating surgeons between October 1997 and July 2000 were followed up clinically and with duplex ultrasound. The technique of ECEA is described. RESULTS: One hundred and fifty-two ECEA were performed, 13 combined with coronary artery bypass grafting (CABG). The combined perioperative stroke and death rate was 2%; 0.65% excluding CABG combined cases. This compares with 2.9% for standard carotid endarterectomy throughout Victoria. Significant restenosis occurred in 2.6% after a mean follow up of 21.7 months. CONCLUSION: ECEA is a simple and safe alternative to standard carotid endarterectomy.

Molecular cloning of the rat TA1/LAT-1/CD98 light chain gene promoter.

The rat LAT-1 (L-amino acid transporter-1) gene is a CD98 light chain highly expressed in cancer and development. As an initial study of the molecular basis underlying regulation of its expression, we cloned 2 kb of the LAT-1 5' flanking region. Inverse RACE and primer extension methods were used to define the transcription initiation site at 80 bp upstream from the translational start site. Functional studies carried out in normal hepatic cells using constructs containing progressive 5' deletion from region -1958 to -185 showed 3-5-fold beta-galactosidase activities over control. The presence of an activator site(s) between -52 and -185 was indicated by low activities conferred by the construct spanning this region.

Overexpression of LAT1/CD98 light chain is sufficient to increase system L-amino acid transport activity in mouse hepatocytes but not fibroblasts.

l-amino acid transporter-1 (LAT1) is a highly conserved gene identified as a light chain of the CD98 amino acid transporter and cellular activation marker. In our previous studies we found increased expression of LAT1 in primary human cancers. We have demonstrated also that LAT1 response to arginine availability is lost in transformed and tumorigenic cells such that expression is constitutively high. System l-amino acid transport activity correlates with changes in LAT1. To assess the functional relevance of increased LAT1 expression and the requirement for 4F2 heavy chain, we overexpressed these CD98 subunits together and separately in nontransformed hepatocytes and fibroblasts. Antigen tags in the expression constructs confirmed that expressed proteins were localized to both cytoplasmic and plasma membrane locations within the cells. Overexpression of LAT1 alone in mouse hepatocytes, but not fibroblasts, was sufficient to increase system l transport, and these cells displayed a growth advantage in conditions of limited arginine. Our results suggest that loss of regulation leading to constitutive expression of LAT1 can contribute to oncogenesis. We hypothesize that the altered LAT1 expression observed in hepatocarcinogenesis gives cells a growth or survival advantage through increased transport activity in a tumor microenvironment of limited amino acid availability.

Irreversible maternal brain injury during pregnancy: a case report and review of the literature.

Maternal brain death or massive injury leading to persistent vegetative state during pregnancy is a rare event. Since 1979, 11 cases, including the current one, of irreversible maternal brain damage in pregnancy have been reported. In all but one, the pregnancies were prolonged with a goal of achieving delivery of a viable infant. Current advances in medicine and critical care enable today's physician to offer prolonged life-support to maximize the chances for survival in the neonate whose mother is technically brain dead. We present a case at our institution and review all previously published cases in the English literature for comparison as well as make management recommendations.

Efficacy of screening for fetal Down syndrome in the United States from 1974 to 1997.

OBJECTIVE: To estimate the 16-week prevalence of Down syndrome in the United States from 1974 to 1997 and to determine the efficacy of maternal age cutoffs and triple screens for detecting it antenatally. METHODS: Using natality statistics for the United States from 1974 to 1997 of maternal-age-specific live births to women 13-49 years old, we evaluated advanced maternal age (35-49 years at delivery) and the triple serum test (maternal serum alpha-fetoprotein, hCG, and unconjugated estriol) as screening tests for Down syndrome. Efficacy was evaluated using sensitivity, false-positive rate, positive predictive value, and likelihood ratio (likelihood ratio = sensitivity/false-positive rate). RESULTS: In 1974, the estimated second-trimester prevalence of Down syndrome was one in 740, but by 1997 that had increased to one in 504. The proportion of Down syndrome fetuses at 16 weeks' gestation in women 35-49 years old increased from 28.5% in 1974 to 47.3% in 1997. However, live births to women 35-49 years old increased more rapidly from 4.7% in 1974 to 12.6% in 1997. The likelihood ratio for maternal age to identify an affected pregnancy decreased during the study period and was substantially lower than that using the serum test. CONCLUSION: A maternal age cutoff of 35 years in the 1990s resulted in high false-positive rates and was less efficacious based on likelihood ratio and positive predictive value. Serum testing of all pregnant women would reduce the number of amniocenteses and decrease procedure-related losses.

TA1/LAT-1/CD98 light chain and system L activity, but not 4F2/CD98 heavy chain, respond to arginine availability in rat hepatic cells. Loss Of response in tumor cells.

Tumor associated gene-1/L amino acid transporter-1 (TA1/LAT-1) was recently identified as a light chain of the CD98 amino acid transporter and cellular activation marker. Our previous studies with primary rat hepatocyte cultures demonstrated that TA1 RNA levels were responsive to media amino acid concentrations, suggesting adaptive regulation. High level TA1 expression associated with transformed cells also suggested a role in tumor progression. The present study examined the relationship of TA1/CD98 expression, adaptive response, and associated amino acid transport to neoplastic transformation using a panel of well characterized rat hepatic cell lines. We found 1) increased expression of TA1 in response to amino acid depletion, specific for arginine but not glutamine; 2) loss of TA1 response to arginine in gamma-glutamyl transpeptidase-positive transformed and tumorigenic cells; 3) no appreciable response of 4F2/CD98 heavy chain to arginine levels; and 4) correlation of system L amino acid transport activity in response to arginine with changes in TA1/LAT-1 mRNA but not total immunoreacting protein. Our results suggest this CD98 light chain may act as an environmental sensor, responding to amino acid availability and that its regulation is complex. We hypothesize that altered TA1 expression is an early event in hepatocarcinogenesis giving neoplastic cells a growth or survival advantage, particularly under conditions of limited amino acid availability.

Comprehensive fetal ultrasonographic growth measurements in triplet gestations.

OBJECTIVE: Our purpose was to create tables and graphs of ultrasonographically derived fetal growth parameters in longitudinally studied triplet gestations from a single center. STUDY DESIGN: All triplet pregnancies managed by our division from 1987 through 1998 were identified. All had first-trimester dating sonograms and complete obstetric sonograms obtained by means of 3.5- or 5.0-MHz curvilinear transducers with freeze-freeze capability and on-screen calipers. Sonograms to assess fetal growth were obtained every 2 to 4 weeks, from 16 to 18 weeks' gestation until delivery. Fetal parameters obtained with each sonogram included biparietal diameter; head circumference; bicerebellar diameter; abdominal circumference; femur, humerus, tibia, and fibula lengths; estimated fetal weight; and head circumference/abdominal circumference ratio. Regression analysis was performed with JMP and Cricket Graph software packages, and lines of best fit with 95% confidence intervals were generated. RESULTS: A total of 443 ultrasonographic examinations were performed for 33 triplet pregnancies (99 fetuses). Each had between 3 and 6 sonograms obtained, all between 16 and 35 weeks' gestation. Scatterplots of each of the fetal growth parameters against gestational age were created with regression lines of best fit and 95% confidence intervals. All growth parameters were dependent on gestational age. CONCLUSION: A comprehensive set of fetal growth measurements in triplets from the United States is now available and can be used to assess longitudinal fetal growth.

Maternal chorioamnionitis and umbilical vein interleukin-6 levels for identifying early neonatal sepsis.

OBJECTIVE: The purpose of this study was to determine whether elevated levels of umbilical vein IL-6 would be a better marker for early neonatal sepsis than the clinical signs of maternal chorioamnionitis. METHODS: Patients delivering preterm because of spontaneous preterm labor or premature rupture of the membranes were evaluated for clinical signs of chorioamnionitis, which was defined as a temperature of > or =100.4 degrees F along with > or =2 of the following: significant maternal tachycardia (> or = 120 bpm), fetal tachycardia (> or =160 bpm), purulent discharge, uterine tenderness, and leukocytosis (WBC > or =18,000 cells/mm3). Umbilical vein blood was assayed for interleukin-6. An elevated interleukin-6 level was determined to be 25 pg/mL. Infants were evaluated for evidence of early neonatal sepsis. The abilities of clinical chorioamnionitis and interleukin-6 levels > or =25 pg/mL to predict early neonatal sepsis were compared. RESULTS: There were 28 patients delivering 14 (50%) neonates with evidence for early neonatal sepsis. The incidence of suspected neonatal sepsis in women with and without clinical chorioamnionitis was 6/10 (60%) vs. 8/18 (44.4%), P = 0.43. Using receiver operator characteristic curves, the best cutoff for interleukin-6 was found to be 25 pg/mL. The compared sensitivity, specificity, and positive and negative predictive values of clinical chorioamnionitis vs. interleukin-6 levels > or =25 pg/mL for predicting early neonatal sepsis were 42.9% vs. 92.9%, 71.4% vs. 92.9%, 60% vs. 92.9%, and 55.6% vs. 92.9%, respectively. CONCLUSIONS: Elevated umbilical vein levels of interleukin-6 predict those preterm infants with early sepsis better than the presence of clinical chorioamnionitis.

Relationship of amniotic fluid markers of intra-amniotic infection with histopathology in cases of preterm labor with intact membranes.

OBJECTIVE: To evaluate the correlation of amniotic fluid (AF) markers (AFMs) of intra-amniotic infection with histopathologic findings in cases of preterm labor with intact membranes, between 22 and 36 weeks' gestation. STUDY DESIGN: We reviewed the charts of patients admitted in preterm labor with intact membranes between January 1993 and December 1996. Those having amniocentesis were identified, and AFMs were compared with histopathology in patients who delivered within 48 hours of the amniocentesis. The AFMs evaluated were glucose, polymorphonuclear leukocytes, Gram stain, and culture. All placentae were reviewed by a single pathologist blinded to the AF findings. Histologic evidence of acute inflammation was defined by findings of both subchorial intervillositis and marginating choriodeciduitis. The sensitivities, specificities, and positive and negative predictive values of the various AFMs were calculated. RESULTS: Of 556 women with intact membranes presenting in preterm labor, 181 (32.6%) had amniocentesis and 88 delivered within 48 hours of the amniocentesis. Histopathologic chorioamnionitis was seen in 53 patients (60.2%). The findings (with their sensitivity, specificity, and positive and negative predictive values) were: polymorphonuclear leukocytes at > 10/high-power field (22.6%, 97.2%, 92.3%, and 46.1%), positive Gram stain (26.4%, 94.6%, 87.5%, and 47.3%), culture (28.3%, 92.1%, 83.3%, and 47.9%), and glucose of < 15 mg/dl (28.3%, 94.6%, 88.2%, and 47.9%), respectively. Using a receiver-operator characteristic curve for different level of AF glucose, a glucose level of < 20 mg/dl was the most sensitive AF predictor of histologic chorioamnionitis. CONCLUSION: Histopathologic evidence of chorioamnionitis was present in 60.2% of cases of preterm births due to preterm labor in women who at our institution were offered and accepted amniocentesis and subsequently delivered within 48 hours. AFMs may be useful predictors of histologic chorioamnionitis. The most efficient AFM for chorioamnionitis in this group of patients was glucose at < 20 mg/dl.

Clinical and ultrasonographic features of dextroposition of the fetal heart.

OBJECTIVE: Our purpose was to characterize the findings associated with dextroposition of the fetal heart. STUDY DESIGN: A fetal echocardiography database was retrospectively searched from January 1990 through December 1996 to identify all cases referred or diagnosed with dextroposition of the fetal heart. Dextroposition was defined as most of the normally connected fetal heart found on the right side of the fetal chest. Intracardiac and extracardiac fetal anomalies were reviewed. All available karyotypes and postnatal examinations were reviewed. RESULTS: During the study period 2882 fetal echocardiograms were performed, of which 297 (10.3%) were abnormal. Of these, 14 had dextroposition. Associated anomalies included atrioventricular canal (29%), diaphragmatic hernia (21%), and aneuploidy (14%). Isolated dextroposition with no other significant anomalies was seen in only 1 case. In another, no anomalies were noted except for suspected agenesis of 1 lobe of the right lung; karyotype and postnatal evaluation revealed no other abnormalities in both cases. CONCLUSIONS: Dextroposition of the fetal heart was seen in 0.5% of our fetal echocardiograms and was associated with significant anomalies in 86% of our cases. When diagnosed, a targeted ultrasonogram, fetal echocardiogram, and karyotype should be offered.

Management of parvovirus infection in pregnancy and outcomes of hydrops: a survey of members of the Society of Perinatal Obstetricians.

OBJECTIVE: Our purpose was to investigate the evaluation and management of parvovirus infection during pregnancy. STUDY DESIGN: Surveys were mailed to members of the Society of Perinatal Obstetricians residing in the United States and Canada in July 1997. They were asked about their evaluation and management of parvovirus infection, including whether they repeated and confirmed serologic studies, what their initial and follow-up evaluations included, whether they had had any cases of parvovirus-associated hydrops in the past 2 years, and if so, what were the management and outcomes of the hydropic fetuses. RESULTS: Surveys were mailed to 1623 members of the Society of Perinatal Obstetricians and 541 completed surveys were returned. Sixty-eight percent of the respondents repeated and confirmed serologic studies. Eighty-nine percent used ultrasonography in their initial management of pregnant patients with recent parvovirus infection, 7.5% used amniocentesis for polymerase chain reaction, and 2% used fetal blood sampling. The outcomes of the 539 cases of parvovirus-induced hydrops included spontaneous resolution in 34%, death without intrauterine transfusion in 30%, resolution after intrauterine transfusion in 29%, death after intrauterine transfusion in 6%, and pregnancy termination in 1%. Almost all cases of nonimmune hydrops reported occurred between 16 and 32 weeks. CONCLUSIONS: Approximately one third of the cases of parvovirus-induced nonimmune hydrops resolved spontaneously, whereas 83.5% of hydropic fetuses transfused survived.

Resolution of human parvovirus B19-induced nonimmune hydrops after intrauterine transfusion.

Our objective is to report our experience with cases of prolonged recovery from nonimmune hydrops secondary to human parvovirus B19 infection occurring after intrauterine transfusion. We reviewed cases referred to our unit over a 10 year period for exposure to parvovirus B19 infection. Those cases with serologic evidence of recent infection were identified. The cases requiring intrauterine transfusion were reviewed for demographic details, time of exposure, parvovirus B19 serology, gestational age at detection of nonimmune hydrops, number and results of fetal blood samples, duration from intrauterine transfusion to resolution of hydrops, and neonatal outcome. Of 38 cases identified through serologic evidence of recent parvovirus B19 infection, 35 (92.1%) did not develop hydrops, and these were followed by serial ultrasonography for 8 weeks from the time of exposure. Three cases (7.9%) developed hydrops and required intrauterine transfusion; in two the transfusion was intravascular and in one it was intraperitoneal. The mean duration from intrauterine transfusion to resolution of hydrops was 8 weeks 2 days. Pregnancy outcome in all cases was normal. In cases of nonimmune hydrops secondary to parvovirus B19 infection, resolution of the hydrops after intrauterine transfusion may take up to 12 weeks with a normal pregnancy outcome.

Iatrogenic monoamniotic twins as a complication of therapeutic amniocentesis.

BACKGROUND: Therapeutic amniocentesis has been accepted widely as a safe and efficacious way to treat the polyhydramnios-oligohydramnios sequence associated with twin-twin transfusion syndrome. CASE: A 28-year-old woman, gravida 2, para 1, diagnosed with twin-twin transfusion syndrome at 28 weeks' gestation was treated with serial amniocenteses. The dividing membrane was ruptured inadvertently during therapeutic amniocentesis, with subsequent complete disruption of the amniotic membrane. Iatrogenic monoamniotic twins with cord entanglement and knotting resulted. CONCLUSION: Creation of monoamniotic twins by disruption of the dividing membrane can be a complication of therapeutic amniocentesis for twin-twin transfusion syndrome. Such disruption may result in the same morbidity and mortality that are seen in naturally occurring monoamniotic twins.

Monoamniotic twins: improved perinatal survival with accurate prenatal diagnosis and antenatal fetal surveillance.

OBJECTIVE: Our goal was to report our 10-year experience with monoamniotic twins and to compare that experience with cases reported in the literature. STUDY DESIGN: Records of all monoamniotic twin pregnancies managed at the University of Connecticut Health Center from March 1986 to August 1996 were reviewed. A MEDLINE search from January 1966 to August 1996 was performed, and each report was screened for accuracy of diagnosis. Only cases with umbilical cord entanglement of nonconjoined like-sex twins, the obstetrician's confirmation at delivery, or pathologic confirmation of monoamniotic placentation were included. Data collected were as follows: birth outcome, gestational age at delivery, birth weight, gender, Apgar scores, hematocrit, cord knotting, and neonatal complications. Cases from the literature were divided into those with prenatal diagnosis and those without. RESULTS: Thirteen monoamniotic pregnancies resulting in 26 infants who were born alive were managed at our center. The average gestational age at diagnosis was 16.3 weeks. All had antenatal fetal surveillance including serial sonograms and nonstress tests. The average gestational age and birth weight at delivery were 32.9 weeks and 1669 gm, respectively. Cord entanglement was noted in all cases, with knotting in 8 of 13. Two pairs of 26 newborns had evidence of twin-twin transfusion syndrome. Eight of 13 monoamniotic pregnancies were delivered because of nonreassuring results of nonstress test, two because of preterm labor, two electively because of lung maturity, and one because of intrauterine growth restriction. Two of the 26 infants died in the neonatal period, one of congenital heart disease and one of sepsis and asphyxia. The MEDLINE search revealed 96 articles with a total of 202 sets of monoamniotic twins. Comparison of cases (13 sets) with the historic control group without prenatal diagnosis (77 sets) showed a 71% reduction in relative risk of perinatal mortality. CONCLUSIONS: With accurate prenatal diagnosis, intensive fetal surveillance, and appropriately timed delivery, perinatal survival of monoamniotic twins is improved; it was 92% in this series.

Value of umbilical artery and vein levels of interleukin-6 and soluble intracellular adhesion molecule-1 as predictors of neonatal hematologic indices and suspected early sepsis.

This study was designed to evaluate the relationship of suspected early neonatal sepsis to umbilical artery and vein levels of interleukin-6 (IL-6) and soluble intracellular adhesion molecule-1 (sICAM-1). Umbilical artery and vein samples from 17 preterm and 6 term pregnancies were assayed for IL-6 (pg/ml) and sICAM-1 (ng/ml). Neonates were categorized as having probable or suspected sepsis vs. no sepsis within 3 days of birth. Levels of IL-6 and sICAM-1 were evaluated based on sepsis status. Neonatal hematologic parameters were correlated with umbilical artery (ua) and vein (uv) levels of IL-6 and sICAM-1. Sensitivity, specificity, positive and negative predictive values for detecting neonates having probable or suspected early sepsis were calculated. There were significant differences of IL-6 levels between suspected sepsis and no infants in the umbilical artery (P < 0.002) and vein (P < 0.0001). The sensitivity, specificity, positive and negative predictive values for detection of suspected early neonatal sepsis using umbilical artery IL-6 levels > 7 pg/ml were 88.5%, 66.6%, 58.8%, 91%, and for umbilical vein levels > 7 pg/ml these values were 88.5%, 93.3%, 88.5%, and 93.3%. Umbilical artery and vein IL-6 levels correlated with both absolute band counts and immature/total neutrophil ratios. sICAM-1 levels were not affected by designated sepsis status. Umbilical cord blood IL-6 (but not sICAM-1) is potentially useful as a marker for suspected early neonatal sepsis.

Late prenatal ultrasound features of hydrometrocolpos secondary to cloacal anomaly: case reports and review of the literature.

Cloacal anomalies are extremely rare and have variable presentations. Prenatal diagnosis can be difficult especially if they present in late gestation. Here we present two cases diagnosed in the late third trimester and review the literature regarding prenatal diagnosis of cloacal anomalies.

Second-trimester ultrasound markers for detection of trisomy 21: which markers are best?

OBJECTIVE: To investigate which second-trimester ultrasound markers for aneuploidy are the most diagnostically efficient in detecting fetal trisomy 21. METHODS: All second-trimester genetic sonograms performed since November 1, 1992 for women at increased risk for fetal trisomy 21 were analyzed retrospectively. Statistical analysis included descriptive statistics, the test of proportions, and univariate and multivariable logistic regression analysis using trisomy 21 as the dependent variable and ten aneuploidy ultrasound markers as independent variables. RESULTS: There were 581 normal fetuses, 23 with trisomy 21 and four with other chromosomal abnormalities. When one or more abnormal ultrasound markers were present, the sensitivity and false-positive rate for trisomy 21 were 87% and 13.4%, respectively. After adjusting for confounders, multivariate logistic regression analysis showed the best combination of ultrasound markers for detecting trisomy 21 to be nuchal fold thickening (relative risk [RR] 85.5; 95% confidence interval [CI] 20.4, 357.7), pyelectasis (RR 25.2; 95% CI 6.7, 95.0), and short humerus (RR 20.4; 95% CI 4.5, 92.1). The model combining these three ultrasound markers yielded a sensitivity of 87% and a false-positive rate of 6.7%. CONCLUSION: By using only three ultrasound markers (combination of nuchal fold thickening, pyelectasis, and short humerus) the false-positive rate is decreased from 13.4% to 6.7% without any compromise in the sensitivity (87%). The clinical usefulness of evaluating the various second-trimester ultrasound markers needs to be evaluated in prospective studies.

Iliac wing angle as a marker for trisomy 21 in the second trimester.

OBJECTIVE: To evaluate the fetal iliac wing angle in detecting trisomy 21 in the second trimester of pregnancy. METHODS: Using an axial view of the fetal pelvis, the angle between the right and left iliac wings (iliac wing angle) was measured ultrasonographically at the time of the second-trimester ultrasound or genetic amniocentesis in 377 singleton fetuses. Trisomy 21 was diagnosed by karyotype results from the amniocentesis or newborn examination with karyotype if trisomy 21 was suspected based on phenotypic features. Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were calculated using multiple cutoff points. A receiver operating characteristic (ROC) curve was used to identify the optimum iliac wing angle. Descriptive statistics and Student t test were utilized for analyses with a P of less than .05 considered significant. RESULTS: The average gestational age was 18.8 weeks (range 13-32). Karyotypes were available in 128 fetuses. The overall prevalence of trisomy 21 was 11 of 377 (2.9%). The mean (+/-standard deviation) iliac wing angle in the normal fetuses was 68.2 degrees (+/-15.4 degrees) and 98.5 degrees (+/-11.3 degrees) in fetuses with trisomy 21 (P < .001). Using an ROC-derived absolute cutoff of 90 degrees, an abnormal iliac wing angle had sensitivity of 90.9% (ten of 11), specificity of 94.5% (346 of 366), NPV of 99.7% (346 of 347), and PPV of 33.3% (ten of 30) to detect trisomy 21. CONCLUSION: Fetuses with trisomy 21 have greater iliac wing angles than do normal fetuses. Using an ROC-derived absolute cutoff of 90 degrees, we could detect 90.9% of fetuses with trisomy 21 with a PPV of 33% in our high-risk population. These findings suggest that iliac wing angle is a useful marker in antenatal screening for trisomy 21.