PubMed Health⌕ Search

Biomedical subjects

M L Denbow

Publications and source records attributed to M L Denbow.

At least 19 recordsLinked to original sources
PubMed2006

Detection of cell-free fetal DNA in maternal urine.

OBJECTIVE: To evaluate the presence of cell-free fetal DNA signals in maternal urine as a potential source of material for non-invasive prenatal diagnosis. STUDY DESIGN: Patients referred to the regional fetal medicine unit who underwent prenatal diagnosis by chorionic villus sampling (CVS) were asked to give blood and urine immediately before the procedure. Maternal blood and urine were centrifuged at 10,000 g for 10 min. Plasma (1 mL) and urine (1 mL) supernatant were transferred to a clean tube and centrifuged again. The plasma (0.8 mL) and urine (0.8 mL) supernatant were removed without disturbing the cell pellet and stored at - 80 degrees C. Following DNA extraction, each sample was tested for the presence of Y chromosome associated DYS14 gene using real-time polymerase chain reaction (PCR). The total amount (maternal and fetal) of DNA in each sample was estimated using a quantitative real-time PCR assay. RESULTS: Twenty patients were enrolled in the study. CVS was performed at a median gestational age of 13 weeks (range 11 + 5 - 14 + 1). There were 12 male and 8 female fetuses, as confirmed by karyotype. Y chromosome DNA was not detected in any of the 20 samples of maternal urine, including 12 of the 20 samples in which Y chromosome DNA was detected in maternal plasma (all of whom were subsequently confirmed to be carrying a male fetus). There was considerable variation in the amount of total free DNA detected in maternal urine. CONCLUSIONS: Cell-free fetal DNA either was not present or did not amplify in maternal urine.

Biomarkers↗
PubMed2005

Outcome of fetal pleural effusions treated by thoracoamniotic shunting.

OBJECTIVE: Fetal pleural effusions are uncommon, and treatment options for moderate or severe effusions include drainage and thoracoamniotic shunting. However, relatively few records of effusions treated by thoracoamniotic shunting are available in the literature, so our objective was to study the outcome after thoracoamniotic shunting in our unit. METHODS: We searched the database of our tertiary fetal medicine unit for all cases of fetal pleural effusion treated by thoracoamniotic shunting between 1997 and 2003 inclusive, and studied the maternal and neonatal records. RESULTS: Ninety-two cases of fetal pleural effusion were studied, of which 21 had undergone a thoracoamniotic shunt. Sixteen of these 21 fetuses (76%) had associated hydrops, of which seven (44%) survived and, of the five (24%) without associated hydrops, three (60%) survived. There were two procedure-related losses. No shunted cases were associated with abnormal karyotype or proven maternal infection, but it is probable that three cases had been caused by an underlying genetic syndrome. CONCLUSION: The survival of fetuses with severe pleural effusions after thoracoamniotic shunting in this study was 48%.

Amniotic Fluid↗
PubMed2004

Derivation of rate of arterio-arterial anastomotic transfusion between monochorionic twin fetuses by Doppler waveform analysis.

We aimed to determine rates of interfetal transfusion along arterio-arterial (AA) anastomoses in monochorionic twins in vivo from analysis of Doppler waveform patterns. Twenty-one monochorionic twin pregnancies in which an AA anastomosis was identified antenatally underwent serial Doppler velocimetry. Unidirectional AA anastomotic flow rates increased with increasing gestational age (log y = 8 x 10(-9)x - 5 x 10(-8); p = 0.0002). The mean net rate of flow through an AA anastomosis at 28 weeks gestation was 7.6 x 10(-8) l/s (SD = 4.9 x 10(-8) l/s). This flow was significantly related to the distribution of arterio-venous (AV) anastomoses (p = 0.009) and birthweight discordancy (p = 0.006). We derived estimates of flow along individual AV anastomoses by assuming that net AA countertransfusion is shared equally among uncompensated AV anastomoses, and speculate that the median AV flow rate at 28 weeks is in the order of 6 x 10(-8) l/s. In conclusion, this study demonstrates that flow rates along AA anastomoses can be quantified antenatally. These are the first estimates of flow rates in vivo along placental anastomoses. Although AA net flows are modest, chronic unbalanced counterflow of this magnitude in the absence of compensatory superficial anastomoses could lead to significant haemodynamic compromise.

Arteries↗
PubMed2000

Preclinical development of noninvasive vascular occlusion with focused ultrasonic surgery for fetal therapy.

OBJECTIVE: This study was undertaken to investigate the ability of focused ultrasonic surgery to occlude blood flow in vivo. STUDY DESIGN: A 5-mm linear track exposure of 1.7-MHz focused ultrasound was applied across the femoral vessels for 5 seconds. Free field spatial peak intensities in the range of 1,000 to 4,660 W x cm(-2) were used. Vascular occlusion was confirmed after demonstration of an absent distal arterial pulse and an absent flow signal on magnetic resonance angiography and subtracted (after minus before) contrast-enhanced dual-echo steady-state sequences. RESULTS: The minimum intensity for consistent vascular occlusion was 1,690 W x cm(-2) at a focal depth of 5 mm when the transducer was moved at 1 mm x s(-1) orthogonal to the direction of blood flow. CONCLUSIONS: This study demonstrates that focused ultrasonic surgery can achieve reproducible vascular occlusion in vivo. Potential obstetric applications include noninvasive ultrasonographically guided occlusion of placental vessels mediating interfetal transfusion in monochorionic twins.

Animals↗
PubMed2000

Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome.

OBJECTIVE: We sought to correlate placental vasculature with fetal growth and outcome in monochorionic twins. STUDY DESIGN: Eighty-two patients with consecutive monochorionic pregnancies underwent biweekly ultrasonography for determination of fetal growth and well-being. After delivery, blinded placental injection studies delineated vascular anastomoses and territory share. Degree of balance in arteriovenous anastomoses equaled the number of arteriovenous anastomoses in one direction minus the number in the other. RESULTS: Pregnancies affected by fetofetal transfusion syndrome (n = 21) had numbers of arteriovenous and venovenous anastomoses that were similar to those in pregnancies without fetofetal transfusion syndrome but fewer arterioarterial anastomoses (P <.0001). Fetofetal transfusion syndrome occurred in 78% of pregnancies with >/=1 arteriovenous and no arterioarterial anastomoses. Birth weight discordancy correlated with placental territory discordancy (P <.0001) and the degree of balance in arteriovenous anastomoses (P =.004). The larger placental share twin had a greater growth velocity than its smaller placental share co-twin (P =.008) for all but one anastomotic pattern. Where arteriovenous anastomoses were aligned with the net venous outflow to the fetus with the smaller territory, co-twins had similar birth weights and growth velocities irrespective of placental share. Fetal survival was higher in pregnancies with an arterioarterial anastomosis (P =.01) but lower with a venovenous anastomosis (P =. 01). Survival of both fetuses was inversely associated with birth weight discordancy (P <.0001). CONCLUSION: Although interrelationships among the various types of anastomoses are complex, our data suggest that the placental territory share and the pattern of arteriovenous anastomoses influence fetal growth, that arterioarterial anastomoses protect against fetofetal transfusion syndrome, and that venovenous anastomoses reduce perinatal survival.

Arteriovenous Anastomosis↗
PubMed2000

Ex vivo delineation of placental angioarchitecture with the microbubble contrast agent Levovist.

OBJECTIVE: The aim of this study was to delineate placental vasculature with the microbubble contrast agent Levovist (99.9% galactose and 0.1% palmitic acid; Schering AG, Berlin, Germany), with the ultimate goal of delineating placental vascular anatomy in utero. STUDY DESIGN: A placental lobule from each of 11 term human placentas was perfused on the fetal side of the circulation under physiologic conditions. Randomly assigned dose-concentration combinations of Levovist were administered through a chorionic artery into the corresponding placental lobule, and the resultant echoenhancement with power Doppler imaging was recorded for digital analysis. Interplacental variability was corrected for by averaging the results of three injections at each dose-concentration combination. RESULTS: Echoenhancement was seen at all dose-concentration combinations in the injected lobule but not in adjacent control lobules. The three dose-concentration combinations that achieved optimal maximal integrated intensity and duration of action for both chorionic vessel and villus enhancement were 100 microL/kg of 400-mg/mL Levovist, 200 microL/kg of 400-mg/mL Levovist, and 400 microL/kg of 200-mg/mL Levovist. CONCLUSION: Microbubble contrast injection into the fetal vasculature enabled power Doppler imaging echoenhancement both in chorionic vessels and within the villus tree. We speculate that fetal injection of contrast agent may be applied to the delineation of placental lesions or areas of interfetal transfusion, although its applicability will be hindered by the need for fetal blood sampling.

Blood Vessels↗
PubMed2000

Antenatal factors at diagnosis that predict outcome in twin-twin transfusion syndrome.

OBJECTIVE: We sought to identify clinical factors at diagnosis that predict outcome in twin-twin transfusion syndrome. STUDY DESIGN: In this retrospective series 23 patients with twin-twin transfusion syndrome were seen in a tertiary referral fetal medicine center over a 3-year period. Ten antenatal factors were assessed to determine their ability to predict outcome by use of ordered logistic regression. These factors were the following: (1) absent or reversed end-diastolic flow in the umbilical artery, nonvisible bladder, anhydramnios, and estimated fetal weight of <3rd percentile in the donor; (2) pulsatile umbilical vein, either absent or reversed end-diastolic flow in the ductus venosus, or both, and tricuspid-mitral valve regurgitation in the recipient; and (3) gestational age at presentation, estimated fetal weight discordancy, absent arterioarterial anastomosis, and spontaneous rupture of the membranes or cervical change as pregnancy factors. Management comprised serial amnioreduction (n = 10), selective feticide (n = 5; 4 also had amnioreduction), septostomy (n = 4; 1 also had amnioreduction), and delivery (n = 2). Two patients miscarried before treatment. RESULTS: The chance of survival of both twins fell and double deaths increased linearly with increasing number of adverse factors (P =.026). A low chance of survival was independently associated with absent or reversed end-diastolic flow in the donor umbilical artery (P =.02) and with a pulsatile umbilical vein or absent or reversed end-diastolic flow in the ductus venosus (P =.03) of the recipient. The probability of at least one twin surviving was only 33% if there was absent or reversed end-diastolic flow in the donor umbilical artery or 37% when abnormal venous recordings were seen in the recipient. An arterioarterial anastomosis detected at diagnosis also influenced prognosis, with all twins surviving when an arterioarterial anastomosis was identified (P =.04). CONCLUSIONS: Three factors identified at diagnosis independently predict poor survival in twin-twin transfusion syndrome-absent or reversed end-diastolic flow in the donor umbilical artery, abnormal pulsatility of the venous system in the recipient, and absence of an arterioarterial anastomosis. These may have a role in the counseling of parents and in selecting the appropriate treatment strategy.

Arteries↗
PubMed2000

Doppler detection of arterio-arterial anastomoses in monochorionic twins: feasibility and clinical application.

The accuracy of in-vivo detection of arterio-arterial anastomoses (AAA) in monochorionic (MC) twins and its predictive value for twin-twin transfusion syndrome (TTTS) was assessed in 105 consecutive MC twins scanned at fortnightly intervals. AAA were sought using spectral and colour energy Doppler and ultrasound findings were compared with placental injection studies. AAA were identified in vivo in 59 (56%) pregnancies and at injection study in 68 (65%). The overall sensitivity and specificity was 85 and 97.3% respectively for the detection of AAA. Detection rates were higher at later gestations, with anterior placentae and with larger diameter AAA. The median insonation time to detect an AAA was 10 min (range 1-30). Where an AAA was identified, 15% of pregnancies (nine of 59) developed TTTS compared to 61% (28 of 46) when no AAA was seen (odds ratio 8.6). We conclude that AAA can be detected in vivo with high sensitivity and specificity without undue prolongation of scanning times and have a role in risk stratification in the antenatal assessment of MC twins.

Arterio-Arterial Fistula↗
PubMed2000

Twin fetuses: intravascular microbubble US contrast agent administration--early experience.

PURPOSE: To explore the feasibility of administering SH U 508A by using a single-needle procedure at ultrasonography (US) in twin pregnancies to confirm interfetal transfusion in monochorionic twins and delineate placental angioarchitecture in pregnancies with twin-twin transfusion syndrome. MATERIALS AND METHODS: Fourteen twin pregnancies were studied over 12 months: seven with monochorionic twins, including six with twin-twin transfusion syndrome; two of unknown chorionicity; and five with known dichorionic twins discordant for fetal karyotype or anomaly and undergoing selective feticide in the third trimester. Bolus injection of 100 microL/kg of estimated fetoplacental weight of 400 mg/mL of SH U 508A was performed in the intrahepatic vein of one twin, and evidence of interfetal transfusion was sought by means of digital analysis of power Doppler signals in the contralateral twin. RESULTS: Contralateral twin echo enhancement was seen in four of the nine ultimately histopathologically proved monochorionic twins. As expected, no evidence of echo enhancement in the contralateral twin was seen in any of the five dichorionic twin pregnancies. There was no evidence of fetal compromise associated with the procedure. CONCLUSION: These pilot results suggest that microbubbles can be used to demonstrate interfetal transfusion but not to delineate placental vascular anatomy.

Adult↗
PubMed1999

High failure rate of umbilical vessel occlusion by ultrasound-guided injection of absolute alcohol or enbucrilate gel.

The success rate for injected umbilical vascular occlusion in the published literature exceeds 85 per cent. In this study we assessed the efficacy of two forms of injected sclerosants in achieving umbilical vessel occlusion. 12 cases of attempted ultrasound-guided occlusion over a 2 1/2 year period were reviewed. These were monochorionic (MC) twins (n=6), dichorionic twins (n=3) and singletons (n=3) undergoing fetocide for severe anomalies, or impending fetal demise. Absolute alcohol (n=6), enbucrilate gel (n=5) or both (n=1) were used in an attempt to achieve vascular occlusion. Complete vessel occlusion was achieved in only a third of cases (4/12), three with absolute alcohol and one with enbucrilate gel. In MC twins occlusion was successful in two of six cases. In contrast to previously published data, this large series, containing more cases than the total previously reported, shows considerably poorer success rates for injected umbilical vascular occlusion. Injection of currently available sclerosants can no longer be recommended for umbilical vascular occlusion in human fetuses.

Enbucrilate↗
PubMed1999

First-trimester cord entanglement in monoamniotic twins.

OBJECTIVE: Monoamniotic twinning occurs in only 1% of twin pregnancies, but carries a high perinatal mortality rate. Early and reliable diagnosis is essential if attempts are to be made to reduce the complication rate. We report color Doppler demonstration of cord entanglement in the first trimester, which is diagnostic of monoamnionicity. METHODS: Two patients with twin pregnancies were examined in the first trimester with pulsed and color Doppler insonation of their umbilical arteries. RESULTS: Cord entanglement was suspected and proved by demonstrating differing fetal heart rate patterns in the same direction on umbilical artery Doppler analysis of a common mass of cord vessels. Following appropriate counselling, medical amnioreduction was induced at 20 weeks of gestation to reduce fetal movements and worsening cord entanglement. Delivery was by elective Cesarean section at 32 weeks' gestation and monoamnionicity was confirmed. CONCLUSION: We report a new sign for the demonstration of monoamnionicity in twin pregnancies in the first trimester. This should improve the reliability of early diagnosis, but further studies are required to confirm that, if cord entanglement occurs, it is usually present by the end of the first trimester.

Amnion↗
PubMed1998

Neonatal cranial ultrasonographic findings in preterm twins complicated by severe fetofetal transfusion syndrome.

OBJECTIVE: To investigate cranial ultrasonographic findings in survivors of monochorionic pregnancies complicated by fetofetal transfusion syndrome. STUDY DESIGN: Case details of all monochorionic twin pregnancies complicated by fetofetal transfusion syndrome were obtained from the Centre for Fetal Care database for a 3-year period. Fetofetal transfusion syndrome was diagnosed according to ultrasonographic criteria. Eligible for entry were twin pregnancies resulting in live-born preterm infants and complicated by fetofetal transfusion syndrome severe enough to require amnioreduction. Cranial ultrasonographic scans performed within 48 hours of birth were reviewed for evidence of abnormality. RESULTS: Seventeen pregnancies were eligible for inclusion in the study. Median gestational age was 25 weeks (between 17 and 29 weeks) at diagnosis and 30 weeks (between 25 and 35 weeks) at delivery. Three infants died before ultrasonography could be performed. The remaining 31 twin infants received an early cranial ultrasonographic scan. One of the 31 had a major cerebral infarct; 10 others had evidence of other, more minor, antenatally acquired lesions. CONCLUSIONS: Both donor and recipient survivors from pregnancies complicated by fetofetal transfusion syndrome are at significant risk for antenatally acquired cerebral lesions. Long-term neurologic follow-up studies are indicated to determine the clinical significance of these lesions.

Brain↗
PubMed1998

The consequences of monochorionic placentation.

Monochorionic (MC) placentation occurs in two-thirds of monozygous twins and approximately 0.3% of all spontaneous conceptions. Vascular anastomoses within the placenta allow intertwin transfusion to occur, which is in most cases a normal event. However, imbalance in this flow may lead to the clinical sequelae observed, with acute, chronic or reverse intertwin transfusion. Acute transfusion describes the events following the death of one of an MC twin pair in utero, with an approximately 1 in 4 chance of demise or neurological damage in the co-twin. Chronic intertwin transfusion, otherwise termed feto-fetal transfusion syndrome, arises following the gradual flux of blood from one twin (the donor) to its sibling fetus (the recipient). The ensuing polyhydramnios places the pregnancy at risk of preterm amniorrhexis and/or labour, notwithstanding the specific sequelae seen in these fetuses following chronic in utero insult. Reverse transfusion describes the most bizarre form of intertwin transfusion: acardiac twinning. Retrograde perfusion of one of the twins with deoxygenated blood leads to the formation of a non-viable acardiac parasite and a 'pump twin' struggling to maintain the cardiac output required to perfuse both twins.

Chorion↗
PubMed1998

Colour Doppler energy insonation of placental vasculature in monochorionic twins: absent arterio-arterial anastomoses in association with twin-to-twin transfusion syndrome.

OBJECTIVE: To determine in vivo whether monochorionic pregnancies complicated by twin-to-twin transfusion syndrome are associated with absence of haemodynamically-compensatory arterio-arterial anastomoses. DESIGN: Forty monochorionic pregnancies were prospectively recruited for an ultrasonographic survey of the chorionic plate using colour Doppler energy. Arterio-arterial anastomoses were identified by their characteristic bidirectional interference pattern on spectral Doppler. Angioarchitecture was confirmed by postnatal injection study. SETTING: Fetal medicine tertiary referral centre in London. MAIN OUTCOME MEASURES: Presence of arterio-arterial anastomoses, development of twin-to-twin transfusion syndrome, survival. RESULTS: Arterio-arterial anastomoses were detected by colour Doppler energy in 21 pregnancies (53%), and there were no false positives. An arterio-arterial anastomosis was more commonly found in unaffected (n=28) compared to pregnancies affected by twin-to-twin transfusion syndrome (n=12), both by colour Doppler energy [20/28 (71%) is 1/12 (8%); delta=63%, 95% CI 40%-86%] and by postnatal injection study [25/28 (89%) vs 3/12 (25%); delta=64%, 95% CI 37%-91%]. In pregnancies in which no arterio-arterial anastomoses were detected, a diagnosis of twin-to-twin transfusion syndrome was made in 58%, and the perinatal loss rate was 40%, compared with one case of twin-to-twin transfusion syndrome (5%) (P < 0.001) and a loss rate of 12% (P=0.005) in pregnancies in which an arterio-arterial anastomosis was detected. CONCLUSION Twin-to-twin transfusion syndrome is associated with an absence of functional arterio-arterial anastomoses in vivo in monochorionic twin pregnancies. This contributes to our understanding of the pathophysiology of twin-to-twin transfusion syndrome and confirms ex vivo studies demonstrating that twin-to-twin transfusion syndrome is associated with a paucity of superficial anastomoses. Prospective studies are indicated to determine the utility of colour Doppler energy for arterio-arterial anastomoses in predicting risk in monochorionic pregnancies.

Arterio-Arterial Fistula↗
PubMed1998

Prevalence, causes and outcome of vulval pain in a genitourinary medicine clinic population.

A detailed assessment was completed on 150 consecutive new female patients attending a walk-in genitourinary medicine clinic, in order to elicit the features of vulval pain. Twenty patients (13.3%) experienced vulval pain, and of these, 15 (75%) had an infective cause demonstrated. Candidiasis was demonstrated in more than half (55%) of them and one-fifth had genital herpes. Of the 5 patients in whom no infection was present, 2 were diagnosed with the vulvar vestibulitis syndrome (VVS) following their referral to the dedicated vulval clinic.

Adolescent↗
PubMed1997

The aetiology and management of twin-twin transfusion syndrome.

Twin-to-twin transfusion syndrome presents in the mid-trimester with gross discordance in amniotic fluid volume, and complicates 10-15 per cent of monochorionic twins. Recent studies suggest a primary vascular basis in which a paucity of the bidirectional superficial anastomoses normally found in monochorionic twins is unable to compensate for haemodynamic imbalance resulting from unidirectional transfusion along deeper arterio-venous anastomoses. It is associated with high rates of perinatal mortality from ruptured membranes, hydrops and growth restriction, and a significant morbidity from cardiac and neurological sequelae in particular. Serial aggressive amnioreduction is the current treatment of choice, with survival in around two thirds of cases. In the remaining third, with features suggesting a poor outcome, selective fetocide may have a role. Current attempts at vascular ablative therapies have been associated with inferior survival rates, but the long term therapeutic goal remains the identification and ablation of the shared chorionic vasculature.

Chorion↗