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Biomedical subjects

N M Fisk

Publications and source records attributed to N M Fisk.

At least 37 records · Page 2Linked to original sources
PubMed2003

Identification of fetal mesenchymal stem cells in maternal blood: implications for non-invasive prenatal diagnosis.

Strategies for genetic prenatal diagnosis on fetal cells in the maternal circulation have been limited by lack of a cell type present only in fetal blood. However, the recent identification of mesenchymal stem cells (MSC) in first trimester fetal blood offers the prospect of targeting MSC for non-invasive prenatal diagnosis. We developed protocols for fetal MSC enrichment from maternal blood and determined sensitivity and specificity in mixing experiments of male fetal MSC added to female blood, in dilutions from 1 in 10(5) to 10(8). We then used the optimal protocol to isolate fetal MSC from maternal blood in the first trimester, using blood taken after surgical termination of pregnancy as a model of increased feto-maternal haemorrhage. In model mixtures, we could amplify one male fetal MSC in 2.5 x 10(7) adult female nucleated cells, yielding a 100% pure population of fetal cells, but not one fetal MSC in 10(8) nucleated cells. Fetal MSC were identified in one of 20 post-termination maternal blood samples and confirmed as fetal MSC by XY fluorescence in-situ hybridization (FISH), immunophenotyping and osteogenic and adipogenic differentiation. We report the isolation of fetal MSC from maternal blood; however, their rarity in post-termination blood suggests they are unlikely to have a role in non-invasive prenatal diagnosis. Failure to locate these cells routinely may be attributed to their low frequency in maternal blood, to sensitivity limitations of enrichment technology, and/or to their engraftment in maternal tissues soon after transplacental passage. We speculate that gender microchimerism in post-reproductive maternal tissues might result from feto-maternal trafficking of MSC in early pregnancy.

Adult↗
PubMed2002

Ultrasound-guided umbilical cord occlusion using bipolar diathermy for Stage III/IV twin-twin transfusion syndrome.

OBJECTIVES: To evaluate bipolar diathermy as a technique for selective fetocide in the treatment of advanced (Stage III/IV) twin-twin transfusion syndrome (TTTS). METHODS: A prospective observational study in two tertiary referral fetal medicine centres: Queen Charlotte's Hospital, London, UK and Haemek Hospital, Afula, Israel. Fifteen cases of TTTS (14 twins and one triplet pregnancy) were treated by selective occlusion of either the donor (n=8) or recipient's (n=7) umbilical cord using ultrasound-guided bipolar diathermy. Following each procedure, patients were scanned serially for fetal growth, liquor volume and umbilical Doppler measurements. Procedural complications and obstetric outcome were recorded. Postnatal placental injection studies were performed. RESULTS: Overall co-twin survival in Stage III/IV TTTS was 13/14 (93%). There were no treatment failures. The incidence of preterm prelabour rupture of membranes (PPROM) within 3 weeks of the procedure was 3/15 (20%). In those cases where pre-procedure umbilical artery Dopplers were abnormal, the Doppler findings normalised post-procedure in all non-cord-occluded fetuses. Growth velocities of surviving donors were similar to those of surviving recipients. CONCLUSIONS: Bipolar diathermy appears an effective technique for the selective reduction of monochorionic twins complicated by severe as well as preterminal TTTS, with recipient and donor fetuses being equally appropriate choices for fetocide. We suggest that for advanced-stage disease where the parents can contemplate this option, cord occlusion as a single preemptive procedure maximises the opportunity for intact survival of a single survivor.

Diathermy↗
PubMed2002

Validation of the Quintero staging system for twin-twin transfusion syndrome.

OBJECTIVE: To validate an established staging system for twin-twin transfusion syndrome. METHODS: Prospective observational study in a tertiary referral fetal medicine center of 52 consecutive cases of twin-twin transfusion syndrome. Each pregnancy was assessed longitudinally for a variety of prognostic factors including fetal biometry, amniotic fluid volume, arterial and venous Doppler sonogram abnormalities, and the presence of hydrops. Data were used to determine stage at diagnosis and first treatment, and worst stage throughout pregnancy. Perinatal outcome was assessed by stage. Management comprised serial amnioreduction, septostomy, selective reduction, or delivery, alone or in combination. RESULTS: Median gestation at presentation and first treatment were both 21 weeks (range 14-34 and 15-34), and at delivery it was 29 weeks (range 16-40). Sixty-three percent of pregnancies (33 of 52) were at least stage III at presentation. Forty-five percent of pregnancies (22 of 49) progressed to a more advanced stage. Overall survival was 47% (47 of 100), with no difference between donor and recipient fetuses (40% [20 of 50] versus 54% [27 of 50] [chi(2) P =.5]). Survival rates were 58% (15 of 26), 60% (six of ten), 42% (20 of 48), 43% (six of 14), and 0% (none of two) for stages I-V, respectively, with no significant influence of stage at presentation on survival. Survival was poorer where stage increased, versus decreased (27% [12 of 44] versus 94% [17 of 18] chi(2) P <.001). Kaplan-Meier survival curves indicated that staging at presentation identified pregnancies at greater risk of earlier rather than later gestational perinatal loss. CONCLUSION: The Quintero staging system did not distinguish good from bad outcome at presentation, and thus should be used with caution in guiding initial management of twin-twin transfusion syndrome. However, prognosis was influenced by a change in stage, and pregnancies progressing to higher stage disease were at increased risk of earlier perinatal loss. Staging may thus be more useful in monitoring disease progression.

Adult↗
PubMed2002

Influence of twin-twin transfusion syndrome on fetal cardiovascular structure and function: prospective case-control study of 136 monochorionic twin pregnancies.

OBJECTIVE: To test the hypothesis that identical twins show no inter-twin differences in cardiovascular structure or physiology in fetal life unless there has been twin-twin transfusion syndrome. DESIGN: Unselected prospective case-control observational study of fetoplacental haemodynamics including echocardiography at a median of 24 (16.7 to 32.3) weeks, with postnatal confirmation of congenital heart disease or normality. SETTING: Fetal medicine unit. PATIENTS: 136 women with monochorionic diamniotic twin pregnancies, of which 47 fetal twin pairs (35%) had twin-twin transfusion syndrome. RESULTS: There were no haemodynamic differences between the bigger fetus (twin 1) and the smaller co-twin (twin 2) in uncomplicated monochorionic diamniotic pairs. In twin-twin transfusion syndrome, recipient fetuses had increased aortic and pulmonary velocities compared with their donor co-twins (mean (SD): 0.73 (0.23) m/s and 0.63 (0.14) m/s), respectively, v 0.53 (0.16) m/s and 0.48 (0.10) m/s in donor twins; p = 0.003 (aortic) and < 0.0001 (pulmonary)), and also in comparison with twin 1 and twin 2. The overall prevalence of congenital heart disease was increased above that in singletons (3.8% v 0.56%; 6.9% in twin-twin transfusion v 2.3% in uncomplicated monochorionic diamniotic twins), with inter-twin discordance for defects. The prevalence in recipient twins was 11.9% (p = 0.014 v uncomplicated control twins). CONCLUSIONS: Fetuses with an identical genome but no circulatory imbalance have similar cardiovascular physiology but discordant phenotypic expression of congenital heart disease. The high prevalence of congenital heart disease in monochorionic diamniotic twins merits detailed fetal echocardiography.

Adult↗
PubMed2001

Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow.

Human mesenchymal stem/progenitor cells (MSCs) have been identified in adult bone marrow, but little is known about their presence during fetal life. MSCs were isolated and characterized in first-trimester fetal blood, liver, and bone marrow. When 10(6) fetal blood nucleated cells (median gestational age, 10(+2) weeks [10 weeks, 2 days]) were cultured in 10% fetal bovine serum, the mean number (+/- SEM) of adherent fibroblastlike colonies was 8.2 +/- 0.6/10(6) nucleated cells (69.6 +/- 10/microL fetal blood). Frequency declined with advancing gestation. Fetal blood MSCs could be expanded for at least 20 passages with a mean cumulative population doubling of 50.3 +/- 4.5. In their undifferentiated state, fetal blood MSCs were CD29(+), CD44(+), SH2(+), SH3(+), and SH4(+); produced prolyl-4-hydroxylase, alpha-smooth muscle actin, fibronectin, laminin, and vimentin; and were CD45(-), CD34(-), CD14(-), CD68(-), vWF(-), and HLA-DR(-). Fetal blood MSCs cultured in adipogenic, osteogenic, or chondrogenic media differentiated, respectively, into adipocytes, osteocytes, and chondrocytes. Fetal blood MSCs supported the proliferation and differentiation of cord blood CD34(+) cells in long-term culture. MSCs were also detected in first-trimester fetal liver (11.3 +/- 2.0/10(6) nucleated cells) and bone marrow (12.6 +/- 3.6/10(6) nucleated cells). Their morphology, growth kinetics, and immunophenotype were comparable to those of fetal blood-derived MSCs and similarly differentiated along adipogenic, osteogenic, and chondrogenic lineages, even after sorting and expansion of a single mesenchymal cell. MSCs similar to those derived from adult bone marrow, fetal liver, and fetal bone marrow circulate in first-trimester human blood and may provide novel targets for in utero cellular and gene therapy.

Adipose Tissue↗
PubMed2001

Simultaneous fetal cell identification and diagnosis by epsilon-globin chain immunophenotyping and chromosomal fluorescence in situ hybridization.

Isolating fetal erythroblasts from maternal blood offers a promising noninvasive alternative for prenatal diagnosis. The current immunoenzymatic methods of identifying fetal cells from background maternal cells postenrichment by labeling gamma-globin are problematic. They are nonspecific because maternal cells may produce gamma-globin, give poor hybridization efficiencies with chromosomal fluorescence in situ hybridization (FISH), and do not permit simultaneous visualization of the fetal cell identifier and the FISH signal. We describe a novel technique that allows simultaneous visualization of fetal erythroblast morphology, chromosomal FISH, and epsilon-globin labeled with AMCA (7-amino-4-methylcoumarin-3-acetic acid). AMCA was chosen as the fluorescent label to circumvent the problem of heme autofluorescence because the mean difference in relative fluorescence intensity between fetal erythroblasts stained positive for antiglobin antibody and autofluorescence of unstained cells was greater with AMCA (mean 43.2; 95% confidence interval [CI], 34.6-51.9; SD = 14.0) as the reporting label compared with fluorescein isothiocyanate (mean 24.2; 95% CI, 16.4-31.9; SD = 12.4) or phycoerythrin (mean 9.8; 95% CI, 4.8-14.8; SD = 8.0). Median FISH hybridization efficiency was 97%, comparable to the 98% (n = 5 paired samples) using Carnoy fixative. One epsilon-positive fetal erythroblast was identified among 10(5) maternal nucleated cells in 6 paired mixture experiments of fetal erythroblasts in maternal blood (P <.001). Male epsilon-positive fetal erythroblasts were clearly distinguishable from adult female epsilon-negative erythroblasts, with no false positives (n = 1000). The frequency of fetal erythroblasts expressing epsilon-globin declines linearly from 7 to 14 weeks' gestation (y = -15.8 x + 230.8; R(2) = 0.8; P <.001). We describe a rapid and accurate method to detect simultaneously fetal erythroblast morphology, intracytoplasmic epsilon-globin, and nuclear FISH. (Blood. 2001;98:554-557)

Adult↗
PubMed2001

In utero therapy for lower urinary tract obstruction.

Lower urinary tract obstruction has a significant impact on neonatal and child health. Pulmonary hyperplasia and renal impairment could be direct or indirect consequences of this condition leading to significant morbidity and mortality. Evaluation of fetuses with suspected lower urinary tract obstruction is performed not only to confirm the diagnosis but also to assess renal prognosis. Ultrasound examination and urinary analysis aid in the evaluation of these fetuses. The decision to perform fetal intervention in these cases is a difficult one. Vesico-amniotic fetal shunting, open fetal surgery and more recently endoscopic fetal surgery for this condition are available as possible modalities of fetal intervention. Case selection for fetal intervention is extremely important in order to both avoid unnecessary intervention in those unlikely to survive, and also to avoid procedure related complications in fetuses likely to do well without intervention. Vesico-amniotic shunting has the advantage of bypassing the obstruction, however it is often associated with complications. Open fetal surgery is not usually recommended because of the complications and high fetal loss rate. Endoscopic surgery to visualise and treat the cause of lower urinary tract obstruction has been tried. Fetal endoscopic surgery is in its infancy and endoscopic procedures are limited to a few groups. This current review addresses evaluation, case selection and therapeutic options for lower urinary tract obstruction in utero. It also discusses the limited data against which the efficacy of the various options can be assessed. The current state of fetal intervention is detailed in the present review.

Amnion↗
PubMed2001

Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent single intrauterine death.

To assess the role of fetal blood sampling and intrauterine transfusion in monochorionic (MC) multiple pregnancy complicated by single intrauterine death (IUD), we reviewed ten cases over a 4-year period in a tertiary referral centre which underwent fetal blood sampling within 24 h of death of its MC co-twin. Intrauterine rescue transfusion was performed in all seven anaemic fetuses (hematocrit; Hct < 30%) to raise the fetal Hct to > or = 40%. The rationale was to prevent death and/or brain injury. Two fetuses, which were severely acidaemic at blood sampling, died in utero within 24 h of the procedure. In two cases, the surviving twins manifested abnormal sonographic findings of the fetal brain 2-5 weeks later and underwent late termination. In two cases, the pregnancies continued uneventfully until delivery at 35 and 40 weeks' gestation with good neonatal outcome. In one case the co-twin delivered 1 week later at 29 weeks but died within 12 h. Fetuses without anaemia were not transfused and had normal clinical outcomes. We suggest that intrauterine rescue transfusion before the development of severe acidaemia in anaemic surviving MC co-twins may prevent fetal death, but does not necessarily prevent brain injury. Until its role becomes clearer, we recommend that its use be restricted to situations in which the parents and the local jurisdiction allow late termination as an option if brain injury subsequently manifests on ultrasound.

Acidosis↗
PubMed2001

Obstetricians say yes to maternal request for elective caesarean section: a survey of current opinion.

AIM: To determine what proportion of obstetricians would agree to elective pre-labour CS for 'maternal request'. METHODS: Every fifth consultant on an alphabetical list of obstetricians in England and Wales obtained from the RCOG (243) was surveyed by post and asked (a) "Would you agree to perform an elective CS on a woman with an uncomplicated singleton cephalic pregnancy at term for 'maternal request?"' and (b) if yes, in relation to this 'Has your practice changed over recent years?" RESULTS: 155 questionnaires were returned (63% response rate -- four unanswered, leaving 151 for analysis). One hundred and four (69%) consultants said they would agree to 'maternal request' for CS. Of the 'yes' respondents, 62 (60%) claimed their practice had changed recently. CONCLUSION: This survey demonstrates that a majority of obstetricians are now prepared to agree to maternal request for CS in the absence of obstetric indications.

Attitude of Health Personnel↗
PubMed2001

Umbilical cortisol levels as an indicator of the fetal stress response to assisted vaginal delivery.

OBJECTIVES: While it is well established that delivery by elective caesarean section is less stressful for the fetus than normal vaginal delivery, little attention has been paid to the effect on the baby of an assisted delivery. STUDY DESIGN: We examined cortisol levels in venous cord blood from seven babies born by forceps, 10 by ventouse extraction, 28 by unassisted normal vaginal delivery, and 12 born by elective caesarean. Paired maternal bloods were taken immediately after delivery. RESULTS: Cord blood cortisol values were significantly different in the different groups (one-way ANOVA, P < 0.0001). The forceps group had the highest values and the caesarean group the lowest; both were different from the normal vaginal delivery group (P=0.019 and P=0.046, respectively). There was no effect of length of labour, or method of pain relief on cortisol levels. Maternal values were similar in the different groups, confirming that the differences observed derived from the fetus. CONCLUSIONS: There is increasing evidence that the stress experienced by the fetus or neonate can have long-term effects on the function of the hypothalamic-pituitary-adrenal axis in later life. We speculate that the stress caused by some assisted deliveries may contribute to this.

Cesarean Section↗
PubMed2001

Development of three-dimensional power Doppler ultrasound imaging of fetoplacental vasculature.

To develop an off-line system for three-dimensional (3-D) ultrasound (US) reconstruction of fetoplacental vasculature using colour segmentation and reconstruction software and to determine sources of error in fully freehand ultrasound image acquisition. US images were acquired freehand with the Acuson Sequoia (5C 2-MHz transducer) using power Doppler. After digital transfer to a personal computer, CQ Analysis software (Kinetic Imaging Ltd, Liverpool, UK) was used to segment the colour information from these images, and the resulting 8-bit grey-scale images were used for 3-D rendering using commercial software (VoxBlast, Vaytek Inc., Fairfield, IA, USA). 2-D scanning, software and freehand acquisition accuracy were assessed using a linear test rig and distance and volume phantoms (Dansk Phantom Service Ltd); 2-D scanning accuracy was within 1.3%, and software reconstruction accuracy within 1% for x and y planes and up to 3% for the z plane. Fully freehand acquisition was associated with a 12% to 18% mean percentage error in distance measurement in the plane of acquisition. Volumetric reconstruction inaccuracy was between 1.5% and 19.7% for precisely separated images and between 16.2% and 39.2% for fully freehand image acquisition. Rendered 3-D US vascular images clearly delineated vascular anatomy within the placenta and cord. Fully freehand 3-D US does have a role in off-line reconstruction of vascular anatomy, although variability in the z plane precludes its use for volumetric measurement. (E-mail: a.welsh@ic.ac.uk)

Female↗
PubMed2001

Freehand three-dimensional Doppler demonstration of monochorionic vascular anastomoses in vivo: a preliminary report.

OBJECTIVES: To demonstrate the three-dimensional vascular anatomy of monochorionic placental anastomoses in vivo, both arterioarterial and arteriovenous. DESIGN: Two-dimensional placental mapping techniques were used to locate arterioarterial and arteriovenous anastomoses. A freehand sweep was performed across the anastomotic site, and multiple images were stored to disk, at 17 Hz. These were then segmented to show only color information (vascular flow) using purpose-designed software (CQ analysis) and the files reconstructed into a three-dimensional volume, for multidirectional viewing and movie generation. RESULTS: Both arterioarterial and arteriovenous anastomoses could be visualized in detail. Reconstruction of a dual volume of gray-scale and segmented color images allowed recreation of the vascular anatomy within the placental substance, as well as retention of the original directional flow information. CONCLUSIONS: Detailed anastomotic anatomy can be demonstrated three dimensionally in vivo. Given the increasing evidence implicating various anastomotic configurations in pathological intertwin transfusion, this technique may prove useful in the antenatal assessment and treatment of monochorionic twin pregnancies.

Arterio-Arterial Fistula↗
PubMed2001

Quantitative digital analysis of regional placental perfusion using power Doppler in placental abruption.

PURPOSE: To apply digital imaging techniques to the quantification of placental vascularity using power Doppler. MATERIALS AND METHODS: Regional placental blood flow was measured in a case of large placental abruption, shortly after presentation and 1 week later. Images were stored digitally and analysed using purpose-designed software (CQ Analysis) to extract and measure vascular energy information. The integrated color energy (ICE) was determined in the main body of placental tissue and in a cotyledon isolated by the retroplacental clot. RESULTS: Initial assessment at 25 weeks showed only a small difference in integrated energy between normal placenta and the isolated cotyledon (ICE ratio 1.44, P < 0.04). One week later, perfusion in the isolated cotyledon had fallen both on qualitative and quantitative assessment (ICE ratio 3.98, P < 0.0001). This area subsequently became devascularized. CONCLUSION: Placental perfusion may be quantified using digital power Doppler analysis. Further studies are indicated to evaluate its role in assessing regional and/or global placental perfusion as well as fetal organ perfusion.

Abruptio Placentae↗
PubMed2001

Twin-to-twin transfusion syndrome results from dynamic asymmetrical reduction in placental anastomoses: a hypothesis.

Although placental vascular anastomoses between the fetoplacental circulations are ubiquitous in monochorionic twin pregnancies, the factors regulating their formation and maintenance are not understood. Increasing evidence implicates asymmetric anastomotic patterns in the aetiology of severe twin-to-twin transfusion syndrome (TTTS). The authors propose that anastomoses between placental circulations in monochorionic twins occur in a random manner at the embryological stage of connection of embryonic and extra-embryonic circulations. Placental expansion is then associated with random disruption of anastomoses and regression of their associated villus districts. TTTS develops as discordant loss of anastomoses results in asymmetrical flow resistance. Pregnancies with fetal growth concordance but discordant nuchal translucency at 10-14 weeks are at increased risk of developing subsequent severe TTTS because these clinical features indicate significant pressure differentials in the presence of a placentoplacental circulation, consistent with the presence of numerous, asymmetric anastomoses. However, since the anastomotic pattern is dynamic in the first half of pregnancy this hypothesis predicts that it will not be possible to devise a clinical test at 12 weeks that will predict with certainty the outcome of monochorionic twin pregnancies in relation to TTTS because this depends on random subsequent events.

Arteriovenous Anastomosis↗