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Biomedical subjects

Nicholas M Fisk

Publications and source records attributed to Nicholas M Fisk.

At least 37 records · Page 2Linked to original sources
PubMed2004

Reversal of twin-twin transfusion syndrome: frequency, vascular anatomy, associated anomalies and outcome.

OBJECTIVE: To determine the frequency of reversal of transfusional gradient and phenotype in a large cohort of prospectively studied cases of twin-twin transfusion syndrome (TTTS) and seek evidence of clinical or placental anastomotic associations. METHODS: Consecutive cases of TTTS seen over an eight-year period with serial documentation of ultrasonic growth, liquor volume and fetal and placental Doppler studies were reviewed. Postnatal injection studies were inspected. RESULTS: Reversal of TTTS occurred in 5 of 96 affected pregnancies (5%). Two of the five cases had underlying aneuploidy or genetic syndrome, higher than the 2% frequency found in cases without reversal of TTTS (p < 0.05). Placental anastomotic configurations provided no consistent explanation for reversal of phenotype. CONCLUSION: This study documents the frequency of reversal of the direction of TTTS, and suggests that it is a heterogeneous condition. Reversal of donor-recipient phenotype may be explained by haemodynamic changes secondary to underlying aneuploidy/genetic syndromes, to the presence of multiple anastomoses in either direction or following laser ablation. This series together with previous case reports argues for a high level of suspicion for underlying aneuploidy, genetic syndrome or structural defects where there is reversal of the donor-recipient phenotype.

Cohort Studies↗
PubMed2004

Cardiovascular and endocrine responses to cutaneous electrical stimulation after fentanyl in the ovine fetus.

OBJECTIVE: The purpose of this study was to determine whether physical stimulation is stressful to the ovine fetus, as judged from physiologic changes that are similar to those reported for other stressors (such as hypoxia); whether any stress response could be blocked by clinically used doses of fentanyl; and whether fentanyl alone had any potentially deleterious physiologic effects in the fetus. STUDY DESIGN: We investigated the effect of fentanyl analgesia on the cardiovascular and endocrine response to cutaneous electrical stimulation in the late gestation (>125 days) ovine fetus (n=7 fetuses). Chronically implanted catheters and blood flow probes were used to measure fetal arterial blood pressure, heart rate, carotid and femoral blood flow, pH, Po(2), Pco(2), lactate, cortisol, and beta-endorphin levels before, during, and for 1 hour after 5 minutes of cutaneous electrical stimulation to the lip, forelimb, and abdomen, in a crossover design. Clinically used 30 or 150 microg doses of fentanyl (which approximated 10 or 50 microg/kg estimated fetal weight) or saline solution were given intravenously to the fetus 2 minutes before stimulation. RESULTS: When compared with the control, stimulation caused a significant rise in fetal heart rate (P=.003; mean maximal rise, 48.6+/-14.0 beats/min, 0-10 minutes after the start of stimulation) but caused no change in any other parameters studied. Neither dose of fentanyl attenuated the changes in heart rate that were observed in response to stimulation alone. Fentanyl alone significantly increased fetal heart rate, carotid blood flow, and lactate and cortisol levels and significantly decreased pH and Po(2). CONCLUSION: Cutaneous electrical stimulation in the fetal sheep causes an increase in heart rate, which fentanyl does not block. Fentanyl itself has significant effects on the cardiovascular and endocrine system, which might adversely affect the fetus.

Analgesics, Opioid↗
PubMed2004

Fetal stem cells.

Fetal stem cells can be isolated from fetal blood and bone marrow as well as from other fetal tissues, including liver and kidney. Fetal blood is a rich source of haemopoietic stem cells (HSC), which proliferate more rapidly than those in cord blood or adult bone marrow. First trimester fetal blood also contains a population of non-haemopoietic mesenchymal stem cells (MSC), which support haemopoiesis and can differentiate along multiple lineages. In terms of eventual downstream application, both fetal HSC and MSC have advantages over their adult counterparts, including better intrinsic homing and engraftment, greater multipotentiality and lower immunogenicity. Fetal stem cells are less ethically contentious than embryonic stem cells and their differentiation potential appears greater than adult stem cells. Fetal stem cells represent powerful tools for exploring many aspects of cell biology and hold considerable promise as therapeutic tools for cell transplantation and ex vivo gene therapy.

Bone Marrow Cells↗
PubMed2004

Doppler for artery-artery anastomosis and stage-independent survival in twin-twin transfusion.

OBJECTIVE: Treatment selection in twin-twin transfusion syndrome is increasingly determined by disease severity. We investigated whether detection of arterio-arterial anastomoses predicts perinatal survival. METHODS: An artery-artery anastomosis was sought by Doppler and disease stage was determined in 105 cases of twin-twin transfusion syndrome at presentation, first treatment, and worst stage. Outcome measures were perinatal, double, and any (1 or more babies) survival rates. RESULTS: After exclusion of 10 noninformative pregnancies, perinatal, double, and any survival rates were 61%, 44%, and 77%, respectively. When an anastomosis was detected at each of the 3 time points, perinatal and double survival rates were higher than when one was not (at first treatment, perinatal survival 83% versus 53%, respectively, P =.003; double survival 78% versus 33%, P <.001). Perinatal and double survival (P < or =.01) were poorer with more advanced stage, but any survival rates were not influenced by stage or anastomosis detection. Multiple logistic regression demonstrated that anastomosis detection at treatment increased the chance of perinatal (odds ratio [OR] 5.1, 95% confidence interval [CI] 1.6, 15.9) and double survival (OR 19.3, 95% CI 2.7, 138), independently of stage. For stages I-III at treatment, anastomosis detection predicted better perinatal (100% versus 63%, 100% versus 59%, and 83% versus 44%, respectively) and double survival rates (100% versus 52%, 100% versus 46%, and 78% versus 26%). Stage III, with anastomoses detected, had better perinatal (83% versus 63%) and double survival (78% versus 52%) than did stage I without detection. CONCLUSION: Antenatal detection of artery-to-artery anastomosis predicts higher perinatal and double survival in twin-twin transfusion syndrome, independently of disease stage. LEVEL OF EVIDENCE: II-3

Arterio-Arterial Fistula↗
PubMed2003

Fetal cystoscopy in the management of fetal obstructive uropathy: experience in a single European centre.

OBJECTIVE: To audit diagnostic and therapeutic fetal cystoscopy for suspected posterior urethral valves (PUV). METHODS: In 13 fetuses, (14-28 weeks) the bladder was entered with a 1.3 mm embryo-fetoscope and intravesical findings documented. In 10 fetuses, an attempt was made to treat the obstruction by saline hydro-ablation (n = 4) and/or guide-wire passage (n = 9). Renal function was assessed post-natally at 10 to 34 months. RESULTS: The bladder wall was visualised in 12/13 cases and the bladder neck in 11; in 10 cases the upper urethra was entered, and the obstruction visualised in five. PUV were 'seen' in 4/9 confirmed cases, but also in one case of urethral atresia, while in two others the degree of resistance to guide-wire passage suggested atresia or prune belly. Therapeutic attempts were technically successful, at least initially, in 6/10 cases. Of the five cases with confirmed PUV and normal fetal urinary electrolytes, two have acceptable renal function at follow-up. Hydro-ablation in one case resulted in resolution of sonographic signs of obstruction, and ablated valves were confirmed post-natally. CONCLUSIONS: Semi-rigid fetal cystoscopy allows entry into the upper urethra in most obstructive uropathies, although bladder neck angulation precludes visualisation of the site of obstruction in the majority. Guide-wire passage or hydro-ablation may allow relatively atraumatic ablation of PUV in utero without the chronic bladder decompression associated with vesico-amniotic shunting. However, current technical limitations need to be overcome, possibly by the use of flexible or angled fetoscopes, before the role of cystoscopic treatment can be formally evaluated.

Cystoscopy↗
PubMed2003

Twin-twin transfusion syndrome: the influence of intrauterine laser photocoagulation on arterial distensibility in childhood.

BACKGROUND: In twin-twin transfusion syndrome (TTTS), the donor and recipient fetus are exposed to differing volume loads and show discordant intertwin vascular compliance in childhood despite identical genotype. We hypothesized that discordance is prevented by intrauterine endoscopic laser ablation of placental anastomoses, which abolishes intertwin transfusion. We tested this by examining pulse wave velocity (PWV) in brachial arteries of twin survivors of TTTS treated with and without laser therapy. METHODS AND RESULTS: One hundred children (50 twin pairs, 27 with TTTS) were studied. Group 1 comprised 14 monochorionic (MC) twin pairs with TTTS treated symptomatically; group 2 comprised 13 MC twin pairs with TTTS treated by laser. The control groups comprised 12 MC twin pairs without TTTS (group 3) and 11 dichorionic twin pairs (group 4). Fetal cardiovascular data, predictive factors for, and duration of TTTS and cord blood were collected prospectively. We measured blood pressure and PWV photoplethysmographically at a median corrected postnatal age of 11 months (range, 1 week to 66 months). Both TTTS groups showed marked intertwin PWV discordance, unlike MCDA control subjects. The PWV discordance seen in laser treated twin pairs resembled that of dichorionic control subjects (heavier individual with higher PWV), whereas group 1 showed the opposite (negative) intertwin discordance (ANOVA F (1,45)=4.5, P=0.04). No significant differences in blood pressure or intrauterine growth were observed between TTTS groups. CONCLUSIONS: Vascular programming is evident in monozygotic twins with intertwin transfusion and is altered but not abolished by intrauterine therapy to resemble that seen in dichorionic twins.

Arteries↗
PubMed2003

Distal urinary obstruction.

Despite the sound experimental basis and initial promise of early animal models, the results of antenatal intervention have been disappointing, with high rates of misdiagnosis of urethral valves, complications from vesicoamniotic shunting, perinatal mortality, and long-term renal impairment and bladder dysfunction in survivors. The recent development of a cystoscopic approach might obviate some of these problems, but to date the procedure been limited by technical difficulty in negotiating the urethrovesical angle. Overcoming these difficulties through equipment modifications might allow definitive testing of whether or not alleviating distal urinary obstruction in utero is beneficial.

Animals↗
PubMed2003

Fetal renal impairment.

Renal function in utero deals chiefly with urine production rather than the excretion of metabolites, which are cleared by the placenta. Fetal renal impairment (FRI) in bilateral renal disease thus presents as oligohydramnios or anhydramnios; this can lead to lung hypoplasia and early neonatal death. As in the adult, FRI can be divided into prerenal, renal and postrenal causes. Causes of prerenal FRI include intrauterine growth restriction, unbalanced intertwin transfusion in monochorionic twins and maternal drug ingestion. Bilateral renal agenesis, multicystic dysplasia and both the autosomal dominant and recessive forms of polycystic kidney disease are examples of renal causes, whereas postrenal etiologies are usually caused by lower urinary tract obstruction (LUTO). When both kidneys are affected and there is severe mid-trimester oligohydramnios, the prognosis is poor. Although animal studies have shown that prolonged LUTO leads to lung hypoplasia and renal damage, and that decompression of the fetal kidney in early pregnancy restores fetal pulmonary and renal function, the value of fetal therapy such as vesico-amniotic shunting remains controversial, with a high procedure-related complication rate and a high incidence of end-stage renal failure in childhood. Fetal cystoscopic treatment of posterior urethral valves in utero may obviate some of these difficulties but remains an investigational procedure.

Animals↗
PubMed2003

CD34+ cells from first-trimester fetal blood are enriched in primitive hemopoietic progenitors.

OBJECTIVE: The purpose of this study was to investigate whether purified CD34(+) cells from first-trimester fetal blood are a source of primitive and committed hemopoietic progenitors. STUDY DESIGN: CD34(+) cells from first-trimester fetal blood and term cord blood were assayed for committed hemopoietic progenitor cells, high proliferative potential colony-forming cells, and long-term culture-initiating cells. RESULTS: First-trimester CD34(+) cells that were compared with cells at term generated fewer hemopoietic progenitor cells and fewer high proliferative potential colony-forming cells with lower recloning efficiency(P <.001). First-trimester CD34(+) cells tended to contain more long-term culture-initiating cells, both in bulk cultures and by limiting dilution analysis. The ratio between committed and primitive progenitors was 3 in the first-trimester and 20 in the term cord blood, respectively. CONCLUSION: First-trimester fetal blood is enriched in primitive (compared with committed) hemopoietic progenitors and may be an advantageous source of stem cells for prenatal therapy.

Antigens, CD34↗
PubMed2003

A double-blind randomized study of fetal side effects during and after the short-term maternal administration of indomethacin, sulindac, and nimesulide for the treatment of preterm labor.

OBJECTIVE: The purpose of this study was to establish whether nimesulide causes fewer fetal side effects than indomethacin or sulindac after short-term maternal exposure for tocolysis. STUDY DESIGN: This was a double-blind, double-dummy prospective randomized study with three drug treatment groups (n = 10 per group) that were comprised of subjects who were at 28 to 32 weeks of gestation with preterm contractions. The subjects were treated in the delivery suites of two busy inner-city teaching hospitals; the intervention consisted of 48 hours of treatment and with 72 hours of follow-up observation with indomethacin 100 mg (twice daily), sulindac 200 mg (twice daily), or nimesulide 200 mg (twice daily). The amniotic fluid index, hourly fetal urine production, and ductal Doppler pulsatility index observations were monitored before the treatment and at 4, 24, 48, 72, and 120 hours after the treatment was started. The statistical analysis used repeated measures analysis of variance, Bonferroni test, and Bland-Altman agreement. Significance assumed when the probability value was <.05. RESULTS: Each drug caused a significant reduction in all three observations over the 48-hour treatment period, which recovered to pretreatment levels by 72 hours after treatment. There were no significant differences among drugs for any of these effects. CONCLUSION: Nimesulide causes similar short-term fetal side effects to indomethacin and sulindac.

Adult↗
PubMed2003

Characterization of first trimester fetal erythroblasts for non-invasive prenatal diagnosis.

Isolating fetal erythroblasts from first trimester maternal blood offers a promising non-invasive alternative for prenatal diagnosis. The aim of this study was to characterize the biological properties of first trimester primitive erythroblasts to facilitate their enrichment from first trimester maternal blood. Primitive erythroblasts were the predominant cell type until 12 weeks gestation, after which time their numbers declined steeply; 100% were epsilon-globin-positive versus <0.06% definitive erythroblasts. Buoyant densities of first trimester fetal erythroblasts ranged from 1.077 to 1.130 g/ml, and optimal recoveries were obtained with Percoll 1118. Although primitive erythroblasts carried a negative surface charge and were resistant to NH(4)Cl lysis, these properties had only a limited role in fetal cell enrichment. Immunophenotyping showed that primitive, like definitive, erythroblasts were GPA+, CD47+, CD45- and CD35-, whereas CD71 expression was weak/undetectable on primitive erythroblasts but strongly positive on 100% of definitive erythroblasts; primitive erythroblasts were also CD36- whereas definitive erythroblasts were CD36+. We therefore used CD45/GPA selection of Percoll 1118-separated cells to demonstrate successful enrichment of male epsilon-globin-positive fetal erythroblasts from model mixtures, and as proof of principle from some first trimester maternal blood samples. Fetal cell enrichment protocols based on first trimester epsilon-globin-positive primitive erythroblasts may allow reliable enrichment of fetal cells from maternal blood for early non-invasive prenatal diagnosis of genetic disorders.

Ammonium Chloride↗
PubMed2003

The case for tocolysis in threatened preterm labour.

The failure of tocolytics to improve neonatal outcomes in placebo-controlled trials has wrongly been interpreted as evidence that they do not work. While delivery is unequivocally prolonged by 24 hours, 48 hours and 7 days, the time gained was not exploited to optimise neonatal outcome. These trials typically studied women at relatively advanced gestational ages with predictably good outcomes, enrolled them in tertiary centres where they could not benefit from in-utero transfer, and had low levels of corticosteroid administration. No study has been powered to detect clinically meaningful differences that might be expected to accrue from 1-7 days prolongation of gestation. Despite this, Bayesian interpretation suggests that tocolytics do improve neonatal outcome. The largest placebo-controlled study showed clear trends towards better survival in fetuses <28 weeks, lower rates of cerebral palsy and higher Bayley mental scores. Meta-analysis of neonatal morbidity in the beta-agonist trials suggests a near-significant reduction in respiratory distress syndrome (RDS), together with trends towards reduced intraventricular haemorrhage, necrotising enterocolitis, and patent ductus arteriosus. Finally, there is the Orwellian analogy that tocolytics don't work, but some work better than others. Although calcium antagonists have not been evaluated against placebo, meta-analysis of comparative trials with beta-agonists demonstrate a significantly lower incidence of RDS and neonatal jaundice, presumably mediated through the reduced chance of delivery within 48 hours and 7 days. Development of tocolytics that are safe for mother and baby should facilitate adequately-powered placebo-controlled studies, which both focus on women most likely to benefit and capitalise on the 1-7 days gained.

Adrenergic beta-Agonists↗
PubMed2003

Non-invasive fetal electrocardiography in singleton and multiple pregnancies.

OBJECTIVES: To document the duration of fetal cardiac time intervals in uncomplicated singleton pregnancies using a novel non-invasive fetal electrocardiography (fECG) system and to demonstrate this technique's ability to acquire recordings in twin and triplet pregnancies. DESIGN: Prospective cross sectional observational study. SETTING: Antenatal wards and clinics, day assessment unit and centre for fetal care at a tertiary referral hospital, London, UK. POPULATION OR SAMPLE: Three hundred and four singleton and multiple pregnancies, 15-41 weeks of gestation. METHODS: Using electrodes sited on the maternal abdomen, a fetal electrocardiography (fECG) system was developed and tested on 304 pregnant women from 15 to 41 weeks of gestation, of whom 241 were uncomplicated singletons, 58 had twin and 5 had triplet pregnancies. The composite abdominal signals were stored on a laptop computer and the fECG derived off-line using a digital signal processing technique. For singletons, linear regression was used to analyse PR, QRS, QT and QTc intervals, and construct time-specific reference ranges. MAIN OUTCOME MEASURE: Duration of fECG time intervals as a function of gestational age. Success of signal separation in singleton, twin and triplet pregnancies. RESULTS: For singletons, a total of 250 recordings was obtained from 241 individuals with a signal separation success rate of 85% (213/250). Success rates were significantly poorer between 27 and 36 weeks of gestation (2 x k chi(2), P < 0.0001), with 84% (31/37) of separation failures occurring during this period. P, Q, R and S waves were seen in all cases where fetal signals were separated and were used to generate fECG time interval reference ranges. In 22% (43/199) of analysed cases, no T waves were identified, 63% (27/43) of whom were < or =24 weeks of gestation. In twins and triplets, separate fetal signals were obtained in 78% (91/116) and 93% (14/15), respectively; P, Q, R and S waves were evident in all averaged fECGs, while T waves were identified in 59% (54/91) and 57% (8/14). CONCLUSIONS: This study provides reference ranges with gestation for fECG intervals derived non-invasively from normal singleton pregnancies and demonstrates the feasibility of obtaining complete fECG recordings non-invasively across a wide gestational range in pregnancies of all pluralities. The fECG time intervals described will enable the identification of pathological fECG recordings from high risk pregnancies where fECG abnormalities are suspected.

Cardiotocography↗