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Biomedical subjects

N M Fisk

Publications and source records attributed to N M Fisk.

At least 91 records · Page 5Linked to original sources
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

Permeability of human placenta and fetal membranes to thyrotropin-stimulating hormone in vitro.

We determined the placental transfer of TSH in an in vitro model of dually perfused isolated lobule in 28 human term placentas by adding varying concentrations (5-60 microIU mL(-1)) of TSH as a single bolus dose to the closed maternal circulation. Transmembrane transfer of TSH was also studied by adding 45 microIU mL(-1) to the maternal or fetal compartment of a dual chamber of fetal membranes in culture. Passage of freely diffusible markers creatinine and antipyrine were also studied in this model. TSH concentration was measured by third generation chemiluminescence assay with a sensitivity of 10 mIU mL(-1). In the perfusion experiments, at physiologic concentrations the slow decline of TSH in the maternal circulation was associated with a small linear increase in fetal levels to 0.11 +/- 0.04% of initial dose at 2 h. The placental transfer rate was 0.08 microIU min(-1). Increasing maternal concentrations of TSH were associated with proportional increases in transfer rate (y = 0.002x; R2 = 0.99) and placental uptake (y = 0.01x; R2 = 0.97). The placental permeability of TSH was 2.4 x 10(-4) mL min(-1) g(-1) and was proportional to its coefficients of diffusion in water and molecular size. The transmembrane transfer and permeability of TSH was comparable to those of the placenta. We conclude that TSH crosses the human term placenta and fetal membranes sparingly.

Biological Transport↗
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↗
PubMed1997

Medical amnioreduction with sulindac to reduce cord complications in monoamniotic twins.

OBJECTIVE: Cord entanglement is a common complication of monoamniotic twins and it is associated with high perinatal mortality. Apart from preterm delivery, no treatment has previously been used to reduce the risks of this complication. We postulated that reducing amniotic fluid volume would stabilize fetal lie and reduce the risk of cord compression. STUDY DESIGN: Cord entanglement was documented in three cases of monoamniotic twins in the midtrimester. Sulindac was administered to the mother. Amniotic fluid index, fetal urine output, and umbilical artery and ductus arteriosus Doppler waveforms were investigated before and during treatment by use of real-time and pulsed Doppler techniques. RESULTS: Sulindac was associated with a dose-related reduction in amniotic fluid index and fetal urine production without alteration in fetal flow velocity waveforms. Fetal lie stabilized after commencement of treatment. All six twins were delivered with no complications. CONCLUSION: Medical amnioreduction with sulindac is a new management option in monoamniotic twins to reduce cord complications.

Amniotic Fluid↗
PubMed1997

Pharmacokinetics and pharmacodynamics of TRH during pregnancy.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of thyrotropin-releasing hormone (TRH) in pregnant women. METHODS: Twenty-four pregnant and eight nonpregnant women were given 400 micrograms TRH as either intravenous infusion or bolus. Serial venous samples were collected for TRH, TSH, thyroxine, and prolactin assay. RESULTS: When given as bolus, mean (+/- standard error of the mean) peak plasma concentration (50 +/- 5.2 and 73 +/- 5.1 ng/mL, P < .01), elimination half life (4.3 +/- 0.3 and 6.3 +/- 0.4 minutes, P < .001), and area under the curve (156.4 +/- 14.8 and 340.1 +/- 32.8 ng/mL/minute, P < .001) in pregnant subjects were reduced compared with controls, whereas plasma clearance (45.4 +/- 6.5 and 23.6 +/- 2.1 mL/kg/minute, P < .01) and volume of distribution (27.8 +/- 1.8 and 19.0 +/- 1.3% body weight, P < .01) were increased. When given by infusion, steady-state concentration (6.6 +/- 0.5 and 9.8 +/- 0.9 ng/mL, P < .01) and elimination half-life (4.6 +/- 0.5 and 6.3 +/- 0.3 minutes, P < .05) were lower in pregnant subjects than in controls. Thyrotropin-releasing hormone kinetics were independent of mode of administration. Although basal TSH and thyroid hormone concentrations were similar in patients and controls, the TSH response to TRH was blunted in pregnant subjects compared with controls (9.3 +/- 0.6 and 16.4 +/- 1.4 microIU/mL, P < .001). The basal (3187 +/- 488 and 147 +/- 16 mIU/L) and maximal prolactin response (6193 +/- 426 and 1316 +/- 106 mIU/L) were increased in pregnant subjects compared with controls (P < .001). CONCLUSION: The peak plasma concentration and elimination half-life of TRH are reduced during pregnancy because of the increased volume of distribution and rapid clearance. Mode of administration does not affect TRH pharmacokinetics, but the maternal pharmacodynamic response differs in patients receiving bolus compared with infusion.

Adult↗
PubMed1997

Relationship between change in amniotic fluid index and volume of fluid removed at amnioreduction.

OBJECTIVE: To determine the relationship between the change in amniotic fluid index (AFI) and the volume of fluid removed at amnioreduction. METHODS: In a prospective study of 20 twin and 19 singleton pregnancies undergoing amnioreduction for severe polyhydramnios, AFI was measured immediately before and after the procedure and was correlated with the volume of fluid withdrawn. RESULTS: A significant linear relationship was found between AFI change and the volume drained in all pregnancies (Y = -4.2X; R2 = 0.49; P = .002). This relationship was similar in singleton and twin pregnancies. However, there was a significant absolute difference in AFI change between singleton and twin pregnancies of 7.9 cm (95% confidence interval 0.41, 15.2; P = .04). CONCLUSION: These findings support the use of the four-quadrant AFI as a semiquantitative index of amniotic fluid volume. This relationship can be used to predict the drainage volume required to achieve a target AFI with amnioreduction and thus avoid repeated AFI measurements during the procedure itself.

Adult↗
PubMed1997

Survey of obstetricians' personal preference and discretionary practice.

OBJECTIVE: To determine obstetricians personal choices in relation to Down syndrome screening and mode of delivery for themselves or their partners. STUDY DESIGN: Structured anonymous postal survey. All 282 obstetric consultants, senior registrars and registrars in NHS obstetric units within London's M25 region were surveyed. RESULTS: The response rate was 73% (206). Fifty one per cent (105) chose to have elective amniocentesis/CVS without a previous screening test when maternal age was > or = 35 years and 11% (23) when < 35 years. Of the remainder, the majority wanted both maternal serum screening and nuchal translucency rather than a single screening test. In relation to mode of delivery, 17% (33) of obstetricians chose elective caesarean section (CS) in the absence of any clinical indication. Of those who chose CS, 88% did so out of fear of perineal damage. However when faced with a mid-cavity instrumental delivery in the second stage, only 5% (8) wanted CS, the remainder choosing operative vaginal delivery. With an uncomplicated breech presentation, only 27% (55) opted for external cephalic version while 57% (114) chose elective CS. CONCLUSION: This study demonstrates interventionist attitudes among a sizeable percentage of obstetricians in relation to antenatal screening and their own preferred mode of delivery. It suggests that obstetricians regard management options not normally available to pregnant women as valid choices for themselves or their partners.

Adult↗
PubMed1997

Effect of antenatal administration of thyrotrophin releasing hormone on fetal flow velocity waveforms.

AIM: To determine whether antenatal administration of thyrotrophin releasing hormone (TRH), to promote lung maturation, alters blood flow through the fetal middle cerebral, umbilical artery, or ductus arteriosus and through the maternal uterine arteries. METHODS: The effect of transplacentally administered TRH on the fetal circulation was prospectively evaluated in 30 patients between 24 and 34 weeks' gestation. TRH (400 micrograms) was given to the mother intravenously either as a bolus or an infusion. Fetal effects were determined by measuring the maximum velocity and pulsatility index (PI) in middle cerebral artery, ductus arteriosus, uterine artery and umbilical artery Doppler waveforms. Measurements were made immediately before, and 10 and 60 minutes after maternal TRH administration. RESULTS: Intravenous injection of TRH had no significant effect on PI in the uterine, umbilical, or middle cerebral artery and the ductus arteriosus within 60 minutes of administration in either group. CONCLUSION: The antenatal use of TRH in conjunction with steroids for fetal lung maturity does not affect utero-placental or fetal haemodynamic variables, as measured by Doppler. These findings, therefore, do not support the suggestion that antenatal intravenous administration of TRH either as bolus or infusion may have immediate adverse vascular effects in the fetus.

Adolescent↗
PubMed1997

Maternofetal transfer of thyrotrophin-releasing hormone: effect of concentration and mode of administration.

We studied the effect of maternal concentration and mode of administration on transfer rate of TSH-releasing hormone (TRH) in an in vitro model of dually perfused isolated lobule of human term placenta. Varying concentrations (4-40 microg dL(-1)) of TRH were added either to the open maternal circulation to mimic an infusion or as a single bolus dose to the closed maternal circulation. TRH was measured by RIA. Perfusion efficiency in each experiment was determined by using antipyrine and creatinine as diffusable markers. At a concentration equivalent to the usual clinical dose of 400 microg, transplacental transfer of TRH was 0.4 +/- 0.1%, with an fetal/maternal ratio of 0.01 +/- 0.003. Placental clearance rate (y = 0.07x; R2 = 0.97; p < 0.001; n = 28) and uptake of TRH (y = 0.40x; R2 = 0.95; p < 0.001) in the closed experiments increased exponentially with increasing maternal concentration. Placental clearance (y = 0.05x; R2 = 0.99; p < 0.001; n = 30), and uptake of TRH (y = 0.35x; R2 = 0.98; p < 0.01) under steady state also correlated with maternal TRH concentration. For a given concentration, placental clearance and uptake of TRH was comparable whether given as a bolus or an infusion. We conclude that TRH is transferred sparingly across the human term placenta and its transfer rate is a function of the maternal concentration of TRH and not its mode of administration.

Cesarean Section↗
PubMed1997

Transport and metabolism of thyrotrophin-releasing hormone across the fetal membrane.

To determine the transfer and metabolism of TRH by human fetal membranes, the bidirectional transport and uptake of TRH was investigated by adding 125I-labeled TRH (100,000 cpm) or commercial TRH either to the maternal or the fetal compartment of an in vitro model of cultured human fetal membranes obtained from term and preterm placenta. Transmembrane transfer was also studied in the presence of 200 microM p-hydroxy-mercuriphenyl-sulphonic acid (p-HMSA), a dipeptidase enzyme inhibitor. Creatinine and heparin were used as an internal markers. Metabolites of TRH were separated from intact molecules by gel filtration on Sephadex G-10. The structural integrity of the membrane was confirmed by electron microscopy. The transmembrane transfer of radiolabeled and commercial TRH were comparable across both preterm and term placenta. When transport was studied from the maternal to fetal side, the maternal concentration of TRH declined rapidly from 100% at time 0 to 19.31 +/- 2.26% at 8 h with a concomitant increase in the fetal concentration from undetectable to a maximum of 2.56 +/- 0.38% with a fetomaternal ratio of 0.16 +/- 0.01. Transfer of TRH from the fetal to maternal compartment was similar to that of maternal to fetal. Chromatography of maternal and fetal media showed that TRH was metabolized by the membrane into small molecular weight fragments. Treatment of the membrane with p-HMSA increased TRH transport from the maternal to fetal compartment to 18.12 +/- 0.91 (P < 0.001) with an fetomaternal ratio of 0.35 +/- 0.02 (P < 0.001). Although transmembrane transfer of TRH from the fetal to maternal side was also increased by p-HMSA, levels achieved were less than that from maternal to fetal (12.26 +/- 1.50%; P < 0.05). These results suggest that the human fetal membrane acts as an enzymatic barrier to the bidirectional transfer of TRH from 24 weeks gestation.

Biological Transport↗
PubMed1997

Liposomal thyroxine: a noninvasive model for transplacental fetal therapy.

Drugs that cross the placenta sparingly are currently given directly to the fetus by invasive procedures. We investigated whether anionic small unilamellar (SUV) liposomes of different lipid compositions enhanced the transfer and uptake of T4 in an in vitro model of perfused human term placenta. T4-encapsulated anionic liposomes were prepared using lecithin (F-SUV) or distearoyl phosphatidylcholine (S-SUV) with cholesterol and dicetylcholine. The size distribution, encapsulation efficiency, and stability were determined in blood-based media. The transfer kinetics of free and liposomally encapsulated T4 were studied in a dually perfused isolated lobule of human term placenta, with creatinine and liposomal carboxyfluorescein as marker substances. Concentrations of T4 and rT3 were measured by RIA. T4 crossed the placenta sparingly (1.9 +/- 0.5%) because it was metabolized to rT3 (9.2 +/- 1.3%). Transplacental transfer of T4 was significantly increased by F-SUV (15.8 +/- 2.1%; P < 0.001) and S-SUV liposomes (7.1 +/- 1.2%; P < 0.001), with a concomitant decrease in fetal rT3 levels (P < 0.001). Placental uptake of F-SUV (13.5 +/- 2.0%; P < 0.001) was greater than that of S-SUV liposomes (6.7 +/- 0.8%; P < 0.001). Our data suggest that anionic liposomes increase transplacental transfer of T4. If confirmed in vivo, liposomes may provide an alternative noninvasive method of drug delivery to the fetus.

Chromatography↗
PubMed1997

The effect of transmission bandwidth on diagnostic accuracy in remote fetal ultrasound scanning.

Six subspecialists with considerable experience in fetal ultrasound viewed a selection of pre-recorded ultrasound scans. Scans from 18 patients recorded on VHS video-tape were supplied from five centres in the UK and Ireland, each made on a high-resolution ultrasound machine by an experienced sonologist at a referral centre. Each observer viewed the scans on a large display monitor in an individual viewing booth. The scans were viewed in random order, at randomly selected bandwidths. Observers, who were blinded to both recording and bandwidth, assessed the technical quality on a five-point Likert scale. They also recorded their diagnosis. The six observers each carried out 32 viewing sessions, which gave a total of 192 viewings. There was no significant difference in the perceived technical quality of the scans between the two bandwidths used (P = 0.09). Of the 84 recordings transmitted at 1920 kbit/s, 71 (85%) were diagnosed correctly or 'half correctly' and 13 (15%) were misdiagnosed. Of the 95 recordings transmitted at 384 kbit/s, 66 (69%) were diagnosed correctly or 'half correctly' and 29 (31%) were misdiagnosed. This difference was significant (P = 0.03). The results indicate that although there were no perceived differences in technical quality between recordings transmitted at 384 or 1920 kbit/s, diagnostic accuracy was marginally worse at the lower bandwidth. This suggests that the higher bandwidth conveys more detail and information to the observer, which in turn enables more accurate diagnosis. However, further work is required before a definitive choice can be made about the optimum transmission bandwidth for remote fetal ultrasound studies.

Female↗