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Biomedical subjects

Nicholas M Fisk

Publications and source records attributed to Nicholas M Fisk.

48 records · Page 3Linked to original sources

Acute increase in femoral artery resistance in response to direct physical stimuli in the human fetus.

OBJECTIVE: To determine whether fetal response to needling resembles the fetal 'brain sparing' response seen with hypoxaemia. DESIGN: Prospective observational study. SETTING: Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, London. POPULATION: Eighty-five pregnant women undergoing invasive procedures associated with fetal prenatal diagnosis and/or management. METHODS: The femoral artery and the middle cerebral artery pulsatility index were measured by Doppler ultrasonography before and after 89 invasive procedures (fetal blood sampling, transfusion, bladder or cyst aspiration, shunt insertion and amniocentesis, between 17 and 36 weeks). Cases in which the fetal body was transgressed were compared with 'control' fetuses undergoing invasive procedures which did not directly involve needling the fetus (amniocentesis and placental cord insertion procedures). MAIN OUTCOME MEASURES: Femoral artery and middle cerebral artery pulsatility index. RESULTS: The femoral artery pulsatility index rose after transgression [median change (Delta) 0.73; 95% confidence interval (CI) 0.51 to 0.98]. In contrast, there was no significant change in femoral artery pulsatility index after non-transgression procedures (mean Delta 0.28; 95% CI -0.20 to 0.76). Analysis confirmed the fall in middle cerebral artery pulsatility index after transgression procedures (median Delta -0.19; 95% CI -0.07 to -0.35), but there was also a significant fall in middle cerebral artery pulsatility index after non-transgression procedures (mean Delta -0.47; 95% CI -0.23 to -0.71). CONCLUSIONS: The human fetus mounts a peripheral haemodynamic response to invasive procedures involving transgression of the fetal body, which is consistent with the brain sparing effect. However, the change in middle cerebral artery pulsatility index in both transgression and control procedures suggests that the changes and mechanisms may be more complex than previously thought.

Blood Flow Velocity↗

Temporal and geographical variation in UK obstetricians' personal preference regarding mode of delivery.

OBJECTIVE: To assess UK obstetricians' preferences about mode of delivery for themselves or their partners and determine whether these changed since 1995. STUDY DESIGN: All 313 registered obstetricians in London and one in five (279) sample of those outside London were sent a structured anonymous postal questionnaire. RESULTS: The response rate was 54%. In a hypothetical uncomplicated first singleton pregnancy with a cephalic presentation at term, 15% chose elective caesarean section (CS) (17% in London versus 13% outside London). The overall rate for London has not changed since 1995 (17 versus 17%), although the difference between women and men was less (31 versus 8% in 1995 and 21 versus 14% in 1999, respectively). The number choosing elective CS increased with estimated foetal weight > 4.0kg (40%) and > 4.5kg (65%) and with breech presentation both in a first pregnancy (69%) and after a previous vaginal delivery (49%). CONCLUSION: The overall attitude of London obstetricians to mode of delivery for themselves or their partners has not changed since 1995 and is similar to those of UK obstetricians elsewhere.

Breech Presentation↗

Expandability of haemopoietic progenitors in first trimester fetal and maternal blood: implications for non-invasive prenatal diagnosis.

OBJECTIVES: Selective amplification of rare fetal cells in maternal blood is a potential strategy for non-invasive prenatal diagnosis. We assessed the proliferative potential of first trimester fetal progenitors compared to maternal ones. METHODS: Fetal and maternal haemopoietic progenitors were cultured separately and in two model mixtures: (i) co-cultures of male fetal nucleated cells mixed with maternal nucleated cells and (ii) co-cultures of malefetal CD34+ cells with maternal CD34+ cells. Cell origin was detected by X-Y fluorescence in situ hybridisation (FISH) RESULTS: The frequency of haemopoietic progenitors in first trimester fetal blood (predominantly CFU-GEMM) differed from those in peripheral blood from pregnant women (predominantly BFU-e). First trimester haemopoietic progenitors formed larger colonies (p=0.0001) and their haemoglobinisation was accelerated compared to those of maternal origin (p<0.001). CD34+ fetal haemopoietic progenitor cells could be expanded four times more than their maternal counterparts (median 235.8-fold, range 174.0-968.0 vs 71.9-fold, range 41.1-192.0; p=0.003). While selective expansion of fetal cells was not observed in the mononuclear cell model, the CD34+ cell rare event mixtures produced a 463.2-fold (range 128.0-2915.0) expansion of fetal cells. CONCLUSION: Selective expansion of first trimester fetal haemopoietic progenitors may be useful for amplifying fetal cells from maternal blood.

Antigens, CD34↗

The twin-twin transfusion syndrome.

The aetiology of twin-twin transfusion syndrome (TTTS), which affects 10-15% of monochorionic (MC) twin pregnancies, remains poorly understood. Although all MC twins have placental vascular anastomoses, unbalanced intertwin transfusion has been shown by ex vivo injection and in vivo Doppler studies of chorionic plate vasculature to be mediated by > or =1 arterio-venous anastomoses (AVA) in association with absent bi-directional arterio-arterial anastomoses (AAA). TTTS presents in the mid trimester with the oligo-polyhydramnios sequence, the donor may have a small or non-visible bladder and abnormal umbilical artery Doppler, while the recipient has a large bladder and may develop cardiac hypertrophy, triscupid regurgitation, and eventually hydrops. Recently, discordant renal renin angiotensin expression, endothelin and atrial natriuretic peptide have been implicated in the pathogenesis. Survival has increased from <20% to <60-70% with modern treatments, although survivors remain at increased risk of antenatally acquired cerebral white matter injury, and neurodevelopmental sequelae are documented in c.10% (range 5-23%). The recent introduction of a staging system for TTTS facilitates selection of therapy with less invasive amnioreduction and septostomy preferred for early stage disease, and more aggressive modalities such as laser ablation and cord occlusion with their attendant risk of procedure related fetal loss, reserved for advanced stage disease.

Developmental Disabilities↗

Serial aggressive platelet transfusion for fetal alloimmune thrombocytopenia: platelet dynamics and perinatal outcome.

OBJECTIVES: Our purpose was to describe the fetal loss rate and platelet dynamics in fetal alloimmune thrombocytopenia managed by serial platelet transfusions. METHODS: Retrospective analysis over 10 years of consecutive pregnancies affected by fetal alloimmune thrombocytopenia requiring in utero platelet transfusions. RESULTS: There were 2 perinatal losses in 12 pregnancies managed by 84 platelet transfusions. One was obviously procedure related from exsanguination despite platelet transfusion. The attributable procedure related fetal loss rate was 1.2% per procedure but 8.3% per pregnancy. The median rate of fall in fetal platelet count per day after transfusion was lower at the placental cord insertion (n = 54) 40.5 x 10(9)/L (range, 5.4-96.1 x 10(9)/L) compared with that at the intrahepatic vein (n = 30) 50.9 x 10(9)/L,(range, 29.5-91 x 10(9)/L) (P = .0009). CONCLUSION: Pooling our results with those previously published yields a cumulative risk of serial weekly transfusions of approximately 6% per pregnancy, indicating the need for development of less invasive approaches.

Blood Specimen Collection↗

X-linked inheritance of Dandy-Walker variant.

We report a family in which two sisters had three male fetuses with isolated Dandy-Walker variant (DWV) diagnosed on antenatal ultrasound. DWV is one part of a spectrum of abnormalities related to Dandy-Walker malformation (DWM) which commonly occur in association with other anomalies with or without chromosome abnormalities. The majority of cases are sporadic but rare reports of recurrence in siblings exist. This is the second report suggesting that isolated DWM/DWV can be inherited as an X-linked recessive trait.

Adult↗

High transduction efficiency of circulating first trimester fetal mesenchymal stem cells: potential targets for in utero ex vivo gene therapy.

We recently reported the existence of fetal mesenchymal stem cells in first trimester fetal blood. Here we demonstrate that fetal mesenchymal stem cells from as early as eight weeks of gestation can be retrovirally transduced with 99% efficiency without selection. Circulating fetal mesenchymal stem cells are known to readily expand and differentiate into multiple tissue types both in vitro and in vivo, and might be suitable vehicles for prenatal gene delivery. With advances in early fetal blood sampling techniques, we suggest that genetic disorders causing irreversible damage before birth could be treated in utero in the late first/early second trimester by genetically manipulated autologous fetal stem cells.

Female↗

Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy.

Fetal cells enter maternal blood during pregnancy and persist in women with autoimmune disease. The frequency of subsequent fetomaternal microchimerism in healthy women and its cell type is unknown. To test the hypothesis that fetal mesenchymal stem cells persist in maternal organs, we studied female bone marrow and ribs. Male cells were identified by XY fluorescence in-situ hybridisation in marrow-derived mesenchymal stem cells and in rib sections from all women with male pregnancies, but not in controls (9/9 vs 0/5, p=0.0005). We conclude that fetal stem cells transferred into maternal blood engraft in marrow, where they remain throughout life. This finding has implications for normal pregnancy, for obstetric complications that increase fetomaternal trafficking, and for graft survival after transplantation.

Aged↗