... editors Nagy A Habib Natasa Levicar Myrtle Y Gordon Long Jiao Nicholas Fisk Imperial College ... more ... editors Nagy A Habib Natasa Levicar Myrtle Y Gordon Long Jiao Nicholas Fisk Imperial College London, UK Stem Cell Repair and ... M. Watt, Jon Smythe, Andreas Fox, Youyi Zhang, Nita Fisher, Grigorios Tsaknakis, Sinead Forde, Sarah Hale, Dacey Ryan, Emma Frith and Enca ...
Selective conservation in preterm premature rupture of the membranes (PPROM) reduces risks of inf... more Selective conservation in preterm premature rupture of the membranes (PPROM) reduces risks of infection and pulmonary hypoplasia associated with expectant management by delivering those at greatest risk, while permitting continuation of pregnancy in the remainder. Although patient selection has traditionally been a clinical decision, more accurate criteria are now available. The role of biochemical, biophysical and microbiological predictors of chorioamnionitis and fetal pulmonary status in PPROM is reviewed, and the resultant modifications to selective conservative management discussed.
There is concern about the medical, social, and economic consequences of multiple pregnancy after... more There is concern about the medical, social, and economic consequences of multiple pregnancy after in-vitro fertilisation (IVF). The most effective way to limit the risk of such a pregnancy is to replace only one or two embryos simultaneously. This strategy, however, is thought to reduce pregnancy rates. We analysed the rates of multiple pregnancies and live-births in all clinics in the UK in relation to their elective two-embryo transfer (ETT) policies. Our results suggest that replacement of two embryos eliminates the chance of triplets without affecting overall success rates.
Alport syndrome is a hereditary glomerulopathy caused by a mutation in type IV collagen genes, wh... more Alport syndrome is a hereditary glomerulopathy caused by a mutation in type IV collagen genes, which disrupts glomerular basement membrane, leading to progressive glomerulosclerosis and end-stage renal failure. There is at present no cure for Alport syndrome and cell-based therapies offer promise to improve renal function. Here, we found that human first trimester fetal chorionic stem cells (CSC) are able to migrate to glomeruli and differentiate down the podocyte lineage in vitro and in vivo. When transplanted into 7-week old Alport 129Sv-Col4α3tm1Dec/J (-/-) mice, a single intraperitoneal injection of CSC significantly lowered blood urea and urine proteinuria levels over the ensuing two weeks. In addition, nearly two thirds of transplanted -/- mice maintained their weight above the 80% welfare threshold, with both males and females weighing more than aged-matched non-transplanted -/- mice. This was associated with less renal cortical fibrosis and interstitial inflammation compared...
OBJECTIVE: To investigate whether maternal anxiety in the third trimester is associated with an i... more OBJECTIVE: To investigate whether maternal anxiety in the third trimester is associated with an increased uterine artery resistance index.DESIGN: Cohort based study.SUBJECTS: 100 pregnant women, with a mean gestation of 32 weeks.OUTCOME MEASURES: Self rating Spielberger questionnaire for state anxiety and trait anxiety, and uterine blood flow waveform patterns as assessed by colour Doppler ultrasound.RESULTS: A significant association was found between uterine artery resistance index and scores for both Spielberger state anxiety and trait anxiety (rs=0.31, P<0.002 and 0.28 P<0.005 respectively). Women with state anxiety scores >40 (n=15) had a higher mean uterine resistance index than those with scores </= 40 (mean difference with mean resistance index 24%, 95% confidence interval 12% to 38%; P<0.0001). Similarly, women with trait anxiety scores >40 (n=32) had a higher mean resistance index than those with scores </= 40, although to a lesser extent. The presence of notches in the waveform pattern produced by uterine artery blood flow was found in 4/15 (27%) women with high state anxiety scores compared with 4/85 (5%) with low anxiety scores (P<0.02).CONCLUSIONS: This study shows an association between maternal anxiety in pregnancy and increased uterine artery resistance index. It suggests a mechanism by which the psychological state of the mother may affect fetal development, and may explain epidemiological associations between maternal anxiety and low birth weight. The influence of maternal anxiety may be one mechanism by which the intrauterine environment contributes to later disease in offspring.
Summary Four fetuses with obstructive uropathy had club foot diagnosed on ultrasound before 18 we... more Summary Four fetuses with obstructive uropathy had club foot diagnosed on ultrasound before 18 weeks of pregnancy in the presence of normal amniotic fluid volume. One had trisomy-I8 while the karyotype in the others was normal. Oligohydramnios in the presence of obstructive ...
Fetal cells enter the maternal circulation from the early first trimester of pregnancy, where the... more Fetal cells enter the maternal circulation from the early first trimester of pregnancy, where they persist in tissue decades later. We investigated in mice whether fetal microchimeric cells (FMCs) can be detected in maternal kidney, and whether they play a role in kidney homeostasis. FMCs were identified in vivo in two models: one an adaptive model following unilateral nephrectomy, the other an injury via unilateral renal ischaemia reperfusion. Both models were carried out in mothers that had been mated with transgenic mice expressing luciferase transgene under the control of collagen type I, and had given birth to either 1 or 3 litters. FMCs were detected by Y-probe fluorescent in situ hybridization (FISH) and bioluminescence, and the cell number quantified by real-time polymerase chain reaction. In the adaptive model, the remaining kidney showed more cells by all 3 parameters compared with the nephrectomized kidney, while ischaemia reperfusion resulted in higher levels of FMC participation in injured compared to contralateral kidneys. Bioluminescence showed that FMCs switch on collagen type I transcription implicating mesenchymal lineage cells. After injury, Y-probe in situ hydridization was found mainly in the tubular epithelial network. Finally, we compared FMCs with bone marrow cells and found similar dynamics but altered distribution within the kidney. We conclude that FMCs (1) are long-term sequelae of pregnancy and (2) are recruited to the kidney as a result of injury or adaptation, where they activate the transcriptional machinery of matrix proteins.
... editors Nagy A Habib Natasa Levicar Myrtle Y Gordon Long Jiao Nicholas Fisk Imperial College ... more ... editors Nagy A Habib Natasa Levicar Myrtle Y Gordon Long Jiao Nicholas Fisk Imperial College London, UK Stem Cell Repair and ... M. Watt, Jon Smythe, Andreas Fox, Youyi Zhang, Nita Fisher, Grigorios Tsaknakis, Sinead Forde, Sarah Hale, Dacey Ryan, Emma Frith and Enca ...
Selective conservation in preterm premature rupture of the membranes (PPROM) reduces risks of inf... more Selective conservation in preterm premature rupture of the membranes (PPROM) reduces risks of infection and pulmonary hypoplasia associated with expectant management by delivering those at greatest risk, while permitting continuation of pregnancy in the remainder. Although patient selection has traditionally been a clinical decision, more accurate criteria are now available. The role of biochemical, biophysical and microbiological predictors of chorioamnionitis and fetal pulmonary status in PPROM is reviewed, and the resultant modifications to selective conservative management discussed.
There is concern about the medical, social, and economic consequences of multiple pregnancy after... more There is concern about the medical, social, and economic consequences of multiple pregnancy after in-vitro fertilisation (IVF). The most effective way to limit the risk of such a pregnancy is to replace only one or two embryos simultaneously. This strategy, however, is thought to reduce pregnancy rates. We analysed the rates of multiple pregnancies and live-births in all clinics in the UK in relation to their elective two-embryo transfer (ETT) policies. Our results suggest that replacement of two embryos eliminates the chance of triplets without affecting overall success rates.
Alport syndrome is a hereditary glomerulopathy caused by a mutation in type IV collagen genes, wh... more Alport syndrome is a hereditary glomerulopathy caused by a mutation in type IV collagen genes, which disrupts glomerular basement membrane, leading to progressive glomerulosclerosis and end-stage renal failure. There is at present no cure for Alport syndrome and cell-based therapies offer promise to improve renal function. Here, we found that human first trimester fetal chorionic stem cells (CSC) are able to migrate to glomeruli and differentiate down the podocyte lineage in vitro and in vivo. When transplanted into 7-week old Alport 129Sv-Col4α3tm1Dec/J (-/-) mice, a single intraperitoneal injection of CSC significantly lowered blood urea and urine proteinuria levels over the ensuing two weeks. In addition, nearly two thirds of transplanted -/- mice maintained their weight above the 80% welfare threshold, with both males and females weighing more than aged-matched non-transplanted -/- mice. This was associated with less renal cortical fibrosis and interstitial inflammation compared...
OBJECTIVE: To investigate whether maternal anxiety in the third trimester is associated with an i... more OBJECTIVE: To investigate whether maternal anxiety in the third trimester is associated with an increased uterine artery resistance index.DESIGN: Cohort based study.SUBJECTS: 100 pregnant women, with a mean gestation of 32 weeks.OUTCOME MEASURES: Self rating Spielberger questionnaire for state anxiety and trait anxiety, and uterine blood flow waveform patterns as assessed by colour Doppler ultrasound.RESULTS: A significant association was found between uterine artery resistance index and scores for both Spielberger state anxiety and trait anxiety (rs=0.31, P<0.002 and 0.28 P<0.005 respectively). Women with state anxiety scores >40 (n=15) had a higher mean uterine resistance index than those with scores </= 40 (mean difference with mean resistance index 24%, 95% confidence interval 12% to 38%; P<0.0001). Similarly, women with trait anxiety scores >40 (n=32) had a higher mean resistance index than those with scores </= 40, although to a lesser extent. The presence of notches in the waveform pattern produced by uterine artery blood flow was found in 4/15 (27%) women with high state anxiety scores compared with 4/85 (5%) with low anxiety scores (P<0.02).CONCLUSIONS: This study shows an association between maternal anxiety in pregnancy and increased uterine artery resistance index. It suggests a mechanism by which the psychological state of the mother may affect fetal development, and may explain epidemiological associations between maternal anxiety and low birth weight. The influence of maternal anxiety may be one mechanism by which the intrauterine environment contributes to later disease in offspring.
Summary Four fetuses with obstructive uropathy had club foot diagnosed on ultrasound before 18 we... more Summary Four fetuses with obstructive uropathy had club foot diagnosed on ultrasound before 18 weeks of pregnancy in the presence of normal amniotic fluid volume. One had trisomy-I8 while the karyotype in the others was normal. Oligohydramnios in the presence of obstructive ...
Fetal cells enter the maternal circulation from the early first trimester of pregnancy, where the... more Fetal cells enter the maternal circulation from the early first trimester of pregnancy, where they persist in tissue decades later. We investigated in mice whether fetal microchimeric cells (FMCs) can be detected in maternal kidney, and whether they play a role in kidney homeostasis. FMCs were identified in vivo in two models: one an adaptive model following unilateral nephrectomy, the other an injury via unilateral renal ischaemia reperfusion. Both models were carried out in mothers that had been mated with transgenic mice expressing luciferase transgene under the control of collagen type I, and had given birth to either 1 or 3 litters. FMCs were detected by Y-probe fluorescent in situ hybridization (FISH) and bioluminescence, and the cell number quantified by real-time polymerase chain reaction. In the adaptive model, the remaining kidney showed more cells by all 3 parameters compared with the nephrectomized kidney, while ischaemia reperfusion resulted in higher levels of FMC participation in injured compared to contralateral kidneys. Bioluminescence showed that FMCs switch on collagen type I transcription implicating mesenchymal lineage cells. After injury, Y-probe in situ hydridization was found mainly in the tubular epithelial network. Finally, we compared FMCs with bone marrow cells and found similar dynamics but altered distribution within the kidney. We conclude that FMCs (1) are long-term sequelae of pregnancy and (2) are recruited to the kidney as a result of injury or adaptation, where they activate the transcriptional machinery of matrix proteins.
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