Nicholas Fisk | The University of New South Wales (original) (raw)

Papers by Nicholas Fisk

... 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 ...

Obstetrical & Gynecological Survey, 1988

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.

The Lancet, 2002

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.

Stem cells and development, Jan 5, 2016

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...

Archives of Disease in Childhood Fetal and Neonatal Edition, 2004

Objectives: To study the effect of acute stress, caused by intrauterine needling at the intrahepa... more Objectives: To study the effect of acute stress, caused by intrauterine needling at the intrahepatic vein (IHV), on fetal plasma concentrations of corticotrophin releasing hormone (CRH), and to compare paired fetal and maternal samples for CRH concentration to determine the extent of their joint control. Design: Venous blood samples were obtained from fetuses (gestational age 17-38 weeks) undergoing fetal blood sampling (n = 29) or intrauterine transfusion (n = 17) through either the IHV or the placental cord insertion (PCI). Setting: The Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, London, UK. Patients: Pregnant women undergoing clinically indicated fetal blood sampling or intrauterine blood/ platelet transfusion. Results: Fetal plasma cortisol increased with intrahepatic vein transfusion (mean (SD) cortisol response D64.7 (54.5) nmol/l; p , 0.0001, n = 11), and fetal corticotrophin concentrations were higher after IHV (n = 7) than PCI needling (n = 6). Neither fetal nor maternal plasma CRH increased after IHV transfusion. Fetal CRH levels did not rise with gestation, whereas maternal CRH levels did (r = 0.58; n = 36; p , 0.0001). There was a modest correlation between paired maternal and fetal values (r = 0.36; n = 36; p = 0.03). Conclusions: Acute fetal stress, caused by IHV needling of the fetal abdomen, resulted in hypothalamicpituitary-adrenal axis activation, as shown by a rise in fetal cortisol and corticotrophin. However, it did not result in measurable CRH release into fetal plasma. This suggests that fetal plasma CRH is not derived from the hypophyseal-portal circulation, but from another source, presumably the placenta.

Int J Gynecol Obstet, 1992

ovulatory volunteers with proven fertility were evaluated for at least one complete menstrual cyc... more ovulatory volunteers with proven fertility were evaluated for at least one complete menstrual cycle in the follicular, periovulatory, and luteal phases. Multiple cycles were studied in IO volunteers. The results showed that the contractions increase in frequency, amplitude, and percentage toward the fundus throughout the follicular and periovulatory phases. The pattern is essentially reversed in the luteal phase. There is reproducibility of these patterns from cycle to cycle. We conclude that there is a definite identifiable pattern of subendometrial myometrial contractility that varies with the phases of the normal menstrual cycle and recurs in a similar fashion from cycle to cycle.

European Journal of Obstetrics and Gynecology and Reproductive Biology, Jan 9, 2000

Invasive diagnostic and therapeutic techniques are increasingly applied to the fetus. It is not k... more Invasive diagnostic and therapeutic techniques are increasingly applied to the fetus. It is not known if the fetus feels pain during such procedures, but the fetus does mount signi®cant stress hormonal and circulatory changes in response to these from 18±20 weeks. Perinatal stress may have long-term neurodevelopmental implications. During open fetal surgery, maternal general anaesthesia provides fetal anaesthesia. However, in closed procedures, fetal analgesia presents dif®culties. The optimal drug, dose, and route of administration remain to be determined. #

Bmj, Jan 16, 1999

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.

Plos One, 2008

Objective: To test the hypothesis that cervical shortening in polyhydramnios reflects the degree ... more Objective: To test the hypothesis that cervical shortening in polyhydramnios reflects the degree of excess amniotic fluid, and increases with normalisation of amniotic fluid volume.

Cell Res, 2010

We have investigated the ability of fetal mesenchymal stem cells (fMSCs) to differentiate into br... more We have investigated the ability of fetal mesenchymal stem cells (fMSCs) to differentiate into brown and white adipocytes and compared the expression of a number of marker genes and key regulatory factors. We have shown that the expression of key adipocyte regulators and markers during differentiation is similar to that in other human and murine adipocyte models, including induction of PPARγ2 and FABP4. Notably we found that the pre-adipocyte marker Pref-1, is induced early in differentiation and then declines markedly as the process continues, suggesting that fMSCs first acquire pre-adipocyte characteristics as they commit to the adipogenic lineage, prior to their differentiation into mature adipocytes. After adipogenic induction, some stem cell isolates differentiated into cells resembling brown adipocytes and others into white. Detailed investigation of one isolate showed that the novel brown fat determining factor PRDM16 is expressed both before and after differentiation. Importantly these cells exhibited elevated basal UCP-1 expression, which was dependent on the activity of the orphan nuclear receptor ERRα, highlighting a novel role for ERRα in human brown fat. Thus fetal MSCs represent a useful in vitro model for human adipogenesis, and provide opportunities to study the stages prior to commitment to the adipocyte lineage. They also offer invaluable insights into the characteristics of human brown fat.

Molecular Human Reproduction, Apr 1, 2003

Isolating fetal erythroblasts from ®rst trimester maternal blood offers a promising non-invasive ... more Isolating fetal erythroblasts from ®rst trimester maternal blood offers a promising non-invasive alternative for prenatal diagnosis. The aim of this study was to characterize the biological properties of ®rst trimester primitive erythroblasts to facilitate their enrichment from ®rst trimester maternal blood. Primitive erythroblasts were the predominant cell type until 12 weeks gestation, after which time their numbers declined steeply; 100% were e-globin-positive versus <0.06% de®nitive erythroblasts. Buoyant densities of ®rst 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 de®nitive, erythroblasts were GPA+, CD47+, CD45± and CD35±, whereas CD71 expression was weak/undetectable on primitive erythroblasts but strongly positive on 100% of de®nitive erythroblasts; primitive erythroblasts were also CD36± whereas de®nitive erythroblasts were CD36+. We therefore used CD45/GPA selection of Percoll 1118-separated cells to demonstrate successful enrichment of male e-globin-positive fetal erythroblasts from model mixtures, and as proof of principle from some ®rst trimester maternal blood samples. Fetal cell enrichment protocols based on ®rst trimester e-globin-positive primitive erythroblasts may allow reliable enrichment of fetal cells from maternal blood for early non-invasive prenatal diagnosis of genetic disorders.

J Obstet Gynaecol, 1991

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 ...

Cells Tissues Organs 193 379 392, May 1, 2011

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.

Clinicas De Perinatologia, 2003

Annals of the Academy of Medicine Singapore, Oct 1, 2003

Archives of Disease in Childhood Fetal and Neonatal Edition, Sep 1, 1997

Aim-To determine whether antenatal administration of thyrotrophin releasing hormone (TRH), to pro... more 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 eVect of transplacentally administered TRH on the fetal circulation was prospectively evaluated in 30 patients between 24 and 34 weeks' gestation. TRH (400 µg) was given to the mother intravenously either as a bolus or an infusion. Fetal eVects 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.

American Journal of Obstetrics and Gynecology, Oct 1, 1990

Two patients with severe alloimmune thrombocytopenia were managed by weekly intrauterine platelet... more Two patients with severe alloimmune thrombocytopenia were managed by weekly intrauterine platelet transfusions at 25 to 36 weeks. In one patient high-dose immunoglobulin was also administered weekly to the mother, and high maternal and fetal immunoglobulin levels were achieved. Fetal platelet counts were similar in both patients. The only variable that affected fetal platelet concentration was the posttransfusion platelet count from the previous transfusion. (AM J