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Biomedical subjects

C Lees

Publications and source records attributed to C Lees.

At least 19 recordsLinked to original sources
PubMed2001

Individualized risk assessment for adverse pregnancy outcome by uterine artery Doppler at 23 weeks.

OBJECTIVE: To provide individualized risk prediction of severe adverse pregnancy outcome based on uterine artery Doppler screening at 23 weeks. METHODS: Color Doppler assessment of the uterine arteries was carried out in 5121 women attending for routine care at 23 weeks in two inner-city obstetric units. The mean uterine artery pulsatility index (PI) was calculated, and the likelihood ratios in relation to PI were generated for severe adverse outcome. This was defined as fetal death, placental abruption, and delivery before 34 weeks associated with preeclampsia and birth weight less than the 10th centile. RESULTS: The likelihood of severe adverse pregnancy outcome increased quadratically with mean uterine artery PI. This relationship was not affected by maternal age, ethnicity, or parity. At a mean PI of 1.45, the 95th centile for our population, the likelihood ratio for severe adverse pregnancy outcome was 5. Cigarette smoking had an additional contribution to PI in predicting severe adverse outcome, roughly doubling the risk for a given PI. CONCLUSION: The individualized risk of severe adverse pregnancy outcome can be determined by uterine artery Doppler screening at 23 weeks and knowledge of cigarette smoking history. Such individualized risk would allow ultrasound resources and clinical follow-up to be tailored to the pregnant woman for the most appropriate use of antenatal care.

Adult↗
PubMed2001

Fetal Doppler velocimetry at high altitude.

OBJECTIVES: To determine impedance and velocity characteristics of the fetal circulation using Doppler ultrasound, at extremely high altitude (4300 m) in the Peruvian Andes compared to an ethnically similar population at sea level. METHODS: This was a cross-sectional study of 196 women resident at high altitude (Cerro de Pasco, 4300 m above sea level) and 196 women resident at sea level (Lima) with normal singleton pregnancies. Pulsatility index (PI), maximum velocity (Vmax) and minimum velocity (Vmin) in the umbilical artery, the descending aorta, the middle cerebral artery and the ductus venosus were compared between the two populations using fractional polynomial regression analysis. RESULTS: The PI was higher at high altitude than at sea level in the umbilical artery (regression coefficient = 0.112, P < 0.001), and not significantly different in the descending aorta, middle cerebral artery and ductus venosus. Vmax was lower at high altitude than at sea level in all three arterial vessels assessed; Vmin was lower in two: the umbilical artery and the descending aorta. The high-altitude/sea-level ratios for umbilical artery Vmax and Vmin were 0.93 and 0.82, respectively (P < 0.001 for each), the ratios for descending aorta Vmax and Vmin were 0.93 and 0.89, respectively (P = 0.003 and P < 0.001, respectively), and the regression coefficient for the middle cerebral artery Vmax was -2.844 (P = 0.003). There was no significant difference in the middle cerebral artery Vmin or in the ductus venosus Vmax and Vmin. CONCLUSIONS: Despite the lower ambient oxygen at high altitude and an increase in umbilical artery PI, the fetal circulation does not exhibit a 'brain sparing effect'. This and the overall decrease in blood flow velocities in the fetal circulation at high altitude may be due to the increased fetal hematocrit, which will result in increased blood viscosity.

Adult↗
PubMed2001

Prenatal ultrasound diagnosis of Leroy I cell disease.

Leroy I cell disease is a rare autosomal recessive disorder which progressively leads to death within the first decade of life. Invasive prenatal diagnosis is possible but is only undertaken in families who have previously had an affected child. We describe the antenatal ultrasound diagnosis of the disease in a case referred at 30 weeks' gestation for suspected polyhydramnios.

Adult↗
PubMed2001

Vasoactive mediator release by fetal endothelial cells in intrauterine growth restriction and preeclampsia.

OBJECTIVE: Preeclampsia and fetal growth restriction are associated with poor placental perfusion, which may be accompanied by a compensatory release of vasoactive substances in the fetoplacental circuit. This study examines the effects of preeclampsia and fetal growth restriction on nitric oxide and prostacyclin signaling pathways in fetal endothelial cells. STUDY DESIGN: Human umbilical vein endothelial cells from 30 control pregnancies, 18 pregnancies with preeclampsia, and 9 pregnancies with intrauterine growth restriction were cultured. Intracellular cyclic guanosine monophosphate accumulation and 6-keto-prostaglandin F1alpha production were determined. RESULTS: Intracellular accumulation of cyclic guanosine monophosphate was significantly higher in the preeclampsia group and lower in the growth restriction group than in the control group (9.8, 1.8, and 3.9 pmol/microg protein for 5 minutes, respectively), whereas 6-keto-prostaglandin F1alpha production was not significantly different in the 3 groups. CONCLUSION: The data suggest that the fetoplacental vascular response to preeclampsia is to increase production of cyclic guanosine monophosphate, perhaps to maintain vessel dilatation and maximum flow through placental villi. In fetal growth restriction the umbilical vein endothelial cells do not or cannot respond to chronic hypoxia by increasing cyclic guanosine monophosphate, which may lead to fetoplacental vasoconstriction.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

A role for IL-5 in the induction of cytotoxic T lymphocytes in vivo.

IL-5 is generally regarded as a Th2 cytokine involved in eosinophil maturation and function and in B cell growth and antibody production, but without any well-established effects on T cells. Early reports suggested that IL-5 could stimulate the production of cytotoxic T lymphocytes (CTL) in vitro, but no evidence has been obtained to date for such a role in studies with IL-5-deficient (IL-5-/-) mice. Here we demonstrate that when oxidized mannan MUC1 fusion protein (M-FP) is used as an antigen in mice, IL-5 is required for the optimal generation of the CTL response. IL-5 was as effective as IL-2 for the induction of CTL from spleen cells in vitro and both CD4+ and CD8+ T cells from M-FP-immunized animals could be shown to secrete IL-5 in culture. In IL-5-/- mice, CTLp frequency was greatly diminished resulting in the inability to reject MUC1- tumors. Clearly, IL-5 is produced by functional T cells, especially the Tc1 type, after M-FP immunization and is required for an optimal CTL response to this antigen.

Amino Acid Sequence↗
PubMed2000

One-stage screening for pregnancy complications by color Doppler assessment of the uterine arteries at 23 weeks' gestation.

OBJECTIVE: To estimate the value of screening for preeclampsia and fetal growth restriction by performing color Doppler assessment of uterine arteries at 23 weeks' gestation in predicting adverse pregnancy outcome. METHODS: Women with singleton pregnancies who attended routine ultrasonography at 23 weeks had color Doppler uterine artery imaging. Bilateral uterine artery notches were noted and left and right uterine artery pulsatility indices (PI) were measured. A mean PI of more than 1.45 was considered increased. Screening characteristics for predicting preeclampsia and delivery of small-for-gestational-age infants were calculated. RESULTS: Of 1757 pregnancies, increased PI was present in 89 (5.1%) and bilateral notches were noted in 77 (4.4%). Twenty-three of 65 women (35.3%; 95% confidence interval [CI] 23.9, 48.2) had increased PI and later developed preeclampsia, and 8 of 10 (80%; 95% CI 44.4, 97. 5) with preeclampsia required delivery before 34 weeks. The respective values for women with bilateral notches were 21 of 65 (32. 3%; 95% CI 21.2, 45.1) and 8 of 10 (80%; 95% CI 44.4, 97.5). The sensitivity of increased PI was 30 of 143 (21%; 95% CI 14.6, 28.6) for delivery of an infant with birth weight below the tenth percentile and 7 of 10 (70% 95% CI 34.8,93.3) for birth weight below the tenth percentile delivered before 34 weeks. The respective values for bilateral notches were 19 of 143 (13.3%; 95% CI 8.2, 20) and 5 of 10 (50%; 95% CI 18.7, 81.3). CONCLUSION: A one-stage color Doppler screening program at 23 weeks identified most women who subsequently developed serious complications of impaired placentation associated with delivery before 34 weeks. The screening results were similar when the high-risk group was defined as women with increased PI or bilateral notches.

Adolescent↗
PubMed2000

Doppler obstetric ultrasound: a graphical display of temporal changes in safety indices.

OBJECTIVE: To investigate ultrasound use and exposure in pregnant women undergoing Doppler ultrasound investigation of the maternal and fetal circulation using Doppler ultrasound techniques. METHODS: Sample graphical displays were generated showing duration of each mode, thermal and mechanical index levels and overall elapsed time of scan and modes. RESULTS: The displays revealed combinations of scanner settings which delivered higher output intensity levels and which we subsequently altered in our practice to reduce ultrasound exposure. CONCLUSION: A display of this type would enable monitoring of output levels and exposures, especially for operators undergoing training in Doppler applications. It would also identify poor practice where there is prolonged exposure at high output levels. Such a display, in combination with accurate output measurement from manufacturers and independent laboratories, would help to ensure the safe use of ultrasound in fetal assessment.

Body Temperature↗
PubMed2000

Fetal biometry at 4300 m compared to sea level in Peru.

OBJECTIVES: The aim of this study was to compare ultrasound fetal size at high altitude and sea level. METHODS: Three hundred and thirty-four women in Cerro de Pasco at 4300 m (14,100 ft) altitude and 278 women in Lima (sea level) were recruited to the study. Ultrasound fetal biometry was carried out between 14 and 42 weeks of gestation. Biparietal diameter, occipitofrontal diameter, abdominal circumference and femur length were measured and head circumference and estimated fetal weight were derived from these data. Two hundred and seventy-seven women (82.9%) in Cerro de Pasco and 216 (77.7%) in Lima had normal singleton pregnancies and certain menstrual dates. These women were selected for statistical analysis. Fractional polynomial regression analysis on gestational age was performed, controlling for maternal height and parity. RESULTS: Fetal biometry measurements were significantly smaller in Cerro de Pasco compared with Lima. When gestation bands were compared this effect was present from 25 to 29 weeks onwards, and was greater in the abdominal circumference than in the head circumference and femur length (ratios Cerro de Pasco: Lima, 0.96, 0.97 and 0.98, respectively). Estimated fetal weight was also significantly lower in Cerro de Pasco (ratio 0.88), as were birthweights (ratio 0.88). If the centiles derived from the Lima population were applied for Cerro de Pasco, 11.2% of all estimated fetal weights would be below the fifth centile, and 1.08% above the ninety-fifth. CONCLUSIONS: These data suggest that at high altitude, all fetal biometry measurements follow a lower trajectory than at sea level. Specific biometry charts should therefore be used for obstetric ultrasound at high altitude.

Altitude↗
PubMed2000

Fetal cells in maternal blood of pregnancies with severe fetal growth restriction.

The aim of this study was to examine whether, in pregnancies with severe early onset fetal growth restriction, the number of fetal erythroblasts in maternal blood is increased. The percentage of fetal erythroblasts in maternal blood, enriched by triple density gradient centrifugation and anti-CD71 magnetic cell sorting, was determined in 10 singleton pregnancies with severe intrauterine growth restriction in which there was Doppler ultrasound evidence of impaired placental perfusion. The values were compared to those of 10 normal pregnancies at the same gestational range of 22-26 weeks. In the growth restricted pregnancies the median number of fetal erythroblasts per 100 nucleated cells in maternal blood enriched for fetal cells was significantly higher than the median value in the control pregnancies (8.5% compared with 1%; P < 0.001). These data suggest that impaired uteroplacental perfusion and severe fetal growth restriction may be associated with placental damage leading to increased feto-maternal cell traffic. Alternatively the rate of transfer of fetal cells into the maternal circulation is not altered but in growth restriction the proportion of fetal erythroblasts in fetal blood is increased.

Antigens, CD↗
PubMed2000

Increased fetal erythroblasts in women who subsequently develop pre-eclampsia.

In pregnancies complicated by pre-eclampsia (PET) and/or intrauterine growth restriction (IUGR) there is an increased number of fetal cells in the maternal circulation. The aim of this study was to investigate whether this increase in fetal cells precedes the onset of these pregnancy complications. Doppler ultrasound studies at 24 weeks gestation have shown that increased impedance to flow in the uterine arteries identifies pregnancies with impaired placental perfusion that subsequently develop PET and/or IUGR. We obtained maternal blood from 18 pregnancies with abnormal Doppler results at 22-24 weeks gestation and from 10 normal controls. Fetal erythroblasts were enriched from maternal blood by triple density gradient centrifugation and magnetic cell sorting with CD71 antibody, and the percentage of these erythroblasts was determined. The median proportion of fetal erythroblasts in the group with abnormal Doppler results was 4.5% (range 1-12%), which was significantly higher than in the control group [median 1% (range 0-3%; P < 0.001)]. Furthermore, within the group with abnormal Doppler the median proportion of fetal erythroblasts was higher in the 10 cases which subsequently developed PET and/or IUGR [median 5.5% (range 3-12%)], than in those with normal pregnancy outcome [median 2% (range 1-5%; P < 0.01)]. These findings suggest that impaired placental perfusion is associated with an increase in feto-maternal cell traffic, which precedes the onset of PET and/or IUGR by several weeks.

Adult↗
PubMed1999

Maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate and intravenous ritodrine.

OBJECTIVE: To determine the maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate compared with ritodrine for acute tocolysis. METHODS: Sixty women in preterm labor were enrolled in this study that was part of a multicenter study of glyceryl trinitrate. Once randomized, the women received transdermal glyceryl trinitrate or intravenous ritodrine for acute tocolysis. Measurements of maternal pulse, blood pressure (BP), and fetal heart rate (FHR) were recorded for up to 24 hours and compared over the treatment course. RESULTS: Changes from baseline in mean maternal heart rate, FHR, and maternal BP (mean arterial pressure [MAP]) were compared between the glyceryl trinitrate and ritodrine groups over the entire treatment course. The mean change from baseline in maternal heart rate was 21.1 beats per minute less (95% confidence interval [CI] 15.7, 26.5, P < .001), and the mean maternal heart rate was 21.8 beats per minute lower (95% CI 16.9, 26.7, P < .001) in the glyceryl trinitrate group. The mean change in FHR was 9.2 beats per minute less (95% CI 3.8, 14.6, P = .001) and the mean FHR significantly lower (6.9 beats per minute, 95% CI 1.9, 11.9, P = .008) during glyceryl trinitrate treatment. Ritodrine had a significantly hypotensive effect on MAP (95% CI -4.3, 0.0, P = .03). Mean arterial pressure was not significantly different over the treatment course. CONCLUSION: At doses required for acute tocolysis, transdermal glyceryl trinitrate had minimal effects on maternal pulse, BP, and FHR, and significantly fewer adverse cardiovascular effects than intravenous ritodrine. Thus, transdermal glyceryl trinitrate might be a safer treatment for women in preterm labor.

Administration, Cutaneous↗
PubMed1999

Assessment of umbilical arterial and venous flow using color Doppler.

OBJECTIVE: To estimate the umbilical artery and vein blood volume flow using B-mode and Doppler ultrasound in the second and third trimesters of pregnancy. DESIGN: This was a cross-sectional study of 129 singleton, healthy pregnancies at 23-33 weeks' gestation. The umbilical artery and vein cross-sectional area, time-averaged velocity and pulsatility index were measured in a free loop of cord, and the fetal weight was estimated. Ranges for each parameter were obtained; from these the blood flow for the vein and artery was calculated, and the average flow corrected for fetal weight was derived. RESULTS: The median time for examination was 6 min. The mean cross-sectional area and time-averaged velocity for both the vein and artery increased linearly with gestation. The umbilical artery flow correlated closely with the average vein flow (r = 0.9, p < 0.001). There was a significant, though poor, inverse correlation between the umbilical artery pulsatility index and the average umbilical flow (r = -0.25, p < 0.05). The average umbilical flow (calculated from the mean of arterial and venous flow), corrected for estimated fetal weight, decreased from 189.2 ml/kg per min at 23 weeks to 176.2 ml/kg per min at 33 weeks' gestation. CONCLUSION: The estimates of fetal umbilical flow obtained by this Doppler method are consistent with previously published data. Averaging the arterial and venous flow is theoretically advantageous in reducing the inherent errors in estimating either the arterial or the venous flow. This method of measuring umbilical flow may have clinical potential in assessing fetal health and disease processes.

Blood Flow Velocity↗
PubMed1999

The role of insulin-like growth factor binding protein-1 phosphoisoforms in pregnancies with impaired placental function identified by doppler ultrasound.

This study was performed to investigate the hypothesis that insulin-like growth factor binding protein-1 (IGFBP-1) is involved in the pathogenesis of trophoblast invasion and impaired placentation in human pregnancy. The role of total and non-phosphorylated IGFBP-1 in women with fetal growth restriction and in high risk pregnancies identified by uterine artery Doppler ultrasound screening was examined. This was a prospective study of women booked for antenatal care having second trimester anomaly scans and Doppler screening between 22-26 weeks gestation. Women were divided into three groups and compared: normal uterine artery Doppler and normal fetal growth (control group, n = 10); abnormal Doppler and normal fetal growth [bilateral uterine artery notches (BN; n = 16); abnormal Doppler and intrauterine growth restriction (IUGR; n = 8)]. Maternal serum was collected, stored and assayed simultaneously for total and non-phosphorylated IGFBP-1. There was elevated total and non-phosphorylated IGFBP-1 (mean 44.99 +/- 12.19 and 29.61 +/- 10.38 microg/l respectively) in the IUGR group compared with controls (mean 17.96 +/- 3.24 and 12.18 +/- 1.55 microg/l, P < 0.05). This finding suggests that the various IGFBP-1 isoforms, the degree of phosphorylation and the ratios of these different forms locally may be important during trophoblast invasion and may be implicated in clinical manifestations of impaired placentation later in the second trimester.

Female↗
PubMed1999

Vasa previa: an avoidable obstetric tragedy.

UNLABELLED: Vasa previa is a rarely reported condition in which the fetal blood vessels, unsupported by either the umbilical cord or placental tissue, traverse the fetal membranes of the lower segment of the uterus below the presenting part. The condition has a high fetal mortality due to fetal exsanguination resulting from fetal vessels tearing when the membranes rupture. Despite improvements in medical technology, vasa previa often remains unsuspected until this fatal fetal vessel rupture occurs. Significant reduction in the fetal mortality from this condition depends on a high index of suspicion leading to antenatal diagnosis, and elective delivery by cesarean. We believe transvaginal ultrasound in combination with color Doppler is the most effective tool in the antenatal diagnosis of vasa previa and should be utilized in patients at risk, specifically those with bilobed, succenturiate-lobed, and low-lying placentas, pregnancies resulting from in vitro fertilization, and multiple pregnancy. Where there has been antepartum or intrapartum hemorrhage, especially when associated with fetal heart irregularities, we also recommend a test to exclude fetal blood in the vaginal blood. Similarly, amnioscopy before amniotomy may help to diagnose this condition. Cesarean delivery is the method of delivery of choice, and aggressive resuscitation of the affected neonate may be life saving. With a high index of suspicion, antenatal diagnosis using transvaginal sonography in combination with color Doppler, elective delivery by cesarean, and aggressive resuscitation of the neonate where fetal vessel rupture has occurred, the mortality from this complication may be considerably reduced. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to identify the risk factors and associated conditions for vasa previa, to identify the various clinical presentations and management of vasa previa, and to be aware of the diagnostic tools available to make the antepartum diagnosis of vasa previa.

Cesarean Section↗
PubMed1998

Engraftment of severe combined immune deficient mice receiving allogeneic bone marrow via In utero or postnatal transfer.

Although in utero transplantation (IUT) has been shown to be effective in treating human severe combined immune deficiency (SCID), the relative merit of IUT as compared with postnatal bone marrow transplantation (BMT) for SCID is unknown. Therefore, comparative studies were undertaken in mice to determine the engraftment outcome in these two settings. Because T-cell depletion (TCD) reduces graft-versus-host disease (GVHD) severity but compromises alloengraftment, studies were performed with TCD or non-TCD BM and GVHD risk was assessed using a tissue scoring system and by the adoptive transfer of splenocytes from engrafted mice into secondary recipients. Non-SCID recipients received pre-BMT irradiation to simulate those circumstances in which conditioning is required for alloengraftment. IUT recipients of non-TCD and especially TCD BM cells in general had higher levels of donor T-cell and myeloid peripheral blood (PB) engraftment than nonconditioned SCID recipients. Increased TCD or non-TCD BM cell numbers in adult SCID recipients resulted in similar levels of PB engraftment as IUT recipients. However, under these conditions, mean GVHD scores were higher than in IUT recipients. The majority of adoptive transfer recipients of splenocytes from IUT recipients were GVHD-free, consistent with the in vitro evidence of tolerance to host alloantigens. Total body irradiation (TBI)-treated mice that had the highest engraftment had evidence of thymic damage as denoted by a higher proportion of thymic and splenic T cells with a memory phenotype as compared with IUT recipients. IUT mice had vigorous thymic reconstitution by 3 weeks of age. Our data indicate that IUT has a number of advantages as compared with postnatal BMT. Future studies examining the fine specificity of immunoreconstitution in IUT versus postnatal BMT are indicated.

Adoptive Transfer↗
PubMed1998

Mouse mucin 1 (MUC1) defined by monoclonal antibodies.

Mucins are highly expressed in many different human cancers and numerous murine monoclonal antibodies (MAbs) to human mucins, particularly Mucin 1 (MUC1), have been produced. However, no such antibodies to murine mucin 1 (muc1) have been described and we now describe 6 different antibodies produced to murine muc1 and to human MUC1 cytoplasmic tail, either by immunising rats, or muc1 o/o mice with synthetic peptides or a fusion protein composed of glutathione-s-transferase (GST) linked to the tandem repeat region of muc1. The antibodies to both the extracellular tandem repeat region and to the cytoplasmic tail were found to react with mucin-containing murine tissues such as breast, stomach, colon, ovary, kidney and pancreas, and the staining patterns were similar to those found in humans. The reagents reacted specifically with muc1 peptides and tissues; however, some cross reactivity with other mucin-derived peptides was noted, particularly those containing the amino acid sequence TSS. Three different epitopes (TSS, TAVLSGTS and LSGTSSP) of the M30, M70 and MFP25 MAbs were detected. Of interest was the finding that some of the antibodies reacted with murine lymphocytes; it was not clear whether these reactions were due to mucin 1 on mouse lymphocytes (MUC1 was considered to be absent from human lymphocyte), or due to cross reaction with a sialic adhesion molecule on lymphocytes. The antibodies should prove valuable reagents when studying differentiation and expression in murine glandular tissues and the ontogeny of mucin-secreting tumours.

Animals↗
PubMed1998

Oxidised mannan antigen conjugates preferentially stimulate T1 type immune responses.

It is desirable to be able to produce either T1 or T2 responses and we have found that, in mice, mannose--coupled antigens stimulated T2 type responses antibodies and CTLs, whereas if oxidized, mannose--coupled antigens stimulated T1 responses little antibody and a potent CTL response. In addition, the cytokine profiles support the T1rT2 differentiation with these immunizations, in that oxidized mannan antigen gives IFNg, IL-2 and IL-12 production, whereas in the absence of oxidization, IL-4 and not the other cytokines is produced. A number of antigens have been examined--particularly Mucin 1 and the delivery method using mannose may be applicable to the other antigens.

Animals↗