Metal foil targets were irradiated with 1 mum wavelength (lambda) laser pulses of 5 ps duration a... more Metal foil targets were irradiated with 1 mum wavelength (lambda) laser pulses of 5 ps duration and focused intensities (I) of up to 4x10;{19} W cm;{-2}, giving values of both Ilambda;{2} and pulse duration comparable to those required for fast ignition inertial fusion. The divergence of the electrons accelerated into the target was determined from spatially resolved measurements of x-ray K_{alpha} emission and from transverse probing of the plasma formed on the back of the foils. Comparison of the divergence with other published data shows that it increases with Ilambda;{2} and is independent of pulse duration. Two-dimensional particle-in-cell simulations reproduce these results, indicating that it is a fundamental property of the laser-plasma interaction.
In this paper, three different experimental configurations designed to study jet propagation phys... more In this paper, three different experimental configurations designed to study jet propagation physics are presented. Each configuration uses a different target design: conical dimples in solid surfaces, hollow cones filled with foam and angled thin foils. When irradiated with a laser, these targets result in the launching of a plasma jet, the properties of which can be controlled by judicious choices of the target and laser parameters. Experimental results from these targets are shown, and the physics which may be studied with each of these targets is briefly discussed.
ABSTRACT In this work we present experimental research related to laboratory astrophysics using a... more ABSTRACT In this work we present experimental research related to laboratory astrophysics using an intense laser. The goal of these experiments is to investigate some of the complex features of young stellar objects and astrophysical outflows, in particular the plasma jet interaction with the interstellar medium. The relevance of these experiments to astrophysics is measured through similarity criteria (scaling laws). These ensure the similarity between the astrophysical object and the laboratory provided that the dimensionless numbers are equivalent. Consequently, measurements of the plasma parameters are crucial to link laboratory research to astrophysics as they are needed for the determination of these dimensionless numbers. In this context, we designed experiments to generate plasma jets using an intense laser, and to study the evolution in vacuum and in an ambient medium.
ABSTRACT The development activity of a new experimental technique for the study of the fast elect... more ABSTRACT The development activity of a new experimental technique for the study of the fast electron transport in high density matter is reported. This new diagnostic tool enables the X-ray 2D imaging of ultrahigh intensity laser plasmas with simultaneous spectral resolution in a very large energy range to be obtained. Results from recent experiments are discussed, in which the electron propagation in multilayer targets was studied by using the Kα. In particular, results highlighting the role of anisotropic Bremsstrahlung are reported, for the sake of the explanation of the capabilities of the new diagnostics. A discussion of a test experiment conceived to extend the technique to a single-shot operation is finally given.
Malignant melanoma is an extremely aggressive form of cancer. Adrenal metastases are found in 50%... more Malignant melanoma is an extremely aggressive form of cancer. Adrenal metastases are found in 50% of cases of malignant melanoma, and are most often clinically and biochemically silent. Clinical presentation varies, and the diagnosis of adrenal metastases is often made incidentally, and frequently years after treatment of the primary lesion. An adrenal mass lesion seen on a CT scan, greater than 5 cm in diameter, with central or irregular areas of necrosis/haemorrhage (and no lipomatous component) is characteristic of a metastasis from malignant melanoma, in the setting of normal gland function. If these features are bilateral, they are pathognomonic. Oval, low-attenuation (on CT) adrenal masses less than 3 cm in diameter should not be considered benign in a patient with any prior history of melanoma. Careful imaging review of the adrenal glands should be undertaken in all patients with malignant melanoma. Early diagnosis of these distant metastases has important prognostic and therapeutic implications. The four cases presented illustrate the spectrum of presentations and clinical course of adrenal metastases from malignant melanoma. The accompanying CT images show the characteristic appearances of adrenal metastases.
We report a prospective, blinded comparison of compression ultrasound (US) and Tc-99m erythrocyte... more We report a prospective, blinded comparison of compression ultrasound (US) and Tc-99m erythrocyte-labelled venous blood pool scintigraphy (BPS) in patients presenting with symptoms of deep venous thrombosis (DVT). Contrast venography (CV) was used as the gold standard. Ninety-eight lower limbs of 76 patients were examined. DVT was present at CV in 38 of 98 limbs and was isolated to the calf veins in eight. Sensitivity and specificity of ultrasound for femoropopliteal thrombus were 81.5% and 96% and of venous blood pool scintigraphy were 55% and 96%. For deep venous thrombosis in the whole limb sensitivity and specificity of ultrasound were 74% and 90% and of venous blood pool scintigraphy were 61% and 88%. In the calf sensitivity and specificity of US were 61% and 94% and of venous blood pool scintigraphy were 61% and 89%. Excluding equivocal venous blood pool scintigraphy results, the predictive values of a positive and negative venous blood pool scintigraphy study for the whole limb were 84% and 86%. The predictive values of a positive and negative ultrasound where the examination was adequate were 82% and 86%. US is a more sensitive alternative to CV than BPS for femoropopliteal DVT. When neither US nor CV can be performed, BPS remains a useful initial test for DVT, provided it is unequivocally positive or negative.
BJOG: An International Journal of Obstetrics and Gynaecology, 2006
To explore women's views on being referred to and attending a specialist antenata... more To explore women's views on being referred to and attending a specialist antenatal hypertension clinic. Qualitative interview study. A pregnancy hypertension clinic in a large teaching hospital in the East Midlands. Twenty-one women (aged 18 years and above) attending the pregnancy hypertension clinic for the first time during their current pregnancy. Women who had been referred to and attended a specialist antenatal clinic participated in semi-structured interviews. Data analysis was based on the constant comparative method. Women's experiences and perceptions of being referred to and attending a specialist antenatal clinic. Being referred to the clinic conferred an 'at risk' status on women. Some women welcomed the referral but others experienced it as unsettling. Many were unclear about why they had been identified as being at risk or had difficulties in accepting the legitimacy of the reason for referral. Women were often inadequately informed about why they were referred to the clinic, what they could expect and the benefits of attending the clinic over management in the community. Although attendance at the clinic was cited as a source of reassurance, the reassurance was often made necessary by concern raised by the initial referral. Women's accounts suggest that the interface between community and secondary antenatal services needs improvement to minimise possible adverse effects from identifying women as being 'at risk' during pregnancy.
We present experimental results of plasma jet, interacted with an ambient medium, using intense l... more We present experimental results of plasma jet, interacted with an ambient medium, using intense lasers to investigate the complex features of astrophysical jets. This experiment was performed in France at the LULI facility, Ecole Polytechnique, using one long pulse laser to generate the jet and a short pulse laser to probe it by proton radiography. A foam filled cone target was used to generate high velocity plasma jet, and a gas jet nozzle produced the well known ambient medium. Using visible pyrometry and interferometry, we were able to measure the jet velocity and electronic density. We get a panel of measurements at various gas density and time delay. From these measurements, we could underline the growth of a perturbed shape of the jet interaction with the ambient medium. The reason of this last observation is still in debate and will be presented in the article.
Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant ... more Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks' gestation (and up to 41 weeks' gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks' gestation, PlGF <5th centile had high sensitivity (0.96; 95% confid...
Condensation: Term placental inter-villus space lining is a mosaic of endothelial cells, trophobl... more Condensation: Term placental inter-villus space lining is a mosaic of endothelial cells, trophoblast and fibrin: component area percentages alter in pre-eclampsia indicating "poor-repair" aetiology.
OBJECTIVE: To estimate, in maternal red blood cell alloimmunization, the diagnostic value of feta... more OBJECTIVE: To estimate, in maternal red blood cell alloimmunization, the diagnostic value of fetal ultrasonography and Doppler blood flow velocity in the evaluation and prediction of fetal anemia.
Pulmonary hypertension is found in about 10% of patients with systemic lupus erythematosis (SLE).... more Pulmonary hypertension is found in about 10% of patients with systemic lupus erythematosis (SLE). Pulmonary hypertension may be present at the time of diagnosis or may develop after the diagnosis of SLE or anti-phospholipid syndrome (APS). It often presents in the reproductive years and has a significant impact on pregnancy outcome, being a significant cause of indirect maternal deaths. In our observational case series of three patients there were two deaths (66%). In cases 1 and 2 the pulmonary hypertension developed during pregnancy and deteriorated rapidly with markedly abnormal mean pulmonary artery pressures of 80 and 70 mmHg respectively prior to death. Both patients died within 48 hours of delivery. In case 3 the pulmonary hypertension was milder and was diagnosed very early in pregnancy. The patient received multidisciplinary care from the first trimester and the management of the pregnancy, delivery and the early puerperium was planned. Careful epidural anaesthesia was used and the patient had invasive monitoring on the intensive therapy unit (ITU) for 72 hours. Women with pulmonary hypertension need to be aware of the high risk of maternal mortality associated with pregnancy but we believe that an improvement in outcome can be achieved by careful assessment and the use of a multidisciplinary approach from early in pregnancy.
Journal of Family Planning and Reproductive Health Care, 2001
To assess the accuracy and consistency of blood pressure measurement techniques among individual ... more To assess the accuracy and consistency of blood pressure measurement techniques among individual clinicians and the reliability of the equipment in everyday use. Professional survey. The senior nurse at each of 28 clinics was sent two questionnaires about equipment, and 55 health professionals were sent a questionnaire about their measurement technique. Faulty equipment, date of last service, named individual responsible for equipment, knowledge of protocols regarding mercury spillage, correct technique for measuring blood pressure, training in blood pressure measurement. An 82% response rate on equipment showed it to be in relatively good condition, although maintenance problems and some potentially dangerous health and safety issues were highlighted. A 67% response rate on measurement technique showed that there was considerable variation in individual measurement technique that could lead to inappropriate action. This study has lead to replacing all mercury with aneroid devices, and to the development of staff guidelines and updating on measurement techniques. A re-audit will be carried out to complete the cycle.
To determine what threshold for proteinuria could best predict clinical outcome and whether this ... more To determine what threshold for proteinuria could best predict clinical outcome and whether this threshold could be applied universally to any biochemical assay. A prospective observational study of hypertensive pregnancies referred for further assessment after in a UK University hospital (n=197). Twenty-four hour urine protein was measured by two different assays [benzethonium chloride assay (BCA) and Bradford assay]. The differences between the two assays were calculated from Receiver Operating Characteristic (ROC) curves. Commonly used thresholds for defining preeclampsia (0.3 and 0.5 g/24 hours) were explored for both assays for the prediction of adverse clinical outcomes (severe hypertension, Birthweight&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10th percentile, preterm delivery, and a composite biochemical/haematological derangement). The two assays are not equivalent. The prevalence of&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;300 mg/24 hour proteinuria and, hence, the prevalence of preeclampsia differed between the two assays. ROC curve analysis demonstrates that the two assays are similar in terms of overall performance as predictive tests. However the threshold of 300 mg/24 hours performs poorly as a predictor of clinical risk. Likelihood ratios (LR) for the BCA at the 300 mg/L threshold for each clinical outcome do not achieve statistical significance. At the 500 mg/L threshold, the LR+for the BCA assay does achieve statistical significance for severe hypertension (LR+:1.51 95% CI 0.99-2.28) and for birthweight&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10th percentile (LR+:1.72 95% CI 1.11-2.66). For the Bradford assay at the 300 mg/24 hour threshold, the LR+does achieve statistical significance for birthweight&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10th percentile (LR+:1.71 95% CI 1.41-4.31). However, at the 500 mg/24 hour threshold, the LR+is significant for severe hypertension (LR+:2.15 95% CI 1.07-4.34), birthweight&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10th percentile (LR+:2.79 95% CI 1.4-5.54) and biochemical disease (LR+:2.47 95% CI 1.22-5.01). This study suggests that thresholds for proteinuria need to be higher (possibly&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=0.5 g/24 hours) and there is the need for a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;gold standard&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; proteinuria assay against which all other measures of quantification can be assessed.
We undertook this study to determine the accuracy and reliability of patient initiated blood pres... more We undertook this study to determine the accuracy and reliability of patient initiated blood pressure measurement and recording. We recruited 72 women from the antenatal hypertension clinic in a university teaching hospital. All were at high risk for preeclampsia and were asked to measure and record their blood pressure three times per day at home using a validated blood pressure device with an internal memory. From 979 measurements taken only 28 (2.9% were inaccurate). The inaccurate readings were restricted to three women. On further questioning two women admitted that the device had been used by other family members thus making comparison with the memory impossible. Thus the true nonconcordance rate amongst participants was 1/72 (1.4%). We conclude that blood pressure recordings taken and documented by high-risk women at home are accurate. This allows more frequent measurements to be taken without the inconvenience of additional visits to hospital and may therefore lead to the earlier detection of preeclampsia.
Previous experiments have demonstrated the stable expression of factor IX (FIX) protein in mice a... more Previous experiments have demonstrated the stable expression of factor IX (FIX) protein in mice and canine models of hemophilia B following portal vein gene transfer with a recombinant adeno-associated virus (rAAV) vector encoding FIX. Here, we present the results of studies that further optimized the rAAV vector transgene cassette used to express FIX and explored the use of the less-invasive intravenous (i.v.) route of vector administration for the treatment of hemophilia B. First, a liver-specific promoter was evaluated in conjunction with cis-acting regulatory elements in mice. Constructs that included both the beta-globin intron and the woodchuck hepatitis virus post-transcriptional regulatory element resulted in the highest level of FIX expression in vivo. Using this optimized vector, we demonstrate that i.v. injection was feasible for hepatic gene transfer in mice, achieving 70-80% of portal vein expression levels of FIX. In further studies using the Chapel Hill strain of hemophilia B dogs, we demonstrate for the first time FIX expression and partial correction of the bleeding disorder following i.v. administration of an AAV vector.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2001
The early detection of pre-eclampsia is a major challenge in obstetric care. We report a case whe... more The early detection of pre-eclampsia is a major challenge in obstetric care. We report a case where pre-eclampsia was detected by home blood pressure monitoring between routine antenatal visits. This novel management approach allows early diagnosis and optimises antenatal care in fulminating disease. #
Pre-eclampsia remains a leading cause of maternal death, with 72% of pre-eclampsia cases associat... more Pre-eclampsia remains a leading cause of maternal death, with 72% of pre-eclampsia cases associated with substandard care. 1 One in 10 pregnant women develop partial signs or symptoms (73 000 a year in the United Kingdom); about 20% of these progress to pre-eclampsia. 2 3 This article summarises recommendations from the Pre-Eclampsia Community Guideline (PRECOG) Group 4 under the auspices of the charity Action on Pre-eclampsia. The recommendations cover the assessment of women with suspected pre- ...
Metal foil targets were irradiated with 1 mum wavelength (lambda) laser pulses of 5 ps duration a... more Metal foil targets were irradiated with 1 mum wavelength (lambda) laser pulses of 5 ps duration and focused intensities (I) of up to 4x10;{19} W cm;{-2}, giving values of both Ilambda;{2} and pulse duration comparable to those required for fast ignition inertial fusion. The divergence of the electrons accelerated into the target was determined from spatially resolved measurements of x-ray K_{alpha} emission and from transverse probing of the plasma formed on the back of the foils. Comparison of the divergence with other published data shows that it increases with Ilambda;{2} and is independent of pulse duration. Two-dimensional particle-in-cell simulations reproduce these results, indicating that it is a fundamental property of the laser-plasma interaction.
In this paper, three different experimental configurations designed to study jet propagation phys... more In this paper, three different experimental configurations designed to study jet propagation physics are presented. Each configuration uses a different target design: conical dimples in solid surfaces, hollow cones filled with foam and angled thin foils. When irradiated with a laser, these targets result in the launching of a plasma jet, the properties of which can be controlled by judicious choices of the target and laser parameters. Experimental results from these targets are shown, and the physics which may be studied with each of these targets is briefly discussed.
ABSTRACT In this work we present experimental research related to laboratory astrophysics using a... more ABSTRACT In this work we present experimental research related to laboratory astrophysics using an intense laser. The goal of these experiments is to investigate some of the complex features of young stellar objects and astrophysical outflows, in particular the plasma jet interaction with the interstellar medium. The relevance of these experiments to astrophysics is measured through similarity criteria (scaling laws). These ensure the similarity between the astrophysical object and the laboratory provided that the dimensionless numbers are equivalent. Consequently, measurements of the plasma parameters are crucial to link laboratory research to astrophysics as they are needed for the determination of these dimensionless numbers. In this context, we designed experiments to generate plasma jets using an intense laser, and to study the evolution in vacuum and in an ambient medium.
ABSTRACT The development activity of a new experimental technique for the study of the fast elect... more ABSTRACT The development activity of a new experimental technique for the study of the fast electron transport in high density matter is reported. This new diagnostic tool enables the X-ray 2D imaging of ultrahigh intensity laser plasmas with simultaneous spectral resolution in a very large energy range to be obtained. Results from recent experiments are discussed, in which the electron propagation in multilayer targets was studied by using the Kα. In particular, results highlighting the role of anisotropic Bremsstrahlung are reported, for the sake of the explanation of the capabilities of the new diagnostics. A discussion of a test experiment conceived to extend the technique to a single-shot operation is finally given.
Malignant melanoma is an extremely aggressive form of cancer. Adrenal metastases are found in 50%... more Malignant melanoma is an extremely aggressive form of cancer. Adrenal metastases are found in 50% of cases of malignant melanoma, and are most often clinically and biochemically silent. Clinical presentation varies, and the diagnosis of adrenal metastases is often made incidentally, and frequently years after treatment of the primary lesion. An adrenal mass lesion seen on a CT scan, greater than 5 cm in diameter, with central or irregular areas of necrosis/haemorrhage (and no lipomatous component) is characteristic of a metastasis from malignant melanoma, in the setting of normal gland function. If these features are bilateral, they are pathognomonic. Oval, low-attenuation (on CT) adrenal masses less than 3 cm in diameter should not be considered benign in a patient with any prior history of melanoma. Careful imaging review of the adrenal glands should be undertaken in all patients with malignant melanoma. Early diagnosis of these distant metastases has important prognostic and therapeutic implications. The four cases presented illustrate the spectrum of presentations and clinical course of adrenal metastases from malignant melanoma. The accompanying CT images show the characteristic appearances of adrenal metastases.
We report a prospective, blinded comparison of compression ultrasound (US) and Tc-99m erythrocyte... more We report a prospective, blinded comparison of compression ultrasound (US) and Tc-99m erythrocyte-labelled venous blood pool scintigraphy (BPS) in patients presenting with symptoms of deep venous thrombosis (DVT). Contrast venography (CV) was used as the gold standard. Ninety-eight lower limbs of 76 patients were examined. DVT was present at CV in 38 of 98 limbs and was isolated to the calf veins in eight. Sensitivity and specificity of ultrasound for femoropopliteal thrombus were 81.5% and 96% and of venous blood pool scintigraphy were 55% and 96%. For deep venous thrombosis in the whole limb sensitivity and specificity of ultrasound were 74% and 90% and of venous blood pool scintigraphy were 61% and 88%. In the calf sensitivity and specificity of US were 61% and 94% and of venous blood pool scintigraphy were 61% and 89%. Excluding equivocal venous blood pool scintigraphy results, the predictive values of a positive and negative venous blood pool scintigraphy study for the whole limb were 84% and 86%. The predictive values of a positive and negative ultrasound where the examination was adequate were 82% and 86%. US is a more sensitive alternative to CV than BPS for femoropopliteal DVT. When neither US nor CV can be performed, BPS remains a useful initial test for DVT, provided it is unequivocally positive or negative.
BJOG: An International Journal of Obstetrics and Gynaecology, 2006
To explore women&amp;amp;#39;s views on being referred to and attending a specialist antenata... more To explore women&amp;amp;#39;s views on being referred to and attending a specialist antenatal hypertension clinic. Qualitative interview study. A pregnancy hypertension clinic in a large teaching hospital in the East Midlands. Twenty-one women (aged 18 years and above) attending the pregnancy hypertension clinic for the first time during their current pregnancy. Women who had been referred to and attended a specialist antenatal clinic participated in semi-structured interviews. Data analysis was based on the constant comparative method. Women&amp;amp;#39;s experiences and perceptions of being referred to and attending a specialist antenatal clinic. Being referred to the clinic conferred an &amp;amp;#39;at risk&amp;amp;#39; status on women. Some women welcomed the referral but others experienced it as unsettling. Many were unclear about why they had been identified as being at risk or had difficulties in accepting the legitimacy of the reason for referral. Women were often inadequately informed about why they were referred to the clinic, what they could expect and the benefits of attending the clinic over management in the community. Although attendance at the clinic was cited as a source of reassurance, the reassurance was often made necessary by concern raised by the initial referral. Women&amp;amp;#39;s accounts suggest that the interface between community and secondary antenatal services needs improvement to minimise possible adverse effects from identifying women as being &amp;amp;#39;at risk&amp;amp;#39; during pregnancy.
We present experimental results of plasma jet, interacted with an ambient medium, using intense l... more We present experimental results of plasma jet, interacted with an ambient medium, using intense lasers to investigate the complex features of astrophysical jets. This experiment was performed in France at the LULI facility, Ecole Polytechnique, using one long pulse laser to generate the jet and a short pulse laser to probe it by proton radiography. A foam filled cone target was used to generate high velocity plasma jet, and a gas jet nozzle produced the well known ambient medium. Using visible pyrometry and interferometry, we were able to measure the jet velocity and electronic density. We get a panel of measurements at various gas density and time delay. From these measurements, we could underline the growth of a perturbed shape of the jet interaction with the ambient medium. The reason of this last observation is still in debate and will be presented in the article.
Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant ... more Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks' gestation (and up to 41 weeks' gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks' gestation, PlGF <5th centile had high sensitivity (0.96; 95% confid...
Condensation: Term placental inter-villus space lining is a mosaic of endothelial cells, trophobl... more Condensation: Term placental inter-villus space lining is a mosaic of endothelial cells, trophoblast and fibrin: component area percentages alter in pre-eclampsia indicating "poor-repair" aetiology.
OBJECTIVE: To estimate, in maternal red blood cell alloimmunization, the diagnostic value of feta... more OBJECTIVE: To estimate, in maternal red blood cell alloimmunization, the diagnostic value of fetal ultrasonography and Doppler blood flow velocity in the evaluation and prediction of fetal anemia.
Pulmonary hypertension is found in about 10% of patients with systemic lupus erythematosis (SLE).... more Pulmonary hypertension is found in about 10% of patients with systemic lupus erythematosis (SLE). Pulmonary hypertension may be present at the time of diagnosis or may develop after the diagnosis of SLE or anti-phospholipid syndrome (APS). It often presents in the reproductive years and has a significant impact on pregnancy outcome, being a significant cause of indirect maternal deaths. In our observational case series of three patients there were two deaths (66%). In cases 1 and 2 the pulmonary hypertension developed during pregnancy and deteriorated rapidly with markedly abnormal mean pulmonary artery pressures of 80 and 70 mmHg respectively prior to death. Both patients died within 48 hours of delivery. In case 3 the pulmonary hypertension was milder and was diagnosed very early in pregnancy. The patient received multidisciplinary care from the first trimester and the management of the pregnancy, delivery and the early puerperium was planned. Careful epidural anaesthesia was used and the patient had invasive monitoring on the intensive therapy unit (ITU) for 72 hours. Women with pulmonary hypertension need to be aware of the high risk of maternal mortality associated with pregnancy but we believe that an improvement in outcome can be achieved by careful assessment and the use of a multidisciplinary approach from early in pregnancy.
Journal of Family Planning and Reproductive Health Care, 2001
To assess the accuracy and consistency of blood pressure measurement techniques among individual ... more To assess the accuracy and consistency of blood pressure measurement techniques among individual clinicians and the reliability of the equipment in everyday use. Professional survey. The senior nurse at each of 28 clinics was sent two questionnaires about equipment, and 55 health professionals were sent a questionnaire about their measurement technique. Faulty equipment, date of last service, named individual responsible for equipment, knowledge of protocols regarding mercury spillage, correct technique for measuring blood pressure, training in blood pressure measurement. An 82% response rate on equipment showed it to be in relatively good condition, although maintenance problems and some potentially dangerous health and safety issues were highlighted. A 67% response rate on measurement technique showed that there was considerable variation in individual measurement technique that could lead to inappropriate action. This study has lead to replacing all mercury with aneroid devices, and to the development of staff guidelines and updating on measurement techniques. A re-audit will be carried out to complete the cycle.
To determine what threshold for proteinuria could best predict clinical outcome and whether this ... more To determine what threshold for proteinuria could best predict clinical outcome and whether this threshold could be applied universally to any biochemical assay. A prospective observational study of hypertensive pregnancies referred for further assessment after in a UK University hospital (n=197). Twenty-four hour urine protein was measured by two different assays [benzethonium chloride assay (BCA) and Bradford assay]. The differences between the two assays were calculated from Receiver Operating Characteristic (ROC) curves. Commonly used thresholds for defining preeclampsia (0.3 and 0.5 g/24 hours) were explored for both assays for the prediction of adverse clinical outcomes (severe hypertension, Birthweight&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10th percentile, preterm delivery, and a composite biochemical/haematological derangement). The two assays are not equivalent. The prevalence of&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;300 mg/24 hour proteinuria and, hence, the prevalence of preeclampsia differed between the two assays. ROC curve analysis demonstrates that the two assays are similar in terms of overall performance as predictive tests. However the threshold of 300 mg/24 hours performs poorly as a predictor of clinical risk. Likelihood ratios (LR) for the BCA at the 300 mg/L threshold for each clinical outcome do not achieve statistical significance. At the 500 mg/L threshold, the LR+for the BCA assay does achieve statistical significance for severe hypertension (LR+:1.51 95% CI 0.99-2.28) and for birthweight&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10th percentile (LR+:1.72 95% CI 1.11-2.66). For the Bradford assay at the 300 mg/24 hour threshold, the LR+does achieve statistical significance for birthweight&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10th percentile (LR+:1.71 95% CI 1.41-4.31). However, at the 500 mg/24 hour threshold, the LR+is significant for severe hypertension (LR+:2.15 95% CI 1.07-4.34), birthweight&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10th percentile (LR+:2.79 95% CI 1.4-5.54) and biochemical disease (LR+:2.47 95% CI 1.22-5.01). This study suggests that thresholds for proteinuria need to be higher (possibly&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=0.5 g/24 hours) and there is the need for a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;gold standard&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; proteinuria assay against which all other measures of quantification can be assessed.
We undertook this study to determine the accuracy and reliability of patient initiated blood pres... more We undertook this study to determine the accuracy and reliability of patient initiated blood pressure measurement and recording. We recruited 72 women from the antenatal hypertension clinic in a university teaching hospital. All were at high risk for preeclampsia and were asked to measure and record their blood pressure three times per day at home using a validated blood pressure device with an internal memory. From 979 measurements taken only 28 (2.9% were inaccurate). The inaccurate readings were restricted to three women. On further questioning two women admitted that the device had been used by other family members thus making comparison with the memory impossible. Thus the true nonconcordance rate amongst participants was 1/72 (1.4%). We conclude that blood pressure recordings taken and documented by high-risk women at home are accurate. This allows more frequent measurements to be taken without the inconvenience of additional visits to hospital and may therefore lead to the earlier detection of preeclampsia.
Previous experiments have demonstrated the stable expression of factor IX (FIX) protein in mice a... more Previous experiments have demonstrated the stable expression of factor IX (FIX) protein in mice and canine models of hemophilia B following portal vein gene transfer with a recombinant adeno-associated virus (rAAV) vector encoding FIX. Here, we present the results of studies that further optimized the rAAV vector transgene cassette used to express FIX and explored the use of the less-invasive intravenous (i.v.) route of vector administration for the treatment of hemophilia B. First, a liver-specific promoter was evaluated in conjunction with cis-acting regulatory elements in mice. Constructs that included both the beta-globin intron and the woodchuck hepatitis virus post-transcriptional regulatory element resulted in the highest level of FIX expression in vivo. Using this optimized vector, we demonstrate that i.v. injection was feasible for hepatic gene transfer in mice, achieving 70-80% of portal vein expression levels of FIX. In further studies using the Chapel Hill strain of hemophilia B dogs, we demonstrate for the first time FIX expression and partial correction of the bleeding disorder following i.v. administration of an AAV vector.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2001
The early detection of pre-eclampsia is a major challenge in obstetric care. We report a case whe... more The early detection of pre-eclampsia is a major challenge in obstetric care. We report a case where pre-eclampsia was detected by home blood pressure monitoring between routine antenatal visits. This novel management approach allows early diagnosis and optimises antenatal care in fulminating disease. #
Pre-eclampsia remains a leading cause of maternal death, with 72% of pre-eclampsia cases associat... more Pre-eclampsia remains a leading cause of maternal death, with 72% of pre-eclampsia cases associated with substandard care. 1 One in 10 pregnant women develop partial signs or symptoms (73 000 a year in the United Kingdom); about 20% of these progress to pre-eclampsia. 2 3 This article summarises recommendations from the Pre-Eclampsia Community Guideline (PRECOG) Group 4 under the auspices of the charity Action on Pre-eclampsia. The recommendations cover the assessment of women with suspected pre- ...
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