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Norman J.E.,Queens Medical Research Institute | Shennan A.,Stthomas Hospital | Bennett P.,Imperial College London | Robson S.,Newcastle University | And 6 more authors.
BMC Pregnancy and Childbirth | Year: 2012

Background: Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the " progesterone" group having a lower incidence of preterm birth.Methods/Design: The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 - 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites.Discussion: OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome.Trial registration: ISRCTN14568373. © 2012 Norman et al.; licensee BioMed Central Ltd.


Wang Y.,University of Illinois at Urbana - Champaign | Fruhwirth G.,Stthomas Hospital | Cai E.,University of Illinois at Urbana - Champaign | Ng T.,King's College London | Selvin P.R.,University of Illinois at Urbana - Champaign
Nano Letters | Year: 2013

Quantum dots are promising candidates for single molecule imaging due to their exceptional photophysical properties, including their intense brightness and resistance to photobleaching. They are also notorious for their blinking. Here we report a novel way to take advantage of quantum dot blinking to develop an imaging technique in three-dimensions with nanometric resolution. We first applied this method to simulated images of quantum dots and then to quantum dots immobilized on microspheres. We achieved imaging resolutions (fwhm) of 8-17 nm in the x-y plane and 58 nm (on coverslip) or 81 nm (deep in solution) in the z-direction, approximately 3-7 times better than what has been achieved previously with quantum dots. This approach was applied to resolve the 3D distribution of epidermal growth factor receptor (EGFR) molecules at, and inside of, the plasma membrane of resting basal breast cancer cells. © 2013 American Chemical Society.


Polygerinos P.,King's College London | Ataollahi A.,King's College London | Schaeffter T.,Stthomas Hospital | Razavi R.,Stthomas Hospital | And 3 more authors.
IEEE Transactions on Biomedical Engineering | Year: 2011

This paper presents a novel, magnetic resonance imaging (MRI)-compatible, force sensor suitable for cardiac catheterization procedures. The miniature, fiber-optic sensor is integrated with the tip of a catheter to allow the detection of interaction forces with the cardiac walls. The optical fiber light intensity is modulated when a force acting at the catheter tip deforms an elastic element, which, in turn, varies the distance between a reflector and the optical fiber. The tip sensor has an external diameter of 9 Fr (3 mm) and can be used during cardiac catheterization procedures. The sensor is able to measure forces in the range of 0-0.85 N, with relatively small hysteresis. A nonlinear method for calibration is used and real-time MRI in vivo experiments are carried out, to prove the feasibility of this low-cost sensor, enabling the detection of catheter-tip contact forces under dynamic conditions. © 2006 IEEE.


Patel M.X.,King's College London | Bowskill S.,King's College | Couchman L.,King's College | Lay V.,King's College | And 3 more authors.
Journal of Clinical Psychopharmacology | Year: 2011

Olanzapine therapeutic drug monitoring (TDM) is the measurement of plasma olanzapine to assess adherence and guide dosage. We have audited data from an olanzapine TDM service, 1999-2009. Multiple linear regression analysis was conducted to investigate the contribution of dose, age, sex, body weight, and smoking status to the plasma olanzapine concentration. There were 5856 samples from 3207 patients. The prescribed olanzapine dosage was 2.5 to 95 mg/d. No olanzapine was detected in 6% of samples. For olanzapine dosages of 2.5 to 20 mg/d, only 35% of results were within a suggested target range of 20 to 39 ng/mL. At doses above 20 mg/d, 30% to 59% of results were 60 ng/mL or greater depending on dose band. In patients aged 17 years or younger (92 samples), median plasma olanzapine was higher than that in adult patients at almost all olanzapine doses. Multiple linear regression analysis of results from 627 adults from whom complete data were available showed that dose, smoking status, sex, age, and body weight together explained 24% the variance in plasma olanzapine. Degree of adherence, timing of sample postdose, drug-drug interactions, and pharmacogenetic factors also may have contributed to the observed variance. However, it is clear that female nonsmokers had higher plasma olanzapine concentrations for a given dose than male smokers. Olanzapine TDM is useful in assessing adherence and may have a role in limiting olanzapine dosage to minimize the risk of long-term toxicity. © 2011 Lippincott Williams & Wilkins.


Poston L.,King's College London | Poston L.,Stthomas Hospital
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2010

Children born to mothers, rather than to fathers, with type 1 diabetes (type 1 DM) or type 2 diabetes (type 2 DM) may have a greater susceptibility to diabetes and obesity in later life, inferring a role for in utero or early post-natal influences on the developing child. This review summarises the studies contributing to this hypothesis, noting some of the controversies including the potential for residual confounding and the influence of maternal BMI. Animal models demonstrate that maternal hyperglycaemia leads to persistent disorders of offspring pancreatic b cell secretory capacity, abnormal insulin signaling in insulin-sensitive tissues and abnormal development of the hypothalamus, associated with aberrant control of energy regulation and obesity in adult life. Prospective studies, particularly follow-up of children born to diabetic mothers participating in RCTs of improved glycemic control are needed to accurately assess the transgenerational influences of maternal diabetes and to evaluate mechanisms inferred from animal data. © 2010 Elsevier Ltd. All rights reserved.


Dennis M.,University of Edinburgh | Sandercock P.,University of Edinburgh | Reid J.,Borders General Hospital | Graham C.,University of Edinburgh | And 4 more authors.
Stroke | Year: 2013

Background and Purpose-Most randomized controlled trials of venous thromboembolism prophylaxis have focused on reduction of deep vein thrombosis, predominantly asymptomatic deep vein thrombosis, detected on imaging. We aimed to estimate the effects of graduated compression stockings on venous thromboembolism events, survival, and functional status at 6 months after stroke. Methods-The CLOTS Trials adopted an international multicentre, parallel group design, with central randomization and a 1:1 treatment allocation. In CLOTS Trial 1, 2518 immobile stroke patients were allocated thigh-length graduated compression stockings or not, and in CLOTS trial 2, 3014 to thigh-length or below-knee graduated compression stockings. We measured vital status, Oxford Handicap Scale, and quality of life (EQ5D-3 L) at 6 months. Results-We compared survival in patients enrolled in Trials 1 and 2 with a Cox proportional hazards model, including variables included in our minimization algorithm. In both trials, allocation to thigh-length graduated compression stockings was associated with a very slight, but nonsignificant, increased hazard of death in the first 6 months (Trial 1: hazard ratio, 1.087; 95% confidence interval, 0.913-1.295; and Trial 2: hazard ratio, 1.037; 95% confidence interval, 0.892-1.205). There were no statistically significant differences in venous thromboembolism events, Oxford Handicap Scale, or EQ5D-3 L between the treatment groups in CLOTS Trials 1 or 2. Conclusions-Although underpowered to detect clinically important effects on long-term outcomes, our results effectively exclude a >10% relative reduction in the hazard of death within 6 months associated with the use of thigh-length stockings. No other long-term benefits were apparent. © 2013 American Heart Association, Inc.


Sivasubramaniyam S.,Stthomas Hospital
CPD Bulletin Clinical Biochemistry | Year: 2012

Adipose tissue is a highly specialised connective tissue consisting mainly of lipid-filled adipocytes but also contains a variety of stromal-vascular cells. It was traditionally viewed as a limitless reservoir for energy storage that also provides thermal insulation and mechanical padding. This view changed in the early 90's following the discovery of leptin and its extensive physiological and pathophysiological endocrine functions. This provided the blue print for the subsequent identification of a wide array of other adipose derived hormones known as adipokines. Hence, adipose tissue is now widely accepted to have additional endocrine functions. This review aims to explore the most important and well understood adipokines - leptin, adiponectin, resistin and retinol binding protein 4. In this review the structure of the adipokines, their receptors, control of secretion, physiological and pathophysiological functions as well any clinical significance and potential for pharmacological modulation will be explored.


Clarke R.E.J.,Stthomas Hospital
CPD Bulletin Clinical Biochemistry | Year: 2012

Clinical demand for vitamin D measurement is increasing as additional biological effects are postulated for vitamin D, and in light of the significant level of deficiency that has been found in many populations. The measurement of vitamin D is complicated by the multiple metabolites present in serum and the various assays available. This review briefly explores the main issues regarding 25-hydroxyvitamin D measurement and the problems encountered. In particular the measurement of 25-hydroxyvitamin D2 and D3, the use of exogenously spiked calibrators and the role of vitamin D binding protein are discussed. The advantages and disadvantages of the main methods used are summarised especially automated immunoassays and liquid chromatography mass spectrometry. © 2012 Rila Publications Ltd.


Davies K.,Stthomas Hospital | Allan L.,Stthomas Hospital | Roblin P.,Stthomas Hospital | Ross D.,Stthomas Hospital | Farhadi J.,Stthomas Hospital
Breast | Year: 2011

Skin sparing mastectomy (SSM) followed by immediate breast reconstruction (IBR) is not only oncologically safe but provides also significant benefits both cosmetically and functionally. The superiority of this technique can only be fully established, however, by developing a framework for minimising complications. The present study seeks to elucidate the key factors affecting outcome. Methods: Data for all skin sparing mastectomies with immediate autologous and implant based reconstructions, performed in a three year period (2006-2008) was retrospectively collated. Complications were classified into major and minor. Patients were excluded who had flap loss due to vascular complications. Results: The total number analysed was 151. 17.2% had major complications, 23% had minor and 61% had no complications. The Wise and the " tennis" incision had significantly higher rates of wound dehiscence when compared with the periareolar incision (p = 0.025, p = 0.098). There was no significant difference between diathermy or blade dissection techniques, or the use of subcutaneous adrenaline infiltration. Increasing BMI was associated with increased skin flap necrosis and wound dehiscence, and an excised breast mass of greater than 750 g and a sternal notch to nipple length of greater than 26 cm are associated as well with increased flap-related complications (p = 0.0002, p = 0.0049). Conclusion: Factors such as Wise pattern and tennis racquet incision, BMI and breast mass and sternal notch to nipple length adversely affect skin sparing mastectomy flap morbidity. These factors should be factored in to patient selection and operative planning especially for obese and large breasted women undergoing skin sparing mastectomy with immediate breast reconstruction. © 2010 Elsevier Ltd.


PubMed | Stthomas Hospital
Type: Journal Article | Journal: Breast (Edinburgh, Scotland) | Year: 2011

Skin sparing mastectomy (SSM) followed by immediate breast reconstruction (IBR) is not only oncologically safe but provides also significant benefits both cosmetically and functionally. The superiority of this technique can only be fully established, however, by developing a framework for minimising complications. The present study seeks to elucidate the key factors affecting outcome.Data for all skin sparing mastectomies with immediate autologous and implant based reconstructions, performed in a three year period (2006-2008) was retrospectively collated. Complications were classified into major and minor. Patients were excluded who had flap loss due to vascular complications.The total number analysed was 151. 17.2% had major complications, 23% had minor and 61% had no complications. The Wise and the tennis incision had significantly higher rates of wound dehiscence when compared with the periareolar incision (p=0.025, p=0.098). There was no significant difference between diathermy or blade dissection techniques, or the use of subcutaneous adrenaline infiltration. Increasing BMI was associated with increased skin flap necrosis and wound dehiscence, and an excised breast mass of greater than 750g and a sternal notch to nipple length of greater than 26cm are associated as well with increased flap-related complications (p=0.0002, p=0.0049).Factors such as Wise pattern and tennis racquet incision, BMI and breast mass and sternal notch to nipple length adversely affect skin sparing mastectomy flap morbidity. These factors should be factored in to patient selection and operative planning especially for obese and large breasted women undergoing skin sparing mastectomy with immediate breast reconstruction.

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