Keyhole vs Open Surgery For Ruptured Abdominal Aortic Aneurysm

MedicalResearch.com Interview with:

ruptured Abdominal Aortic Aneurysm as seen on CT- Wikipedia James Heilman, MD

A ruptured abdominal aortic aneurysm  as seen on CT

 

 

Professor JT Powell PhD, MD, FRCPath
Faculty of Medicine,
Department of Surgery & CancerImperial College London

 

 

 

MedicalResearch.com: What is the background for this study?

Response: The mortality from ruptured abdominal aortic aneurysm (AAA) remains very high causing about 6000 deaths each year in the UK.  The only hope for survival is an emergency operation to repair the burst aorta.  Even so the mortality may be as high as 45% within a month of repair using open surgery.

It has been suggested that minimally invasive repair using keyhole or endovascular techniques would lower the mortality to about 25% within a month of repair.  However not all shapes of aorta are suitable for endovascular repair (also called EVAR).

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Diagnostic Accuracy of FFR-CT Varies Across Spectrum of Coronary Artery Disease

MedicalResearch.com Interview with:
Dr Christopher Michael Cook MBBS Bsc(Hons) MRCP

MRC Clinical Research Fellow
NHLI, Cardiovascular Medicine, Imperial College London 

MedicalResearch.com: What is the background for this study?

Response: FFR-CT is a novel non-invasive technique for estimating the functional significance of a coronary stenosis from CT coronary angiography images. A number of meta-analyses already exist for determining the diagnostic accuracy of FFR-CT (compared to invasive FFR as the reference standard). However, although knowing the overall diagnostic accuracy of FFR-CT is reassuring, in clinical practice a clinician knows not only whether the FFR-CT is positive or negative, but also its actual value. The purpose of this study was to provide clinicians a means of interpreting the diagnostic accuracy of any individual FFR-CT result that may be received in clinical practice.

MedicalResearch.com: What are the main findings?

Response: The main finding of this study is that the diagnostic accuracy of FFR-CT varies markedly across the spectrum of disease. For vessels with FFR-CT above 0.90, 98% met the invasive FFR guideline criterion for deferral. At the other end of the spectrum, for vessels with FFR-CT below 0.60, 86% met the invasive FFR guideline criterion for stenting. However, in between, FFR-CT gives less certainty as to whether the invasive FFR will meet the stenting criterion or not.

MedicalResearch.com: What should readers take away from your report?

Response: Readers can combine the findings of our study with patient specific factors in order to judge when the cost and risk of an invasive angiogram may safely be avoided. Because we now have a more complete picture of what different levels of FFR-CT mean in terms of invasive FFR, it is apparent that a single cut-off value for FFR-CT in deciding on invasive coronary angiography need not always apply. For example, in the asymptomatic patient, further investigations may not be desirable even if an FFR-CT still left a substantial possibility of a positive invasive FFR. Conversely, in the symptomatic patient, the patient and clinician would likely pursue invasive angiography unless the possibility of a positive FFR is very remote.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This study adopted novel methodology to ascertain the probability that both FFR-CT and invasive FFR agreed on the functional classification of a stenosis, for any given individual FFR-CT value. This type of analysis could be used to determine if further iterative versions of the FFR-CT software translate into improved diagnostic performance, particularly in more intermediate disease severities. 

MedicalResearch.com: Is there anything else you would like to add?

Response:

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Cook CM, Petraco R, Shun-Shin MJ, Ahmad Y, Nijjer S, Al-Lamee R, Kikuta Y, Shiono Y, Mayet J, Francis DP, Sen S, Davies JE. Diagnostic Accuracy of Computed Tomography–Derived Fractional Flow Reserve A Systematic Review . JAMA Cardiol. Published online May 24, 2017. doi:10.1001/jamacardio.2017.1314

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

 

 

iFR Can Assess Need For Coronary Revascularization Without Adenosine

MedicalResearch.com Interview with:

Dr. Justin Davies PhD Senior Reserch Fellow and Hononary Consultant Cardiologist National Heart and Lung Institute, Imperial College Londo

Dr. Davies

Dr. Justin Davies PhD
Senior Reserch Fellow and Hononary Consultant Cardiologist
National Heart and Lung Institute,
Imperial College London

MedicalResearch.com: What is the background for this study?

Response: We know from the FAME study that compared to angiography alone, FFR guided revascularization improves long-term clinical outcomes for our patients. Despite this, adoption of FFR into everyday clinical practice remains stubbornly low. One major factor for this is the need for adenosine (or other potent vasodilator medications) in order to perform an FFR measurement. Adenosine is expensive, unpleasant for the patient, time consuming and even potentially harmful.

iFR is a newer coronary physiology index that does not require adenosine for its measurement. In the prospective, multi center, blinded DEFINE FLAIR study, 2492 patients were randomly assigned to either FFR guided revascularisation or iFR guided revascularization and followed up for a period of 1 year.
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11 Cancer Types Have Strong Connection to Obesity

MedicalResearch.com Interview with:

Dr Maria Kyrgiou MSc, PhD, MRCOG Clinical Senior Lecturer & Consultant in Gynaecologic Oncology IRDB - Department of Surgery and Cancer, Imperial College London West London Gynaecological Cancer Centre, Queen Charlotte's & Chelsea-Hammersmith Hospital, Imperial Healthcare NHS Trust

Dr. Kyrgiou

Dr Maria Kyrgiou MSc, PhD, MRCOG
Clinical Senior Lecturer & Consultant in Gynaecologic Oncology
IRDB – Department of Surgery and Cancer, Imperial College London
West London Gynaecological Cancer Centre, Queen Charlotte’s & Chelsea-Hammersmith Hospital, Imperial Healthcare NHS Trust 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Obesity has become a major public health challenge and it’s prevalence worldwide has more than doubled amongst women n the last four decadesExcess body weight has been associated with an increased risk of developing and dying from numerous cancers. Although the reported associations may be potentially causal, some of the associations may be flawed due to inherent study biases such as residual confounding and selective reporting of positive results.

We included 204 meta-analyses investigating associations between adiposity and the development or death from 36 primary cancers and their sub-types. Adiposity was associated with a higher risk of developing esophageal adenocarcinoma, gastric cardia, colon and rectal cancer in men, biliary tract system, pancreatic, postmenopausal breast among HRT non-users, endometrial, ovarian, and kidney cancer and multiple myeloma.

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Allergic Rhinitis: Three Years of Immunotherapy Gives Longer Lasting Symptom Control

MedicalResearch.com Interview with:
Stephen R. Durham, MD

Imperial College, London, and Royal Brompton and Harefield Hospitals
NHS Foundation Trust
London, United Kingdom

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Allergic rhinitis affects 1 in 4 the UK population and may compromise sleep and work/school performance and be associated with bronchial asthma. When nasal steroids and antihistamines do not work or cause side effects, allergen immunotherapy is an alternative. Immunotherapy using high doses of grass pollen allergen as monthly injections or daily tablets under the tongue are highly effective. Treatment for 3 years not only gives sustained improvement on treatment but also long-term benefits and disease remission for at least 2-3 years after stopping treatment.

This single centre study at Imperial College London and Royal Brompton Hospital London included 106 adults with severe Hayfever followed up for 3 years, 2 years on treatment and 1 year after stopping treatment. In this double-blind trial, 3 randomised groups took sublingual immunotherapy, subcutaneous immunotherapy and placebo treatment. 92 completed the trial. Results showed that 2 years treatment with both modalities did not result in persistent benefit at year 3, although the researchers found that both treatments were effective compared to placebo during years 1 and 2.

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Handful of Nuts a Day Can Reduce Chronic Diseases

MedicalResearch.com Interview with:

Dr. Dagfinn Aune Department of Epidemiology and Biostatistics School of Public Health Imperial College London St. Mary's Campus London  UK

Dr. Dagfinn Aune

Dr. Dagfinn Aune
Department of Epidemiology and Biostatistics
School of Public Health
Imperial College London
St. Mary’s Campus London  UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is a growing body of evidence suggesting that intake of nuts may reduce the risk of coronary heart disease, but the relation between nut intake and other diseases like cancer and stroke, and the relation with mortality and less common causes of death is not clear. Also it is not clear how much nuts are needed to reduce the risk.

So our current meta-analysis reviewed the data from 20 studies (29 publications) on nut intake and different health outcomes. We found that a nut intake of approximately one serving per day (28 g/d or a handful) was associated with a reduced risk of coronary heart disease (by 30%), total cancer (15%), all-cause mortality (22%) and mortality from respiratory disease (50%), diabetes (40%), and infections (75%), although there were few studies in the latter three analyses. We found that most of the benefit was observed up to an intake of around 20 grams per day. Similar results were found for total nuts, tree nuts and peanuts (which are botanically defined as legumes), but peanuts were also associated with reduced risk of stroke, while only tree nuts were associated with reduced cancer risk. We also calculated the number of deaths that potentially could be avoided, under the assumption that the observed associations are causal, and arrived at 4.4 million deaths in North and South America, Europe, Southeast Asia and the Western Pacific (unfortunately we did not have data on nut intake from West Asia and Africa so we were not able to include those areas).

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Cancer Drugs, Survival and Ethics

MedicalResearch.com Interview with:

Peter Wise MD Charing Cross Hospital and Imperial College School of Medicine London, UK

Dr. Peter Wise

Peter Wise MD
Charing Cross Hospital and
Imperial College School of Medicine
London, UK

MedicalResearch.com: What is the background for this analysis?

Response: As a medical ethicist, I wished to know how much patients with advanced – metastatic – cancer knew about the drugs that were being used to treat it. What were their perceptions of likely treatment success and how did that tally with our knowledge of what drugs could actually achieve – and at what cost to the body and to the pocket. Did patients actually have a choice – and how did the drugs get approved for use in the first place?

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New Ibuprofen Formulation May Avoid Cardiac Side Effects

MedicalResearch.com Interview with:

Dr Nicholas Kirkby BHF Intermediate Fellow | Vascular Biology National Heart & Lung Institute | Imperial College London London

Dr Nicholas Kirkby

Dr Nicholas Kirkby
BHF Intermediate Fellow | Vascular Biology
National Heart & Lung Institute | Imperial College London
London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We know drugs like ibuprofen, called ‘non-steroidal anti-inflammatory drugs’ cause an increase in the risk of heart attacks. These side effects cause very real concerns for the many millions of people who rely on them. They are also the reason why there are no new drugs in this class and why they have been withdrawn (2011) for use as a preventative treatment for colon cancer. Previous research from our group suggests that L-arginine supplements may prevent the cardiovascular side effects caused by these drugs. Our findings here suggest that a particular formulations of ibuprofen, called ibuprofen arginate, which is already available in many parts of the world, can act like an L-arginine supplement and that this could potentially protect the cardiovascular system.

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Digital Mobile Technology Gives Some Arm Function To Stroke Patients

MedicalResearch.com Interview with:

Dr Paul Bentley MA MRCP PhD Clinical Senior Lecturer in Clinical Neuroscience Honorary Consultant Neurologist Neurology Dept Imperial College NHS Healthcare Trust Charing Cross Hospital London

Dr Paul Bentley

Dr Paul Bentley MA MRCP PhD
Clinical Senior Lecturer in Clinical Neuroscience
Honorary Consultant Neurologist
Neurology Dept
Imperial College NHS Healthcare Trust
Charing Cross Hospital
London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: gripAble was designed to help people with arm disability practise physiotherapy when a physiotherapist is not available, or in between physiotherapy sessions. We know that the amount of physiotherapy provision in the UK, after stroke or arm injury, is typically below that which is recommended by professional bodies. Furthermore, increasing research suggests that higher-intensity training can boost functional outcomes. The innovation was designed to help people with a range of disabilities including severe paralysis engage with computer games with their weak arm. At the same time its designed to be portable for use at home or in bed, and low-cost.

gripAble also enables remote measurement and monitoring of arm function, by setting users a series of calibrated tasks played out on the tablet screen. This way doctors and physiotherapists can assess the needs of a patient, and gain an idea of how well a patient is responding to home physiotherapy.

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People In Most Countries Have Gotten Taller Over Last Century

MedicalResearch.com Interview with:

Prof. Majid Ezzati, PhD Faculty of Medicine, School of Public Health Chair in Global Environmental Health Imperial College, London Adjunct Professor of Global Health and Department of Global Health and Population Harvard T.H. Chan School of Public Health

Prof. Majid Ezzati

Prof. Majid Ezzati, PhD
Faculty of Medicine, School of Public Health
Chair in Global Environmental Health
Imperial College, London
Adjunct Professor of Global Health and
Department of Global Health and Population
Harvard T.H. Chan
School of Public Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Human height is strongly influenced by the environment that we grow up in, from pregnancy through to late adolescence. If we have good nutrition, few illnesses and good healthcare, we are more likely to grow taller. In turn, height has a strong effect on our health in adulthood. Taller people on average live longer, have lower risk of heart disease (although they do have slightly elevated risks of some cancers).

We have collated the largest-ever database of height. We analysed 1472 studies with measured height on 18.6 million individuals. We made estimates of height for 18-year-old men and women from 1914 and 2014. Height has increased in every country in the world, but this has been very uneven. The tallest men in the world are now the Dutch, and the tallest women are the Latvians. The countries that have seen the most growth are South Korea for women and Iran for men. We have seen large increases in height in East Asia, and stagnation in much of the West over the last few decades. In parts of Africa height has actually decreased by 5-10 cm over this period.

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Role of microRNAs in Driving Breast and Lung Cancer Metastases Identified

MedicalResearch.com Interview with:

Dr Olivier E Pardo PhD Team Leader Imperial College Division of Cancer Hammersmith Hospital London UK

Dr. Olivier Pardo

Dr Olivier E Pardo PhD
Team Leader
Imperial College
Division of Cancer
Hammersmith Hospital
London UK 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Pardo: Metastatic dissemination, the ability of tumour cells to go and colonise organs distant from the primary disease site, is the principal cause for failing to cure patients with cancer. This is particularly true in the case of breast cancer where resection of local disease offers good chances of cure but metastatic dissemination that may appear at a later stage carries very poor prognosis. Surgical resection is also the only true curative strategy for localised lung cancer. Hence, a better understanding of the mechanisms controlling the dissemination of tumour cells is likely to propose novel targets for combination therapy that will improve the survival of cancer patients.

Here, we showed that an enzyme, named MARK4, controls the ability of lung and breast cancer cells to move and invade. When we lower MARK4 levels, it prevents cancer cells from moving by changing their internal architecture, making them unfit to invade. Consequently, these cells were unable to efficiently form metastasis in mouse cancer models. Confirming the role of this enzyme in cancer, we show that breast and lung cancer patients with increased levels of MARK4 in their tumours have poorer prognosis.

We found that what controls the levels of MARK4 in cells is miR-515-5p, a small oligonucleotide sequence called a microRNA. When present in the cells, miR-515-5p prevents the expression of MARK4. Incidentally, the loss of miR-515-5p correlates with increased metastasis and poorer prognosis in mouse cancer models and patients, respectively.

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Vaginal Seeding After C-Section Can Transfer Harmful Germs To Baby

MedicalResearch.com Interview with:

Dr. Aubrey Cunnington Faculty of Medicine, Department of Medicine Clinical Senior Lecturer Imperial College, London

Dr. Aubrey Cunnington

Dr. Aubrey Cunnington
Faculty of Medicine, Department of Medicine
Clinical Senior Lecturer
Imperial College, London

Medical Research: What is the background for this study? What are the main findings?

Dr. Cunnington: We noticed that increasing numbers of women who were having Caesarean section deliveries at our hospitals were requesting for their vaginal fluid to be swabbed onto their babies after birth – a process often termed “vaginal seeding”. The idea behind this, is that it transfers all the natural bacteria (microbiota) from the mother’s vagina to the baby. We know that early on in life, babies born by Caesarean section have different bacteria living on their bodies and in their guts to those of babies born by vaginal delivery. Some people think these differences in the microbiota may be responsible for differences in long-term health, although a causal link is unproven. The hope is that vaginal seeding might reduce the risk of the baby developing some diseases like obesity and asthma in the future. Unfortunately we are a long way from having the evidence to show that this is possible, and we do not know whether vaginal seeding is really safe. Babies born by elective Caesarean section are at lower risk of transfer of some potentially harmful bacteria and viruses from the birth canal, but these harmful bacteria and viruses could be transferred to the baby on a swab and potentially cause a devastating infection.

MedicalResearch.com Editor’s note:  ‘Vaginal Seeding’ is also known as “microbirthing”,   

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Harmful Effects of Air Pollution Can Last Decades

MedicalResearch.com Interview with:

Dr Rebecca Ghosh, Research Associate Small Area Health Statistics Unit (SAHSU) MRC-PHE Centre for Environment and Health Imperial College London St Mary's Campus, Norfolk Place, Londo

Dr. Rebecca Ghosh

Dr Rebecca Ghosh, Research Associate 
Small Area Health Statistics Unit (SAHSU)
MRC-PHE Centre for Environment and Health
Imperial College London
St Mary’s Campus, Norfolk Place, London 

Medical Research: What is the background for this study? What are the main findings?
Dr. Ghosh: Since the 1950s a lot of evidence has accumulated that high levels of air pollution cause harmful effects on health.  However there is limited evidence on the very long term (>25 years) effects of air pollution.  Our study is one of the longest running to date looking at air pollution and mortality, following 368,000 people in England and Wales for 38 years.  We estimated air pollution exposures throughout England & Wales for 1971, 1981, 1991 and 2001 using data from historic air pollution monitoring networks, the first time this has been done.

We found that air pollution exposure in 1971 was still associated with a small increased risk of death in 2002-9, over 30 years later, suggesting that harmful effects of air pollution are extremely long-lasting.  However, risks from an individual’s past exposures waned over time and their more recent exposures gave the highest mortality risks.

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Selective Targeting Can Improve Deep Brain Stimulation For Parkinson’s

Dr. Ilse S. Pienaar Honorary Lecturer in Neuroscience at Imperial College London (& Snr. Lecturer in Cellular Pathology, Northumbria University) Centre for Neuroinflammation & Neurodegeneration Division of Brain Sciences Faculty of Medicine Imperial College London Hammersmith Hospital Campus London United KingdomMedicalResearch.com Interview with:
Dr. Ilse S. Pienaar

Honorary Lecturer in Neuroscience at Imperial College London
(& Snr. Lecturer in Cellular Pathology, Northumbria University)
Centre for Neuroinflammation & Neurodegeneration
Division of Brain Sciences Faculty of Medicine
Imperial College London
Hammersmith Hospital Campus
London United Kingdom

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Pienaar: A highly heterogeneous brainstem structure, the pedunculopontine nucleus (PPN) has been deemed a promising target for the delivery of deep-brain stimulation (DBS), to alleviate aspects of Parkinson’s disease (PD), especially gait and postural instability. However, optimal therapeutic targeting of the PPN has been hampered due to DBS being unable to discriminate between cell types being targeted. We optomised a novel technique, Designer Receptors Exclusively Activated by Designer Drugs (DREADD) in a rat model of PD, by which to target only the PPN cholinergic neurons. A series of behavioral tests revealed that selective stimulation of the PPN cholinergics completely reverses gait problems and postural instability in the PD rats.

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Hospital Autopsy Rate Drops To Near Zero

Mr. Angus Turnbull Imperial College School of Medicine, London UKMedicalResearch.com Interview with:
Mr. Angus Turnbull
Imperial College School of Medicine,
London UK

Medical Research: What is the background for this study? What are the main findings?

Mr. Turnbull: Autopsy has been used to advance medical knowledge and understanding of pathological processes for millennia but increasing evidence indicates its decline in the UK and elsewhere. This study not only confirms that but suggests autopsy for learning purposes has almost disappeared.

In the United Kingdom autopsy is divided into medico-legal autopsy (that required by law under the jurisdiction of HM Coroner) and consented autopsy (performed with the consent of the bereaved or their family). Over the past half-century, small single site studies have noted a marked decline in consented autopsy rates, however there has been no study for over 20 years to determine the extent of the decline nationwide.

This study examined all acute NHS Trusts within England, NHS Boards in Scotland and Wales and Social Care Trusts in Northern Ireland. We found that the average autopsy rate (the percentage of adult inpatient deaths which under go consented autopsy) in the United Kingdom in 2013 was only 0.7%. The study showed that in nearly a quarter (23%) of all NHS Trusts in the United Kingdom, consented autopsy is now extinct.

These findings may have implications for training, for research and for learning from mortality – a key aspect of patient safety. Continue reading

Dietary Fiber May Reduce Risk Of Diabetes

Dagfinn Aune, PhD student Norwegian University of Science and Technology and Imperial College LondonMedicalResearch.com Interview with:
Dagfinn Aune, PhD student
Norwegian University of Science and Technology and
Imperial College London

Medical Research: What is the background for this study? What are the main findings?

Response: There are more than 360 million people worldwide that are affected by diabetes, and this number is projected to increase to more than 550 million by 2030, with serious consequences for the health and economy of both developed and developing countries. While previous research has found an association between increased dietary fibre intake and a reduced risk of developing type 2 diabetes, most of these data come from the United States, and amounts and sources of fiber intake differ substantially between countries. In this article the we evaluated the associations between total fiber as well as fiber from cereal, fruit, and vegetable sources, and new-onset type 2 diabetes in a large European cohort across eight countries, in the EPIC-InterAct Study (and included 12403 type 2 diabetes cases and 16835 sub-cohort members). We also conducted a meta-analysis where we combined the data from this study with those from 18 other independent studies from across the globe.

We found that participants with the highest total fiber intake (more than 26 g/day) had an 18% lower risk of developing diabetes compared to those with the lowest total fiber intake (less than 19g/day), after adjusting for the effect of other lifestyle and dietary factors. When the results were adjusted for body mass index (BMI) as a marker of obesity, higher total fiber intake was found to be no longer associated with a lower risk of developing diabetes, suggesting that the beneficial association with fiber intake may be mediated at least in part by BMI. In other words, dietary fiber may help people maintain a healthy weight, which in turn reduces the chances of developing type 2 diabetes.

In a meta-analysis of the EPIC-InterAct study and 18 other independent studies (>41000 type 2 diabetes cases) we found that the risk was reduced by 9% for each 10 g/day increase in total fiber intake and 25% for each 10 g/day increase in cereal fiber intake. There was no statistically significant association between fruit or vegetable fiber intake and diabetes.

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Do Intra-aortic Balloon Pumps Improve Heart Attack Survival?

intra-aortic balloon pump, WikipediaMedicalResearch.com Interview with:
Sayan Sen, PhD

International Centre for Circulatory Health, National Heart and Lung Institute
Imperial College London
London, United Kingdom

Medical Research: What is the background for this study? What are the main findings?

Dr. Sayan Sen: Intra-aortic balloon pumps (IABP) are often used in Acute Myocardial Infarction, particularly in patients with cardiogenic shock. We analysed the available Randomized Controlled Trials (RCT) and observational studies, spanning 30 years, to establish the evidence for this use.

There is no identifiable group of patients with Acute Myocardial Infarction that have been demonstrated to derive a mortality benefit from insertion of an IABP. The studies, including over 17000 patients, have studied mortality in patients receiving IABP in comparison to mortality of patients that received no IABP in the era of no reperfusion, fibrinolysis and primary percutaneous intervention.  This lack of mortality reduction with IABP in AMI is consistent in patients with and without cardiogenic shock across both RCTs and observational studies; questioning the continued use of this technology in Acute Myocardial Infarction.

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Test Can Help Predict Toxic Reactions To New Medications

Professor Jane A. Mitchell Head of Vascular Biology Section Head of Cardiothoracic Pharmacology National Heart and Lung Institute, Institute of Cardiovascular Medicine & Science,    Imperial College, LondonMedicalResearch.com Interview with:
Professor Jane A. Mitchell
Head of Vascular Biology Section
Head of Cardiothoracic Pharmacology
National Heart and Lung Institute,
Institute of Cardiovascular Medicine & Science,
Imperial College, London

Medical Research: What is the background for this study? What are the main findings?

Response: In 2006 a drug called TGN1412 was given to 6 healthy male volunteers as a final test for safety. The drug had passed all of the preclinical tests and showed no problem when it was given to laboratory animals. However when it was given to people it caused a catastrophic side effect known as a ‘cytokine storm response’. All 6 volunteers became sick very quickly and needed immediate hospital treatment, they nearly died and remain at risk of immune problems still. We found a way to mimic the effects of TGN1412 in the laboratory using stem cell technology to engineer two different types of cells from the same donor to be grown and mixed together in a dish. Our test is better than the current tests used because it mimics better the human body and uses cells from one individual donor.
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Zinc Isotopes May Be Breast Cancer Biomarker

Fiona Larner, PhD Postdoctoral Research Associate Department of Earth Sciences, University of Oxford, South Parks Road, Oxford, UK Department of Earth Science & Engineering, Imperial College London, Exhibition Road, South Kensington, London, UKMedicalResearch.com Interview with:
Fiona Larner, PhD
Postdoctoral Research Associate
Department of Earth Sciences, University of Oxford, South Parks Road, Oxford, UK
Department of Earth Science & Engineering, Imperial College London, Exhibition Road, South Kensington, London, UK

Medical Research: What is the background for this study? What are the main findings?

Response: Zinc has been identified to have a role in breast tissue and breast cancer for over a decade. Zinc has several isotopes (different versions of zinc due to varying numbers of neutrons), which require slightly different amounts of energy to go through biological processes. By measuring the changes in the zinc isotopic signature, we can probe it’s behaviour to a greater resolution to that currently available in medical institutions. We looked at the isotopic signatures in different tissues of healthy patients and those with breast cancer in order to understand the mechanisms involved in more detail and in search for a biomarker that uses these signatures to diagnose breast cancer.

We found that breast cancer tissue preferentially retains the lighter isotopes of zinc to a greater extent than healthy breast tissue. This means that the partnering heavy isotopes must be ejected from the cell, and may provide a biomarker for cancer in the future.

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Brain Enzyme May Regulate Appetite For Sugar

MedicalResearch.com Interview with:
Dr James Gardiner

Reader in Molecular Physiology
Imperial College Hammersmith Campus
London 0NN

Medical Research: What is the background for this study? What are the main findings?

Response: It is well known that glucose is a preferred food and is consumed in preference to other nutrients. Food intake is controlled by the brain in part this it is regulated by part of the brain called the hypothalamus.   Glucokinase is an important component of glucose sensing and is expressed in the hypothalamus and specifically in the arcuate nucleus. A hypothalamic mechanism regulating glucose intake has not previously been identified.

Using a rodent model we demonstrated that increasing glucokinase activity in the arcuate nucleus increased food intake and body weight. If glucose was available as separately then glucose intake is increased but not weight. Decreasing glucokinase activity in the arcuate nucleus had the opposite effect, reducing glucose intake when it was available.   Our results suggest that glucokinase controls glucose appetite and hence the amount of glucose consumed. This is the first time a mechanism controlling the intake of a specific nutrient has been described.

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Supplement May Reduce Cardiovascular Risks Linked to NSAIDS

MedicalResearch.com Interview with:
Dr. Jane A. Mitchell
National Heart and Lung Institute
Imperial College, London, UK

Medical Research: What is the background for this study? What are the main findings?

Dr. Mitchell: Anti-inflammatory drugs (NSAIDs) work by inhibiting the enzyme COX-2. COX-2 selective anti-inflammatory drugs, like Vioxx, were introduced to reduce gastrointestinal side effects associated with these drugs. However, COX-2 inhibitors as well as most older NSAIDs are associated with increased risk of heart attacks although the precise mechanisms underlying these side effects are not completely understood.

The main findings of this study are:

1) COX-2 is highly expressed in the kidney where its genetic deletion leads to changes in more than 1000 genes.

2) Analysis of these genes revealed changes in 2-3 specific genes that regulate levels of ADMA, an endogenous inhibitor of the nitric oxide released by vessels, that can be reversed by giving more of the substrate for NO, L-arginine.

3) Further studies showed that ADMA was indeed increased in the plasma of mice where COX-2 gene was knocked out or in normal mice given a COX-2 inhibitor.

4) In mice where COX-2 was knocked out the release of nitric oxide from vessels was reduced and this could be reversed by supply L-arginine.

5) ADMA was also increased in human volunteers taking a COX-2 inhibitor

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Controlling Insulin Release With Photoswitchable Sulfonylurea

Dr. David Hodson PhD Faculty of Medicine, Department of Medicine Imperial College LondonMedicalResearch.com: Interview with:
Dr. David Hodson PhD
Faculty of Medicine, Department of Medicine
Imperial College London

Medical Research: What is the background for this research?

Dr. Hodson: Type 2 diabetes represents a huge socioeconomic challenge. As well as causing significant morbidity due to chronically elevated glucose levels, this disease is also a drain on healthcare budgets (~$20billion in the UK per year). While current treatments are effective, they are sometimes associated with side effects, usually due to off-target actions on organs such as the heart and brain. In addition, the ability to regulate blood glucose levels more tightly may decrease complications stemming from type diabetes (e.g. nerve, kidney and retina damage). As a proof-of-principle that the spatiotemporal precision of light can be harnessed to finely guide and control drug activity, we therefore decided to produce a light-activated anti-diabetic. Continue reading