Researchers show hypnosis alters brain activity

Hypnosis is increasingly being used in clinical settings, as a way of helping people lose weight or stop smoking. The United Kingdom’s National Institute for Health and Clinical Excellence (NICE) recently approved the technique for treatment of irritable bowel syndrome, but despite such endorsements there is still a great deal of scepticism about whether there really is a hypnotic state.

New research from the University of Hull, published 12 November in Consciousness and Cognition, however shows that hypnosis is real. Psychologists have discovered that basic brain activity undergoes change when people are hypnotised.

Dr William McGeown and his colleagues in the department of Psychology and Centre for Clinical Neuroscience hypnotised university students and looked at brain activity, using functional magnetic imaging (fMRI).

The research team included Professor Irving Kirsch, a world-known expert in hypnosis, Professor Annalena Venneri, an expert in brain imaging techniques and Professor Giuliana Mazzoni, an expert in suggestion and suggestibility.

Hypnosis studies usually require participants to do a task and researchers look at their brain activity during this time. In this experiment however, students’ brain activity was monitored in the rest periods between each task. This is the first time a hypnosis study has investigated brain activity in this manner; studying participants in rest whilst they are not performing any particular task.

The participants’ brain activity was also scanned without the hypnotic induction so that the resting states in and out of hypnosis could be compared.

The researchers first tested students for their ability to respond to a range of hypnotic suggestions, including suggestions to see a cat that was not there, to hear non-existent music, and to forget what had happened to them during the hypnotic session. They then invited subjects who could respond to these suggestions, and some that could not, to have their brains examined in an fMRI scanner while under hypnosis. Hypnosis altered anterior brain activity only in those subjects who were able to respond to suggestions. These are the people who may be termed “highly suggestible”.

The study led to the unexpected finding that hypnosis decreases activity in areas of the brain that support the so called “default mode” network. Activity in this network generally occurs when people are resting, day dreaming or letting their minds wander.

Dr McGeown said: “These results are unequivocal; the changes in anterior brain activity observed in our study occurred only in highly suggestible subjects, those most open to the idea of hypnosis. By contrast, no changes in brain activity were detected in these areas in the low suggestible subjects. This shows that the changes were due to hypnosis and not just simple relaxation.”

He concluded: “Our study shows that hypnosis is real; it corresponds to a unique pattern of brain activation which was not observed in any other experimental condition and was not seen in people who were not hypnotizable.”
Carotid endarterectomy safer than carotid stenting

Dr Frans Moll, MD Professor of Vascular Surgery, University Medical Center Utrecht (Netherlands) presented a randomised comparison of carotid stenting (CAS) vs. carotid endarterecomy (CEA) in symptomatic patients to show that carotid endarterectomy (CEA) is safer than carotid stenting (CAS) at the 36th annual VEITH symposium in New York.

In a multicentre, open randomised trial with independent neurological assessment of outcome events blinded to allocated treatment, 1710 patients with recent relevant symptoms and extra cranial internal carotid artery stenosis (>50%) were randomised. Patient and lesion should be suitable for both treatments, and management discussed at a multidisciplinary meeting. Several stents were approved for use in this trial, and protection devices were recommended at discretion of interventionalist but not mandatory. Aspirin plus clopidogrel were provided prior to stenting.

Primary endpoint was the 30 day rate of any stroke, myocardial infarction or death. In total, 853 patients were randomly allocated to CAS and 857 allocated to CEA. Patient characteristics were equally randomised at baseline. In the CEA group 21 patients received no procedure and 15 changed to CAS. In the CAS group 16 received no procedure, and 9 change to CEA procedure. Therefore in the CEA group, 857 patients were analysed by Intention-to-treat (ITT) up to 120 days post randomisation, and 821 analysed per protocol up to 30 days post procedure. In the CAS group, 853 were analysed by ITT up to 120 days post randomisation, and 828 analysed per protocol up to 30 days post procedure.

ITT analysis for primary short-term outcome revealed 72 events (8.5%) in the allocated CAS group versus 43 events (5.1%) in the allocated CEA group (hazard ratio 1.73 range 1.18 – 2.52: log rank p-value 0.004). Analysis for type of event revealed any stroke in 65 versus 34, any MI in 3 vs. 4, and non stroke/non MI death in 7 versus 5 for allocated CAS versus allocated CEA respectively. Stroke differentiation between CAS and CEA group revealed fatal stroke in 9 versus 2, disabling stroke in 17 versus 19, and non-disabling stroke in 39 versus 14 patients respectively. Per protocol 30 day short-term outcome analysis restricted to allocated treatment initiated, showed any stroke in 58 (7.0%) for CAS versus 27(3.3%) for CEA respectively (risk ratio 2.13 range 1.36 – 3.33; p < 0.001).

Dr Moll concluded: “There is strong evidence that CEA is safer than CAS in the primary ITT analysis (any stroke, death or peri-op MI, 8.5% vs. 5.1%, p=0.004). There were twice as many strokes after CAS than after CEA in the per protocol analysis (7.0% vs. 3.3%; p=0.001). This difference in outcome was largely driven by non-disabling stroke. CEA is the treatment of choice for suitable patients with recently symptomatic carotid stenosis.”
Researchers reveal how irritants trigger coughing

Scientists have revealed how environmental irritants such as air pollution and cigarette smoke cause people to cough, in research published 23 November 2009 in the American Journal of Respiratory and Critical Care Medicine. The authors of the study, from Imperial College London and the University of Hull, have identified the reaction inside the lungs that can trigger coughing when a person is exposed to particular irritants in the air. They suggest that their findings may ultimately lead to the development of new treatments for chronic coughing.

The study indicates, for the first time, how coughing can be triggered when a person is exposed to certain irritants in the air. It shows that the irritants can switch on receptor proteins called TRPA1 on the surface of nerve endings in the lungs. This switches on sensory nerves, which then trigger a cough reflex. The researchers say coughing could potentially be treated by blocking TRPA1 receptors, to stop irritants in the air from setting off this chain reaction. They hope that this could ultimately help millions of people whose lives are affected by chronic coughing.

To reach their conclusions, the researchers first looked at sensory nerves from mice, guinea pigs and humans, and showed that the receptors on the sensory nerves were activated by a number of irritants, including a key compound in cigarette smoke (acrolein) and a chemical called cinnamaldehyde. The researchers then blocked the receptors and showed that these substances no longer activated the nerves.

● Citation: Belvisi M. et al, TRPA1 Agonists Evoke Coughing in Guinea-Pig and Human Volunteers" American Journal of Respiratory and Critical Care Medicine, 23 November 2009
Breast density associated with cancer recurrence

A new study finds that women treated for breast cancer are at higher risk of cancer recurrence if they have dense breasts. Published in the 15 December 2009 issue of Cancer, the study’s results indicate that breast cancer patients with dense breasts may benefit from additional therapies following surgery, such as radiation.

Previous studies indicate that women with dense breast tissue are at increased risk of breast cancer. Researchers have suspected that high breast density may also increase the risk of cancer recurrence after lumpectomy, but this theory has not been thoroughly studied.

Researchers led by Steven A. Narod, MD, of the Women’s College Research Institute in Toronto, reviewed the medical records of 335 patients who had undergone lumpectomy for breast cancer. Investigators monitored the patients for cancer recurrence and compared recurrence with breast density as seen on mammogram, categorised as low density (50% dense tissue).

The researchers found that patients with the highest breast density had a much greater risk of cancer recurrence than did women with the lowest breast density. Over ten years, women in the highest breast density category had a 21% chance of cancer recurrence, compared with a 5% chance among women in the lowest category. The difference in the recurrence rates at ten years was even more pronounced for women who did not receive radiation. In those women, 40% with high-density breast tissue had a recurrence compared with none of the patients with low density.

“The composition of the breast tissue surrounding the breast cancer is important in predicting whether or not a breast cancer will return after surgery,” concluded Dr Narod. The authors say their findings indicate that women with low breast density, who have a low chance of recurrence after surgery, may not need radiation but that women with high breast density could significantly benefit from the additional therapy.

● Citation: Cil T et al, “Mammographic density and the risk of breast cancer recurrence following breastconserving surgery.” Cancer, 15 November 2009. DOI: 10.1002/cncr.24638
Chronic diarrhoea may be caused by hormone deficiency

A common type of chronic diarrhoea may be caused by a hormone deficiency, according to new research published in the November issue of Clinical Gastroenterology and Hepatology. The authors of the paper, from Imperial College London, with collaborators from King’s College London and the University of Edinburgh, say their results could help more doctors recognise this type of diarrhoeal illness, and may lead to the development of more effective tests and treatments to help improve the lives of many people suffering with chronic diarrhoea.

Chronic idiopathic bile acid diarrhoea affects an estimated one in 100 people in the UK and it can cause people to have up to ten watery bowel movements a day, often for months at a time. This type of diarrhoea occurs when an overload of bile acid reaches the colon and causes excess water to be secreted into the bowel.

The study suggests that bile acid diarrhoea is caused by the body producing too much bile acid, because of a deficiency in a hormone called FGF19, which normally switches off bile acid production. The authors of the study say that new hormone-based treatments could be developed in the future to treat the condition and doctors could potentially test people’s hormone levels to diagnose it.

Dr Julian Walters, lead author of the study from the Division of Medicine at Imperial College London, commented: “If patients are diagnosed, we have treatments that can remove bile acid from the colon, alleviate the symptoms and improve their quality of life. However, the current test used to diagnose the condition is not available in many countries and requires patients to attend the hospital twice. This means many people are not diagnosed. Our new findings mean that in the future doctors may be able to diagnose the condition by doing a quick and simple blood test.”

Bile acid is produced by enzymes in the liver, to help the body digest fats. Its production is controlled by a hormone called Fibroblast Growth Factor 19 (FGF19). Over 90% of the bile acid is absorbed from the intestine back into the blood and is then reused. In healthy people, when bile acid is absorbed by the intestine, the body makes more FGF19 to stop new bile acid from being produced.

However, results of the study suggest that people with bile acid diarrhoea make less FGF19, so the hormone 'switch' fails to stop the liver from producing more bile acid than the body needs. Because of this, more is produced than the intestine can absorb. This then irritates the colon and the resulting watery secretion causes diarrhoea.

The researchers say that testing the amount of FGF19 in people's blood could lead to a fast, easy and cheap way of diagnosing bile acid diarrhoea. They also hope today’s findings will help scientists develop new treatments to increase the production of FGF19 and reduce the amount of bile acid being made in patients.

● Citation: Walters J et al, “A New Mechanism for Bile Acid Diarrhea: Defective Feedback Inhibition of Bile Acid Biosynthesis”, Clinical Gastroenterology and Hepatology, 1 November 2009.

Non-invasive technique alters conditioned fear in humans Scientists have for the first time selectively blocked a conditioned fear memory in humans with a behavioural manipulation. Participants remained free of the fear memory for at least a year. The research builds on emerging evidence from animal studies that reactivating an emotional memory opens a 6-hour window of opportunity in which a training procedure can alter it.

“Our results suggest a nonpharmacological, naturalistic approach to more effectively manage emotional memories,” said Elizabeth Phelps, PhD, of New York University.

Phelps and colleague Joseph LeDoux, PhD, led the research team. Their findings are reported online 9 December 2009 in the journal Nature. “Inspired by basic science studies in rodents, these new findings in humans hold promise for being translated into improved therapies for the treatment of anxiety disorders, such as post-traumatic stress disorder (PTSD),” said Thomas R. Insel, MD, director of the US National Institute of Mental Health, which funded the research.

The results add support to the hypothesis that emotional memories are reconsolidated – rendered vulnerable to being modified – each time they are retrieved. That is, reactivating a memory opens what researchers call “reconsolidation window”, a time-limited period when it can be changed.

“This adaptive update mechanism appears to have evolved to allow new information available at the time of retrieval to be incorporated into the brain’s original representation of the memory,” explained Phelps.

“Timing may have a more important role in the control of fear than previously appreciated,” Phelps suggested. “Our memory reflects our last retrieval of it rather than an exact account of the original event.”

The researchers suggest: “Using a more natural intervention that captures the adaptive purpose of reconsolidation allows a safe and easily implemented way to prevent the return of fear.”
Funds for stem cell studies for AML, AMD

The UK’s Medical Research Council (MRC) has awarded approximately £5 million (about US$8 million) towards stem cell studies addressing age-related macular degeneration (AMD) and acute myeloid leukaemia (AML). The projects involves both UK and US research teams, and have been funded as part of an international collaboration between the MRC and the Californian Institute for Regenerative Medicine (CIRM).

The jointly-funded initiative has brought leading researchers together to add momentum to the development of stem cell treatments that can eventually be used in the clinic. The first programmes to emerge from this enterprise will be expected to begin Phase I clinical trials within four years.

The first project concerns age-related macular degeneration, a leading cause of blindness among the elderly. The study will be led by Professor Pete Coffey at the UCL Institute of Ophthalmology and Professor Mark Humayun at the University of Southern California.

The second project, for acute myeloid leukaemia, will be led by Professor Paresh Vyas at the University of Oxford and Professor Irving Weissman at Stanford University.
Study shows link between influenza virus and fever

Viruses are microscopically sized parasites. They plant their genes in the cells of their victim in order to ‘reprogramme’ them. The infected cells then no longer produce what they need to live, making lots of new viruses instead.

Luckily, in most cases this hostile takeover does not go unnoticed. This is ensured by the cells’ own sensors that recognise alien genetic material. One of them is RIG-I. When RIG-I encounters virus genes, it ensures that the body releases interferon. The interferon then in turn puts killer cells on combat standby, which then destroy the infected cells.

Yet this is only part of the truth. “According to our results RIG-I appears to play a far more prominent role in the defence against viruses than was previously thought,” Dr Jürgen Ruland from the University Hospital Rechts der Isar at the Technical University of Munich explained. As a result, many virus infections are accompanied by a high temperature. That is also what happens with influenza, for example. This symptom cannot be explained by interferon release alone.

In most cases it is cytokines which trigger the fever. “We have now been able to show, for the first time, that RIG-I also cranks up the production of a central cytokine in the case of a virus infection,” Dr Hendrik Poeck explained. He and his colleagues Dr Michael Bscheider and Dr Olaf Groß are the primary authors of the study. This is a reference to interleukin 1, probably the most important cytokine known today.

Do cytokines cause more severe courses of a disease? When RIG-I comes into contact with a virus gene, it does two things. On the one hand, it ensures that certain immune cells produce prointerleukin, the precursor of interleukin 1, en masse. At the same time it activates an enzyme via a complicated signalling pathway which transforms pro-interleukin into interleukin 1. “This interleukin 1 then ensures that the typical symptoms of a virus infection such as fever or shivering occur,” Professor Veit Hornung from the Bonn University Clinic explained.

As yet the researchers do not know how important this newly discovered immune mechanism is for the successful defence against the virus. The release of interleukin may also have negative consequences. “There is the hypothesis that an overproduction of cytokines may lead to extremely severe courses of virus diseases,” Professor Gunther Hartmann said. Medicines that prevent such a ‘cytokine storm’ may therefore alleviate the progress of the disease.

● Citation: Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1beta production. Hendrik Poeck et al. Nature Immunology, doi: 10.1038/ ni.1824
Preeclampsia can lead to reduced thyroid function

Scientists have found that a history of preeclampsia – dangerously high blood pressure and a suite of other symptoms that complicate some pregnancies – can dramatically increase the likelihood that a woman will experience low thyroid function later in life.

The research, by Howard Hughes Medical Institute investigator Ananth Karumanchi and colleagues, was reported online 17 November 2009, in the British Medical Journal.

It’s been known for some time that a history of preeclampsia raises a woman’s risk for high cholesterol, high blood pressure, heart disease and stroke later in life. Karumanchi’s new research shows that preeclampsia can also reduce production of thyroid hormones, which can cause a variety of signs and symptoms including low energy, weight gain, and dyslipidemia. The study also identifies a common underlying mechanism that contributes to both conditions.
Monetary gain stimulates striatum area of brain

Monetary gain stimulates activity in the brain. Even the mere possibility of receiving a reward is known to activate an area of the brain called the striatum. A team of Japanese researchers report in the January 2010 issue of Cortex the results of a study in which they measured striatum activation in volunteers performing a monetary task and found highrisk/ high-gain options to cause higher levels of activation than more conservative options. They also found levels of activation to increase with the amount of money owned.

Dr Tadashi Ino and colleagues, from the Department of Neurology at the Rakuwakai-Otowa Hospital and the Research Center for Nano Medical Engineering at Kyoto University, used functional magnetic resonance imaging (fMRI) to study hemodynamic changes in the brains of 17 healthy volunteers performing a monetary task. The volunteers were given an initial stock of money and then required repetitively to press one of two buttons, which resulted in either an increase or decrease of the money stock, depending on whether their choice agreed or disagreed with a number that appeared randomly after the button had been pressed. One button was a low-risk option and the other involved high-risk, so that more money was gained or lost when choosing the high-risk option. The volunteers were also able to keep track of the total money stock throughout the task.

They found higher levels of activation in volunteers when choosing high-risk/high-gain options, compared to lowrisk/ low-gain, and when gaining money, compared to losing money. It did not matter how much money was gained, since small gains stimulated the volunteers’ striatum as much as large gains. They also found that overall striatum activity increased with the total amount of money in stock.

According to the authors, these results show that “risky tactics and pleasure of monetary gain are correlated with activation of the striatum” and that this finding demonstrates “the concept of the striatum as a major rewardrelated brain structure”.

● Citation: “Differential activation of the striatum for decision making and outcomes in a monetary task with gain and loss” Tadashi Ino, et al Cortex, Volume 46, Issue 1 (January 2010), published by Elsevier in Italy.
Low-temperature hydrogen peroxide inactivates prions

New research shows that the low-temperature hydrogen peroxide sterilisation technology used in the Sterrad NX Systems, by Advanced Sterilization Products (ASP), is able to inactivate prions, protein-based infectious agents linked to bovine spongiform encephalopathy (BSE, also known as “mad cow disease”) and other fatal brain diseases. Until now, the only WHO approved process for full inactivation of prions, which have an unusually high level of resistance to sterilisation methods, was combination of soaking in aggressive chemicals and high-temperature steam (special prion cycle at 134 degrees C, 18 minutes). These findings were published in the August 2009 issue of Infection Control and Hospital Epidemiology.

ASP had the test conducted at several independent laboratories in France and Germany. “Since there is no cure at this time, prion diseases can pose a significant threat to the public and to healthcare facilities that attempt to treat individuals with prion-related maladies,” said Dr Pascal Clayette, SPI-BIO, CEA, Fontenay-aux-Roses, France. “Complicating the challenge of prion inactivation is that the currently recommended procedures are often damaging to the materials used in medical devices.”

Klaus Roth, SMP, Tubingen, Germany, commented: “These data are exciting for infection prevention specialists because it is important to have an effective and less damaging sterilisation solution, which will enable hospitals and clinics to prevent spread of prions, while at the same time protect valuable surgical equipment from potential damage caused by high-temperature steam sterilisation.”

The Sterrad System is engineered using ASP’s gas plasma technology. ASP is a division of Ethicon, a Johnson & Johnson company.
Scientists test digital plaster for monitoring vital signs

A wireless digital ‘plaster’ that can monitor vital signs continuously and remotely is being tried out with patients and healthy volunteers at Imperial College Healthcare NHS Trust in the UK, in a new clinical trial run by Imperial College London researchers.

Toumaz Technology’s Sensium digital ‘plaster’ or ‘patch’ is a disposable device that sticks to a patient’s chest. It is designed to allow patients to have their health monitored continuously without being wired up to bulky, fixed monitoring machines, potentially freeing some patients from their hospital beds.

The digital plaster is based on innovative technology created by engineers at Imperial College London. It contains a wireless, smart, ultra-low power sensor platform in a silicon chip, which can monitor a range of vital signs like body temperature, heart rate and respiration in real-time.

The intention is that healthcare professionals will be able to download this information using a mobile phone, enabling them to pick up on any critical changes in their patients’ status on a 24-7 basis and allowing early detection and treatment of any unforeseen complications.

The data can also be integrated automatically into the patient’s electronic medical record.

The team that developed the Sensium digital plaster from Toumaz Technology, a spin-out from Imperial College London, hope that it will enable some patients to recover from surgery and illness at home rather than in hospital. It should also mean that hospital in-patients have greater mobility. In addition, it could allow doctors to extend continuous monitoring of vital signs to a broader range of patients.

The disposable plaster has a working life of several days, after which it can be replaced, ensuring that infection control can be maintained.

“We’re hoping that the plaster will improve the health and wellbeing of a vast range of patients – from patients on a general hospital ward to people with chronic diseases like diabetes and cardiovascular disease who want to have their health monitored without having to keep visiting the hospital. At the same time, the plaster should free up doctors and nurses’ time by allowing them to keep an eye on patients without continuously checking bits of machinery,” said Professor Chris Toumazou FRS, who led the team that developed the plaster and is CEO and co-founder of Toumaz Technology and the Director of the Institute of Biomedical Engineering at Imperial College London.

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