Medical Science 2014 by Karolinska Institutet

A magazine from Karolinska Institutet

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2014

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Contents

2014 4

Meet the Vice-Chancellor

Advances 5

Heart attack: A novel way to self repair 6 Hunting for new diseasecausing microﬂora 7 Dying parents: Teens need timely information 8 Imagined ugliness studied 9 Cure on the ﬂoor 10 Old age secrets revealed 11 Llamas against disease 25 HPV vaccination depends on parents’ education

Tricking the brain. “We percieve things as we expect them to be.”

In focus 18 A bank of cells saving lives 20 Research prevents kids drowning in Bangladesh 22 “Thousands of cancer cases are preventable” 38 A nose for good taste 46 Severe PMS to be treated

Meet the researchers 12 They trick the brain 24 Before the Nobel Prize winner was revealed 34 She is doing research for women’s freedom 43 A pioneer for bleeders 50 The worst shift of her life

Biomedicum. An ultramodern laboratory.

Stroke. Improving the odds for recovery.

In depth 26 Stroke – a race against the clock

Also

Reproduction. Women’s own choice in focus.

16 Timeline on tuberculosis 44 High impact publications 48 KI News

A magazine from Karolinska Institutet at Karolinska Institutet 2014

English Language Edition

2014

nosy The Sense of Smell – a new weapon against disease

ALSO: STROKE / CELL BANK / PMS / ALL ABOUT KI

Cover: Istockphoto

Nosy. Disease detected by sense of smell.

Medical Science–2014

Vice-Chancellor of Karolinska Institutet

EAR READERS, Karolinska Institutet is one of the world’s leading medical research universities. This has recently been confirmed in two international rankings of higher education institutions. Our university is well-funded and has a modern, growing infrastructure that is at the forefront of development. The fact that Karolinska Institutet is a university with only one faculty creates special opportunities in this context. Our vision is to make a decisive contribution to the improvement of human health. Karolinska Institutet’s research is geared to achieving scientific breakthroughs and discoveries that change our view of normal life processes as well as health and disease. The results of the research undertaken are intended, as far as possible, to lead to practical applications within the healthcare field and to significant innovations. Experimental research, by tradition, is strong within Karolinska Institutet. During the next 5-year period, new environments will be developed which will further strengthen experimental research through offering an optimal infrastructure for our different activities, facilitating crossover research between different disciplines as well as offering scope for new recruitments. With the cutting-edge laboratory Biomedicum, basic research will take a step closer to patient-level clinical research, like university healthcare, for the benefit of people’s health around the world. As things stand, around 60 per cent of our research is already carried out in environments that are embedded in – or located in close connection to – actual university healthcare delivery. This offers good conditions for clinical and translational research, register-based research, the generation of unique biobanks and biomarker-related research. RECRUITMENT OF THE HIGHEST COMPETENCE within all areas is of prime importance for Karolinska Institutet, as for every organisation with the ambition of being a leader in its field. Consequently, to recruit internationally prominent senior and junior researchers comprises a critically important step. The dedication, creativity and, hard day-to-day work of many different individuals are the essential building blocks in the work of moulding a successful university. Karolinska Institutet’s success depends first and foremost on the people who work here: on students, junior researchers, faculty, technical personnel and administrative staff, who are driven by a sense of enthusiasm and loyalty. Great challenges – and opportunities – lie before us. The common, incapacitating illnesses of the modern age are still awaiting effective prevention; methods that enable early diagnosis, and knowledge of the inner, molecular mechanisms of the diseases. The latter is a prerequisite for individually formulated – thereby more effective – and, in the best case, curative treatments. In this edition of Medical Science you will find topical examples of breakthroughs that derive from the targeted research which is carried out at our university.

Medical Science–2014

Editor-in-chief Christina Bostedt Director of Communications Karolinska Institutet Editors Helena Mayer Cecilia Odlind medicinskvetenskap@ki.se Art Direction Johan Blomgren & Per Boström Content Innovation Design Johan Sundqvist Print Kaigan 2014 Translation Språkservice, Space 360 Web ki.se

Communications and Public Relations Office, Karolinska Institutet, SE-171 77 Stockholm, Sweden ISSN 1104-3822

Photo by: Gunnar Ask

Anders Hamsten:

Medical Science is an annual English language edition of the Karolinska Institutet popular science magazine Medicinsk Vetenskap. Here you can read selected examples of current research at our university.

The latest in medical research

Broken. Help with self-help may be on its way.

How the heart can repair itself after a heart attack A more eﬀective treatment after a heart attack can become reality. This is the hope of researchers behind a completely new method to repair damaged tissue. ust as a chef uses a recipe when cooking, the cell uses its ingenious messengers – mRNA – as a template for manufacturing new proteins. Now a team of researchers from Karolinska Institutet and Harvard University has found a method that involves administering mRNA in synthetic form and “requesting” heart cells to manufacture an angiogenic protein that can help the heart heal after a heart attack. In a recent study, the researchers added mRNA,

Photo by: Getty Images

which codes for the growth factor VEGF-A, to the hearts of mice. In this way, they succeeded in reprogramming the heart’s stem cells to form new blood vessels – Kenneth Chien. instead of Photo by: Ulf Sirborn scar tissue. The mice that were given synthetic mRNA within 48 hours of a heart attack had both improved cardiac function and prolonged survival.

“This is the first step towards using the heart as a protein factory and getting it to regenerate new tissue following a heart attack,” says Kenneth Chien, professor of Cardiovascular Research at the Department of Cell and Molecular Biology. Previous experiments with stem cell transplantation and gene therapy have been associated with a lot of difficulties. The use, as in this case, of modified mRNA that is not broken down by the body’s immune defence can open the door to a whole new way of

treating diseases in the future. Kenneth Chien points out that the research is still in the early stages. Among the things that need to be found is a good way of introducing mRNA into the cells in the heart. Pharmaceutical giant AstraZeneca has high hopes for the new technique and has invested SEK 1.5 billion in anticipation of ﬁnding a cure, not only for cardiovascular diseases, but also metabolic diseases and cancer. Christine Kilefors Nature Biotech September 2013 Medical Sceince–2014

Advances here is a lot to suggest that our microflora – all the bacteria and viruses that we have on and in our bodies – may underlie more diseases than we are currently aware of. But we still lack a great deal of knowledge about which microbes are involved and what it is that makes them sometimes cause disease. Now, researchers are turning to the latest technology to move forward. A new project will use large-scale DNA sequencing to look for pathogenic viruses and bacteria in selected patient groups. Samples from healthy subjects will be compared with samples from patients suffering from disorders such as skin diseases, diarrhoea, schizophrenia and cancer. One goal is to find previously unknown links between these diseases and specific microbes, but researchers also expect to gain greater knowledge about how disturbances in the microflora can lead to disease and to identify completely new viruses. “Thanks to today's advanced gene analysis methods, to be implemented in collaboration with the Science for Life Laboratory, we will quickly generate a great deal of new knowledge. Hopefully, this can then lead to applications such as Björn Andersson. diagnostic tools and Photo by: Stefan eventually drugs or Zimmerman vaccines,” says Björn Andersson, professor at the Department of Cell and Molecular Biology and coordinator of the five-year project in collaboration with Uppsala University. Cecilia Odlind

Crowded. Conceptual image taken in ultraviolet light of a woman's hands covered in bacteria.

The large-scale hunt in our microﬂora Can disorders such as psoriasis or schizophrenia be triggered by an infection? This is a question researchers are asking in their large-scale genetic analyses to step up the pace in search of previously unknown disease-causing bacteria and viruses.

The goal: Creating a virtual twin of the brain Photo by: Istockphoto, Getty Images

The brain is the most complex structure in the universe. The EU ﬂagship initiative in neuroscience – The Human Brain Project – is mobilising Europe's most powerful computers and sharpest brains for the most ambitious attempt to date to build a computer-simulated version of the human brain. “We use the computer to build up the brain's cells, networks and systems, which we link together. Then we can see how all the small components relate to the whole, and how the brain allows us, for example, to perceive the world around us and remember things,” says Professor Sten Grillner, Karolinska Institutet, which is part of the project leadership. The simulated brain will be used to interpret results from biological experiments and to provide answers to questions about what is going on in various diseases. Sten Grillner believes it will be able to perceive and interpret its surroundings and react in an appropriate manner, and can thus to some extent be said to think for itself. “When we better understand how the brain works, we will be in a position to develop improved methods of diagnosis and treatment for brain disorders,” he says. Selma Wolofsky 6

Medical Science–2014

The brain consists of 100 billion neurons, each of which can have 1 000s of links to other cells, which means more possible links than the number of stars in the Milky Way.

Uninformed. Distrust of the care received by a dying parent increases the risk of depression in teenagers long after their loss. A timely discussion can help.

Discussion before a parent's death important for young Teenager's reliance on a dying parent's care was highest if an informative conversation took place before death. n a first major study, researchers at Karolinska Institutet studied children's own experiences of, and confidence in, the medical care received by a seriously ill and dying parent and of the impact on their mental health. The results show that confidence of teenage children in the care of a dying parent was highest if the family had been provided with an informative discussion before the parent died. The study had the participation of more than 600 young people who had lost a parent to cancer when they themselves were aged 13 to 16. They answered a questionnaire six-nine years after their parent's death. Just over 80 per cent responded that they had experienced moderate to high confidence in the care of the parent's last week of life. This confidence was linked to whether and at what point they had been informed by physicians about the disease, treatment and impending death. Those only receiving information after the parent's death and those

Photo by: Getty Images, Istockphoto

not receiving any information at all had little conﬁdence in the care given in the last week of their parent's life. Distrust of the parent's healthcare was associated with an increased risk of depression several years after the loss. “You have to tell the children when death is drawing near and also explain why a cure Tove Bylund is no longer possible. Grenklo. Photo by: Ulf Sirborn The healtcare needs to create structures for these discussions so that the children don't fall through the cracks,” says Tove Bylund Grenklo, doctoral student at the Department of Oncology-Pathology, Karolinska Institutet and at the private hospital and nursing home, Stockholms Sjukhem. Journal of Clinical Oncology July 2013

Increased survival rates for patients with Hodgkin lymphoma Each year, around 160 people contract Hodgkin lymphoma, a form of cancer of the lymphatic system, in Sweden. In contrast to other types of lymphoma, a large number of the patients who develop Hodgkin are between the ages of 20-30. In a recently published study, all cases of Hodgkin lymphoma reported to the Swedish Cancer Registry between 1973 and 2006, a total of 5,462 patients, were included. The results show that the mortality rate of treatment-related illness, primarily of the blood vessels within the heart and brain, has decreased since the mid-1980s, most probably as a result of the concentrated efforts made to counteract side effects such as these. "In addition to the continuing alterations within the health care programme to reduce the side effects of both radiotherapy and medical therapy to the blood vessels, it is likely that the long-term follow up of patients and recommendations to stop smoking have also contributed to the improvements", says Sandra Eloranta, Sandra Eloranta. doctoral Photo by: Gunilla Sonnebring student at the Department of Medical Epidemiology and Biostatistics and ﬁrst author of the study. The researchers also believe that this positive development shall continue amongst patients who received their diagnosis in the early 2000s. And new ways of treatment will spare patients from 'over-treatment'. Journal of Clinical Oncology February 2013 Medical Science–2014

Advances

Faster diagnosis of chest pain A thesis from the Department of Medicine, Huddinge presents a new method for quickly ruling out acute heart attack or other serious acute coronary disease among those seeking emergency treatment for chest pain. The method uses results of measurements by a new sensitive method to detect blood troponin, a substance that is released from the heart during a heart attack, and uses risk scores that take into account the patient's medical history, age, and ECG. During the winter, a number of hospitals will start testing the method in a major study.

Obsessive-compulsive. Persons suffering from body dysmorphic disorder, imagined ugliness, experience strong concern about things in their appearance that perhaps only they themselves see.

Great interest in study on imaginary ugliness Jesper Enander and Associate Professor Christian Rück, are studying whether cognitive behavioural therapy via the internet can help people who have body dysmorphic disorder. What is body dysmorphic disorder?

lllustration by: Ispot. Photo by: Istockphoto

percent higher risk of extremely premature delivery. That's what overweight women had compared to women of normal weight, according to a new study in JAMA. The higher the Body Mass Index the pregnant woman had, the higher the risk that she would give birth prematurely. The overweight and obesity related risk of medically indicated preterm delivery was substantially explained by increased risks of obesity-related diseases. Medical Science–2014

“It's a strong ﬁxation on something you are unhappy with in your appearance, such as nose shape or size, skin texture or the level of hair growth. A person who has body dysmorphic disorder can spend hours thinking about, concealing, correcting or otherwise controlling the perceived defect. It can become a social handicap, where those aﬀected believe that people around them are staring or feel disgusted.” Who is affected?

“Body dysmorphic disorder is a relatively unknown and probably underdiagnosed psychiatric diagnosis that has seen relatively little research, but it is estimated that it will aﬀect one to two per cent of the population at some point. The symptoms often ﬁrst appear around puberty. The cause is not fully known, but one can say that it's a complex mix of genetics, psychology and environment.”

How can body dysmorphic disorder be treated?

“Antidepressants may give a slight improvement and increase disease awareness, but cognitive behavioural therapy, CBT, appears more promising. Studies show that CBT can break the obsessivecompulsive-like behaviour. We are now investigating whether CBT via the internet may be appropriate for these patients, who are often reluctant to talk about the problem face to face. Online, the step to seeking help and undergoing treatment might be smaller. Even before the study began, there was a very great interest in participating.” Eva Ristoff

Jesper Enander is a psycologist and doctoral student at the Department of Clinical Neuroscience at Karolinska Institutet. Photo by: Christian Rück

Photo by: Professor Micha Ilan, Tel Aviv-universitetet

Magical? Haliclona fascigera is one of the sponges being tested for anti-tumour properties.

Scouring the ﬂoor for a cure

Can sponges be the source of future cancer drugs? Researchers from eleven universities are collaborating in the interdisciplinary EU project SPECIAL to ﬁnd the answer. The anti-tumour effect of around 300 different species of tropical marine sponges will be examined in cell cultures. Several previously unknown molecules with an anti-cancer effect have already been identiﬁed. The next step will be to examine which types of tu-

mours the molecules are active against, how they exert their effect, and whether they have serious side effects that make them unsuitable as medicines. “Several of today's cancer drugs are derived from marine organisms, so the idea is not novel. We now hope to ﬁnd even more,” says Rolf Lewensohn, a professor at the Department of OncologyPathology and in charge of Karolinska Institutet's part of the project. Cecilia Odlind Medical Science–2014

Advances Research spotlight on 105-year-olds Want to live to a ripe old age? Physical activity at least once a month will extend your life by an average of two years.

Exercise and friends just as important in old age Of the children born in Sweden today, it is predicted that more than half will live to celebrate their 100th birthday. But what is the trick? A new thesis reveals the secrets behind really old age. he message from this research is unmistakable: the importance of a healthy lifestyle and a rich social network continues throughout life. Eﬀorts to encourage physical activity, social engagement and giving up smoking are of considerable importance even for the very oldest people,” says Debora Rizzuto, researcher at the Aging Research Center at Karolinska Institutet. The research is based on data from the Kungsholmen Project, a population study with 1,800 participants aged 75 years or older. The results show that a healthy lifestyle and social relationships are strongly associated with survival for persons who have passed their 75th birthday. Those who are physically active at least once a month

Medical Science–2014

live two years longer on average than those who are not. Non-smokers in the same age group who participate in at least one exercise activity a month and have a rich social life can add another three years on top of this. This connection, albeit a slightly weaker one, is also valid for the chronically ill. “Genetic factors also play a major role in longevity, but even people with a genetic predisposition to certain diseases can increase their initial longevity prognosis by changing Debora Rizzuto. their lifestyle,” reasons Photo by: Francesca Debora Rizzuto. Mangialasche

Ann-Cathrine Johnsson

Why do some individuals achieve a very old age and don’t contract metabolic diseases such as diabetes and cardiovascular disease? The newly started EU funded research project HUMAN, which is coordinated by Karolinska Institutet, will try to uncover the genetic mystery behind healthy aging. The project will generate 'humanised' mouse models with livers and pancreatic beta cells originating from human donors using stem cell technology, making it possible to study the gene functions in human-derived organs. The human cells to be used originate either from patients affected by severe metabolic diseases or from individuals that enjoyed a complete lack of disease and exceptional longevity; 105 years or more. The project HUMAN (Health and the understanding of metabolism, aging and nutrition) consists of 17 partners from Sweden, France, Italy, Netherlands, United Kingdom, Germany and Switzerland. Jill Jönsson

Respectable. “I have never used miracle creams, but I smile often. And I take the stairs every day,” says Fulvia, 109 years from Sarzana, Italy, who participates in the study.

D I D Y O U K N O W T H AT…

… llama antibodies can be used in the ﬁght against infectious diseases?

In the future, heart problems might be treated via the brain.

Cause of heart problems now found in the brain

Photo by: Getty Images, Istockphoto, Paolo Garagnani (Fulvia)

It has long been known that a lack or surplus of thyroid hormone can lead to heart problems, however hormonestarved cells in the brain may be a new part in this puzzle. t's far in the future, but if we learn to control these neurons, we'd be able to treat certain cardiovascular problems via the brain rather than directly in the heart,” says Jens Mittag, research team leader at the Department of Cell and Molecular Biology, Karolinska Institutet. The researchers have identiﬁed a previously unknown group of heat-sensitive neurons in the mouse brain that adjust heart rate and blood pressure to the ambient temperature. Another peculiarity of the new neurons is that they are dependent on the thyroid gland for their development – when they are not reached by the right quantity of thyroid hormone, their function is impaired, with heart problems as a result. The fact that people with a lack or surplus of thyroid hormone often have

heart problems has previously been assumed to be due to the hormone affecting the heart directly. But the new study shows that the hormone also affects the heart indirectly via the brain, something which opens the door to a whole new way of tackling heart problems. “An immediate conclusion is that it is still important to identify and treat pregnant women who have thyroid horJens Mittag. mone deficiencies, as this Photo by: Private might damage fetal production of these neurons, something which could give the fetus cardiovascular disease in the long term,” says Jens Mittag. Ola Danielsson

Over the course of evolution, the form of antibodies – an important part of the body's immune defence – developed by llamas and camels is diﬀerent to that in humans. Some of their antibodies have unique characteristics, such as resistance to acidic pH, enzymes and heat. “These characteristics have proven useful in drug delivery in that the antiLennart bodies Hammarström. can be Photo by: Ulf Sirborn administered orally without being destroyed in the stomach or facing any immunological barriers,” says Lennart Hammarström, Professor of Clinical Immunology at the Department of Laboratory Medicine, Karolinska Institutet. His research team has now demonstrated that young children in Bangladesh with severe rotavirus infection had less diarrhoea after drinking a solution of llama antibody fragments prepared from yeast. Every year, rotavirus infection reaps the lives of over 500,000 children in low-income countries. Helena Mayer Gastroenterology October 2013 Medical Science–2014

A tale of three researchers

They trick the brain If we can get our brain where we want it, there is a lot to gain. We have met three researchers who are trying to outsmart the smartest part of our body. Photos by: Mattias Ahlm

Medial Scienceâ&#x20AC;&#x201C;2014

“We perceive things as we expect them to be”

Name: Predrag Petrovic Title: Researcher in Cognitive Neuroscience at the Department of Clinical Neuroscience. Researches: How our perception of reality is formed in the brain.

“My research is based on the assumption that our perception of reality is a compromise between the impressions that reach the brain and its expectations of what is going to happen. By altering these expectations, you can get people to experience the world and themselves in a new way. In one experiment, for example, we had subjects look at a spinning cylinder through a pair of 3D glasses, which we had said would cause the cylinder to look like it was spinning in a certain direction. Actually, the glasses were irrelevant, but because the subjects believed that the rotation would change when they put them on, that’s exactly what happened. The same is true of medication. If we get a patient to believe that a pill will relieve pain – then that is what will happen. The brain reinterprets the pain signals reaching it in a way that is consistent with the

expectation that the pain will cease. The altered perception of reality in psychosis, I think can be explained as an imbalance that allows the signals reaching the brain to become too strong. The brain is then compelled to invent a reality that explains why the impressions are so intrusive. So, in the mind of a psychotic person, something as mundane as the sound of an aeroplane might be assigned a very dramatic interpretation, such as al-Qaeda being on the verge of a suicide attack. But delusions are not something that only sick people have; they occur throughout the population to varying degrees. One example is the feeling that someone you see on the street is out to get you. Those who have the strongest tendencies of this kind probably run the greatest risk of developing a psychosis. Through studying how the perception of reality is formed, I have become more humble in my meetings with patients. I know that no one experiences reality exactly as it is, we only create more or less of it in our heads.”

As told to: Ola Danielsson

Medical Science–2014

A tale of three researchers

“In my job as a physiotherapist, I regularly experience that good feeling when the patient is on board – when he or she suddenly understands the point of the treatment. The result of that motivation and expectation which has then arisen in the patient, thanks to the trust built up between us, is an example of a non-specific treatment effect that interests me. It began in earnest with a study in which we observed dramatic effects of acupuncture used to treat nausea caused by cancer radiotherapy. The interesting thing was that simulated acupuncture, using a blunt needle that only brushes against the skin, provided just as good relief as normal acupuncture. The effect may have been due, for example, to the treatment entailing regular rest and physical contact, that patients felt cared for and most of all that they had an expectation that the treatment would help. The placebo effect has previously been seen a little like a problem to be minimised, in order to bring out the true effect of a treatment. But a new view is emerging where we see the placebo effect as an ever-present factor that can be studied – not only in experiments but in clinical care situations – and that healthcare can make better use of in an ethically justifiable manner. Through a detailed study of what influences treatment effects, we are now trying to understand how the person administering treatment can enhance the patient’s expectancy. A more systematic use of such knowledge might not only result in healthier patients but also in economic gains for society.”

As told to: Cecilia Odlind 14

Medical Science–2014

Name: Anna Enblom Researches: Effects of expectations in the treatment situation. Title: Physiotherapist and researcher in Integrative Medicine at the Department of Clinical Neuroscience, Karolinska Institutet and at the Department of Medical and Health Sciences, Linköping University.

Photo by: Martin Andersson

“The placebo is an underused trick”

“We’re always being fooled” “It seems obvious to perceive our own bodies as our own. But for me as a researcher, it’s very strange. It’s an amazing feat of your brain to be able to distinguish between your own body and those of others, and to determine where your own body ends and begins. I got the idea for one of my experiments when I was bored during a lecture. I wondered what would happen if my eyes ﬂew away and looked at myself from the outside. Would I feel like I went with my eyes or stayed in my body? I tried to trick the brain by moving the visual perspective using video cameras, but it turned out that this was not sufficient. But if we simultaneously touch the real body and the illusory body – then there is a feeling of being outside your body. Since then, I have learned to

manipulate the body image in many ways. I’ve had subjects experience having three arms and changing bodies with another person. Most recently, we have succeeded in evoking the experience of having an invisible hand in thin air, thus very similar to that felt by amputees with phantom sensations. But my favourite so far is probably the Pinocchio illusion where you feel your nose getting really long. These illusions are interesting because they help us to understand why the brain interprets reality as it does, in its normal state or in the event of various diseases. And for the brain, there is no real difference between illusion and reality. In a way, it’s always fooling us into believing that reality takes a certain form, even when that form is true.”

As told to: Ola Danielsson

Name: Henrik Ehrsson Title: Professor of Cognitive Neuroscience at the Department of Neuroscience. Researches: How we feel that our own bodies are our own.

Medical Science–2014

Cause: The tubercle bacillus Mycobacterium tuberculosis that is spread when people with the disease cough, sneeze or spit. Symptoms: Chronic cough with blood-tinged sputum, fever, night sweats, weight loss. Symptoms from other infected organs. Affects: A third of the world’s population has been exposed to the infection. Every year, 8 million people get the disease, 2 million die.

From historic retreat to resistant threat Through the ages, tuberculosis has swept back and forth and taken more lives than almost any other disease. It affects more people today than at any time in history.

1500 f Kr

Text by: Ola Danielsson

1800 / Romanticised misery. In the 1800s, many believed that the sick possessed an uncommon energy and considered their scrawny appearance beautiful. In some circles, it was believed that the sick were vampires who sucked the life out of others.

1882 / The tubercle bacillus is discovered. Robert Koch identiﬁes “the tubercle bacillus” (today known as Mycobacterium tuberculosis) as the cause of tuberculosis. For the ﬁrst time, it was possible to begin to develop a cure.

1800

1865 / It’s contagious! Jean-Antoine Villemin succeeds in infecting a rabbit and proves that tuberculosis is an infectious disease. Many had previously thought that the disease was hereditary.

1900

1890 / Foundations are laid for a diagnosis method. The same Robert Koch extracts the substance tuberculin from the tubercle bacillus and shows an immune response and fever chills when he injects it in himself. This leads to a test for tuberculosis. 16

Medical Science–2014

1500 BC / The Egyptians had it. Egyptian murals and traces of DNA in mummies are the earliest evidence of tuberculosis. But the disease is believed to have plagued humans long before that.

1920

1900 / The sanatorium era. In the absence of drugs, it is thought that rest, fresh air and seclusion from the outside world in a sanatorium is the best treatment for tuberculosis patients.

1940

1943 / The first medicine. The first antibiotic preparation against tuberculosis, streptomycin, is isolated and the following year cures the first patient. But antibioticresistant forms are soon discovered.

1921 / The ﬁrst vaccine. A tuberculosis vaccine is developed by Albert Calmette. Twenty years later, the World Health Organisation immunises 14 million people in its biggest initiative to date.

Photo by: Istockphoto, Getty Images

Timeline Tuberculosis

1950 / Mysterious retreat. The tuberculosis epidemic in Europe and the United States diminishes sharply. This is partly due to better living conditions, but to this day, researchers still do not understand why the retreat of the disease was so great. In other parts of the world, the epidemic continues at full strength.

1993 / Global comeback. The World Health Organisation classiﬁes the tuberculosis epidemic as a global emergency.

1970

1950

1990

1969 / One in three is infected. Researchers test 600,000 U.S. marines and discover that latent tuberculosis infection is common in the United States and other countries with a low incidence of tuberculosis. We now know that one third of the world’s population carries the tuberculosis infection, which may ﬂare up if the immune defence weakens.

Markus Maeurer. Photo by: Ulf Sirborn T O D AY

New treatment to repair the lungs Future challenges Better detection of resistance Most cases of antibiotic-resistant tuberculosis are not detected, treated incorrectly or not at all. Now researchers are trying to develop more simple tests for use on site in the poor areas that are hardest hit.

2013 / Promising drugs. The ﬁrst new drug against tuberculosis since 1963 is approved by the Food and Drug Administration of the United States. The drug bedaquiline is expected to be effective against antibiotic-resistant tuberculosis.

Cost reduction Treatment of a patient with antibiotic-resistant tuberculosis costs about SEK 1 million. Now researchers are trying to develop more inexpensive methods that can also be used in low-income countries.

Vaccine development It is only a matter of time before resistance to new forms of antibiotics arises, so researchers are attaching great hope to a future vaccine that can prevent the disease.

Sources: Zero death from tuberculosis: progress, reality and hope: Zumla A, Kim P, Maeurer M, Schito M, Lancet Infect Dis, april 2013. The history of tuberculosis: Thomas M. Daniel, Respiratory Medicine, August 2006, Tuberculosis, Drug Resistance, and the History of Modern Medicine, Keshavjee et al NEJM, September 2012, Doctors Without Borders.

2010

Treating antibiotic-resistant tuberculosis is expensive and takes a long time. The lung tissue is destroyed by the long lasting inﬂammation, and the patient might not survive even if the infection is cured. In a new research project, Markus Maeurer, professor at the Department of Laboratory Medicine, is testing a new supplementary treatment that can improve the effectiveness of antibiotics. Mesenchymal stromal cells are taken from the patient’s spinal marrow and cultivated outside the body.When they are returned in greater numbers, they help to build up the lung tissue and also direct the attack of the immune defence against the bacteria. “It looks promising. Because the patients recover faster, the cost will also be lower. We hope that this method will be used in countries that lack resources, where today multi-drug-resistant tuberculosis is basically a death sentence.” The treatment is now being tested in South Africa, where the incidence of tuberculosis has increased by 400 per cent over the last 15 years. Medical Science–2014

Hello there Cecilia Götherström

Cecilia Götherström is a stem cell researcher at the Department of Clinical Science, Intervention and Technology and is coordinator of the National Cord Blood Bank in Stockholm.

who wants more cells in the bank

A bank worth more than gold The National Cord Blood Bank stores the most valuable of gold nuggets – stem cells that can save the seriously ill. For a couple of years, surplus cells have also been used for research. Text by: Eva Ristoff Photo by: Jacob Sjöman Why the need for a bank for cord blood?

“Blood from umbilical cords contains haematopoietic stem cells and can be used for transplantation in the case of diseases such as leukaemia, metabolic diseases, and certain immunological diseases. These are often otherwise treated with transplanted bone marrow or stem cells from adults. It can be difﬁcult to ﬁnd a donor match, especially for non-Europeans, and for about one third of patients no suitable donor is found. Cord blood stem cells, which are easier to match with the recipient than bone marrow, can then be of decisive importance.” How is collection done?

“Before the birth, parents are asked about the donation of umbilical cord blood. Almost everyone says yes. We collect about one decilitre of blood when the baby is born. We take samples to check that the mother is healthy and to count and determine the type of the stem cells. The cells can be stored for 20-25 years in a nitrogen freezer without being destroyed, and can be taken out when a patient in Sweden or another country needs them.” 18

Medical Science–2014

How is the bank used by researchers?

“If the quantity of stem cells in the collected blood is less than what is needed to treat a patient, they can be used for research if the parents have given their consent. A lot of this has to do with developing ways to cultivate and multiply the coveted stem cells in the laboratory. If this can be done, the blood from one donor could be suﬃcient for several courses of treatment. We also want to understand how stress during the birth aﬀects the cells and their suitability for transplantation. There, we compare stem cells from various types of deliveries; normal, with vacuum extraction, and caesarean section. Some 30 Swedish research projects currently use stem cells from the bank.

The blood bank was opened to researchers in 2011, so there are no results yet.” Some time ago, it was reported that it is better for the baby to wait a few minutes before clamping the umbilical cord. How do you check this?

“We want to ensure that blood donation poses no risk to the baby. At the same time, three quarters of the cord blood has passed over to the baby after one minute, so if you wait longer than that before collection, there will be too few stem cells left to be enough for a transplant. So we compare the pluses and minuses, both for the cells and for the baby, of clamping the umbilical cord immediately, after one minute or waiting more than three minutes. We expect to see results in early 2014.”

Medicine in numbers

Pregnant treasure troves for stem cell researchers Pregnancy represents a unique source of perinatal stem cells, which researchers hope to be able to use in the future to replace diseased or abnormal tissue. ey are now evaluating which sources are the most suitable to use. Chorionic villi - tiny, ﬁnger-like projections on the part of the placenta that has the genetic makeup of the fetus. Amn iot ic ﬂ ui

Stem cells from here are taken in connection with prenatal diagnosis and are used in research on how to use the child's own cells to treat abnormalities.

Placenta Place nta

Umbilical cord blood Contains unique stem cells that can become bloodforming cells and which have been used for over 20 years in the treatment of diseases such as leukaemia.

Amniotic ﬂuid Used to produce stem cells for various kinds of research.

Wharton's jelly - connective tissue in the umbilical cord.

Fetal tissue from early abortions These tissues can give rise to immature cells that have an extra great potential to become other types of cells, such as neurons or heart cells. They are already used today to treat a severe bone disease, and there is a bank for stem cells from fetal tissue.

Skin or muscle tissue from fetuses in late abortions Researchers try to use these tissues to cultivate larger pieces of tissue for transplantation. In the future, it is hoped that it will be possible to take tissue samples from live fetuses in the womb. Babies who have already been prenatally diagnosed with severe disorders, such as spina biﬁda, could undergo surgery soon after birth if a full transplant consisting of the child's own tissue were to be ready at delivery.

In all the above cases, parents must give their consent to the collection and use of cells or tissue. SOURCE: CECILIA GÖTHERSTRÖM

PALOMA PÉREZ LUCERO/ TT NYHETSBYRÅN

Medical Science–2014

Perspective: Drowning

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Medicinsk Vetenskap №1–2013

Research keeps children

above water

An abundance of waterbodies and lack of swimming skills make drowning the leading cause of death among children in Bangladesh. Research from Karolinska Institutet is now being used to reduce the number of lives lost.

Photo by: Per Liljas

ears come to Zaeda Khatun’s eyes as she relives that fateful day a year ago when her two-year-old son lost his life. “I had just prepared our meal to break the fast and was waiting to hear the call to prayer when I looked around for Shahidul. Suddenly he was gone.” Just as in the rest of Bangladesh, the countryside where Zaeda lives is made up of a web of waterbodies. Zaeda found her son head-down in the water-ﬁlled ditch behind her house. “I ran there, screaming, and many neighbours came. I don’t remember anything else after that.”

SHAHIDUL’S FATE is one met by large numbers of Bangladeshi children every year. The extent, however, was unknown until 2004, when the Bangladesh Health Injury Survey, BHIS - the world’s largest study of injuries in developing countries - showed that drowning is the leading cause of death for Bangladeshi children. Researcher Fazlur Rahman’s doctoral thesis from Karolinska Institutet in 2000 was behind the study’s methods. His colleague Aminur Rahman, who at the time was in the middle of his thesis at Karolinska Institutet, focused on how Bangladesh could use the results of the study to deal with the problem. Since 2007, they have both worked on translating Aminur Rahman’s theory into practice. “It took me longer to present my thesis than for many others because I was combining my research with my work on the BHIS,” says Aminur Rahman when I meet him at his oﬃce in Dhaka. “But the advantage was that I could

collect a large amount of data. Many theses were based on around a hundred cases – I had a total of 600,000.” In his research, Aminur Rahman found that virtually all the cases of drowning in Bangladesh occurred during the day when the children’s mothers were busy doing housework. He also found that the parents were unaware that the highest risk was found among children under five and that their notions of first aid could often be directly harmful, such as holding the children upside down and shaking them or massaging their tummies. Aminur Rahman developed a couple of robust, local methods to address the risk of drowning, implemented them in a sub-district and then compared the results with a control group in another sub-district. Among other things, he employed a number of women to set up simple day-care in their homes, parents were taught the importance of putting up barriers so their toddlers would not easily be able to slip outside, and some in the village were selected for first aid training. After two years, drowning accidents in the community where the methods had been applied had decreased by 55 per cent, whereas in the other community they had increased by 44 per cent. After Aminur Rahman completed his doctoral thesis, he and Fazlur founded the organisation CIPRB, Centre for

“Teaching a child to swim in this way costs about ﬁfty Swedish kronor”

Injury Prevention and Research, Bangladesh. With support from sources such as UNICEF and AusAID, they have launched several projects using Aminur Rahman’s methods and have developed a swimming school for children aged ﬁve or older – SwimSafe. The swimming instructors have been taught by Australian trainers in Dhaka. In six years, they have taught more Aminur Rahman. than 260,000 children to swim in simple bamboo platforms, which are built locally and lowered into the ponds where people wash clothes and cattle. “Teaching a child to swim in this way costs about ﬁfty Swedish kronor,” says Aminur Rahman. AFTER LONG HAVING a primary focus on infant health, the Government of Bangladesh has become increasingly alert to the drowning risk. Aminur Rahman has also travelled to nearby countries, such as Cambodia and Thailand, to be an advisor in similar projects. After her son died, Zaeda Khatun moved from her house and got rid of all of the things that reminded her of little Shahidul. But both of her surviving children are now in the village’s small day-care group set up by CIPRB. Eventually, they will also be receiving swimming lessons. And in due time Aminur Rahman himself might learn to swim. “I’ve done research on it, started swimming schools and even helped write primary school books about how to swim, but I don’t yet know how to do it myself,” he laughs. Per Liljas Medical Science–2014

The disease: Breast cancer

Cause: A combination of lifestyle factors and genetics. Giving birth to many children early in life and breastfeeding for a long time provides some protection. Symptoms: A lump may arise in the armpit or breast, which may change form. The nipple may become retracted or begin to bleed. Often no symptoms at all. Affects: In 2011, just over 7,700 Swedes were diagnosed with breast cancer, 40 were men. In 2008 almost 1.4 million people worldwide were diagnosed.

“Women will know their breast density just as well as they know their shoe size,” says Per Hall, who believes density will become a very important factor in risk assessment.

“Thousands of cancer cases are preventable” Do you know how dense your breasts are? No, thought not. But in a few years, it will be common knowledge for Swedish women. This is what breast cancer researcher Per Hall believes. Text by: Annika Lund Photo by: Gustav Mårtensson 22

Medical Science–2014

he number of women being diagnosed with breast cancer is steadily increasing. And nobody really knows why. But the disease is more common in women who have given birth to few children and had their ﬁrst child late in life – and Swedish women give birth to fewer and fewer children later and later in life. However, this is not believed to explain the entire increase, so the advance of the disease is ‘a sad mystery’ according to Per Hall, Professor of Radiation Epidemiology at the Department of Medical Epidemiology and Biostatistics. “But what is most sad is that we accept this. You see, we do almost nothing at all to prevent people from getting the

THE CHANGE HE HIMSELF wants to

bring about concerns the mammography programme. Screening all women in the same way using intervals based on age is, according to him, “completely insane”. Per Hall instead wants women at their first mammography control to have their individual risk for the disease calculated on the basis of the breasts’ mammographic density, lifestyle factors and a genetic analysis. The women should then be offered examinations at differently spaced intervals. In the case of higher risk, mammography should be supplemented with ultrasound. Per Hall thinks that those who run the highest risk of getting the disease should also receive preventive medication. “If we know that a particular woman runs a 30 per cent risk of getting breast cancer in her lifetime and we can halve that risk – isn’t it unethical not to? How can we with open eyes allow some women to be diagnosed with the disease – even though we can avoid it?” How women should be screened in the future and what medicines to use at what doses – these are as yet unanswered questions. For this reason, Per Hall wants to start a study that will provide the data to determine this. Previous research has identified statins, aspirin and metformin as possible preventive treatments, but more central to the discussion are the anti-hormones that are currently administered to prevent disease recurrence. These work by reducing the effect of oestrogen on breast tissue – and

“We do almost nothing at all to prevent people from getting the disease – even though we are able to” published research shows that they can greatly reduce the onset of breast cancer if given to healthy individuals. “Because the medicines have side effects, we should only give medicines to those who will benefit from a preventive treatment. With this strategy, I think we can reduce the incidence by, let’s say 2,000 cases per year. Actually, I think we can avoid even more breast cancer cases because preventive treatment with anti-hormones is extremely effective in the right patient group,” says Per Hall. IT HAS LONG BEEN KNOWN that tumours develop more often in mammographically dense breasts, that is breasts with a lot of breast tissue. Why density plays a role is not fully understood – but one of several plausible explanations is that the denser breasts are, the more cells there are that can be transformed into cancer cells. Denser breasts also appear to contain more oestrogen receptors – and oestrogen plays an important role in the development of the disease. An estimated 80 per cent of all breast cancer is hormone dependant. The relationship between mammographic density and breast cancer is therefore still under exploration. It is however clear that the relationship is considered strong and highly relevant to risk assessment. Per Hall and his colleagues recently published a study including women who have had surgery for breast cancer. Many of them received anti-hormones, and those with a great decrease in density ran half the risk of recurrence compared with women who had little or no density reduction. “When we show this to oncologists, we are met with almost unbounded enthusiasm. Density reduction is a very powerful marker for assessing the risk of recurrence. We have no other marker that is as powerful – the size of the tumour, for example, gives nowhere near the same clear indication. This says something about the central importance of mammographic density,” says Per Hall.

Journal of Clinical Oncology April 2013

More recent results from Per Hall’s research team: Gene variants increase risk In about a thousand places in our genome, abnormalities may arise that increase the risk of breast cancer. Researchers have succeeded in calculating this in a major EU research collaboration known as COGS. The researchers have so far found around 80 abnormalities that increase the risk for breast cancer and they expect to identify the vast majority within a few years. Then it will be easier to calculate the individual risk of getting the disease. Nature Genetics March 2013 nature.com/icogs Radiation increases the risk of heart attack Women who have been treated with radiation for breast cancer run an increased risk of having a heart attack. The greatest risk is run by women who also have other risk factors like diabetes, smoking or high BMI. The study covers 2,200 irradiated breast cancer patients and shows that the risk is highest in the ﬁrst ten years following radiotherapy. New England Journal of Medicine March 2013 Medical Science–2014

Icon: Kirill Ulitin/The Noun Project

disease – even though we are able to.” Per Hall has plenty of drastic statements of this kind – he is skilled at creating public opinion. He learned this early in his career as a young oncologist at Radiumhemmet (Department of Oncology, Karolinska University Hospital). A tighter budget no longer allowed radiation treatment for all patients. The head at the time, Jerzy Einhorn, made sure the dilemma became known through the media. When the general public was told that older patients would be given lower priority, politicians hastened to inject more money. “If the public sees something as very wrong, it is diﬃcult for a politician to stand against the prevailing opinion. If you want to succeed in making an important change, you have to work on a broad front with respect to the public and work on a focused front with respect to politicians,” says Per Hall.

A researcher’s tale

“The world’s press was waiting” Chair of the Nobel Committee at Karolinska Institutet, Juleen Zierath, tells Medical Science about the moment it was clear who was to receive the Nobel prize in physiology or medicine. As told to: Cecilia Odlind Photo by: Tomas Söderlund

Name: Juleen Zierath Title: Professor of Clinical Integrative Physiology at the Department of Molecular Medicine and Surgery. Chair of the Nobel Committee at Karolinska Institutet. 24

Medical Science–2014

“On 7 October 2013, we presented the proposal for this year’s laureates in Physiology or Medicine to the 50 professors of the Nobel Assembly. By that time, the Nobel Committee had been working very hard for a whole year on the different proposals and we had many instructive and lively debates. The assembly adopted our proposal, but a few hours still remained before the laureates were to be announced. Downstairs, the world’s press was waiting. The feeling, of being one of the few people to know something that will soon explode across the world, is exciting. Since becoming Chair of the Nobel Committee, I’ve become a public figure. There are many situations where people will approach me to say who they think should get the prize. Many people think I have a much greater influence over who should receive the prize than I actually have. There are even instances of people thinking that it is me who decides who will get the economics or the peace prizes. I’m also regularly contacted by researchers who nominate themselves. I’ve been sent documentation in foreign languages as thick as a phone book and lengthy descriptions of experiments they say I should perform to understand that they should be awarded the Nobel Prize. Then I explain that self-nominations are not allowed. As the first woman in this position, I’ve received extra attention. Personally, I’m a bit dismayed that young female researchers around the world today seem to feel much the same lack of female role models that I myself experienced at the beginning of my career 30 years ago. I’d be happy to be their role model. But I don’t want to limit myself to only putting women forward. I think that science is strengthened by diversity in all its forms. Today, many other groups are also underrepresented in research, for example, researchers from certain parts of the world.”

Advances No serious adverse reactions to HPV vaccine

Health beneﬁt. Girls with highly educated parents more often gets HPV vaccine.

Highly qualiﬁed parents more disposed to vaccines Whether or not a girl has a cervical cancer vaccination might depend on her parents' education. esearchers followed up 124,000 girls and women in Sweden who, between 2006 and 2010, received the HPV vaccine, which can provide protection against genital warts and cervical cancer. Part of the purpose was to study who took the vaccine. It was a full 15 times more common for children of parents with a university education to be vaccinated than children of parents with a low level of education. Previously, girls of 13-17 years of age Lisen Arnheimwere oﬀered the vaccine Dahlström. Photo by: Stefan at a reduced price, with Zimmerman others having to pay the

Photo by: Getty Images, Istockphoto

full price. Since 2012, the vaccination is part of the Swedish vaccination programme and so is offered free of charge to all girls between the ages of 10 and 12 and, for a limited time, also to girls aged 13-18. “In the future, the distribution is likely to be more equal. You don't have to arrange the vaccination yourself, and confidence in the vaccine is likely to increase when it is offered as part of a programme,” says Lisen Arnheim-Dahlström, researcher at the Department of Medical Epidemiology and Biostatistics and responsible for the study funded by the pharmaceutical company Merck Sharp & Dohme, which sells the vaccine. Eva Ristoff Journal of the National Cancer Institute March 2013

According to a patient data registry study no signiﬁcant increase of a wide range of diseases was shown in HPVvaccinated girls relative to their unvaccinated peers according to Swedish and Danish researchers. The study included almost a million Swedish and Danish girls born between 1988 and 2000, and compared roughly 300,000 girls who had been HPV vaccinated with 700,000 who had not. All the girls were between 10 and 17 at time of vaccination, and the vaccines had been administered at some time between 2006 and 2010. The researchers then used patient registries in Denmark and Sweden to study the incidence of any serious adverse effects of the vaccine. The researchers examined 53 different diagnoses requiring hospital or specialist care, including blood clots, neurological diseases, and autoimmune diseases such as type 1 diabetes. They found that none of these diseases were more common in the vaccinated group than in the unvaccinated group. “You could see our study as part of a societal alarm system, and as such it did not alert us to any signs that HPV vaccination carries a risk of serious adverse events,” says Lisen Arnheim-Dahlström, researcher at the Department of Medical Epidemiology and Biostatistics. “We will, of course, be continuing to monitoring HPV vaccination.” British Medical Journal October 2013 Medical Science–2014

Every minute counts. During a stroke, two million brain cells die every minute when the blood can not deliver oxygen and energy to them. Time to treatment is therefore very critical. 26

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T H E M E : ST R O K E

Stroke

– a race against the clock

Every 17 minutes someone in Sweden suffers a stroke. The consequences for the victim can be anything from death to a virtually full recovery, depending on the severity of the attack and how quickly treatment can be administered. Researchers are now trying to find new ways to reduce the damage caused by stroke and improve the odds of making a recovery. It is first and foremost a race against time. Text by: Fredrik Hedlund Photo by: Istockphoto

FOR EVERY MINUTE that a blood vessel is blocked during a clot-induced stroke, two million brain cells die and the brain ages by three weeks. And the longer it takes for the clot to be treated, the greater the damage will be. Since the extent of the damage in brain tissue is directly related to how well patients do afterwards, it is absolutely essential to limit the damage as much as possible. “The research relates to how we can reduce the acute damage of stroke,” says Nils Wahlgren, Professor of Neurology at the Department of Clinical Neuroscience at Karolinska Institutet. Every year, more than 30,000 people in Sweden suﬀer a stroke, which is one every 17 minutes, around the clock. Stroke is by far Sweden’s most expens-

ive physical disease because it leads to more days under hospital and nursing home care than any other physical disease. The annual cost weighs in at just over 16 billion kronor. A stroke can be caused by two completely diﬀerent problems in the brain. The most common cause is a blood clot that clogs a blood vessel in the brain and prevents the blood from supplying oxygen and energy to the parts of the brain beyond the blockage. About 85 per cent of all stroke victims have a stroke because of a clot. The remainder are instead caused by bleeding in which a blood vessel ruptures and blood ﬂows into the brain. This can both damage brain tissue directly and stop the blood from supplying oxygen and energy, just as in the case of a clot.

Despite these completely different causes, the symptoms of stroke are often very similar. The national stroke campaign has launched the AKUT test to make it easier to recognise a stroke. The effect of a stroke on the victim varies greatly. Studies have shown that about 20 per cent die and 30 per cent become functionally dependent, which means they need the help of another person for basic things like going to the toilet. And as many as 50 per cent are functionally independent. But Nils Wahlgren says there are many distinctions that this picture fails to make. “Half being functionally independent sounds like a very good figure, but a lot of problems lurk underneath. Patients can have various degrees of disruption to neurological functions that might Medical Science–2014

T H E M E : ST R O K E

ways to fewer stroke cases Mia von Euler, Associate Professor in Neurology and Head of Karolinska Institutet Stroke Research Network at Södersjukhuset, lists three areas for improvement to be investigated in a new research project. 28

Medical Science–2014

young, otherwise completely healthy individuals,” says Nils Wahlgren. NILS WAHLGREN AND SEVERAL of his colleagues at Karolinska Institutet are world leaders in a number of areas of stroke research. One example is research on improving thrombolysis - the clotbusting treatment used for the majority of patients whose stroke was caused by a blood clot (or thrombus). Doctors use a medication called “tissue plasminogen activator”, tPA, to dissolve clots in the brain. The disadvantage of this medication is that it is typically only possible to use it up to 4.5 hours after the first stroke symptoms. After this time, its effect is reduced, increasing the chances of symptomatic bleeding due to the risk of the blood-brain barrier, which normally protects the brain from foreign substances, being opened in an uncontrolled manner. But Ulf Eriksson, Professor of Vascular Biochemistry at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, might have found an unusually successful solution to this problem. Ulf Eriksson’s research focuses primarily on identifying and functionally describing the body’s own signalling molecules. Just over ten years ago, he was working on the production of new growth factors and discovered a factor that turned out to be activated by tPA. He asked himself whether it might have something to do with the risk of bleeding in the case of late tPA treatment. And indeed it did. “It turned out that the tPA-activated growth factor we had identified could single-handedly open the blood-brain barrier in a way almost identical to that during a stroke,” says Ulf Eriksson. Together with colleagues from the United States, he charted the mechanism

1. Better handover from hospitals to health care centres when stroke patients are discharged. “The primary health care centres do not always find these patients, and we want to find out how common this is and why.” 2. Treating atrial fibrillation. “There is an under-treatment of atrial fibrillation, which is a risk factor for stroke. Doctors and patients fear that treatment with the anticoagulant Waran can lead to bleeding in the event of a fall and

at the receptor level and as luck would have it, he found that there was already an approved drug that blocked that very receptor. Imatinib, or Glivec as the drug is called at the pharmacy, is currently used to treat quite a rare form of blood cancer known as chronic myeloid leukaemia, CML. In animal experiments, Ulf Eriksson was able to show that imatinib administered to mice with stroke caused by a blood clot in the brain reduced both the blood-brain Ulf Eriksson. barrier’s permeability Photo by: Ulf Sirborn and the problems of bleeding in the case of late tPA treatment. “By administering imatinib, we were able to extend this treatment window. You might say that we separate the good effect of tPA, that is to dissolve blood clots in the brain, from the harmful effects,” says Ulf Eriksson. Thanks to a major grant, researchers have now been able to set up their own clinical trials on an academic basis. “If we get indications that the treatment reduces bleeding or fluid inflow, we hope to garner interest from industry. This has the potential to be a very important treatment,” says Nils Wahlgren, who is leading the study. But they are not there yet. The study was carried out during 2013 and concluded by the end of the year. But even if the pharmaceutical industry’s interest in paying for further clinical development is not aroused immediately, Nils Wahlgren believes that there are opportunities for further development. This is because he is also coordinator of the world’s largest database for the treatment of stroke called SITS, “Safe Implementation of Treatments in Stroke”, which currently

the treatment may be considered as too complicated for some patients. However, in recent years, there have been several new anticoagulants, and thanks to the information about them, we are happy to note an increase also in prescriptions of the older treatment. Now we will follow up on the treatments to understand what it is that determines who gets treatment and who does not.”

3. Preventing recurrence due to discontinued treatment. “The reality is that some patients discontinue their life-long treatment after a stroke. The solution may be better written information that is individually designed. A patient who has suffered a stroke caused by a clot should not be given information about strokes caused by bleeding. As the treatments are different, this could be totally confusing.”

Photo by: Märta Thisner

present a major intrusion on their daily lives; they may no longer be able to work, drive a car or engage in previous hobbies, like playing the piano. There are many things that can have a huge impact on their lives, even if they are not dependent on someone else’s help for basic needs,” he says. In addition, a stroke involves a higher risk of depression several months after the acute phase, as well as an increased risk of developing dementia in later life. But according to Nils Wahlgren, there are also those who will make a full recovery, but there are unfortunately no definite figures for this as it is not quite certain what is meant by a full recovery. “Perhaps you are back and look fine, but there are still some small details that affect you. I think that if you have suffered a stroke, it always leaves its mark on you in some way,” he says. So the best thing, of Nils Wahlgren. course, is to avoid bePhoto by: Ulf Sirborn ing hit by stroke. But there is no preventive treatment to protect otherwise healthy people against stroke. It is rather a matter of managing risk factors. Two important risk factors for stroke are high blood pressure and diabetes. These should be treated so that they stay within the threshold values for each condition. Also, the risk can always be reduced by healthy living, exercise and not becoming too overweight. Another very important risk factor is untreated cardiac fibrillation, which increases the risk of blood inside the heart forming a clot that can then be torn loose and become lodged once it reaches the brain. “Going around with untreated cardiac fibrillation is a very great risk, except in

Blood clot the leading cause of stroke About 85 per cent of stroke cases are caused by a blood clot. Quick treatment is necessary to limit the damage. Area with dead brain cells. Area that can be saved if treatment is given.

Two million neurons die every minute around the clot.

0 hours: Blood clot lodges in the brain Blood ﬂow in the vessel is cut off, and brain cells around the clot immediately begin to die from lack of oxygen and energy.

1 hour: The clot can be dissolved or withdrawn The infarction, the area with dead cells, spreads in the penumbra (Latin for ‘almost shadow’), the area with brain cells that might potentially die, but that can be saved if the clot is dissolved or withdrawn.

3 hours: The brain has aged ten years If the clot remains in place, the infarction will spread more and more. 360 million brain cells have now died, and the brain's life has decreased by 10-11 years.

4.5 hours: The clot can still be withdrawn Dissolving the clot is now less effective and is associated with greater risks, but it is still possible to withdraw large clots mechanically by means of a thrombectomy, a procedure developed, among others, by researchers at Karolinska Institutet. The catheter is Doctors navigate through the blood vessels 2 mm wide

Thrombectomy involves using x-rays to navigate a telescopic catheter from the groin all the way up to the brain. The clot is removed and withdrawn via the same route. BLOOD VESSEL TELESCOPIC

CATHETE

Two types of bleeding can cause a stroke

The blood vessel ruptures.

In strokes caused by bleeding, the Bleeding inside the Bleeding under the brain, brain primarily affects older in the subarachnoid space, more damage progresses in a similar people. Over time, high blood frequently affects younger manner as with a clot, but pressure or diabetes has persons. This is often due to depending on the type of bleeding, created small weakenings a congenital aneurysm (Greek the starting point diﬀers from of the blood vessels, known for ‘dilation’), which causes individual to individual. as microaneurysms. a weakening of the blood vessel. SOURCE: NILS WAHLGREN

PETRA FRID/TT NYHETSBYRÅN Medicinsk Vetenskap №1–2013

encompasses over 80,000 stroke patients from 1,300 centres in 60 countries. By means of the contact network from the database, he can do research that would otherwise be financially impossible in an academic environment. “We can turn to our 1,300 centres around the world and ask who would be interested in participating in a clinical trial. In this way, we can carry out a pretty economical academic study,” he says. And using the contact network in the database is something that already enables a study of an entirely different method, which is used to remove blood clots so large that it takes a long time to dissolve them with tPA. This involves something called thrombectomy, which simply put means the mechanical removal of the blood clot that is blocking the vessel like pulling a cork out of a bottle - though it is slightly more complicated. A sort of telescopic catheter is inserted in the patient’s groin and can then be navigated up through the aorta via the neck vessels, continuing up to the vessels in the brain while the patient is awake. Using contrast fluid and x-rays, the

The robot suit HAL is now being tested in Sweden as a way to quickly get started with walking training after stroke.

Medicinsk Vetenskap №1–2013

doctor can see the clot’s precise location in the brain, navigate to it and with a special instrument withdraw it all the way down and out through the groin. “Important factors are the time until the clot is removed and the patient’s capacity for a back-up supply to the brain,” says Staffan Holmin, Professor of Clinical Neuroimaging at the Department of Clinical Neuroscience at Karolinska Institutet. If the vessel is opened in time, the patient can often improve very quickly. “We have a lot of fantastic cases where patients come in extremely ill and go home a couple of days later,” he says. Staffan Holmin is one of the four interventional neuroradiologists who perform the mechanical clot removal and is also vice chairman of the Department of Neuroradiology at the Karolinska University Hospital, which for several years has been among the world’s leading exponents of this technique. But despite good experiences, the technique must be proven scientifically in international studies if it is to gain a greater user base. And the positive

patient cases give rise to an ethical dilemma. “With the experience we’ve had at our hospital, we can’t really be drawing lots to see which half of the patients won’t be treated. This view is shared by many other leading hospitals,” says Nils Wahlgren. Instead, he has used the database to recruit 30 hospitals around the world that have extensive experience of thrombectomy Staffan Holmin. and 30 hospitals that Photo by: Private are highly skilled in dissolving clots with tPA, but that do not have the opportunity to withdraw them. The research study then involves comparing how patients do at the various hospitals and seeing if it can be shown which method is best. If everything goes to plan, there will be an answer in 2014. Recently, new results were published in the New England Journal of Medicine which showed that recovery after a blood clot in the brain was not better if the clot was removed mechanically. But Nils Wahlgren does not think these results will be of great significance because the techniques used today have been refined. “The studies were done with an older technique, and most subjects were only given drugs and not mechanical treatment. The studies don’t actually say anything about the modern thrombectomy procedure,” says Nils Wahlgren. Staffan Holmin also uses the technique with the telescopic catheter in experimental research projects whereby he has succeeded in creating a new, better and more clinically relevant means of inducing stroke in laboratory animals. This method makes it easier to obtain answers about the condition of brain tissue during the acute phase, which can then be used to tailor treatment for different stroke patients. He has also developed new microcatheter-based methods for delivering stem cells for transplantation or other types of substance locally to the brain or to other organ systems. Because all stroke treatment is a race against time, Nils Wahlgren is also running a study to see how much it is possible to shorten what is known as the “door to needle time”. “We have seen that in Stockholm, as well as internationally, it takes about 60 minutes from door to needle. For a year now, we have been leading an interna-

Photo by: Carin Wesström

T H E M E : ST R O K E

Discover a Stroke in Time

Face

Arm

Speech

Time

Can the person smile and show his/her teeth? If one side of the mouth droops - call the emergency telephone number!

Can the person lift his/her arms and keep them up for 10 seconds? If one arm falls - call the emergency telephone number!

Can the person repeat a phrase like “The weather is nice today”? If the person slurs or cannot ﬁnd the words - call the emergency telephone number!

During a stroke, two million brain cells die every minute, so every second counts. Never hesitate - call the emergency telephone number directly!

tional study whose goal is to get down to under 40 minutes,” he says. The possibility of shortening the times has been shown by his colleagues in Helsinki, where they have gone from 55-60 minutes all the way down to 25 minutes. Another interesting line of research that has not come as far relates to elevated blood sugar levels in the acute stroke phase. It has been shown that elevated blood sugar increases the risk of death, bleeding and becoming functionally dependent. And this applies to all patients, not just those who have diabetes. “We are beginning to suspect that there are some very, very important things to study here,” says Nils Wahlgren.

ping into new neurons in the brain, but we still do not know what this means with respect to regaining functions after an injury,” says Jörgen Borg, Professor of Rehabilitation Medicine at the Department of Clinical Sciences, Karolinska Institutet, whose research is about improving the rehabilitation process after acquired brain injuries in adults. But re-learning demands hard work immediately after the stroke, in which training is used to try to push brain network activity to become functional again. “It is known that training that starts early and is intensive makes a difference to the pace of recovery, and there is BUT REGARDLESS of how good emersupport for the end result being better,” gency treatment is in the future, there says Jörgen Borg. will always be a great need for rehabiliThe realisation that the brain is plastic tation following a stroke. Brain tissue and that the connections between dies and essential functions disappear, neurons can be rebuilt throughout life but not necessarily forever. There is in order to re-learn and to learn new the possibility of re-learning and of things became an established truth in learning new things because the brain scientific circles in the 1960s and 1970s is plastic, which means that the brain’s and is fundamental to today’s rehabilifunctional networks can be rebuilt tation programmes. Now, research has throughout life. Most people have been a lot to do with understanding what is taught that we are born with a certain going on inside the brain so as to indivinumber of brain cells, a number that dualise rehabilitation. can only go down. Think again, for that “Modern brain imaging has meant is not the case at all. a great deal to our understanding “No, that’s what all the old of the brain’s plasticity and textbooks say, and it is a adaptability after an injury. truth that has had to be What appears to be the Take the revised. We now know same clinically can AKUT test and that there are stem have different explanalearn to recognise a cells, we know they tions, and we believe stroke: are capable of develounderstanding this is

strokekampanjen. se/sprak/engelska

one of the keys to being able to design individualised treatment programmes,” says Jörgen Borg. But it is also a matter of completely new aids. At present, Jörgen Borg and his team are conducting a small pilot study with the robot suit HAL, “Hybrid Assisted Limb”, from the Japanese company Cyberdyne. It is a kind of Robocop-like supportive skeleton that attaches to the outside of the leg and helps patients to start Jörgen Borg. training to walk more Photo by: Ulf Sirborn quickly. “It is an expression of the ambition to find new ways to intensify early training,” says Jörgen Borg. What then does the future have in store for the field of stroke? The proportion of patients who become functionally dependent after a stroke is slowly decreasing, something which may indicate both better treatment and better rehabilitation. At the same time, there is an increasing tendency of stroke in the slightly younger age groups, which could be caused by an increased incidence of diabetes and obesity. But the greatest difference in the future will probably be due to demographic change. “In 2000, 13 per cent of the population was over 70 years of age. In 2050, 20 per cent will be. We can expect an increase in the number of stroke cases because of this factor,” says Nils Wahlgren. Medical Science–2014

Icons by: Davide Eucalipto, Edward Boatman, Sébastien Desbenoit

Learn to recognise the symptoms of stroke and call an ambulance quickly.

T H E M E : ST R O K E

Back from the

Silence

Three stroke attacks left Göran Skytte unable to read, write or speak. This is the story of an amazing comeback - and of gratitude. Text by: Fredrik Hedlund Photo by: André de Loisted

have been hit by stroke - and by gratitude. These are the words Göran Skytte wrote in his first column after the three stroke attacks he suffered at the end of April 2012. The column was published in the newspaper Svenska Dagbladet at the end of August, nearly four months to the day after he became ill. By which time, he had also managed to write a book. Göran Skytte - journalist, author, filmmaker, consultant and selfemployed - does not know what it means to while away the hours. “I have worked extremely hard for many years. This often means that I start at five in the morning and finish late at night. And work with many different things,” he says.

24 APRIL 2012 was Göran Skytte’s first day off for a very long time. It was the beginning of a period in which he would take time off from all his other projects to write his new book; maybe not what most people would call time off, but that is how he describes it. During the day, he felt that something was not quite right. Then when he woke up in the night and needed to go to the toilet, his legs gave way and he was unable to walk. He managed to get back to his bed and felt dizzy, nauseous and had a massive headache. But he did not call the hospital. “I don’t have any phobias or ‘manly notions’ of not calling for healthcare. On the contrary, one of my daughters is a doctor, but it was as if I was in some sort of state of paralysis. I took the newspaper, but being unable to read the text, I fell asleep,” he says. The next day, shortly after lunch came the 32

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second stroke. Then he called. The ambulance arrived in less than seven minutes, and he was taken to the University Hospital in Malmö. There he was allowed to go to the toilet and lock the door from the inside. And then came the third stroke, the most severe. “I managed to get out under my own steam. Just a few seconds later, I wasn’t able to do anything, and there was a total commotion,” says Göran Skytte. He was rushed by ambulance to the University Hospital in Lund, where there are better facilities for looking after serious stroke cases. It was then Göran Skytte realised the real gravity of the situation. On the ﬁrst day, the doctors in Lund considered operating, but on day two, they decided that this was not needed and that his stroke could instead be medicated. During those two days in Lund, Göran Skytte had time to think and get his bearings. He realised that at times he was hovering between life and death. “BUT DURING THE ENTIRE TIME ,

I had no fear, no dread, and I was perfectly calm. What I saw was a light. Peace, calm, stillness, light and no fear,” he says. As a believing Christian of several years’ standing, he places his experience in the context of his faith. “My faith gave me a peace and a security that I had never previously known. Those who don’t believe think it’s balderdash. In my case, that very faith was massively reinforced,” he says. At the same time, he emphasises repeatedly that the doctors and other healthcare

Peaceful. “During the entire time I had no fear, no dread, and I was perfectly calm,” Göran Skytte says.

professionals “were also completely crucial to things ending well”. He understood that he had now come through the danger of dying in an acute stage. Now it was a matter of coming back to life, because as things stood, he had lost many of the abilities that had been a matter of course. He tried, for example, to read Svenska Dagbladet’s editorial page. “I didn’t have the slightest inkling of what I was reading. It was all a mishmash. I was able to read the words in the first paragraph with a great deal of effort, but I didn’t understand what they meant,” he says. Neither was he able to write, speak without slurring, or walk. “My life’s consisted of reading, writing and speaking. They’re the three things I’ve done my entire life. I’ve stood on a stage and communicated in various ways. Now it had dawned on me that I could not read, I could not write and I could not speak,” he says. He resolved to make small, but measurable progress every day. “I picked up the paper again and began to read that paragraph, and I thought I’d read this paragraph at various times every day until I understood what it says. Seven weeks later, I had read 2 500 pages of literature.” It was the same for his writing. From an initial, totally illegible handwritten message via an arduously written e-mail on a computer to his new book. And he did the same for his speech. “The whole time, I tried to talk - with the staff, I talked out loud to myself in the room, I sang manageable snippets. And in mid-July, I went to Finland and spoke publicly at four gatherings,” says Göran Skytte. The latest science suggests that early and intensive training is important for regaining lost faculties after a stroke. And that was exactly what Göran Skytte was doing. “At this point, I knew nothing about brain research, nothing about stroke, nothing about the advances of science, but it seems as if I was somehow intuitively doing the right things anyway. If you want to put a name on it, I suppose it’s a kind of intuitive sense of life,” he says. Today he says that he has undergone a fundamental change in his entire attitude to life. “Many people prefer to close their eyes to the fact that everyone can be hit by a serious illness, that everyone without exception will die and that it can happen at any time whatsoever. My own experience of my stroke is that this insight can be an extremely valuable asset. Suddenly I cannot take it for granted that I’ll get up in the morning. Who thinks about the fact of walking around and breathing? In reality, everything is completely wonderful and amazing,” he says. “I feel I have received the opportunity for a new life and I feel an enormous gratitude for that,” says Göran Skytte. Medical Science–2014

Interview

Researching for womenâ&#x20AC;&#x2122;s

freedom KRISTINA GEMZELL DANIELSSON believes that women should be able to decide for themselves if and when they want to become pregnant. For this reason, her research focuses on contraception, safe abortion and infertility. Text by: Lotta Fredholm Photo by: Linus Hallgren

Medical Scienceâ&#x20AC;&#x201C;2014

“ABSOLUTELY FREEZING, isn’t it?!” says Kristina Gemzell Danielsson as we meet outside her office in January, before quickly stepping to the kitchenette to get herself a hot cup of coffee. I myself am accustomed to the sub-zero climate, but she has just landed after two weeks in Thailand and Cambodia. Work-related, of course – in Thailand, she attended a conference on abortion. “Many other countries allow abortion in certain situations, when all’s said and done, but in Thailand, things are terribly restrictive. This is problematic because women have such a low position, resulting in a lot of violence and many unwanted pregnancies,” says Kristina Gemzell Danielsson and recalls media reports a few years ago of a large number of aborted fetuses being found stashed away in a temple. International work is nothing new for Kristina Gemzell Danielsson, who has headed the World Health Organisation Collaborating Centre for Human Reproduction at Karolinska Institutet and Karolinska University Hospital since 2000. It is one of the first in the world and opened as early as 1972. Here, medical abortion was developed – where the woman herself is able to induce an abortion by means of a drug. The procedure may be wholly or partially carried out at home and has had an enormous global impact to reduce the risk of death and injury associated with unsafe abortion, for example, relating to non-sterile instruments. The best thing is, of course, if the unwanted pregnancy can be prevented, and an important part of Kristina Gemzell Danielsson’s research focuses on developing new and better contraception. ONE LINE OF INQUIRY is to study the endometrium, the inner mucous membrane of the uterus. The team has developed a model whereby it can cultivate human mucous membrane and study how it is affected by various 36

Medical Science–2014

factors. It is possible that its receptivity to a fertilised egg can be improved as a part of infertility treatment. “Previously, it was thought that it was all about the egg, but it has been shown that there is a really exciting dialogue between the mother and the embryo,” says Kristina Gemzell Danielsson. Endometrial properties can also be manipulated in the other direction, to prevent implantation. It is here that her team has actually identiﬁed a factor

“I’m disappointed that we in Sweden today are demonstrating such a lack of history. We were a pioneering nation.”

Reproductive health is politically charged, but Kristina Gemzell Danielsson has always believed that she does the most good as a researcher.

that they are now patenting. The idea is that if it can be blocked, this could be a way to prevent a fertilised egg from attaching. But a contraceptive method of this kind is in the future. In the meantime, she would like to push the IUD (intrauterine device) as a form of contraception. A hearing on reproductive health held at Karolinska Institutet last summer was attended by Melinda Gates as the representative of the Gates Foundation. She became interested in the data presented by Kristina Gemzell Danielsson on women’s adherence to contraception. “She is American, and there is a perception in the USA that the IUD is a type of abortion method – something that medically speaking is completely erroneous. In any case, this means that they haven’t included the IUD in their programmes, but these data got

her interested,” says Kristina Gemzell Danielsson. One study investigated how common it was for women in 18 developing countries to stop using their contraception in an average year. This showed the IUD to be the best by far, with only 15 per cent stopping, while the ﬁgures stood at 60 per cent for condoms and 45 per cent for the pill. “This isn’t really that strange. You can stop taking the pill if you have a falling out. And then you make up again… It requires more careful consideration to stop using the IUD,” says Kristina Gemzell Danielsson. She believes that the IUD should be used more by Swedish teenage girls. The pill needs to be taken every day, and if a single one is missed, that month’s protection is gone. “And, of course, at that age, you have a lot of other things in your head to think about,” she says. There are myths about the IUD, for example, that it can start moving around the body. Another mistaken belief is that woman must have previously given birth. “It does make for easier insertion of the IUD into the uterus, since the passage is then wider, but it is not at all a prerequisite,” says Kristina Gemzell Danielsson. THE FACT IS THAT this year the Swedish market will see the launch of a sort of mini IUD that she has helped to develop. It delivers lower doses of hormone, but above all, it is smaller and thus easier to insert. Another line of research is male contraceptives as a complement to condoms – a contraceptive that does not really impress Kristina Gemzell Danielsson. “Condoms protect against sexually transmitted diseases, but in the young and highly fertile, they are moderately eﬀective – even when used perfectly,” she says, adding that studies show that perfect use is not that common. Currently under way is a sort of hor-

Kristina Gemzell Danielsson on ...

Name: Kristina Gemzell Danielsson Title: Professor of Obstetrics and Gynaecology, in particular migration-related reproductive health, at the Department of Women’s and Children’s Health, Karolinska Institutet. Director of the WHO Collaborating Centre for Research in Human Reproduction since 2000. Age: 50 years. Family: Three daughters and a husband. Home: House in Bromma outside Stockholm. Relaxes by: Jogging, baking bread and reading fiction. Most recently, “Innan floden tar oss” by Helena Thorfinn, journalist and programme officer at SIDA. “A book set in Bangladesh that reflects the reality I face.”

mone gel that the man applies to the skin. The product is being tested in the United States, but in terms of Swedish clinical trials, she is still awaiting the go-ahead. In an opinion article published in the Swedish newspaper Svenska Dagbladet last autumn, she and some colleagues express their concern that Sweden has the highest rate of teenage abortions in the EU – 20/1000 young people compared to the Netherlands, for example, where the proportion is 6/1000. One factor is the cost of birth control pills and other contraceptives – the article is entitled “Contraception only for the rich” – and she believes that they should be heavily subsidised for young people up to the age of 25. “I’m disappointed that we in Sweden today are demonstrating such a lack of history. We were a pioneering nation, with good access to contraception and good sex education in schools, but things have changed for the worse,” she says. How important then was the pill when it came to Sweden almost 50 years ago?

“It was and is completely fundamental to the development of society and to equality. It’s easy to get paranoid today, but Sweden is becoming more

… the media The media is sex-obsessed, whilst at the same time scaring young people away from effective contraception. The fact that contraceptive pills increase the risk of blood clots is nothing new, but the risk is even higher during pregnancy, with higher oestrogen levels. I wish that journalists were more balanced and understood the evaluation of risks and beneﬁt.

and more like the USA where lobby groups use sophisticated means to work against abortion and now also against effective contraception. It strikes at the freedom of women,” she says. All her research areas – from infertility and contraception to abortion – can be said to be different sides of the same coin: that women themselves should be free to determine their own lives. “These are basic things that I’ve always been interested in, and maybe that’s the ‘fault’ of my background,” says Kristina Gemzell Danielsson, referring to her famous relative, Carl Gemzell. IN THE 1960S , he was a pioneer of hormonally stimulated ovulation in women who had difficulties becoming pregnant, something which resulted in “the Gemzell Children”. She already knew in medical school that she wanted to be a gynaecologist, and when she met her future husband who was from Stockholm, it so happened that she switched campus from Lund and spent her last semester studying at Karolinska Institutet. Here she met her future supervisor Professor Marc Bygdeman, and her thesis was about infertility and the endometrium. “I knew I’d come to the right place!” says Kristina Gemzell Danielsson, looking happy. On the wall by the door hangs the prestigious award from the International Federation of Gynaecology and Obstetrics, FIGO, which she received last autumn – “In recognition of her international and national efforts to promote the advancement of science and research in obstetrics/gynaecology. And for her career-long work to improve healthcare for women.” “Imagine that! Giving the prize to me, a European woman who also works with contraception and abortion. I was extremely impressed by their boldness and I really am very proud!”

… politics The issues I am interested in easily become political. Abortion and contraception are still controversial as it is about giving women control – something that is very alarming. But I have not considered working politically. I think I do more good with my research.

Medical Science–2014

Curious about the sense of smell

A nose for good taste The nose is an expert in telling good from bad. Now researchers are trying to use the power of smell to detect the worst of the worst of the bad - diseases. Text by: Ola Danielsson Photo by: Getty Images

NASAL AL TU TURBINES that create turbulence, seaweed-like se hairs that swirl around and receptors that open a world of unlimite unlimited experience; poetry as olfactory researchers re Johan Lundström and Mats Olsson O enumerate things I did not ot know existed. e This apparatus grants me access tto the scent, smell and stench that the wo world has to oﬀer, an ability that carries a lot of weight in nature. The ability to detect chemical substances, something we humans call smells, was the ﬁrst sense to emerge in evolution and is found in all living organisms. “Smells can go round corners and travel great distances, day or night. It’s the optimum signal to use,” says Johan Lundström, researcher at the Department 38

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of Clinical Neuroscience, Karolinska Institutet. His own interest in the sense of smell is something he traces to a dog he once had, the German Shepherd Ella. She had an ability to deduce information about other dogs by sniﬃng the ground, and he was intrigued. “I began to wonder whether we humans have the same ability,” he says. Ella later became a police dog and spent her last days sniﬃng out cocaine and bombs. Johan Lundström moved to the USA doing research on chemical communication in humans. Back in Sweden, he is now starting an olfactory laboratory at Karolinska Institutet together with Mats Olsson, Professor of Experimental Psychology, who is also

Right on target. The nose can distinguish between about 10,000 different odors. But if you only rely on the smell, it is difficult to know what you sniff on.

CURIOUS ABOUT THE SENSE OF SMELL

SO SMELL DOES NOT tell me that much about the world that I do not already know. On top of that, most novel odours smell bad. “Of the millions of olfactory substances perceptible to humans, the majority give rise to an unpleasant sensation,” says Mats Olsson. But this is precisely the point: The sense of smell translates chemical substances into a qualitative experience, a feeling that is either pleasant or unpleasant. In this way, the nose lets us know what is good for us and what we should stay away from. When we engage in something good, such as eating a well prepared meal, our sense of smell rewards us bounteously. This is because we eat with our noses - around 90 per cent of the ‘taste’ we perceive when we eat is actually aroma sensations that arise when substances from the food stimulate the more than 400 types of olfactory receptors in the nose. However, substances that we breathe in and smell also travel in the opposite direction, from the nose and down into the throat. “Everything you smell, you swallow. Every time you think the toilet smells bad, you’re in essence swallowing a bit of faecal matter,” Johan Lundström informs us. 40

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“Our sense of smell is actually extremely well developed, but our brains are wired so that we don’t pay it that much attention” And anyone who has had food poisoning knows how it feels when the olfactory system really puts its foot down. The distaste of what you ate that day can stay with you for years. It is known as food aversion. But Johan Lundström says that our sense of smell can sometimes lead us the wrong way. If we get sick in the evening, a deﬁnite feeling of revulsion becomes associated with the dinner, which was the last thing we ate before getting sick. But since it takes some time to become sick, it is often the meal before that - lunch - which is the true culprit. The sense of smell is closely linked to the amygdala and hippocampus, brain regions that are important in terms of emotions and memory. But it is not the smells that the brain attaches importance to, but what it believes is the cause of the smell. A nameless odour that is not associated with any object at all soon vanishes from our memory. It is virtually impossible to recall. And strangely enough, the name an odour is given determines how it smells.

“If you say ‘smell this vomit’ and pass across a jar of parmesan cheese, a lot of people will wonder who’s thrown up into the jar. If the jar is instead introduced with the words ‘smell this cheese’, the same person might think it smells deliciously good,” says Johan Lundström, who in his research seeks to understand how smell works together with the other senses to create an overall experience. JOHAN LUNDSTRÖM HAS shown that people are more sensitive to unpleasant smells than pleasant ones, and that sensitivity to speciﬁc smells can be increased signiﬁcantly - if they are presented together with low-level electric shocks. The smell does then have the disadvantage of beginning to smell bad, but Johan Lundström hopes that the research will lead to a greater understanding of how olfactory learning works in the brain and to new ways of training up the sense of smell in people with impaired faculties. Dogs are well known for their ability to smell, and sharks can detect a few tasty drops of blood in the water for miles. We humans, however, are not known for having sensitive noses. On the contrary - researchers concluded in the 1800s that the human sense of smell is almost non-existent. Since then, research on sight and other senses has made great advances, but the sense of smell has been almost completely ignored. Johan Lundström sees this as a real oversight.

Three scents that divide us

Asparagus gives in some people rise to a very special scent from the urine, which only certain people have the ability to smell. Coriander is either loved or hated. The aromatic plant is said to have derived its name from a considered smelling bedbug, Koris, in Greek.

Androstenon found in male sweat. One-third think that it smells strongly of urine, one-third that it smells like a ﬂower and a third feel nothing.

Photo by: Istockphoto

studying how we are affected by the sense of smell. As I listen, the aroma factory in my nose wafts library and steaming fresh coffee into my consciousness, a pleasant smell. But why is smell important? If I want to know what I have in my cup or where I am, there is no doubt that it is easiest to use my eyes. Mats Olsson explains that smell does not compete with the other senses, but complements them. The fact is that a smell carries very little information that helps us identify what we are smelling. In Mats Olsson. surprisingly few cases, Photo by: Ulf Sirborn fewer than 50 per cent, do fully healthy people succeed in correctly naming common aromas such as coffee, lemon or vanilla if they do not already know what they are smelling. “If someone looking at a pen isn’t able to identify the object, you get worried. But with smell, it’s different. Usually, it’s the context that enables us to know what smell we are perceiving,” says Mats Olsson.

An individual part of the brain. The olfactory bulb is like an extension of the nose within the brain. It sends olfactory signals to many other parts of the brain.

Subconscious. Smells are to a large extent processed at a subconscious level, which leads to us being affected by smells without even knowing it.

Emotional. The olfactory bulb sends direct signals to the amygdala, which is thought to regulate the onset of strong emotions like pleasure or fear.

Super sensitive. There are sensory cells in the nasal cavity with over 400 different receptors, which capture odorants. There are two ways to get there; via the nose, or through the back, via the throat.

Permanent. The olfactory bulb is closely linked to the hippocampus, which is important for the brain to process memory. We are bad at remembering smells, but smells are good at stirring memories. Researchers at Stockholm University have proven that memories associated with smells are often related to things that happened before the age of ten, while memories that are triggered by images are related to later episodes in life. Memories triggered by smells are also more emotionally charged than other memories.

Medicinsk Vetenskap â&#x201E;&#x2013;2â&#x20AC;&#x201C;2013

CURIOUS ABOUT THE SENSE OF SMELL

“It’s not true that humans have a bad sense of smell in general. It’s actually extremely well developed, but our brains are wired so that we don’t pay it that much attention,” he says, referring to more recent scientific experiments that have gone to the bottom of the matter. In one of these, subjects were asked to crawl on all fours, blindfolded, and follow the trail of chocolate that had been drawn along the ground. Johan Lundström. But capturing the Photo: Private fleeting nature of the sense of smell is not easy. An aroma often gives rise to different perceptions at different times - what smells good to a person in the morning may smell bad to the same person in the evening, when the sense of smell also tends to be up to 50 per cent lower. Even the subjects’ noses are in a constant state of flux. Every month the millions of olfactory receptors disappear and are then pieced back together - in a way that no one understands. “Every month you get a new sense of smell. How we can still experience the same smells is one of the mysteries of olfactory research,” says Johan Lundström. For some people, who have the olfactory disorder parosmia, their sense of smell appears to have been incorrectly assembled. The result is a badly wired sense of smell that mostly perceives pleasant aromas as negative - banana can smell of poo, and vanilla can smell of rotten eggs. The only thing that has been shown to help in some cases is to burn away the entire sense of smell and let it grow back. “No one knows how it works, but sometimes the sense of smell is then restored,” says Johan Lundström. Smells are largely processed on a subconscious level in the brain - we detect and are influenced by many more smells than we are aware of. And the big difference between humans and other species is not how good a sense of smell we have, but what smells it is programmed to register. “Animals hunting are really good at sensing the smell of meat. We humans are very sensitive to other scents, such as certain substances found in sweat,” says Johan Lundström. Sweat in particular is massively 42

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relevant in the research quest for olfactory substances that may play a role in human social communication - the equivalent of urine’s key role in the canine world. A substance in sweat has been identified as the communication link behind the tendency of women living under the same roof to synchronise their menstrual cycles. Mats Olsson has shown that the same substance, found abundantly in male sweat, can affect the mood of women, even if its smell is masked so that it cannot be perceived. THE COMPOSITION OF SWEAT can be affected by diseases, and it is well known that various diseases are associated with certain scents, which historically has been important knowledge for physicians. Mats Olsson wondered if humans might be extra sensitive to the smell of disease, so that it is possible for the nose to help detect a disease before it makes itself known in other ways. He tested this by giving subjects a substance that activated their immune systems as if they were coming down with an illness. When others then got to smell the shirts of those simulating sick people, it did indeed turn out that they thought the shirts smelled worse than those worn by control persons. “The effect is faint, yet fully measurable. You can imagine this as having been important during evolution, being able to pick up on which people are in the process of becoming sick and to give them a wide berth,” said Mats Olsson. Johan Lundström has been thinking along the same lines and has shown that people are sensitive to the smell of old people. “It’s not a bad smell, but there is a peculiar odour that can be perceived in old people’s homes, for example. It appears that the smell of old people is actually the smell of immune reactions. They simply have more ailments,” says Johan Lundström.

“Every month you get a new sense of smell. How we can still experience the same smells is one of the mysteries of olfactory research”

The researchers have not yet identified the scent molecules that convey the smell of disease. But the realisation that diseases and immune reactions leave scent trails has led researchers to try to develop new diagnostic methods based on the detection of olfactory substances. Johan Lundström, in collaboration with other researchers, are developing an electronic nose that is currently being trained to recognise olfactory substances indicative of skin cancer, breast cancer and even brain injuries. The project, funded by the United States Army, aims in part to be able to quickly sniff out signs of brain injuries sustained by soldiers in the field, much like scanning items at the supermarket. “Smell detection can also have many applications in conventional healthcare because it is much quicker and simpler than the more common methods of diagnosis such as biopsies or blood samples,” says Johan Lundström. At present, Johan Lundström is examining how odours affect how we perceive strangers. The results have not yet been fully compiled, but the research suggests that the body odour of strangers makes us unfavourably disposed towards the outside world. A picture of a neutral face can suddenly be perceived as an angry face if the picture is first applied with a body odour, even if it is too faint to be perceived consciously. So, the sense of smell makes us xenophobic?

“Yes, but it’s a very good function to have. You can look at it as if the odours make us more on the ball and alert to what’s going on around us when we encounter new people. In today’s society, we might not need to be on our guard all the time, but in the past this has probably been crucial,” says Johan Lundström. When people rank their ﬁve senses in order of importance, smell usually ends up in last place. At the same time, olfactory research is gaining a lot of ground, and sometimes olfactory researchers extol it to the skies. But Mats Olsson calls for moderation. “The sense of smell aﬀects us in other ways than we usually think, but in today’s society you can manage quite well without a sense of smell compared to how it is to live without sight or hearing, for example. But, sure, life would be duller without smells. Some of them I would miss a lot, like the smell of my children,” he says.

A researcher’s tale

“She was bleeding to death” 60 years ago patients with bleeding disorders died young. Today they can live long. As told to: Helena Mayer Photo by: Mattias Ahlm “When I and Birger Blombäck began research in blood coagulation back in the 1950s, the average living age of haemophiliacs was only 16 years. Their lives were marked by long hospital stays due to major bleedings especially in joints, which were extremely painful and could lead to invalidization. During an experiment to purify the substance fibrinogen, which is involved in coagulation, one purified fraction (called I-0) was found to stop bleeding in two types of hereditary bleeding disorders, Haemophilia A and von Willebrand’s disease (VWD). In 1957, as one of the first in the world, we were able to produce the first batch of concentrate of a clotting factor from donated blood plasma. We sent it to the south of Sweden to save the life of a VWD girl who was bleeding to death due to her menstruation. Patients could now be treated during operations and joint bleeds, and soon prophylactic treatment could be used. I’ve met a lot of gratitude, and it’s good to see patients grow up and not have to go through bleeding and joint problems. But sadly, many died in the 1980s and 1990s after becoming infected with HIV and hepatitis via certain concentrates from blood plasma, which was a catastrophe. Today, haemophiliacs can go to school, work, travel, play sports and live a long life, even if the most severely ill have to treat themselves with coagulation factors three times a week. At last, even haemophiliacs in poor countries are beginning to slowly gain access to this expensive treatment. The challenges today are to develop new long-acting drugs and the best treatment for those who have developed antibodies against the factor they are lacking. Using gene therapy to transform severe haemophiliacs into milder haemophiliacs, has recently suceeded, and I hope this research will lead to major changes.”

Name: Margareta Blombäck Title: Professor Emerita of Coagulation Research at the Department of Molecular Medicine and Surgery, Karolinska Institutet. Researches: Coagulation of the blood, how blood clots form and how to break them up.

Medicinsk Medical Vetenskap Science–2014 №2–2012

Top publications A selection of the most recent publications from Karolinska Institutet in the world’s leading scientiﬁc journals.

Commonly used antihypertensive drugs may help treating a form of heart failure that affects the elderly and women.

Common heart failure drugs could beneﬁt more patients

Medical Science–2014

ska University Hospital analysed data from about 40,000 patients from the large Swedish Heart Failure Registry. The result showed that patients with HFPEF who were treated with ACEinhibitors or angiotensin receptor blockers - which are commonly used drugs to lower the blood pressure - had better survival than untreated patients. The ﬁnal decrease in mortality was 10 per cent. In heart failure, stress hormones are secreted that are damaging to the heart in the long term, and ACE-inhibitors and angiotensin receptor blockers both work to stop the adverse eﬀects of these hormones. “Since we have not made a so-called randomized study, were the patients are randomly allocated to either getting

treatment or a control group receiving placebo, we must still be careful not to draw too far-reaching conclusions from the results,” says Associate Professor Lars Lund at the Department of Medicine, who led the study. “However, the large number of patients and the extensive statistical adjustments suggest a strong likelihood of a beneﬁt from ACE-inhibitors and angiotensin receptor blockers, drugs that are in comparison not that expensive.” Association between use of renin-angiotensin system antagonists and mortality in patients with heart failure and preserved ejection fraction – a prospective propensity score-matched cohort study Lund LH, Benson L, Dahlström U, Edner M JAMA November 2012

Photo by: Istockphoto

Heart failure aﬀects three per cent of the overall JAMA population, and exists November in two forms: reduced 2012 ability to contract the heart and reduced ability to relax the heart. The former aﬀects younger patients, mostly men, and is treatable. The latter, called HFPEF (heart failure with preserved ejection fraction), afLars Lund. fects older patients and Photo by: Stefan women, and until now Zimmerman there has not been any treatment available against the disease. In a novel study, a team comprising researchers at Karolinska Institutet, Linköping University, and KarolinPublished in:

Adults with ADHD committed fewer crimes when on medication Previous research has shown that people with NEJM ADHD are more likely to November commit crime. Research2012 ers have now been studying over 25,000 individuals with ADHD from different registries during 2006-2009. The results demonstrate links between ADHD medication and a reduced Henrik Larsson. risk of criminality. For example, the incidence of Photo by: Ulf Sirborn criminal behaviour was lower amongst medicated individuals than unmedicated ones. And in the same individual comparing periods of medication with no medication, they also found that ADHD drugs were associated with a significant risk reduction of 32 per cent. Other conclusions are that the observed association not differs between males and females, and applies as much to petty crime as to serious and violent crime. “We have shown that ADHD medication probably reduces the risk of crime,” says Henrik Larsson, Associate Professor at the Department of Medical Epidemiology and Biostatistics. “However, we need to point out that most medical treatments can have adverse side effects, so risks must be weighed up against benefits and the individual patient’s entire life situation taken into consideration before medications are prescribed.”

Surprising. Scarring limits the consequences of a spinal cord injury, new research shows.

Published in:

Medication for attention deﬁcit hyperactivity disorder and criminality Lichtenstein P, Halldner L, Zetterqvist J, Sjölander A, Serlachius E, Fazel S, Långström N, Larsson H NEJM November 2012

Approximately 30-40 per cent of long term convicted criminals have ADHD.

Stem cell scarring aids recovery from spinal cord injury Spinal cord injuries sever nerve fibres that conduct signals between the brain and the rest of the body, causing various degrees of paralysis. Functional impairment is often permanent, since the cut nerve fibres do not grow back. The lack of regeneration has been attributed to a blockage from scar tissue, and therapeuJonas Frisén. tic strategies have been Photo by: designed around inhabiMartin Stenmark tation of scar formation. In a recent study conducted on mice, researchers focused on spinal cord stem cells, one of the main sources of the scar tissue that is formed after spinal cord injury. They found that when blocking scar formation by preventing the stem cells from forming new cells after an injury, the injury gradually expanded, and more nerve fibres were severed and died. “Our results suggest that more, rather than less, stem cell scarring could limit the consequences of a spinal cord injury,” says principal investigator Jonas Frisén, Professor of Stem Cell Research at the Department of Cell and Molecular Biology. Published in:

Science November 2013

Resident neural stem cells restrict tissue damage and neuronal loss after spinal cord injury in mice Sabelström H, Stenudd M, Réu P, Dias DO, Elﬁneh M, Zdunek S, Damberg P, Göritz C, Frisén J Science November 2013

In short Faster biological ageing linked to increased cancer risk Identiﬁcation of seven loci affecting mean telomere length and their association with disease Codd V, Magnusson P, Hägg S, Pedersen N and others within the ENGAGE consortium Nature Genetics March 2013 Cell memory mechanism discovered Transcription factor binding in human cells occurs in dense clusters formed around cohesion anchor sites Yan J, Enge M, Whitington T, Dave K, Liu J, Sur I, Schmierer B, Jolma A, Kivioja T, Taipale M, Taipale J Cell August 2013 Different neuronal groups govern right-left alternation when walking Dual mode operation of neuronal networks involved in left-right alternation Talpalar AE, Bouvier J, Borgius L, Fortin G, Pierani A, Kiehn O Nature June 2013 No increased risk of stillbirth and infant mortality when a pregnant woman uses SSRI drugs Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality Stephansson O, Kieler H, Haglund B, Artama M, Engeland A, Furu K, Gissler M, Nørgaard M, Beck Nielsen R, Zoega H, Valdimarsdóttir U JAMA January 2013 Tailored doses of cytostatic improve survival rate Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study Gungör T, Teira P, Slatter M, Hassan M et al The Lancet October 2013 Mental illness related to premature death in epilepsy patients Premature mortality in epilepsy and the role of psychiatric comorbidity over 41 years: a total population study Fazel S, Wolf A, Långström N, Newton CR, Lichtenstein P The Lancet July 2013 Molecular switch controls the destiny of self-eating cells The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy Fullgrabe J, Lynch-Day MA, Heldring N, Li W, Struijk RB, Ma Q, Hermanson O, Rosenfeld MG, Klionsky DJ, Joseph B Nature July 2013 Medical Science–2014

In focus: PMS

Cause: Actually unknown, but some women are more sensitive to degradation products from progesterone. Symptoms: Depression, irritability, anxiety or mood swings before menstruation. Affects: Up to 30 per cent of all women have “more minor complaints”. Between two and ﬁve per cent have PMDD, Premenstrual Dysphoric Disorder, which involves severe complaints.

“Crying spells and ﬁts of rage are commonplace” Text by: Annika Lund Photo by: Jezzica Sunmo

remenstrual Syndrome, PMS, is a relatively young field of research. This is true despite the fact that some patients have great problems that diminish their quality of life and that of their families. These problems may be severe dejection, anger, anxiety or extreme mood swings for a time before menstruation – crying spells and fits of rage are part of the picture. For some women, the symptoms already begin at ovulation and then cease with menstruation. That means that they are severely affected for two weeks and then feel satisfied with life for two weeks. And so it begins again, with anxiety and mood swings. “Some women have recurrent thoughts of suicide or such severe anxiety attacks that they regularly seek emergency psychiatric care. Others are on the verge of divorce once a month because they are so annoyed with their husbands – feelings that completely cease shortly afterwards, at which point they don’t understand their previous thoughts and feelings at all,” says gynaecologist Marie Bixo, Professor of Obstetrics and Gynaecology at the Department of Clinical Research and Education at Södersjukhuset.

Medical Science–2014

Despite the problems being cyclical, it is relatively common for women not to realise that the complaints are linked to the menstrual cycle. A previous study shows that nearly half do not seek help at all. And those who do perhaps turn to psychiatric care or the medical centre just as often as they turn to their gynaecologist. The healthcare system can also fail to understand the situation – Marie Bixo tells of a woman who had been diagnosed with and received treatment for bipolar disorder without this having an eﬀect. Her complaints disappeared when she received treatment for PMS. “I agree that it’s strange that some people don’t link the symptoms to menstruation. Maybe because some are so totally engulfed by their complaints when they’re happening and are then so relieved when they disappear. They never get any respite to take a step back and see the pattern,” says Marie Bixo. HER ADVICE IS TO KEEP a diary of the symptoms. If they are due to PMS, the pattern will be clear, and some will be relieved from simply knowing what the symptoms are due to. Relief may also be obtained by exercising more and stressing less. However, some women have more extensive complaints and

Some women have such severe PMS that they have suicidal thoughts. Many never seek help for their complaints, even though these bring a great deal of suﬀering. Unfortunate, according to Professor Marie Bixo, who wants to spread the message that help is available.

might then be offered medication. This is mainly SSRIs, Selective serotonin reuptake inhibitors, that have proven to be effective. One of these is approved for the indication PMDD, Premenstrual Dysphoric Disorder, which is a more severe form of PMS. There is also a special kind of contraceptive pill that has proven to work. IT IS NOT REALLY KNOWN what PMS is due to. But the symptoms appear only if the woman has ovulated and they always disappear at, or shortly after, the start of menstruation. For this reason, progesterone, which increases sharply from ovulation until menstruation, has been identified as important in this context. When it is metabolized, various residual products form, such as allopregnanolone – a substance that affects women to varying extents. According to the current theory, allopregnanolone in some individuals can affect the GABA system, which is an alleviating and calming system, so that it no longer functions as it should. The calming effect ceases, enabling anxiety, worry and aggression to take over. Other brain functions can also be adversely affected by allopregnanolone, such as the ability to concentrate and learn.

Unique. Marie Bixo is currently conducting the ﬁrst clinical trial that has had PMS in its sights from the outset.

“It is extremely fascinating what powerful eﬀects hormones can have on the brain. It’s revolutionary, and only makes me more and more fascinated,” says Marie Bixo. Those who are sensitive to allopregnanolone may get PMS, and the highly sensitive can get PMDD. Why some women seem more sensitive to allopregnanolone is not known, but it is probably genetic. The complaints appear to get stronger with age, also for unknown reasons. TODAY A POTENTIAL new drug is in the pipeline. Together with a team of researchers, Marie Bixo has developed a substance that prevents the eﬀect of allopregnanolone on the brain. The substance has been successfully tested on mice and healthy human subjects, and will now be tested in a phase I/II study. 120 women with PMDD are currently being recruited from women’s clinics across Sweden. The study is expected

“PMS has had to play second fiddle in the same way as menopausal complaints” to be completed in spring 2014, and if the results are promising, a larger phase III study will be carried out. If this all culminates in a drug, it will in that case be the first to have had PMS and PMDD in its sights from the outset. The SSRI that is approved for this indication was originally developed to treat depression. According to Marie Bixo, it is in many ways difficult to conduct studies on women’s diseases. “Women’s diseases are not a particularly high research priority. Unfortunately. It’s difficult to get funding. There are many prejudices about these dis-eases, and it is also considered difficult to study

women precisely because they are influenced by hormonal cycles that are seen to interfere with the research findings. Which prejudices do you have in mind? “As recently as 50 years ago, it was considered natural that women were more sensitive individuals, so any complaints were simply part and parcel of menstruation and weren’t anything people thought needed relief. PMS has had to play second fiddle in the same way as menopausal complaints,” says Marie Bixo. Which view do you want to highlight? “Some women are very much affected by PMS and PMDD. We can help them. They represent a small group of women who have big problems that affect their quality of life. I think all women feel their menstrual cycle in some way and we don’t wish to medicalise it. Our focus is rather on helping those who need help in order to function normally in everyday life.” Medical Science–2014

KI news

A cuttingedge laboratory giant In 2013 Karolinska Institutet started to build an ultramodern, purpose-built facility for experimental medical research. The aim is to enhance conditions for world class research at one of the world’s foremost medical universities. The new laboratory Biomedicum, gives Karolinska Institutet more research space with its 55,000 square meters or so of premises space. It will be one of Europe’s largest laboratories and provide new opportunities to make more effective use of shared infrastructure when it’s completed in 2018. The Biomedicum project will also contribute to the development of Stockholm as one of the world’s leading life science regions. Biomedicum will have space for approximately 1,700 researchers and other personnel. In bringing the scientific activities of separate disciplines together under one roof, the new research laboratory will provide opportunities for crossover research. Also planned are a number of meeting nodes and a core of shared facilities allowing expensive equipment to be utilized more effectively.

Photo by: Berg/C.F. Møller Architects

A treasure trove of illustrated medical history – now online

The Hagströmer Medico-Historical Library in Haga Courthouse is a research library for the history of books and medicine that contains over 30,000 images, the majority printed before 1860. The recently launched Wunderkammer website is a digital gallery of parts of the Library’s art treasures. Filippo Palizzi’s satirical drawing reproduced here is from the 1840s and shows a charlatan dentist pulling out a horse jaw from the patient’s mouth. wunderkammer.ki.se Medical Science–2014

Biomedicum, right next to Aula Medica

Sweden to invest heavily in toxicological research In 2014 the Swedish Toxicology Sciences Research Center will start to operate. Via high-tech research and knowledge and method development, Swetox shall create solutions for assessing security and health effects of certain chemicals, medicines and endocrine disruptors. Swetox is a unique cooperation between 11 universities, coordinated by Karolinska Institutet. It is the largest Swedish investment in toxicological research to date.

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The moment

“No one could have saved their lives” The death of six young patients in a single shift moved Maaret Castrén to begin researching cardiac arrest. Today, she is the only Professor of Emergency Medicine in Sweden and Finland. As told to: Anders Nilsson Photo by: Mattias Ahlm

Medical Science–2014

Name: Maaret Castrén Titel: Professor of Emergency Medicine at the Department of Clinical Science and Education, Södersjukhuset at Karolinska Institutet and at Åbo University, Finland.

Help improve human health “I see myself communicating both with physicians and patients, trying to change healthcare services to the best they can be.” Dina Titkova, Bioentrepreneurship

Study one of our 6 Global Master’s Programmes in health and life sciences, all in English and with an international focus. A degree at Karolinska Institutet may very well be the ﬁrst step towards a PhD in the same or another well renowned partner university somewhere in the world. It can open doors to a global future.

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