Tag Archives: LBK

Angels’ hair, two students and a laser microscope

AnnaBofin_portrettBlog by: Anna M. Bofin
Professor of Medicine (Pathology)

Breast cancer is a disease of the milk-producing glandular cells, the ductal and lobular cells of the breast. In order to survive, cancer cells need nutrients, support and an environment that they thrive in so that they can grow, multiply and spread. At an early stage, cancer cells establish a close dialog with the tissues and cells that surround them. They encourage blood vessels to develop in order to supply them with glucose and oxygen and they stimulate cells in surrounding tissue, stromal cells, to build a scaffold that can support the growing population of cancer cells.

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Filed under Cancer, NTNUmedicine, Research

Cardiovascular disease is associated with increased risk of rheumatoid

Blogger: Vibeke VidemVibeke Videm. Foto: Geir Mogen

Twice as many of those who got rheumatoid arthritis between the HUNT2 population-based health survey in 1995-1997 and the next survey (HUNT3) in 2006-2008, reported previous cardiovascular disease at HUNT2. They either had angina or had suffered a myocardial infarction or stroke. The data indicate that there may be a causative link.

(…) chronic inflammation in one part of the body intensifies chronic inflammatory processes in other parts

Atherosclerosis, the most common cause of cardiovascular disease, is caused by chronic inflammation in the vessel walls. Rheumatoid arthritis is due to a gradual process with increasing dysregulation of the immune system that finally leads to inflammation in the joints. The inflammation due to atherosclerosis probably intensifies the process leading to rheumatoid arthritis. The study was recently published in the scientific journal  Arthritis Research and Therapy.

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Filed under Cardiovascular, Generic Health Relevance, Inflammatory and Immune System, NTNUmedicine, Research, Stroke

Prize for PCOS-research

Blogger: Elisabeth DarjElisabeth Darj

 

The Gemzell prize at Uppsala University has this year been awarded to Eszter Vanky, researcher at NTNU.

Eszter Vanky, associate professor at the Department of Laboratory Medicine, Children’s and Women’s Healt, received this honor at Uppsala University 20. march 2014 and gave the prestigious “Gemzell lecture of the year”.

Eszter Vanky was nominated for her research in endocrinology, on women with polycystic ovary syndrome (PCOS) and gave a very and interesting lecture at Uppsala University with the title; “PCOS i blant frustrerende, alltid spennande” (PCOS sometimes frustrating, always interesting) . She described for the audience diagnose, pregnancy complications for PCOS-women and treatment in a pedagogic and inspiring way.

Carl Axel Gemzell was an internationally respected Swedish gynecologist and endocrinologist (1910-2007). Gemzell worked in Sweden and USA and contributed significantly to the treatment with gonadotropins to infertile women. He purified protein hormones from pituitaries and introduced stimulation of the ovaries. This was the beginning of assisted human reproduction. He developed several hormone tests, and one of his students developed the modern pregnancy test.

Eszter Vanky

Eszter Vanky receives prize for her research on PCOS

Skilled international researchers has since 1977 been nominated to the Gemzell prize. Only once before has a Norwegian researcher been awarded the Gemzell prize and held the “Gemzell lecturer of the year”. This was Arne Sunde in 2009, also from NTNU.

Eszter Vanky has previously received Norwegian prizes for her research.

 

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Filed under Metabolic and Endocrine, NTNUmedicine, Reproductive Health and Childbirth, Research

Is pre-eclampsia a risk factor for cerebral palsy

Blogger: Kristin Melheim Strand, forskerlinjestudentportrettbilde

 

 

 

 

 

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Filed under Neurological, NTNUmedicine, Reproductive Health and Childbirth, Research

Genetic profiling and side-effects of blood cancer treatment in children

Blogger: Bendik Lund Bendik Lund

 

 

 

During treatment of childhood blood cancer, great variations in side-effects are seen – both in terms of prevalence and seriousness. Some children get more serious side-effects than others. Potentially, the diversity in the toxicity burden for individual patients could reflect the normal genetic variation between patients.

A bone marrow smear at high magnification taken at diagnosis. Most of the blue cells are leukaemic cells. Normal red blood cells are also seen. (Photo: Bendik Lund)

A bone marrow smear at high magnification taken at diagnosis. Most of the blue cells are leukaemic cells. Normal red blood cells are also seen. (Photo: Bendik Lund)

In parallel with the biotechnological development over the last 10-15 years, we have gained extensive knowledge about the normal sequence variation in DNA, which differs from person to person. This sequence variation might explain some of the differences between people, for example height, hair colour, risk of diseases and the body’s reactions to medicines (pharmacogenetics).

There are many types of DNA-variations and one of the most common ones is single nucleotide polymorphism (SNP), where one letter in our genetic code has been replaced by another letter. DNA consists of long chains of base pairs (letters, totalling around 3 billion) and a SNP occurs approximately for every 300th base pair.

We wanted to study what role the natural genetic variation plays in the development of side effects in children treated for leukaemia (cancer of the blood). The most common form of blood cancer in children is acute lymphoblastic leukaemia, and 30-40 children are diagnosed in Norway every year with this type of leukaemia. The treatment consists of chemotherapy given over a period of 2.5 years, and the survival rate today is around 85%. The treatment causes many side effects including reduced immune function and infections. In some cases, the treatment can lead to so serious side effects that the patient dies from the toxicity.

Knowledge about pharmacogenetic variation is already used in the standard treatment for acute lymphoblastic leukaemia when using the chemotherapy 6-mercaptopurine. This drug is dosed based on the patient’s SNP variants for the enzyme that metabolises 6-mercaptopurine (TPMT-genetic variants).

We have collaborated with a research group at the laboratory in Copenhagen (Bonkolab, Rigshospitalet) and, based on existing literature, around 2300 candidate genes that could be significant for children with acute lymphoblastic leukaemia have been identified. Furthermore, the group has made a cost-efficient analysis method where 34,000 genetic variants (SNPs) per patient within these genes (extended candidate gene model) are analysed. Samples from several patients can also be analysed in the same sample tube (multiplexing).

The test tube to the left contains a blood sample from a healthy person. The test tube to the right contains a blood sample form a child with leukaemia. “Leukaemia” means “white blood”, and one can clearly see why when looking at the white layer of cells in the test tube to the right. (Photo: Bendik Lund)

The test tube to the left contains a blood sample from a healthy person. The test tube to the right contains a blood sample form a child with leukaemia. “Leukaemia” means “white blood”, and one can clearly see why when looking at the white layer of cells in the test tube to the right. (Photo: Bendik Lund)

We used this method in a study where we included 69 Danish children with leukaemia and compared the gene variant pattern with clinical data for infections that occurred during the first 50 days of treatment. We identified a SNP profile which with great accuracy can predict the risk for infections in this early phase of the treatment, where many infections are life-threatening.

If these findings are confirmed in similar studies, we may in the future be able to quickly determine whether a patient has an increased risk for serious infections by taking a simple blood test. If the patient is at high risk for serious infections, the treatment could be adapted accordingly for example giving prophylactic antibiotics, or by reducing the intensity of the chemotherapy. Hopefully this will lead to less side effects and higher survival rates.

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Filed under Blood, Cancer, Child and youth, Infection, NTNUmedicine, Research

A tiny fragment of tissue can tell a long story….

Blogger: Anna Mary BofinAnna Bofin

 

 

 

 

James Paget (photo: wikipedia.org)

James Paget (photo: wikipedia.org)

“Many of the cells of cancers, for example, may be somewhat like gland cells, yet a practised eye can distinguish them; they are heaped together disorderly and seldom have any lobular or laminar arrangements such as exists in the natural glands or epithelia”

These words were written in 1853 by James Paget who was a surgeon and pathologist, and they describe cancer cells as we see them under the microscope. The cells are different from normal cells. They are mutineers only interested in their own survival at the expense of their host.

To this day, the initial diagnosis of breast cancer is still made by a pathologist examining a tissue sample under a microscope. We know that breast cancers differ greatly in their appearance and that these differences can be explained by differences in their molecular characteristics. These differences are exploited today to give the individual woman a tailor-made treatment based on a set of special tests that have been tried and proven useful for this purpose.

We know that tissue samples from breast cancer harbour even more information that could help us to understand the causes of the disease, determine more effective treatment and avoid overtreatment.

fotokollasje1brystkreft

Normal breast tissue (left), breast cancer, ductal type (right)

The Breast Cancer Subtypes research group at NTNU has studied over 900 cases of breast cancer from women in Nord-Trøndelag who took part in a breast cancer screening program organised by the Cancer Registry of Norway over 60 years ago. These women lived in an era before hormone replacement therapy became common and before the implementation of mammography screening. They received limited treatment, often only surgery, making it possible to study the near natural course of this disease.

These samples have now been reclassified into subtypes based on their molecular composition rather that their appearance under the microscope. Follow-up shows that there are differences in survival according to molecular subtype and that most of these differences occur during the first five years after diagnosis. These results were recently published in Breast Cancer Research and Treatment.

Mothers and daughters

Could there be differences in the types of cancer that occur in these two generations?

Like their mothers and grandmothers before them, women in Nord-Trøndelag have continued to contribute to research through their participation in the Nord-Trøndelag Health Study (HUNT). The next step for the Breast Cancer Subtypes research group is to study breast cancer tissue samples from women who took part in HUNT2 between 1995-97. In contrast to their mothers, these women have had access to the contraceptive pill, hormone replacement therapy and mammography screening. Could there be differences in the types of cancer that occur in these two generations?

fotokollasje2brystkreft

Breat cancer, lobular type (top left), HER2 protein on the cell membrane (top right), HER2 gene amplification in cell nuclei (bottom left), breast cancer, ductal type (bottom right)

A further question that the Breast Cancer Subtypes group is addressing is survival.

Ultimately, the aim of this work is a better understanding of this complex disease in order to provide the individual woman with a more accurate diagnosis and a more effective treatment of her cancer.

Follow-up over several decades makes it possible to study the molecular characteristics of cancers that have a very good prognosis as well as those with a poor prognosis. Using advanced technology, it is possible to stain and analyse hundreds of tissue samples in a standardised way and study the molecular characteristics of the different cancers. When these data are linked to survival data it will be possible to identify cancers with very good prognosis requiring little or no additional treatment, and others that require individual, tailor-made treatment strategies based on the characteristics of the individual cancer.

Ultimately, the aim of this work is a better understanding of this complex disease in order to provide the individual woman with a more accurate diagnosis and a more effective treatment of her cancer.

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Can ultrasound predict prolonged labour?

Erik Andreas TorkildsenBlogger: Erik Andreas Torkildsen

 

 

 

 

Most women give birth naturally and without problems, but sometimes labour becomes prolonged. Common causes are weak contractions, the position of the baby, or that the baby is too large for the mother’s pelvis. Traditionally the midwives and doctors assess the progression of labour using their hands. Ultrasound is mostly used for check-ups during pregnancy, and seldom used during labour itself.

We therefore wished to investigate whether ultrasound could be a useful tool during prolonged labour.

A hundred-and-ten first-time mothers at Stavanger University Hospital where examined using ultrasound during labour in the period 2009-2010. We studied whether the level and rotation of the baby’s head in the pelvis could predict the probability of normal delivery or caesarean. Ultrasound was compared with traditional clinical examinations.

In the first study we found that there was a great chance of caesarean if labour stopped when the head was high up in the birth canal, but if the head had passed the mid-section of the canal (the tightest part), 90% of the women had a normal delivery. Ultrasound could predict the progression of labour better than traditional clinical examination.

Gravid mage (iStockPhoto).In the second study, two and three dimensional (2D vs. 3D) ultrasound techniques were compared. The results showed that 2D and 3D were equally good techniques. 3D examinations, however, are more complicated and the equipment more expensive, and therefore 2D could be favoured as a simple method giving good information directly in the delivery room.

The rotation of the baby’s head in the pelvis during labour was estimated using ultrasound in the third study. Rotation is necessary for the baby to pass through the birth canal. The study showed that the rotation of the head alone could not predict caesarean vs. vaginal birth. This is probably because the head has to rotate no matter the outcome.

We studied four suggested ultrasound methods to measure the head’s level. The results showed that they corresponded well, and that all four were better than standard clinical examination.

From this we conclude that ultrasound can be a useful tool during delivery. The ultrasound examination is also more objective than clinical examinations, and ultrasound can help decide who needs a caesarean and when.

 

Erik Andreas Torkildsen’s viva on the subject takes place on 20. September at 12.14, at Stavanger University Hospital. The trial lecture “The control of labour – contemporary science” will be held at 10.15 the same day.

Torkildsen’s main supervisor has been Torbjørn M. Eggebø (Stavanger) and the second supervisor has been professor Kjell A. Salvesen (NTNU, Trondheim).

The project has been a collaboration between the Women’s clinic in Stavanger and the National Centre for Foetal Medicine, St. Olavs Hospital, Trondheim.

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Understanding viral respiratory tract infections in young children

Ingvild Bjellmo Johnsen and her co-workers from NTNU work on viral infections and especially viral respiratory tract infections in young children, which is the leading cause of death in developing countries. Knowledge about these mechanisms may lead to development of effective anti-viral treatment and prevent misuse of antibiotics.

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Filed under Child and youth, Infection, NTNUmedicine, Research

HUNT-data contributes to new insights on ankylosing spondylitis

Blogger: Vibeke VidemVibeke Videm. Foto: Geir Mogen

 

 

 

 

We have known for some time that genetics play a great part in the risk for developing ankolysing spondylitis (Bekhterev’s disease), which leads to inflammation causing pain and stiffness of joints – especially in the back and pelvis. Through an international research collaboration studying genetic material from more than 10,000 patients with ankylosing spondylitis, 13 new genetic loci have been identified that affect the risk for the disease. This is a doubling of the number of known genetic risk loci. The results have recently been published in the journal Nature Genetics.

From the 70s it has been known that almost all patients with ankylosing spondylitis have a genetic variant called HLA-B27.

From the 70s it has been known that almost all patients with ankylosing spondylitis have a genetic variant called HLA-B27.

An Australian research group lead by Professor Matthew Brown at the University of Queensland in Brisbane, Australia, was very positive to including patients from the Nord-Trøndelag health study (HUNT) in Norway. Through the questionnaires from HUNT, we have access to far more information about lifestyle factors than what is common in such international genetic studies. As only a fraction of those with the genetic disposition for ankylosing spondylitis actually develop the disease, we believe that lifestyle factors may also affect the risk. We are therefore now conducting follow-up studies on the HUNT data to investigate this connection further.

The HUNT participants have given us an invaluable contribution, for which we are very grateful.

The fact that so many people from the county of Nord-Trøndelag have contributed to HUNT, and done so repeatedly, means we have data on the impact of changes in lifestyle factors over long periods. The HUNT participants have given us an invaluable contribution, for which we are very grateful. We are now counting on HUNT4 taking place, and hope for an equal willingness to contribute.

From the 70s it has been known that almost all patients with ankylosing spondylitis have a genetic variant called HLA-B27. The connection between ankylosing spondylitis and HLA-B27 is actually one of the strongest known genetic associations for common diseases where more than one gene plays a part. The knowledge of several more risk genes forms the basis for the development of new medication which can slow the inflammation by affecting the underlying mechanisms.

Researchers from 17 countries in Europe, East Asia, North America, Australia, New Zealand and Latin America have collaborated on the new study. Because the impact of each individual genetic risk variable is small and the interaction between them is complicated, we need very large patient numbers to establish clear patterns. This underlines the benefit of international collaboration – this type of knowledge is impossible to obtain through single group efforts.

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Filed under Inflammatory and Immune System, Musculoskeletal, Research

The first meeting – pregnancy ultrasound

Kari Williamson

Blogger: Kari Williamson

 

 

 

 

You lie there with gel on your stomach and glance towards the ultrasound screen. There he is, the little one, who will arrive in four-five months’ time. The emotions, questions, the joy, the worry, they all crowd in – and the midwife gives and understanding nod.

This is how many of us imagine the experience of the first ultrasound consultation offered to all pregnant women in Norway at week 18. There is a lot of technological and medical research and innovation behind this half-hour consultation, but what about the human aspect? What about the pregnant woman and her partner? How do they experience this meeting?

Ultrasound is offered to all pregnant women in week 18 of the pregnancy.

This is what midwife Liv Øyen at NTNU and the National centre for foetal medicine at St. Olavs Hospital has looked at in more detail. After nearly 30 years as a midwife and around 14 years as an ultrasound-teacher, the meetings with pregnant women and their partners have been many. And some central questions have emerged:

  • What is the pregnancy ultrasound all about?
  • How should it be done? How should it be communicated?
  • What do the pregnant women themselves think about this offer at week 18?

Medical and personal

The pregnancy ultrasound is primarily for medical reasons. The information brochure from the Norwegian Directorate of Health on pregnancy ultrasound, says that the consultation is a check-up on the foetus and the uterus to gain information about the age of the foetus, the number of foetuses, the location of the placenta and the foetus’ anatomy and development.

But if you ask expecting parents about the pregnancy ultrasound, this is not their main concern. Of course they want to know if everything is ok medically, but it is the experience of seeing their child for the first time that they talk about. There is actually a new life in there, and someone is about to become a parent.

Øyen has interviewed eight pregnant women for her master thesis, and the responses indicate that they wish for the midwife to acknowledge the impact of this first visual meeting. They also want a dialogue – not just a monologue of technical and medical data. In short, they want to be met as human beings, as a family.

This may sound difficult to achieve in a mere 30-minute consultation, but Øyen does not believe it actually takes much. The key is to see the persons coming in through the door and make them feel acknowledged.

This is something Øyen wishes to bring into the ultrasound training for midwives by introducing theories such as Tor-Johan Ekeland’s on therapeutic communication. The theory states that communication and information are not the same thing – in order to really communicate, there has to be a relationship in place.

Ultrasound image of a hand.

Øyen’s aim is therefore to educate compassionate midwives who see the couples coming through the door and focus on the person rather than just the technology. “The most important thing is to create a bond between mother, father and child. This is the pivotal point,” one of the women in the survey said.

It is after all call pregnancy CARE.

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