Parto induzido aumenta risco para mulheres e bebês

Induzindo problemas

Com o aumento crescente no número de partos programados, é importante para os médicos e para as futuras mães entenderem os riscos associados com a indução eletiva do parto.

Tentando mensurar esses riscos, uma equipe de médicos da Universidade de Rochester, nos Estados Unidos, pesquisou mulheres que estavam dando à luz seu primeiro filho.

As conclusões mostram que induzir o trabalho sem uma razão médica - apenas por conveniência - está associado com problemas para a mãe, incluindo o aumento das taxas de cesárea, maior perda de sangue e um período de permanência no hospital mais longo.

E essa indução não traz qualquer benefício para o recém-nascido.

Partos com maior risco

Os pesquisadores descobriram que cerca de 34% das mulheres que optaram pela indução eletiva do trabalho de parto acabaram tendo uma cesariana, contra uma taxa de 20% entre as mulheres que aguardaram o parto natural.

Da mesma forma que a indução eletiva, afirmam os autores do estudo, a cesariana "pode ser vista ingenuamente como rotineira e sem risco, quando na verdade ela é uma grande cirurgia e, como toda cirurgia, aumenta o risco de infecções, complicações respiratórias e a necessidade de cirurgias adicionais, resultando em maior tempo de recuperação."

Para cada 100 mulheres que se submeteram à indução eletiva, houve um adicional de 88 dias de permanência no hospital, representando custos acrescidos para a mãe e para o hospital.

Nos partos induzidos, os bebês foram mais propensos a precisar de oxigênio imediatamente após o parto.

Eles também se mostraram mais propensos a exigir atenção especializada de especialistas da unidade de terapia intensiva neonatal.

Conveniência versus bem-estar

"Os benefícios de um procedimento devem sempre superar os riscos. Se não houver quaisquer benefícios médicos para induzir o trabalho de parto, é difícil justificar fazê-lo eletivamente quando sabemos que isso aumenta os riscos para a mãe e o bebê," afirma o Dr. Christopher Glantz um dos autores do estudo, que foi publicado no Journal of Reproductive Medicine.

Nos Estados Unidos, tem aumentado o número de partos programados, por conveniência das mães ou dos médicos, ou de ambos.

Isso tem sido considerado um problema pelos especialistas - ainda assim um problema considerado menos grave do que a cesárea eletiva em larga escala, como ocorre no Brasil.

Embora médicos e mães possam considerar que a indução do trabalho de parto não faz mal, ele não funciona tão bem quanto o parto natural - como se está essencialmente partindo do zero, sem a progressão natural dos organismos da mãe e do bebê, a chance de surgirem problemas é muito maior.

"Como profissional e como mãe, eu sei como pode ser tentador agendar o parto para deixar sua vida em ordem, mas há uma razão para que os bebês permaneçam no útero pelo tempo total natural da gravidez," disse a Dra. Loralei Thornburg, especializada em medicina materno-fetal. "Por que colocar você e seu bebê em risco se você não precisa fazer isso?"

Os médicos afirmam que as conclusões só se aplicam ao primeiro parto - mães que passaram por parto induzido mas que já haviam tido um filho por parto natural não-induzido não tiveram aumento nos riscos.

Transgenic Fungi May Be Able to Combat Malaria and Other Bug-Borne Diseases

ScienceDaily (Feb. 26, 2011) — New findings by a University of Maryland-led team of scientists indicate that a genetically engineered fungus carrying genes for a human anti-malarial antibody or a scorpion anti-malarial toxin could be a highly effective, specific and environmentally friendly tool for combating malaria, at a time when the effectiveness of current pesticides against malaria mosquitoes is declining.

This stink bug has been infected with a fungi. St. Leger and his team also are creating transgenic fungi designed to control stink bugs, bed bugs, locusts and other pests. 

In a study published in the February 25 issue of the journal Science, the researchers also say that this general approach could be used for controlling other devastating insect and tick bug-borne diseases, such as or dengue fever and Lyme disease. "Though applied here to combat malaria, our transgenic fungal approach is a very flexible one that allows design and delivery of gene products targeted to almost any disease-carrying arthropod," said Raymond St. Leger, a professor of Entomology at the University of Maryland.

"In this current study we show that spraying malaria-transmitting mosquitoes with a fungus genetically altered to produce molecules that target malaria-causing sporozoites could reduce disease transmission to humans by at least five-fold compared to using an un-engineered fungus," St. Leger said.

St. Leger, his post doctoral researcher Weiguo Fang and colleagues at the Johns Hopkins School of Public Health and the University of Westminster, London created their transgenic anti-malarial fungus, by starting with Metarhizium anisopliae, a fungus that naturally attacks mosquitoes, and then inserting into it genes for a human antibody or a scorpion toxin. Both the antibody and the toxin specifically target the malaria-causing parasite P. falciparum. The team then compared three groups of mosquitoes all heavily infected with the malaria parasite. In the first group were mosquitoes sprayed with the transgenic fungus, in the second were those sprayed with an unaltered or natural strain of the fungus, and in the third group were mosquitoes not sprayed with any fungus.

The research team found that compared to the other treatments, spraying mosquitoes with the transgenic fungus significantly reduced parasite development. The malaria-causing parasite P. falciparum was found in the salivary glands of just 25 percent of the mosquitoes sprayed with the transgenic fungi, compared to 87 percent of those sprayed with the wild-type strain of the fungus and to 94 percent of those that were not sprayed. Even in the 25 percent of mosquitoes that still had parasites after being sprayed with the transgenic fungi, parasite numbers were reduced by over 95 percent compared to the mosquitoes sprayed with the wild-type fungus.

"Now that we've demonstrated the effectiveness of this approach and cleared several U.S. regulatory hurdles for transgenic Metarhizium products, our principal aim is to get this technology into field-testing in Africa as soon as possible," St. Leger said. "However, we also want to test some additional combinations to make sure we have the optimized malaria-blocking pathogen."

Noting that the University of Maryland has pioneered the science and practice of creating transgenic fungi, St Leger said that he and colleagues at Maryland and at partnering institutions are already working to create genetically engineered fungi that can be used to reduce transmission of other illnesses, like Lyme disease and sleeping sickness. In related work, they are employing genes encoding highly specific toxins to produce hypervirulent pathogens that can control pests like locusts, bed bugs and stink bugs.

"Insects are a critical part of the natural diversity and the health of our environment, but our interactions with them aren't always to our benefit," said St. Leger, who is widely recognized for research that employs insects and their pathogens as models for understanding how pathogens in general cause disease, adapt and evolve, and in the application of that understanding to the creation of new methods for safely reducing crop destruction, disease transmission and other damaging insect impacts.

The Malaria Challenge

Infection by malaria-causing parasites results in approximately 240 million cases around the globe annually, and causes more than 850,000 deaths each year, mostly children, according to the World Health Organization. Most of these cases occur in sub-Saharan Africa, but the disease is present in 108 countries in regions around the world. Treating bed nets and indoor walls with insecticides is the main prevention strategy in developing countries, but mosquitoes are slowly becoming resistant to these insecticides, rendering them ineffective.

"Malaria prevention strategies can greatly reduce the worldwide burden of this disease, but, as mosquitoes continue to acquire resistance to currently used methods, new and innovative ways to prevent malaria will be needed, experts say.

One such strategy is killing Anopheles mosquitoes by spraying them with the pathogenic fungus M. anisopliae. Previous studies by African, Dutch and British scientists have found that this method nearly eliminates disease transmission but only when mosquitoes are sprayed soon after being infected by the malaria parasite. The difficulties with this strategy are that it requires high coverage with fungal biopesticides to ensure early infection, and is not sustainable in the long term. If spraying mosquitoes with M. anisopliae kills them before they have a chance to reproduce and pass on their susceptibility, mosquitoes that are resistant to the fungus will soon become predominant and the spray will no longer be effective.

The approach developed by St. Leger and his colleagues avoids these problems because their engineered strains selectively target the parasite within the mosquito, and allow the fungus to combat malaria when applied to mosquitoes that already have advanced malaria infections. In addition "Our engineered strains slow speed of kill enable mosquitoes to achieve part of their reproductive output, and so reduces selection pressure for resistance to the biopesticide," St. Leger said. "Mosquitoes have an incredible ability to evolve and adapt so there may be no permanent fix. However, our current transgenic combination could translate into additional decades of effective use of fungi as an anti-malarial biopesticide."

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, funded this research.

Simpler Way of Making Proteins Could Lead to New Nanomedicine Agents

ScienceDaily (Feb. 25, 2011) — Researchers have developed a simple method of making short protein chains with spiral structures that can also dissolve in water, two desirable traits not often found together. Such structures could have applications as building blocks for self-assembling nanostructures and as agents for drug and gene delivery.

Researchers found that elongating side chains with charged ends enabled short proteins to coil into a stable helix.

Led by Jianjun Cheng, a professor of materials science and engineering at the University of Illinois, the research team will publish its findings in the Feb. 22 edition of the journal Nature Communications.

Materials scientists have been interested in designing large polymer molecules that could be used as building blocks for self-assembling structures. The challenge has been that the molecules generally adopt a globular, spherical shape, limiting their ability to form orderly aggregates. However, polypeptides -- chains of amino acids such as proteins -- can form helical structures. Short polypeptide chains that adopt a spiral shape act like cylindrical rods.

"If you have two rigid rods, one positive and one negative, right next to each other, they're going to stick to each other. If you have a way to put the charge on the surface then they can pack together in a close, compact way, so they form a three-dimensional structure," Cheng said.

However, it is difficult to make helical polypeptides that are water-soluble so they can be used in solution. Polypeptides gain their solubility from side chains -- molecular structures that stem from each amino acid link in the polypeptide chain. Amino acids with positive or negative charges in their side chains are needed to make a polypeptide disperse in water.

The problem arises when chains with charged side chains form helical structures. The charges cause a strong repulsion between the side chains, which destabilizes the helical conformation. This causes water-soluble polypeptides to form random coil structures instead of the desired helices.

In exploring solutions to the riddle of helical, water-soluble polypeptides, researchers have tried several complicated methods. For example, scientists have attempted grafting highly water-soluble chemicals to the side chains to increase the polypeptides' overall solubility, or creating helices with charges only on one side.

"You can achieve the helical structure and the solubility but you have to design the helical structure in a very special way. The peptide design needs a very specific sequence. Then you're very limited in the type of polypeptide you can build, and it's not easy to design or handle these polypeptides," Cheng said.

In contrast, Cheng's group developed a very straightforward solution. Since the close proximity of the charges causes the repulsion that disrupts the helix, the researchers simply elongated the side chains, moving the charges farther from the backbone and giving them more freedom to keep their distance from one another.

The researchers observed that as they increased the length of the side chains with charges on the end, the polypeptides' propensity for forming helices also increased.

"It's such a simple idea -- move the charge away from the backbone," Cheng said. "It's not difficult at all to make the longer side chains, and it has amazing properties for winding up helical structures simply by pushing the distance between the charge and the backbone."

The group found that not only do polypeptides with long side chains form helices, they display remarkable stability even when compared to non-charged helices. The helices seem immune to temperature, pH, and other denaturing agents that would unwind most polypeptides.

This may explain why amino acids with large hydrophobic side chains are not found in nature. Such immutability would preclude dynamic winding and unwinding of protein structures, which is essential to many biological processes. However, rigid stability is a desirable trait for the types of applications Cheng's group explores: nanostructures for drug and gene delivery, particularly targeting cancerous tumors and stem cells.

"We want to test the correlation of the lengths of the helices and the circulation in the body to see what's the impact of the shape and the charge and the side chains for clearance in the body," Cheng said. "Recent studies show that the aspect ratio of the nanostructures -- spherical structures versus tubes -- has a huge impact on their penetration of tumor tissues and circulation half-lives in the body."

Cheng plans to create a library of short helical polypeptides of varying backbone lengths, side chain lengths and types of charge. He hopes to simplify the chemistry even further and make the materials widely accessible. His lab already has demonstrated that helical structures can be effective gene delivery and membrane transduction agents, and building the library of soluble helical molecules will allow further investigation of tailoring such nanostructures for specific biomedical applications.

The National Science Foundation and the National Institutes of Health supported this work. Illinois co-authors were graduate students Hua Lu and Yugang Bai and undergraduate student Jason Lang. "Hua Lu, a fifth year graduate student in my group, is the first author of the publication and made the most significant contribution to this work," Cheng said. Yao Lin and Jin Wang, of the University of Connecticut, and professor Shiyong Liu, of the University of Science and Technology of China, also collaborated with Cheng's group on the paper.

Migrating Cells Flow Like Glass: Research Advances Understanding of Wound Healing, Cancer Metastasis, and Embryonic Development

ScienceDaily (Feb. 25, 2011) — By studying cellular movements at the level of both the individual cell and the collective group, applied physicists have discovered that migrating tissues flow very much like colloidal glass.

This is an artist's representation of epithelial cells (black) approaching the glass transition (blue). Increasingly large groups of cells (green, purple, red) are able to move together more rapidly than the surrounding cells.

The research, led by investigators at Harvard's School of Engineering and Applied Sciences (SEAS) and the University of Florida, advances scientists' understanding of wound healing, cancer metastasis, and embryonic development.

The finding was published online Feb. 14 in Proceedings of the National Academy of Sciences.

Cells often move from one part of the body to another. In a developing embryo, for example, cells in the three germ layers have to arrange themselves spatially so that the cells that will become skin are all on the outside. Similarly, as a cancerous tumor expands, the cells proliferate and push others aside. In wound healing, too, new cells have to move in to replace damaged tissue.

It is well known that cells accomplish these movements through internal cytoskeletal rearrangements that allow them to extend, retract, and divide. At some point during the migration, though, the new tissue settles into place and stops.

"We're trying to understand it from a fundamental point of view," says principal investigator David Weitz, Mallinckrodt Professor of Physics and Applied Physics at SEAS. "What we're really trying to get at is, why do things stop moving?"

The glass under discussion here is not the kind used in windows -- though that is part of the larger category. Glasses include any amorphous materials that are viscous enough to remain solid for a reasonable period of time (often considered to be 24 hours) but which flow over longer periods (see sidebar).

Cream that is churned into butter goes through a sort of glass transition, as the increasing density of particles in the fatty emulsion forces it to become solid. Like any glass, butter will lose its form if the temperature rises.

As supercooled fluids and colloids (like cream) become more dense and approach the glass transition, the particles exhibit certain characteristic motions.

"We study this extensively," says Weitz, who leads the Experimental Soft Condensed Matter Group at SEAS. "We take small particles, and we increase their concentration more and more until they stop moving and they become a glass -- and we understand how that behaves very well."

Living cells, though, add several levels of complexity to the system: they vary in size, shape, and rigidity; they divide; they sense their environment; and they exert their own forces on their surroundings.

"What is really surprising to us in this research with tissues," says Weitz, "is that many of the features that inert particles exhibit as their concentration increases are also exhibited by cells. The real qualitative difference is that small particles move only because of thermal motion, whereas cells actually move themselves."

To simulate and study the migration of living tissue, Weitz's team deposited thousands of epithelial cells -- specifically, canine kidney cells -- onto a polyacrylamide gel containing the protein collagen. The researchers watched them grow and move under a microscope while measuring the individual and collective cellular movements, as well as the changes in density caused by proliferation.

The researchers found that when the cells are in a confluent layer (meaning that the cells are close enough to be touching), they flow like a liquid. However, when cell density increases past a certain threshold, the tightly packed cells begin to inhibit each other's movement. As a result, some cells are able to travel in groups, while others hardly get to move at all.

In other words, they behave just like a supercooled fluid or colloidal suspension transitioning into a glass.

"The implications for biological processes are very surprising," says lead author Thomas E. Angelini, formerly a postdoctoral researcher at SEAS and now an Assistant Professor at the University of Florida.

"Imagine a model wound in which a large group of cells are removed from the middle of a confluent layer," he says. "Cells will migrate inward to fill the void. Our results demonstrate that the low density of cells in the center of the wound is analogous to a raised temperature in the center of a molecular glass, causing flow within the hotter region."

"You could say that a wound is melted glass."

Weitz and Angelini's co-authors include Edouard Hannezo, of the Ecole Normale Superieure, in France; Xavier Trepat, of the Institut de Bioenginyeria de Catalunya, the Universitat de Barcelona, and Ciber Enfermedades Respiratorias, in Spain; Manuel Marquez, of YNano, LLC; and Jeffrey J. Fredberg, of the Harvard School of Public Health.

The research was supported by the National Science Foundation's Division of Materials Research, the Harvard Materials Research Science and Engineering Centers, and the University of Malaga.

Animal rights and wrongs - Nature 470, 435 (24 February 2011)

The results of a Nature poll of scientists involved in animal research reveal that nearly one-quarter of respondents have been negatively affected by animal-rights activists, or seen it happen to someone they know. In some places, including the United Kingdom, the figure is higher than one-third. The large number of people affected will surprise many of Nature's readers. Researchers have suffered fire bombings, physical attacks, destruction of personal property and campaigns of harassment. But the statistics do not necessarily reflect the current prevalence of violent activist behaviour — rather, they reveal how such activity instils a lingering fear that is difficult to forget (see page 452).

The survey shows how corrosive animal-rights extremism can be. It is clear that many of those who perpetrate it remain unrepentant and determined to continue their efforts to terrorize researchers, but there are positive signs. Little more than 15% of poll respondents who were affected by activism said the tactics drove them to change the direction or practice of their research, and several who did make changes said that they mostly became more selective about who they talked to or how they presented their work on the Internet.

“There is no excuse for institutions not to explain what goes on within their walls.”

There are welcome signs that the tide of violent activity may be turning, especially in the United Kingdom. Several factors could be at work. Tougher legislation might be having an effect; in the past few years, Britain and the United States have both introduced laws that reinforce the seriousness of acts of vandalism intended to bully and blackmail those connected to animal research. Groups in favour of such research have also helped to calm the violence. Pro-Test, an organization based in Oxford, UK, which this week celebrates its fifth anniversary, has managed to counter a campaign of misinformation and intimidation that almost scuttled plans to build a biomedical research facility at the University of Oxford (seepage 457). Other groups have begun to follow Pro-Test's lead, including an offshoot at the University of California, Los Angeles, which has been repeatedly targeted by activists. Proactive campaigns and pressure on lawmakers to protect the public's investment in research have aided the backlash against extremism. But these are only part of the solution.

Scientists regularly face the dilemma of how open to be about their animal research. Non-disclosure, even in the scientific literature, is common, according to a recent survey by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research. Such a lack of openness, it added, could impede reproduction and replication of previous work (C. Kilkenny et al. PLoS ONE 4, e7824; 2009). Findings such as these have led many journals, including Nature, to adopt more-explicit rules about what is to be reported in the literature (see http://go.nature.com/5zbqp4).

Talking to the public remains crucial. Sometimes, the threat of violence means that individual researchers will not wish to engage directly with the public and should even be cautioned against doing so. But there is no excuse for institutions that house animal research — including most research universities — not to have vigorous and well-defined programmes to explain what goes on within their walls. Institutions should publicize the high standards that they are required to meet before they can use animals. They should also discuss their strategies to replace animals with more sophisticated research tools, refine research practice and reduce the overall number of animals used. If they have no such strategies, institutions should develop them as a priority.

Some scientists who work with animals are already willing to explain the importance of their research. Others should follow their lead. Nature's survey found that more than 50% of researchers were encouraged by their institutions to engage with the public, yet not much more than one-quarter felt they were given the necessary training or support. This is unacceptable: the resources are out there, including tips on how to communicate effectively and how best to respond to personal threats.

Activists often attempt to marginalize researchers, isolating them from their institutions and the wider community. If researchers build better and stronger bonds with both, they can ensure that it is the extremists who are marginalized.

Chemical Compounds in Trees Can Fight Deadly Staph Infections in Humans

ScienceDaily (Feb. 25, 2011) — Most people would never suspect that a "trash tree," one with little economic value and often removed by farmers due to its ability to destroy farmland, could be the key to fighting a deadly bacterium. Now, a University of Missouri researcher has found an antibiotic in the Eastern Red Cedar tree that is effective against methicillin-resistant Staphylococcus aureus(MRSA), a "superbug" that is resistant to most medications.

Methicillin-resistant Staphylococcus aureus (MRSA), a “superbug” that is resistant to most medications, sickened more than 94,000 people in 2005 and killed more than 19,000 in the US, according to a report from the Centers for Disease Control.

"I wanted to find a use for a tree species that is considered a nuisance," said Chung-Ho Lin, research assistant professor in the MU Center for Agroforestry at the College of Agriculture, Food and Natural Resources. "This discovery could help people fight the bacteria as well as give farmers another cash crop."

MRSA is an evolving bacterium that is resistant to most medications. For most people, the infection is isolated to the skin. However, it can spread to vital organs causing toxic shock syndrome and pneumonia, especially in people with weakened immune systems. The incidence of disease caused by MRSA bacteria is increasing worldwide. Thirty years ago, MRSA accounted for 2 percent of all staph infections. By 2003, that number had climbed to 64 percent. In 2005, more than 94,000 people developed life-threatening MRSA infections in the United States, according to a Centers for Disease Control report. Nearly 19,000 people died during hospital stays related to these infections.

While the Eastern Red Cedar has few commercial uses, it is present in the U.S. in large numbers and its range extends from Kansas to the eastern United States. An estimated 500 million trees grow in Missouri. Lin began his investigation by building on existing research showing the anti-bacterial potential of chemical compounds derived from the tree.

Lin, George Stewart, professor and department chair of Pathobiology in the College of Veterinary Medicine, and Brian Thompson, postdoctoral fellow in the Bond Life Sciences Center, identified, isolated and tested 17 bioactive compounds and has plans to analyze more compounds. Scientists found that a relatively small concentration of a chemical compound found in the Eastern Red Cedar- 5 micrograms per milliliter -- was effective against MRSA. The team tested the compound's effectiveness against many versions of MRSA in a test tube with promising initial results.

"We found this chemical from the cedar needles, an abundant and renewable resource that can be collected annually," co-researcher Brian Thompson said. "Because the compound is in the needles, we don't have to cut down the trees."

In addition to its potential use in fighting MRSA, researchers found that some chemical compounds in the tree are able to fight and kill skin cancer cells present in mice. It may also be effective as a topical acne treatment. Stewart said the compounds are years away from commercial use, as they must go through clinical trials. The team's research was presented recently at the International Conference on Gram-Positive Pathogens.

Personalized Medicine: Towards Customized Treatment of Breast Cancer

ScienceDaily (Feb. 25, 2011) — Breast cancer can develop very differently in different women. Researchers in Norway are improving breast cancer diagnostics and treatment by identifying the various tumour types. The objective is to find out as much as possible about the various tumour types so that each patient can receive precisely the right treatment at the right time. Women respond differently to available treatments. At Oslo University Hospital and the Norwegian University of Science and Technology (NTNU) in Trondheim, researchers are capturing the complexities of breast cancer tumours. Their projects receive funding under the Research Council's National Programme for Research in Functional Genomics in Norway (FUGE).

Breast cancer is the most common type of cancer in women. This extremely complex disease is attacking more and more women, and both the way it develops and its outcome can vary greatly from case to case.

Women also respond differently to available treatments. At Oslo University Hospital and the Norwegian University of Science and Technology (NTNU) in Trondheim, researchers are capturing the complexities of breast cancer tumours. Their projects receive funding under the Research Council's National Programme for Research in Functional Genomics in Norway (FUGE).

Different tumours, same treatment

"For breast cancer patients, we currently have only a few different treatment principles from which to choose," explains Professor Gunhild M. Mælandsmo. "This means that many patients receive the same treatment even though their tumours may be very different. Our objective is to find out as much as possible about the various tumour types so that each patient can receive precisely the right treatment at the right time. There are still many people who die from breast cancer -- which plainly shows we are not yet able to treat everyone effectively."

"One of our objectives is to figure out how to identify the patients with the most serious prognoses," says Professor Ingrid Gribbestad. "Can we tell, for example, from the molecular structure of the tumours? If so, then new medicines that are particularly effective against certain structures can be developed."

Professor Gribbestad heads a breast cancer research project in Trondheim, while Professor Mælandsmo and Therese Sørlie are heading projects in Oslo. They have all entered into a cooperation agreement in order to make use of each other's methods and findings. Whereas the Trondheim researchers are using magnetic resonance (MR) tomography to characterise tumours, the Oslo researchers are focusing on molecular changes. MR is a medical imaging technique for detailed visualisation of internal human and animal tissue.

Testing on animal models

"Cancer develops when the genes in a cell are damaged," explains Professor Anne-Lise Børresen-Dale, who works on the project with Professor Sørlie. "This is why research on genetic material is so crucial for our understanding of cancers."

The Oslo researchers study the genetic background of breast cancer patients as well as the DNA, RNA and proteins of their tumours. Then, for comparison, they test out various treatments on animals that have received implanted tumours with various genetic profiles and severity from the patients. After some treatment time, the animal subjects are shipped to Trondheim, where they undergo MR scanning.

"We can see whether the MR signals are different for genetically different tumours," adds Professor Gribbestad, "and if so, whether there are any distinctive characteristics to use when we analyse patients' MR images. Certain characteristics, for instance, may suggest that the patient's tumour is especially difficult to treat."

Up to 15 subtypes

Professor Gribbestad and her colleagues have also developed a new method called metabolomics. A specialised magnetic resonance machine enables them to study biochemical processes of patients' tissue samples. Do different processes occur in a benign tumour compared to a malignant one?

"By identifying these biochemical processes," says Professor Gribbestad, "we may be able to develop medicines that can stop the processes that lead to harmful progression in certain breast cancer patients. This method is unique in that it allows us to quickly identify the processes without destroying the tumour tissue, so that the tissue can be used again in future studies."

In 2000 the scientific journal Nature presented the work of Sørlie and Børresen-Dale in identifying five subtypes of breast cancer. The researchers believe, moreover, that once they refine their identification of tumours in individual patients, they may discover that there are as many as 15 subtypes.

New treatment principles

The goal is customised treatments targeted at each tumour subtype. Current treatment alternatives include surgery, chemotherapy, radiation, and hormonal (anti-oestrogen) therapy. The researchers are seeking new treatment possibilities through activities such as patient trials to test the antibody drug Avastin.

Avastin is designed to choke off the blood supply to a tumour by blocking the formation of new blood vessels. Women with locally advanced breast cancer who are undergoing treatment at Oslo University Hospital are now offered chemotherapy in combination with Avastin. Samples of their tissue, blood and bone marrow are collected for future analysis.

"We intend to find out which kinds of proteins and genes are expressed in the patients who respond to treatment versus those who don't," says Professor Mælandsmo. "This would enable us to customise Avastin treatment based on a patient's genetic profile."

"Large-scale studies on this type of treatment are underway," says Professor Børresen-Dale, "but they are not doing molecular profiles. So they may determine that a substance works, but not for whom and why."

Veterinary Anaesthesia and Analgesia - Volume 37, Issue 5 Pages 393–16

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   RESEARCH PAPER: Comparison of two different methods for physiologic dead space measurements in ventilated dogs in a clinical setting (pages 393–400)
   

   Martina Mosing, Lukas Staub and Yves Moens

   Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00548.x

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2. RESEARCH PAPER: Comparison between two methods for cardiac output measurement in propofol-anesthetized dogs: thermodilution and Doppler (pages 401–408)
   

   Patricia Cristina Ferro Lopes, Marlos Gonçalves Sousa, Aparecido Antonio Camacho, Roberta Carareto, Celina TD Nishimori, Paulo SP Santos and Newton Nunes

   Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00552.x

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3. RESEARCH PAPER: Incidence of elevation of cardiac troponin I prior to and following routine general anaesthesia in dogs (pages 409–416)
   

   Fabio Cilli, Hatim IK Alibhai, Elizabeth Armitage-Chan, Adrian Boswood, Richard A Hammond, Shailen Jasani and David C Brodbelt

   Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00554.x

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   RESEARCH PAPER: Sedative and cardiorespiratory effects of dexmedetomidine and buprenorphine administered to cats via oral transmucosal or intramuscular routes(pages 417–424)
   

   Luiz Cesar P Santos, John W Ludders, Hollis N Erb, Karen L Basher, Pati Kirch and Robin D Gleed

   Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00555.x

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   RESEARCH PAPER: Romifidine as a constant rate infusion in isoflurane anaesthetized horses: a clinical study (pages 425–433)
   

   Lindsey Devisscher, Stijn Schauvliege, Jeroen Dewulf and Frank Gasthuys

   Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00556.x

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6. RESEARCH PAPER: Comparison of an implantable telemetry device and an oscillometric monitor for measurement of blood pressure in anaesthetized and unrestrained green iguanas (Iguana iguana) (pages 434–439)
   

   Sathya K Chinnadurai, Ryan DeVoe, Amie Koenig, Nadia Gadsen, Amanda Ardente and Stephen J Divers

   Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00557.x

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      RESEARCH PAPER: Segmental dorsolumbar epidural analgesia via the caudal approach using multiple port catheters with ketamine or lidocaine or in combination in cattle (pages 451–459)
      

      Rafael DeRossi, Rodrigo A Bertoni, Rafael HS Ruzzon, Alexandre B Verde-Selva and Fabrício O Frazílio

      Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00559.x

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   2. RESEARCH PAPER: Ultrasound-guided nerve blocks of the pelvic limb in dogs(pages 460–470)
      

      Yael Shilo, Peter J Pascoe, Derek Cissell, Eric G Johnson, Philip H Kass and Erik R Wisner

      Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00560.x

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   3. CASE REPORT: Suspected acute meperidine toxicity in a dog (pages 471–477)
      

      Francis J Golder, Jeffrey Wilson, M Paula Larenza and Owen T Fink

      Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00553.x

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2. 1. Abstracts presented at the 34^th American College of Veterinary Anesthesiologists Annual Meeting, 9^th–12^th September 2009, Chicago, IL, USA (pages 1–16)
      

      Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00561a.x

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1. RESEARCH PAPER: Evaluation of cardiovascular, respiratory and biochemical effects, and anesthetic induction and recovery behavior in horses anesthetized with a 5% micellar microemulsion propofol formulation (pages 440–450)
   

   Marlis L Rezende, Pedro Boscan, Scott D Stanley, Khursheed R Mama and Eugene P Steffey

   Article first published online: 16 AUG 2010 | DOI: 10.1111/j.1467-2995.2010.00558.x

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