On 1 January 2009 the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) will launch ten new Collaborative Research Centres. They will be initially funded for the next four years with a total of approximately 90 million euros. Among other things, the new Collaborative Research Centres will study the origins of diseases caused by viruses and bacteria, scarring of the liver and kidneys, and the human skin. Other topics include the optimisation of planning, production and utilisation processes in lightweight engineering and the improvement of communications between humans and technical systems. Four Transregional Collaborative Research Centres are among the ten institutions, distributed among several locations.

In addition to these institutions, the responsible Grants Committee of Germany’s central research funding organisation also agreed to continue 28 Collaborative Research Centres for an additional period. The DFG thus will fund a total of 250 Collaborative Research Centres as of next year. In 2009, they will receive around 480 million euros, including 20% overhead funding to cover indirect costs resulting from the research projects.

The Grants Committee’s autumn meeting also observed the Collaborative Research Centres’ 40th anniversary: in the autumn of 1968 the first 18 Collaborative Research Centres were launched – with total funding amounting to 4.4 million Deutschmarks. This new type of collaborative research was seen as a “minor revolution” DFG President Professor Matthias Kleiner remembers in an anniversary speech to the Grants Committee. In both the universities and the DFG, Kleiner said, the Collaborative Research Centres had also initially given rise to apprehension – 40 years on, they have more than fulfilled expectations. “Universities can bundle their resources, create local priorities and promote top-level research with the aid of Collaborative Research Centres,” the DFG President underlined. In particular their concentrated quality, their interdisciplinary approach and the endurance of funding projects for up to 12 years make the Collaborative Research Centres a “programme for quantifiable, top-level research”. The Collaborative Research Centres, and their variations the Transregional Collaborative Research Centres and Transfer Projects, also contribute to promoting young researchers, to international research cooperation and to cooperation between science and the private sector. The conclusion of the DFG President following 40 years of Collaborative Research Centres: “The whole world is envious of this programme.”

The new Collaborative Research Centres in detail: (in alphabetical order by host university)

Collaborative Research Centre/Transregional Collaborative Research Centre 57, “Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease” deals with an extremely important scientific and clinical topic. Researchers at several sites study fibroses, i.e. the pathological growth of connective tissue in the liver and kidneys. This type of scarring can often lead to death and is also expensive to treat. The new project aims to decipher the still largely unknown pathophysiological fundamentals of fibrotic diseases. Identification of common molecular mechanisms in the kidneys and liver is especially important. It will only be possible to develop innovative therapies on this basis. (Host university: Rhineland-Westphalian Technical University of Aachen; Spokesperson: Professor Christian Trautwein; other universities involved: Rheinische Friedrich-Wilhelms University, Bonn, University of the Saarland, SaarbrГјcken.)

Detailed research into special molecules, atoms and ions with unpaired electrons is at the centre of Collaborative Research Centre 813, “Chemistry at Spin Centres – Concepts, Mechanisms, Applications” The so-called spin centres display unusual magnetic properties and high chemical reactivity; both may be extremely important for the development of innovative materials. Among other things, the researchers involved at Bonn University and the JГјlich Research Centre want to develop new theoretical and experimental methods for studying spin centres and their transformation mechanisms. The knowledge gained will be utilised for developing new reactions and multifunctional materials. (Host university: Rheinische Friedrich-Wilhelms University, Bonn; Spokesperson: Professor Frank Neese; also involved: JГјlich Research Centre)

The “Management of Uncertainty in Load-bearing Systems in Mechanical Engineering” is the topic of the newly launched Collaborative Research Centre 805 In it, engineering scientists of various disciplines and mathematicians study the subject of “uncertainty”, which is prevalent in mechanical engineering in all phases of the development, production and utilisation of products and can have grave economical and safety consequences. This applies primarily to load-bearing systems in lightweight engineering, which aim to combine high load-bearing capacity, low weight and low production costs. With the aid of a particularly complex aircraft undercarriage, the Collaborative Research Centre aims to clarify how uncertainty and the resulting errors of judgement can be managed. This will help to optimise planning, production and utilisation processes. (Host university: Technical University of Darmstadt; Spokesperson: Professor Holger Hanselka; also involved: Fraunhofer Institute for Operational Strength and System Reliability, Darmstadt)

How do viruses and bacteria cause diseases – Collaborative Research Centre 796 “Control Mechanisms of Microbial Effectors in Host Cells” aims to acquire new, fundamental knowledge on this pivotal medical problem. The scientists involved will study molecular mechanisms relating to the origins of disease. They are particularly interested in the structural and molecular principles and mechanisms of the interactions between virulence factors and host factors. By incorporating both plant and human systems, the Collaborative Research Centre aims to cover as wide a spectrum of interactions between the two fields as possible. In addition, new virulence factors such as protease shall be investigated. In a holistic view, this will allow both universal and special mechanisms of the origins of diseases to be recognised. (Host university: Friedrich-Alexander University of Erlangen-NГјrnberg, Erlangen; Spokesperson: Professor Uwe Sonnewald; also involved: Fraunhofer Institute for Integrated Circuits IIS, Erlangen)

Developing a range of optimisation options for sheet metal elements is the aim of the new Collaborative Research Centre/Transregional Collaborative Research Centre 73 based in Erlangen-NГјrnberg, Dortmund and Hannover. Under the main heading of “Manufacturing Complex Functional Elements using Fine Gauge Sheet Secondary Forming Elements – Sheet Metal Mass Forming” the scientists involved aim to investigate how the functionality and complexity of sheet metal components can be increased. Scientific principles must be established for facilitating material flux not only in the plane, but also out of the sheet metal plane in fine gauge sheets. On the other hand, the focus is on the development of new, more robust and flexible production processes by a unique combination of sheet metal forming processes with the mass forming process. This should allow the number of individual components required to be reduced and heavy-duty, reduced weight elements to be produced in small and large numbers. This also involves a considerable improvement in efficiency in an important branch of industry. (Host university: Friedrich-Alexander University of Erlangen-NГјrnberg, Erlangen; Spokesperson: Professor Marion Merklein; other universities involved: Gottfried Wilhelm Leibniz University of Hannover, Technical University of Dortmund)

So-called redox research was previously involved primarily with the occurrence and affects of oxidative stress in disease development. Understanding reactive oxygen species as signal molecules for the physiological functions of a cell, in contrast, is a relatively new field of research. This is precisely where Collaborative Research Centre 815; “Redox Regulation: Generator Systems and Functional Consequences”, comes in. The objective is to better understand the role of redox signals in physiological processes and in the transition to pathophysiological processes. Research approaches for the targeted treatment of a variety of diseases will be developed from the information gathered. (Host university: Johann Wolfgang Goethe University of Frankfurt am Main; Spokesperson: Professor Bernhard BrГјne; also involved: Chemotherapy Research Institute, Georg-Speyer-Haus, Frankfurt am Main)

Collaborative Research Centre/Transregional Collaborative Research Centre 71, “Geometric Partial Differential Equations” studies a whole series of high-calibre mathematics problems. In it, mathematicians from various disciplines study analytical problems in geometrical contexts, together with mathematical physicists. These can either be based in differential geometry or involve applications requiring geometrical modelling. The geometrical problems originate among others in geometrical measure theory and the calculus of variations. The planned work on the so-called Willmore Functional may prove to be particularly important in this respect. In terms of applications, topics ranging from quantum dynamics to the mathematical principles of solid-state physics will be tackled. The main objective is to study geometrical partial differential equations using analytical and numerical methods and computer-aided simulation, and to describe geometrical and physical phenomena. (Host university: Albert-Ludwigs University of Freiburg; Spokesperson: Professor Ernst Kuwert; other universities involved: Eberhard Karls University of TГјbingen; University of Zurich)

Newly launched Collaborative Research Centre 803, “Functionality Controlled by Organisation in and between Membranes” The structure, functions and dynamics of biological membranes have fascinated scientists of wide-ranging disciplines for a long time. Membranes are essential to all life forms, because they provide the structures necessary for forming enclosed compartments and thus separate biochemical reactions in living cells from their environment. Nevertheless, how the membrane environment impacts on the functioning of membrane proteins and how proteins modulate the membrane structure at the molecular level generally remain a mystery. In the newly launched Collaborative Research Centre 803, “Functionality Controlled by Organisation in and between Membranes” biologists and physicists now want to gather quantitative data on the interaction of membrane lipids and proteins in an in-depth unification of theory and experiment. For example, protein and lipid functions will be predicted, and universal structural and functional origins identified. In this way, better understanding of the dynamic processes in biological membranes should be possible. (Host university: Georg-August University of GГ¶ttingen; Spokesperson: Professor Claudia Steinem, also involved: Max-Planck Institute for Biophysical Chemistry, GГ¶ttingen)

The newly launched Collaborative Research Centre 829 deals with the human skin and its function as a shield Under the title of “Molecular Mechanisms Regulating Skin Homeostasis”, the scientists involved aim to investigate how the various components contributing to the skin’s barrier function, which protects against external damage, communicate. Conversely, the molecular mechanisms that disturb equilibrium, and which may thus lead to chronic inflammatory and allergic diseases or to healing disorders, will also be clarified in more detail. Ultimately, these investigations will allow the development of new therapeutic approaches, facilitating highly targeted intervention in the disturbed metabolic pathways leading to disease. This means that the work of the Collaborative Research Centre is also of considerable medical and clinical importance from a long-term perspective. (Host university: University of Cologne; Spokesperson: Professor Thomas Michael Krieg; also involved: German Sport University Cologne, Max-Planck Institute for the Biology of Ageing, Cologne)

The highly topical problem facing Collaborative Research Centre/Transregional Collaborative Research Centre 62, “A Companion Technology for Cognitive Technical Systems” is how communication between humans and technical systems can be improved. The engineers, computer scientists and neurobiologists involved are especially interested in how emotions may be better expressed and handled in this communication process. The aim of their work is the systematic and interdisciplinary study of cognitive capabilities – and their implementation in technical systems. Characteristics such as individuality, adaptability, availability, cooperativeness and reliability represent the main focus. Implementation of these so-called companion characteristics in cognitive technical systems is intended to allow these systems to be perceived and accepted by their users as reliable, trustworthy and emphatic assistants. The newly launched Collaborative Research Centre/Transregional Collaborative Research Centre thus aims to build the foundation for a technology which provides human users with a new dimension in their interactions with technical systems. (Host university: University of Ulm; Spokesperson: Professor Susanne Biundo-Stephan; other universities involved: Otto-von-Guericke University of Magdeburg; also involved: Leibniz Institute for Neurobiology, Magdeburg)

###

Further Information

Contact at DFG Head Office is Dr. Klaus Wehrberger, Head of the Collaborative Research Centres, Research Centres and Excellence Clusters Division

A special Collaborative Research Centre 40th anniversary supplement has been issued with the DUZ magazine. The complete magazine can be viewed online at: dfg.de/forschungsfoerderung/koordinierte_programme/sonderforschungsbereiche/download/spektrum_beiheft_sfb_0809.pdf

More information on the Collaborative Research Centres can also be found at: www.dfg.de/sfbdfg.de/sfb

Source: Dr. Eva-Maria Streier

Deutsche Forschungsgemeinschaft

New research shows women who don’t receive a clot-busting drug after a stroke fare worse than men who are not treated. The study is published in the March 2, 2010, print issue of Neurology®, the medical journal of the American Academy of Neurology.

“Women need to be treated for stroke as soon as possible,” said study author Michael D. Hill, MD, MSc, FRCPC, with the University of Calgary in Alberta, Canada. “We found that women who weren’t treated had a worse quality of life after stroke than men. However, the good news is that women who were treated responded just as well as men to the treatment.”

For the study, scientists examined information from a stroke database on 2,113 people who had experienced a stroke. Of those, 232 were treated with the clot-busting drug known as tissue plasminogen activator (tPA) and 44 percent were women. Men and women were separately placed in groups based on whether they received tPA within three hours after their stroke. After six months, the people were interviewed by phone about their ability to function and quality of life.

The study found that women who did not receive the clot-busting drug were 12 percent less likely than men to have a good outcome six months later, or 58 percent of the women compared to 70 percent of men. However, women who were treated with these medications fared about the same as men who took the clot-buster drug.

“There could be many reasons why women who weren’t treated with the clot-busting drug fared worse than men, including biological reasons,” said Hill. “One social reason may be that more than 30 percent of women were widowed compared to seven percent of men at the time of stroke, and therefore did not have a spouse who could act as a caregiver. Also, post-stroke depression is more common in women than in men, which slows down recovery.”

The study was supported by the Canadian Stroke Network, one of Canada’s Networks of Centers of Excellence program, and the Ontario Ministry of Health and Long-Term Care.

The American Academy of Neurology, an association of more than 22,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as multiple sclerosis, restless legs syndrome, Alzheimer’s disease, narcolepsy and stroke.

Source: American Academy of Neurology (AAN)

We commonly think of sleep as a healing process that melts away the stresses of the day, preparing us to deal with new challenges. Research has also shown that sleep plays a crucial role in the development of memories.

An important component of anxiety disorders, including posttraumatic stress disorder (PTSD), is the formulation of memories associated with fear.

Therefore, researchers decided to evaluate whether sleep deprivation after exposure to an aversive event might eliminate the associated fear, due to the lack of memory consolidation that would typically occur during sleep.

They evaluated healthy volunteers who were shown video clips of both safe driving and unexpected motor vehicle accidents. Half of the volunteers were then deprived of sleep while the other half received a normal night’s sleep.

Later testing sessions revealed that sleep deprivation eliminated the fear-associated memories through both fear recognition and physiological fear reactions, suggesting a possible therapy for individuals with PTSD or other anxiety disorders.

Dr. Kenichi Kuriyama, corresponding author, explained: “Sleep deprivation after exposure to a traumatic event, whether intentional or not, may help prevent PTSD. Our findings may help to clarify the functional role of acute insomnia and to develop a prophylactic strategy of sleep restriction for prevention of PTSD.”

“It would be nice if the benefits of sleep deprivation upon fear learning could be produced more easily for survivors of extreme stress,” noted John Krystal, M.D., Editor of Biological Psychiatry and Professor and Chair of Psychiatry at Yale University. “New insights into the neurobiology of sleep dependent learning may make it possible for these people to take a medication that disrupts this process while leaving restorative elements of sleep intact.”

Further research is necessary, but these findings indicate that sleep deprivation is a promising avenue for the possible treatment and prevention of PTSD.

Sources: Elsevier, AlphaGalileo Foundation.

Meridian Bioscience, Inc., Cincinnati, Ohio (NASDAQ:VIVO) announced that the company has been granted a Special 510(k) clearance to update the TRU FLU package insert to include analytical sensitivity claims with two strains of 2009 H1N1 virus cultured from positive respiratory specimens. TRU FLU is a rapid test which identifies influenza A and B in human specimens.

Meridian’s TRU FLU and TRU RSV® products are unique in that they feature a closed test system that allows a specimen to be contained within the device once it has been inserted. While the performance characteristics of the device with clinical specimens that are positive for the 2009 H1N1 influenza virus have not been established, the analytical sensitivity claims with the two strains adds an additional important product benefit.

John A. Kraeutler, Chief Executive Officer, commented, “Meridian is working diligently to provide our global customers who are facing an influenza pandemic with product features that will assist them from a testing standpoint. We must provide our customers with tools that allow them to do their jobs in a rapid, safe and effective manner, thus improving patient care.”

Source
Meridian Bioscience, Inc.

Scientists at the Erasmus MC-University Medical Center in Rotterdam, The Netherlands and Applied Biosystems (NYSE:ABI), an Applera Corporation business, have made significant advances in testicular cancer research by identifying and analyzing a set of specific microRNA molecular markers that are involved in the development of testicular tumors. The study, which will be published in the November issue of The Journal of Pathology (Vol. 213 issue 3), provides new information about the unique cellular events that cause testicular cancer. These findings could potentially lead to earlier identification of the disease and new approaches for treating the cancer.

Although testicular cancer is relatively rare in the general population, it is the most common cancer in men between the ages of 15 and 44 years old1. This study has found that normal and cancerous cells contain distinctly different amounts of molecules called microRNAs. The findings also showed that a tumor’s microRNA expression pattern provides vital information about the malignancy of the tumor. This new information could help clinicians to identify testicular cancer patients more quickly and more accurately, and provide more precise prognoses than current approaches.

MicroRNAs are short non-coding RNA molecules that regulate gene expression. They play an important role in many biological processes, particularly in cell differentiation and development. MicroRNAs have also been implicated in a number of different diseases, including various cancers. Research related to microRNAs is one of the fastest growing areas in biology.

The researchers in this study, who included Prof Leendert Looijenga, group leader within the department of pathology at the Erasmus Medical Center, which is affiliated with the Josephine Nefkens Institute in Rotterdam, and Simone GГјnther, Ph.D. and Jon Sherlock, Ph.D. from Applied Biosystems, profiled the expression patterns of 157 microRNA molecules in a series of different testicular tumors and normal testicular tissue samples.

To conduct this research, the scientific team deployed a high-throughput, quantitative PCR-based approach to compare the microRNA expression profiles of multiple cell tumor samples in parallel. The real-time PCR workflow comprised an Applied Biosystems 7900HT Real-Time PCR System, running a variety of chemistries that included Applied Biosystems TaqMan® MicroRNA Assays configured in a panel format, and Applied Biosystems TaqMan® Array Human MicroRNA Panel.

The use of this real-time PCR workflow enabled the researchers to accurately determine the relative levels of mature microRNAs across a large number of different tumor samples, including those microRNAs present at levels too low to detect and quantify using other methods. The large dynamic range of the TaqMan® Assays allowed researchers to measure, in parallel, a broad range of target microRNA levels. The RT-qPCR data were analyzed using Real-Time StatMiner©, a data analysis software tool designed by Integromics™, Spain (integromics) in collaboration with Applied Biosystems.

“These findings have provided us with a new level of information for understanding the biology of cancer and these will also be applicable to breast, lung, colon and other cancers,” said Prof Leendert Looijenga, group leader within the Department of Pathology at the Erasmus Medical Center. “The contribution from Applied Biosystems in this study was particularly important in helping us to interpret our findings in the relevant biological context, and the accuracy and sensitivity of the TaqMan chemistries gave us great confidence in our results.”

Applied Biosystems is a global leader in the development and commercialization of instrument-based systems, consumables, software, and services for the life-science market. Combined with microRNA isolation kits and analysis products from Ambion, Inc., an Applied Biosystems business, the company offers one of the life-science industry’s most comprehensive lines of microRNA analysis tools. The microRNA TaqMan® Arrays, along with a complete line of TaqMan® Array Gene Signature Panels and more than 700,000 individual TaqMan® Gene Expression Assays, are available on the Applied Biosystems website. More information about Applied Biosystems’ complete line of microRNA analysis solutions is available at: mirna.appliedbiosystems.

1. Statistics from Cancer Research UK

About Applera Corporation and Applied Biosystems

Applera Corporation consists of two operating groups. The Applied Biosystems Group serves the life science industry and research community by developing and marketing instrument-based systems, consumables, software, and services. Its customers use these tools to analyze nucleic acids (DNA and RNA), small molecules, and proteins to make scientific discoveries and develop new pharmaceuticals. The Applied Biosystems’ products also serve the needs of some markets outside of life science research, which we refer to as “applied markets.” These include the fields of human identity testing (forensic and paternity testing); biosecurity, which refers to products needed in response to the threat of biological terrorism and other malicious, accidental, and natural biological dangers; and quality and safety testing, such as testing required for food and pharmaceutical manufacturing. Applied Biosystems is headquartered in Foster City, CA, and reported sales of approximately $2.1 billion during fiscal 2007.

The Celera Group is primarily a molecular diagnostics business that is using proprietary genomics and proteomics discovery platforms to identify and validate novel diagnostic markers, and is developing diagnostic products based on these markers as well as other known markers. Celera maintains a strategic alliance with Abbott for the development and commercialization of molecular, or nucleic acid-based, diagnostic products, and it is also developing new diagnostic products outside of this alliance. Through its genomics and proteomics research efforts, Celera is also discovering and validating therapeutic targets, and it is seeking strategic partnerships to develop therapeutic products based on these discovered targets. Information about Applera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at applera. Information about Applied Biosystems is available at appliedbiosystems.

Sleep apnoea can lead to daytime sleepiness, which in turn increases the risk of road accidents. In an article to be published in November’s ERJ, German researchers show that a driving simulator could allow easy, objective assessment of the accident risk. They also confirm the potential road safety benefits of the standard treatment provided to sleep apnoea sufferers.

Road accidents are now one of the leading causes of death in developed countries. And, while accusing fingers are rightly being pointed at speed and alcohol, sleepiness at the wheel also plays a significant role, which may be seriously underestimated.

Since daytime sleepiness is one of the main signs of sleep apnoea, sufferers from the condition are thus particularly vulnerable. They are thought to have an accident rate between two and seven times higher than that of the general population.

In view of this, doctors are tending increasingly (and in some countries have an obligation) to make judgements about their apnoeic patients’ safety at the wheel. But how is the risk to be judged objectively, and with what diagnostic tool?
Maritta Orth and her team, of Bergmannsheil University Hospital in Bochum, Germany, recommend a driving simulator, such as the C.A.R.® (Computer Aided Risk Simulator), which was used in the study they publish in November’s ERJ.

Simulator more effective than neuropsychological tests

The German team tested the driving performance of 31 patients with obstructive sleep apnoea. The simulator placed the subjects in monotonous driving conditions for 60 minutes at an average virtual speed of 100 kilometres/hour (62 miles/hour). Various weather conditions (wind, sunshine, rain, snow, etc.) and a range of obstacles (such as animals, pedestrians and other vehicles) were integral to the simulation.

The results obtained by Orth and her colleagues show first of all that, on average, untreated apnoea sufferers experienced 2.7 “accidents” (collisions with other vehicles or pedestrians, veering off the carriageway) in such a driving simulation, with a further 12.4 lapses of concentration. The ERJ study also demonstrates the ineffectiveness of neuropsychological tests or polysomnographic tracing to predict increased accident risk. No correlation could be demonstrated between driving performance and polysomnographic parameters or neuropsychological test results.

Positive airway pressure’s effectiveness confirmed

Most importantly, the German study shows that the usual treatment for sleep apnoea, namely continuous positive airway pressure (CPAP), delivered through a mask worn over the nose and mouth at night, can significantly improve safety behind the wheel.

Orth’s team measured apnoeic subjects’ driving performance before treatment and then two and 42 days after the start of treatment.

The results in November’s ERJ are unambiguous: not only were attention and alertness improved after 42 days’ treatment, as were sleepiness scores and polysomnographic traces; but a safer driving performance could be seen even before the other improvements. The comparative accident rate fell sharply as soon as treatment began (2.7 before the start of CPAP, 1.5 after two days and 0.9 at 42 days).

In parallel to these results, the German team emphasises the qualities of the simulator used in the study, which it found particularly well suited to this type of investigation.

“The C.A.R.® driving simulator is the best tool for comparing obstructive sleep apnoea sufferers’ driving abilities before and under CPAP”, the authors state.
Its scope appears very broad: already tested for multiple sclerosis sufferers, it could be used to assess the road safety implications of many other conditions.
It could also prove useful in evaluating the effect of drug treatments on driving performance.

Title of original article:
Driving simulator and neuropsychological testing in OSAS before and under CPAP therapy

The European Respiratory Journal is the peer-reviewed scientific publication of the European Respiratory Society (more than 7,500 specialists in lung diseases and respiratory medicine in Europe, the United States and Australia).

EUROPEAN RESPIRATORY JOURNAL (ERJ), Vol. 26, No 5
erj.ersjournals

A simple, inexpensive blood test performed at birth to screen for immune disorders could dramatically increase the chance of survival for babies born with such potentially fatal disorders as severe combined immunodeficiency disease (SCID).

Physicians at Duke University Medical Center have performed stem cell transplants in 136 infants with SCID in the past 22 years. The survival rate for 38 infants receiving transplants in the first 3.5 months of life is 97 percent, but the rate drops to 69 percent for infants who were transplanted after that age, Rebecca Buckley, M.D., reports in the April 23, 2004, Annual Review of Immunology.

The main cause for the drop in survival rate is serious infections SCID babies develop in the first few months of life. Infants with SCID have little or no immune system. Without treatment, they die of infection before their first or second birthdays. But for infants without a known family history of SCID, the average age of referral for immune testing is approximately 6 months, Buckley said. “The tragedy is that most patients are critically ill by then,” she said.

Buckley believes that all newborns should be screened for immune deficiency disorders at birth. “SCID is a pediatric emergency. There is no screening for any primary immunodeficiency disease at birth or during childhood and adulthood in any country. Thus, most patients are not diagnosed until they develop a serious infection, which certainly adversely affects the outcome of therapy,” said Buckley, a professor in Duke’s division of pediatric allergy and immunology.

Early treatment also reduces costs — a transplant in the first three months of life can cost less than $50,000, but the cost of care skyrockets up to millions of dollars for seriously ill patients, with less guarantee of success.

And SCID patients who received stem cell transplants from related donors within the first 28 days of life developed a more robust immune system, with higher levels of T cell reconstitution and output from the thymus gland. T cells are white blood cells that are essential for normal function of the immune system, Buckley reports.

Nearly all SCID cases can be diagnosed at birth by counting the number of lymphocytes, a type of white blood cell, present in umbilical cord blood, Buckley said. Infants with SCID have a profound deficiency of lymphocytes, due to the deficiency of T cells that help fight infections.

Children with other immune disorders could also be identified through this test, which costs an average of $50 at a commercial laboratory. Researchers at the National Humane Genome Research Institute are developing a test for immunodeficiency disorders that could be performed on the small blood sample now taken from newborns to screen for certain metabolic disorders.

Nine forms of SCID have been identified in the past 10 years, caused by mutations of single genes. However, Buckley has treated 30 patients without mutations in the known SCID genes, making it likely other causes are yet to be discovered.

The most common form of SCID is X-linked recessive, a mutation inherited on the X chromosome. Because X-linked recessive genes are expressed in girls only if a child receives two copies of the gene — one from each parent — the disease is more common in boys, who only need one copy for an X-linked recessive gene to be expressed. SCID-X1 accounts for 46 percent of U.S. cases.

The incidence of SCID has been projected to range from one in every 100,000 to 500,000 births — more frequent than disorders such as Huntington’s disease. “However, no one truly knows how common this disease is. I suspect that it is much more common than thought because a lot of SCID patients probably die before their disease is recognized,” Buckley said.

Buckley and her colleagues at Duke University Medical Center treat SCID patients via stem cell transplants derived from donor bone marrow, typically from a parent or matched sibling.

Transplant recipients do not need pretransplant chemotherapy or prophylactic treatment for graft-versus-host disease. Infants with SCID have a complete absence of T cell function, so they cannot reject the transplants. The bone marrow is processed to remove T cells, preventing the donor T cells from attacking the recipient, known as graft-versus-host disease. Mature, donor-derived, T cells typically appear in SCID patients within 90 to 120 days after transplant. The success of treatment varies among different forms of SCID.

Clinicians are striving to improve the success of transplant therapy and create more robust immune systems by giving higher numbers of stem cells in preparations nearly devoid of T cells, Buckley added. “If the imperfect results seen with stem cell therapy in the past were due to an insufficient number of stem cells, this approach should result in better immune reconstitution. The only remaining obstacle would then be to ensure diagnosis is made early before untreatable infections develop,” she said.

Of the 136 SCID patients treated at Duke, 105 (77 percent) are alive. None show any evidence of susceptibility to opportunistic infections and most are in good general health. The oldest is 22 years of age. All 15 recipients of marrow from perfectly matched donors and 89 of the 121 recipients of T cell-depleted marrow from related donors are among the survivors.

Of the 38 infants transplanted during the first 3.5 months of life, 37 (97 percent) survive, compared to 68 survivors among the 98 transplanted after that age (69 percent success). Twenty-four of the 31 deaths occurred from viral infections. Graft-versus-host-disease (GVHD) occurred in 40 of the 121 patients given T cell-depleted parental bone marrow, but most of the GVHD was mild and required no treatment; there were no deaths from GVHD. In 35 of 40 GVHD cases, the complication occurred when there was persistence of transplacentally transferred maternal T cells.

Becky Oskin , 919-684-4966 or 919-684-4148
becky.oskinduke.edu

Following ongoing lobbying by the British Veterinary Association (BVA) and other veterinary bodies the Veterinary Medicines Directorate has dropped controversial plans for a new veterinary medicines category – POM EA (prescription-only medicine extended administration).

The proposed category has been discussed at the Veterinary Products Committee (VPC) since 2009. The original purpose was to provide a new category under which a veterinary surgeon would make a clinical assessment and, if appropriate, issue a Veterinary Permission of Extended Administration (VPEA) allowing the animal holder to obtain the prescribed POM EA medicine (from a veterinarian, pharmacist or SQP) for up to 36 months from the date of authorisation.

The BVA, along with its specialist divisions, opposed POM EA from the outset and failed to see that there was any justification for a new category. Veterinary surgeons are already able to write prescriptions for extended use and, as most health plans are reviewed annually, anything beyond a yearly assessment would be unacceptable on health and welfare grounds. An additional category would have also taken the UK even further out of step with the rest of the EU.

The BVA submitted written comments and attended a stakeholder meeting with the VMD to discuss concerns. Despite the VMD suggesting revisions to the original proposal the BVA and other stakeholders maintained that the new category was unnecessary.

Following these consultations VPC decided, at a meeting in March, not to progress the proposal any further.

Commenting, Harvey Locke, President of the BVA, said:

“We are extremely pleased that the Veterinary Products Committee has listened to our concerns and decided to drop its plans for POM EA.

“The BVA felt strongly that the proposed new category was unnecessary at best and potentially harmful to animal health and welfare at worst.

“In all fields of practice veterinary surgeons would not feel comfortable prescribing for such long periods without regular contact with the animals they care for.”

Notes

1. The minutes of the Veterinary Products Committee meeting are available on the VMD website. The relevant section is paragraphs 7.1 to 7.6.

2. The original concept note circulated for consultation is available on the BVA website. The BVA issued a press release on 30 October 2009.

Source:

British Veterinary Association

Fires raging in central Africa are generating a high amount of pollution that is showing up in data from NASA’s Aura Satellite, with the ominous shape of a dark red butterfly in the skies over southern parts of the Democratic Republic of the Congo and northern Angola.

An image of the pollution from agricultural fires in central Africa was created from data of nitrogen dioxide (NO2) levels over the period from July 7 to 12, 2011. It was created from Ozone Measuring Instrument (OMI) data using the NASA Giovanni system by Dr. James Acker at NASA’s Goddard Space Flight Center in Greenbelt, Md.

Each year, people in the region burn croplands to clear fields after harvests. Burning is also used to create new growth in pastures and move grazing animals to new locations.

NO2 forms during fires when nitrogen reacts with oxygen. In fact, NO2 is formed in any combustion process where the oxygen is provided by Earth’s atmosphere.

Detection of NO2 is important because it reacts with sunlight to create low-level ozone or smog and poor air quality. The OMI instrument that flies aboard NASA’s Aura satellite is able to detect NO2. Low-level ozone (smog) is hazardous to the health of both plants and animals, and ozone in association with particulate matter causes respiratory problems in humans.

OMI measures NO2 by the number of molecules in a cubic centimeter. The highest concentrations appear in dark red and are coming from extreme northern Angola and south central part of the Democratic Republic of the Congo. The high concentration coming from the DRC appears to look like a butterfly.

OMI data is archived at the NASA Goddard Earth Sciences Data and Information Services Center (GES DISC), and is provided by KNMI, the Koninklijk Nederlands Meteorologisch Instituut (Royal Netherlands Meteorological Institute). Dr. P.F. Levelt is the Principal Investigator of OMI, Dr. J. Tamminen is the Finnish Co-PI, and Dr. P.K. Bhartia leads the U.S. OMI science team. Dr. James Gleason (NASA) and Pepijn Veefkind (KNMI) are PIs of the OMI NO2 product.

Source:
Rob Gutro

NASA/Goddard Space Flight Center

A human study found that trimethoprim-sulfamethoxazole (TMP-SMX), an antibiotic, was more effective at preventing recurrent urinary tract infections (UTIs) among premenopausal females than cranberry capsules. The researchers, from the Academic Medical Center, Amsterdam, reported their findings in the journal Archives of Internal Medicine. They added that the antibiotic may raise the risk of resistance.

Recurrent UTIs are common among premenopausal females. Approximately half of all women are thought to be affected at some time. About 1 in every 3 women develops recurrent urinary tract infection. In such cases they are typically prescribed a low-dose antibiotic as a preventive measure.

The authors wrote:

“However, this may lead to drug resistance not only of the causative microorganisms but also of the indigenous flora.”

Although previous studies had demonstrated that cranberries and cranberry products can prevent UTIs, none of them ever compared the fruit with TMP-SMX, an antibiotic which is normally prescribed to prevent UTI recurrence.

Dr. MariГ«lle A.J. Beerepoot and team carried out a double-blind, non-inferiority trial comparing TMP-SMX with cranberry capsules. They recruited 221 patients, all of them premenopausal females who had had at least three UTIs during the previous twelve months.

The women were randomly selected into two groups:

TMP-SMX group – they took 480 mg of TMP-SMX every night, as well as one placebo capsule twice a day.
Cranberry group – they took 500mg of cranberry twice a day, as well as one placebo tablet at night.

They were checked once a month for UTI, and then for three months after the trial had ended. The women were given a questionnaire, and urine and feces samples were collected. Those who experienced UTI-like symptoms were asked to provide urine samples.

During the twelve-month period there were 1.8 recurrences in the TMP-SMX group compared to 4 in the cranberry group. The TMP-SMX group recurrences occurred after about 8 months, and 4 months in the cranberry group.

Antibiotic resistance tripled among those in the TMP-SMX group, but returned to normal 3 months after they discontinued with the medication.

TMP-SMX appears to be better at preventing UTI recurrences than cranberry tablets, the authors reported. However, there is the risk that this may be achieved with the price of higher antibiotic resistance.

The authors wrote:

“From clinical practice and during the recruitment phase of this study, we learned that many women are afraid of contracting drug-resistant bacteria using long-term antibiotic prophylaxis and preferred either no or nonantibiotic prophylaxis. In those women, cranberry prophylaxis may be a useful alternative despite its lower effectiveness.”
Accompanying Commentary: Cranberries as Antibiotics?

Bill J. Gurley, Ph.D., from the University of Arkansas for Medical Sciences, Little Rock, commented on the team’s findings. He explained that although botanical dietary supplements are not specifically aimed at treating, curing or preventing illnesses..:

“..most U.S. consumers, however, have expectations of health benefits from the dietary supplements they consume.”

Such factors as poor water solubility, or the type of metabolism that occurs may interfere with cranberry capsule effectiveness, he wrote.

Cranberry’s much lower risk of antibiotic resistance certainly makes it a useful preventive substance for recurring, UTIs, he wrote.

“..such a marked reduction in antibiotic resistance certainly favors the therapeutic potential of cranberry as a natural UTI preventative.”

Gurley added:

“Because optimal doses have not been established for many botanicals, clinical efficacy trials have often yielded negative or inconclusive results.”

Further studies, using varying doses of cranberry products may provide more useful data on effectiveness.

Arch Intern Med. 2011;171[14]:1270-1278