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Zebrafish to shed light on human mitochondrial diseases

University of Oregon discovery to benefit studies on COX deficiencies

Zebrafish can now be used to study COX deficiencies in humans, a discovery that gives scientists an unprecedented window to view the earliest stages of mitochondrial impairments that lead to potentially fatal metabolic disorders, according to researchers at the University of Oregon.

COX deficiencies refer to a breakdown of cytochrome coxidase, an enzyme located in the mitochondrion of every cell. Mitochondria are crucial cellular workhorses that provide chemical energy. Research of the deficiency has been stymied by a lack of model organisms, with mice being introduced as the first model by Japanese researchers just seven years ago.

COX involves multiple proteins and assembly factors, and deficiencies of any one of them can negatively affect metabolic tissues, including the brain, muscle and eyes. Deficiencies during the prenatal period are considered to be a potential cause of miscarriages and have been led to prenatal screenings, but scientists still don’t understand the metabolic requirements of tissues and organs during early development.

The case for zebrafish (Danio rerio) as an alternative research model is described in a paper posted online ahead of regular publication by the Journal of Biological Chemistry. The comprehensive UO study, led by doctoral student Katrina N. Baden, could speed research and point to specific targets to test potential drug therapies, said co-author Karen Guillemin, a professor of molecular biology and member of the UO Institute of Molecular Biology.

Katy Baden, whose research has established the zebrafish as a model for studying human diseases linked to COX deficiencies, is shown in the Zebrafish International Resource
Center.

“Mitochondrial impairments are emerging as important in many human diseases, but there have been few models for understanding exactly what is happening during the early development of the diseases,” Guillemin said. “The use of mice is limited, because knocking out protein expression in mice mitochondria to mimic human-disease states results in large numbers of deaths in utero. Therefore, the symptoms that researchers have wanted to study have not been assessable in mice.”

Baden, a veterinarian, performed several experiments, using RNA-blocking reagents known as morpholinos to reduce gene expression of both a critical COX subunit and Surf1, an assembly-factor protein that when mutated can lead to Leigh syndrome, a severe neurological disorder. She targeted a variety of proteins, alone and in combination, and then added back components to rescue each deficiency. Normal COX activity declined as much as 50 percent in the experimental conditions and resulted in developmental defects in endodermal tissue, cardiac function and swimming behavior in the zebrafish.

“The unique characteristics of zebrafish make them an ideal model for studying the effects of mitochondrial deficiencies on early development,” said Baden, who earned her doctorate in July and is now the veterinarian at the UO-based Zebrafish International Resource Center. “Because they develop outside of a uterus and are transparent in early stages, I was able to visualize the effects that molecular alterations have on cell biology, nervous system development, cardiac function and fish behavior.”

The external and transparent embryo, Guillemin said, will allow scientists to create specific deficits that mirror those in humans. “The transparency of the embryo will let us see primary defects, what happens in the earliest stages, rather than having to settle for seeing secondary downstream defects later in the disease state,” she said.

“Different tissues respond differently to specific losses in mitochondria.”

Baden and Guillemin said that the use of zebrafish will improve scientific understanding of the mechanisms of mitochondrial associated pathology in people and speed the identification of new treatments for mitochondrial diseases.

Other researchers who were co-authors on the study were James G. Murray, director of assay development for Mitosciences Inc. of Eugene and former post-doctoral researcher in the UO Institute of Molecular Biology (IMB), and Roderick A. Capaldi, professor of biology, member of the IMB and chief scientific officer and co-founder of Mitosciences.

The research was funded in part through two grants to Guillemin from the National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) and the Eugene and Clarissa Evonuk Memorial Graduate Fellowship in Environmental or Stress Physiology to Baden.

Sources: Karen Guillemin, assistant professor of biology, 541-346-5360, guillemin@molbio.uoregon.edu; Katrina N. Baden, veterinarian, Zebrafish International Resource Center, 541-346-6028, kbaden@uoregon.edu

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September 14, 2007 Posted by | Global Health Vision, Global News, Historical Medicine, Mitochondrial Diseases, University of Oregon | 1 Comment

Study shows an electronic medical records system can pay for itself within 16 months

CHICAGO (July 12, 2007) — A new study to be published in the July issue of the Journal of the American College of Surgeons shows that one academic medical center recouped its investment in electronic health records within 16 months. The new analysis counters concerns of health care providers reluctant to invest in electronic medical records systems.

The widespread loss of paper medical records in New Orleans after Hurricane Katrina is one of several factors behind the recent push to get surgeons and other health care providers to go electronic, according to David A. Krusch, MD, FACS, of the University of Rochester Department of Surgery and co-author of the study.

“Health care providers most frequently cite cost as primary obstacle to adopting an electronic medical records system. And, until this point, evidence supporting a positive return on investment for electronic health records technologies has been largely anecdotal,” said Dr. Krusch.

The study measured the return on investment of installing electronic health records at five ambulatory offices representing 28 providers within the University of Rochester (NY) Medical Center. Starting in November 2003, the offices implemented a Touchworks EHR system from Chicago-based Allscripts over the next five months. The study compared the cost of activities such as pulling charts, creating new charts, filing time, support staff salary, and transcription when done electronically in the third quarter of 2005, versus the cost of those same activities performed manually in the third quarter of 2003.

The University of Rochester Medical Center estimated that the new electronic medical records system reduced costs by $393,662 per year, nearly two-thirds of that coming from a sharp reduction in the time required to manually pull charts. Given that its electronic system cost $484,577 to install and operate, it took the University of Rochester Medical Center 16 months to recoup its investment. After the first year, it cost about $114,016 annually to operate the new system, which translates to a savings of $279,546 a year for the medical center, or $9,983 per provider.

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The complete study, “A Pilot Study to Document the Return on Investment for Implementing an Ambulatory Electronic Health Record at an Academic Medical Center”, will appear in the July issue of the Journal of the American College of Surgeons. In addition to Krusch, Dara L. Grieger, MD, of the University of Rochester Department of Surgery and Stephen H. Cohen, MN, CPE, also co-authored the article.

The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and to improve the care of the surgical patient. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 71,000 members and it is the largest organization of surgeons in the world. For more information, visit http://www.facs.org.

Contact: Sally Garneski
pressinquiry@facs.org
Weber Shandwick Worldwide

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Demonic possession and miraculous healing

PA110/07 — June 25 2007

Latest research into health in medieval Europe — taking in everything from demonic possession to miracles of healing — is to be revealed at The University of Nottingham.

Experts from all over the world are gathering at the University to exchange their latest findings on concepts of ‘Health and the Healthy Body’ in early medieval times, 400-1200AD.

Their research focuses on our ancestors’ view of sickness, spiritual healing, diet, disability, burial rituals, exorcism, divine intervention, Hebrew medical manuscripts and Christian concepts of the healthy body.

Scholars of the period are particularly interested in how attitudes and beliefs that originated centuries ago continue to resonate today. Until recently there was very little study of early medieval health and illness – but research findings are already suggesting that it may be time to re-think the way we regard this key aspect of life in the early Middle Ages.

The two-day conference, ‘Disease, Disability and Medicine in Early Medieval Europe’ brings together leading experts in the field from the USA, Norway, Germany, Israel and the UK on July 6-7, 2007.

Co-organiser Dr Christina Lee, of The University of Nottingham’s School of English Studies, said: “I am delighted to host the second workshop at The University of Nottingham. We are working closely with colleagues who look at modern attitudes towards disease and this event will once again be a forum for discussion between disciplines.

“We have to look towards the past to understand the ways in which attitudes towards diseases develop. The success of healing is linked to prevalent cultural views. Ethical codes played a major role in past approaches in dealing with the sick, but today we tend regard most of them as superstition.

“Our own reaction to disease and healing, such as for example the hotly-debated stem cell research, is also linked to contemporary views. By looking at past societies we may be able to understand more about our own attitudes. There is a question of what position the sick and impaired hold within a society or how much illness is accepted as part of life, which may differ from modern views where the prevalent idea is that afflictions should be cured and the expectation that bodies should ‘function’ normally.”

Lectures at the conference include:

· ‘Demon possession in Anglo-Saxon England’, Peter Dendle, Pennsylvania State University, USA. Part of an ongoing study of early medieval demonology and constructs of evil — how prevalent was demonic possession and exorcism and how often did it touch on the day-to-day lives of the Anglo-Saxons?

· ‘Healing from God: physically impaired people in miracle reports’, Klaus-Peter Horn, University of Bremen, Germany. Research focusing on pilgrimages by physically impaired people — and how much help they could receive from relatives, neighbours, servants on the long road to miraculous healing.

· ‘You are what you eat: Christian concepts of the healthy body in Old Norse Society’, Anne Irene Riisoy, University of Oslo, Norway. An overview of the dietary regulations introduced in church legislation in Norway and Iceland, with animals that had been a common feature of the pre-Christian menu — such as horses, cats and dogs — acquiring taboo status.

· ‘”This should not be shown to a gentile”: Medico-magical entries in medieval Franco-German Hebrew manuscripts and their social significance’, Ephraim Shoham-Steiner, Ben-Gurion University, Israel. Includes a discussion of texts detailing short potions, charms and medical remedies in the pages of Hebrew manuscripts.

· ‘Miraculous healing in Medieval Iceland’, Joel Anderson, University of Oslo, Norway. Includes a look at stories of saintly healing miracles and how they were viewed by contemporary Icelandic society, particularly miracles attributed to Bishop Guðmundr Arason ‘the Good’, 1161-1237.

Dr Lee will give a session with the title ‘In good company’, looking at burial patterns of people with disease in Anglo-Saxon England.

Dr Sara Goodacre, of The University of Nottingham, will give a lecture entitled ‘The history of modern Europeans: a genetic perspective’. She will present new data showing geographic trends in patterns of maternally and paternally inherited genetic variation with the British Isles, and what these findings suggest about likely patterns of male and female migration.

The meeting, sponsored by the Wellcome Trust, aims to be a forum for scholars working on the topic in a variety of disciplines and regions of Northern Europe, including all aspects of disease, disability and medicine.

Conference organisers are hoping to build bridges between experts in archaeology, palaeopathology — the study of ancient diseases — the history of medicine, as well as the history of religion, philosophy, linguistic and historical sciences.

The event takes place in the School of English Studies, at The University of Nottingham. It is a collaboration between Dr Lee at Nottingham and Dr Sally Crawford and Robert Arnott, of the University of Birmingham.

Academics wishing to attend should request a registration form from Rebecca Peck in the School of English Studies at The University of Nottingham, before June 30, on: Rebecca.peck@nottingham.ac.uk

— Ends —

Notes to editors: The University of Nottingham is Britain’s University of the Year (The Times Higher Awards 2006). It undertakes world-changing research, provides innovative teaching and a student experience of the highest quality. Ranked by Newsweek in the world’s Top 75 universities, its academics have won two Nobel Prizes since 2003. The University is an international institution with campuses in the United Kingdom, Malaysia and China.

More information is available from Dr Christina Lee, School of English Studies, University of Nottingham, on +44 (0)115 846 7194, christina.lee@nottingham.ac.uk; or Media Relations Manager Tim Utton in the University’s Media and Public Relations Office on +44 (0)115 846 8092, tim.utton@nottingham.ac.uk

The full programme and registration form can de downloaded from: http://www.nottingham.ac.uk/english/conference/ddme.htm

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June 25, 2007 Posted by | Global, Global Health Vision, Global News, Historical Medicine, Medical History, News, News Australia, News Canada, News Israel, News Jerusalem, News UK, News US, Research, University of Nottingham, Virginia, Washington DC, World News | Leave a comment