Terminal Dehydration: Experience, Perceptions Of End-Of-Life Palliative Care Nutrition And Hydration – Podcast
Most palliative care patients, at the end-of-life, will have a significantly decreased food or drink intake, if any at all.
Such cessation can be due to lack of energy, anorexia, dysphasia or nausea and this absence of nutrition leads to isotonic dehydration: the loss of salt and water from the body. Whilst potentially distressing for the families and health professionals, isotonic dehydration can be beneficial for the patient.
To discuss the reactions and perceptions of families and health professionals to medically administered nutrition and hydration, Dr Pamela van der Riet talked with Hamish Holewa for IPP-SHR podcasts. Noted were benefits associated with reduced issues with fluids, less incontinence and vomiting and some documentation relating to decreased pain. Despite such benefits, decreasing of medically administered hydration and nutrition to a palliative patient can be distressing to the family.
Education, open discussion and a team approach for staff in acute care and families, as well as basic care for the patient, was seen as very important in easing the experience and burden on all in palliative care.
Visit Podcast page with transcription and additional details
Listen to Podcast
International Program of Psycho-Social Health Research
Comprehensive Biomedical Textbook Provides Industry With Latest Engineering And Technology References
A Practicum for Biomedical
Engineering & Technology Management Issues, a new reference book
edited by Leslie R. Atles, CCE, CBET, provides the industry’s most
comprehensive collection of management, technology and reference
information. “Designed for students, managers and the continuing
professional education needs, the 948-page book helps the biomedical
community achieve its common goal of world-class healthcare service,”
according to Rich Eng, General Manager of GE Healthcare’s Monitoring
Solutions and Diagnostic Cardiology Services, who wrote the book’s
foreword. The book is available online from Kendall/Hunt Publishing
Company and can be ordered from Amazon.com.
Practicum features 55 chapters from 30 authors, covering the entire
scope of information needed for technician/engineer education. In
addition, the book includes material adapted (and now updated) from
the 1995 book Affinity Reference Guide for Biomedical Technicians.
Atles, then part of Marquette Electronics, co-authored this highly
popular book with Scott Segalewitz, Chairman of the Biomedical
Engineering Technology Program at Penn State University-New Kensington.
Eng noted that, “The sense of teamwork from the book’s contributors
enables biomeds from around the world to pursue a vision of seeing
people ‘live life to the fullest.’ That’s why we supported Les Atles’
efforts to update the original information and expand the scope of
the book to create A Practicum for Biomedical Engineering &
Technology Management Issues.”
Breadth of information builds bridges
Professionals and educators already consider Practicum, introduced
early this year, an indispensable addition to their reference
libraries and incorporate it as a core part of their curriculum.
“The list of Practicum authors reads like a ‘who’s-who’ in our
field,” said Paul Kelley, Manager, Biomedical Engineering, Washington
Hospital, Fremont, Calif. “I thought that the breadth of information
would be invaluable to my entire team, so it was easy to convince my
administration to buy copies for all our engineering staff.”
While other texts may go deeper into any given subject, Kelley
believes that no other reference book provides such complete coverage
of the BMET/CBET field. “To gather this much information, you would
have to buy a library of books,” stated Kelley (see list of sample
chapters below).
“Every OEM, independent service provider and in-house technician/
clinician should have this book in their reference library. It puts
information specific to our business just a finger tip away,” said
John Noblitt, CBET, Biomedical Equipment Technology Director at
Caldwell Community College, Hudson, N.C. Noblitt uses the Practicum
as part of teaching courses on instrumentation and safety and standards.
Noblitt added that, “People have a mental picture of biomeds sitting
at an electronics bench changing out transistors, but so much of our
real job focus on building bridges between the clinical and
technological sides of our business. Practicum helps me teach
students how to build bridges. The scope of this book gives them
insight on the motivations and priorities of their managers,
clinicians, IT staff and other constituencies.”
Guide to book contents
Sample chapters/subjects from A Practicum for Biomedical Engineering
& Technology Management Issues:
1. A Brief History of Clinical Engineering and Biomedical Equipment
Technology
2. Establishing an In-House Biomedical Program (Business Planning and
Execution)
3. Quality Assurance
5. Managing Medical Device Safety
8. HIPAA and Medical Device Security
9. Use Errors: The Benefits and Challenges of In-service Education
11. Computerized Maintenance Management Systems
12. Human Factors Engineering
14. Evidence-based Medical Equipment Maintenance Management
21. Customer Satisfaction: A Key Metric for Biomedical and Clinical
Engineering
23. Emergency Preparedness Plan: The Role of Clinical Engineers and
BMETs
28. Distance Education and the Talking Head
34. Introduction to Cardiac Physiology and Cardiac Devices
35. Telehealth: I Can See the Highway, but Where is the Ramp?
36. An Introduction to DICOM (Digital Imaging Communications in
Medicine)
In addition to these topics, Practicum include such reference guides
as those for Electrical Safety Codes and Standards, Cardiac
Physiology, Defibrillators, Infusion Devices, Lasers, Computer
Networks and Ultrasound.
About the author
Les Atles, CCE, CBET has worked in the field of biomedical / clinical
engineering for the past 34 years. Early in his career, Atles spent
16 years managing an in-house biomedical program in a midsized
specialty medical center in Los Angeles and became very involved in
the California Medical Instrumentation Association (CMIA). He is
currently active in CMIA as President of their Lifetime Member Board
of Directors Advisory Group and employed as the Director of
Technology Management for an independent service organization. Atles
also worked for Marquette Electronics (now part of GE Healthcare) as
National Biomedical Advisor. There, he started a Biomedical Advisory
Group allowing the company to work closer with and focus on the
biomedical community.
About GE Healthcare
GE Healthcare provides transformational medical technologies and
services that are shaping a new age of patient care. Our expertise in
medical imaging and information technologies, medical diagnostics,
patient monitoring systems, performance improvement, drug discovery,
and biopharmaceutical manufacturing technologies is helping
clinicians around the world re-imagine new ways to predict, diagnose,
inform, treat, and monitor disease, so patients can live their lives
to the fullest.
GE Healthcare’s broad range of products and services enable
healthcare providers to better diagnose and treat cancer, heart
disease, neurological diseases, and other conditions earlier. Our
vision for the future is to enable a new “early health” model of care
focused on earlier diagnosis, pre-symptomatic disease detection, and
disease prevention. Headquartered in the United Kingdom, GE
Healthcare is a $17- billion unit of General Electric Company (NYSE:
GE). Worldwide, GE Healthcare employs more than 46,000 people
committed to serving healthcare professionals and their patients in
more than 100 countries.
GE Healthcare
Genes May Predict Vascular Malformation
A pair of studies, led by Medical College of Wisconsin scientists at Children’s Research Institute in Milwaukee, may translate into rapid molecular tests to distinguish between hemangiomas and congenital blood or lymph vessel malformations in infants. Hemangiomas are common birthmarks consisting of benign tumors of blood vessels. The studies appear in the January 29, 2009 issue of the journal Blood.
“Our findings may lead to earlier diagnosis, precise classification and ultimately, targeted therapy for infants with hidden congenital vascular malformations,” says study author Ramani Ramchandran, Ph.D., associate professor of pediatrics in the division of developmental biology.
In the first paper, the team used genetic manipulations to study blood vessel formation in the fast-developing and conveniently transparent zebra fish embryo. They identified sucrose non-fermenting receptor kinase-1 (Snrk-1), as a gene that plays a role in the creation, migration and differentiation into arteries and veins of angioblasts, the parent cell of all blood vessels.
In the second paper, similar zebra fish embryo studies revealed that Dusp-5, a vascular-specific gene that is expressed in these parent cells and in the established blood vessels, counteracts the function of Snrk-1 to control the population of parent cells. Most importantly, the team then identified mutations in Dusp-5 and Snrk-1 genes in the affected tissues of humans with vascular malformations, thus linking the Snrk-1/Dusp-5 signaling pathway to human disease.
While the pathway these genes target in humans is novel, and remains undiscovered, it may provide the breakthrough needed to identify potential causes of vascular malformation, according to Dr. Ramchandran. He noted that these and other issues are under active investigation in his laboratory.
“We believe that specific mutations in Dusp-5 and Snrk-1 may provide keys to distinguish between hemangiomas and vascular malformations. Vascular malformations fall into different classes based on the affected vessel type. For example, venous malformations affect veins and arterial malformations affect arteries. Mutations in Snrk-1 may actually help classify vascular malformations as venous or lymphatic malformations and thus distinguish them from other malformations,” he says.
“Ultimately, we plan to expand the mutation study to include more patients to determine the predictability, severity and correlation of disease to mutations, and identify the cell type that harbors the mutation. Then, we can model the structure of the mutated protein to generate drugs that selectively target the diseased tissue.
Co-investigators on the first study were Chang Zoon Chung, Ph.D., Medical College Research Scientist in the department of pediatrics’ division of developmental biology; and researchers from the National Institutes of Health (NIH)’s Genome Technology Branch of the National Human Genome Research Institute; the Mayo Clinic College of Medicine department of biochemistry and molecular biology, and the University of Massachusetts Dartmouth. The study was supported in part by the NIH, and by seed grants from Children’s Research Institute and the Medical College.
Co-investigators on the second study were Paula E. North, M.D., Ph.D., professor of pediatrics and chief of pediatric pathology; Mark Horswill, M.S., research associate in genetics, and postdoctoral fellows Keguo Li, Ph.D., and Ganesh Samant, Ph.D..
Dr. Chung and Dr. Pramanik, postdoctoral fellows in Dr. Ramchandran’s laboratory, and research technologist Maija Garnaas, were co-first authors of this study, which was funded by seed grants from the Medical College and Children’s Research Institute.
Medical College of Wisconsin
8701 Watertown Plank Rd.
Milwaukee
WI 53226
United States
http://www.mcw.edu
What Causes Motor Complications Of Parkinson’s Treatment?
People with Parkinson’s disease commonly suffer a slowing or freezing of movement caused by the death of neurons that make dopamine, a key chemical that allows brain cells to send and receive messages essential to voluntary movements. Patients regain the ability to move, seemingly miraculously, by taking L-DOPA or related drugs that mimic the missing dopamine. After a few years on L-DOPA, however, most patients again lose motor control but in an opposite way. Instead of too little, there is too much movement, like involuntary nodding and rocking side effects known as L-DOPA-induced dyskinesias.
“L-DOPA-induced dyskinesias are a major problem for patients, and there is a great need to help with these drug side effects,” said MIT Institute Professor Ann Graybiel, a prominent Parkinson’s researcher at the McGovern Institute for Brain Research at MIT.
Graybiel and her colleagues have identified two molecules whose expression in the brain is altered in the brains of animals with L-DOPA-induced dyskinesias. The results may lead to new approaches to the treatment of dyskinesias in Parkinson’s patients, of which there are more than 1 million in the United States alone.
“We’re very excited because these genes are concentrated in precisely the places that lose dopamine in Parkinson’s disease, so they might be reasonable targets to go after therapeutically,” Graybiel said. This research was published Jan. 26 in the advance online issue of Procedings of the National Academy of Sciences.
The two related genes, named CalDAG-GEFI and CalDAG-GEFII, which are believed to be involved in signaling inside neurons, are expressed in the striatum, a brain structure essential for the control of movement and the main target of the dopamine-containing nerve tract that degenerates in Parkinson’s disease.
In a rat model of Parkinson’s disease, the two genes showed opposite changes when the animals were treated with L-DOPA. CalDAG-GEFI showed decreased expression while CalDAG-GEFII was increased.
“Moreover, the changes in the rat brain were proportional to the severity of the drug-induced dyskinesias. The more exaggerated the movements, the greater the dysregulation of these genes,” said first author Jill Crittenden, a research scientist in the Graybiel Lab.
These CalDAG-GEF genes are thought to work by controlling the activity of other important signaling molecules (Ras, Rap and ERK) that are expressed in many different parts of the body and have many different biological functions. Other labs have shown that inhibiting Ras or ERK in animal models of dyskinesias prevents these involuntary movements.
“But because Ras and ERK do so many things, they are not promising drug targets because blocking them would probably have many unwanted effects,” Crittenden said. “Because the CalDAG-GEF molecules control ERK and because they are so enriched in the very part of the brain that controls these involuntary movements, regulating them could have therapeutic value for dyskinesia without causing other problems.”
This study was funded by the Stanley H. and Sheila G. Sydney Fund, the National Institutes of Health, National Institute of Child Health and Human Development and the National Parkinson Foundation. Coauthors Ippolita Canturi-Castelvetri, Lauren Kett and Anne Young (Massachusetts General Hospital); Esen Saka (Hacettepe University, Turkey); Christine Keller-McGandy and Ledia Hernandez (MIT); and David Standaert (University of Alabama, Birmington) contributed to this study.
About the McGovern Institute at MIT
The McGovern Institute for Brain Research at MIT is led by a team of world-renowned neuroscientists committed to meeting two great challenges of modern science: understanding how the brain works and discovering new ways to prevent or treat brain disorders. The McGovern Institute was established in 2000 by Patrick J. McGovern and Lore Harp McGovern, who are committed to improving human welfare, communication and understanding through their support for neuroscience research. The director is Robert Desimone, formerly the head of intramural research at the National Institute of Mental Health. Further information is available at: http://web.mit.edu/mcgovern
McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT)
Bldg. 46-3160, 77 Massachusetts Ave.
Cambridge
MA 02139
United States
http://web.mit.edu/mcgovern
Winter Weather Hospitalizes Thousands, Kills Hundreds
Frigid temperatures, which each year cause hypothermia and other cold-related heath problems, resulted in more than 6,000 hospitalizations and 827 deaths in 2006, according to the latest News and Numbers from the Agency for Healthcare Research and Quality.
AHRQ’s analysis of 6,182 cold weather-related hospitalizations found:
– Men accounted for about 40 percent more hospitalizations for exposure to cold weather than women.
– People age 65 and older were the most likely to be hospitalized about 7 times more likely than people age 18 to 44 and 3 times as likely as people age 45 to 64.
– The most common reasons for cold weather-related hospitalizations included hypothermia (which can cause loss of physical and mental abilities and, in extreme cases, death), frostbite, respiratory failure, and pneumonia.
This AHRQ News and Numbers is based on Hospital Stays Resulting from Excessive Heat and Cold Exposure Due to Weather Conditions in U.S. Community Hospitals, 2005 (http://www.hcup-us.ahrq.gov/reports/statbriefs/sb55.jsp), but updated to reflect 2006 statistics from the Nationwide Inpatient Sample, a database of hospital inpatient stays that is nationally representative of inpatient stays in all short-term, non-Federal hospitals. The data are drawn from hospitals that comprise 90 percent of all discharges in the United States and include all patients, regardless of insurance type, as well as the uninsured.
Agency for Healthcare Research and Quality (AHRQ)
540 Gaither Rd.
Rockville
MD 20850
United States
http:// www.ahrq.gov
Worm Provides Clues About Preventing Damage Caused By Low-Oxygen During Stroke, Heart Attack
Neurobiologists at Washington University School of Medicine in St. Louis have identified pathways that allow microscopic worms to survive in a low-oxygen, or hypoxic, environment.
They believe the finding could have implications for conditions such as stroke, heart attack and cancer. Sensitivity to low oxygen helps determine how damaging those medical conditions can be. The researchers report their findings in the Jan. 30 issue of the journal Science.
“In stroke and heart attack, cells die because they lack oxygen,” explains principal investigator C. Michael Crowder, M.D., Ph.D. “In cancer, the opposite is true. Cancer cells are hypoxia-resistant in many cases, and their potential to spread throughout the body tends to correlate with their degree of hypoxia resistance.”
Crowder says it may be possible to develop more effective therapies for stroke and heart attack, on one hand, and cancer, on the other, when scientists better understand how cells protect themselves from oxygen deprivation. In the case of stroke and heart attack, therapies would involve making healthy cells resistant to hypoxia. Cancer therapies might work more effectively if it were possible to make hypoxia-resistant cells more vulnerable to low oxygen levels.
In new experiments, Crowder’s team manipulated genes in the worm Caenorhabditis elegans to alter the organism’s sensitivity to a low-oxygen environment. They did that by identifying a gene that controls the translation of genetic information into specific proteins. Mutant copies of the gene cut translation rates in half, which conferred 100% survival to the animals compared to 100% death in non-mutant worms.
Crowder says that inhibiting translation likely protects cells from hypoxia by reducing energy consumption because making proteins consumes a lot of energy. The researchers were surprised by the degree of resistance to hypoxia when the translation rate was cut. They wanted to find out whether increasing hypoxia resistance was explained only by the fact that the cells were using less energy.
In a second experiment, the researchers introduced another mutation into the worms to evaluate its effect on the original mutation. The second mutation affects a process known as protein folding.
“In some cells, hypoxia has been shown to generate unfolded proteins,” says Crowder, the Dr. Seymour and Rose T. Brown Professor in Anesthesiology and professor of developmental biology. “So then you have this load of unfolded proteins that may be toxic and promote cell death from hypoxia. We wondered whether suppressing translation in the cell might make it resistant to hypoxia by reducing the load of unfolded proteins, and that’s what we saw.”
Folding is important in allowing proteins to function properly. Every protein has shapes and pockets and active sites that bind to other proteins and perform various functions. If a particular protein doesn’t “fold” into the proper shape, it can’t do its job. It’s not clear why that might be toxic, but this study suggests fewer improperly folded proteins make exposure to low oxygen less toxic.
Connecting these discoveries to potential stroke and heart attack therapies will involve several steps. First, Crowder plans to move beyond C. elegans to see whether these techniques also will protect neurons in mammals.
“If that happens, then I think there’s hope that, eventually, we could target this process for therapy,” Crowder says. “At this point in time, I think we’re really just scratching the surface of the basic mechanisms of what controls hypoxic injury. It may be that protein translation doesn’t ultimately end up being the answer, but maybe it will lead us to an answer. It already has led us to this unfolded protein response that seems to have potential as a therapy.”
The challenge in treating stroke is that most cells in the brain continue to get plenty of oxygen. Only the part of the brain directly affected by the stroke becomes hypoxic. So Crowder says potential therapies need to protect brain cells affected by hypoxia without harming other cells that continue to experience normal oxygen levels. Targeting the unfolded protein response is attractive because, in theory, therapies would not bother cells with adequate oxygen but would react with the improper protein folding that occurs in cells not getting enough oxygen. Whether such a strategy will work is unknown.
“Many people have thought they made very promising inroads into stroke therapy over the last 50 years, and none of those treatments have been good enough,” Crowder says. “We have no illusions that finding ways to reduce cell death from hypoxia will be easy. But using this approach of randomly mutating genes and seeing what happens helped us to find this unfolded protein response. It works in the worm, so now let’s see what happens in mammals.”
Anderson LL, Mao X, Scott BA, Crowder CM. Survival from hypoxia in C. elegans by inactivation of aminoacyl-tRNA synthetases. Science, vol. 323, pp. 630-633 Jan. 30, 2009
This study was supported by that National Institute of Neurological Disorders and Stroke of the National Institutes of Health, a Neuroscience of Brain Disorders Award from the McKnight Endowment Fund for Neuroscience and an American Heart Association Established Investigator Award.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s Hospitals. The School of Medicine is one of the leading medical research, teaching, and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s Hospitals, the School of Medicine is linked to BJC HealthCare.
Washington University in St. Louis
1 Brookings Dr., Campus Box 1070
St. Louis
MO 63130
United States
http://wustl.edu
New Pathway Is A Common Thread In Age Related Neurodegenerative Diseases
How are neurodegenerative diseases such as Alzheimer’s initiated, and why is age the major risk factor? A recent study of a protein called MOCA (Modifier of Cell Adhesion), carried out at the Salk Institute for Biological Studies, provides new clues to the answers of these fundamental questions.
Under normal circumstances, MOCA is a key member of the squadron charged with keeping Alzheimer’s disease at bay. A team of researchers led by Salk professor David Schubert, Ph.D., demonstrated what happens when MOCA goes on furlough. In the process Schubert identified a novel pathway with broad implications for both Alzheimer’s and other age-related neurodegenerative diseases.
Their findings, reported in the current issue of the Journal of Neuroscience, show how neurodegenerative disease starts, initiating in the nerve ending and inducing gradual changes, like a chain reaction over a long time. The animal model used in the study also will allow scientists to better understand the processes behind the formation of the protein aggregates that are common to most neurodegenerative diseases. In addition, it will provide new opportunities to target the earliest steps for therapy.
MOCA was initially identified as a protein that binds to presenilin, a molecule that when mutated causes familial Alzheimer’s disease. MOCA is only found in neurons and regulates the expression of the beta amyloid protein responsible for the Alzheimer’s plaques that are the hallmark of the disease. To better understand MOCA’s function, Qi Chen, Ph.D., a senior scientist in Schubert’s laboratory, created a line of mice genetically engineered to lack the gene for MOCA.
“Because of the initial studies in cultured cells that we had done, we expected these mice to develop plaques,” explains Schubert. “What we found was that they develop ataxia a motor coordination problem as they age.” Chen then studied the pathology of these mice and found that it reflected a common feature of most age-related neurological diseases, not just Alzheimer’s.
The main problem turned out to be the degeneration of axons, the long projections that conduct impulses away from neurons. The axonal degeneration was caused by the accumulation of protein aggregates. Although the mice were not born with the problem, they acquired it, along with the ataxia, as they aged, and the ataxia worsened over time.
The aggregates started out small, initially causing few or no symptoms, but as they built up in the axons, they began to destroy the cytoskeleton, the internal framework of the cells, increasingly interfering with the transmission of signals from the nerve cells. Eventually the affected axons died, followed by the death of the nerve cell itself.
“Protein aggregates are common features of most age-related neurological diseases,” says Chen, the first author of the study. “So is axon degeneration; we see it in Alzheimer’s, ALS, and Huntington’s disease. Motor problems such as ataxia may be the most obvious manifestation because the aggregates appear in the long axons of the spinal cord. But the axonal aggregates also appear in the brain and may be the first step in the events that lead to age-associated neurological disease.”
After documenting the sequence of physiological and behavioral events that characterize the axon degeneration, Chen then sought to piece together the molecular pathway behind it, starting with MOCA and connecting findings from disparate studies that previously had identified parts of the pathway. He ended up with a single, step-by-step process for axon degeneration that for the first time linked together a number of diseases and conditions, including a form of mental retardation in humans.
“We had known that MOCA affected the cytoskeleton for some time, but no one had put together clear evidence showing how the sequential age-associated changes in the cytoskeleton of the nerve take place. Dr. Chen was able to do this, thereby connecting the disease pathology with the molecular biology,” says Schubert. “Now we know that MOCA is essential to the functional integrity of axons and have defined a complete pathway for axon degeneration.”
The study was funded with support from the National Institutes of Health, the Bundy Foundation, the Alzheimer’s Association, and the Shirley Foundation for Alzheimer’s Research.
In addition to Chen and Schubert, Paul E. Sawchenko, Ph.D., professor and laboratory head, and Charles A. Peto, both of the Salk Institute’s Laboratory of Neuronal Structure and Function, and Andrew Mizisin, Ph.D., professor, and G. Diane Shelton, Ph.D., adjunct professor, in the Department of Pathology at the University of California, San Diego, contributed to the study.
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health, and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.
Salk Institute for Biological Studies
10010 N Torrey Pines Rd.
La Jolla
CA 92037-1099
United States
http://www.salk.edu
Researchers Identify Protein That May Explain ‘Healthy’ Obesity
Mice whose fat cells were allowed to grow larger than fat cells in normal mice developed “healthy” obesity when fed a high-fat diet, researchers at UT Southwestern Medical Center found in a new study.
The fat but healthy mice lacked a protein called collagen VI, which normally surrounds fat cells and limits how large they can grow, like a cage around a water balloon. The findings appear online and in a future edition of Molecular and Cellular Biology.
“The mice lacking collagen VI fared much better metabolically than their counterparts that retained this particular collagen,” said Dr. Philipp Scherer, director of the Touchstone Center for Diabetes Research at UT Southwestern and the study’s senior author. “The mice without collagen VI don’t develop inflammation or insulin resistance. They still get obese, but it’s a ‘healthy’ obesity.”
When people take in more calories than needed, excess calories are stored in adipose or fatty tissue. The fat cells are embedded in and secrete substances into an extracellular matrix, a type of connective tissue that provides support to fat tissue, like scaffolding. Collagen VI is one component of the extracellular matrix. Too much of this connective tissue prevents individual cells from expanding and can lead to fibrosis and eventually inflammation.
Inflammation is thought to be an underlying cause of metabolic disorders in humans, said Dr. Scherer. Large fat cells are often considered a bad omen, he said, because they typically lead to increased cell death and systemic insulin resistance. Under normal circumstances, fat cells continue to grow until they reach a point where the extracellular matrix they’ve built around themselves is so strong that it’s no longer flexible.
“In this particular case, however, the large fat cells are not as inflamed as they would normally be,” Dr. Scherer said. “Fat cells that lack collagen VI can grow to a huge size without becoming inflamed, suggesting that collagen VI directly affects the ability of fat cells to expand.”
Dr. Scherer said the current finding is clinically relevant and probably will translate well from the mice to humans. “Our study highlights the fact that collagen VI, and possibly other extracellular matrix constituents, are extremely important in modulating fat-cell physiology,” he said.
The next step is to determine precisely how collagen VI functions in the body.
“We need to get a better grip on targets that may allow us to interfere in this process. Unfortunately collagen VI can’t be knocked out in humans, but we may be able to manipulate it,” Dr. Scherer said.
Other UT Southwestern researchers involved in the study were Dr. Zhao Wang, postdoctoral researcher in internal medicine, as well as volunteer faculty members Drs. Nicola Abate and Manisha Chandalia, who are now on staff at the UT Medical Branch at Galveston. Scientists from the Albert Einstein College of Medicine, Merck Research Laboratories and the University of Padua in Italy also participated.
The work was supported by the National Institutes of Health.
Visit http://www.utsouthwestern.org/endocrinology to learn more about UT Southwestern’s clinical services in endocrinology, including diabetes treatment.
Dr. Philipp Scherer — http://www.utsouthwestern.edu/findfac/professional/0,2356,92752,00.html
UT Southwestern Medical Center
5323 Harry Hines Blvd.
Dallas
TX 75390-9060
United States
http://www.utsouthwestern.edu
Scientists Reverse Early MS With Patients’ Own Stem Cells
A small trial at a US hospital where patients with early stage MS had their own immune system stem cells transplanted back into their bodies
appears to have reversed the neurological dysfunction of the early stages of the disease by causing their immune systems to “reset”. The scientists said
the results should now be confirmed with a larger, randomized trial.
The trial was the work of researchers from Northwestern University’s Feinberg School of Medicine in Chicago, plus colleagues from other research
centres in and outside the US, and is published early online in The Lancet Neurology on 30 January; it will appear in the March print
issue.
The patients on the small phase I/II trial experienced improvements in several areas affected by their MS, including walking, ataxia (loss of muscle
coordination), limb strength, vision, and incontinence. They continued to improve for 24 months after receiving the transplants and then
stabilized.
MS (Multiple Sclerosis) is an autoimmune disease where the person’s own immune system attacks their central nervous system causing all kinds of
neurological dysfunction such as loss of control over muscles and loss of ability to take in information through the senses.
The early stage is called relapsing-remitting MS and the person has intermittent symptoms from which they partially or fully recover and then relapse
into again. These include visual impairment, fatigue, sensory problems, limb weakness or paralysis, tremors, lack of coordination, problems with
balance, changes in bowel and bladder, and psychological changes.
After about 10 to 15 years of relapsing-remitting MS, patients enter another stage called secondary progressive MS, where symptoms steadily become worse
and irreversible.
Lead researcher on the team, Dr Richard Burt, who works at using immunotherapy for autoimmune diseases at the Feinberg School said:
“This is the first time we have turned the tide on this disease.”
For the trial, Burt and colleagues recruited 21 patients aged 20 to 53 who had had MS for an average of 5 years. They all had relapsing-remitting multiple
sclerosis that had been treated with interferon beta for at least 6 months but with no response.
First, they had to destroy the patients’ immune system with chemotherapy, then they injected them with their own stem cells that had been harvested before
the chemo. This seeded a new immune system. The procedure is called “autologous non-myeloablative haematopoietic stem-cell transplantion”.
After an average follow-up of three years after receiving their transplants (which took place between January 2003 and February 2005), 17 patients
(81 per cent) improved by at least one point on a disability scale. And for all patients, the disease had stopped progressing. Five patients relapsed in the
early days, but then experienced remission after further immunosuppression.
Burt said that they focused on destroying only the immune system part of the bone marrow and then regenerating it, a procedure that is less toxic than
traditional chemotherapy for cancer.
But amazingly, when the new immune system is created, the patient’s new white blood cells are self-tolerant, as Burt explained:
“In MS the immune system is attacking your brain.”
“After the procedure, it doesn’t do that anymore,” he said.
The authors concluded from the trial that this type of stem cell transplantation in patients with relapsing-remitting MS “reverses neurological deficits”,
and Burt said the results were “promising and exciting”, but to get real proof, you need a randomized trial, which he has already launched.
Burt has been working with MS patients for some time; in earlier research he tried transplanting immune system cells into patients with late-stage MS
but it didn’t help them like it did the early stage patients in this trial.
“Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II
study.”
Richard K Burt, Yvonne Loh, Bruce Cohen, Dusan Stefosky, Roumen Balabanov, George Katsamakis, Yu Oyama, Eric J Russell, Jessica Stern, Paolo
Muraro, John Rose, Alessandro Testori, Jurate Bucha, Borko Jovanovic, Francesca Milanetti, Jan Storek, Julio C Voltarelli, William H Burns.
The Lancet Neurology published online ahead of print 30 January 2009.
doi:10.1016/S1474-4422(09)70017-1
Click here for
Abstract.
Sources: Journal Abstract, Northwestern University press release via ScienceDaily.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Weight Loss Reduced Incontinence In Overweight And Obese Women
A new study from the US found that moderate weight reduction helped to reduce urinary incontinence among overweight and obese
women.
The research was the work of first author of Dr Leslee Subak from the University of California, San Francisco (UCSF), and colleagues, and is
published online in the 29 January issue of the New England Journal of Medicine. Subak is an obstetrician/gynecologist at the Women’s
Continence Center in the UCSF Women’s Health Centre.
In their background information the authors wrote that obesity was already known to be a risk factor for urinary incontinence, but there wasn’t enough
evidence on whether losing weight could help obese women with incontinence.
For the study, Subak and colleagues randomly assigned 338 overweight and obese women diagnosed with urinary incontinence to one of two groups.
Most of the women were aged between 40 and 65 (average age was 53) and all were experiencing at least 10 urinary incontinence episodes a week
before the study.
One group (226 patients) went through an intensive 6 month weight-loss program comprising diet, exercise, and other lifestyle changes, while the
other group (112 patients) just went to structured education classes that told them about the benefits of weight loss (the controls).
The results showed that:
- At the start of the intervention period, the BMI (body mass index, the weight in kilos divided by the square of the height in metres) and the weekly
number of incontinence episodes were similar in both groups.
- After 6 months, the women in the intensive weight loss group had a mean weight loss of 8 per cent (7.8 kg) compared with 1.6 per cent (1.5 kg) in
the education only group (the controls).
- The mean weekly number of incontinence episodes went down by 47 per cent in the intensive weight loss group, compared with only 28 per cent
in the control group.
- Compared with the control group, the intensive weight loss group had no more significant numbers of urge-incontinence episodes a week, but
they had significantly fewer of the stress-incontinence type.
- A higher proportion of the women in the weight loss group had a clinically relevant drop of 70 per cent in overall frequency of all-, stress-, and
urge-incontinence episodes.
Subak and colleagues concluded that:
“A 6-month behavioral intervention targeting weight loss reduced the frequency of self-reported urinary-incontinence episodes among overweight and
obese women as compared with a control group.”
Reduction in urinary incontinence may now count as one more of the many health improvements that moderate weight reduction can bring to women who are overweight, they
added.
“Weight Loss to Treat Urinary Incontinence in Overweight and Obese Women.”
Leslee L. Subak, M.D., Rena Wing, Ph.D., Delia Smith West, Ph.D., Frank Franklin, M.D., Ph.D., Eric Vittinghoff, Ph.D., Jennifer M. Creasman,
M.S.P.H., Holly E. Richter, Ph.D., M.D., Deborah Myers, M.D., Kathryn L. Burgio, Ph.D., Amy A. Gorin, Ph.D., Judith Macer, B.Sc., John W. Kusek,
Ph.D., Deborah Grady, M.D., M.P.H., for the PRIDE Investigators.
Volume 360, Number 5, 481-490, January 29, 2009.
Click here for Abstract.
Sources: Journal Abstract.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
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