Human Biology

Ms. Mary Harney TD, Minister for Health and Children, launched the Immunisation Guidelines 2008 produced by the National Immunisation Advisory Committee of the Royal College of Physicians of Ireland.

The Minister said that “immunisation is a simple, safe and effective way to protect children against certain diseases. Immunisation against infectious disease has saved more lives than any other public health intervention, apart from providing clean water. The Primary Childhood Immunisation Programme provides for the immunisation of children against a range of potentially serious infectious diseases. Under the Programme, parents may have their children immunised free of charge.

The Programme is a key element of the health services in Ireland today and the schedule of immunisation is based on recommendations of the National Immunisation Advisory Committee (NIAC) of the Royal College of Physicians of Ireland. The Minister thanked NIAC for the time and effort that went into the deliberations on this very important piece of public health work.”

The Immunisation Guidelines for Ireland 2008 update the previous NIAC guidance which was published in 2002. Significant new changes to the childhood immunisation schedule have been recommended. These include:

- Replacing the 5 in 1 vaccine with a 6 in 1 vaccine to include Hepatitis B vaccine
- The addition of Pneumococcal conjugate vaccine (PCV)
- Changes in the timing of Meningococcal C vaccine
- Changes in the timing of Haemophilus influenza vaccine (Hib)

The objective of the Childhood Immunisation Programme is to achieve 95% uptake and even though this rate has not yet been achieved in Ireland our uptake rates are rising steadily thanks to the efforts of all those involved in immunisation. The Minister said that we must continue to strive to achieve this target.

The Minister said”I would like to take this opportunity to once again urge all parents to have their children immunised against the diseases covered by the Primary Childhood Immunisation Programme in order to ensure that both their children and the population generally have maximum protection against the diseases concerned.”

Department of Health and Children

Using equipment not all that different from what a runner might take on a jog, veterinary researchers at Kansas State University are working to make life more comfortable for cattle.

A jogger’s heart rate monitor and an instrument similar to a pedometer are a few of the tools K-State researchers are using to measure discomfort in cattle undergoing two routine procedures, castration and dehorning.

Hans Coetzee, assistant professor of clinical sciences, is working with David Anderson, professor of clinical sciences, and Brad White, assistant professor of clinical sciences. They are developing a model that can evaluate pain management drugs for cattle. Although producers and veterinarians sometimes use aspirin and other anti-inflammatory drugs, there are no pharmaceuticals approved by the U.S. Food and Drug Administration specifically for pain management in cattle. It is also unknown what doses are appropriate and how well they work.

“Producers and veterinarians want to effectively treat and prevent pain in livestock, but because these drugs don’t have approval from the Food and Drug Administration for cattle they are limited in what they can do,” Coetzee said. “Our goal is to give producers the means to address consumers’ concerns about the welfare of farm animals.”

The researchers received a $325,000 grant from the U.S. Department of Agriculture to develop a model to assess pain in cattle. Coetzee said ultimately this model will help the FDA evaluate drugs for cattle by knowing how well they work and to recommend proper dosing.

“Managing pain is an inherently good idea, but it is critical to put science behind it because cattle can not communicate their pain,” Coetzee said.

The researchers are basing their model on two common practices, dehorning and castration. The frequency of these practices makes them useful to study. More important, Coetzee said these are routine livestock management procedures that the cattle are undergoing whether the researchers study them or not.

“We’re studying common procedures, so we’re not inflicting pain on the animal for the purpose of the experiment,” he said. “Our goal is to improve the quality of life of the animals in our care without causing unnecessary discomfort.”

The researchers took a variety of measurements. They used thermal imaging cameras to measure skin temperature. As cattle become stressed, blood moves toward the heart and brain, cooling the surface of the body.

To see how cattle are moving around, they attached an accelerometer to the legs. Similar to a walker’s pedometer, the accelerometer measures the up and down movements of the leg. Coetzee said the researchers anticipated that the more uncomfortable cattle are, the less they would move around. In fact, they found the opposite to be true, as if the cattle want to “walk it off.”

To measure heart rate, they attached a monitor like on a jogger might strap to his or her arm. To affix these monitors to the cattle’s considerably larger midsections, the researchers wrapped the monitors to the animals with bandages.

The researchers borrowed an apparatus used by barrel racers to gauge speed as a way to measure how quickly cattle exited the chute. Their assumption was that the more uncomfortable the animal was, the faster it would leave. Although the experiment didn’t accurately account for discomfort, it did tell the researchers other important data. How slowly cattle moved out of the chute indicated the effectiveness of sedatives, Coetzee said.

They also took blood samples to measure for levels of cortisol, which indicates stress level.

Each animal was its own control group, Coetzee said, which meant that all of these measurements were taken before and after the procedures. He said this was important because each animal had a unique stress level to begin with.

“We have some animals that are by nature a little more excitable than others,” he said.

Coetzee presented the research at several conferences last fall and most recently in November 2008 for the FDA.

Another facet of the research is looking at the weight of cattle given pain relievers versus those who weren’t. The researchers gave some of the cattle drinking water spiked with a pain-relieving drug. Coetzee said the animals with the spiked water maintained their weight after the procedures, whereas the untreated animals initially lost weight.

“We’re finding that maybe there is some additional benefit to pain relief other than just the ethical considerations,” he said.

###

Source: Hans Coetzee

Kansas State University

Pediatric Nursing Journal presented its 2008 Humanitarian Award to Kathleen A. McCarty, RN, EdD, who operates the pediatrics ward at a rural hospital in Zimbabwe and serves as the region’s only health care provider. McCarty received her award at an awards presentation on Saturday, June 28, 2008, during the 24th Annual Pediatric Nursing Conference in Las Vegas, NV.

McCarty is the clinical officer at Chidamoyo Christian Hospital, Kari, Zimbabwe, a position she has held for 21 years. She offers residents in the region their only access to general medicine, pediatrics and minor surgical care through many inpatient and outpatient clinics. In addition to managing a very busy pediatric department (with plans to expand), McCarty also runs the outpatient clinic, oversees 16 immunization and pre-natal clinics in outlying villages and offers free HIV counseling and testing to patients.

While caring for patients is McCarty’s primary goal, she also mentors and shares her expertise with doctors, nurses, medical students and other individuals and volunteers. A well-known and highly respected leader in Zimbabwe, McCarty offers her compassion, dedication and spirit to her patients. Her desire to transform nursing practice in the region is inspiring to her patients and to other nurses.

“In a country where political turmoil and violence are commonplace, children suffer. And when half the population are children who have limited access to care, Kathy is a true model of courage and inspiration to the people and nurses in Zimbabwe,” says Pediatric Nursing Editor Veronica Feeg, PhD, RN, FAAN.

Jannetti Publications, Inc., which is located in Pitman, NJ, publishes Pediatric Nursing journal. Past Humanitarian Award winners include Paul Newman, Rosalynn Carter, Marian Wright Edelman and Mattie Stepanek.

For additional information about the Pediatric Nursing 25th Annual Conference (June 25-27, 2009, Orlando, FL) or to request a registration brochure, call (856) 256-2300 or write to: Anthony J. Jannetti, Inc., East Holly Avenue, Box 56, Pitman, NJ 08071-0056. For more information about Pediatric Nursing, visit pediatricnursing.

Pediatric Nursing

Babies born extremely prematurely may be left with lung abnormalities
in adulthood, such as emphysema, Australian researchers have found.
The study, funded by the Raine Foundation, followed up babies born up
to four months premature in the 1980s and weighing as little as 635
g. All of the young adults taking part in the study had abnormal CT
scans of their lungs. 84% had areas of emphysema and 75% had abnormal
lung function tests, the researchers report in the upcoming issue of
the European Respiratory Journal (ERJ).

Due to major improvements in neonatal care since the 1980s, an ever
increasing number of babies are surviving extreme prematurity, and
many have respiratory difficulties as infants. The first babies to
benefit from this improved care are only now reaching adulthood.
“This study reinforces the importance of stopping, or preferably
never taking up, cigarette smoking, particularly if there is a
history of preterm birth,” Daniel Chambers of the Prince Charles
Hospital and Andrew Wilson of the Princess Margaret and Royal Perth
Hospitals in Australia said. “Overall, most of the subjects in this
study had good, if not entirely normal, lung function despite having
a very difficult time as babies.”

The authors stress that the results are preliminary and much larger
studies are required before accurate predictions can be made about
how an individual baby’s lungs will develop.

Nevertheless, Chambers states, “I think we can provide some
reassurance for individuals and the parents of babies being born
prematurely today that despite the ventilator, and then the 24-hour-a-
day oxygen even when they’ve finally made it home, your baby has a
great chance of having good lung health in adulthood.”

Since the adults in this study were born there have been further
improvements in neonatal care, so hopefully outcomes will be even
better in the future.
The researchers are now conducting a larger study in Queensland and
Western Australia.

Title of Original Article
Emphysema in young adult survivors of moderate-to-severe bronchopulmonary
dysplasia
European Respiratory Journal (Erj), Vol. 32, No 2

The European Respiratory Journal is the peer-reviewed scientific
publication of the European Respiratory Society (more than 8,000
specialists in lung diseases and respiratory medicine in Europe, the
United States and Australia).

European Respiratory Journal

Tuomas Jartti (University of Wisconsin, Madison, USA) and his team
examined detailed viral aetiologies of recurrent moderate-to-severe
respiratory illnesses in 27 infants from families with allergies or
asthma.

The demographic and clinical data of these recurrently ill infants
were compared with 258 children with fewer illnesses.

This is the first long-term prospective study using virus strain
specific diagnostics for rhinoviruses, and it reveals several
interesting findings.

First, frequently ill infants had higher exposure to other children
and more wheezing illnesses than less symptomatic children.
In addition, rhinoviruses were the most common virus detected, and
could be associated with wheezing illnesses, as well as milder common
colds.

Mixed viral infections were fairly common in these frequently ill
infants, and were associated with more severe symptoms.
Finally, detection of the same virus strain for more than two weeks
was unusual (only 5% of all 244 positive findings) and most prolonged
illnesses were caused by consecutive infections with different viruses.

In conclusion, this study demonstrates that rhinovirus infections
occur early, pervasively, and repetitively in these high-risk infants
and that prolonged illnesses in this age group are usually caused by
a series of infections, rather than extending infection with a single
virus.

Title of Original Article
Serial viral infections in infants with recurrent respiratory illnesses
European Respiratory Journal (Erj), Vol. 32, No 2

The European Respiratory Journal is the peer-reviewed scientific
publication of the European Respiratory Society (more than 8,000
specialists in lung diseases and respiratory medicine in Europe, the
United States and Australia).

European Respiratory Journal

Have a cookie before breast-feeding, mom? Eating special cookies enriched with conjugated linoleic acid (CLA) can increase the level of these potentially healthful fatty acids in breast milk, reports a recent study in the journal Nutrition Research.

Led by Athena A. Moutsioulis of University of New Hampshire, the researchers designed a study to find out how long it takes for CLA that mothers eat in foods to appear in breast milk. Conjugated linoleic acid is a group of fatty acids with possible health benefits, including anticancer and antioxidant effects.

In the study, seven nursing mothers ate cookies made with CLA-enriched butter or with regular butter. The women then pumped samples of their breast milk every four to six hours for two days. The enriched cookies contained about eight times more CLA than the regular cookies.

Breast milk from women who ate the CLA-enriched cookies had significantly higher levels of CLA. Across the 48-hour study period, CLA levels were 46 percent higher in milk from women who ate CLA-enriched cookies, compared to those who ate regular cookies. Levels of CLA in breast milk were highest between 8 and 28 hours after the mothers ate the CLA-enriched cookies. Nutrition researchers are interested in the health benefits of CLA, including possible reductions in heart disease risk. High levels of CLA are found naturally in foods such as butter, milk, cheese, and certain meats. Most CLA studies in humans have used commercially available supplements, which may not be the same as the CLA found in natural food products.

Previous studies have shown long-term increases in breast milk CLA levels in women who ate cheese and alpine butter for up to eight weeks. The new results suggest that higher levels of CLA in breast milk can be achieved in the short term as well – within a few hours after eating CLA-enriched foods.

Despite its small size and other limitations, this pilot study suggests that CLA appearance in human breast milk can be increased by an acute ingestion of a CLA-rich food in the maternal diet,” the researchers write. Given the possible benefits of CLA on infant health and development, further studies are needed to see how CLA intake from natural foods affects CLA levels in breast milk, and whether higher CLA levels translate into additional health benefits for breast-fed babies.

###

Notes:

The article appears in the July issue of Nutrition Research, published by Elsevier.

About Nutrition Research

Nutrition Research (nrjournal/) rapidly publishes original papers and review articles covering basic and applied research on all aspects of the nutritional sciences. It includes articles on nutritional biochemistry and metabolism; nutrient requirements in health and disease; digestion and absorption of foods; nutritional anthropology and epidemiology; the influence of socioeconomic, cultural and political factors on nutrition of the individual and the community; the impact of nutrient intake on disease response, work performance and behavior; the consequences of nutritional deficiency on growth and development, endocrines, nervous system and immunity; food intolerance and allergy; nutrient drug interactions; nutrition and aging; nutrition and cancer; obesity; intervention programs.

About Elsevier

Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier’s 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect (sciencedirect/), MD Consult (mdconsult/), Scopus (info.scopus/), bibliographic databases, and online reference works.

Elsevier (elsevier/) is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc (reedelsevier/), a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier’s ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

Source: Jayne Dawkins

Elsevier

A new analysis of a 2005 survey of American schoolchildren has identified factors that may be used to help improve school safety. The research, published in BioMed Central’s open access journal Annals of General Psychiatry, gives detailed information about the carrying of guns, blades and clubs.

13,707 students participated in the study, 6,664 (50.5%) were male and 7,193 (49.5%) were females. Overall, 10.2% of males and 2.6% of females reported carrying a weapon on school property. An estimated 29.8% of males and 19.3% of females had carried weapons elsewhere.

The analysis was carried out by Emmanuel Rudatsikira, from the Loma Linda University, California, and his colleagues. They showed that the variables most associated with the carrying of weapons were being male and being a member of certain self-selected racial groups. Pupils who identified themselves as white were more likely to carry weapons than those who identified themselves as black.

The authors point out that, “We do not believe that there are any inherent genetic differences that determine race and that affect the way that adolescents behave. We take the view that racial categorization has facilitated the distribution of social and economic resources (housing, school districts, wealth, social networks) that may consequently influence adolescent behaviors and perceptions toward violent behavior”.

The results were surprising. The authors state that as the poor are likely to live in violent neighbourhoods, they would be more likely to feel unsafe and therefore carry weapons to school, “We would have expected that minorities such as African Americans, being largely disadvantaged in the United States, would be more likely to bear weapons.” Rudatsikira suggests some explanations for this apparent discrepancy “If black students felt less threatened at school, it’s less likely they’ll carry weapons. Alternatively, the schools they attend may be more vigilant in policing weapon carrying as a possible result of high violence and weapon bearing in black neighbourhoods.”

Other factors associated with weapon carrying were substance use, depression, having been a victim of theft or property damage at school, having been raped, having been threatened with a weapon or having been involved in a physical fight.

###

Notes:

1. Correlates of weapon carrying among high school students in the United States
Adamson S Muula, Emmanuel Rudatsikira and Seter Siziya
Annals of General Psychiatry 2008, 7:8 doi:10.1186/1744-859X-7-8

Article available at the journal website: annals-general-psychiatry/content/7/1/8

All articles are available free of charge, according to BioMed Central’s open access policy.

2. Annals of General Psychiatry is an Open Access, peer-reviewed, online journal covering the wider field of Psychiatry, Neurosciences and Psychological Medicine.

Annals of General Psychiatry is aimed at publishing articles on all aspects of psychiatry. Primary research articles are our priority. Both basic and clinical neuroscience contributions are encouraged. The journal strongly supports and follows the principles of evidence-based medicine.

3. BioMed Central (biomedcentral/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.

Source: Graeme Baldwin


BioMed Central

A national analysis of physician office and emergency department records shows that the types of skin infections caused by community-acquired MRSA doubled in the eight-year study period, with the highest rates seen among children and in urban emergency rooms.

The study, conducted at the University of California, San Francisco, examined annual data from the National Center for Health Statistics of patient visits for skin and soft-tissue infections from 1997 to 2005. The results appear in the July 28, 2008 issue of the Archives of Internal Medicine.

During that time period, office and emergency room visits for all skin infections rose from 8.6 million nationwide to 14.2 million, according to Adam Hersh, MD, PhD, lead author on the paper and a fellow in the divisions of general pediatrics and of pediatric infectious diseases at UCSF.

The vast majority of that increase was attributable to visits for abscesses or cellulitis, which Hersh called the hallmark signs of infections from the variety of staph bacteria known as MRSA, or methicillin-resistant Staphylococcus aureus.

Those infections rose from 4.6 million to 9.6 million during the study period.

“This shows that community-acquired MRSA infections are occurring nationwide and affect all subsets of the population,” Hersh said. “But there clearly are some subsets that are disproportionately affected, such as children.”

The increase was predominantly seen among children and among patients who visit emergency rooms in urban areas at so-called safety net hospitals. Those are hospitals in which at least half of the patients receive Medicaid or are uninsured.

From 1997 to 2005, the number of visits for abscesses or cellulitis nearly quadrupled in safety-net emergency departments, from 1.3 people per 1,000 total population to 4.9. Among children, the incidence nearly tripled from 10.1 patients per 1,000 children to 27.6. By contrast, incident rates among patients older than 45 rose less than 50 percent, from 27.9 to 41.3 patients per 1,000 adults in that age group.

By comparison, the number of patients who sought medical care for any skin infection rose from a rate of 32.1 to 48.1 visits per 1,000 people during the same period.

Previous studies at UCSF and other urban medical centers have indicated that MRSA had begun to spread outside hospital settings in the late 1990s, but until now, no one had been able to verify those suspicions with hard data or to indicate the extent of MRSA nationwide, Hersh said. There also was no way of assessing whether the rise was due to population shifts or to people visiting emergency rooms instead of family physicians.

“This validates what San Francisco physicians have been suspecting for several years,” says Henry Chambers, MD, a co-author of the study and UCSF professor of medicine at San Francisco General Hospital. “This is the first national report to look at the impact of MRSA on public health nationwide.”

Chambers is lead scientist of a large multi-centered clinical trial recently funded by the National Institutes of Health to study treatment of community-acquired MRSA infections.

While the rate of this rise is dramatic, public health researchers say these infections can be limited with simple behavioral changes in hygiene.

“This is certainly a cause for increased awareness among clinicians and the public nationwide, but it is not cause for alarm,” said Erica Pan, MD, MPH, a UCSF assistant professor of pediatric infectious diseases and a medical epidemiologist at the San Francisco Department of Public Health. Pan was not involved in this study, but works frequently with the UCSF team on MRSA research.

“A simple way to avoid these and many other infections is to practice good hygiene habits, such as routine hand-washing with soap and water, as well as by covering open cuts and wounds when participating in sports or other activities involving skin-to-skin contact with other people,” she said. “If you notice that you or your child has a skin infection that does not seem to get better on its own after a few days, consult a medical provider.”

The study also found a shift in prescribing practices among physicians seeing these patients. The number of prescriptions written for medications effective against MRSA infections more than tripled over the study period. At the start of the study, less than 8 percent of antibiotics prescribed nationwide for skin infections were those effective for MRSA infections. By 2005, 28 percent were in that category.

“We had anticipated seeing a rise in office visits for abscesses due to the emergence of community-acquired MRSA, but we were somewhat surprised by the rapid changes in antibiotic prescribing,” Hersh said. “It is evidence of growing awareness of community-acquired MRSA nationwide among physicians.”

Hersh acknowledged that the data, which is the most recent available, is too old to show what is happening right now, or even last month, but does confirm that the emergence of community-acquired MRSA in the 1990s led to a rapid increase in the number of patients with skin and soft tissue infections nationwide.

It also raises opportunities for further research, including determining the risk factors for developing an abscess and how best to care for patients with recurrent infections, he said.

###

Ralph Gonzales, MD, MSPH, a professor in the UCSF departments of medicine and of epidemiology and biostatistics, is the senior author on the paper. It was co-authored by Judith H. Maselli, MSPH, also with UCSF.

The research was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

The San Francisco Department of Public health has further information on preventing MRSA infections and “Frequently Asked Questions” on its web site at www.mrsasf.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For further information, please visit ucsf.edu/.

Source: Kristen Bole

University of California – San Francisco

The My Child Matters program is part of the International Union Against
Cancer’s (UICC) campaign and is dedicated to improving information
dissemination about cancer in children to health professionals and the
general public, to improve early diagnosis and access to care, and to
support children with cancer and their families in the developing
world. The first report from the My Child Matters program, published in
the August edition of The Lancet Oncology, found
that low- and middle-income countries still have poor pediatric cancer
survival rates. The descriptive study also found that the level of
pediatric cancer care and available resources is highly variable
between countries.

This first report from the program focuses on data collected between
Sept 5, 2005 and May 26, 2006. Prof Raul Ribeiro (St Jude
Children’s Research Hospital, Memphis, TN, USA) and colleagues studied
pediatric oncology care and 5-year survival in ten countries that
received support from My Child Matters. These low- to middle-income
countries included:

Bangladesh
Egypt
Honduras
Morocco
The Philippines
Senegal
Tanzania
Ukraine
Venezuela
Vietnam

The researchers conducted face-to-face interviews with clinicians,
hospital managers, health officials, and other health-care
professionals in order to gather data on several important elements of
pediatric care and to gather baseline survival data for use in future
comparative studies. They focused on the availability of national
pediatric cancer programs, hospital units dedicated to pediatric
cancer, tools for diagnostic work, and drugs to fight cancer
as well as antibiotics. The data were also compared with national
incidence data for pediatric cancer acquired from the population-based
registries in order to make sure that the survey provided accurate and
relevant data. The survey data were also correlated with variables that
described demographic, health, and socioeconomic factors derived from
global health organizations.

One conclusion of the study was that between countries, there was a
large variation in pediatric oncology care. Additionally, there often
was no agreement between the number of patients reported receiving
medical care in the program survey and the official number predicted by
the population-based incidence data. In 70% of the countries, the
authors labeled the access to pediatric care or management as extremely
poor. Five-year survival rates were estimated to be:

5% to 10% in Bangladesh, the Philippines, Senegal,
Tanzania, and Vietnam
30% in Morocco
40% to 60% in Egypt, Honduras, the Ukraine, and Venezuela

Correlations demonstrated that survival varies directly with several
variables including: per capita annual total health-care expenditure,
per capita gross domestic product, per capita gross national
income, number of physicians and nurses per 1000 population,
and annual government health-care expenditure per capita.

“Detailed surveys can provide useful data for baseline assessment of
the status of paediatric oncology, but cannot substitute for national
cancer registration. Alliances between public, private, and
international agencies might rapidly improve the outcome of children
with cancer in these countries,” conclude the researchers.

Baseline status of paediatric oncology care in ten low-income
or mid-income countries receiving My Child Matters support: a
descriptive study
Raul C Ribeiro, Eva Steliarova-Foucher, Ian Magrath, Jean
Lemerle, Tim Eden, Caty Forget, Isabel Mortara, Isabelle Tabah-Fisch,
Jose Julio Divino, Thomas Miklavec, Scott C Howard, Franco Cavalli
The Lancet Oncology (2008). Vol 9:
pp. 721-9.
Click
Here to View Journal Web Site

: Peter M Crosta

Scientists at Stanford University School of Medicine have discovered that a commonly available non-addictive drug can prevent symptoms of withdrawal from opioids with little likelihood of serious side effects. The drug, ondansetron, which is already approved to treat nausea and vomiting, appears to avoid some of the problems that accompany existing treatments for addiction to these powerful painkillers, the scientists said.

Opioids encompass a diverse array of prescription and illegal drugs, including codeine, morphine and heroin. In 2007, about 12.5 million Americans aged 12 and older used prescription pain medications for non-medical purposes, according to the National Survey on Drug Use and Health, administered by the federal government’s Substance Abuse and Mental Health Services Administration.

“Opioid abuse is rising at a faster rate than any other type of illicit drug use, yet only about a quarter of those dependent on opioids seek treatment,” said Larry F. Chu, MD, assistant professor of anesthesia at the School of Medicine and lead author of the study that will be published online Feb. 17 in the Journal of Pharmacogenetics and Genomics. “One barrier to treatment is that when you abruptly stop taking the drugs, there is a constellation of symptoms associated with withdrawal.” Chu described opioid withdrawal as a “bad flu,” characterized by agitation, insomnia, diarrhea, nausea and vomiting.

Current methods of treatment are not completely effective, according to Chu. One drug used for withdrawal, clonidine, requires close medical supervision as it can cause severe side effects, while two others, methadone and buprenorphine, don’t provide a satisfactory solution because they act through the same mechanism as the abused drugs. “It’s like replacing one drug with another,” said co-investigator Gary Peltz, MD, PhD, professor of anesthesia.

“What we need is a magic bullet,” said Chu. “Something that treats the symptoms of withdrawal, does not lead to addiction and can be taken at home.”

The researchers’ investigation led them to the drug ondansetron, after they determined that it would block certain receptors involved in withdrawal symptoms.

The scientists were able to make this connection thanks to their having a good animal model for opioid dependence. Mice given morphine for several days develop the mouse equivalent of addiction. Researchers then stop providing morphine to trigger withdrawal symptoms. Strikingly, these mice, when placed into a plastic cylinder, will start to jump into the air. One can measure how dependent these mice are by counting how many times they jump. Like humans, dependent mice also become very sensitive to pain when they stop receiving morphine.

But the responses vary among the laboratory animals. There are “different flavors of mice,” explained Peltz. “Some strains of mice are more likely to become dependent on opioids.” By comparing the withdrawal symptoms and genomes of these different strains, it’s possible to figure out which genes play a major role in addiction.

To accomplish this feat, Peltz and his colleagues used a powerful computational “haplotype-based” genetic mapping method that he had recently developed, which can sample a large portion of the genome within just a few hours. This method pinpoints genes responsible for the variation in withdrawal symptoms across these strains of mice.

The analysis revealed an unambiguous result: One particular gene determined the severity of withdrawal. That gene codes for the 5-HT3 receptor, a protein that responds to the brain-signaling chemical serotonin.

To confirm these results, the researchers injected the dependent mice with ondansetron, a drug that specifically blocks 5-HT3 receptors. The drug significantly reduced the jumping behavior of mice as well as pain sensitivity – two signs of addiction.

The scientists were able to jump from “from mouse to man” by sheer luck: It turns out that ondansetron is already on the market for the treatment of pain and nausea. As a result, they were able to immediately use this drug, approved by the Food and Drug Administration, in eight healthy, non-opioid-dependent humans. In one session, they received only a single large dose of morphine, and in another session that was separated by at least week, they took ondansetron in combination with morphine. They were then given questionnaires to assess their withdrawal symptoms.

Similar to mice, humans treated with ondansetron before or while receiving morphine showed a significant reduction in withdrawal signs compared with when they received morphine but not ondansetron. “A major accomplishment of this study was to take lab findings and translate them to humans,” said principal investigator J. David Clark, MD, PhD, professor of anesthesia at Stanford University School of Medicine and the Palo Alto Veterans Affairs Health Care System.

Chu plans on conducting a clinical study to confirm the effectiveness of another ondansetron-like drug in treating opioid withdrawal symptoms in a larger group of healthy humans. And the research team will continue to test the effectiveness of ondansetron in treating opioid addiction.

The scientists warned that ondansetron will not by itself resolve the problems that arise with continued use of these painkillers. Addiction is a long-term, complex process, involving both physical and psychological factors that lead to compulsive drug use. “This is not a cure for addiction,” said Clark. “It’s naГЇve to think that any one receptor is a panacea for treatment. Treating the withdrawal component is only one way of alleviating the suffering. With luck and determination, we can identify additional targets and put together a comprehensive treatment program.”

Collaborators on this study included De-Yong Liang, PhD, the study’s co-lead author, previously a research associate in the Department of Anesthesia and currently a research associate at the Palo Alto Institute for Research and Education; Xiangqi Li, MD, a life science research assistant in the department; Nicole D’Arcy, a medical student: Peyman Sahbaie, MD, a research associate at the institute; and Guochun Liao, PhD, of the pharmaceutical company Hoffman-La Roche. This work was supported by grants to Clark from the National Institutes of Health and the National Institute on Drug Abuse, and grants to Chu from the NIH and the National Institute of General Medical Sciences.

The researchers are working with the Stanford University Office of Technology Licensing to seek a patent for the use of ondansetron and related medicines in the treatment of drug addiction.
What are Opioids?
For more information on what opioids are, and opioid-induced constipation (OIC), please see:
All About Opioids and Opioid-Induced Constipation (OIC)

Stanford University Medical Center integrates research, medical education and patient care at its three institutions – Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford. For more information, please visit the Web site of the medical center’s Office of Communication & Public Affairs at mednews.stanford.edu.

Source: Rosanne Spector

Stanford University Medical Center