A comparison of two strategies for treating severe sepsis or septic shock finds that using lactate levels measured in blood samples showed a similar short-term survival rate compared to a treatment regimen using central venous oxygen saturation measured using a specialized catheter, according to a study in the February 24 issue of JAMA.

In the United States, the rate of severe sepsis hospitalizations has doubled during the last decade, with estimates indicating that at least 750,000 persons are affected annually. Approximately 500,000 patients with severe sepsis in the United States are initially treated in emergency departments every year. Among suggested treatment strategies is the controversial issue of the method of determining tissue oxygen delivery, according to background information in the article.

“Citing a single-center study, the Surviving Sepsis Campaign guidelines recommend the use of central venous oxygen saturation (ScvO2) or mixed venous oxygen saturation to assess the balance of tissue oxygen delivery and consumption; however, since its publication in 2001 a substantial amount of controversy about this single-center study has been generated in the scientific community. Additionally, recently published practice surveys have indicated that the time, expertise, and specialized equipment required to measure ScvO2 collectively pose a major barrier to the implementation of protocol-driven quantitative resuscitation programs. In contrast, lactate clearance, derived from calculating the change in lactate concentration from 2 blood specimens drawn at different times, potentially represents a more accessible method to assess tissue oxygen delivery,” the authors write.

Alan E. Jones, M.D., of the Carolinas Medical Center, Charlotte, N.C., and colleagues compared outcomes between early resuscitation for patients with severe sepsis or septic shock targeting lactate clearance as the marker of adequate oxygen delivery vs. targeting ScvO2 measured using a central venous catheter connected to a computerized system. The primary measured outcome was death while in the hospital. The randomized trial included 300 patients with severe sepsis and evidence of hypoperfusion (decreased blood flow to the body tissues) or septic shock who were admitted to the emergency department at 1 of 3 hospitals between January 2007 and January 2009. The patients were randomly assigned to one of the two resuscitation protocols.

The researchers found that 34 patients (23 percent) in the ScvO2 group died while in the hospital compared with 25 (17 percent) in the lactate clearance group, with the observed difference not reaching the predefined threshold difference of 10 percent. There were no differences in treatment-related adverse events between the groups.

“These data support the substitution of lactate measurements in peripheral venous blood as a safe and efficacious alternative to a computerized spectrophotometric catheter in the resuscitation of sepsis,” the authors write.

(JAMA. 2010;303[8]:739-746)

Editorial: Disassembling Goal-Directed Therapy for Sepsis ““ A First Step

In an accompanying editorial, Roger J. Lewis, M.D., Ph.D., of the Harbor-UCLA Medical Center, Los Angeles, comments on the findings of this study.

“…the study by Jones et at is an important first step to identifying less burdensome approaches to the initial management of critically ill patients with severe sepsis and septic shock. Substantial further progress most likely will depend on appropriately designed, rigorously conducted clinical trials (requiring novel strategies, such as adaptive design) that can efficiently and practically address the complicated questions inherent in identifying the optimal and least burdensome combination of resuscitation targets.”

(JAMA. 2010;303[8]:777-779)

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On the Net:

• JAMA

A new study has shown that nearly 50,000 U.S. medical patients die every year of blood poisoning or pneumonia picked up in hospitals, AFP reported.

The study, led by researchers from the Center for Disease Dynamics, Economics and Policy at Washington-based Resources for the Future, showed that hospital-acquired sepsis and pneumonia in 2006 claimed 48,000 lives, led to 2.3 million extra patient-days in hospital and cost 8.1 billion dollars.

The study, published in the Archives of Internal Medicine on Monday, said the two hospital-acquired infections — also called nosocomial infections — accounted for about one-third of the 1.7 million infections U.S. patients pick up every year while in the hospital.

Nearly half of the 99,000 deaths a year from hospital-acquired infections reported by the Centers for Disease Control and Prevention (CDC) are also likely caused by the two infections.

According to the study, patients who underwent invasive surgery during their initial hospitalization were more likely to pick up a secondary infection while in the hospital, and elective surgery patients were at even higher risk of nosocomial infection.

The researchers estimated that 290,000 patients in U.S. hospitals picked up sepsis, or blood poisoning, during their hospitalization in 2006, and 200,000 developed pneumonia.

The study used the largest database of hospital records in the United States, which covered hospital discharges in 40 states.

It was discovered that hospital-acquired pneumonia extended a patient’s stay in the hospital by 14 days and added some 46,400 dollars to the final price tag, while sepsis extended the time spent in hospital by nearly 11 days and added 32,900 dollars on average to the final bill.

Ramanan Laxminarayan, one of the lead authors of the study, said improving hygiene in clinical settings could prevent the two infections and others picked up in hospitals.

“The magnitude of harm from these infections is deplorable and it is unconscionable that patients continue to experience harm from their interactions with the health system,” said two critical care doctors, in a commentary piece also published in the Archives of Internal Medicine.

David Murphy and John Pronovost of Johns Hopkins University’s department of medicine wrote in the commentary: “What is glaringly obvious is that preventable harm remains a substantial problem and that investments in research to reduce these harms are woefully inadequate given the magnitude of the problem.”

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On the Net:

• Center for Disease Dynamics, Economics and Policy
• Archives of Internal Medicine

Genetic approach could safely reduce or eliminate spread of disease affecting millions

A new strain of mosquitoes in which females cannot fly may help curb the transmission of dengue fever, according to UC Irvine and British scientists.

Dengue fever causes severe flulike symptoms and is among the world’s most pressing public health issues. There are 50 million to 100 million cases per year, and nearly 40 percent of the global population is at risk. The dengue virus is spread through the bite of infected female Aedes aegypti mosquitoes, and there is no vaccine or treatment.

UCI researchers and colleagues from Oxitec Ltd. and the University of Oxford created the new breed. Flightless females are expected to die quickly in the wild, curtailing the number of mosquitoes and reducing ““ or even eliminating ““ dengue transmission. Males of the strain can fly but do not bite or convey disease.

When genetically altered male mosquitoes mate with wild females and pass on their genes, females of the next generation are unable to fly. Scientists estimate that if released, the new breed could sustainably suppress the native mosquito population in six to nine months. The approach offers a safe, efficient alternative to harmful insecticides.

Study results appear in the early online edition of the Proceedings of the National Academy of Sciences for the week of Feb. 22. The research is receiving funding support from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative, which was launched to support breakthrough advances for health challenges in the developing world.

“Current dengue control methods are not sufficiently effective, and new ones are urgently needed,” said Anthony James, Distinguished Professor of microbiology & molecular genetics and molecular biology & biochemistry at UCI and an internationally recognized vector biologist. “Controlling the mosquito that transmits this virus could significantly reduce human morbidity and mortality.”

Using concepts developed by Oxitec’s Luke Alphey, the study’s senior author, researchers made a genetic alteration in the mosquitoes that disrupts wing muscle development in female offspring, rendering them incapable of flight. Males’ ability to fly is unaffected, and they show no ill effects from carrying the gene.

“The technology is completely species-specific, as the released males will mate only with females of the same species,” Alphey said. “It’s far more targeted and environmentally friendly than approaches dependent upon the use of chemical spray insecticides, which leave toxic residue.”

“Another attractive feature of this method is that it’s egalitarian: All people in the treated areas are equally protected, regardless of their wealth, power or education,” he added.

James and Alphey have pioneered the creation of genetically altered mosquitoes to limit transmission of vector-borne illnesses. While their current work is focused on the dengue fever vector, they noted that this approach could be adapted to other mosquito species that spread such diseases as malaria and West Nile fever.

Image Courtesy CDC

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On the Net:

• University of California – Irvine
• Anthony James
• Oxitec
• FNIH
•  Proceedings of the National Academy of Sciences

COLUMBUS, Ohio ““ A new study suggests that the bacteria that cause typhoid fever collect in tiny but persistent communities on gallstones, making the infection particularly hard to fight in so-called “carriers” ““ people who have the disease but show no symptoms.

Humans who harbor these bacterial communities in their gallbladders, even without symptoms, are able to infect others with active typhoid fever, especially in developing areas of the world with poor sanitation. The disease is transmitted through fecal-oral contact, such as through poor hand-washing by people who prepare food.

Typhoid fever is rare in the United States, but it affects an estimated 22 million people worldwide, causing symptoms that include a high fever, headache, weakness and fatigue, and abdominal pain. It leads to hundreds of thousands of deaths each year.

Scientists and physicians have known for decades that these bacteria, Salmonella enterica serovar Typhi, accumulate in the gallbladder. In fact, the most widely accepted treatment of chronic typhoid infection is removal of the gallbladder.

“We’re trying to get to the heart of why this is. Why does Salmonella sit in a pool of highly concentrated detergent, which is what bile is, but not die?” said John Gunn, professor of molecular virology, immunology and medical genetics at Ohio State University and senior author of the study. “It’s got to survive in some way, and a good way to survive is by forming a biofilm.”

Biofilms ““ in this case, the collection of bacteria on gallstones ““ typically do not respond well to antibiotics or the human immune response. But now that the biofilms themselves have been discovered in association with asymptomatic typhoid infection, they present a potential treatment alternative to expensive and invasive gallbladder removal, Gunn said.

Specifically, targeting a sugar polymer on the bacterial surface that promotes development of the biofilm might be a strategy to prevent biofilm formation in the first place, he said.

The research appears this week in the online early edition of the Proceedings of the National Academy of Sciences.

Gunn and colleagues observed this biofilm formation in mice infected with a strain of Salmonella bacteria similar to the strain that causes typhoid fever in humans. The scientists also detected these biofilms on gallstones in about 5 percent of humans in a Mexican hospital who had their gallbladders removed because of complications from gallstones. Typhoid fever is widespread in Mexico.

“The mouse data coupled with the human data suggest strongly that biofilms lay a foundation that allows for establishment and maintenance of chronic typhoid infection,” said Gunn, also a vice director of Ohio State’s Center for Microbial Interface Biology.

And the researchers suspect biofilms are at play in the gallbladder’s association with typhoid fever because in most cases, the only way to treat a biofilm-related infection is to remove whatever the biofilm has attached to from the body. For example, infections that form on catheters, implanted joints or artificial heart valves typically result from biofilms, and the only way to clear the infection is to remove those devices.

“Information in our lab and in the literature that gallstones were associated with how people became carriers of typhoid bacteria, that organisms were confined to one site, and that antibiotics are ineffective so one has to remove the gallbladder for successful therapy ““ it all fit with biofilm-related disease,” Gunn said.

In the study, the researchers fed mice either normal food or a high-cholesterol diet for eight weeks, intending to induce gallstones in the animals on the fatty diet. The scientists then gave these mice a type of Salmonella bacteria designed to mimic a chronic human typhoid infection without causing actual illness in the mice. A control group of mice received no bacteria.

The number of bacteria harbored in the gallbladders of mice with gallstones increased over time, becoming abundant within 21 days, and was significantly higher than bacteria in mice that did not have any stones. No bacteria were detected in mice that weren’t given the infection, even if they had gallstones.

In the infected mice, the Salmonella bacteria also could be seen in the gallbladder lining and in bile as well as on the surface of the gallstones. The gallstones were the focus of this study because Gunn’s lab has determined in previous experiments that Salmonellae are attracted to cholesterol-coated surfaces.

There are two common types of gallstones ““ cholesterol stones and brown or black stones composed primarily of calcium bilirubinate, which can be found in bile. Gunn’s test-tube research to date had suggested that Salmonella Typhi bacteria bind particularly well to cholesterol gallstones to form biofilms, and this current study supported that.

Three weeks after infection, biofilms covered about 50 percent of the surfaces of the gallstones removed from the infected mice.

“What we think is that having gallstones makes you more susceptible to becoming a carrier because it provides that environment for Salmonella to bind to the surface, form a biofilm and establish infection,” Gunn said. “Whether that happens 100 percent of the time, nobody knows.”

In a second component of the mouse study, the researchers tested fresh fecal pellets from infected mice to test the association between gallstone biofilms and transmission of a typhoid-like infection via feces, a phenomenon called “shedding.” The mice with gallstones shed three times more bacteria than did infected mice without gallstones.

“The mice that had gallstones and were infected with bacteria had a much higher rate of shedding, meaning those bacteria were released, probably because they had more bacteria in the gallbladder itself,” Gunn said.

The mouse data not only supported Gunn’s hypothesis that gallstones present at least one surface on which Salmonella biofilms form and maintain the carrier state of typhoid fever. The researchers also realized they had developed a new mouse model for further study of asymptomatic typhoid carriage.

Gunn and colleagues also obtained data from humans at a hospital in Mexico whose gallbladders were removed as a treatment for gallstone complications. Though none of the patients had ever shown symptoms for typhoid fever, 5 percent of them ended up being carriers of Salmonella Typhi bacteria biofilms on their gallstones. In the single patient determined to be a typhoid carrier who didn’t have biofilm on his gallstones, the stones were dark in color, suggesting they were likely composed of something other than cholesterol, Gunn said.

This ability of a single individual to harbor latent bacteria elsewhere in the gallbladder leads Gunn and colleagues to suspect that biofilms can form elsewhere in the gallbladder ““ perhaps in its lining or persisting within specific cells of the gallbladder wall. Gunn’s lab is exploring those possibilities.

This work is supported by the National Institutes of Health and a graduate education fellowship from Ohio State’s Public Health Preparedness for Infectious Diseases initiative.

Co-authors of the study are Robert Crawford of the Center for Microbial Interface Biology and Department of Molecular Virology, Immunology and Medical Genetics at Ohio State; Roberto Rosales-Reyes and María de la Luz Ramírez-Aguilar of the Universidad Nacional Autonoma de Mexico; Oscar Chapa-Azuela of Hospital General de Mexico; and Celia Alpuche-Aranda of the Instituto Nacional de Referencia Epidemiologica in Mexico.

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Ohio State University

A new study reveals that a growing trend among the baby boomer generation is to take part in the country’s most popular illicit drug.

The Substance Abuse and Mental Health Services Administration said people born in the 1960s and 1970s that reported using marijuana went up from 1.9 percent to 2.9 percent in just six years.

The most dramatic rise was between the age range of 55 to 59-years-old, in which the use of the drug tripled from 1.6 percent in 2002 to 5.1 percent in 2008.

Researchers believe that as the 78 million boomers age, there will be further increases.

Some started using it for recreation or as a way to cope with the aches and pains of getting older, while others never stopped using it.

Political advocates for legalizing marijuana say the number of elderly users may represent an important push to change the laws on the substance.

“For the longest time, our political opponents were older Americans who were not familiar with marijuana and had lived through the ‘Reefer Madness’ mentality and they considered marijuana a very dangerous drug,” Keith Stroup, the founder and lawyer of NORML, a marijuana advocacy group, told the Associated Press.

“Now, whether they resume the habit of smoking or whether they simply understand that it’s no big deal and that it shouldn’t be a crime, in large numbers they’re on our side of the issue.”

Stroup says that every night he sits down to the evening news, pours himself a glass of wine and rolls a joint.  The 66-year-old has used the drug since he was a freshman at Georgetown, but many older adults are revisiting the drug after years of not partaking in it.

“The kids are grown, they’re out of school, you’ve got time on your hands and frankly it’s a time when you can really enjoy marijuana,” Stroup said. “Food tastes better, music sounds better, sex is more enjoyable.”

Marijuana is credited to help with aches and pains, glaucoma, macular degeneration, and other age related problems.  So far, 14 states have passed laws to allow the use of marijuana for medical purposes, but those living in other states have to rely on the drug illegally.

However, there are risks of health problems from aging that can be exacerbated by the regular use of marijuana.

Dr. William Dale, chief of geriatrics and palliative medicine at the University of Chicago Medical Center, told AP that older users might be at risk for falls if they become dizzy.  He also said smoking it increases the risk of heart disease and it can cause cognitive impairment.

He said he’d caution using it even if a patient cites benefits.

“There are other better ways to achieve the same effects,” he todl the news agency.

The director of applied studies at the Substance Abuse and Mental Health Services Administration, Pete Delany, said boomers’ drug use defied stereotypes, but is important to address.

“When you think about people who are 50 and older you don’t generally think of them as using illicit drugs “” the occasional Hunter Thompson or the kind of hippie dippie guy that gets a lot of press maybe,” he told AP. “As a nation, it’s important to us to say, ‘It’s not just young people using drugs it’s older people using drugs.'”

Older marijuana smokers say that they prefer to smoke in privately.  They also said the quality and price of the drug has increased substantially since their youth.

Gunilla Priebe has studied the international research alliance the Multilateral Initiative on Malaria (MIM), which advocates for malaria research in general and the strengthening of research environments in Africa. Malaria research has historically been controlled by interests located in areas outside Africa. This has led to a huge gap in knowledge in relation to the malaria problems that dominate everyday life in those areas where people are most affected by the disease.

Better opportunities for researchers on site

According to MIM, researchers based in Africa have a more comprehensive understanding of malaria and its effects on the population. In addition, a locally based researcher is often more motivated to solve problems that are of considerable significance for the majority of malaria patients.

“Proximity to the environment where the social, political, economic as well as the biological dynamics related to malaria are evident provides the researcher with better opportunities to formulate relevant research questions. If the research is based in Africa it increases the chances of the results being of some practical use,” says Gunilla Priebe.

Africanization brings fresh approach

Gunilla Priebe’s analysis is framed by the concept of “Africanization”, which in relation to scientific knowledge production entails two integrated themes: the meaning of time and location with regard to researchers’ ability to represent a study object correctly and in a relevant manner, and partly the impact of remnants of colonialism on the production of scientific knowledge.

According to Gunilla Priebe, the study of MIM shows that Africanization of malaria research means investments in infrastructure, education and improved forms for research cooperation. In such a case, Africanization will also lead to innovative approaches when it comes to research methods and arguments, as well as enhanced influence from both patient and researcher groups that have in the past been marginalized within malaria research.

Definition of researcher’s role

Based on the conclusions drawn from Theory of science study of MIM, Gunilla Priebe’s recommendation to research organizations, such as philanthropic foundations and national aid and research bodies, is to evaluate the role of research for development in the same way as other “foreign” initiated development cooperation.

“Naturally more money for research into malaria is welcomed, but if the organizations that support research in and about Africa don’t intend to reproduce colonial methods, then these cannot work on the basis of utopian ideals of scientific autonomy. They must also take such issues as the right to co-ownership at each stage of knowledge production into consideration. Neither can they focus solely on financial support or the content and organization of the research; they must also engage with the political and social effects of research and research support,” says Gunilla Priebe.

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• University of Gothenburg

IOS Press announces publication of a special issue of NeuroRehabilitation: An International Journal (NRE) devoted specifically to hypoxic-ischemic brain injury (HI-BI), a significant disruption of brain function due to a deficient supply of oxygen to the brain. This is the first publication to present a consolidated overview of HI-BI. It provides a thorough review of neuropathophysiology, neuroimaging assessment, and evaluation and management of the neurological and neurobehavioral sequelae of these injuries in adults and children.

“This special issue of NeuroRehabilitation on hypoxic-ischemic brain injury will serve as an excellent resource for clinicians assessing and treating this unique patient group given the absence of a comprehensive source of clinical information of this scope and detail,” comments NRE Co-Editor Nathan Zasler, MD, FAAPM&R, FACRM, CBIST, CEO and Medical Director of Tree of Life Services, Inc and Concussion Care Centre of Virginia, Ltd., as well as Clinical Professor of Physical Medicine and Rehabilitation at Virginia Commonwealth University, Richmond, VA.

Guest Editor of this special issue David B. Arciniegas, Director of the Neurobehavioral Disorders Program and Associate Professor of Psychiatry and Neurology, University of Colorado School of Medicine; and Medical Director, Brain Injury Rehabilitation Unit, HealthONE Spalding Rehabilitation Hospital, talks about the challenges of treating patients with HI-BI. He states, “As with the approach to HI-BI adopted in the TBI (Traumatic Brain Injury) Act of 2008, applying a certain measure of care-by-analogy is understandable and unavoidable ““ doing so allows those of us working with persons with HI-BI and their families to organize and deliver care that supports their neurological and functional recovery, assists with adaptation to disability, and, to the greatest extent possible, facilitates re-entry into the community and workforce. “¦”We hope that our readers and others interested in this subject will find this issue of NeuroRehabilitation informative and useful.”

The issue includes contributions by globally recognized experts:

* Hypoxic-ischemic brain injury: Addressing the disconnect between pathophysiology and public policy. David B. Arciniegas, HealthONE Spalding Rehabilitation Hospital and University of Colorado Denver, introduces the issue and defines the set of clinical conditions within the spectrum of HI-BI.

* Hypoxic-ischemic brain injury ““ pathophysiology, neuropathology and mechanisms. Katharina M. Busl, Massachusetts General Hospital, and David M. Greer, Harvard Medical School, contribute a critical overview of the pathophysiology of HI-BI.

* Neuroimaging of hypoxic-ischemic brain injury
      Deborah M. Little, Marilyn F. Kraus, Catherine Jiam, Michael Moynihan, Michelle Siroko, Evan Schulze and Elizabeth K. Geary, University of Illinois College of Medicine, discuss current neuroimaging techniques and their current and potential applications to the clinical evaluation of persons with HI-BI.

* Neurocognitive outcomes following neonatal encephalopathy. Jennifer Armstrong-Wells, Timothy J. Bernard, Richard Boada and Marilyn Manco-Johnson, The Children’s Hospital and the University of Colorado Denver, focus on perinatal HI-BI, or neonatal encephalopathy.

* Neurological sequelae of hypoxic-ischemic brain injury. Christine Lu-Emerson and Sandeep Khot, University of Washington, explore the neurological aftermath of HI-BI injuries.

* Cognitive sequelae of hypoxic-ischemic brain injury: A review. C. Alan Anderson, Denver Veterans Affairs Medical Center and University of Colorado Denver, and David B. Arciniegas, HealthONE Spalding Rehabilitation Hospital and University of Colorado Denver, offer a review of the broad spectrum of post-hypoxic cognitive impairments and their treatments.

* The syndrome of delayed post-hypoxic leukoencephalopathy. David Shprecher University of Utah and Lahar Mehta Evergreen Neuroscience Institute, address the under-recognized problem of delayed post-hypoxic leukoencephalopathy.

* Hypobaric hypoxic cerebral insults: The neurological consequences of going higher. Edward H. Maa, Denver Health and Hospitals and University of Colorado Denver, offers insights on hypobaric (high-altitude) HI-BI.

* Neurological and neurobehavioral sequelae of obstructive sleep apnea. Jean C.G. Tsai University of Colorado Denver, provides a thorough review of HI-BI consequences of OSA.

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On the Net:

• IOS Press
• NeuroRehabilitation

Los Angeles, London, New Delhi, Singapore and Washington DC ““ Can patients near death safely receive sedation at home, fully respecting their own and their families’ wishes? This practice, which is on the rise, is coming under increasing scrutiny and debate by palliative care researchers and practitioners. Now palliative care specialists from a team based in Spain have documented their experiences and data, and developed a standard checklist to help other clinicians. Their research appears in the journal Palliative Medicine, published by SAGE.

Physicians use specific sedatives to relieve intolerable suffering as patients near death ““ a practice known as palliative sedation (PS). The rate of PS use varies widely from 3-52% in terminally ill patients according to the literature – a wide range considering it is considered ethical and legally acceptable for those with irreversible and advanced disease. This raises questions over whether the definition of PS, or its setting could be behind these differences.

Despite a trend for PS in patients’ homes increasing in recent years, academics know very little about what kinds of sedation are administered ““ or who is receiving it ““ at home. Some fear that using PS, particularly at home, should not replace thorough assessment and treatment of patients’ physical symptoms, or their psychological or spiritual distress. A set of standard guidelines offers one solution.

Alberto Alonso-Babarro from Hospital Universitario La Paz, Madrid led the study into home PS, which was conducted in Madrid by a palliative home care team (PHCT) composed of two physicians, two nurses, a nurse assistant, a part-time social worker, and an administrative clerk. The PHCT regularly follows up patients with progressive, incurable diseases with many symptoms who are referred by acute care hospitals, medical oncologists or family physicians.

Alonso-Babarro and his team retrospectively reviewed medical records from 370 patients, all of whom had been followed by a palliative home care team. They developed a decision-making and treatment checklist, which they used to assess how frequently PS was used for cancer patients dying at home, and how effective it was. A total of 245 patients (66%) died at home, and 125 patients (34%) died at a hospital or hospice.

Twenty-nine of 245 patients (12%) who died at home received PS. Those who received it had a younger mean age (58) than those who did not (69), but there were no other differences detected between these two patient groups. The most common reasons for using PS were delirium (62%) and dyspnea (laboured breathing), in the case of 14% of patients. The vast majority of patients were given the sedative drug midazolam for PS, with less than a tenth receiving levomepromazine, an anti-psychotic sedative used in Europe and Canada, but not currently registered in the US.

On average, patients died 2.6 days after PS, and in almost half of cases the decision to use PS was taken with both the patient and his or her family. In other cases the family made the decision. Importantly, the authors concluded that using PS does not hasten death.

Other interesting findings were that at home, PS was used at a lower rate than in hospital (where 20-50% of palliative patients have PS). Hospitalised patients often have a greater symptom burden, or may be more agitated and so prone to delirium than in a home setting, the authors suggest.

There is also controversy in the palliative care literature around psycho-existential suffering, where cultural context appears to play a role. In particular, a multi-centre study found that patients in Spain had a higher rate of PS for this reason than in other countries. Alonso-Babarro suggests that lack of agreement on treatment between the patients and their families in Spain could be a significant factor in this distress. “Incorporating the patient’s wishes regarding PS in advanced directives or discussing these issues with patients prior to the final days of their lives may help avoid unnecessary patient and caregiver stress and burden,” he suggests.

“We concluded that palliative sedation may be used safely and efficaciously to treat dying cancer patients with refractory symptoms at home,” said Alonso-Babarro, who added: “To our knowledge, this is one of first studies addressing PS in the home setting to demonstrate the safety and efficacy of at-home PS administered by a PHCT.”

The checklist his team developed recommends beginning PS with midazolam followed by levomepromazine if midazolam proves ineffective. If both midazolam and levomepromazine fail, phenobarbital is the next option to consider. The team also recommends these medications should be injected.

The team hope that their checklist will provide other researchers and clinicians with an easy-to-use decision aid and treatment tool to facilitate the PS process. Researchers will need to carry out further multi-centre prospective home-based studies to replicate their findings.

In some cases, PS may be the only way to achieve a peaceful death at home, thus ensuring that the wishes of the patients and their caregivers are respected.

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SAGE Publications UK

Interest in checklists grows, but they’re no magic wand

In the wake of Johns Hopkins’ success in virtually eliminating intensive-care unit bloodstream infections via a simple five-step checklist, the safety scientist who developed and popularized the tool warns medical colleagues that they are no panacea.

“Checklists are useful, but they’re not Harry Potter’s wand,” says Peter Pronovost, M.D., Ph.D., a professor of anesthesiology and critical care medicine at Johns Hopkins University School of Medicine and a patient safety expert. “The science needed to best develop focused, unambiguous and succinct checklists for medicine’s thousands of diagnoses and procedures is in its infancy, and there can be unintended consequences of reliance on simple tools.”

In a review by Pronovost and other Johns Hopkins researchers recently published in the journal Critical Care, the authors say it’s clear that use of aviation-like safety checklists based on scientific evidence can work, and that more hospitals should use them to help prevent errors and reduce costs associated with medical mistakes.

But says Pronovost, whose eponymous checklist is credited with preventing thousands of central-line infections at Hopkins, throughout the state of Michigan and elsewhere, they need to be accompanied by a “change in the culture of arrogance still widespread in medical care.”

Culture change, he says, “insists,” for example, that nurses are empowered to question doctors who don’t follow the steps properly and that every single member of the health care team toss out long-held beliefs that infections are an inevitable cost of being in the hospital.

“Just having a checklist on a piece of paper isn’t going to be enough,” he says.

In the Critical Care review, Pronovost and his colleagues took a step back and applied a rigorous scientific analysis of checklists, looking especially for which ones have the potential to work best in varying situations.

For example, some checklists are like grocery lists, a basic catalog of what needs to be accomplished by just one person in order for a process or procedure to be completed properly. In an operating room, the anesthesiologist has a checklist that assists her in making sure that every step is followed to ensure the anesthesia machine is working properly before a patient is put under.

“But that sort of checklist doesn’t work in all cases,” Pronovost says. “Central-line infection checklists work best, for example, when there is what we call a challenge and response, in which one person reads a series of items and a second person verifies that each item had been completed. With the check and balance of another person, the list is more likely to be completed properly.”

Pronovost also warns of checklist overload. “Creating too many checklists “” especially those that are not proven to improve patient safety “” or using checklists where they are not truly needed can be distracting and time-consuming,” he says, “and over-reliance on them can lead to a false sense of safety.”

“Each step in the diagnosis, treatment and monitoring process poses risks for error that we need to defend against,” the Johns Hopkins researcher says. “We do not know how many checklists are too many, when they are most useful, when we have overloaded the checklist users or how strictly the benefits are being measured.”

In fact, the Johns Hopkins team says, the underuse of checklists that do work is a problem in part caused by the paucity of scholarly research on how best to use them, how to build and implement them, how to measure their effectiveness in improving patient outcomes, and how they can best be sustained in a culture that is slow to change.

Pronovost’s central-line safety checklist was created after reviewing the literature and guidelines on how to best prevent bloodstream infections in ICUs and selecting the five for which evidence showed they were most likely to accomplish that goal. The checklist was piloted in a small setting (one ICU at The Johns Hopkins Hospital) before undergoing a test on a larger scale (the state of Michigan’s ICUs). After the work was published in the New England Journal of Medicine, he get calls from not only doctors asking him to design checklists for them, but CEOs, financial-industry executives and even a man who wanted a checklist for sailing a boat.

While standardization is at the heart of any checklist, Pronovost says checklists need to be continually assessed to be sure they are still accomplishing their goals “” in this case, keeping bloodstream infection rates near zero. It is important not only to be able to tell patients that the checklist is being used, but to be able to answer the bigger question: Am I safe in the hospital?

“There’s a lot more research to do and a lot of work to be done,” Pronovost says.

Other Johns Hopkins researchers on the paper include Bradford D. Winters, M.D., Ph.D.; Ayse P. Gurses, Ph.D.; Harold Lehmann, M.D., Ph.D.; and J. Bryan Sexton, Ph.D, M.A.

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On the Net:

• Johns Hopkins University School of Medicine
• Critical Care
• Peter Pronovost, M.D., Ph.D.
• Quality & Safety Research Group

Walking heels-first is less work than walking on your toes or balls of the feet

Humans, other great apes and bears are among the few animals that step first on the heel when walking, and then roll onto the ball of the foot and toes. Now, a University of Utah study shows the advantage: Compared with heel-first walking, it takes 53 percent more energy to walk on the balls of your feet, and 83 percent more energy to walk on your toes.

“Our heel touches the ground at the start of each step. In most mammals, the heel remains elevated during walking and running,” says biology Professor David Carrier, senior author of the new study being published online Friday, Feb. 12 and in the March 1 print issue of The Journal of Experimental Biology.

“Most mammals ““ dogs, cats, raccoons ““ walk and run around on the balls of their feet. Ungulates like horses and deer run and walk on their tiptoes,” he adds. “Few species land on their heel: bears and humans and other great apes ““ chimps, gorillas, orangutans.”

“Our study shows that the heel-down posture increases the economy of walking but not the economy of running,” says Carrier. “You consume more energy when you walk on the balls of your feet or your toes than when you walk heels first.”

Economical walking would have helped early human hunter-gatherers find food, he says. Yet, because other great apes also are heel-first walkers, it means the trait evolved before our common ancestors descended from the trees, he adds.

“We [human ancestors] had this foot posture when we were up in the trees,” Carrier says. “Heel-first walking was there in the great apes, but great apes don’t walk long distances. So economy of walking probably doesn’t explain this foot posture [and why it evolved], even though it helps us to walk economically.”

Carrier speculates that a heel-first foot posture “may be advantageous during fighting by increasing stability and applying more torque to the ground to twist, push and shove. And it increases agility in rapid turning maneuvers during aggressive encounters.”

 The study concludes: “Relative to other mammals, humans are economical walkers but not economical runners. Given the great distances hunter-gatherers travel, it is not surprising that humans retained a foot posture, inherited from our more arboreal [tree-dwelling] great ape ancestors, that facilitates economical walking.”

Measuring the Costs of Different Modes of Walking and Running

Carrier conducted the study with Christopher Cunningham, a doctoral student in biology at the University of Utah; Nadja Schilling, a zoologist at Friedrich Schiller University of Jena, Germany; and Christoph Anders, a physician at University Hospital Jena. The study was funded by the National Science Foundation, Friedrich Schiller University of Jena and a German food industry insurance group interested in back pain.

The study involved 27 volunteers, mostly athletes in their 20s, 30s and 40s. Each subject walked or ran three different ways, with each step either heel-first, ball-of-foot first with the heel a bit elevated or toes first with the heel even more elevated.

In his lab, Carrier and colleagues measured oxygen consumption ““ and thus energy use ““ as 11 volunteers wore face masks while walking or running on a treadmill. They also walked on a “force plate” to measure forces exerted on the ground.

Part of the study was conducted at Anders’ lab in Germany, where 16 people walked or ran on a treadmill as scientists monitored activity of muscles that help the ankles, knees, hips and back do work during walking and running.

Findings of the experiments included:

* “You consume more energy when you walk on the balls of your feet or your toes than when you walk heels-first,” Carrier says. Compared with heels-first walkers, those stepping first on the balls of their feet used 53 percent more energy, and those stepping toes-first expended 83 percent more energy.

* “The activity of the major muscles of the ankle, knee, hip and back all increase if you walk on the balls of your feet or your toes as opposed to landing on your heels,” says Carrier. “That tells us the muscles increase the amount of work they are producing if you walk on the balls of your feet.”

* “When we walk on the balls of our feet, we take shorter, more frequent strides,” Carrier says. “But this did not make walking less economical.” Putting the heel down first and pivoting onto the ball of the foot makes the stride longer because the full length of the foot is added to the length of the step. But that has no effect on energy use.

* The researchers wondered if stepping first on the balls of the feet took more energy than walking heel-first because people are less stable on their toes or balls of the feet. But increased stability did not explain why heel-first walking uses less energy.

* Stepping heel-first reduced the up-and-down motion of the body’s center of mass during walking and required less work by the hips, knees and ankles. Stepping first onto the balls of the feet slows the body more and requires more re-acceleration.

* Heels-first steps also made walking more economical by increasing the transfer of movement or “kinetic” energy to stored or “potential” energy and back again. As a person starts to step forward and downward, stored energy is changed to motion or kinetic energy. Then, as weight shifts onto the foot and the person moved forward and upward, their speed slows down, so the kinetic energy of motion is converted back into stored or potential energy. The study found that stepping first onto the balls of the feet made this energy exchange less efficient that walking heels-first.

* Heel-first walking also reduced the “ground reaction force moment” at the ankle. That means stepping first onto the ball of the foot “decreases the leverage, decreases the mechanical advantage” compared with walking heel-first, Carrier says.

In sum, walking heel-first is not more economical because it is more stable or involves fewer, longer strides, but because when we land on our heels, less energy is lost to the ground, we have more leverage, and kinetic and potential energy are converted more efficiently.

Form and Function of the Foot

If heel-first walking is so economical, why do so many animals walk other ways?

“They are adapted for running,” Carrier says. “They’ve compromised their economy of walking for the economy of running.”

“Humans are very good at running long distances. We are physiologically and anatomically specialized for running long distances. But the anatomy of our feet is not consistent with economical running. Think of all the animals that are the best runners ““ gazelles, deer, horses, dogs ““ they all run on the ball of their feet or the tips of their toes.”

When people run, why is there no difference in the amount of energy they expend when stepping first onto their heels versus the balls of their feet or toes?

The answer is unknown, but “if you land on your heel when you run, the force underneath the foot shoots very quickly to the ball of your foot,” Carrier says. “Even when we run with a heel plant, most of the step our weight is supported by the ball of our foot. Lots of elite athletes, whether sprinters or distance runners, don’t land on their heel. Many of them run on the balls of their feet,” as do people who run barefoot. That appears to be the natural ancestral condition for early human runners, he adds.

“The important thing is we are remarkable economical walkers,” Carrier says. “We are not efficient runners. In fact, we consume more energy to run than the typical mammal our size. But we are exceptionally economical walkers.”

“This study suggests that one of the things that may explain such economy is the unusual structure of our foot,” he adds. “The whole foot contacts the ground when we walk. We have a big heel. Our big toe is as long as our other toes and is much more robust. Our big toe also is parallel to and right next to the second toe.”

“These features are distinct among apes, and provide the mechanical basis for economical walking. No other primate or mammal could fit into human shoes.”

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Image 1: English photographer Eadweard Muybridge (1830-1904), who pioneered the use of multiple cameras to capture motion, is shown walking heel-first as humans usually do. A new University of Utah study shows that stepping onto the heel first requires much less energy than putting the ball of the foot or the toes onto the ground first. Photo Credit: Eadweard Muybridge (public domain)

Image 2: A University of Utah student walks by placing the ball of his foot down first while the heel is somewhat elevated. Humans normally do not walk that way because it requires 53 percent more energy than walking heel-first, according to a new University of Utah study. Images like this were used during analysis of study results. Photo Credit: David Carrier, The University of Utah

Image 3: The heels-first walking pattern typical of humans is demonstrated by a University of Utah student who participated in a study showing that people save a lot of energy by planting their heels down first rather than walking on their toes or the balls of their feet. Photo Credit: David Carrier, The University of Utah

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On the Net:

• University of Utah
• Journal of Experimental Biology

A newly designed system of identifying molecules for treating hepatitis C should enable scientists to discover novel and effective therapies for the dangerous and difficult-to-cure disease of the liver, says Zhilei Chen, a Texas A&M University assistant professor of chemical engineering who helped develop the screening system.

The system, Chen explains, enables researchers to study the effects of molecules that obstruct all aspects of the hepatitis C virus (HCV) life cycle. That’s a significant milestone in HCV research, says Chen, noting that previous methods of developing drug treatments for the virus have been limited by the fact that researchers were only able to study one aspect of the HCV life cycle. Chen’s findings appear in the most recent edition of the scientific journal Proceedings of the National Academy of Sciences.

First identified in 1989 and responsible for hepatitis C, an infectious disease affecting the liver, HCV has infected an estimated 180 million people worldwide. Spread by blood-to-blood contact, HCV can cause chronic infection that leads to dangerous scarring of the liver, liver failure, liver cancer and death.

Although new infections resulting from blood transfusions are rare thanks to screening measures that began in 1990, the overall number of people facing death or serious liver disease from HCV is steadily rising because people often live decades with the virus before showing symptoms, Chen says. In addition, injection drug users are at high risk for infection from contaminated needles.

The only existing therapy for HCV is a physically and emotionally taxing 48-week course of treatment that cures less than half of all patients who undergo it, Chen says. The particularly grueling nature of the treatment ““ it’s been compared to chemotherapy ““ as well as the high financial costs associated with it often result in many patients opting to forego the therapy.

Because Chen’s newly developed screening system enables the discovery of small, low-cost molecules that block the HCV life cycle, she believes it could contribute to new, more affordable and more effective therapies for hepatitis C.

The screening system uses an innovative way to “see” cells that are infected with HCV.

“Typically when a virus infects a cell, it’s not obvious to detect; it’s not easy to distinguish an infected cell from an uninfected cell,” Chen says. “Much in the same way a person who is infected with HCV does not initially feel anything, when a cell is initially infected nothing really observable happens. This makes it difficult to distinguish HCV infection in cells.”

To address this challenge, Chen “tweaked” the cells she was studying by inserting a gene into them that triggers cell death if HCV enters that cell. This allowed Chen to easily measure the extent of infection in her genetically engineered cells by quantifying the degree of cell death within the cell cultures she was examining.

These engineered cells were grown in miniature compartments in the presence of infectious HCV, and a different chemical was added to each compartment.

“We could then look and see which cells were able to survive because if you have chemicals that don’t inhibit HCV, the cells will die, but if you have a molecule that blocks the HCV life cycle, the cells will grow,” Chen says. “And because we were able to look at the complete life cycle of the virus with our system, we discovered inhibitors of the virus across three different stages: entry into cells, reproduction within cells, and final escape from infected cells to attack new cells.”

Testing about 1,000 different chemicals, Chen found several that strongly inhibited the HCV life cycle. Some of the inhibitors, she said, obstruct virus entry into a cell. Others inhibit virus replication, meaning that infected cells won’t be able to support the reproduction and growth of the virus as much. Chen also found effective inhibitors that keep the virus from escaping the cell even if it grows well inside the cell.

“Since this virus changes all of the time, you really want to hit it across multiple aspects simultaneously,” Chen says. “Nevertheless, most current efforts to block the HCV life cycle focus only on its replication within cells due to the long-time absence of a system that allows for convenient screening of molecules blocking other aspects of the virus’ life cycle such as entry into cells and release from cells.

“Our system is well-suited to large-scale drug screening efforts because the technology is simple to use and can be easily scaled up to test extremely large collections of compounds using a robotic system,” Chen says. “We anticipate that this system will enable the discovery of many more new and more potent HCV antivirals.”

Working with Chen to develop the system were Karuppiah Chockalingam and Rudo Simeon, postdoctoral associate and graduate student, respectively, from Texas A&M and Charles Rice, professor from Rockefeller University.

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On the Net:

• Texas A&M University
• PNAS

Children and adolescents who refuse to attend school should not be given doctors’ sick notes. In the current issue of Deutsches Óžrzteblatt International (Dtsch Arztebl Int 2010; 107[4]), child and adolescent psychiatrist Martin Knollmann and colleagues explain the causes of school avoidance and describe measures to tackle the problem.

Truancy assumes psychiatric relevance only if it occurs frequently and is accompanied by psychiatric symptoms. Children typically play truant for the first time at the age of about 11 years, whereas anxiety related school avoidance occurs in children as young as 6 years. School avoiders seem to be exposed to more stressful life events, but physical disorders such as asthma or obesity may also play a part.

In contrast to truancy, of which parents are usually unaware, children displaying school avoiding behavior often stay at home. They often express fears and anxieties, especially in the morning, and complain of diffuse physical symptoms.

The authors assume that a proportion of 5% to 10% of children is regularly absent from schools in Germany. How many of these children have mental health problems is not known. In adolescents, school avoidance is clearly more common than in children, and some studies have shown that boys are affected twice as often as girls.

In school avoidance, the primary objective of treatment is to quickly re-establish regular school attendance. Sick notes or prescriptions for residential care breaks are usually not advisable because the child’s behavior may deteriorate as a result.

Appropriate treatment options include cognitive behavior therapies, in combination with antidepressants if required. Exclusively child and adolescent psychiatric treatment, however, is usually not sufficient; those children who are affected need a support network consisting of school staff, youth services, and medical professionals.

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On the Net:

• Deutsches Aerzteblatt International

Type-2 diabetes, an increasingly common complication of obesity, is associated with poor impulse control. Researchers writing in BioMed Central’s open access journal BioPsychoSocial Medicine suggest that neurological changes result in this inability to resist temptation, which may in turn exacerbate diabetes.

Hiroaki Kumano, from Waseda University, Japan, worked with a team of researchers to assess response inhibition, a measure of self-control, in 27 patients with type-2 diabetes and 27 healthy controls. He said, “Patients with type 2 diabetes are required to make strict daily decisions; for example, they should resist the temptation of high-fat, high-calorie food, which is frequently cued by specific people, places and events. Appropriate behavior modification thus depends on the patient’s ability to inhibit impulsive thoughts and actions cued by these environmental stimuli”.

In order to gauge the patients’ ability to resist such impulsive behavior, the researchers used a test in which participants had to quickly press a button in response to the correct signal on a computer screen, while pressing the button in response to the wrong symbol counted against their score. They found that patients with diabetes performed significantly worse at the test, suggesting that they struggled to control the impulse to press the button. Other results showed that the inhibitory failure observed in diabetic patients was mainly explained by cognitive impairment of impulsivity control, rather than by deficits in motor performance, error monitoring and adjustment. According to Kumano, “This suggests the possibility that the neuropsychological deficits in response inhibition may contribute to the behavioral problems leading to chronic lifestyle-related diseases, such as type 2 diabetes”.

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On the Net:

• BioMed Central
• BioPsychoSocial Medicine

Kidney dialysis patients often need repeated procedures, such as balloon angioplasty, to open blood vessels that become blocked or narrowed at the point where dialysis machines connect to the body. These blockages can impact the effectiveness of hemodialysis, a life-saving treatment to remove toxins from the blood when the kidneys are unable to do so. But a new FDA-approved stent graft can keep these access points open longer, reducing the number of procedures these patients may need, according to research from the University of Maryland published in the February 11, 2010, edition of the New England Journal of Medicine.

“This is the first large-scale randomized study to find a therapy to be superior to the gold standard of balloon angioplasty. We found that using this new stent for dialysis patients whose access grafts have become narrowed improves graft function. It also clearly reduces the need for repeated invasive procedures and interruption of dialysis,” explains lead author Ziv Haskal, M.D., chief of vascular and interventional radiology at the University of Maryland Medical Center. Dr. Haskal is also professor of diagnostic radiology and nuclear medicine, and surgery at the University of Maryland School of Medicine.

The prospective multi-center study took place at 13 sites across the country and enrolled nearly 200 patients. Ninety-seven patients received angioplasty with the new stent, which is a small metal scaffold inserted in the patient’s arm, compared to 93 who received angioplasty alone.

In the study, patients with the stent graft were more than twice as likely to have open vessels compared to the angioplasty only group after six months. The recurrence of vessel narrowing, restenosis, was nearly three times lower with the stent group, (27.6 percent vs. 77.6 percent). In later follow-up, some patients still had functioning grafts two years after the stent graft was first implanted.

“Results of this research should change the way we treat hemodialysis patients. In this study, patients who received angioplasty alone were twice as likely to need additional procedures compared to those who had the stent in addition to angioplasty,” adds Dr. Haskal. “That can translate into cost savings and improved quality of life for these patients, who already spend about nine to 12 hours a week in dialysis. We can now start considering grafts as something that may last for years in dialysis patients, instead of months.”

According to the researchers, the cost to treat dialysis access failure amounts to about $1 billion per year, and the number of patients needing hemodialysis is expected to continue to grow substantially over the next decade.

Kidney failure patients often have a synthetic portal, known as an access graft, embedded into their arm before they begin hemodialysis. The access graft works like an artificial blood vessel, allowing needles to be inserted repeatedly, so the blood can be circulated out of the body, filtered in a machine and then returned to the patient’s circulatory system. Patients must undergo dialysis several times a week. (Another less commonly used form of dialysis, peritoneal dialysis, filters waste by using the peritoneal membrane inside the abdomen. Patients inject a special solution into the body, which is later drained from the abdomen after the toxins are filtered. Peritoneal dialysis can be done at home, but must be done every day.)

For hemodialysis, scar tissue naturally forms at the edges of the access grafts. That scarring can impede blood flow, requiring doctors to perform angioplasty to open the vessels. In that outpatient procedure, doctors insert a balloon into the blood vessel and inflate the balloon to open the narrowed artery or vein. Following angioplasty, vessel narrowing frequently recurs, requiring repeated procedures, up to several times a year. If scarring becomes too severe and repeated angioplasties do not work, the patient may need another procedure put in an access graft at a different site on the arm. Other therapies have been compared to balloon angioplasty, but, until now, none has shown benefit in a prospective randomized study.

“More than 350,000 Americans are currently receiving dialysis. These patients need those access grafts to be as durable as possible because they only have so much space on their arms for the surgical creation of new access grafts. Our research has shown that using this stent graft to treat failing accesses keeps them open longer that the existing gold standard; it offers a real, longer-term solution for patients, reducing the need for repeated surgeries. This research suggests that physicians may need to make a fundamental change in their approach to treating hemodialysis patients,” says Dr. Haskal. This self-expanding metal stent graft creates a scaffold to keep the blood vessel open. It is encapsulated by polytetrafluoroethylene, the same material from which most dialysis grafts are made. The device allows the physician to mimic the effect of surgery at the scarred area without actually performing surgery.

“This study offers strong evidence of the benefit of using this new stent therapy for hemodialysis patients. It represents the type of important clinical research with direct patient benefit undertaken by physicians at the University of Maryland School of Medicine,” says E. Albert Reece, M.D., Ph.D., M.B.A, vice president for medical affairs, University of Maryland, and dean, University of Maryland School of Medicine.

Dr. Haskal is leading another large study that is currently enrolling patients to assess the benefits of the device over a longer period of time. The other sites participating in this study were the Hospital of the University of Pennsylvania; University of Texas, Southwestern Medical Center; Oregon Surgical Consultants, Portland, OR; Open Access Vascular Access Center, Miami, FL; Vascular Access Center, Augusta, GA; Tucson Vascular Surgery; Indiana University School of Medicine; Bamberg County Hospital and Nursing Center, Bamberg, SC; and Vascular Access Center of Frontenac Grove, Frontenac, MO. This study was funded by Bard Peripheral Vascular, Inc., manufacturer of the Flair Endovascular stent graft.

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On the Net:

• University of Maryland Medical Center
• New England Journal of Medicine

Family history, infection and stress all may play a role in raising a woman’s risk of having a premature baby ““ but they don’t fully explain why some women give birth too soon and others don’t, according to a review article published today in the New England Journal of Medicine.

Only if scientists of all disciplines work together and share information ““ databases, biological samples and new perspectives ““ will the research community be able to determine how to prevent spontaneous preterm birth and spare babies from the serious consequences of an early birth, according to “The Enigma of Spontaneous Preterm Birth,” by Louis Muglia, MD, PhD, of Vanderbilt University Medical Center and Michael Katz, MD, senior vice president for Research and Global Program at the March Dimes.

Premature birth is a leading cause of infant death in the United States, and only about half of these deaths have a known cause, Drs. Muglia and Katz note.

More than 543,000 babies are born too soon each year in the United States. Worldwide, about 13 million babies are born prematurely each year. Babies who survive an early birth face serious risks of lifelong health problems, including learning disabilities, cerebral palsy, blindness, hearing loss and other chronic conditions.

Medical problems, such as preeclampsia, which is extremely high blood pressure in the mother, or fetal distress, do not fully explain the increase of induced deliveries, which often result in late preterm births, birth between 32 and 36 weeks gestation.

“The decision to induce delivery in order to improve fetal viability must be balanced by recognition of the need to minimize the impairments that arise from preterm birth,” the authors wrote. “Making this decision will remain a challenge for practitioners, because inducing delivery ““ by whatever method ““ before full term has adverse consequences for the newborn, even when it happens close to term.”

Family history of preterm birth, stress, race, infection, inflammation and genetics do appear to play a role. One of every three preterm births occurs to a mother who has an infection in her uterus, but may have no symptoms. Recent research has shown that the genes of the mother seem to make the greatest contribution to preterm birth risk, and genes in the fetus may also play a role.

The New England Journal of Medicine review article is a summary of a three-day symposium held in December 2008, entitled “Preventing Prematurity: Establishing a Network for Innovation and Discovery.” It was cosponsored by the Burroughs Wellcome Fund and the March of Dimes and brought together the top investigators in preterm birth prevention research.

The authors note in their article that technological advances allow clinicians to save premature infants from death and some complications by treating the consequences of prematurity. However, “prevention is what is needed, and current research is being directed toward reaching this goal,” the authors wrote.

The third biennial symposium, a meeting by invitation only, will be held in December, 2010.

The article was published in the Feb. 11, 2010, issue of the New England Journal of Medicine, Vol. 362, No. 6, pages 529-35.

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On the Net:

• March of Dimes Foundation
• New England Journal of Medicine

A new study from The Montreal Neurological Institute and Hospital ““ The Neuro – at McGill University is the first to discover a molecular link between Parkinson’s disease and defects in the ability of nerve cells to communicate. The study, published in the prestigious journal Molecular Cell and selected as Editor’s Choice in the prominent journal Science, provides new insight into the mechanisms underlying Parkinson’s disease, and could lead to innovative new therapeutic strategies.

Parkinson’s, a neurodegenerative disease affecting approximately 100,000 Canadians and over 4 million people worldwide, a number expected to double by the year 2030, causes muscle stiffness and tremor and prevents people from controlling their movements in a normal manner. The disease is characterized by the degeneration and death of dopamine neurons in specific regions of the brain, causing neurological impairment. It is not known exactly what causes the death of these neurons.

Mutations in the parkin gene are responsible for a common inherited form of Parkinson’s disease. By studying defects in the genes and proteins of patients with inherited forms of Parkinson’s, principal author of the study at The Neuro, Dr. Edward Fon, is learning about the molecular mechanisms involved in the death of dopamine neurons.

The function of the parkin protein is not yet well defined. Scientists learn about the function of a protein by studying normal and mutated forms as well as investigating what the protein binds to. These kind of studies provide clues as to what processes the protein may be involved in. It is known that parkin is involved in the degradation of other proteins. However, how defects in this function are linked to Parkinson’s remains unclear. To further understand how a mutated parkin protein causes Parkinson’s, Dr. Fon and his colleagues looked at where mutations are found on the gene and focused on understanding the function of region that is commonly mutated and searched for proteins that bind to this particular domain of the protein.

They identified that parkin binds to a protein called endophilin-A, a protein discovered at The Neuro in 1997 by Dr. Peter McPherson, a co-investigator on the current study. Endophilin-A is central to the process of synaptic transmission, specifically synaptic vesicle trafficking. Synaptic transmission is the process whereby one nerve cell communicates with another. It involves the release of neurotransmitters from a synaptic vesicle at the surface of the cell.  The neurotransmitter travels across the gap or synapse and is brought into (or endocytosed) the communicating neuron.  Synaptic vesicles are spheres that transport and release neurotransmitters, the “Ëœsignal’ required for the propagation of nerve cell signals across the synapse. The binding protein, endophilin-A plays an important role in regulating synaptic vesicle endocytosis, that is the formation, as well as recycling of synaptic vesicles. 

“One of the most consistent and intriguing findings associated with both dominant and recessive forms of Parkinson’s, including those due to parkin mutations, have been defects in synaptic transmission, possibly related to altered synaptic vesicle endocytosis, recycling or release,” says Dr. Fon. “Yet, until now, the molecular mechanisms involved have remained completely unknown. Thus, by linking parkin to endophilin-A, a protein at the heart of synaptic vesicle endocytosis and recycling, our findings provide a molecular link between recessive Parkinson’s genes and defects in synaptic transmission. This now gives us a whole new set of potential treatment targets.”

“This provides a novel and critical molecular link between the parkin gene and synaptic regulation,” says Dr. Jean-Francois Trempe, post-doctoral student in Dr. Kalle Gehring’s lab at McGill, who studied the structural biology of the binding of the two proteins.”The strength and specificity of the interaction makes it a very clear and interesting finding, and indicates that we are heading in the right direction.”

“Our next studies will investigate the function of the parkin-endophilin-A interaction, adds Dr. Fon. “We believe that, if the parkin is mutated then the proper functioning of endophilin-A will be affected as it binds parkin, thereby disrupting synaptic vesicle recycling. This could potentially lead to the death of dopamine neurons by depriving neurons of neurotransmitters necessary for neuronal survival and functioning.”

“Dr. Fon’s new findings will improve our understanding of the defects in the genes and proteins of people who suffer from Parkinson’s disease,” says Dr. Anthony Phillips, Scientific Director at the Canadian Institutes of Health Research (CIHR) Institute of Neurosciences, Mental Health and Addiction. “CIHR is proud to support research that may pave the way to innovative new therapeutic strategies to cure Parkinson’s, which affects too many Canadians.”

There is as yet, no known cure for Parkinson’s disease. A number of drugs and clinical treatments have been developed which can help to control or minimize the symptoms of this disabling and debilitating disease.

As a world-class academic medical centre and a designated National Parkinson Foundation (NPF) Center of Excellence, The Neuro not only delivers first class clinical care but, also conducts innovative research that leads to important discoveries about the disease and significant advancements in medical care and treatments for patients.

This work was supported by CIHR, the Canadian Foundation for Innovation, the R.H. Tomlinson Fellowship program, and the Fonds de la Recherche en Sant© du Qu©bec.

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On the Net:

• Montreal Neurological Institute and Hospital
• Molecular Cell
• Science

New research from the Hood Center for Children and Families at Dartmouth Medical School (DMS) for the first time sheds light on the significant potential negative impact that food product placements in the movies could be having on children.

The study, which appears in the current edition of the journal Pediatrics, shows that most of the “brand placements” for food, beverage, and food retail establishments that are frequently portrayed in movies, are for energy-dense, nutrient-poor foods or product lines. In addition, the study shows for the first time that product placements in movies may be a far more potent source of advertising to children in terms of food choices than previously understood.

“The current situation in the United States is very serious in terms of the health of our children, and we have to look seriously at all of the factors that may be contributing to it, including the impact of product placements in movies,” says Lisa Sutherland, Ph.D. the lead author of the study. Sutherland says that the diet quality of U.S. children and adolescents has declined markedly during the past 20 years, and current estimates suggest that only one percent of children eat a diet consistent with the U.S. Department of Agriculture’s (USDA) My-Pyramid food guidance. Additionally, fewer than one fifth of adolescents meet the dietary recommendations for fat or fruit and vegetable intakes, and during the last 20 years obesity rates have doubled for children aged 6 to 11 years and tripled for adolescents aged 12 to 19 years.

“While the issue of food advertising and its effect on children has been well documented in numerous studies, comparatively little is known about product placement in movies and how it affects the food and beverage preferences and choices of children and adolescents,” Sutherland said. The study notes that while there are similarities between television advertising and movie product placement, such as the low nutritional quality of the majority of branded products, there are also interesting differences. Recent studies that examined television ads during adolescent programming found fast food and ready-to-eat cereals and cereal bars to be the most prevalent during children’s programming. In contrast, the Dartmouth study found that sugar-sweetened beverages, comprised largely of soda, accounted for the largest proportion of all of the movie-based food product brand placements, accounting for one of every four brand placements overall.

The study notes that of particular concern are the food and beverage product placements in comedies and PG-rated and PG-13″“rated movies, which are often geared specifically to older children and teenagers, who are at an age where they are gaining independence with respect to their food choices. Although the impact of this type of advertising on children is not fully known, it provides a likely avenue by which brand loyalty and product preference can be built in addition to eating patterns. The study also revealed that six companies accounted for 45 percent of all brand placements and included PepsiCo, Coca-Cola, Nestle USA, McDonald’s, Dr. Pepper/Snapple Group and Burger King.

The study acknowledges that many companies have made pledges not to direct advertising at children in order to encourage healthier dietary choices, and that while this is a step in the right direction, more clearly needs to be done. In addition, the study’s authors say that a number of studies to date that focused on other health-related behaviors, including alcohol and tobacco use, showed that movies contain frequent portrayals of these risk behaviors and often include brand appearances of the products. They say it is well established that children who view these risk behaviors in movies are more likely to engage in the behavior themselves.

“This is an area of study which clearly requires more research,” says Sutherland who was part of a team of advisers that, in 2006, helped to develop the Guiding Stars program used by supermarkets to help shoppers better identify the nutritional values of food products. “At a time in their development where children and adolescents are very susceptible to outside influences, we have to carefully examine the influence of all the factors that are combining to create what may end up being lifelong habits around food and lifestyle choices. Certainly, food-product placement in movies is one of many factors, but it is one that may be far more influential than previously realized and perhaps the least well understood.”

Co-authors included Todd MacKenzie, Ph.D., Lisa A. Purvis, MPH, MBA, and Madeline Dalton, Ph.D. all with Dartmouth Medical School.

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On the Net:

• Dartmouth-Hitchcock Medical Center
• Pediatrics

The most comprehensive study to date of secondhand smoke exposure among children in England is published Feb. 8 in the journal Addiction. The study, carried out by researchers from the University of Bath’s School for Health, reveals that exposure to household secondhand smoke among children aged 4-15 has declined steadily since 1996.

The researchers wanted to find out if there were ways to predict the levels of secondhand smoke encountered by children in private households, and whether those levels were changing over time. Using eight surveys conducted between 1996 and 2006, researchers took saliva samples from over 19,000 children aged 4-15 years. The saliva samples were analyzed for a substance called cotinine, an indicator of tobacco smoke exposure.

The results show that the average cotinine levels among non-smoking children declined by 59% from 1996 to 2006, indicating that children’s exposure to secondhand smoke has decreased markedly since the mid-nineties. The researchers point out that the largest decline was between 2005 and 2006, a time of increased public debate and public information campaigns about secondhand smoke in the lead-up to the 2007 implementation of smoke-free legislation for public spaces.

The research also reveals that secondhand smoke exposure in non-smoking children is highest when one or both parents smoke, when the children are looked after by carers that smoke, and when smoking is allowed in the home. Dr Michelle Sims, first author of the paper, adds: “the importance of carer and parental smoking and household exposure tells us that reducing exposure in the home is the key to reducing the health risks associated with secondhand smoke exposure in children.”

Dr Anna Gilmore, who led the project, said “this study shows that the factors which most strongly influence children’s exposure are modifiable. Parents and carers can reduce their children’s exposure to smoke by giving up smoking, or failing this, making a decision to smoke outside the house. Stopping others from smoking in their house is also important. The fact that children’s exposure has already fallen so markedly shows that making these changes is feasible.”

Sims M., Tomkins S., Judge K., Taylor G., Jarvis M.J., Gilmore A. “Trends in and predictors of secondhand smoke exposure indexed by cotinine in children in England from 1996-2006.” Addiction 2010; 105:

The paper is an independent report commissioned and funded by the Policy Research Programme in the Department of Health. The views expressed are not necessarily those of the Department.

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On the Net:

• Wiley-Blackwell
• Addiction

Two patients with rare lesions to the brain have provided direct of evidence of how we make decisions ““ and what makes us dislike the thought of losing money.

Researchers at the California Institute of Technology studied a phenomenon known as ‘loss aversion’ in two patients with lesions to the amygdala, a region deep within the brain involved in emotions and decision-making. The results of the study, part-funded by the Wellcome Trust, are published today in the journal Proceedings of the National Academy of Sciences.

Loss aversion describes the avoidance of choices which can lead to losses, even when accompanied by equal or much larger gains. Examples in the everyday life include how we make a decision on whether to proceed with an operation: the more serious the potential complications from the operation ““ even if the risk is low compared to the chances of success ““ the less likely we would be to proceed. It even has implications on organ donation rates ““ if people are required to ‘opt-in’ to a system, they are less likely to move away from the default option.

Dr Benedetto De Martino, a Sir Henry Wellcome Trust Postdoctoral Fellow and first author of the report, explains: “Imagine you’re on Who Wants to Be a Millionaire. You’ve just answered the £500,000 question correctly and have moved on to the final question. You’re down to your 50:50 lifeline but don’t know the answer. If you get it right, you’ll win £1 million; if you get it wrong, you’ll drop back to £32,000. The vast majority of people would take the ‘loss averse option’ and walk away with £500,000.”

This new study has explored whether loss aversion is mediated by the amygdala, as is currently hypothesized. The researchers studied two patients affected by a rare genetic condition which has led to the formation of lesions to the amygdala. These lesions prevent the patients from perceiving, recognizing or feeling fear. For example, the patients can recognize all other emotions in a person’s face, but if shown a fearful face they cannot say what emotion that person is experiencing.

Each patient ““ together with twelve ‘healthy’ controls ““ took part in a task designed to test whether the chance of losing money affected people’s likelihood to gamble

At the beginning of the experiment, each participant was given $50 with which to gamble on the outcome of flipping a coin, which carries a 50:50 chance of winning (or losing). However, each time, the amount that the volunteers could win or lose varied. For example, one time they might stand to win $50 or lose $20 depending on the outcome. The second time, they might stand to win $30 or lose $40.

The researchers found that, as expected, the healthy individuals were less likely to gamble when the difference between the potential winnings and potential losses was smaller ““ for example, whilst they might gamble if they stood to win $50 but lose only $10, they would be less likely to gamble if they stood to win only $20 but lose $15. When the potential losses outweighed the potential gains, the controls would not gamble.

However, the two patients with impaired amygdala activity were much less affected by the disparity between potential gains and losses; occasionally, even when the potential losses outweighed the potential gains they would choose to gamble, showing a lack of loss aversion.

“A fully-functioning amygdala appears to make us more cautious,” explains Ralph Adolphs, the Bren Professor of Psychology and Neuroscience. “We already know that the amygdala is involved in processing fear, and it also appears to make us ‘afraid’ to risk losing money.”

“It may be that the amygdala controls a very general biological mechanism for inhibiting risky behavior when outcomes are potentially negative, such as the monetary loss aversion which shapes our everyday financial decisions,” comments Dr De Martino, a visiting researcher from UCL (University College London).

“Loss aversion has been observed in many economic studies, from monkeys trading tokens for food to people on high-stakes game shows,” adds Colin Camerer, the Robert Kirby Professor of Behavioral Economics, “but this is the first clear evidence of a special brain structure which is responsible for fear of those losses.”

Dr De Martino and colleagues also investigated whether, as well as being ‘loss averse’, the patients were also ‘risk averse’. Risk aversion and loss aversion are two similar, but not identical, processes and as such can be easily confused. People who are ‘risk averse’ are less likely to take chances even when they do not stand to lose anything.

The volunteers were again asked to make a decision based on the outcome of a coin toss. However, in this situation, the options were either to take a set amount without gambling (for example, $5), or gamble with a chance of winning $10 or receiving nothing but not losses were involved. In this experiment, both patients and controls showed little difference in their decisions, suggesting that the amygdala goes not control this aspect of risk taking.

The research was supported by the Gordon and Betty Moore Foundation, the Human Frontier Science Program, the Wellcome Trust, the National Institutes of Health, the Simons Foundation, and a global Center of Excellence grant from the Japanese government.

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On the Net:

• Wellcome Trust
• California Institute of Technology
• Proceedings of the National Academy of Sciences

According to new scientific research, boredom could actually kill you.

Researchers say that people who complain of boredom are more likely to die at younger ages, and those who experience excessive moments of monotony are more than two-and-a-half times as likely to die from heart disease or stroke as those who satisfy their brain and body on a regular basis.

The study was conducted on more than 7,000 civil servants over a 25 year period.

Those who actively complained of boredom were nearly 40 percent more likely to have died by the end of the study than those who did not.

Scientists said that those who felt unhappy with their lives often turn to unhealthy life choices including smoking, drinking and over-eating which cut their life expectancy.

The data from 7,524 civil servants between the ages of 35 and 55 who were interviewed between 1985 and 1988, was analyzed by specialists from the Department of Epidemiology and Public Health at University College London. They then checked figures to see who had died by April 2009.

The report, to be published in the International Journal of Epidemiology this week, was co-written by researcher Martin Shipley, who said: “The findings on heart disease show there was sufficient evidence to say there is a link with boredom.” He added that it was important for people who have dull jobs to find other interests to keep boredom from taking over their lives.

Psychologist Graham Price told Mail Online that it is important to distinguish first if people are turning to drinking and drugs because of boredom, or if they have certain predetermined characteristics that lead them to unhealthy practices. People who are unmotivated in, or by, life, should find ways to change their focus away from themselves and on to other people. That is where inspiration may lie to remove the dullness and tedium from one’s life.

The original survey found that one in ten civil servants had been bored within the past month. Women were more than twice as likely than men to suffer boredom. Younger employees and those with more menial jobs were also found to be more prone to boredom. Those who reported tedious feelings on a regular basis were 37 percent more likely to have died by the end of the study.
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On the Net:

• University College London
• International Journal of Epidemiology

Scientists at Emory University School of Medicine have discovered unexpected properties for a precursor to melatonin, the hormone that regulates sleep cycles.

Melatonin is produced from the neurotransmitter serotonin in a daily rhythm that peaks at night. Melatonin’s immediate precursor, N-acetylserotonin, was not previously thought to have effects separate from those of melatonin or serotonin.

Now an Emory team has shown that N-acetylserotonin can stimulate the same circuits in the brain activated by the growth factor BDNF (brain-derived neurotrophic factor).

The results will be published online this week in the Proceedings of the National Academy of Sciences.

The team was led by Keqiang Ye, associate professor of pathology and laboratory medicine, and P. Michael Iuvone, professor of pharmacology and director of research at Emory Eye Center. Researchers from Morehouse School of Medicine and the University of Wisconsin contributed to the paper.

The discovery has implications for the study of how some antidepressants function and may also explain previous observations that N-acetylserotonin has antidepressant activity in animal models of depression.

“Our results suggest that the molecules and pathways involved in mood regulation and circadian rhythms are intertwined,” Ye says.

A lack of BDNF, which pushes brain cells to grow and helps them resist stress, is thought to lie behind depression and several neurodegenerative diseases. Ye and his colleagues have been searching for chemicals that can mimic BDNF by activating TrkB, the receptor for BDNF on cells’ surfaces.

Several widely prescribed antidepressants (selective serotonin reuptake inhibitors such as fluoxetine/Prozac) increase levels of serotonin in the brain, but the connections between serotonin levels and depression are complex. Because antidepressants seem to take weeks to display their effects, scientists have proposed that their real targets are BDNF and TrkB.

“We were exploring whether the serotonin system is involved in TrkB signaling,” Ye says. “We were surprised to find that N-acetylserotonin, but not serotonin or melatonin, can activate TrkB.”

 N-acetylserotonin could stimulate TrkB even when BDNF was not present, both in cell culture dishes and in mice, Ye and his colleagues found. It could also protect neurons from overstimulation in the same way that BDNF can.

Melatonin is produced at several sites in the body: the pineal gland, the retina and the intestine. One of the most common strains of laboratory mice (C57Bl6) is deficient in making N-acetylserotonin and melatonin and develops retinal degeneration.

The authors observed that in the retinas of mice that produce adequate melatonin, TrkB is turned on at night, a pattern that matches the appearance of N-acetylserotonin. However, the pattern of TrkB activation is flat in C57Bl6 melatonin-deficient mice.

Ye’s laboratory is now investigating the mechanism by which N-acetylserotonin activates TrkB. He says that N-acetylserotonin has a short lifetime in the body but similar compounds that are more stable may be useful in treating neurological diseases.

The research was supported by the National Institutes of Health and Research to Prevent Blindness.

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On the Net:

• Emory University
• PNAS

Walter and Eliza Hall Institute researchers have identified a key protein used by the malaria parasite to transform human red blood cells, ensuring the parasite’s survival.

Their discovery means researchers have a clear target against which to develop a new class of anti-malarial drugs that destroy the parasite.

Each year more than 400 million people contract malaria, and more than one million people, mostly children, die from the disease. The most lethal form of the disease is caused by the parasite Plasmodium falciparum, which invades red blood cells and drastically modifies them so it can survive.

Professor Alan Cowman, head of the institute’s Infection and Immunity division, said the parasite remodels the red blood cells by exporting hundreds of so-called ‘effector’ proteins into the cytoplasm of the red blood cell. “These are key virulence proteins that allow the parasite to survive in the human and hide from the human immune system,” Professor Cowman said.

“There has to be a mechanism that allows these effector proteins to be exported but until now we haven’t known what it is.”

Dr Justin Boddey, Dr Tony Hodder, Dr Svenja Gunther, Dr Andrew Pearce and Professor Cowman from the institute, in collaboration with Professor Richard Simpson, Dr Heather Patsiouras and Dr Eugene Kapp of the Ludwig Institute for Cancer Research, Professor Brendan Crabb and Paul Gilson at the Burnet Institute and Dr Tania de Koning-Ward at Deakin University, have identified a protein called Plasmepsin V as being essential for effector proteins to be exported into the red blood cell.

Their research has been published today in the international journal Nature.

Professor Cowman said experimentation had shown that the action of Plasmepsin V on the effector proteins was the first step in priming the proteins to be exported beyond the parasite’s membrane into the red blood cell cytoplasm.

“Plasmepsin V is responsible for determining that all the hundreds of effector proteins are exported. If we could find drugs to block Plasmepsin V the malaria parasite would die,” he said.

Professor Cowman said because Plasmepsin V was a protease it was an attractive drug target.

“Drugs that target proteases have been very effective in combating HIV so, by analogy, drugs that impede the function of Plasmepsin V should also show promise,” he said.

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On the Net:

• Walter and Eliza Hall Institute
• Nature

The cells regarded as the “gate-keepers” of the barrier between blood circulation and the peripheral nerves have been hard to study and even harder to isolate. However, researchers at Baylor College of Medicine have created a laboratory model that will enable scientists to study a wide variety of diseases affecting peripheral nerves.

They describe their model in the January 2010 issue of the Journal of Neuropathology and Experimental Neurology.

Specialized vascular system

“The barrier is known as the blood-nerve barrier and it regulates how peripheral nerves work. Peripheral nerves connect the central nervous system to the muscles of the limbs and sensory organs. This ‘gate keeper’ is a specialized vascular system that allows for proper nerve function by enabling the necessary nutrients in blood to flow in and unwanted material out,” said Dr. Eroboghene E. Ubogu, assistant professor of neurology and director of the Neuromuscular Immunopathology Research Laboratory at BCM.

Ubogu, who is the senior author on the study, added that very little is known about how the human blood-nerve barrier normally works or how it is altered when the peripheral nerves are diseased. The cells that make up the blood-nerve barrier are hard to study and extract because they are surrounded by a large amount of connective tissue, are present deep within the innermost layers and represent less than 1 percent of all cells found in peripheral nerves.

Ubogu and his research colleagues, including lead author research assistant Nejla Yosef and Dr. Robin H. Xia, a postdoctoral research associate, both in the department of neurology at BCM, began by isolating these specialized blood vessel cells from the sciatic nerve, the largest nerve in the body found at the back of the thighs.

“It started as trial and error since methods for this type of work had not been outlined for human peripheral nerves,” Ubogu said. “We looked at how other blood vessel and nerve cells were isolated from humans and other animals and modified those protocols until we achieved our goal.”

It took more than six tries of a process involving multiple steps before Ubogu and his team were successful in isolating the blood vessel cells that make up the blood-nerve barrier.

Prior to developing the blood-nerve barrier model, Ubogu and his colleagues used several laboratory methods to verify that these specialized blood vessel cells, called primary human endoneurial endothelial cells, were the cells that formed blood vessels within the innermost layer of peripheral nerves.

Better view of diseases

These cells were grown in laboratory dishes, and used to develop a blood-nerve barrier model system that behaves very similar to what is seen or expected in humans. This model will allow researchers to study how substances dissolved in the bloodstream, large molecules, drugs, microorganisms and white blood cells are able to enter or exit the peripheral nerves and why their movements may be restricted or permitted in times of health or disease.

“We can now see the gate, and if we understand how it is locked, opened and closed, we may be able to treat certain nerve diseases more effectively or even prevent them,” said Ubogu.

This model will give researchers a better view of how diseases such as HIV and diabetes affect the peripheral nervous system. Guillain-Barr© syndrome and chronic demyelinating inflammatory polyneuropathy (peripheral nerve inflammation that leads to a loss of movement or sensation) are also disorders that can be further investigated because of this research. A better understanding of how drugs get into peripheral nerves is also possible with this model.

“I would like research collaborations to grow from these findings,” Ubogu said. “The hope is that labs already studying peripheral nerve function and disease will be able to use the model to further their work.”

All researchers are with the Neuromuscular Immunopathology Research Laboratory at BCM.

The study was supported Guillain-Barr© Syndrome/Chronic Inflammatory Demyelinating Polyradiculoneuropathy Foundation International Research Grant and by the BCM New Investigator Start-Up Program.

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On the Net:

• BCM
• Journal of Neuropathology and Experimental Neurology