RxPG News : Immunology

Best way to boost adult immunizations is through office-based action, study finds

Wed, 11 Jan 2012 05:00:00 PST

( from http://www.rxpgnews.com ) Promoting immunizations as a part of routine office-based medical practice is needed to improve adult vaccination rates, a highly effective way to curb the spread of diseases across communities, prevent needless illness and deaths, and lower health care costs, according to a new RAND Corporation study.

Increasingly, vaccinations are being offered outside of physician offices at pharmacies, workplaces and retail medical clinics. Even so, office-based medical practice continues to be central to the delivery of recommended vaccinations to adults.

Regardless of where vaccines are actually administered, office-based providers are uniquely positioned to identify patients who need vaccination, to communicate credibly about the benefits and risks of vaccination, and to ensure that vaccination histories are properly maintained, said Katherine Harris, the study's lead author and a senior economist at RAND, a nonprofit research organization.

The RAND study outlines improvements needed to strengthen the role of office-based medical providers to promote vaccination to adult patients. These include creating tools to improve communications between patients and providers about vaccinations, and stronger incentives to encourage health providers to refer patients to community sites that administer vaccinations if they do not offer them.

Diseases that can be readily prevented by vaccines take a heavy toll on adults in the United States despite the wide-spread availability of this generally safe and effective preventive care. The yearly health care and productivity costs blamed on influenza -- a common illness that can be prevented by vaccination -- is as high as $90 billion, depending on the severity of the annual outbreak.

In contrast to childhood vaccination rates, which are generally high, adult vaccination rates remain disappointingly low. Even in the case of influenza, inoculation rates for even those at the highest risk of death do not exceed 70 percent. Vaccines recommended for adults can prevent influenza, pneumococcal sepsis, shingles, hepatitis A and B, pertussis (whooping cough) and the human papillomavirus -- the leading cause of cervical cancer.

Researchers say recent changes in the policy and practice environments provide a unique window of opportunity to improve the delivery of vaccinations to adults. Health care reform legislation promotes preventive care and improves financial access to adult vaccinations.

RAND researchers identified bottlenecks that have stalled delivery of adult vaccinations and propose strategies to overcome these shortcomings. Their effort included a review of past research about adult vaccination, a stakeholder workshop, interviews with experts, and a short telephone survey of adults to learn about the relationship between influenza vaccination and public beliefs and misperceptions about its safety.

The study reports that while medical offices are the location where most adults receive vaccinations, only about one-fourth of physician offices stock all recommended vaccines for adults. Reasons include the fact that some vaccines have a short shelf life and insurance payments for administering adult vaccines may not cover the doctor's costs.

Researchers say one priority is to collect better national information about the patterns of office-based vaccination of adults to pinpoint gaps in practice, which could then be targeted for improvement efforts.

Better guidance should be developed to help health providers effectively promote and administer vaccines, including structured vaccination counseling protocols. Providers also need tools to help them evaluate whether to administer vaccines onsite or refer their patients to community resources such as pharmacies and flu vaccine clinics, according to the study.

Systems also must be developed to credit primary care providers for providing vaccine counseling, whether their patients receive the vaccination on-site or go elsewhere to get it.

Scientists identify cell death pathway involved in lethal sepsis

Thu, 22 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Sepsis, a form of systemic inflammation, is the leading cause of death in critically ill patients. Sepsis is linked with massive cell death; however, the specific mechanisms involved in the lethality of sepsis are unclear. Now, a new study published by Cell Press in the December 23rd issue of the journal Immunity finds that inhibition of a specific cell death pathway called necroptosis protected mice from lethal inflammation. The research may lead to new therapeutic interventions for fatal inflammatory conditions that are notoriously hard to control.

Systemic inflammatory response syndrome (SIRS) is a body-wide inflammatory response that can be caused by an infection, such as in the condition sepsis, or by some sort of physical trauma, such as a severe burn. Sepsis and SIRS are thought to be caused by the cytokine tumor necrosis factor (TNF). However, although research has shown that TNF functions in inflammation, cell death, and survival, the specific mechanisms linking TNF with SIRS are not well understood.

Engagement of TNF receptor 1 activates two diametrically opposed pathways: survival/inflammation and cell death, explains senior study author, Dr. Peter Vandenabeele, from Ghent University and Flanders Institute for Biotechnology (VIB) in Belgium. An additional switch decides, depending on the cellular context, between apoptosis and necroptosis, two different cell death pathways. In our study, we explored the involvement of both of these cell death pathways in SIRS.

Dr. Vandenabeele and colleagues found that while disruption of molecules required for apoptosis had no impact on lethal SIRS, inhibition or genetic deletion of RIPK molecules, which are required for necroptosis, provided complete protection against SIRS lethality. Basically, inhibition of one type of cell death did not protect mice from lethal inflammation while disruption of a different cell death pathway improved survival. The researchers went on to confirm their findings in a clinically relevant setting by demonstrating that RIPK deficiency provided protection in a mouse model of peritonitis.

Taken together, the results demonstrate a crucial role for RIPK in sepsis-mediated lethality and uncover potential therapeutic targets for treatment of SIRS and sepsis. Selectively targeting the necroptosis process may be more advantageous than globally blocking TNF because it leaves space for the important anti-infectious functions of TNF, concludes Dr. Vandenabeele. New insight into the precise regulatory pathways associated with necroptosis and the molecular interactions involved in the RIPK pathways will provide additional targets for intervention in these high mortality pathological conditions, which have previously been classified as uncontrollable.

'Pep talk' can revive immune cells exhausted by chronic viral infection

Tue, 13 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Chronic infections by viruses such as HIV or hepatitis C eventually take hold because they wear the immune system out, a phenomenon immunologists describe as exhaustion.

Yet exhausted immune cells can be revived after the introduction of fresh cells that act like coaches giving a pep talk, researchers at Emory Vaccine Center have found. Their findings provide support for an emerging strategy for treating chronic infections: infusing immune cells back into patients after a period of conditioning.

The results are published this week in Proceedings of the National Academy of Sciences Early Edition.

The first author of the paper is Rachael Aubert, a student in Emory's Immunology and Molecular Pathogenesis program who completed her doctorate in 2009. Senior author Rafi Ahmed, PhD, is director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.

Ahmed's laboratory has extensive experience studying mice infected with lymphocytic choriomeningitis virus (LCMV). Immune responses against LCMV are driven by CD8 or killer T cells, which destroy virus-infected cells in the body. But a few weeks after exposure to LCMV, the mice develop a chronic infection that their immune systems cannot shake off, similar to when humans are infected by viruses like HIV and hepatitis C.

Aubert and her co-workers examined what happened to mice chronically infected with LCMV when they infused CD4 or helper T cells from uninfected mice. After the infusion, the CD8 cells in the infected mice revived and the levels of virus in their bodies decreased by a factor of four after a month. Like coaches encouraging a tired athlete, the helper cells drove the killer cells that were already in the infected mice to emerge from exhaustion and re-engage.

The cell-based treatment was especially effective when combined with an antibody that blocks the molecule PD-1, which appears on exhausted T cells and inhibits their functioning. The antibody against PD-1 helps the exhausted T cells to revive, and enhances the function of the helper cells as well: the combination reduced viral levels by roughly ten-fold, and made the virus undetectable in some mice.

We have not seen this sharp of a reduction in viral levels in this system before, says co-author Alice Kamphorst, a postdoctoral fellow.

The helper cells were all genetically engineered to recognize LCMV, a difference between mouse experiments and potential clinical application. However, it may be possible to remove helper T cells from a human patient and stimulate them so that all the cells that recognize a given virus grow, Kamphorst says.

This is an active area of research and several laboratories are looking at how best to stimulate T cells and re-introduce them, she says.

In addition, she and her co-workers are examining what types of hormones or signaling molecules the helper cells provide the killer cells. That way, that molecule could be provided directly, instead of cell therapy, she says.

The molecule PD-1 was previously identified by Ahmed and colleagues as a target for therapy designed to re-activate exhausted immune cells. Antibodies against PD-1 have been undergoing tests in clinical studies against hepatitis C and several forms of cancer.

Chief scientific officer named first Richard L. Menschel Research Chair at Special Surgery

Tue, 13 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Steven R. Goldring, M.D., chief scientific officer, has been named the first Richard L. Menschel Research Chair at Hospital for Special Surgery. A gift of $5 million from an anonymous donor will permanently endow the position of the Hospital's chief scientific officer.

This chair honors Richard L. Menschel, Hospital for Special Surgery chairman emeritus and a senior director, The Goldman Sachs Group, L.P., who has been a vital proponent of the Hospital's focus on research. In addition to providing leadership for the HSS Reseach Division, Dr. Goldring's research objective is to translate basic research into new therapies for people with mobility disorders, with a focus on expanding the Hospital's clinical registries and advancing its Osteoarthritis Initiative.

Extraordinary advances in medicine can be accomplished when there are partnerships between visionary leaders like Richard Menschel and scientific innovators like Dr. Steven Goldring, said Louis A. Shapiro, president and CEO of Hospital for Special Surgery.

Dr. Goldring is a strong advocate of the physician-scientist. He has led the recruitment of talented scientists in the areas of arthritis and tissue degeneration, autoimmunity and inflammation, musculoskeletal integrity, and tissue engineering, regeneration and repair.

I am truly honored to be the first holder of the Richard L. Menschel Research Chair at Hospital for Special Surgery, said Dr. Goldring. I began my career as a clinician, but I was also fortunate enough to be in an environment that supported and promoted the great importance of research. While our focus is how best to define disease mechanisms, the ultimate goal is to apply what we learn to patient care.

A major initiative that Dr. Goldring will oversee is the expansion of Hospital for Special Surgery's clinical patient registries. These powerful research tools provide the foundation of clinical trials, providing an ongoing collection of confidential clinical and demographic information that can be analyzed to examine health care issues that are critical to understanding the outcome of patient care and refining treatments.

During his tenure Dr. Goldring has taken the Research Division to new levels, said Thomas Sculco, M.D., surgeon-in-chief at Hospital for Special Surgery. His exceptional background as a physician and researcher in arthritic conditions and bone and joint disorders makes him uniquely qualified to lead the Hospital in all areas of investigation.

A priority for any first-rate medical institution is to have a world-class research program, said Mr. Menschel. Dr. Goldring has led Hospital for Special Surgery into a new era of clinical and translational research.

Risk of contracting diabetes to increase in world of 7 billion people

Mon, 14 Nov 2011 05:00:00 PST

( from http://www.rxpgnews.com ) World citizen number 7 billion is less likely to die from infectious diseases like measles or even AIDS, and more likely to contract diabetes or other non-communicable diseases (NCDs), as they are now the leading causes of deaths globally.

14th of November is official World Diabetes Day. In a world of 7 billion people with changing disease patterns, this day is more relevant than ever, according to external lecturer Siri Tellier from the Copenhagen School of Global Health at the University of Copenhagen.

Our new world citizen number 7 billion is more likely to grow up in an urban setting, which increases his or her risk of getting diabetes, as well as chronic obstructive pulmonary disease (COPD), cancer and heart disease, says Siri Tellier, who teaches demography and health in emergencies, while she also lectures on international perspectives on demographic challenges to Chinese university students in Beijing.

World citizen number 7 billion, who was estimated to be born on 31 October, will face very different diseases than that of children born only a few decades ago. As the population of urban areas keeps growing, it rapidly changes the global health challenges.

Until 2008, the majority of the world population lived in rural areas, but since then the majority has become urban, and most future population growth will happen in urban areas of developing countries. And one third of them, a little more than one billion, live in urban slums, says Siri Tellier.

A high proportion of people who move to cities are young adults, and this has several implications for health. Among them are the consequences of leaving their parents behind in rural areas.

Aging parents can no longer depend on their adult children for care. They will often 'live with' chronic NCDs such as diabetes, and will need daily assistance. It's not just a question of the children sending them money from their new home in a big city - who will care for the old people on a daily basis? The household size is shrinking. In rural areas it may be five, in urban areas only two. So in order to meet that challenge, new patterns of caring for older people will be needed, says Siri Tellier.

In the cities of the world, the health challenge is twofold: Firstly, living conditions in slum areas are poor, both with respect to water and sanitation, and access to health care almost non existent. In addition, life in urban areas often entails a shift toward 'modern' life styles, with inadequate nutrition, especially more fatty, salty foods, smoking, alcohol and lack of exercise - all primers for NCDs.

Secondly, when the young newcomers become parents, their own poor health will have influenced the unborn child's predisposition for NCDs.

Increasing numbers of studies show, that healthy ageing begins in the womb, Siri Tellier continues, and explains that if - for example - children are born with low birth weight, they are more likely to develop diabetes later in life

Our new world citizen nr. 7 billion will probably grow up in an urban setting, and will face factors that increase his or her risk of diabetes, as well as COPD, cancer and heart disease.

There is also an increasing awareness of the need to help even healthy, young people gain the habits which will predispose them for health in later life. Parents may have a hard time ensuring that their teenagers develops healthy habits, which will follow him or her throughout life, especially if a lack og these habits do not cause ill health immediately, Siri Tellier points out.

Of course, the good news is that the child is less likely to die from measles, or even AIDS or diarrhoeal diseases. We have reduced the number of child deaths from around 12 million in 1990 to less than 8 million today, and most of the saved lives are through prevention measures such as vaccinations against infectious diseases. That is not only good news, that is fantastic news. Siri Tellier explains.

Flemming Konradsen, Director of the Copenhagen School of Global Health at the University of Copenhagen, shares this optimistic view, and stresses that we must now deal with the non-communicable diseases as seriously as infectious diseases:

Global disease patterns are changing. As many countries around the world have reduced the great killers such as malaria, we must turn the same effort and resources towards NCD's, as they must be prevented now rather than treated later.

In addition to the personal consequences for the patient, NCDs burden developing health care systems with such high expenses, that can halt their development if we do not intervene, says Professor Flemming Konradsen.

Study finds shifting disease burden following universal Hib vaccination

Fri, 11 Nov 2011 05:00:00 PST

( from http://www.rxpgnews.com ) [EMBARGOED FOR NOV. 11, 2011] Vaccination against Haemophilus influenzae type b, or Hib, once the most common cause of bacterial meningitis in children, has dramatically reduced the incidence of Hib disease in young children over the past 20 years, according to a study published in Clinical Infectious Diseases and available online (

The Hib vaccine was successful in reducing disease among children 5 years and younger, and now the epidemiology has changed, said lead author Jessica MacNeil, MPH, of the Centers for Disease Control and Prevention, who, with colleagues, analyzed data for the current epidemiology and past trends in the invasive disease over the past two decades following the introduction of the Hib vaccine in the mid-1980s. Most H. influenzae disease in the United States is now caused by other, non-type b strains of the bacteria.

The study authors warn that the highest rates of disease from non-b type strains are in the oldest and youngest age groups, those 65 and older and infants less than a year old. Among children younger than 5 years old, young infants are the most likely to be diagnosed with the disease. Many of these cases occur during the first month of life, and among those, premature and low-birthweight babies are the most vulnerable.

The number of adults 65 and older who become ill due to H. influenzae is also high compared to the rest of the population, according to the study authors. Among those in this group who become sick, nearly 25 percent of the cases are fatal. Risk factors for this age group are harder to interpret, the authors note, as clinical outcomes may be due to underlying medical conditions.

American Indian and Alaska Native children continue to have a disproportionately large burden of both Hib and non-b type disease compared to others, the study found, but the reasons behind this are not fully understood. Why these groups continue to be at a higher risk than other populations should be the focus of future studies, MacNeil said. Understanding risk factors for H. influenzae disease in this population, such as household crowding, poverty, and poor air quality, could potentially help prevent transmission.

The study authors found that no substantial serotype replacement has been observed among young children in the U.S., which suggests the current Hib vaccine has been effective in preventing H. influenzae illness in this age group. However, the authors note, the burden of disease seen in older adults is an opportunity that could be addressed in the future with an H. influenzae vaccine for adults.

Rheumatoid arthritis patients have low expectations after knee replacement surgery

Sat, 05 Nov 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Compared with osteoarthritis patients, individuals with rheumatoid arthritis who undergo total knee replacement surgery have lower expectations about their postsurgical outcomes, according to a new study by researchers at Hospital for Special Surgery (HSS) in New York City. These reduced expectations, which may be unnecessary, could cause some patients to slack on their postsurgical rehabilitation leading to worse outcomes, say doctors. The study will be presented November 7 at the annual meeting of the American College of Rheumatology.

If rheumatoid arthritis patients are healthy enough to have surgery, they should really expect good outcomes. If patients have lower expectations, then maybe they don't push their physical therapy, and perhaps don't recover as well, said Lisa Mandl, M.D. M.P.H., a rheumatologist at HSS who was involved with the study. It would be a real shame if these patients could have significantly improved function, but for some reason they don't attain it, perhaps connected to their expectations.

Before this study, researchers had known that patients with rheumatoid arthritis (RA) who undergo a total knee replacement are often very satisfied with the surgery, even though they have inferior outcomes to patients with osteoarthritis who undergo the operation. Because satisfaction is determined not only by improvements in pain and function, but by fulfillment of pre-operative expectations, investigators set out to determine if the expectations of the two patient groups differed.

The researchers turned to the HSS Total Joint Replacement Registry, a prospective registry started in 2007 that includes, among other things, data on all patients who seek care at HSS for knee replacement surgery, also known as total knee arthroplasty (TKA). Because roughly 90 percent of patients who undergo TKA have osteoarthritis, they first used the registry to identify patients with RA. They then mined the registry to find osteoarthritis patients that matched these RA patients in terms of age, gender and function. Investigators gauged function using the Lower Extremity Activity Score (LEAS), a score that quantifies how much activity a person is capable of performing. The scale ranges from a person being confined to bed all day to participating in vigorous physical activity such as competitive level sports.

The researchers identified 62 RA patients and matched them to 124 osteoarthritis controls; 81.7 percent were women and the average age was 64.7 years. The average LEAS was 8.7, which corresponds to being able to walk around the house and for several blocks without assistance.

The investigators measured pain, stiffness and function prior to surgery, using a tool called the Western Ontario and McMaster Universities Arthritis Index (WOMAC), and found that patients with RA had worse scores. Even when you try to match these patients to make them similar, it really does seem like this chronic disease makes these patients sicker, less happy, less functional and clearly they have worse expectations, Dr. Mandl said.

The investigators measured patient expectations prior to surgery using a validated tool called the Hospital for Special Surgery Expectations Survey, with 100 being the highest score and 0 being the lowest. RA patients had a lower overall expectation score compared with osteoarthritis patients, 73.7 versus 79.8, a difference that was statistically significant (P=0.03) and clinically meaningful. Patients with RA also had statistically significant lower expectations for several individually measured items such as whether the surgery will improve the ability to walk short distances, improve the ability to go up stairs, improve the ability to perform daily activities such as household chores and improve the ability to exercise.

When people report if they are satisfied, a lot of it is not just related to actual objective measures. It has to do with their expectations preoperatively. So, if you don't expect much and you don't get much, you could be pretty happy, said Dr. Mandl. You might have a person who says, 'I would love to have this surgery and be able to get up and walk to the bathroom without pain.' And when they have their surgery, they can get up and walk to the bathroom without pain, but maybe because that is all they expected, they kind of give up after that. They might not be optimizing their postoperative physical therapy.

Our rheumatoid arthritis patients have just come along extraordinarily in the last decade with, first, the widespread use of traditional medications and now the more widespread use of the potent biological medications, said Susan Goodman, M.D., a rheumatologist at Special Surgery. What we can do as doctors is ensure that we educate our patients properly. In the past, our rheumatoid arthritis patients didn't do as well as other patients and those expectations were realistic, but I think times are changing. RA patients might think 'oh, I'm never going to have great function, why am I pushing myself?' That would be shortchanging themselves. Doctors should explain to RA patients that they should expect good outcomes.

According to Dr. Mandl, doctors should assess patients' preoperative expectations. If they are concerned that patient's expectations are not in line with what they would predict, then doctors should recalibrate what the patient is hoping for, so that they can get the best result they can, she said.

Dr. Mandl says the study also makes her wonder if patients with RA are not choosing to have surgery because they don't think it will make a difference.

RA is an autoimmune disease that causes joint swelling, pain and fatigue among other symptoms. Osteoarthritis is caused by the normal wear and tear of the aging process; it can be encouraged by a high impact injury or obesity.

Hospital for special surgery physician-scientists share advances in rheumatology research

Sat, 05 Nov 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Hospital for Special Surgery physician-scientists who focus on arthritis, lupus, vasculitis and related conditions are traveling from New York City to Chicago this week to share their recent findings at the 75th Annual Scientific Meeting of the American College of Rheumatology (ACR).

Special Surgery investigators will present advances that should influence the future of clinical care. Of the meeting's highlights, results from the nine-year National Institutes of Health (NIH) funded study led by Jane Salmon, M.D., senior author, rheumatologist and Collette Kean Research Professor at Hospital for Special Surgery, found a favorable prognosis for pregnancy outcomes in women with lupus. The study's results will be presented on Monday, Nov. 7 and at an ACR press conference on Tuesday, Nov. 8, at 8:30am CT.

We have demonstrated that with diligent care and counseling, successful pregnancy can be a reality for women faced with lupus, says Dr. Salmon. Historically, doctors have cautioned against becoming pregnant, but with the medical insights we have learned from our research, these women have reason for new hope.

Additional significant topics presented by HSS experts include socioeconomic factors that influence patients' appointment compliance at a specialized lupus clinic, one-year results following a cardiovascular prevention program in lupus and antiphospholipid syndrome patients, expectations for rheumatoid arthritis patients following total knee replacement, use of anti-TNF medications before patients undergo total knee replacement, and the link between mental health and inflammatory flares in Wegener's granulomatosis disease.

The goal for the physicians at Hospital for Special Surgery's Division of Rheumatology is to better understand disease so that we can better care for patients, explained Physician-in-Chief Mary K. Crow, M.D. We hope to take the knowledge we gain at the laboratory bench and apply what we learn to patients who need the most innovative care.

At the meeting, the ACR will also honor three Hospital for Special Surgery faculty members with prestigious awards: Dr. Laura Robbins, DSW, CSW, MSW, senior vice president of education and academic affairs and scientist at Hospital for Special Surgery, will receive the ACR's Lifetime Achievement Award. Dr. Theresa Lu, MD, PhD, pediatric rheumatologist at Hospital for Special Surgery, will receive the Henry Kunkel Young Investigator Award, and Physician-in-Chief Emeritus Stephen A. Paget, M.D. will receive the Distinguished Clinician Scholar Award.

The Lifetime Achievement Award being given to Laura Robbins is the highest honor that the Association of Rheumatology Health Professionals (ARHP) bestows, and is presented to an investigator whose career has demonstrated a sustained and lasting contribution to the field of rheumatology. The Henry Kunkel Young Investigator Award is granted to a young physician scientist, age 45 or younger, who has made outstanding and promising independent contributions to basic and clinical research in the field of rheumatology. The Distinguished Clinician Scholar Award is awarded to a rheumatologist who has made outstanding contributions in clinical medicine, clinical scholarship, or education.

It is remarkable that three Hospital for Special Surgery experts in rheumatologic disease have been honored with ACR Awards, said Dr. Crow, who is also a past president of the ACR. Each of these Special Surgery experts has significantly contributed to the field of rheumatology.

Dr. Robbins, the first ARHP President, focuses on qualitative research as a way to understand the role of culture and ethnicity in rheumatologic patients' health care experience. Dr. Lu is studying the contribution of blood vessels to the altered immune system function that is responsible for autoimmune diseases, including lupus and scleroderma. Dr. Paget served as the hospital's physician-in-chief and chair of the Division of Rheumatology from 1995 to 2010, and today continues to advance delivery of outstanding care to patients and superior education of rheumatology trainees through the hospital's new Rheumatology Education Academy.

Highlights of presentations by Hospital for Special Surgery physician-scientists include:

Stress triggers disease flares in patients with vasculitis

Sat, 05 Nov 2011 04:00:00 PST

( from http://www.rxpgnews.com ) In patients with a devastating form of vasculitis who are in remission, stress can be associated with a greater likelihood of the disease flaring, according to a new study by investigators at Hospital for Special Surgery (HSS).

This is the first study to suggest that mental health is a risk factor in patients with vasculitis, a group of autoimmune disorders characterized by the inflammatory destruction of blood vessels. The study, in a form of the disease known as Wegener's granulomatosis (WG), will be presented on Nov. 8 at the American College of Rheumatology's annual meeting.

When this disease flares, people can be really sick. It often affects the lungs, kidneys, sinuses and nerves. It can cause fevers and rashes. People can die from this illness. It is a very robust, active, inflammatory disease when it is active, said Robert Spiera, M.D., director of the Vasculitis and Scleroderma Program at HSS, who led the study. When patients are in remission, however, they can do very, very well.

He says that doctors caring for patients with this disease should be attentive to their psychological health. This study points out that mental health should be part of your medical assessment, said Dr. Spiera. You should pay attention to the patient's mental well being and be more aggressive about intervening if a patient is in a bad place. Make sure that patients take it seriously.

Prior to this report, a few small studies had suggested that psychological stress can trigger flares of lupus, another autoimmune disease, and doctors have observed that WG patients often say that stress in their lives, caused by perhaps a death of someone close or losing a job, made their disease flare. To investigate this anecdotal evidence in a more quantifiable way, researchers at HSS conducted a retrospective analysis of data from the Wegener's Granulomatosis Etanercept Trial (WGET). The primary objective of this randomized, placebo-controlled clinical trial was to evaluate the safety and efficacy of using etanercept (Enbrel; Immunex Corporation) to get patients with WG into remission and maintain that remission.

All patients in this multicenter trial had active disease at the beginning of the study and most patients went into remission. Checkups occurred every three months. We assessed their disease activity at defined time intervals, in terms of how active their vasculitis was or whether they were in remission, and we also collected information at every visit regarding the patient's physical and mental health, Dr. Spiera said. Investigators measured disease activity using the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis, a validated tool. At every visit, patients also filled out the Short Form 36 Health Survey, which includes a physical and mental component. Summary scores for each component are measured on a scale of 0 to 100, with 100 being the healthiest.

Dirt prevents allergy

Wed, 02 Nov 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Oversensitivity diseases, or allergies, now affect 25 per cent of the population of Denmark. The figure has been on the increase in recent decades and now researchers at the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), University of Copenhagen, are at last able to partly explain the reasons.

In our study of over 400 children we observed a direct link between the number of different bacteria in their rectums and the risk of development of allergic disease later in life, says Professor Hans Bisgaard, consultant at Gentofte Hospital, head of the Copenhagen Prospective Studies on Asthma in Childhood, and professor of children's diseases at the Faculty of Health Sciences, University of Copenhagen.

Reduced diversity of the intestinal microbiota during infancy was associated with increased risk of allergic disease at school age, he continues. But if there was considerable diversity, the risk was reduced, and the greater the variation, the lower the risk.

So it makes a difference if the baby is born vaginally, encountering the first bacteria from its mother's rectum, or by caesarean section, which exposes the new-born baby to a completely different, reduced variety of bacteria. This may be why far more children born by caesarean section develop allergies.

In the womb and during the first six months of life, the mother's immune defences protect the infant. Bacteria flora in infants are therefore probably affected by any antibiotics the mother has taken and any artificial substances she has been exposed to.

I must emphasise that there is not one single allergy bacteria, Professor Bisgaard points out.

We have studied staphylococci and coli bacteria thoroughly, and there is no relation. What matters is to encounter a large number of different bacteria early in life when the immune system is developing and 'learning'. The window during which the infant is immunologically immature and can be influenced by bacteria is brief, and closes a few months after birth.

Our new findings match the large number of discoveries we have also made in the fields of asthma and hay fever, Professor Bisgaard explains. Like allergies, they are triggered by various factors early in life.

The researchers gathered their data from a unique material consisting of 411 children whose mothers have asthma. This cohort was monitored, interviewed and tested continually from when the children were born 12 years ago, and the COPSAC group has published articles at regular intervals with new knowledge about allergy and asthma ever since.

Professor Bisgaard acknowledges the irony of something that used to be perceived as a threat to public health, namely bacteria, now turning out to be a fundamental part of a healthy life. He also points out that there may be other couplings, such as between intestinal flora and diabetes or obesity and other lifestyle diseases affecting modern man in the West.

I think that a mechanism that affects the immune system will affect more than just allergies, he concludes. It would surprise me if diseases such as obesity and diabetes are not also laid down very early in life and depend on how our immune defences are primed by encountering the bacterial cultures surrounding us.

Natural killer cells could be key to anthrax defense

Thu, 27 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) GALVESTON, Texas -- One of the things that makes inhalational anthrax so worrisome for biodefense experts is how quickly a relatively small number of inhaled anthrax spores can turn into a lethal infection. By the time an anthrax victim realizes he or she has something worse than the flu and seeks treatment, it's often too late; even the most powerful antibiotics may be no help against the spreading bacteria and the potent toxins they generate.

Now, though, University of Texas Medical Branch at Galveston researchers have found new allies for the fight against anthrax. Known as natural killer cells, they're a part of the immune system normally associated with eliminating tumor cells and cells infected by viruses. But natural killer cells also attack bacteria -- including anthrax, according to the UTMB group.

People become ill so suddenly from inhalational anthrax that there isn't time for a T cell response, the more traditional cellular immune response, said UTMB assistant professor Janice Endsley, lead author of a paper now online in the journal Infection and Immunity. NK cells can do a lot of the same things, and they can do them immediately.

In test-tube experiments, a collaborative team led by Endsley and Professor Johnny Peterson profiled the NK cell response to anthrax, documenting how NK cells successfully detected and killed cells that had been infected by anthrax, destroying the bacteria inside the cells along with them. Surprisingly, they found that NK cells were also able to detect and kill anthrax bacteria outside of human cells.

Somehow these NK cells were able to recognize that there was something hostile there, and they actually caused the death of these bacteria, Endsley said.

In further experiments, the group compared the anthrax infection responses of normal mice and mice that were given a treatment to remove NK cells from the body. All the mice died with equal rapidity when given a large dose of anthrax spores, but the non-treated (NK cell-intact) mice had much lower levels of bacteria in their blood. This is a significant finding, Endsley said. Growth of bacteria in the bloodstream is an important part of the disease process.

The next step, according to Endsley, is to apply an existing NK cell-augmentation technique (many have already been developed for cancer research) to mice, in an attempt to see if the more numerous and active NK cells can protect them from anthrax. Even if the augmented NK cells don't provide enough protection by themselves, they could give a crucial boost in combination with antibiotic treatment.

We may not be able to completely control something just by modulating the immune response, Endsley said. But if we can complement antibiotic effects and improve the efficiency of antibiotics, that would be of value as well.

A*STAR scientists first to identify stem cell key to lung regeneration

Thu, 27 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Scientists at A*STAR'S Genome Institute of Singapore (GIS) and Institute of Molecular Biology (IMB), have made a breakthrough discovery in the understanding of lung regeneration. Their research showed for the first time that distal airway stem cells (DASCs), a specific type of stem cells in the lungs, are involved in forming new alveoli to replace and repair damaged lung tissue, providing a firm foundation for understanding lung regeneration.

Lung damage is caused by a wide range of lung diseases including influenza infections and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Influenza infection induces acute respiratory distress syndrome (ARDS) which affects more than 150,000 patients a year in the US, with a death rate of up to 50 percent. COPD is the fifth biggest killer worldwide.

The team took a novel approach in tackling the question of lung regeneration. They cloned adult stem cells taken from three different parts of the lungs - nasal epithelial stem cells (NESCs), tracheal airway stem cells (TASCs) and distal airway stem cells (DASCs). Despite the three types of cells being nearly 99 percent genetically identical, the team made the surprising observation that only DASCs formed alveoli when cloned in vitro.

We are the first researchers to demonstrate that adult stem cells are intrinsically committed and will only differentiate into the specific cell type they originated from. In this case, only DASCs formed alveoli because alveolar cells are found in the distal airways, not in the nasal epithelial or tracheal airway, said Dr Wa Xian, Principal Investigator at IMB. This is a big advancement in the understanding of adult stem cells that will encourage further research into their potential for regenerative medicine.

Using a mouse model of influenza, the team showed that after infection, DASCs rapidly grow and migrate to influenza-damaged lung areas where they form pods. These pods mature to new alveoli which replace the alveoli that were destroyed by the infection, leading to lung regeneration.

We have harvested these pods to provide insight into genes and secreted factors that likely represent key components in tissue regeneration.

These secreted factors might be used as biological drugs (biologics) to enhance regeneration of the lung and airways, said Dr Frank McKeon, Senior Group Leader of the Stem Cell and Developmental Biology at GIS.

The research was jointly led by Dr Frank McKeon from GIS and Dr Wa Xian from IMB in collaboration with scientists at the National University of Singapore (NUS), and clinicians at the Harvard Medical School and the Brigham and Women's Hospital in Boston.

Prof Birgitte Lane, Executive Director of IMB, said, This groundbreaking work is a fine example of collaborative research, which has brought us new insight into lung epithelial stem cells. This will have breakthrough consequences in many areas. Dr Edison Liu, Executive Director of GIS, added, We will continue to seek impactful collaborations and build upon this research area where there is a need for novel therapies, which will offer hope for patients suffering from respiratory diseases.

Brain immune cells respond to alcohol

Thu, 29 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) New research from the University of Adelaide suggests that immune cells in your brain may contribute to response to alcohol.

It's amazing to think that despite 10,000 years of using alcohol, and several decades of investigation into the way that alcohol affects the nerve cells in our brain, we are still trying to figure out exactly how it works, says lead researcher Dr Mark Hutchinson from the University's School of Medical Sciences.

Although scientists know much about how alcohol affects nerve cells, there is also a growing body of evidence that alcohol triggers rapid changes in the immune system in the brain. This immune response lies behind some of the well-known alcohol-related behavioural changes, such as difficulty controlling the muscles involved in walking and talking.

In research published in the latest edition of the British Journal of Pharmacology, Dr Hutchinson's team gave a single shot of alcohol to laboratory mice and studied the effect of blocking Toll-like receptors, a particular element of the immune system, on the behavioural changes induced by alcohol. The researchers used drugs to block these receptors. They also studied the effects of giving alcohol to mice that had been genetically altered so that they were lacking the functions of selected receptors.

The results showed that blocking this part of the immune system, either with the drug or genetically, reduced the effects of alcohol. While the research was carried out on mice, Hutchinson's team believe that similar treatments could also work in humans.

Medications targeting Toll-like receptor 4 may prove beneficial in treating alcohol dependence and acute overdoses, says Dr Hutchinson.

This work has significant implications for our understanding of the way alcohol affects us, as it is both an immunological and neuronal response. Such a shift in mindset has significant implications for identifying individuals who may have bad outcomes after consuming alcohol, and it could lead to a way of detecting people who are at greater risk of developing brain damage after long-term drinking.

NIH modifies 'VOICE' HIV prevention study in women

Wed, 28 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A large-scale clinical trial evaluating whether daily use of an oral tablet or vaginal gel containing antiretroviral drugs can prevent HIV infection in women is being modified because an interim review found that the study cannot show that one of the study products, oral tenofovir, marketed under the trade name Viread, is effective.

An independent data and safety monitoring board (DSMB) recommended that the Vaginal and Oral Interventions to Control the Epidemic (VOICE) study discontinue evaluating tenofovir tablets because the study will be unable to show a difference in effect between tenofovir tablets and placebo tablets. The DSMB found no safety concerns with oral tenofovir, which is currently used to treat HIV, or with the other products that will continue to be investigated as the VOICE study proceeds.

As the trial's primary sponsor, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, concurred with the DSMB's recommendation and will modify the study. Because the trial is continuing, the study data remain confidential and restricted to DSMB analysis. Given that data are unavailable, NIAID cannot speculate about why oral tenofovir did not show an effect among VOICE study participants.

Begun in September 2009, the VOICE study, or MTN-003, involves more than 5,000 HIV-uninfected women in South Africa, Uganda and Zimbabwe. The trial was designed to test the safety, effectiveness and acceptability of two different HIV prevention strategies: an investigational microbicide gel containing tenofovir, and oral tablets containing tenofovir either alone or co-formulated with the drug emtricitabine. The tablets, known by the brand names Viread (tenofovir) and Truvada (tenofovir plus emtricitabine), have been taken daily in an approach known as pre-exposure prophylaxis, or PrEP.

After its routine review of the study data on Sept. 16, the DSMB recommended that the investigators stop evaluating oral tenofovir because the study would be unable to show that tenofovir tablets have a different effect than placebo tablets at preventing HIV infection among the study participants. The DSMB therefore recommended that the roughly 1,000 women in the oral tenofovir group stop taking the study product. Further, the DSMB recommended that the VOICE study continue as designed to evaluate tenofovir gel and oral Truvada.

The study team will immediately begin to inform all VOICE participants of this new development and will soon begin the orderly discontinuation of the tenofovir tablets. Participants who were taking oral tenofovir will stop using the product at their next scheduled clinical site visit. They will then return eight weeks later for a final set of tests and procedures before exiting the study. At that visit, they will be provided information about where they can continue to receive HIV testing and counseling, contraception and other medical and support services.

NIAID is pleased that the trial will continue to examine the question of whether tenofovir gel and oral Truvada are safe and effective HIV prevention measures for women and thanks all participants in the VOICE study for their significant contribution to furthering HIV prevention research. This study is an important component of NIH's comprehensive HIV prevention research program articulated in the HHS National HIV/AIDS Strategy Operational Plan.

NIAID remains committed to supporting research to develop HIV prevention tools that women can implement. Slightly more than half of all new HIV infections globally occur in women, mostly through unprotected sex with HIV-infected men. A safe and effective microbicide or oral PrEP regimen would be particularly helpful to women when it is difficult or impossible for them to refuse sex or negotiate condom use with their male partners.

New evidence highlights risk of comorbidities for COPD patients

Mon, 26 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: A new study has shown that people with chronic obstructive pulmonary disease (COPD) or people with reduced lung function are at a serious risk of developing cardiovascular disease.

The findings, which will be presented today (26 September 2011) at the European Respiratory Society's Annual Congress in Amsterdam, suggest that people with COPD and reduced lung function should be routinely screened for cardiovascular disease, as they appear to be at a considerably greater risk of it.

The issue of co-morbidities, when an individual is affected by more than one condition at the same time, is a growing problem for medical professionals. As people are living longer, the presence of co-morbid conditions will increase. Patients are often treated by a specialist for one particular symptom but as the prevalence of co-morbidities increases it will become important for all clinicians to recognise other symptoms.

It is common for patients to have both heart disease and COPD but it is largely unrecognised by doctors because of overlapping clinical manifestations. COPD diagnosis can remain unsuspected in people with heart disease, but having both conditions can lead to a much worse outlook for the individual.

Previously there was very little epidemiological evidence linking the two conditions, but this study is the first to identify that nasal symptoms and cardiovascular disease are common in people with COPD and could link the two conditions.

The researchers collected data on nasal symptoms and cardiovascular disease from 993 patients with COPD and 993 without COPD. In the latter group, the patients were divided into two categories; those with normal lung function and those with restricted lung function. 50.1% of people with COPD had cardiovascular conditions such as heart disease, stroke and hypertension, compared to people with normal lung function (41%).

The results showed that nasal symptoms were common in people who had both COPD and heart disease compared to people with normal lung function: 53% of people with COPD and heart disease had nasal symptoms compared to 35.8% in people with normal lung function and heart disease.

In addition, 62.2% of people with both restricted lung function and heart disease had nasal symptoms, demonstrating that the symptoms could be used as a marker for identifying increased risk of heart disease and COPD in people yet to be diagnosed with either condition.

Dr Anne Lindberg, from the Sunderby Hospital in Sweden, said: Our findings are the first to shed light on the links between both nasal symptoms and cardiovascular condition, in relation to people with COPD and restrictive lung function. This has important implications for clinicians who need to understand the potential overlaps of these conditions when they are treating people with COPD. In addition to raising awareness of these co-morbidities, it will also be important to investigate these links further and look at the effect that co-morbid conditions have on exacerbations and disease progression.

Professor Marc Decramer, President of the European Respiratory Society, said: Clinicians often forget that people with one chronic condition usually have another illness at the same time. Many of the illnesses that are common alongside COPD, such as cardiovascular disease, may also share similar traits and it is vital that we build on research such as this study to identify new therapeutic targets in the future.

The European Respiratory Roadmap, which was launched last month, outlines the need for great coordination between medical specialists. As the population is aging, the presence of co-morbidities will increase. The roadmap suggests that clinicians need to improve their recognition of other conditions to improve patient care and look at how to manage COPD in conjunction with other health conditions.

Scientists disarm HIV in step towards vaccine

Mon, 19 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have found a way to prevent HIV from damaging the immune system, in a new lab-based study published in the journal Blood. The research, led by scientists at Imperial College London and Johns Hopkins University, could have important implications for the development of HIV vaccines.

HIV/AIDS is the third biggest cause of death in low income countries, killing around 1.8 million people a year worldwide. An estimated 2.6 million people became infected with HIV in 2009.

The research shows that HIV is unable to damage the immune system if cholesterol is removed from the virus's membrane. Usually, when a person becomes infected, the body's innate immune response provides an immediate defence. However, some researchers believe that HIV causes the innate immune system to overreact and that this weakens the immune system's next line of defence, known as the adaptive immune response.

In the new study, the researchers removed cholesterol from the membrane surrounding the virus and found that this stopped HIV from triggering the innate immune response. This led to a stronger adaptive response, orchestrated by immune cells called T cells. These results support the idea that HIV overstimulates the innate response and that this weakens the immune system.

Dr Adriano Boasso, first author of the study, from Imperial College London, said: HIV is very sneaky. It evades the host's defences by triggering overblown responses that damage the immune system. It's like revving your car in first gear for too long. Eventually the engine blows out.

This may be one reason why developing a vaccine has proven so difficult. Most vaccines prime the adaptive response to recognise the invader, but it's hard for this to work if the virus triggers other mechanisms that weaken the adaptive response.

HIV takes its membrane from the cell that it infects. This membrane contains cholesterol, which helps to keep it fluid. The fluidity of the membrane enables the virus to interact with particular types of cell. Cholesterol in the cell membrane is not connected to cholesterol in the blood, which is a risk factor for heart disease but is not linked to HIV.

Normally, a subset of immune cells called plasmacytoid dendritic cells (pDCs) recognise HIV quickly and react by producing signalling molecules called interferons. These signals activate various processes which are initially helpful, but which damage the immune system if switched on for too long.

In collaboration with researchers at Johns Hopkins University, the University of Milan and Innsbruck University, Dr Boasso's group at Imperial have discovered that if cholesterol is removed from HIV's envelope, it can no longer activate pDCs. As a consequence, T cells, which orchestrate the adaptive response, can fight the virus more effectively.

The researchers removed cholesterol using varying concentrations of beta-cyclodextrin (bCD), a derivative of starch that binds cholesterol. Using high levels of bCD they produced a virus with a large hole in its envelope. This permeabilised virus was not infectious and could not activate pDCs, but was still recognised by T cells. Dr Boasso and his colleagues are now looking to investigate whether this inactivated virus could be developed into a vaccine.

It's like an army that has lost its weapons but still has flags, so another army can recognise it and attack it, he said.

T cells making brain chemicals may lead to better treatments for inflammation, autoimmune diseases

Fri, 16 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) MANHASSET, NY -- Scientists have identified a surprising new role for a new type of T cell in the immune system: some of them can be activated by nerves to make a neurotransmitter (acetylcholine) that blocks inflammation. The discovery of these T cells is novel and suggests that it may be possible to treat inflammation and autoimmune diseases by targeting the nerves and the T cells. The study was published this week in Science.

The discovery that 2 percent of T cells can make acetylcholine under the control of nerves gives a new insight into how the nervous system regulates immunity, said Kevin J. Tracey, MD, president and chief executive officer of The Feinstein Institute for Medical Research, and principal investigator of the study. The arrival of electrical signals from nerves activates these specialized T cells to produce the acetylcholine necessary to block inflammation, and protect against damage. It is possible to transfer these cells to cross-protect mice from inflammation, and to control these T cells by electrically stimulating the nerves directly.

The present study followed years of work from Dr. Tracey's lab that identified the role of the vagus nerve, named for its wandering course from the base of the brain to the liver, spleen and other organs, in blocking inflammation. Applying electrodes to stimulate the vagus nerve blocked the release of tumor necrosis factor (TNF) and other cytokines that underlie the tissue damage in arthritis, inflammatory bowel disease and other syndromes. Stimulating this nerve pathway led to increased production of acetylcholine, a neurotransmitter that binds to the alpha 7 nicotinic acetylcholine receptor. Activating this receptor on macrophages blocked the release of immune molecules (the cytokines,) suggesting a novel strategy for developing anti-inflammatory agents.

But these results raised an important question because the nerve fibers in spleen release norepinephrine, another neurotransmitter, but not acetylcholine. The search for the cells that produce acetylcholine led these investigators to use nude mice, devoid of T cells. Then they examined the spleen cells that make acetylcholine and that led them to a subset of T cells. Transferring these acetylcholine producing T-cells into nude mice restored the vagus nerve circuit that blocked inflammation.

Our results point to a population of acetylcholine-synthesizing memory T cells in spleen that is integral to the function of the inflammatory reflex, the nerve circuit that regulates inflammation and immunity, said Dr. Tracey. It is as if these T cells occupy a nerve-like function in this important circuit.

It should be possible to target these T cells and to modulate this neural circuitry to develop therapeutic modalities for inflammatory and autoimmune diseases. In the future, it may be possible to isolate these T cells and exploit their anti-inflammatory activity. In the meantime, there is a more direct route to use this discovery for therapy. Rheumatoid arthritis patients in Europe are being studied in clinical trials where vagus nerve stimulators are implanted and turned on to stimulate this circuit and suppress inflammation.

Pharmacists need to provide better information to teenagers on risks and benefits of medicines

Sun, 04 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Hyderabad, India: A large proportion of teenagers regularly and frequently take some form of medication without receiving targeted information about the risks and benefits, according to a review of current research, to be presented at the annual congress of the International Pharmaceutical Federation (FIP) tomorrow (Tuesday).

Dr Priya Bahri will tell delegates that 35% of boys and 45% of girls in Europe and the USA take painkillers for headaches every month. In addition, they take a variety of other medicines for things like stomach aches, sleeping disorders, nervousness, asthma, infectious diseases and for pregnancy prevention. Most teenagers take their medicines appropriately, but there is evidence of accidental or intentional inappropriate use or misuse, she says.

At a time when young people want to be independent of their parents and make their own decisions about their bodies and medications, they feel misunderstood by healthcare professionals, have concerns over side effects and may be confused by information coming from a variety of sources such as their friends, their family, the internet, the news, and the healthcare professionals they encounter, says Dr Bahri, who is the pharmacovigilance lead for guidelines and risk communication at the European Medicines Agency (London, UK), but who was speaking in a personal capacity. [1]

Part of teenage life is starting to make your own health choices. The medicines that teenagers use most frequently and largely autonomously include those for asthma, and painkillers such as paracetamol and ibuprofen. Every month in Europe and the USA, about 35% of boys and 45% of girls use painkillers for headaches. Teenagers also use other medicines: every month 32% use them for stomach aches, 6% for sleeping disorders and 6% for nervousness. The prevalence of asthma, one of the most frequent chronic disorders worldwide, is around 10% in teenagers, so most of those with this condition will be taking medication for it, and it is estimated from worldwide data that around a quarter of teenage girls will be taking some form of contraceptive, including hormonal ones. In addition, girls may be invited to receive the human papilloma virus (HPV) vaccine to protect them against cervical cancer. However, public discussions in the media over the usefulness and safety of these measures make some feel anxious and confused, she says.

Dr Bahri is investigating how well information about medications are communicated to teenagers, and has found that not only is there very little research into this area, but what there is indicates that healthcare professionals, including pharmacists, need to improve the way they talk to young people and communicate the risks and benefits of medicines.

The HPV vaccination programme is a good example of where healthcare professionals could be better prepared for communication with teenagers, she says. There were several incidents in Europe of HPV vaccination-related anxiety attacks among girls receiving the vaccine. In addition, in many countries in the world, older children and adolescents, rather than young children receive various vaccinations, and may develop concerns over them.

Research has found that although pharmacists know about the importance of talking to teenagers about their medications, they tend not to. This was shown in The Netherlands with the example of isotretinoin, which is sometimes prescribed for teenage acne. Isotretinoin causes birth defects and so can only be taken in conjunction with effective contraception, requiring the physician and pharmacist to initiate a conversation with teenage girls. The study showed that the pharmacists knew they should talk to the girls, but it didn't reveal why the majority of them did not comply fully with their role in the country's pregnancy prevention programme when dispensing isotretinoin. Obstacles to communication is an area where much more research needs to be done, says Dr Bahri.

As a pharmacist myself, I know how difficult these conversations can be, but I would advocate that pharmacists should be looking into their communication behaviour and identifying opportunities and successful methods for initiating caring and non-judgemental dialogue. It is vital that pharmacists overcome our own hesitation to talk; we should start the dialogue and listen to questions and concerns. It is important to help teenagers to care for their health, while being aware of their vulnerabilities as well as their capabilities.

She will tell the congress that pharmacists also need to be aware that increasingly medicines are being advertised on the internet to improve school performance, and they need to monitor this and inform teenagers about the risks.

Good communications with teenagers could also be vital for the well-being of the whole family in some circumstances. This can be the case in developing countries and among disadvantaged groups in the developed world, such as those who have migrated and have poor language skills.

Sometimes, in places where teenagers are the only literate person in the family, they may even bear the responsibility of the health of their siblings and the older members of their families, she says.

Dr Bahri concludes: Effective communications with teenagers at the individual and population level is vital, and pharmacists should consider investigating the use of text messages, social media and other web-based forms of communication with this age group, in addition to more traditional methods. We need to bear in mind that some research in different regions of the world has shown that teenagers still expect most information to come directly from their healthcare providers, but not necessarily from pharmacists.

As pharmacists, we should be prepared to handle the needs and feelings of young people in a sensitive manner, taking into account the fact that they are in a vulnerable phase where a bad experience could influence their current and future health behaviour.

Achieving realistic physical activity goals benefits RA patients

Thu, 25 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers from The Netherlands report that patients with rheumatoid arthritis (RA) who have higher levels of self-efficacy for physical activity are more likely to achieve their physical activity goals. According to the study now available in Arthritis Care & Research, a journal of the American College of Rheumatology (ACR), achievement of physical activity goals is associated with lower self-reported arthritis pain and increased health-related quality of life (HRQOL).

The World Health Organization (WHO) estimates that RA, a chronic autoimmune disease causing inflammation in the lining of joints, affects nearly 1% of the world population. In the U.S., the ACR reports 1.3 million adults suffer with RA. Studies indicate that RA patients cite pain and stiffness as the most limiting factors of their illness, and report lower HRQOL than healthy individuals. RA patients who do not engage in regular physical activity have a more pronounced effect from the disease.

For the current study, Keegan Knittle, MSc, from Leiden University in The Netherlands and colleagues surveyed 106 patients with RA to assess physical activity, motivation and self-efficacy for physical activity, level of arthritis pain, and quality of life. After six months, participants were surveyed again and asked to indicate the extent to which they achieved their baseline physical activity goal. Previous research has shown that self-efficacy, described as one's belief in his or her own capabilities to perform a specific behavior, is associated with increased physical activity participation among RA patients.

Results showed that 75% of participants rated their physical activity goal achievement at 50% or more. Higher levels of self-efficacy for physical activity increased the likelihood that patients would achieve their physical activity goals, and goal achievement had a direct positive effect upon quality of life outcomes. Researchers found that patients who achieved their physical activity goal reported less arthritis pain and greater quality of life. No differences were found between men and women who completed the surveys, or between patients newly diagnosed versus those with RA for 10 years or more.

Knittle concluded, "Our results suggest that an increased focus on self-efficacy enhancement, realistic goal-setting, and techniques that increase the likelihood of goal achievement will assist clinicians and researchers develop interventions that have a positive impact on pain reduction and quality of life outcomes for RA patients."

Researchers on the trail of a treatment for cancer of the immune system

Fri, 19 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Infection with Epstein Barr means that the B cells, which are the primary memory cells of the immune system, are hi-jacked.

When the virus has penetrated, researchers observe an excess of a special bio-antenna, a receptor known as EB12, suddenly sprouting from the surface of the B cells. But why they do so remains a mystery.

The receptors are a vital component of the way cells communicate with their surroundings via hormones and other bio-molecules, for example, but in a body consisting of millions of cells and transmitters it can be hard to determine the part each molecule plays.

It is possible that the large numbers of EB12 receptors could actually be the B cells response to the virus and an attempt to combat the infection. Another possibility is that the EB virus reprogrammes the cell for this explosive growth in the number of EB12 receptors. What we know for certain is that more EB12 receptors assist the B cell infected by the EB virus to multiply more rapidly thus spreading the infection faster, says postdoc Tau Benned-Jensen from the Faculty of Health Sciences, University of Copenhagen.

No fewer than 95 per cent of us carry the Epstein Barr Herpes virus.

We often encounter it as kids and it is normally harmless. Are we infected later in life EB virus may cause mononucleosis, and it seems to play a part in some forms of cancer, just as HPV affects the risk of cervical cancer. But we have no drugs to combat the Epstein Barr virus, and no vaccines for it.

Under normal circumstances our immune systems can keep the EB virus infection in a latent state and a truce or stand-off may arise between the immune system and the virus, explains Mette Rosenkilde, professor of pharmacology at the Department of Neuroscience and Pharmacology, University of Copenhagen.

We cannot dispense with the infection and we carry it all life long, but to most of us it is harmless. For people whose immune systems do not function due to disease or because they are suppressed by drugs in conjunction with organ transplants it is a very different matter. Now the Epstein Barr virus is suddenly free to reproduce so uninhibitedly and dramatically that it may lead to cancer, says Mette Rosenkilde.

While researchers know that the B cell EB12 receptors play a part when the cell visits the lymph glands, the immune system's Central Station, we have not yet explained the exact role of the receptor.

So the Danish researchers started by mapping the bio-antenna molecule by molecule and then, as the first in the world, they made a blueprint of a tiny molecule they thought could bind to the B cell EB12 receptor.

When we know what receptors react to, it tells us more about the part they play, Mette Rosenkilde explains, and our tiny molecule, a ligand, blocks the EB12 receptor, preventing it from doing its job.

In time this block may be able to help transplant patients. If we can restrain EB virus reproduction when the immune system is being medically suppressed, we may well be able to avoid cancer, Tau Benned-Jensen says.

On the other hand the EP virus also appears to play a part in other immune diseases such as autoimmune disease, where the ability to adjust the immune system would be beneficial, says Mette Rosenkilde.

And shortly after the Danish researchers published their article on their ligand, the first articles appeared about natural substances in the body, which activate the EB12 receptor and direct the B cell to specific areas in the lymph glands.

Our molecule can inhibit the activation of the new substances, and the next step in our research will be experiments to identify even more biochemical dials to twiddle and to help us develop new drugs, Tau-Benned says.

The discovery has just been published in the

Trauma drama: K-State professor researches drama queen of immune system

Mon, 08 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) MANHATTAN, KAN. -- Kansas State University's Sherry Fleming is investigating the factor that initiates the immune system's drama queen: the one responsible for intestinal cell damage after hemorrhage.

Fleming, an associate professor in the Division of Biology, is using a $140,000 grant from the American Heart Association to identify the molecule responsible for the overreaction that can cause cell death in the intestines after trauma.

What's starting this drama queen situation? A 13-year-old girl doesn't usually become a drama queen without a reason. There's something that initiated the drama -- clothes, shoes, make-up, movies, etc., Fleming said. With hemorrhage, we're looking for the initiating factor in the drama which occurs after trauma.

After a traumatic event, such as the loss of a limb or severe bleeding, the body cuts off blood flow to the intestines, sending more blood to the vital organs like the heart, lungs and brain, Fleming said. During that time, cells in the gut release molecular markers to let the body know that they are not getting oxygen.

After the trauma is resolved, blood flow is returned to the gut and a protein in the blood -- known as beta2 glycoprotein 1 in mice and apolipoprotein H in humans -- binds to the molecular marker on the cell to notify antibodies that there is a problem. The antibodies then activate a cascade of proteins, known as complement, that normally help the immune system by killing bacteria and helping rid tissues of dying cells. However, after a trauma this system can overreact and unnecessarily kill healthy cells.

If you've been in a car accident and sever an arm or start hemorrhaging, you want complement there to protect you from bacteria. So we don't want to stop all complement action entirely, Fleming said.

But Fleming is looking for a way to interrupt the chain of events leading to the over activation of complement following a traumatic event, because trauma patients often develop further complications throughout their body due to the activation of complement, she said.

Many times trauma patients who have lost a lot of blood will end up with acute respiratory distress syndrome or multiple organ dysfunction syndrome, due to the complement system overreacting, Fleming said. So they not only have to deal with the trauma, but also with their immune system attacking things that it shouldn't.

As a possible solution, Fleming and her lab group have developed a peptide that takes the place of the beta2 protein in binding to the molecular marker on the cell's surface, thus preventing the activation of complement.

This treatment is a promising solution, Fleming said. The funding from the American Heart Association will give us the opportunity to make major progress in this research.

NIH funds Emory-led consortium to advance AIDS vaccine research

Mon, 18 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A consortium of leading vaccine researchers at Emory University and partner institutions has received a National Institutes of Health (NIH) grant aimed at developing an effective HIV/AIDS vaccine.

The five-year program project grant of more than $26 million from the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, will fund the Emory Consortium for AIDS Vaccine Research in Nonhuman Primates. The research will be conducted primarily at the Yerkes National Primate Research Center at Emory.

Developing a safe and effective preventive HIV/AIDS vaccine is still a critical part of the fight against this challenging disease that affects more than 30 million people worldwide, says Eric Hunter, PhD, who will lead the consortium.

With the vast experience of Emory's vaccine researchers and our partners, I'm confident we can make significant strides in developing a better HIV vaccine. Hunter is a member of the Emory Vaccine Center, a co-director of the Emory Center for AIDS Research, a professor of pathology and laboratory medicine at Emory University School of Medicine, and a Georgia Research Alliance Eminent Scholar.

The researchers will study how to develop a vaccine that can prevent the earliest stages of mucosal infection from simian immunodeficiency virus (SIV) in nonhuman primate models. SIV is similar to HIV in humans. The series of research projects is expected to provide a better understanding of how SIV is transmitted sexually and the specific immune responses HIV vaccines must generate in humans to block infection at mucosal sites, prevent the establishment of systemic infection, or dramatically reduce the pathogenic effects of infection.

The consortium's work will build on recent significant discoveries in the AIDS vaccine field. A vaccine trial in Thailand (RV144) completed in 2009 showed a modest degree of protection against HIV in humans. The results gave the vaccine research community hope that a vaccine could elicit antibodies that could at least moderately protect against HIV infection. In order to develop a more effective vaccine, however, researchers need to further explore the specific aspects of the immune response (referred to as correlates of immunity) in animal models as well as in human clinical trials, Hunter explains.

More than 90 percent of all HIV infections worldwide occur via mucous membranes, predominantly through sexual contact. In order to develop an effective vaccine, scientists must understand the viral-host interaction during the initial time of mucosal infection.

By the time HIV-infected individuals begin experiencing the symptoms of acute HIV infection, this critical time of opportunity has passed, says Rama Amara, PhD, co-principal investigator of the consortium and a researcher at the Emory Vaccine Center and Yerkes Research Center. Rhesus macaque monkeys provide an effective model for studying mucosal viral infection and ways to stimulate an early protective immune response.

Researchers agree that a successful HIV vaccine will likely need to elicit both effective T-cell and antibody responses. The Emory consortium will work to enhance the quality of antibody responses to HIV infection, building on recent Emory discoveries led by Amara and consortium member Bali Pulendran, PhD, using adjuvants to successfully enhance the effectiveness of vaccines against SIV infection.

Important follow-up questions the team will address include what kind of antigens and delivery system are needed to elicit protective antibodies, where should vaccines be delivered in the body, and how do adjuvants convert a poorly protective vaccine into one that fully protects against infection by the virus?

Lack of clarity about HPV vaccine and the need for cervical cancer screening

Wed, 06 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) The research will be presented today [Thursday 7 July] at the Annual Scientific Meeting of the Society of Academic Primary Care, hosted this year by the Academic Unit of Primary Health Care, University of Bristol.

The HPV vaccination programme, introduced in the UK in 2008, uses HPV vaccine that is effective against the two most common high risk HPV types (16 and 18), and offers 70 per cent protection against cervical cancer. However, vaccinated girls will still need to attend cervical screening in the future to ensure protection against cervical cancer caused by high risk HPV types not included in the vaccine.

Dr Alison Clements and colleagues interviewed parents and vaccination-aged girls about their understanding of the HPV vaccination in relation to vaccine acceptance, and potential future cervical cancer screening behaviour.

They found a lack of clarity amongst both parents and girls about the link between the HPV vaccine and the need for future cervical screening. In some cases parental consent for their daughters to receive the vaccine was based on the false belief that cervical screening would not be necessary. There was also a profound lack of awareness about cervical screening amongst girls of vaccination age.

Dr Clements said: For informed decisions about HPV vaccination to be made, the provision of information about the ongoing need to attend cervical screening is imperative. Our findings have the potential to improve information and educational materials for parents, eligible girls and health professionals. To ensure the uptake of cervical screening is not adversely affected, future invitations for screening will need to stress the importance of attendance regardless of whether the individual has had the HPV vaccination or not.

Hazel Nunn, Cancer Research UK's senior health information manager, said: This is a helpful reminder that renewed efforts are needed to inform girls and their families about the importance of cervical screening in those who have had the HPV vaccination. While the vaccine is very effective at protecting against the two strains of virus which cause most cases of cervical cancer, and one of the biggest steps forward in public health in recent years, it does not protect against all the other strains so the disease can still develop.

Cervical screening can prevent around 34 per cent of cervical cancers in women in their 30s, rising to 75 per cent in women in their 50s and 60s. Women should be reminded of the crucial role of screening in the fight against cervical cancer.

Sport doctors say non-alcoholic wheat beer boosts athletes' health

Thu, 09 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Many amateur athletes have long suspected what research scientists for the Department of Preventative and Rehabilitative Sports Medicine of the Technische Universitaet Muenchen at Klinikum rechts der Isar have now made official: Documented proof, gathered during the world's largest study of marathons, Be-MaGIC (beer, marathons, genetics, inflammation and the cardiovascular system), that the consumption of non-alcoholic weissbier, or wheat beer, has a positive effect on athletes' health. Under the direction of Dr. Johannes Scherr, physicians examined 277 test subjects three weeks before and two weeks after the 2009 Munich Marathon.

The study focuses on the health risks for marathon runners and the potential positive effects of polyphenols. These aromatic compounds occur naturally in plants as pigment, flavor, or tannins, many of which have been credited with health-promoting and cancer-preventative properties. Unique to this study was the combination of different polyphenols that were tested on the large pool of participants. The research team met the scientific requirements of the study by conducting a randomized, double-blind, placebo-controlled trial.

Non-alcoholic Erdinger wheat beer was selected as the test beverage, chosen for its rich and varied polyphenol content and its popularity with marathoners and tri-athletes. The active group drank up to 1.5 liters of the test beverage per day, while a second group consumed an equal amount of an otherwise indistinguishable placebo beverage that contained no polyphenols and was especially produced for the study.

One result from the study was the discovery that, after running a marathon race, athletes experience intensified inflammatory reactions. The immune system is thrown off balance and runners are much more likely to suffer from upper respiratory infections. This heightened susceptibility to illness following strenuous sport activity has been identified as an open window. Furthermore it was shown that non-alcoholic wheat beer containing polyphenols has a positive, health promoting effect on the human body: inflammation parameters in the blood were significantly reduced, and there was a lower frequency of infection with milder symptoms.

Reduced Inflammatory Reaction: Dr. Scherr, who also serves as physician to the German National Ski Team, explains: The analysis of the leukocytes, or white blood cells, which constitute one of the most important parameters for inflammation, revealed values in the active group that were 20% lower than in the placebo group.

Support for the Immune System: Compounds in the test drink had a compensatory or balancing effect on the immune system. Dr Scherr: We were able to prove that it strengthens an immune system that has been weakened by physical stress. It also prevents the system from over-performing.

Prevents Colds: Runners who drank the non-alcoholic wheat beer were up to three times less susceptible to infection than those in the placebo group. Dr. Scherr: Drinking the non-alcoholic test beverage reduces your risk of developing a cold by one third.

Improvement with Upper Respiratory Infections: People in the active group who did succumb to a cold experienced a milder or briefer infection than those in the placebo group. Dr. Scherr: Results showed a Number Needed to Treat (NNT) of eight. That means that for every eight people who had the test drink, one of them was prevented from succumbing to a cold.

In summary, Dr. Scherr explains: The potential for foods containing polyphenols to have a positive effect on athletes' health has already been suggested in several articles. Nevertheless we were ourselves sometimes surprised at how clearly evident this was in the results. We now have scientific confirmation of those assumptions for this test beverage, with its particular combination of polyphenols, vitamins and minerals.

Dr. Scherr presented this study to the approximately 5,000 scientists, physicians, and trainers attending the world's largest congress for sports medicine in Denver (USA) hosted by the American College of Sports (ACSM) at the beginning of June 2011. The study will be published in the January printed edition of the professional journal

Researchers discover biochemical weakness of malaria parasite -- vaccine to be developed

Tue, 07 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Every year, 10,000 pregnant women and up to 200,000 newborn babies are killed by the malaria parasite. Doctors all around the globe have for years been looking in vain for a medical protection, and now researchers from the University of Copenhagen have found the biochemically weakness of the lethal malaria parasite, and will now start developing a vaccine to combat pregnancy related malaria.

The malaria parasite travels via the spit of an infected mosquito to the liver of the new host, where it spreads to the red blood corpuscles and starts to reproduce itself.

Pregnant women and children below the age of five years are particularly vulnerable to malaria because of the parasite's survival mechanisms. The parasite has a protein hook designed to attach it to the placenta and this leads to amnesia of the mother who in worst case can die or deliver prematurely. This increases the maternal mortality - and infant mortality, explains Associate Professor Ali Salanti from the University of Copenhagen's Centre for Medical Parasitology who manages the project.

The body's immune system normally attacks any foreign body but since our spleen constantly filters our blood and removes ruined or deform blood cells, the body's natural defense does not need to check the blood. And the malaria parasite exploits this fact.

An infected red blood corpuscle is more stiff than in its normal state and this would usually trigger the spleen to destroy the cell and parasite, but the malaria parasite has an advanced arsenal of protein hooks. With these hooks the parasite attaches itself to the inner side of the blood vessel and even if our immune system succeeds in defeating one hook, the parasite has 60 different hooks, which again differ from one malaria parasite to another.

Researchers have for years been looking for a vaccine which can attack the malaria parasite's specific placenta hook. This is tricky not least due to the fact that the parasite's hooks are long proteins which are difficult to produce artificially in the lab when developing of a vaccine.

After intensive research efforts, the researchers have now succeeded in identifying a fragment of the placenta hook (VAR2CSA) which not only is crucial for the parasite's ability to attach itself to the placenta, but also is possible to produce artificially for a vaccine.

A vaccine must stimulate the immune system to quickly attack something foreign in the body. Therefore, it was a matter of finding the part of the placenta hook, which the parasite cannot manage without and which we could target a vaccine against, says Associate Professor Ali Salanti.

With a grant of 15 million DKK (approximately 3 million USD) from the Danish National Advanced Technology Foundation and close corporation with two Danish biotech companies, the researchers can now start developing the vaccine and take it through the first trials to test its safety.

Ali Salanti and his colleagues will collaborate with the biotech companies ExpreS2ion Biotechnologies and CMC Biologics A/S to develop a method for mass production of the vaccine.

Once this has fallen into place, the researchers can start up the clinical trials on animals and human beings. If the trials are successful the parasistologists from the University of Copenhagen and their partners will make a significant contribution in reaching the UN's Millennium Development goal number 4 and 5. These two goals encourage every country in the world to work on lowering global child mortality with two thirds and maternal mortality with three quarters.

Adjuvant combo shows potential for universal influenza vaccine

Tue, 07 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at National Jewish Health have discovered how to prime a second arm of the immune system to potentially boost influenza vaccine effectiveness. A combination of two adjuvants, chemicals used to boost the effectiveness of some vaccines, induced CD8, or killer, T cells to join antibodies in response to influenza infection. Since the killer T cells targeted a highly conserved protein that does not change from year to year, the adjuvant strategy suggests potential for a universal flu vaccine.

Most vaccines protect against disease by boosting antibody protection, said lead author post-doctoral fellow Megan MacLeod, PhD. We have shown that the two adjuvants work in concert to generate memory CD8 T cells, which can kill infected cells. We believe that this strategy of stimulating both the cellular and humoral immune responses holds promise for better vaccines.

Vaccines prepare the immune system to respond quickly to an infection with antibodies, Y-shaped molecules that neutralize or otherwise inactivate pathogens.

Aluminum salts, or alum, have been used for nearly a century as an adjuvant to boost the effectiveness of many vaccines. Surprisingly no one is sure even today exactly how it works. The only other adjuvant approved for use in the United States, monophosphoryl lipid A (MPL), is used by GlaxoSmithKline to boost the antibody response of some of its vaccines.

Dr. MacLeod, senior author Philippa Marrack, PhD, and their colleagues evaluated the responses of mice immunized with influenza vaccines containing no adjuvant, each adjuvant alone and both together. They engineered the vaccine so that any immune defense would be provided by killer T cells, not antibodies. Several weeks after the immunization, they infected the mice with influenza A virus.

They found that unvaccinated mice lost about 15 percent of their body weight in the first eight days after infection, then regained some of that weight by 20 days after infection. Mice whose vaccines contained either alum or MPL adjuvants lost less weight but did not fully regain their original weight. Mice whose vaccines contained both adjuvants together lost about 5 percent of their original weight and regained it all back rapidly.

The researchers also found that mice receiving vaccines with both adjuvants had the fewest viral particles in their lungs four days after infection.

Further experiments revealed that alum promoted long-lived CD8 memory cells, but that MPL was required to produce activated cells, ready and able to kill. The findings were published in the May 10, 2011, issue of the

Clinical trial of malaria vaccine begins in Africa

Wed, 25 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) The vaccine, RTS,S, developed by GlaxoSmithKline (GSK) Biologicals and PATH Malaria Vaccine Initiative (MVI), is currently in phase III clinical trials and has previously reduced episodes of malaria in infants and young children by more than 50%. The Liverpool team, in collaboration with the University College of Medicine, Malawi, are working in Blantyre over the next three years to investigate how to maximise its effectiveness when delivered through the childhood immunisation programme.

Malaria is a life-threatening parasitic infection, resulting in more than 200 million reported cases each year and approximately 800,000 deaths. In Africa a child dies of malaria every 45 seconds and the disease accounts for 20% of all childhood deaths. Scientists will assess the possible benefits of providing the vaccine to newborn babies, similar to the routine programme currently used for other vaccines, such as BCG for tuberculosis, Hepatitis-B and oral polio vaccines.

The team will examine the performance of the vaccine as it is administered to infants at different stages between birth and nine months of age, alongside the standard set of immunisations used in national programmes for young children. Studies have so far suggested that the vaccine could be safely integrated with other vaccines in the World Health Organisation's Expanded Programme for Immunisation (EPI) schedule.

Leading the study from Malawi, Dr Desiree Witte, from the University's Institute of Infection and Global Health, said: Young children are particularly susceptible to infection with malaria and it is important that vaccines are introduced into the immunisation programme as early as possible. There is no licensed vaccine available against malaria and currently the candidate vaccine developed by GSK and MVI, is the most clinically advanced malaria vaccine in the world. The evaluation of different immunisation schedules will help define the programme needed for the vaccine to be administered successfully.

Professor Nigel Cunliffe, also from the University's Institute of Infection and Global Health, added: Over the past few years there have been encouraging results from studies of vaccines aimed at tackling some of the major diseases common to children living in Africa, including diarrhoea, pneumonia and malaria. It is hoped that in the near future vaccines against these diseases will become a standard part of the immunisation schedule across the region. It will therefore become increasingly important for us to understand how the vaccines will work when administered alongside each other.

Professor Tom Heikens, Head of the University College of Medicine's Department of Paediatrics and Child Health, Malawi, said: As well as developing this important area of research, the work is allowing postgraduate students at the College to gain valuable insight into child health and the medical challenges Malawi faces. Collaborations such as this contribute greatly to identifying the next generation of researchers to take this important area of study forward.

The research is funded by GlaxoSmithKline Biologicals, Belgium.

New test could give SLE patients a more tolerable life

Mon, 09 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) At present, it can take up to a year before a patient is diagnosed with SLE. This is because the symptoms are diffuse and are often mistaken for other diseases. However, with this blood-based test, it is possible to determine quickly whether someone has the disease or not, says Christer Wingren, associate professor in Immunotechnology at CREATE Health, Lund University.

The test can also determine how far the disease has progressed. There are three different variants of SLE, and all require different treatment. With current methods, it is often difficult to find out which variant a patient has, which makes it difficult for doctors to prescribe the right medication. A third advantage of the new technique is that it also makes it possible to predict when the disease will become active.

Characteristic of SLE is that the disease goes in waves, or flares. Without warning, the disease can flare up and put the patient out of action for a long time. With our test, we hope to be able to predict when an episode is about to happen and in this way prevent it using the right medication, explains Christer Wingren.

If all goes well, hospitals could start using the technique in two to three years.

The test itself comprises a small chip, smaller than a little fingernail, on which the researchers create a grid pattern, known as an array, using specially selected antibodies. The antibodies serve as 'capture molecules'; by placing a drop of blood on the chip, the antibodies bind the proteins, or biomarkers, in the body. In this way, a unique 'fingerprint' is produced for each patient, which reflects the disease.

In our article, we show which pattern of biomarkers (the 'fingerprint') to look for. From a technical point of view, we get a large number of data signals that say whether the marker is present and in what quantity. These measurements are then entered into a computer, which can present them to the doctors in a way that is easy to understand. It is this fingerprint which doctors could use in the future in clinical practice, explains Christer Wingren, who has spent most of the past decade developing the technique, and the past two years adapting it for SLE in particular.

According to Christer Wingren, a number of researchers around the world have attempted to develop something similar, but without success. The Lund researchers' success in the task is partly due to them having found a way to make the antibodies stable and thus more functional. The method has also become highly sensitive.

In order for the research to benefit patients, a number of key biomarker signatures, which form the basis for the test, have been patented. The findings have also been transferred to a newly started company, Immunovia, which was founded by Christer Wingren and three of his colleagues at the Department of Immunotechnology.

The research has its origins in the cancer research that Christer Wingren and a number of other researchers at the translational cancer centre CREATE Health work on. Together with Carl Borrebaeck, Dr Wingren uses an equivalent technological platform that can detect and diagnose different types of cancer. They have very promising data for predicting breast cancer recurrence and diagnosing pancreatic cancer.

Antibodies help protect monkeys from HIV-like virus, NIH scientists show

Thu, 05 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) WHAT: Using a monkey model of AIDS, scientists have identified a vaccine-generated immune-system response that correlates with protection against infection by the monkey version of HIV, called simian immunodeficiency virus (SIV). The researchers found that neutralizing antibodies generated by immunization were associated with protection against SIV infection. This finding marks an important step toward understanding how an effective HIV vaccine could work, according to scientists who led the study at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Scientists administered the SIV vaccine to half of the 129 monkeys in this study and a placebo vaccine to the other half. The scientists then gave each monkey up to 12 doses of one of two forms of SIV through rectal injection to simulate sexual exposure to the virus. The vaccine regimen did not protect the monkeys that received one form of SIV, but it reduced the rate of infection by 50 percent in the monkeys that received the other form of the virus.

To learn how the vaccine worked, the study team examined a variety of immune responses and certain genetic factors in the monkeys that the vaccine protected. The scientists found that SIV neutralizing antibodies and the activation of white blood cells known as helper CD4+ T cells correlated with the protective effect. Also, monkeys that expressed two copies of a gene known to help limit SIV replication were better protected by the vaccine than monkeys that did not, demonstrating that genetic factors can contribute to protection.

This study provides evidence that neutralizing antibodies are an important part of the immune response needed to prevent HIV infection. The ability of the vaccine regimen to protect monkeys from SIV infection is comparable to the results seen in the RV144 trial with 16,000 adult volunteers in Thailand; RV144 was the first HIV vaccine study to demonstrate a modest protective effect, reducing the rate of HIV infection by 31 percent. The new research also provides an animal model to better understand the immune basis for vaccine protection against lentiviruses, a subclass of viruses that includes HIV and SIV. This knowledge will help guide strategies for the future development of AIDS vaccines.

The SIV vaccine regimen used in this study was similar to an HIV vaccine regimen currently being tested in humans in the NIAID-funded clinical trial known as HVTN 505. Both vaccine regimens consist of priming with a vaccine made from DNA that encodes immunodeficiency virus proteins, followed by boosting with an inactivated cold virus (adenovirus) that contains immunodeficiency virus proteins.

Systematic effort helps hospital raise employee flu vaccination rates

Wed, 04 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A systematic effort to improve flu vaccination rates for healthcare workers has increased flu vaccinations rates from 59 percent to 77 percent at the University Health System (UHS) in San Antonio. A report detailing their interventions to increase vaccination was published in the June issue of Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America.

UHS raised its healthcare worker vaccination rate from 59 percent in 2009 to 77 percent in 2010 through quality improvement tools including vaccine kits to individual units, Grand Round presentations, enhanced staff awareness and a dashboard of vaccination rates of each program was promoted on the staff intranet. The increase places the UHS well above national average for healthcare worker vaccination, which tends to hover below 50 percent.

The vaccination push was spearheaded by a quality improvement team with a goal of reaching a vaccination rate of 80 percent. The team developed a list of possible reasons for low immunization rates, and created a set of interventions to combat them.

Under the improvement program, a vaccination kit was provided to each hospital unit so workers could take it without leaving their work area. Multiple educational conferences on the importance of vaccination were held, and a flu information website and blog were added to the health system's website. Hospital newsletters featured articles about immunization, including photographs of hospital leaders being vaccinated. The vaccination campaign was also promoted on telephone hold messages and computer screen savers. To monitor progress, vaccination rates by unit were sent to unit directors weekly and were available to all employees on the website.

The quality improvement tools and techniques the team used led to a significant improvement of the vaccination rate, said Dr. Jose Cadena, a member of the team and an author of the journal report. Our methodology allowed us to adapt and modify interventions over time, adjusting to challenges and opportunities for improvement that emerged.

Making sure healthcare workers are vaccinated is a major public health initiative. Vaccination of healthcare workers helps save patients' lives and reduces the spread of influenza in healthcare settings. It also protects the individual worker from falling ill during influenza outbreaks and from missing work, which further impacts patient care.

Mathematical models have shown that [healthcare worker] influenza vaccination could lead to a 40 percent decreased risk of patients acquiring influenza in the healthcare setting, which makes influenza vaccination a patient safety issue, Dr. Cadena and his colleagues write.

While the vaccination effort was successful in raising immunization rates substantially, it still fell short of its 80 percent goal. Making vaccination a condition of employment, as recommended recently by several professional societies including the Society for Healthcare Epidemiology of America, may be required to achieve higher rates of vaccination, Dr. Cadena said.

Terry Strom, M.D., honored by International Society of Nephrology

Fri, 29 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) BOSTON -- Terry Strom, MD, Co-director of the Transplant Institute at Beth Israel Deaconess Medical Center (BIDMC) and a leader in the field of immune tolerance research, was awarded the 2011 Alfred Newton Richards Award from the International Society of Nephrology during a program held earlier this month as part of the World Congress of Nephrology 2011 in Vancouver, Canada.

The award, which recognizes outstanding basic research in fields relevant to nephrology, is named in honor of Alfred Newton Richards, a renowned physiologist known for the development of the micropuncture procedure.

A Professor of Medicine at Harvard Medical School, Strom's career spans more than 30 years. To date, he has published more than 700 manuscripts in the fields of immunbiology and transplantation and has conducted pioneering investigations of the cellular and molecular bases of immune tolerance, the immune system's ability to recognize and tolerate the body's own cells and molecules in order to prevent organ rejection.

Dr. Strom's groundbreaking work in understanding the basic mechanisms underlying immunosuppressive agents has evolved to include the design of new therapeutics and the development of immune-tolerance therapies for patient care, notes BIDMC Chief Academic Officer Vikas Sukhatme, MD, PhD. His contributions have provided the field of nephrology with a critically important foundation in the biology of immune cells and tolerance, and his work is a tremendous example of how translational science can successfully move basic laboratory discoveries into promising new patient therapies.

Strom has elucidated the basic mechanisms of action of immunosuppressives and has designed new therapeutics, work leading to the development of anti-CD25 monoclonal antibodies. Two new therapies created in the Strom laboratory will soon enter human clinical trials, and his inquiries into the molecular signature of allograft rejection are under development for individualized patient care. Using newly developed molecular and imaging tools, the Strom laboratory is now revealing interactions between the adaptive and innate immune systems that are of both scientific and clinical importance.

A founding member and past president of both the American Society of Transplantation and the Clinical Immunology Society, Strom has trained over 90 doctoral and post-doctoral students who now hold prominent positions in academia and industry throughout the world. At BIDMC's Transplant Institute, which Strom co-directs with Laurence Turka, MD, PhD, he continues to guide and mentor 55 full-time investigators.

Strom was educated as an Illinois State Scholar, and went on to receive an NIH Career Development Award and was honored as Lilly Lecturer of the Royal College of Physicians.. Throughout his prolific career, Strom has been honored with numerous awards, including the 1997 Sandoz Transplant Established Investigator Award of the American Society of Transplant Physicians, the 2001 Roche American Society of Transplantation Distinguished Achievement Award and the Homer Smith Award from the American Society of Nephrology. He has served on the U.S. Senate-appointed Task Force on Transplantation.

BIDMC's Peter Weller, M.D., receives NIH MERIT Award

Wed, 27 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) BOSTON -- Peter Weller, MD, Chief of both the Division of Allergy and Inflammation and the Division of Infectious Diseases at Beth Israel Deaconess Medical Center (BIDMC), is the recipient of an NIH MERIT award from the National Institute of Allergy and Infectious Diseases. A Professor of Medicine at Harvard Medical School, Weller received the award for his longstanding grant, Human Eosinophils: Mechanisms of Functioning.

An acronym for the Method to Extend Research in Time, MERIT Awards are intended to provide long-term research grant support to scientists who have demonstrated a stellar record of research accomplishment. Rather than being awarded through an application process, MERIT awards are given at the discretion of the NIH, with fewer than five percent of investigators selected as MERIT recipients.

This is particularly rewarding because this was the first grant my laboratory received when I joined the former Beth Israel Hospital 27 years ago, says Weller. Over nearly three decades, our studies and those of others have peeled away the onion skin surrounding eosinophils to show that they are not so simple as once thought. This MERIT award will assure the funding to continue this work.

Eosinophils are one of five major types of white blood cells. Eosinophils serve roles in the body's immune system, but the functions of eosinophils are still poorly understood.

Higher-than-normal levels of eosinophils ecome problematic, explains Weller. This can occur when too many of the cells are recruited to a disease site or when the bone marrow overproduces eosinophils. Parasitic diseases, asthma and allergic reactions are among the more common causes of eosinophilia, the term used to describe high levels of eosinophils.

Weller's laboratory, in collaboration with the laboratory of Ann Dvorak, MD, a scientist in BIDMC's Department of Pathology, has greatly expanded the understanding of these white blood cells. In particular, their research has illuminated the role of eosinophils as granulocytes, cells containing preformed granules. The granules of eosinophils contain many proteins called cytokines that act to affect other cells. In eosinophils cytokines are already formed and can be released both from granules within eosinophils and also from granules that are present outside the cells.

In addition, work out of the Weller laboratory has helped to inform the clinical management of eosinophilic disorders and pointed to potential treatments for eosinophil-related diseases. In 2007, BIDMC's Division of Allergy and Inflammation developed the Center for Eosinophilic Disorders, an interdisciplinary program for the evaluation and management of these conditions. Javed Sheikh, MD, is the clinical Director of the Center.

BIDMC is one of only a few national institutions with established expertise in the research and treatment of eosinophil-associated diseases, explains Weller. Both ongoing NIH-funded basic research of eosinophils as well as clinically oriented studies that help us understand the roles of these white blood cells in disease have distinguished us in this field, and the eosinophil-focused programs at BIDMC have benefited from the sustained contributions of both research investigators and trainees and of expert clinicians.

Nasal spray vaccines more effective against flu

Mon, 11 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Nasal vaccines that effectively protect against flu, pneumonia and even bioterrorism agents such as Yersinia pestis that causes the plague, could soon be a possibility, according to research presented at the Society for General Microbiology's Spring Conference in Harrogate. Professor Dennis Metzger describes how including a natural immune chemical with standard vaccines can boost their protective effect when delivered through the nose.

The respiratory tract is a major entry site for various viral and bacterial pathogens. However there are few approved vaccines that can provide optimal protection against them due to the low immune response at muscosal surfaces such as the nasal passage.

Combining standard vaccines for respiratory pathogens with the immune chemical, interleukin-12 (IL-12) and delivering them intranasally to mice has been shown to induce high levels of protection. Vaccines against various respiratory pathogens were tested, including influenza virus, pneumococcal bacteria and Yersinia pestis - a Category A Biothreat. IL-12 is a natural immune chemical, known as a cytokine. It is a powerful stimulator of the immune response through its interactions with other immune chemicals and the white blood cells that produce them.

Professor Metzger from Albany Medical College, New York explains the significance of the findings. Infectious agents still account for around 25% of deaths worldwide and the major killers are acute respiratory infections. However, it is difficult to induce immunity at the site of entry and so standard vaccines are only partially protective, he said. Intranasal vaccination gets around this problem by inducing immunity in the pulmonary passage. This prevents initial infection as well as systemic complications. Up until now, nasal vaccination has only resulted in sufficient immune responses for very specific types of vaccine. We now have evidence that this method could work for a wide range of vaccines when IL-12 is included in formulation, said Professor Metzger.

Nasal vaccines could have a number of other advantages over vaccines that must be injected. Vaccination via a nasal spray is a non-invasive procedure that is easier than administering vaccines by injection. In addition our results have shown that antibodies induced by intranasal vaccination are effective not only in preventing infection but can also protect the pulmonary tract in a therapeutic manner after pathogen exposure, explained Professor Metzger. In the case of a bioterrorism threat or an influenza pandemic, this is significant. The next step is to perform clinical trials to determine whether including IL-12 with intranasal vaccines are effective in the human population.

Allergy vaccine is nothing to sneeze at

Mon, 21 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Monash University researchers are working on a vaccine that could completely cure asthma brought on by house dust mite allergies.

If successful, the vaccine would have the potential to cure sufferers in two to three doses.

Allergies to house dust mites is a leading cause of asthma and the respiratory condition affects more than 2 million Australians and costs more than $600 million in health expenditure each year.

Currently, people allergic to house dust mites must continually clean their environments to remove the microscopic creatures from soft furnishings to avoid an allergic attack. Medications can bring relief for some sufferers, but must be taken regularly. Others respond less well to medications.

Professor El Meeusen, who is working with Professor Robyn O'Hehir, both from the Faculty of Medicine, Nursing and Health Services, believes that a vaccine for people with house dust mite allergies will have a range of health and financial benefits for patients and the government.

We are aiming to develop a vaccine that can be completely delivered in two to three doses. That means a person suffering from a house dust mite allergy will be able to breathe easily from their final dose, Professor Meeusen said.

Allergies cost the Australian economy approximately seven billion dollars every year. The potential reduction in cost to the patient and to the government by eradicating a common allergy such as this is immense.

Professor O'Hehir has also made significant gains in developing a vaccine for people with peanut allergies. Currently there is no specific treatment for peanut allergy with avoidance and emergency treatment of anaphylaxis with adrenaline as the only options. Allergen immunotherapy is available for selected patients with house dust mite allergy but typically injections need to be given regularly for three to five years.

This method of immunisation is quite precarious, because modern medicine still isn't entirely sure how it really works, Professor Meeusen said.

The immunisation is administered in small doses. Too much can cause anaphylactic shock. It's a very fine line.

Laboratory testing has shown that a genetic predisposition exists to be allergic to more than one allergen.

We have already found that being allergic to peanuts also represents the likelihood of developing an allergy to house dust mites, Dr Meeusen said.

In humans it is difficult to look at how the very early stages of allergy occur, because you don't get to see the patient until it is well developed in their allergic response. Our testing enables us to look at the very first time that our models are exposed to the allergen.

From there, the scientists can see which models are going to develop an allergy and which are not, to determine the difference between them.

This research involves using the scientist's knowledge of normal vaccines for infectious diseases to better understand how allergy vaccines work in order to develop more effective and safer products.

New vaccine technology protects mice from hepatitis C virus

Wed, 23 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Immunology: Three percent of the world's population is currently infected by hepatitis C. The virus hides in the liver and can cause cirrhosis and liver cancer, and it's the most frequent cause of liver transplants in Denmark. Since the virus mutates strongly, we have no traditional vaccine, but researchers at the University of Copenhagen are now the first to succeed in developing a vaccine, which provides future hope for medical protection from this type of hepatitis.

The hepatitis C virus (HCV) has the same infection pathways as HIV, says Jan Pravsgaard Christensen, Associate Professor of Infection Immunology at the Faculty of Health Sciences, University of Copenhagen.

Approximately one newly infected patient in five has an immune system capable of defeating an acute HCV infection in the first six months. But most cases do not present any symptoms at all and the virus becomes a chronic infection of the liver.

Poorly treated donor blood and dirty needles are sinners

Every year three or four million more people become infected and the most frequent path of infection is needle sharing among drug addicts or tattoo artists with poor hygiene, such as tribal tattoo artists in Africa and Asia. Fifteen percent of new infections are sexually transmitted, while ten percent come from unscreened blood transfusions.

According to Allan Randrup Thomsen, Professor of Experimental Virology, Egypt is one country with a high incidence of HCV. This is particularly due to lack of caution in the past with regards to screening donated blood for the presence of this virus, he says.

China, Brazil, South East Asia and African states south of the Sahara also have a high incidence, while the disease is also spreading through Eastern Europe, especially Romania and Moldova.

HCV mutates too fast for traditional vaccines

The new vaccine technology was developed by Peter J. Holst, a former PhD student now a postdoc with the Experimental Virology group, which also includes Professor Allan Randrup Thomsen and Associate Professor Jan Pravsgaard Christensen.

The technology works by stimulating and accelerating the immune system, and showing the body's defence mechanisms of the parts of the virus that are more conserved and do not mutate as fast and as often, such as the molecules on the surface of the HCV.

Basically, traditional vaccines work by showing the immune defences an identikit image of the virus for which protection is desired. Antibodies then patrol all entrances with a copy of this image and are able to respond rapidly if the virus attempts to penetrate. But the influenza virus mutates its surface molecules and in the course of a single season it takes on a new guise so that it no longer resembles the original identikit image and the vaccine loses its efficacy.

Professor Randrup explains, Mutations of the surface are Darwin at work, so to speak. The virus tries to outwit the immune defences and if it succeeds we get ill, and our response is new vaccines.

Associate Professor Pravsgaard Christensen says, Viruses like HCV mutate so rapidly that classical vaccine technology hasn't a chance of keeping up. But the molecules inside the virus do not mutate that rapidly, because the survival of the virus does not depend on it.

New vaccine technology gives immune system information about virus' stable parts

According to Professor Randrup, the body's natural defences usually don't see these internal virus molecules until the virus has taken residence in the body.

Our cells constantly show random samples of their contents to the immune defence patrols, and if there are enough foreign bodies among them, the alarm is triggered, says Professor Randrup.

The cells display fragments of the surface molecules and internal genes from the virus, and if you show the immune defences a kind of X-ray of the inner genes, they will respond. Actually, the response is extremely potent, and one of the things it does is summon the specialised CD8 killer cells.

We took a dead common cold virus, an adenovirus that is completely harmless and which many of us have met in childhood, Associate Professor Pravsgaard Christensen explains.

We hid the gene for one of the HCV's internal molecules inside it. At the same time we attached a special molecule on the internal molecule so that when the cells of the mouse body tried to take a sample, they would extract a more extensive section. The immune defences would then be presented with a larger section of the molecule concerned. You may say that the immune defences were given an entire palm print of the internal genes instead of just a single fingerprint.

This strategy resulted in two discoveries from the team. Firstly, the mice were vaccinated for HCV in a way that meant that protection was independent of variations in the surface molecules of the virus. Secondly, the immune defences of the mice saw such an extensive section of the internal molecule that even though some aspects of it changed, there were still a couple of impressions the immune defences could recognise and respond to.

The new technology to be tested in monkeys

Another virus that mutates its surface molecules with extreme rapidity is HIV. It changes skin in the space of 24 hours, and like HCV, we do not yet have a cure or a vaccine. The researchers think that HIV originally migrated to man from monkeys in the 1930s, when it was the simian Immunodeficiency virus that still circulates among a number of species of wild African monkeys.

The Danish Medical Research Council (DMRC) has given postdoc Peter Holst a grant to test our technology for a SIV vaccine for macaque monkeys in the US, says Associate Professor Pravsgaard Christensen.

The University of Copenhagen is also currently negotiating the sale of the patent for the process so that the technology can be developed for use in human vaccines.

The discovery of an effective HCV vaccine has just been published in the

Modell Chair in Pediatric Immunology established

Wed, 16 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) The Children's Hospital of Philadelphia has announced the establishment of the Jeffrey Modell Endowed Chair in Pediatric Immunology Research.

A ceremony on Feb. 15 at the Hospital's Ruth and Tristram Colket, Jr. Translational Research Building recognized the first holder of the chair, pediatric immunologist Jordan S. Orange, M.D., Ph.D. The chair's $2 million endowment will allow Dr. Orange to break new ground in his ongoing research. Dr. Orange is internationally prominent for studying and treating primary immunodeficiency disorders in children.

We appreciate the generosity of Fred and Vicki Modell for their continuing support of Dr. Orange's important work, said Steven M. Altschuler, M.D., chief executive officer of The Children's Hospital of Philadelphia. This gift will advance the efforts by Dr. Orange and the Jeffrey Modell Foundation to translate scientific knowledge into real improvements in children's lives.

Dr. Altschuler presented the endowed chair to Dr. Orange. Fred and Vicki Modell spoke at the ceremony, as did Alan R. Cohen, M.D., physician-in-chief of Children's Hospital.

Dr. Orange is already the director of the Jeffrey Modell Diagnostic Center at Children's Hospital, a premier program among dozens of centers worldwide that have been established by the Jeffrey Modell Foundation to provide expert diagnosis and treatment to patients with primary immunodeficiency diseases. Co-founded by Fred and Vicki Modell in 1986, the Foundation honors the memory of their son Jeffrey, who died at age 15 from complications of primary immunodeficiency.

Primary immunodeficiencies include over 150 genetic disorders in which the immune system's ability to produce specific antibodies to fight off infection is greatly impaired or absent. Early diagnosis and treatment are essential to preventing recurrent infections from doing permanent damage.

Dr. Orange's research focuses on the biology of natural killer cells and the innate immune system, with a clinical focus on primary immunodeficiency disease. He has received funding from the National Institute of Allergy and Infectious Diseases and the United States Immunodeficiency Network to support his laboratory work, and has authored over 100 scientific publications. In 2009 the American Philosophical Society awarded him the Judson Daland Prize for Clinical Investigation, which honors outstanding achievements in patient-oriented research.

Over the past decade, Dr. Orange has redefined the field of human natural killer cell deficiencies in various genetic disorders. He recently collaborated with European researchers who achieved marked clinical improvements in using gene therapy to treat young children with Wiskott-Aldrich syndrome, a rare but often severe immunodeficiency disorder. At Children's Hospital, he is currently conducting clinical trials testing the use of immunotherapy to boost immune function in children with Wiskott-Aldrich syndrome.

In addition to his duties at The Children's Hospital of Philadelphia, Dr. Orange is on the Pediatrics faculty of the University of Pennsylvania School of Medicine and is an elected member of the American Society for Clinical Investigation.

Saint Louis University findings: Don't pitch stockpiled avian flu vaccine

Wed, 09 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) ST. LOUIS -- A stockpiled vaccine designed to fight a strain of avian flu that circulated in 2004 can be combined with a vaccine that matches the current strain of bird flu to protect against a potential pandemic, researchers from Saint Louis University's Center for Vaccine Development have found.

The findings suggest public health officials can get a jump on fighting a pandemic caused by avian flu virus because they won't have to wait for a vaccine that exactly matches the current strain of bird flu to be manufactured. They can begin immunizing against the bird flu by giving an injection of a vaccine made from a related, yet mismatched strain of flu to prime the body for a second shot of a vaccine that matches the current strain.

A cornerstone of pandemic planning is the development of effective vaccines against avian influenza infection, said Robert Belshe, M.D., director of the Center for Vaccine Development at Saint Louis University and the lead author of the paper.

The results of the present study confirm the usefulness of vaccination with an H5 strain that isn't the current dominant strain.

Avian flu -- or H5N1 -- is a highly infectious and deadly virus that circulates in birds and has the potential to genetically mutate and jump between species to infect humans. Because people lack immunity to the virus, public health officials are concerned that the virus can spread quickly to become a pandemic outbreak.

In anticipation of a bird flu pandemic, in 2004 the U.S. government stockpiled 20 million doses of vaccine against the Vietnam strain of avian influenza, which then was the dominant strain of the virus. But the avian flu changes quickly and since then, a different strain of bird flu, known as the Indonesia strain, has replaced the Vietnam strain as the prominent circulating avian flu.

Researchers studied both the vaccine against the Vietnam strain and an investigational vaccine designed to protect against the Indonesia strain in 491 healthy adults. They measured the body's immune response to different combinations of the two avian flu vaccines. They also looked at how long to wait between giving the first and second doses of vaccine.

They found that two doses of vaccine are needed to provide protection against the avian flu. Giving the stockpiled Vietnam avian flu vaccine as the first dose primed the body's system so that a follow up dose of the investigational Indonesia avian flu vaccine triggered a heighten immune response. The immune response to both strains of avian influenza became more robust as the injections of vaccine were spaced further apart.

The longer 180-day interval between priming and boosting vaccine doses gave the best antibody responses, although in a fast-moving pandemic, this is unlikely to be an option, Belshe said.

The most surprising thing we discovered was the value of time. It's incredible how much stronger response you get at six months. There's something going on there that we know nothing about and is a very interesting area for future research.

Other areas of future of research include studying the vaccines in children and adults and examining the use of adjuvants, substances that stimulate the immune response to produce more antibodies so less vaccine is needed, Belshe added.

Public health officials might consider immunizing those who are at risk of serious side effects from influenza with the stockpiled avian flu vaccine, he said.

The vaccine could prime the body's immune system to mount a defense if the person is exposed to the avian flu virus and could be a powerful weapon in the fight against a pandemic, Belshe said.

Study suggests why HIV-uninfected babies of mothers with HIV might be more prone to infections

Tue, 08 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Babies whose mothers have HIV, but who are not HIV-infected themselves, are born with lower levels of specific proteins in their blood called antibodies, which fight infection, compared with babies not exposed to HIV, a new study has found. The finding, published today in the Journal of the American Medical Association, might explain in part why uninfected babies born to women with HIV have a higher risk of illness and death early in life.

Major programmes using antiretroviral drugs have successfully reduced the rate of mother-to-child transmission of HIV from 20-30 per cent to around five per cent in some areas of South Africa and to less than one per cent in developed countries. However, HIV-uninfected infants born to HIV-infected mothers in Africa are more prone to infections such as pneumonia and meningitis, and up to four times more likely to die before their first birthday, compared with babies born to HIV-negative women. Socioeconomic factors are thought to account partially for this discrepancy but differences in the babies' immune systems might also be important.

The new study, by scientists from Imperial College London and Stellenbosch University in South Africa, found that babies born to HIV-infected mothers had significantly lower levels at birth of antibodies against a range of bacterial infections (Hib, pertussis, pneumococcus and tetanus).

Antibodies, which bind to specific pathogens and direct immune cells to attack them, are transferred from mother to child through the placenta late in pregnancy. The study found lower levels of some specific antibodies in mothers with HIV, but also that less antibody is transferred from mother to child across the placenta.

Despite their low antibody levels at birth, the babies in the study responded well to vaccination: they produced similar levels of antibody to some vaccines and higher levels to other vaccines.

It's likely that lower antibody levels in these babies contributes to lower protection against infection before the babies have received their vaccines, said Dr Christine Jones from the Department of Paediatrics at Imperial College London, the study's first author. Although they appear more vulnerable in the first few months of life, the good news is that these babies respond well to vaccination. We might be able to protect them even better against infections, either by vaccinating them earlier or by vaccinating the mother in pregnancy. More research will be needed to establish what the best way of protecting these babies might be.

The study involved 109 HIV-infected and uninfected mothers in a community health centre in Khayelitsha, a rapidly-growing township in Cape Town, South Africa. The researchers measured antibody levels in the mothers at delivery and the infants at birth. They also assessed how the babies responded to routine vaccination by measuring the babies' antibody levels at four months, after they had received their routine vaccines.

Amongst the HIV-negative women in the study, a third also had low antibody levels, showing that protection against infection in their babies might also not be optimal in some women, who are otherwise perfectly healthy.

Genes of the immune system are associated with increased risk of mental illness

Mon, 07 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Genes linked to the immune system can affect healthy people's personality traits as well as the risk of developing mental illness and suicidal behaviour, reveals a thesis from the University of Gothenburg, Sweden.

Inflammation is part of the immune system and is responsible for defending humans against infection as well as fascilitating the healing of injuries, and is therefore vital for our survival. Research has demonstrated that inflammatory processes also have other roles to play as inflammatory substances produced by the body influence mechanisms in the brain involving learning and memory.

Inflammatory substances produced in moderate quantities in the brain can be beneficial during the formation of new brain cells, for example. However, an increase in the levels of these substances as is the case during illness, can result in damage to the brain.

Previous studies have shown that individuals suffering from various mental illnesses have an increased peripheral inflammation, but the reason behind this increase is not known, says Petra Suchankova Karlsson, who wrote the thesis. It has been suggested that the stress that goes with mental illness activates the body's immune system, but it is also possible that inflammation in the body affects the brain, which in turn results in mental illness.

Previous studies have focused on how environmental and psychological factors affect the immune system's impact on the brain. Suchankova's thesis presents, for the first time, results that suggest that several different genes linked to the immune system are associated with healthy people's personality traits. It also demonstrates that some of these genes are associated with an increased risk of developing schizophrenia or suicidal behaviour.

One of the things we studied was a gene variant that increases impulsiveness in people who carry it, says Suchankova. We already knew that the risk of attempting suicide is higher in impulsive people and therefore analysed this gene variant in a group of patients who had attempted to take their life. We found that these patients more often carried the particular gene variant when compared to the general population which meant that this variant was not only associated with increased impulsiveness in healthy individuals but also with increased risk of suicidal behaviour.

The change in the levels of inflammatory substances in the blood of patients suffering from a mental illness as previously noted may have been caused by inflammation-related genes affecting the risk of mental illness, rather than the illness itself leading to a change in levels, as is traditionally believed.

It could well be that some variants of the genes play a role in the development of mental illness by controlling how the brain is formed, perhaps during the embryonic stage, or by affecting the transfer of signal substances, says Suchankova.

The results of this thesis support the proposed role of the immune system in mental illness, and could be used as a basis for further studies that, it is hoped, will lead to the development of new treatment methods.

The thesis has been successfully defended.

Patent awarded for method to dampen immune response

Tue, 18 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) National Jewish Health has been issued a US patent claiming a method to desensitize B cells by inactivating antigen receptors on their surfaces. The method, discovered by John Cambier, PhD, Chairman of the Integrated Department of Immunology at National Jewish Health, holds promise for treatment of B-cell mediated diseases, such as lymphoma and leukemia, rheumatoid arthritis, lupus and rejection of organ transplants. This therapeutic approach has the potential advantage of inactivating B cells instead of killing them as current treatments do. Therefore, this potential therapy could be more rapidly adjusted in response to the changing needs of patients.

B cells are a crucial part of the adaptive immune response, responsible for making antibodies that can neutralize and destroy pathogens. Several diseases, however, are associated with malfunction of B cells. For example, B cells can turn cancerous in diseases such as lymphoma and leukemia. In autoimmune diseases, such as rheumatoid arthritis or lupus, B cells turn against their own bodies and attack their tissues. B cells can also attack transplanted organs, which they recognize as foreign and potentially harmful.

The recently issued patent describes a method to inactivate B cells by disassembling their B-cell receptors. B cells begin producing antibodies after their B-cell receptors encounter foreign protein fragments, known as antigens. The B-cell receptor contains two distinct subunits; a receptor, which engages antigens, and a transducer, which transmits an activating signal to the interior of the cell.

About a decade ago, Dr. Cambier's laboratory, discovered that the two subunits could be separated, which disables the B cell's ability to recognize antigens and produce antibodies. In 2003, National Jewish Health received a patent (#6,503,509) for this method of B -cell desensitization. The most recent patent (#7,825,224) related to this technology claims the use of antibodies that bind to the transducer subunit of the receptor to inactivate the B cell.

Dr. Cambier's laboratory has recently developed several antibodies against one of the transducer elements, CD79, that have already yielded promising results.

In contrast to current therapies for B-cell diseases, this method does not kill B cells, it merely inactivates them, said Dr. Cambier. That could potentially allow for greater flexibility in using a therapy that is developed with this technology. Instead of the months to years it sometimes takes for the effects of current therapy to wane, our method could be reversed within days.

Dr. Cambier has recently received research funding from the State of Colorado and National Jewish Health through the Bioscience Discovery Evaluation Grant Program to further develop this promising technology.

This research funding underlines our commitment to promote the translation of our scientists' research findings into therapeutic or diagnostic products that can ultimately help patients worldwide, said Emmanuel Hilaire, PhD, Manager of the Technology Transfer Office at National Jewish Health. National Jewish is currently exploring various commercialization venues for its licensing, including the creation of a start-up company in Colorado.

Researchers unzip MRSA and discover route for vaccine

Sun, 16 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) University of Rochester Medical Center orthopaedic scientists are a step closer to developing a vaccine to prevent life-threatening methicillin-resistant staphylococcus aureus (MRSA) infections following bone and joint surgery.

Other MRSA vaccine research has failed to produce a viable option for patients because of the inability to identify an agent that can break through the deadly bacteria's unique armor. Most other research has targeted the surface of the bacteria, but the URMC team discovered an antibody that reaches beyond the microbe's surface and can stop the MRSA bacteria from growing, at least in mice and in cell cultures.

The Orthopaedic Research Society invited URMC researchers to present their findings on Jan. 16, 2011, at the ORS annual meeting in Long Beach, Calif. The team is led by Edward M. Schwarz, Ph.D., professor of Orthopaedics and associate director of the URMC Center for Musculoskeletal Research. John Varrone, a second-year graduate student in Schwarz's lab, will discuss the data at ORS and the ongoing search for attractive molecular candidates for use in a vaccine.

Staph infection is the leading cause of osteomyelitis, a serious bacterial infection of the bone. Up to half of these infections are due to MRSA, a particular strain of staph known as a superbug because of its antibiotic resistance. MRSA causes nearly 500,000 hospitalizations and 19,000 deaths a year in the United States. Although improvements in surgical techniques and use of prophylactic antibiotics prevents some MRSA infections, osteomyelitis is expected to remain a serious problem in the future as people live longer and request more joint replacements and reconstructive surgery.

Management of MRSA infections due to bone and joint surgery is very challenging, Schwarz said, and therefore a vaccine to prevent the infection is badly needed.

It is difficult to pin down the source of most post-surgical MRSA infections, but the health and financial consequences are severe. Hospital stays can last up to six months. Standard treatment includes removing the MRSA-colonized prosthetic joint replacement, then an extensive washing and draining of the infected area in an attempt to clear out all bacteria before it seeds in nearby tissue and bone. Antibiotic spacers are usually placed near the joint for six to eight weeks.

A second joint replacement is an option only if the antibiotic-spacer treatment is successful and the health of the patient remains stable. However, the re-infection rate is very high (40 to 50 percent) and remains a risk for months or even years after the initial assault. In some cases the patient never fully regains the use of the infected joint, said Regis O'Keefe, chief of Orthopaedics at URMC and an expert in the treatment of MRSA.

It's essential that we have mechanisms in place to prevent this awful infection, O'Keefe said. We are very excited about our vaccine research. It'll have a phenomenal impact on individuals locally and across the country if we are successful.

Looking into the immune system of bacteria

Mon, 27 Dec 2010 10:10:54 PST

( from http://www.rxpgnews.com ) Studying how bacteria incorporate foreign DNA from invading viruses into their own regulatory processes, Thomas Wood, professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, is uncovering the secrets of one of nature's most primitive immune systems.

His findings, which appear in "Nature Communications," a multidisciplinary publication dedicated to research in all areas of the biological, physical and chemical sciences, shed light on how bacteria have throughout the course of millions of years developed resistance to antibiotics by co-opting the DNA of their natural enemies—viruses.

The battle between bacteria and bacteria-eating viruses, Wood explains, has been going on for millions of years, with viruses attempting to replicate themselves by – in one approach – invading bacteria cells and integrating themselves into the chromosomes of the bacteria. When this happens a bacterium makes a copy of its chromosome, which includes the virus particle. The virus then can choose at a later time to replicate itself, killing the bacterium—similar to a ticking time bomb, Wood says.

However, things can go radically wrong for the virus because of random but abundant mutations that occur within the chromosome of the bacterium. Having already integrated itself into the bacterium's chromosome, the virus is subject to mutation as well, and some of these mutations, Wood explains, render the virus unable to replicate and kill the bacterium.

With this new diverse blend of genetic material, Wood says, a bacterium not only overcomes the virus' lethal intentions but also flourishes at a greater rate than similar bacteria that have not incorporated viral DNA.

"Over millions of years, this virus becomes a normal part of the bacterium," Wood says. "It brings in new tricks, new genes, new proteins, new enzymes, new things that it can do. The bacterium learns how to do things from this.

"What we have found is that with this new viral DNA that has been trapped over millions of years in the chromosome, the cell has created a new immune system," Wood notes. "It has developed new proteins that have enabled it to resists antibiotics and other harmful things that attempt to oxidize cells, such as hydrogen peroxide. These cells that have the new viral set of tricks don't die or don't die as rapidly."

Understanding the significance of viral DNA to bacteria required Wood's research team to delete all of the viral DNA on the chromosome of a bacterium, in this case bacteria from a strain of E. coli. Wood's team, led by postdoctoral researcher Xiaoxue Wang, used what in a sense could be described as "enzymatic scissors" to "cut out" the nine viral patches, which amounted to precisely removing 166,000 nucleotides. Once the viral patches were successfully removed, the team examined how the bacterium cell changed. What they found was a dramatically increased sensitivity to antibiotics by the bacterium.

While Wood studied this effect in E. coli bacteria, he says similar processes have taken place on a massive, widespread scale, noting that viral DNA can be found in nearly all bacteria, with some strains possessing as much as 20 percent viral DNA within their chromosome.

"To put this into perspective, for some bacteria, one-fifth of their chromosome came from their enemy, and until our study, people had largely neglected to study that 20 percent of the chromosome," Wood says. "This viral DNA had been believed to be silent and unimportant, not having much impact on the cell.

"Our study is the first to show that we need to look at all bacteria and look at their old viral particles to see how they are affecting the bacteria's current ability to withstand things like antibiotics. If we can figure out how the cells are more resistant to antibiotics because of this additional DNA, we can perhaps make new, effective antibiotics."

New lung disease network to benefit patients and boost UK economy

Wed, 01 Dec 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Scientists and clinicians in Nottingham are to work more closely with industry to develop new ways of diagnosing and treating lung disease.

Nottingham has been chosen as one of just nine centres across the UK to host a Government-spearheaded 'Therapeutic Capability Cluster', which aims to forge closer links between academia, the NHS and the life sciences industry to speed up the process of getting new drugs from lab bench to bedside.

The new cluster will draw on the world-leading research expertise of scientists at The University of Nottingham and clinical excellence of Nottingham University Hospitals NHS Trust to help pharmaceutical companies develop clinical trials for potential new treatments for a range of respiratory diseases.

Professor Alan Knox, Professor of Respiratory Medicine at The University of Nottingham and Director of the Nottingham Respiratory Biomedical Research Unit, said: This is an exciting opportunity to develop new treatments for patients with lung disease.

The clinical trials that will result from this new cluster will offer respiratory patients in Nottingham the chance to access new drugs being developed to treat their illness and to take part in research which could potentially benefit many more people like themselves.

Collectively in Nottingham and the other cluster centres we have a unique mass of respiratory research expertise. In terms of industry, the specialist guidance we can provide on the design of studies and clinical trials will offer added value to companies planning early phase studies of new medicines. By encouraging companies to carry out these studies in the UK this will stem the loss of business overseas and strengthen the UK economy.

Dr Brian Thompson, Nottingham University Hospitals' Director of Research and Development, said: This relationship between the NHS, academia and the life sciences industry is precisely the innovation model we have been striving to promote for Nottingham.

It presents a perfect opportunity to coalesce our efforts around the ideal partnership structure for biomedical sciences, starting with respiratory diseases.

In recent years, few new chemical compounds have been discovered to effectively treat respiratory illnesses such as asthma and Chronic Obstructive Pulmonary Disease and new therapies have relied upon modifications of existing molecules.

It is hoped that the cluster will support initiatives led by the MRC and NIHR to identify treatments which may be effective for smaller groups of patients suffering from particular symptoms within the overarching diagnosis of one disease, such as asthma.

It will also go hand-in-hand with an initiative sponsored by the MRC and Association of British Pharmaceutical Industries to devise robust new methods of studying human cell systems for the development of drugs for asthma and COPD before they go into clinical trials.

The Respiratory Capability Cluster is supported by the Medical Research Council (MRC), the National Institute for Health Research (NIHR), the Public Health Agency, Welsh Assembly Government, Technology Strategy Board and Chief Scientist Office.

The clusters were born out of the Life Sciences Blueprint published by the Government in July 2009, which recognised the need for a new approach to collaboration in the life sciences which would provide opportunities for partnership between the academic and health service communities and the commercial sector for patient and economic benefit.

It will help to standardise procedures for studies, fast track approval for clinical trials and, hopefully, result in the quicker development of treatments which are also more effective.

Mother Nature and bioterrorists: Rochester battles both with $11.9 million award

Wed, 10 Nov 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Flu viruses are a great threat, whether they stem from Mother Nature or are modified by human hands to create a deadly bioweapon. The University of Rochester Medical Center will tackle both scenarios head on with a five-year contract, totaling approximately $11.9 million, from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The contract will further research into how we can use computer modeling to find ways of boosting human immune responses against and identify new areas of investigation into treatments for a variety of potentially lethal viruses.

This type of research is extremely important because it is going to make the United States better, stronger and faster at developing new vaccines and therapies for flu infections that we don't yet have vaccines for, said Martin Zand, M.D., Ph.D., co-director of the Center for Biodefense Immune Modeling and medical director of Kidney and Pancreas Transplant Programs at the University of Rochester Medical Center.

Throughout the five year contract, researchers will design mathematical models and simulation tools to study how the immune system responds to flu vaccines, attempting to uncover why some people have a good response to a vaccine and others don't. Using data from mice and humans, they hope to use these models to simulate different flu scenarios and test medical interventions that might be developed to limit the extent of a dangerous flu infection in people.

The wonderful thing about models is that we can get some idea of how a virus might evade the immune system, how the immune system might respond, and how we can enhance the immune response without ever having to create or live through a pandemic or bioterrorist attack, Zand noted.

The contract is a five-year renewal of the Center for Biodefense Immune Modeling at the Medical Center, which was initially funded with a $10 million contract in 2005 as part of NIAID's Modeling Immunity for Biodefense program. Researchers spent the past five years developing models of different flu infections, and now they will use this knowledge to further model and study animal and human immune responses to new and existing flu vaccines.

In addition to the modeling and experimental work, the contract will fund development of new mathematical approaches and software tools that will be made available to the entire research community.

NIAID also awarded contracts to three other centers as part of the Immune Modeling for Biodefense program: Mount Sinai Medical Center School of Medicine, Duke University and the Virginia Bioinformatics Institute at Virginia Polytechnic Institute and State University.

This particular NIH program differs from past NIH-funded immunology research by its emphasis on mathematical modeling, combined with cutting-edge immunology experiments and the development of new computational tools for immunology research. Such approaches allow scientists to look at the behavior of the whole immune system over time, as opposed to getting a snapshot of one or two points in time, such as after someone is vaccinated or infected with the flu. Researchers believe this more comprehensive and mathematically-based approach will yield greater understanding of how the flu and other viruses attack the body, how the immune system reacts and how we might be able to intervene.

Using models and simulations is commonplace in many industries, such as the auto and airline industries, where manufacturers test designs before they actually produce cars and planes, said Hulin Wu, Ph.D., co-director of the Center for Biodefense Immune Modeling and professor in the Department of Biostatistics and Computational Biology at the Medical Center. Biomedical research has adopted this same way of doing business, using models to gather information that will help scientists design the most effective vaccines and therapies in the shortest amount of time.

Wu added that models are essential because many immunology experiments can't be done in a lab: We can't infect people with a new strain of the flu virus, but we can use a mathematical model of a human in the computer to learn more about the virus and test potential therapies.

Biomedical research that integrates methods and techniques from mathematical modeling, biocomputing, biostatistics and bioinformatics is an emerging discipline known as systems biology, and is helping fuel biomedical science discoveries in the new century. Wu and Zand are utilizing a systems biology approach to help guide their research.

An example of a study Wu and Zand will begin this year involves collecting blood samples from small groups of people each day, for 11 days after they receive the seasonal flu vaccine. Each day, these samples will be analyzed in a battery of cutting-edge cell, protein and gene expression tests. The research team will do a similar study in mice and compare the human and animal data to garner valuable information about where antibodies or immune cells are and when, what genes are expressed in different places and what cellular markers are present following vaccination: This detailed data will then be used to create models that predict responses to current and future flu vaccines in mice and hopefully one day in people.

Lupus patients: The doctor, nurse and social worker are here to see you

Tue, 09 Nov 2010 05:00:00 PST

( from http://www.rxpgnews.com ) The benefits of collaborative, multidisciplinary care of patients with complex autoimmune diseases like lupus and multiple sclerosis are just beginning to be appreciated by physicians. Hospital for Special Surgery in New York will present evidence of the advantages of such a specialized disease center dedicated to comprehensive lupus care at the 74th Annual Meeting of the American College of Rheumatology in Atlanta.

Every time a patient comes in for an appointment, I am able to greet them personally, to find out what is going on in their lives and what may be bothering them that day, said Pretima Persad, M.P.H., manager of the Mary Kirkland Center for Lupus Care. We provide patients with care that is personalized to their particular situation, such as pregnancy or psychological concerns. We want them to know that their care team is really listening to them.

In addition to check-ins with Ms. Persad before every appointment, patients meet with a nurse and a social worker at Hospital for Special Surgery. Patients feel that they are being provided with an umbrella of care, according to Dr. Doruk Erkan, co-director of the Mary Kirkland Center. In this centralized environment, the patient is the number one focus. We are treating the patient as a whole, not just the disease.

The physicians, nurses, social workers and research coordinators at the Mary Kirkland Center for Lupus Care at Hospital for Special Surgery know that treating patients with lupus requires the coordinated efforts of a number of health care professionals. Each patient-care team member brings individual expertise but is aware that treatment of this chronic disease requires concurrent battle on multiple fronts, said Dr. Kyriakos Kirou, co-director of the center. They are trained to expect the unexpected and to support patients who may be confused and frightened.

Lupus causes the immune system to attack the body's own cells, resulting in inflammation and tissue damage. The disease is unpredictable and periods of illness follow periods of remission with barely a warning that skin, heart, joints, lungs or other parts of the body are being harmed. Nine out of ten patients with lupus are female and the disease can affect virtually any organ system in the body, including the nervous, circulatory and lymphatic systems.

The Mary Kirkland Center is an ideal place for research coordinators to recruit patients for clinical studies, Ms. Persad noted. She stressed that, while participating in research studies that place a focus on the disease can be daunting, the patients know and trust the staff well enough that they are comfortable getting involved.

The Mary Kirkland Center also instituted a formalized educational experience for professionals. Physicians attend lectures focused on lupus and related conditions so that they are able to understand lupus from the perspective of other specialties, according to Ms. Persad. Rheumatologists specializing in lupus care play an integral part in these lectures and in lupus case conferences.

New assessment tool helps shed light on lupus in kids worldwide

Tue, 09 Nov 2010 05:00:00 PST

( from http://www.rxpgnews.com ) A newly designed tool is helping researchers shed light on the quality of life (QoL) of children with lupus around the world, according to research presented at the American College of Rheumatology (ACR) annual meeting, held Nov. 7-11, in Atlanta.

Lupus is a significant disease with a major impact on QoL of children around the world. This is a chronic, unremitting disease that we need to get under better control, said Thomas J.A. Lehman, M.D., chief of Pediatric Rheumatology at Hospital for Special Surgery, who was involved with the study. We have done better at treating the disease and lessening the impact of the disease on children around the world, but we still lack a cure.

Lakshmi Nandini Moorthy, M.D., a pediatric rheumatologist in the ambulatory care center in the Department of Medicine at HSS who served as principal investigator of the study, said the study had a couple of take home points. Parents across multiple cultures seem to perceive that children with lupus have a lower quality of life than their children actually report. That could reflect a greater perception of their child's vulnerability or a parent's own quality of life or anxiety, said Dr. Moorthy, who is also chief of the Division of Pediatric Rheumatology at the Robert Wood Johnson Medical School at the University of Medicine and Dentistry of New Jersey. A second interesting point is that in this particular study, the children in an Asian country report a better quality of life than children in Europe or South America. We need to gather more data and more details to confirm this result.

The study was conducted using a 26 item health-related quality of life assessment tool developed by Dr. Moorthy several years ago while she was a pediatric rheumatology fellow at HSS. Before the SMILEY tool (Simple Measure of Impact of Lupus Erythematosus in Youngsters), there was no good way to measure quality of life in lupus patients. The only tools available were general surveys and those that were developed for juvenile arthritis. Lupus is a very chronic, fluctuating disease. In one person, it can affect their eyes, in another it can affect their kidney or brain, and in another person it can just be a rash that affects their appearance, Dr. Moorthy said. We needed a scale that was general enough to capture all that, but at the same time be specific enough to capture the effects of lupus.

So, Dr. Moorthy developed SMILEY, which includes 26 questions, all of which have five possible responses corresponding with facial expressions ranging from very sad to happy. It is easy to use and score. Questions include how does lupus make you feel about going to school, how does lupus make you feel about the way you look, how does lupus make you feel about your future, and how worried are you about the side effects of your medications.

For the study presented at ACR, 125 children and parents participated from South America (Brazil and Argentina), Europe (Italy, Spain, Netherlands), and Asia (China). Children and parents filled out SMILEY as well as generalized quality of life and physical function scales. Physicians also filled out surveys gauging severity of disease and impact of the disease.

By looking at the SMILEY scores, we can see that lupus has a major impact on the quality of life of children everywhere in the world, and while there are cultural differences in exactly how it impacts them, it has a major impact everywhere, Dr. Lehman explained. The quality of life scores appear to be higher in Asia than in Europe, which was second highest, and South America. We want to look further into why the quality of life scores are different in Asia and how cultural factors and family expectations may play a role in this. Are there differences in how families cope with an ill child that may have a major impact on the quality of life scores and what can we learn from this?

Hospital for Special Surgery scientists share advances in lupus and related conditions

Sun, 07 Nov 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Hospital for Special Surgery physicians who focus on lupus, scleroderma and related conditions are traveling from New York City to Atlanta this week to share their recent findings at the 74th Annual Scientific Meeting of the American College of Rheumatology (ACR).

Special Surgery investigators will present advances that may influence the future of clinical care. Topics include prevention strategies for helping orthopedic patients avoid falls, quality of life in children with lupus, understanding joint pain caused by a commonly used breast cancer medication, lupus-related kidney disease, an international summit to identify antiphospholipid syndrome research questions and innovations in providing personalized care for people with lupus.

With our multidisciplinary team providing comprehensive medical care and patient education in the Mary Kirkland Center for Lupus Care at Hospital for Special Surgery, the patient is the number one focus, explained the Center's co-director Doruk Erkan, M.D., co-author of a poster to be presented at the meeting. We are treating the patient as a whole, not just the disease.

At the meeting, the ACR will also honor three Hospital for Special Surgery faculty members with the designation of Master: Chief Scientific Officer Steven R. Goldring, M.D., Physician-in-Chief Emeritus Stephen A. Paget, M.D., and Attending Rheumatologist Joseph A. Markenson, M.D.

This recognition is one of the highest that the organization bestows. Eligible members are those age 65 and older who have made outstanding contributions to the rheumatology profession through academic achievements and service to patients and students. No more than 15 Master designations are awarded each year.

It is remarkable that three rheumatologists from one institution would be honored by being named Masters, said Mary K. Crow, M.D., physician-in-chief and chair of the HSS Division of Rheumatology, who is also a past president of the ACR. Each of these Special Surgery experts has significantly contributed to the field of rheumatology.

Dr. Goldring, who holds the St. Giles Chair at Special Surgery, oversees basic, clinical and translational research at the hospital and has been a leader in the field of bone remodeling research. Dr. Paget served as the hospital's physician-in-chief and chair of the Division of Rheumatology from 1995 to 2010, and today continues his longstanding research on the development and treatment of rheumatoid arthritis, lupus and related conditions. Dr. Markenson has regularly been a lead investigator of studies and clinical trials on new drugs for people who have rheumatic diseases, including rheumatoid arthritis, osteoarthritis and lupus.

Also at this year's meeting, C. Ronald MacKenzie, M.D., associate attending rheumatologist at HSS, will be announced as the next chair of the ACR Committee on Ethics and Conflict of Interest. Ora B. Singer, M.D., a recent graduate of the HSS rheumatology fellowship program, will receive an ACR Distinguished Fellow Award, and Anant Vasudevan, a Yale University medical student who performed rheumatoid arthritis research at HSS, will receive an ACR Research and Education Foundation/Abbott Medical and Graduate Student Achievement Award.

News from the 2010 American College of Rheumatology Annual Meeting is embargoed until Sunday, Nov. 7, 2010 at 5 p.m. ET.

Highlights of presentations by Hospital for Special Surgery scientists include:

International summit held to stimulate collaborative clinical research on antiphospholipid syndrome

Tue, 02 Nov 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Antiphospholipid Syndrome (APS) is a condition that may be responsible for up to one-third of strokes in people under age 50, up to one-fifth of all cases of blood clots in large veins, and one-quarter of recurrent miscarriages. Nonetheless, relatively few randomized clinical trials have been conducted involving people with APS, and those completed have included small numbers of participants.

To stimulate an international discussion on this topic, the APS Clinical Research Task Force is hosting a summit titled, Breaking Out of the Box, in Miami from Nov. 2-4, 2010. The task force, co-chaired by Hospital for Special Surgery physician-scientists Doruk Erkan, M.D., and Michael D. Lockshin, M.D., was formed as a result of the 13th International Congress on Antiphospholipid Antibodies in April 2010.

The two dozen summit attendees will include experts in the field of APS research from around the world, including Australia, Brazil, Italy, the Netherlands, the United Kingdom and the United States.

APS research has not progressed substantially over the past 25 years, after researchers developed a simple blood test to identify the antibodies, said Dr. Lockshin, director of the Barbara Volcker Center for Women and Rheumatic Disease at Hospital for Special Surgery in New York City. As a result, we are gathering rigorous thinkers to identify critical APS research questions and establish the process for moving forward in a coordinated, strategic international effort.

APS involves the formation of abnormal blood clots in arteries and veins, which puts people at risk for stroke and pregnancy complications. Blood clots form because the immune system mistakenly produces antibodies against phospholipid-binding plasma proteins (aPL).

APS can be diagnosed through repeated blood testing. While no cure exists and the cause is still unclear, treatment includes long-term blood thinning to prevent clots from forming. This condition can occur in conjunction with other autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis.

Several major issues have slowed the progress of APS clinical research, such as the fact that there are few standardized tests to detect the antiphospholipid antibodies, study participants have a range of symptoms, the biology underlying the condition is not completely understood, and smaller efforts have not recruited enough study participants.

There is an urgent need for a true international collaborative approach to design and conduct large-scale clinical trials involving people who have aPL, said Dr. Erkan, clinical co-director of the Mary Kirkland Center for Lupus Care at Hospital for Special Surgery. At this summit, we hope to stimulate dialogue about this condition and formulate a solid research question from which to generate future clinical trials that are feasible, interesting and relevant.

The summit will include presentations about transforming and globalizing APS research, lessons learned from APS research registries, and several group brainstorming sessions for identifying, refining and finalizing research questions. Scientists will conclude by setting a timeline for critical tasks to complete in order to proceed with clinical studies.

The conclusions of the APS Clinical Research Task Force and the preliminary outcomes from the Miami summit will be presented at the upcoming American College of Rheumatology annual scientific meeting in Atlanta, in poster session A on Nov. 8 from 9 a.m.-11 a.m. as Abstract #6, Antiphospholipid Syndrome (APS) Clinical Research Task Force (CRTF) Report.

Virginia Bioinformatics Institute to model immune responses to gut pathogens

Fri, 08 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, has awarded a $10.6 million grant to researchers at the Virginia Bioinformatics Institute (VBI) and collaborators to determine how the human immune system responds to infection by pathogens of the gut. The funding will be used to apply mathematical modeling to the study of immune responses to gut pathogens.

The Center for Modeling Immunity to Enteric Pathogens will generate new hypotheses based on computer simulations of the immune responses in the gut and perform pre-clinical and clinical experiments that will reveal how the immune system works when intestinal pathogens invade the human body, said Josep Bassaganya-Riera, principal investigator of the center, associate professor at VBI, and leader of the Nutritional Immunology and Molecular Medicine Group in VBI's CyberInfrastructure Division.

We want to use powerful computer simulations to uncover the mechanisms of action underlying immune responses to intestinal pathogens and accelerate the discovery of drug targets suitable for the prevention and treatment of diseases and disorders caused by gut pathogens, such as persistent diarrhea, gastric cancer, inflammation, and ulcers, said Bassaganya-Riera.

The research project team will work with a wide range of collaborators and engage the infectious disease and immunology communities to disseminate user-friendly mathematical and computational models for the study of human immunity to infection or vaccination.

Food- and water-borne illnesses that arise from infections with gastrointestinal pathogens cause an enormous health burden around the globe, said Richard Guerrant, director for the Center of Global Health in the Division of Infectious Diseases and International Health at the University of Virginia School of Medicine. Escalating medical costs, lost productivity, and premature death are linked to annual outbreaks of pathogens that target the intestinal tract of humans. This project sets out to address the need for more informed scientific research that translates into effective clinical solutions for gastrointestinal infections. It should open novel approaches to providing much needed health solutions to individuals in both developing and industrialized countries.

The Center for Modeling Immunity to Enteric Pathogens is organized into four major areas: computational/mathematical model development, immunological experimentation, bioinformatics, and education.

Generations of life scientists have worked in a reductionist paradigm to provide crucial insight into the interactions between biological systems at scales ranging from organs, tissues, and cells to molecules, said Stephen Eubank, deputy director of the Network Dynamics and Simulation Science Laboratory at VBI. What's been lacking is a holistic understanding of how all these pieces function together in a real organism with all its messy irregularity, heterogeneity, and complexity across scales.

Microfluidic tool for isolating neutrophils

Mon, 30 Aug 2010 09:39:58 PST

( from http://www.rxpgnews.com ) A team led by Massachusetts General Hospital (MGH) scientists has developed a new microfluidic tool for quickly and accurately isolating neutrophils – the most abundant type of white blood cell – from small blood samples, an accomplishment that could provide information essential to better understanding the immune system's response to traumatic injury. The system, described in a Nature Medicine paper that received advance online release, also can be adapted to isolate almost any type of cell.

"Neutrophils are currently garnering a lot of interest from researchers and clinicians, but collecting and processing them has been a real challenge," says Kenneth Kotz, PhD, of the MGH Center for Engineering in Medicine, lead author of the study. "This tool will allow a new range of studies and diagnostics based on cell-specific genomic and proteomic signatures."

Part of the body's first-line defense against injury or infection, neutrophils were long thought to play fairly simple roles, such as releasing antimicrobial proteins and ingesting pathogens. But recent studies find their actions to be more complex and critical to both chronic and acute inflammation, particularly the activation of the immune system in response to injury.

Studying patterns of gene expression and protein synthesis in neutrophils could reveal essential information about the immune response, but gathering the cells for analysis has been challenging. Standard isolation procedures take more than two hours and require relatively large blood samples. Neutrophils also are sensitive to handling and easily become activated, changing the molecular patterns of interest, and they contain very small amounts of messenger RNA, which is required for studies of gene expression.

Building on their experience developing silicon-chip-based devices that capture CD4 T cells for HIV diagnosis or isolate circulating tumor cells, Kotz's team developed a system that gathers a neutrophil-rich sample from microliter-sized blood samples in less than 5 minutes, reducing the risk of disturbing cells in the process. To meet the requirements for speed and precision, the researchers completely redesigned the geometry, antibody-based coating and other aspects of the cell-capture module at the heart of the device. The samples collected were successful in revealing differences in gene and protein activity relevant to the cells' activation status.

While the laboratory tests were encouraging, samples from critically injured patients need to be handled and processed in real-world clinical environments. Through the efforts of study co-author Lyle Moldawer, PhD, of the University of Florida College of Medicine, the devices were tested at six sites participating in a major National Institutes of Health-sponsored study of the immune response to injury, led by Ronald Tompkins, MD, ScD, chief of the MGH Burns Service and also a study co-author. Analyzing samples from 26 patients with serious burns or other traumatic injuries revealed complex gene expression patterns that shifted during the 28 days after injury, probably reflecting complex interactions between various immune system components.

Kotz says, "Until now, it's been logistically impossible to study neutrophils to the extent we have in this paper." He notes that their analysis of neutrophil samples from trauma patients is the largest such investigation to date and adds, "This technology – which is much faster and gentler than current approaches to isolating cells – can be scaled and modified to capture just about any cell type, and we're working to apply it to other cell-based assays."

Cow vaccines go vroom

Tue, 17 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) In much of Africa, a herd of cattle is more than just cows. It's a savings account, protein store, dowry, funeral fund, symbol of wealth, and hedge against drought. For many smallholder farmers, the loss of even a single cow to disease can spell ruin.

Yet a grievous number of cattle in sub-Saharan Africa get sick: one estimate puts annual losses from disease at $40 billion, some twenty-five percent of the total value of livestock production in the region.

John Barlow, professor of animal sciences at the University of Vermont, thinks the cows in the university's research herd may be able to help.

Many cattle diseases in sub-Saharan Africa might be prevented if we had better vaccines, he says, but the way we have traditionally created vaccines is expensive and takes a lot of time.

That's why he's leading an international project that aims to better understand the molecular workings of cow immune systems -- and accelerate the development of vaccines for two critical cattle diseases: East Coast fever and foot-and-mouth disease.

Barlow and his colleagues in Kenya, Denmark and at the U.S. Department of Agriculture are supported by a new three-year grant from the National Science Foundation.

In the first year, we will be studying the cattle in the University of Vermont herd to understand the diversity of their immune function genes, Barlow says.

Then, applying this knowledge, the team will use a new technology that has been accelerating human vaccine development, but, until now, hasn't been applied to cows: so-called MHC tetramers. These synthetic molecules allow researchers to quickly get a view of what proteins in the invading virus or parasite are likely to spark a strong immune response in the host animal.

These proteins are the key vaccine candidates, says Barlow -- and can be tested in lab cell lines.

The MHC -- or major histocompatibility complex -- is a large family of genes found in most vertebrate animals, including cows. It plays a key role in regulating T-cells, that, in turn, help the organism recognize and attack a wide range of foreigners -- like the foot-and-mouth virus or the parasite the carries East Coast fever. To accomplish this complex task, the MHC itself is a complex set of protein molecules that vary dramatically between individuals -- which is part of the reason some individuals catch a disease while others don't.

We want to understand the diversity of those molecules within cattle populations, says Barlow. The tetramer technology provides synthetic MHC proteins that act much like the real ones. This allows researchers to largely sidestep the traditional method of infecting an animal with the disease, waiting for the infection, and then extracting tissue.

Tetramer technology allows us to efficiently and cheaply evaluate the T-cell response, to either natural infections or vaccines, using core research facilities at the University of Vermont medical school, says Barlow. This technology will be combined with several others, including advanced bioinformatics techniques to sort through the soup of genetic data. All of which promises to provide basic science insights needed for faster and more accurate development of vaccines in developing countries.

Barlow is quick to point out that none of the cows in the UVM herd will be exposed to any diseases -- they're just providing the resource that a highly inbred research herd allows when trying to look at the range of genetic responses. Then, in later years in the project, we'll start to test vaccines in herds in Africa, he says.

We can get the data we need without having to expose many animals to the actual diseases, says Barlow's colleague Bill Golde at the USDA's Plum Island Animal Disease Center. The sequestered animals at this center will be the only ones tested with the actual diseases once promising vaccine candidates have been identified.

Foot-and-mouth disease is a highly contagious virus passed from animal to animal. It hasn't been seen in the United States since 1929. The U.S.D.A. and U.S. cattle interests have every intention of keeping it that way, but it is common in parts of Africa and Asia.

We're studying foot-and-mouth because it's a very small virus that is relatively easy to investigate and there is a strong motivation from the perspective of U.S. global disease control, says Barlow. And for Sub-Saharan Africa it would be good if they could control it since it will improve their ability to export meat once it's controlled there.

In contrast, East Coast fever is caused by a large parasite with a large genome and complex lifecycle. It is hugely important to the smaller shareholder farms in Africa as it kills many cattle, says Barlow. Farmers there are very interested in eradicating and controlling both these diseases.

This goal may be easier to reach because only a few popular breeds dominate herds around the globe resulting in limited genetic diversity in cows. This means that the tetramer technology is likely to be even more illuminating and powerful in cattle than in human immunology.

We're doing basic science on the molecular level, says Barlow, to give the developing world better vaccines.

NIH launches effort to define markers of human immune responses

Wed, 11 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A new nationwide research initiative has been launched to define changes in the human immune system, using human and not animal studies, in response to infection or to vaccination. Six U. S.-based Human Immune Phenotyping Centers will receive a total of $100 million over five years to conduct this research.

Funding for the centers is provided by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Support for the first year of this initiative will come from the American Recovery and Reinvestment Act.

Recognizing the differences in immune system activity before, during and after exposure to an infectious agent or vaccine will help in the development of safer, more effective therapeutics and vaccines, says NIAID Director Anthony S. Fauci, M.D. This research effort also will contribute to the ongoing evolution in our ability to study the immune system.

Investigators will analyze samples from well-characterized groups, including children, the elderly and people with autoimmune diseases such as lupus. These groups represent diverse populations with respect to age, genetics, gender and ethnicity. The research teams will examine immune system elements of these populations before and after exposure to naturally acquired infections or to vaccines or vaccine components. The profile that will emerge of the body's response to vaccination will be based on the most sophisticated and comprehensive assays currently available. This will enable new approaches to examining vaccine safety, not just of individual vaccines but of the processes of immunization in general.

Their studies will focus on immune responses to vaccines against specific viruses and bacteria, such as influenza and pneumococcus, as well as to infection with West Nile virus. The investigators will take advantage of technological developments and advances in creating databases and developing mathematical models to identify and analyze the complex changes in immune profiles.

Each awardee will contribute to the establishment of a centralized infrastructure to collect, characterize and store human samples and analyze the large data sets that will be generated. Eventually, the centers will gather the information from this effort into a centralized Web-based database they will make available to the scientific community to promote and support human immunology research.

This research effort represents a major expansion of efforts to define the principles of human immune regulation, instead of relying on findings from animal models that have limitations and cannot always be extrapolated to people, says Daniel Rotrosen, M.D., director of the Division of Allergy, Immunology and Transplantation at NIAID. The knowledge gained also will improve our understanding of the range of vaccine responses in particular subpopulations, including newborns, young children, the elderly, patients taking immunosuppressive medications and those with underlying diseases of the immune system, such as allergy and autoimmune diseases.

The following six core institutions and principal investigators will participate in the inaugural program:

UR discovers new way to boost vaccines, seeks patent

Wed, 04 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) As the medical community searches for better vaccines and ways to deliver them, a University of Rochester scientist believes he has discovered a new approach to boosting the body's response to vaccinations.

Richard P. Phipps, Ph.D., found that the same molecules used in drugs that treat diabetes also stimulate B cells in the immune system, pushing them to make antibodies for protection against invading microorganisms.

The University of Rochester Medical Center has applied for international patent protection for this discovery.

Phipps believes further research will show that low doses of insulin-sensitizing drugs might be useful as vaccine adjuvants, particularly for people with weakened immune systems who cannot produce a proper antibody response. This would include some infants, the elderly, and patients with chronic health problems that lower immunity.

Currently the only widely approved vaccine adjuvant in the United States is alum. A vaccine adjuvant is a substance added to a vaccine to improve the body's immune response. Various forms of aluminum salts have been used for 70 years. (Adjuvants are added to some vaccines but not all. For example, live viral vaccines given during childhood and seasonal flu vaccines do not contain adjuvants.)

The search is always on for new adjuvants and safe adjuvants, said Phipps, a Dean's Professor of Environmental Medicine and professor of Medicine, Oncology, Ophthalmology, Microbology and Immunology, Pediatrics and Pathology and Laboratory Medicine. We are excited that we've identified a potentially important new and effective adjuvant.

Phipps' discovery grew from years of NIH-funded research investigating a protein called PPAR gamma and its ligands, which are present inside B cells and are involved in inflammation and in regulating the properties of immune cells and cancer cells. The way B cells evolve, or differentiate, is central to the body's immune response.

A closer examination of the role of PPAR gamma in relation to B cell function showed that PPAR levels increase upon B cell activation, according to a study published in 2009 by Phipps' laboratory in the Journal of Immunology.

Thus, researchers theorized that any molecule that binds to and activates PPAR gamma would, in turn, improve B cell secretion of antibodies. Researchers tested both natural and synthetic PPAR gamma ligands and discovered that the synthetic molecules used to create anti-diabetic drugs such as Actos and Avandia stimulated human and mouse B cells to better produce antibodies.

The drawback, Phipps said, is the possibility that too much stimulation would cause the immune system to overreact, triggering autoimmune diseases such as rheumatoid arthritis or lupus. Additional research is needed to better understand this process.

NIH awards National Jewish Health $31 million to lead study of infections associated with eczema

Thu, 22 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The National Institute of Allergy and Infections Disease has awarded a five-year $31 million contract to National Jewish Health, which is leading a consortium of academic medical centers seeking to better understand skin infections associated with atopic dermatitis. The researchers will focus on antibiotic-resistant staphylococcus aureus (MRSA) infections and widespread viral infections of the skin, both of which are more prevalent among atopic dermatitis patients.

MRSA is a significant public health threat that needs to be contained, said principal investigator Donald Leung, MD, PhD, Professor of Allergy and Clinical Immunology at National Jewish Health. We want to find out why these patients are susceptible to staph infections, particularly MRSA, and learn how we can prevent them from developing and spreading to others.

Atopic dermatitis, also known as eczema, is the most common skin disease in the general population, affecting approximately 20 percent of children and two percent of adults in the United States. It is a chronic disease characterized by repeated bouts of dry, itchy, irritated skin, which can make life miserable. Patients from around the country come to National Jewish Health for treatment of their severe atopic dermatitis.

Atopic dermatitis patients are particularly prone to skin infections. Sixty to 90 percent of patients have some staph organisms on their skin, and 30 percent are prone to overt infections, which can cause cracked and oozing lesions on their skin.

Because of their frequent staph infections, and possibly because of repeated antibiotic use to fight the infections, atopic dermatitis patients frequently develop MRSA infections. Although MRSA patients are isolated at National Jewish Health and other hospitals, these patients commonly have contact with friends and family outside the healthcare setting, and could be a source of infections to a wider population.

MRSA infections have emerged in recent years as a significant health problem. They are more difficult to treat, because the staph organisms are resistant to penicillin and several other first-line antibiotics. While they often cause disease no more severe than do non-resistant strains, they can cause severe disease and even death.

Researchers in the Atopic Dermatitis Research Network (ADRN), will seek to better understand why atopic dermatitis patients are susceptible to staph and other bacterial and viral infections. They will evaluate atopic dermatitis patients' genes, innate and adaptive immune responses and skin barrier to identify factors that make them susceptible to these infections. The researchers also plan to conduct a clinical trial to see if vitamin D can help reduce or prevent staph colonization and infection.

NIH expands food allergy research program

Wed, 14 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Today, the National Institutes of Health announce that the Consortium of Food Allergy Research (CoFAR), established in 2005, will be funded for five more years. CoFAR will continue to foster new approaches to prevent and treat food allergies and also expand in scope to include research on the genetic causes underlying food allergy and studies of food allergy-associated eosinophilic gastrointestinal diseases (EGIDs).

Funding for CoFAR is provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), components of NIH.

Food allergies are difficult to manage because even when one strictly avoids allergenic foods, people with food allergies are still at risk of potentially life-threatening accidental exposures, says NIAID Director Anthony S. Fauci. We need to find better ways to treat and prevent food allergy and improve the quality of life of those with the disease.

Food allergy occurs in an estimated 5 percent of children and 4 percent of adults in the United States. The hallmark of this disorder is production of immunoglobulin E (IgE) antibodies in response to a specific food. Once IgE antibody is made, further exposure to the food triggers an allergic response. Symptoms of food allergy can range from hives or stomach cramps to swelling of the larynx, fainting from low blood pressure or anaphylaxis, a life-threatening allergic response to food.

EGIDs are a group of recently recognized allergic diseases that also are associated with production of IgE antibodies as well as other immune responses to food. The most common EGID is eosinophilic esophagitis (EoE), which is characterized by inflammation and accumulation of eosinophils, a subset of immune cells, in the esophagus. The primary symptoms of EoE in children include nausea, vomiting and abdominal pain after eating, while in adults, the primary symptom is difficulty swallowing.

Key research on eosinophils has confirmed the important role they play in inflammatory diseases of the upper GI tract, says Griffin P. Rodgers, M.D., director of NIDDK, co-sponsor of CoFAR. We hope that the new genetic studies involving EGIDs will help researchers identify and develop novel treatments.

The causes of food allergy and EGIDs are unknown. Although these diseases seem to have a genetic component, the genes responsible have yet to be identified. Additionally, some people outgrow their childhood allergies, whereas others develop new ones.

When NIAID established CoFAR in 2005 with five clinical sites, the goal was to help improve understanding of why food allergy develops and how can it be treated or prevented.

During this first phase, CoFAR investigators initiated three clinical trials. One clinical trial is testing if drops containing gradually increasing amounts of peanut protein, given under the tongue, can effectively treat people with peanut allergy. The second trial is evaluating gradually increasing doses of a modified peanut protein, given in a suppository, to treat peanut allergy. In the third clinical trial, volunteers receive egg protein by mouth in gradually increasing doses to treat egg allergy.

CoFAR investigators also initiated an observational study to determine what factors correlate with their allergy continuing or resolving. The study also aims to determine what factors correlate with developing or not developing a new allergy to peanuts. The study has enrolled more than 500 infants, ages 3 to 15 months, with known egg or milk allergy.

All of these studies will continue under the new initiative. In addition, CoFAR will add a new clinical trial to treat peanut allergy, using peanut protein that will be applied on the skin. As part of the program expansion, there will be two new research sites looking for genes associated with food allergy and three consulting sites conducting studies to understand EoE.

We are pleased to continue our support of CoFAR, NIAID's major program dedicated to exploring the causes of food allergy and developing new treatment and prevention strategies, says Daniel Rotrosen, M.D., director of the Division of Allergy, Immunology and Transplantation at NIAID. By expanding CoFAR's research goals to include studies of the genetic components of food allergy, and broadening the research to include food allergy-associated diseases like EoE, we expect that its work will continue to increase our understanding of how food elicits an allergic reaction in certain people.

Two principal investigators will receive funding under the new CoFAR grant: Hugh Sampson, M.D., of Mount Sinai Medical Center, New York City; and Xiaobin Wang, M.D., M.P.H., Sc.D., of Children's Memorial Research Center, Chicago.

Treatment with naturally occurring protein prevents and reverses brain damage caused by meningitis

Tue, 15 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) This bacterium, Escherichia coli K1, is the most common cause of meningitis in premature infants and the second most common cause of the disease in newborns. The ineffectiveness of antibiotics in treating newborns with meningitis and the emergence of antibiotic-resistant strains of bacteria require new strategies, explains Nemani V. Prasadarao, PhD, associate professor of infectious disease at Childrens Hospital Los Angeles.

Meningitis is the irritation of membranes covering the brain and spinal cord. This irritation can result from viral or bacterial infection. Bacterial meningitis can be very serious, possibly resulting in hearing loss, brain damage, or death, even when treated. Although the mortality rate can be decreased through use of antibiotics significant neurological consequences, like mental retardation, still occur in 30 to 40 percent of survivors.

A recent surge in antibiotic-resistant strains of E. coli K1 is likely to significantly increase the rates of illness and death, said Prasadarao. Also, the diagnosis of meningitis is difficult until the bacteria reach the cerebrospinal fluid. By that time, brain damage has begun. With large numbers of circulating bacteria, treatment with antibiotics can result in biochemical reactions that may cause septic shock and ultimately, organ failure. So identifying alternatives to antibiotic therapy is crucial.

One of a class of proteins known as cytokines, IL-10 is involved in immune function. We found that during an episode of bacteremia, when a large number of bacteria are circulating in normally sterile blood, IL-10 acts to clear antibiotic-sensitive as well as antibiotic-resistant E. coli from the circulation of infected mice, said Rahul Mittal, Ph.D., lead author on the paper and a post-doctoral fellow in Prasadarao's lab.

They also determined that E. coli infection produced damage to the mouse brain comparable to that seen in humans. Three-dimensional imaging studies of infected animal and human infant brains showed similar gross morphological changes. When we gave IL-10 to mice 48 hours after infection, those changes to the brain were reversed, said Mittal.

Tumor necrosis factor (TNF) is a cytokine active in producing inflammation. When the researchers replicated these experiments using antibiotic or anti-TNF, brain damage resulting from E. coli infection was not prevented.

The team also discovered a mechanism of action for IL-10 protection. In culture, using mouse and human white blood cells called neutrophils, they found that exposing these cells to IL-10 produced an increase in the number of a certain type of receptor on the surface of the neutrophils. An increase in the CR 3 receptor led to enhanced killing of bacteria.

Another white blood cell, called a macrophage, works to clear bacteria from the blood by engulfing or eating the pathogen. Similar to what was seen in neutrophils, macrophages treated with IL-10 showed an increase in CR 3 receptors that enhanced their ability to destroy invading bacteria.

To confirm that the CR 3 receptor is critical to the protective effect of IL-10 against E. coli, CR 3 expression was suppressed in a group of mice. Before exposing the animals to bacteria, white blood cells were examined and the CR 3 receptor was determined to be absent. These animals were exposed to E. coli and then treated with IL-10. The mice were found subsequently to have bacteria in the CSF and morphological changes indicating brain damage. The protective effect of IL-10 during bacteremia was absent in animals without CR 3 receptors. The researchers further concluded that the crucial increase in CR 3 receptors was a result of IL-10 suppressing an important inflammatory agent, prostaglandin E-2.

Since diagnosing meningitis is difficult until bacteria reach the central nervous system, finding an agent that can clear the bacteria while also preventing or restoring the damaged brain is very exciting, said Mittal.

These studies provide a basis for exploring the use of IL-10 in newborns.

Making cancer killers

Thu, 10 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A team of researchers has developed a method to produce cells that kill tumour cells in the lab and prevent tumours forming in mouse models of cancer. Although the current work is in cells and mouse, if the research transfers to human biology, the new type of cell could be a new source for cell-based anticancer therapies.

The cells were produced by knocking out a single gene essential in the pathways of development of immune cells: the modified cells become a novel type, which the authors call Induced T to Natural Killer Cells (ITNK cells).

Many cell types cooperate in the immune system to battle invaders, such as bacteria and viruses, and to remove abnormal or dead cells. T lymphocytes/T cells play an important part in defending against pathogens and abnormal self cells. They are thought also to play a role in autoimmune disease.

In this research, T cells were transformed into cells similar to another type, Natural Killer (NK) cells, which commonly act against viruses and cancer cells.

We have been examining ways to produce clinically useful immune system cells, explains Peng Li, PhD student and first author on the publication, from the Wellcome Trust Sanger Institute. We had shown that a gene called Bcl11b was essential for normal development of immune system cells - and of particular interest in the development of T cells.

Here we can see the fruits of that work: we show, for the first time, that we can modify the developmental fate of immune system cells to produce a novel type that - if we can see the same effect in humans - could be of enormous value in cancer treatment.

The Bcl11b protein is a master switch that works by regulating the activity of other genes and it was known to be important in the immune system. However, this role in T lymphocyte development is entirely novel.

In the careful research, the team first showed that the Bcl11b gene was active only in T cells in the immune system and that its activity was needed at the earliest stages of production of T cells. When the team knocked out the Bcl11b gene, the mice produced no T cells.

Remarkably, the mice lacking the Bcl11b gene produced a new type of immune system cell - the Induced T to Natural Killer cells, explains Dr Pentao Liu, senior author on the project from the Wellcome Trust Sanger Institute. This is the first time we have seen these cells and the first time a gene regulator like Bcl11b has been shown to carry out such an important role in T cells.

Even more important, we can see that these reprogrammed killer cells can attack cancer cells, whether in test tubes or in mouse models.

The ITNK cells killed melanoma and lymphoma cells in experiment in test tubes and were much more efficient than unmodified Natural Killer cells in the mouse and in human.

But they worked also on cancers. When tumour cells were injected into mice they produced at least tenfold fewer tumour foci in the Bcl11b-deficient than in Bcl11b-competent mice.

Rare hybrid cell key to regulating the immune system

Mon, 24 May 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Toni BakerPublic Relations ManagerMedical College of Georgia706-721-4421 Office 706-732-0401 Beeper706-825-6473 Cell tbaker@mcg.edu

May 24, 2010

Rare hybrid cell key to regulating the immune system

AUGUSTA, Ga. - A cell small in number but powerful in its ability to switch the immune system on or off is a unique hybrid of two well-known immune cell types, Medical College of Georgia researchers report.

This is actually the first cell we know of that has this type of appearance in nature, Dr. Andrew Mellor, molecular geneticist and immunologist who co-directs MCG's Immunotherapy Discovery Institute, said of the cell that looks like a dendritic cell and a B cell but isn't really either.

The discovery of this rare hybrid could have implications for the efficacy of new therapies that manipulate these two cell types to treat diseases such as cancer and rheumatoid arthritis.

When MCG scientists first reported the human equivalent of this cell in Science in 2002, they called it a subset of the dendritic cell that clusters in high exposure areas such as the gut but also roams the body, looking for invaders like a virus or cancer. Dendritic cells show their find to T cells, telling them to ignore or attack by bringing trash-eating macrophages, natural killer cells and the like into the fight.

What seemed most unique about the subset is its ability to express indoleamine 2,3 dioxygenase, or IDO, to turn off T cells. IDO is an enzyme used by fetuses and tumors alike to escape the immune response.

The new studies show that is only part of the cells' distinctiveness. The cells also have the identifying markings of B cells, known for their ability to make antibodies against invaders. In fact, they found the IDO-presenting cells came from the same precursor cell as B cells. But, when the scientists looked at mice missing B cells, they still found the IDO-producing cells. Hence, the cell didn't need to produce antibodies to turn off T cells.

In reality, IDO-expressing cells have properties of both cells, said Burles A. Johnson III, an MCG M.D.-Ph.D. student and first author of the paper published online this week in PNAS. It looks like a B cell and it's not. It looks like a dendritic cell and it is and it isn't, Johnson said.

While their studies are in mice, the cells also are in humans, showing up in some unfortunate places such as the drainage system for tumors, melanoma or even HIV where they likely help the diseases survive.

They also may be showing up in new dendritic cell therapies designed to strengthen the immune response to cancer. If the therapies happen to include some IDO-expressing cells, those could end up helping the cancer, said Mellor, the paper's corresponding author. All you need is a few of these cells in your dendritic cell vaccine and you don't get stimulation any more, you get suppression, Mellor said.

Their confusing face could also cause hybrids to be lost in B cell-depleting therapies designed to lessen the immune system's attack on joints in rheumatoid arthritis. These therapies may also deplete IDO-expressing cells and decrease therapy effectiveness because you are eliminating cells that are there to help you, Johnson said.

This gives us new insight into why these therapies might not be working as well as we think they might, Mellor added. Long-term goals include figuring out how to manipulate the hybrid's activity to benefit patients.

The research was funded by the National Institutes of Health and the Germany-based pharmaceutical company Boehringer-Ingelheim. Mellor is a Georgia Research Alliance Eminent Scholar in Molecular Immunogenetics.

Researchers share insights into RNA

Tue, 11 May 2010 04:00:00 PST

( from http://www.rxpgnews.com ) LA JOLLA, Calif., May 11, 2010 -- Investigators from around the country came to Sanford-Burnham Medical Research Institute (Sanford-Burnham) on Friday, May 7, to share their knowledge of the burgeoning young field of microRNAs. These small non-coding nucleic acids turn off proteins and have been implicated in viral infection, cancer, cardiovascular disease, HIV and numerous other conditions.

The discovery that small RNAs could shut down gene expression was revolutionary, said Tariq Rana, Ph.D., who directs the RNA Biology program at Sanford-Burnham. Dr. Rana organized the symposium with Sanford-Burnham colleagues Rolf Bodmer, Ph.D., and Sumit Chanda, Ph.D.

The symposium, entitled RNAi and microRNA Regulatory Functions, featured a who's who of RNA biologists sharing their understanding of how these small RNAs regulate gene function and contribute to disease.

One of the speakers, Shiv Grewal, Ph.D., senior investigator at the National Cancer Institute, works to understand how RNAi regulates chromatin, the combination of proteins and DNA that makes up chromosomes. Dr. Grewal's research has shown that RNAi machinery stabilizes these critical structures. If you disrupt this process, chromosomes will not segregate properly, said Dr. Grewal. After cell division, one cell will get more and the other will get less, a very common feature in cancer cells.

Deepak Srivastava, M.D., a pediatric cardiologist and director of the Gladstone Institute of Cardiovascular Disease, has been working to understand how the heart develops. His research has shown that microRNAs and proteins work in complementary networks to help progenitor cells choose what kind of heart cells to become. There is a transcriptional network that controls cell fate decisions in the heart, said Dr. Srivastava. Overlaid on that is a translational network controlled by microRNAs that controls how much protein is made of those same transcription factors. But also, those transcription factors control the dose of microRNAs. It's a very coordinated network.

Amy Pasquinelli, Ph.D., associate professor at UC, San Diego, is working to determine how microRNAs bind to their target. We want to understand the pairing rules, said Dr. Pasquinelli. If we can understand those, we can use bioinformatics to predict, simply by looking at the microRNA sequence, where it's going to bind, what gene it will target and what will be the ultimate result.

Other researchers shared their work on a number of topics, including the fundamental roles of microRNAs in biology and epigenetics; developing cutting-edge technologies that use small RNAs to investigate disease processes; high-resolution structures of RNAi machinery; RNA-mediated regulation of herpes infections; and RNA-based treatments for neurodegenerative disorders, AIDS, cancer and metabolic diseases.

New inhalable measles vaccine may lead to vaccines for other diseases

Wed, 05 May 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A team of researchers led by the University of Colorado at Boulder believe a dry powder, inhalable vaccine developed for measles prevention and slated for human clinical trials later this year in India will lead to other inhalable, inexpensive vaccines for illnesses ranging from tuberculosis to cervical cancer.

The inhalable measles vaccine, developed by a team led by CU-Boulder chemistry and biochemistry Professor Robert Sievers, involves mixing supercritical carbon dioxide with a weakened form of the measles virus. The process produces microscopic bubbles and droplets that are dried to make the inhalable powder, which is dispensed into the mouths of patients using a small, cylindrical plastic sack with an opening like the neck of a plastic water bottle.

According to the World Health Organization, measles is one of the leading causes of death among young children. In 2008 there were an estimated 164,000 measles deaths in children worldwide -- nearly 450 deaths a day -- and India accounts for about two-thirds of global measles deaths in infants and children. Clinical trials are the next vital step in making this vaccine widely available, he said.

One of our primary goals of this project is to get rid of needles and syringes, because they frighten some people, they hurt, they can transmit diseases and there are issues with needle disposal, he said. With the new technology, the inhaled powder is sent directly into the lungs, a good target since measles attacks through the respiratory tract, said Sievers. A person taking a deep breath from the sack is effectively vaccinated.

Sievers will give a presentation on the subject at the Eighth European Conference on Supercritical Fluid Applications to be held May 9-12 in Graz, Austria.

Phase One of the clinical trials to test the safety and efficacy of the measles inhalant product are slated to start this summer in Pune, India, and will involve about 180 people, said Sievers. Phase Two of the India clinical trials are expected to involve a larger number of patients.

Sievers, also a fellow at CU's Cooperative Institute for Research in Environmental Sciences, said the measles vaccine development idea grew out of atmospheric chemistry research he and his students were conducting. The team was attempting to determine the chemistry of specific air pollutants in particular regions of the world and how people inhale and process tiny airborne droplets of pollutants.

As part of the measles project, Sievers and his students and colleagues invented and patented a device known as the Carbon Dioxide Assisted Nebulization with a Bubble Dryer, or CAN-BD, in which two mixed streams of fluid are rapidly expanded to atmospheric pressure where the tiny bubbles and droplets are dried by mixing them with warm nitrogen. The resulting, inhalable-sized vaccine bits are embedded in micro-particles of sugars and amino acids, he said.

Aktiv-Dry is a Boulder spinoff company Sievers co-founded in 2002 with Professor John Carpenter of the University of Colorado School of Pharmacy and Brian Quinn, current president of Aktiv-Dry. The company, which employs about 10 people including former CU-Boulder students, currently is developing CAN-BD for the marketplace.

This project came out of the University of Colorado, and Aktiv-Dry is partially owned by the university through the University of Colorado Technology Transfer Office, said Sievers. I've had 40 CU-Boulder students who have earned their doctorates under me through the years, and it was those students and their work that really positioned us at the right time to gain significant funding for this project.

The $20 million Aktiv-Dry research effort is funded by the Grand Challenges in Global Health Initiative, which was created by the Bill and Melinda Gates Foundation through the Foundation for The National Institutes of Health. Sievers' project addresses one of the 14 Grand Challenges -- the needle-free administration of vaccines by pulmonary or nasal aerosols.

David H. McAdams, a CU-Boulder doctoral student in the chemistry and biochemistry department working with Sievers, said he switched his academic focus from atmospheric chemistry particle analytics to participate in the measles project. I saw an opportunity to use the analysis of such particulates to benefit mankind and to help save children by using inhalable vaccines.

The CU team recently tested the durability of the inhalant vaccine by shipping a batch from the Serum Institute of India to CU-Boulder, then shipping the same batch two months later to the East Coast and back to Boulder. The vaccine proved to be stable throughout the shipping process, indicating it likely would be effective under challenging environmental conditions encountered in developing nations, Sievers said.

The cost of an inhalant dose for measles developed by Sievers and his team is about 26 cents -- roughly the cost for an injectable form of the dose. As a practical matter, said Sievers, the treatment of patients with novel technologies should not be more expensive than standard treatment costs.

The new technology could potentially be used to deliver tiny antibiotics particles to treat people with multi-resistant tuberculosis, said Sievers. While the antibiotic inhalant would likely be combined with oral doses and injections, the use of CAN-BD would direct the antibiotic directly to the lungs where the disease is focused, said Sievers.

Another potential use for the CAN-BD technology is treating human papilloma virus, a sexually transmitted disease that causes cervical cancer. More women in India today die of cervical cancer than from breast cancer, which is a much bigger killer in the United States, he said. Current treatment for papilloma virus is a three-dose injection regimen that costs about $300 -- a cost Sievers and his group would like to lower significantly for it to be distributed to women who need it in developing nations.

OB/GYN offices may offer ideal venue for improving vaccine rates among women

Tue, 20 Apr 2010 04:00:00 PST

( from http://www.rxpgnews.com ) DURHAM, NC -- Obstetrician/gynecologist offices may be the ideal venue for boosting vaccination rates among women, say researchers at Duke University Medical Center. They reported today on a successful pilot program focused on providing HPV (human papillomavirus) and Tdap (tetanus, diphtheria, pertussis) vaccines to non-pregnant and post-partum women.

The researchers say the program, funded by the U.S. Centers for Disease Control, could be a model for ob/gyn clinics across the country to increase much-needed immunizations among eligible adults.

Ob/gyns don't typically think of themselves as vaccinators, says Geeta Swamy, MD, Director of Obstetrics Clinical Research at Duke, who presented the findings today at the CDC National Immunization Conference in Atlanta. Even though we vaccinate pregnant women against a variety of diseases that are screened for during pregnancy, we still tend to think of vaccinations as happening at the offices of pediatricians, primary care physicians and family practitioners. But many women seek medical care from their gynecologists, even after they have children. Their annual gynecologist visit is a good opportunity to discuss preventive care which includes vaccinations.

The North Carolina pilot program was set up to improve HPV vaccination rates among non-pregnant women. Preliminary data from one clinic shows that non-pregnant women were already being offered HPV, but when post-partum women were offered the vaccine, the rate of vaccination jumped from 0 to 44 percent. These women would not have been vaccinated if this program was not in place, Swamy said.

Even more significant was the increase in women who received the Tdap vaccine. Nearly 600 women received the vaccine of the 1000 who were offered it, she said. None had been offered it before.

Reaching women who had not been vaccinated is important because rates of pertussis have been on the rise for the last five years despite CDC recommendations that adults and adolescents receive the newer, single dose if they had not received a tetanus shot within the past two years.

Although the disease is not as serious in adolescents and adults, it is life-threatening among infants who aren't fully immunized until at least one year of age. A recent CDC report found mothers were the primary source of infection in 32 percent of infant pertussis cases. Ideally we aim to vaccinate women before they conceive, but any post partum woman should get the vaccine if their last tetanus shot was two years ago or more, says Swamy. If we can vaccinate new moms, we can provide a cocooning effect that protects their infants from this deadly disease.

Swamy believes the program could easily be implemented in ob/gyn offices nationwide as more emphasis is being placed on preventive care. We should be thinking of preventive medicine as something that's done at almost any medical encounter, and not just limiting it to the primary care field. It should be provided by all doctors where it's feasible and within the scope of their care.

National Jewish Health receives grant to learn how families cope with food allergy

Mon, 08 Mar 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Families with food-allergic children face a life of constant vigilance and the looming fear of life-threatening allergic reactions. This fear can have a huge impact on an entire family's life, from heightened anxiety to severe limits on their daily activities. Some families cope well with this situation, while others find it extremely stressful and difficult to manage. Mary Klinnert, PhD, Associate Professor of Pediatrics at National Jewish Health, has received a $450,000 grant from the NIH to study how different families adapt to life with food allergies, and to discover what helps the best-adapted families cope well.

Families with food-allergic children must live with the high likelihood that their child will someday be rushed to the hospital to treat a sudden and severe allergic reaction, said Dr. Klinnert. Although the actual number of food-allergy deaths is low, it can still be very frightening. We believe this grant will help us find ways to help families better cope with this difficult situation.

An estimated 3 million children in the United States have food allergies. More than 50,000 people suffer severe, anaphylactic reactions to food every year. Almost 10,000 children are hospitalized, and about 150 to 200 die.

Families have a range of responses to their children's food allergies. Available data suggest that half of parents with food-allergic children experience a pervasive fear for their child's safety, and a sizable subgroup restrict normal child and family activities because of food allergies. Others do not appreciate the potential severity of a food-allergy reaction and are casual about their precautions and preparations. Previous research by Dr. Klinnert suggests that balanced responders successfully incorporate necessary precautions into their lives without undue anxiety. They realistically understand that their child's chance of having a severe food-allergy reaction is 'very likely,' but that the chance of dying is 'very unlikely.'

The goal of Dr. Klinnert's research is to better understand the various coping strategies these different groups use.

Dr. Klinnert and her colleagues will seek to develop an interview-based measure of families' food-allergy management and adaptation. They will study 60 families of children age 6-12 with confirmed food allergies. Parents will complete a questionnaire about the impact of the child's food allergy on the family. Parents and children will also complete a self-evaluation on general anxiety levels. All families will participate in a video-recorded interview discussing how they handle food-allergy management at home. Doctors will individually and collaboratively review and create a scale based on responses.

With this tool it will be possible to evaluate families' adaptation to their children's food allergies, to determine how many families have significant distress or difficulty managing, and to develop services for families with difficulties coping, said Dr. Klinnert.

NIAID media availability: Food allergy-related disorder linked to master allergy gene

Sun, 07 Mar 2010 05:00:00 PST

( from http://www.rxpgnews.com ) WHAT:Scientists have identified a region of a human chromosome that is associated with eosinophilic esophagitis (EoE), a recently recognized allergic disease. People with EoE frequently have difficulty eating or may be allergic to one or more foods. This study further suggests that a suspected so-called master allergy gene may play a role in the development of this rare but debilitating disorder.

EoE is characterized by inflammation and accumulation of a specific type of immune cell, called an eosinophil, in the esophagus. Symptoms of EoE vary with age: In young children a major symptom is spitting up food, while in older children and adults, the condition may cause food to become stuck in the esophagus. These symptoms may improve when a person with EoE is restricted to a liquid formula diet that contains no protein allergens or is placed on a diet that lacks six highly allergenic foods (milk, soy, eggs, wheat, peanut and seafood). EoE is not the same as more common food allergies, which also have serious consequences. Little is known about what causes EoE, but the disease runs in families suggesting that specific genes may be involved.

Investigators led by Marc Rothenberg, M.D., Ph.D., at Cincinnati Children's Medical Center Hospital, and supported by the National Institute of Allergy and Infectious Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases, both part of the National Institutes of Health, performed a genome-wide association analysis in children with EoE and healthy children. This type of study detects markers of genetic variation across the entire human genome and allows researchers to zero in on a region of a chromosome to identify genes that influence health and the development of disease.

In this study, the investigators identified changes in genes within a region on chromosome 5 that were highly associated with EoE. One of the genes in this region encodes a protein called thymic stromal lymphopoietin (TSLP). When the investigators measured the expression levels of this gene in children with EoE, they found it was more highly expressed than in children without the disorder. This result suggests that TSLP plays some role in EoE.

TSLP is made by epithelial cells, which line internal and external surfaces of the body. It has already been described as a master switch that may turn on other allergic diseases, such as asthma and atopic dermatitis (eczema).

Future research is needed to determine if these findings might lead to a genetic test for TSLP and whether drugs that block the production or function of TSLP might be useful in treating EoE.

IOM report on national vaccine plan

Fri, 11 Dec 2009 05:00:00 PST

( from http://www.rxpgnews.com ) WASHINGTON -- While vaccines help prevent many diseases in the United States, we lack immunization protection against several serious illnesses, says a new report from the Institute of Medicine that identifies priority areas for updating the National Vaccine Plan. The revised plan should include a strategy to accelerate development of high-priority vaccines, said the committee that wrote the report. In addition, it should emphasize the importance of expanding funding for safety research and monitoring, and include the development of a national communications strategy to clarify the importance of vaccines and bolster public confidence in the immunization system.

The National Vaccine Plan aims to provide centralized coordination of the various components involved in protecting Americans from vaccine-preventable illnesses and vaccine-related adverse reactions. The immunization system engages many partners -- including multiple government agencies and departments, vaccine researchers, manufacturers, public health officials, health care providers, and the public -- in identifying vaccine needs, researching and developing new products, assessing safety, and getting people immunized. The U.S. Department of Health and Human Services (HHS) released a draft update to the plan in 2008 and requested that IOM conduct an independent assessment of issues that merit priority attention.

The updated plan should call for a greater proportion of vaccine research and development to be directed at specific goals, such as producing vaccines against diseases for which there are none or developing a single vaccine that would work against all influenza viruses, the committee said. The majority of vaccine research and development stems from the focus and interests of individual researchers rather than a set of priority targets identified through a centralized planning process.

Given the absence of a framework to set a national vaccine-safety research agenda, the National Vaccine Plan should call for expanded funding for safety research and include establishing a permanent group to advise the government on safety issues, the report says. Little vaccine research supported by the National Institutes of Health appears to be geared toward safety, the committee noted. Moreover, as the number and kinds of vaccines have increased, funding to monitor safety has not. The monitoring system has successfully caught problems such as a rare but severe intestinal injury linked to a discontinued rotavirus vaccine, but the Immunization Safety Office within the Centers for Disease Control and Prevention needs more resources to do its work. A new vaccine safety advisory group could guide efforts to address potential safety concerns and the development of a research agenda with clear priorities.

Noting that a proliferation of misinformation about vaccines' effectiveness and safety has contributed to diminished public understanding of and confidence in the value of immunization, the committee called for the National Vaccine Plan to include the development of a national communications strategy that engages the latest techniques and methods, such as social networking. Outreach efforts by federal agencies and other public health groups have been disjointed and reactive and not as effective as they should be, the committee said. The effort should boost health care providers' abilities to talk about the benefits and risks of vaccines with patients as well as increase the public's understanding of vaccines.

The National Vaccine Plan should also include a strategy to eliminate financial barriers to immunization, such as lack of health plan coverage for all recommended vaccines and insufficient reimbursements that do not cover all of a clinic's costs of providing vaccines, the report added. Certain subgroups, such as the elderly and people with lower incomes, tend to have greater difficulty getting the vaccines they need. The plan also should promote the use of health information technology to monitor disease incidence, rapidly detect potential safety signals, and measure vaccine coverage. Tracking patients' immunization status should be an integral part of electronic health records, the report says.

The National Vaccine Program Office (NVPO), which Congress intended to coordinate vaccine activities across government agencies, requires a heightened profile and more resources to carry out its role and to implement the National Vaccine Plan, the committee said. The HHS secretary should clarify NVPO's role as the central coordinator for critical immunization activities and give it the necessary funding to fulfill this role.

Coordination is at the heart of the National Vaccine Plan, and it needs to be strengthened, said committee chair Claire V. Broome, adjunct professor, department of global health, Rollins School of Public Health, Emory University, Atlanta. While the immunization system has functioned well through the years, we may have missed opportunities, for example, to expand our use of cutting edge vaccine science or to use new communication methods to get accurate information on vaccines to the public. The National Vaccine Plan and the National Vaccine Program Office can provide the central coordination needed, given sufficient resources and support from HHS.

American adults receiving flu vaccine at about the same rate as in 2008, study finds

Wed, 09 Dec 2009 05:00:00 PST

( from http://www.rxpgnews.com ) American adults are not being vaccinated against the seasonal flu any more often than they were last year, despite increased public discussion of the importance of influenza vaccines resulting from the worldwide outbreak of the H1N1 virus, according to a new RAND Corporation study.

As of the middle of November, about 32 percent of all U.S. adults and 37 percent of adults recommended to receive a flu vaccination had been inoculated against the seasonal influenza, according to the study.

Researchers also found that 17 percent of all adults and 19 percent of those recommended for vaccination intended to receive the seasonal flu vaccine by the end of the vaccination season.

It does not appear that the increased public discussion of the role of influenza vaccines has had a significantly impact on the public's behavior, said Katherine Harris, the study's lead author and a senior economist at RAND, a nonprofit research organization. Most of the results from our latest survey look much like those from last year,

Health officials recommend the seasonal flu vaccine for about 70 percent of American adults, including people over age 50, those with high-risk medical conditions, health care workers and those who care for children under age 5. There are different recommendations for the H1N1 flu vaccine, which protects against the pandemic influenza strain.

One difference from last year noted by new survey is that adults began getting the seasonal flu vaccine earlier this year. Uptake of the seasonal vaccine during September was nearly three times as high -- about 9 percent in 2009 versus 3 percent in 2008. Yet, vaccine uptake through mid-November this year was comparable to uptake during the same period last year.

In addition, about half of health care workers had been vaccinated by the middle of November this year, roughly the same proportion that was vaccinated during the entire season last year. However, 40 percent of health care workers reported they had no intention of being vaccinated despite the risk of transmitting influenza to patients.

The findings are from a representative national survey conducted during the middle of November that asked more than 5,000 adults about their vaccination status and related issues. The survey is the latest in a series done by RAND and supported by GlaxoSmithKline, a manufacturer of flu vaccine.

Researchers say the study was designed to help inform public health officials and others about progress toward vaccinating adults prior to the end of the vaccination season while action can still be taken to improve uptake.

The study found that 29 percent of adults stated that they did not have the time to get vaccinated. In addition, seasonal flu vaccine availability may be a significant reason more adults have not been vaccinated. Among those intending to be vaccinated, about 38 percent said there was no vaccine available when they tried to get inoculated.

This finding highlights one of the public health challenges that we face in a year when a pandemic flu has made an appearance, Harris said. The early surge of uptake was attributed to additional awareness about seasonal flu vaccination in a pandemic year. It's important to keep this early interest in mind when planning for future pandemics.

Other finding from the study include:

Faulty immune memory can trigger cold sores

Thu, 12 Nov 2009 12:36:10 PST

( from http://www.rxpgnews.com ) A faulty immune memory can trigger infections that may lead to cold sores and even cancer in some people, say researchers.

The memory circuit, identified by the research team, involves a gene and protein called DOCK8, which helps white blood cells form synapses, tiny points of cell contact, that are responsible for memory in the brain.

An increased understanding of immune memory would not only lead to enhanced vaccines but also improve the treatment of cancer, transplant rejection, auto-immunity and allergies.

'Vaccines that provoke long-lasting immunity are among the greatest advances delivered by health research, but the circuits that determine whether they work or not have been among the most difficult to decipher,' said Chris Goodnow from the John Curtin School of Medical Research in Australia and co-leader of the research team.

Lapses of immunological memory also explain the reactivation of infections responsible for cold sores, shingles, yeast infections, and possibly some forms of cancer.

Katrina Randall, clinical immunologist and co-research team leader said: 'Immunity normally lasts for years after we are immunised or infected because our immune system remembers the shape and 'fingerprints' of an infecting microbe...'

'When immunological memory wanes we become susceptible to infection again. For some vaccines like the tetanus vaccine this occurs after several years, and for many experimental vaccines their memory has so far proved just too short to be useful.'

The findings were published in the latest issue of Nature Immunology.

NIAID announces new award to study the effects of radiation and aging on the human immune system

Thu, 12 Nov 2009 05:00:00 PST

( from http://www.rxpgnews.com ) The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has awarded nearly $9.7 million over five years to the Radiation Effects Research Foundation (RERF), Japan, to study the effects of atomic bomb radiation and aging on the human immune system. For the first time, experts in both the United States and Japan will systematically analyze biological samples from the unique population of elderly Japanese atomic bomb survivors to better understand the health consequences of exposure to ionizing radiation on the natural aging process.

As people grow older, their immune systems also age, leading to a gradual decline in the body's ability to fight infections, respond to vaccinations and prevent the development of cancer. The aging of the immune system, known as immunosenescence, is a major contributing factor to disease and death among the elderly. Radiation exposure appears to accelerate immunosenescence, although the molecular events that cause immunosenescence are not well understood.

According to the World Health Organization, in 2000 there were approximately 600 million people worldwide 60 years and older; WHO estimates that this number will jump to 1.2 billion by 2025 and 2 billion by 2050.

Understanding how the immune system ages will help us find better ways to care for this growing population, says NIAID Director Anthony S. Fauci, M.D.

This study will take advantage of the unique cohort of atomic bomb survivors who were exposed to varying levels of radiation in 1945. Using state-of-the-art technology, investigators will analyze blood samples from survivors to determine how radiation exposure alters the normal age-related decline of the immune system and identify the cellular and molecular changes that occur. They also will determine how the observed immune changes are related to disease and infection. One goal is to understand how exposure to ionizing radiation and aging affect a person's ability to respond to vaccination.

We will gain valuable information that will benefit not only the general public but also patients undergoing radiation for cancer treatment and those who could be exposed to radiation from an industrial accident or even a terrorist attack, says Daniel Rotrosen, M.D., director of NIAID's Division of Allergy, Immunology, and Transplantation, which oversees this award. This collaboration complements NIAID's program to develop medical countermeasures against radiological and nuclear threats.

Yoichiro Kosunoki, Ph.D., Kei Nakachi, Ph.D., and Tomonori Hayashi, Ph.D., of the Department of Radiobiology/Molecular Epidemiology at RERF, will lead a team of nine experts in Japan and in the United States:

Yoko Hirabayashi, M.D., National Institute of Health Sciences, Tokyo, Japan

New Mount Sinai research finds 9/11 responders twice as likely to have asthma

Tue, 03 Nov 2009 05:00:00 PST

( from http://www.rxpgnews.com ) First responders who were exposed to caustic dust and toxic pollutants following the 2001 World Trade Center (WTC) terrorist attacks suffer from asthma at more than twice the rate of the general U.S. population, according to data presented today by Mount Sinai School of Medicine researchers at CHEST 2009, the 75th annual international scientific assembly of the American College of Chest Physicians (ACCP), in San Diego.

As many as eight percent of the workers and volunteers who engaged in rescue and recovery, essential service restoration, and clean-up efforts in the wake of 9/11 reported experiencing post-9/11 asthma attacks or episodes. Asthma is typically seen in only four percent of the population.

Although previous WTC studies have shown significant respiratory problems, this is the first study to directly quantify the magnitude of asthma among WTC responders, said Hyun Kim, ScD, Instructor of Preventive Medicine at Mount Sinai School of Medicine (MSSM) and lead author of the analysis. Eight years after 9/11 the WTC Program is still observing responders affected by asthma episodes and attacks at rates more than twice that of people not exposed to WTC dust.

Researchers examined the medical records of 20,843 WTC responders who received medical screenings from July 2002 to December 2007 as part of the Mount Sinai School of Medicine-coordinated WTC Program. Results were compared with the U.S. National Health Survey Interviews adult sample data for the years 2000 and 2002 to 2007.

In the general population, the prevalence of asthma episodes and/or attacks in the previous 12 months remained relatively constant at slightly less than four percent from 2000 to 2007. In contrast, among WTC responders, while fewer than one percent reported asthma episodes occurring during the year 2000, eight percent reported asthma episodes in the years 2005 to 2007. In an age-adjusted ratio, WTC responders were 2.3 times more likely to report asthma episodes/attacks that had occurred during the previous 12 months when compared to the general population of the United States.

Of the study's rescue and recovery workers, 86 percent were men and the average duration of work at WTC sites was 80 days. The study followed uniformed and other law enforcement and protective service workers (42 percent of subjects), as well as construction workers and other responders who had engaged in paid and volunteer WTC-related rescue and recovery, essential service restoration and/or debris removal and clean-up efforts.

It is important to note that this report focused on findings from baseline or initial visit examinations, said Philip J. Landrigan, MD, Ethel H. Wise Professor and Chair of MSSM's Department of Preventive Medicine and Principal Investigator of the WTC Program Data and Coordination Center. The data show an increasing percentage of responders reporting asthmatic episodes, rising to double that seen in the general population. It is clearly vital that we continue to track responders' health and look further into the medical outcomes of this population.

Asthma and other chronic lung conditions remain a significant burden for rescue and recovery workers responding to the attacks on the World Trade Center, said Kalpalatha Guntupalli, MD, FCCP President of the American College of Chest Physicians. The significant chronic health problems associated with the WTC attacks only reinforces the need for stronger disaster preparedness plans as well as long-term medical follow-up for 9/11 responders and individuals who respond to disaster-related events.

Progress made on group B streptococcus vaccine

Fri, 30 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) WHAT: Scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have completed a Phase II clinical study that indicates a vaccine to prevent Group B Streptococcus (GBS) infection is possible. GBS is the most common cause of sepsis and meningitis in newborns in the United States, according to the Centers for Disease Control and Prevention (CDC). It can also cause severe illness in pregnant women, the elderly and adults with chronic illnesses. Colonization of the genital or gastrointestinal tract is a critical risk factor for infections due to GBS.

The researchers, led by Sharon L. Hillier, Ph.D., from the Magee-Womens Research Institute at the University of the Pittsburgh, found that the vaccine used in the study can cause a modest but sustained reduction in genital and gastrointestinal GBS bacterial colonization.

The GBS bacterium, which is commonly found in the gut and genital tracts, can infect the fetus during gestation and birth or after delivery. Pregnancy-related infections can lead to serious consequences for women including stillbirth. Currently, one-third of pregnant women in the United States test positive for asymptomatic GBS and receive antibiotics during labor to prevent infection of the newborn. Although this antibiotic strategy is highly effective, the broad use of antibiotics in pregnant women is of concern to public health officials. Many women are allergic to penicillin and penicillin-type antibiotics that are the preferred treatment, and GBS is increasingly resistant to other common antibiotics.

Dr. Hillier and her colleagues conducted a double-blind, randomized trial of the GBS vaccine that included a total of 650 sexually active, non-pregnant women ages 18 to 40 who were GBS-negative in the vagina and rectum at the beginning of the study. Approximately one-half of the women were in the control group and received a licensed tetanus and diphtheria toxoids (Td) vaccine instead of the GBS vaccine. The women were followed for 18 months after they were vaccinated and checked for GBS bacteria at regular intervals. The goal of the study was to see whether vaccination could prevent or decrease colonization by one of the most common subtypes of GBS bacteria: Type III.

Although the vaccine had a modest effect on bacterial colonization (36 percent in the vagina and 43 percent in the rectum), it provided some protection over the entire period of the study. The GBS vaccine also was found to be safe and well-tolerated, and elicited a strong immune response. The next step to prevent GBS disease would be to develop vaccines that provide protection against a broader range of GBS types and test them in clinical trials.

WHEN: Dr. Hillier will present these findings on Friday Oct. 30, 2009, at 10:00 a.m. at the 47th Annual Meeting of the Infectious Diseases Society of America in Philadelphia.

WHO: Fran A. Rubin, Ph.D., Program Officer for Group A streptococci, Group B streptococci, Maternal Immunization Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases

UC Davis leads attack on deadly new diseases

Fri, 23 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) In hopes of preventing the next global pandemic and a possible deathtoll into the millions, UC Davis today launches an unprecedentedinternational effort to find and control diseases that move betweenwildlife and people.

The global early warning system, named PREDICT, will be developedwith funding of up to $75 million over five years and is one of fivenew initiatives of the U.S. Agency for International Development(USAID) known in combination as the Emerging Pandemic ThreatsProgram. Building on its long-standing programs in diseasesurveillance and response, USAID is developing these initiatives tohelp prepare the world for infectious diseases like H1N1 flu, avianflu, SARS and Ebola.

UC Davis' primary PREDICT partners, which have formed a globalconsortium to implement PREDICT around the world, are: WildlifeConservation Society, Wildlife Trust, Global Viral Forecasting Inc.,and Smithsonian Institution.

Predicting where new diseases may emerge from wild animals, anddetecting viruses and other pathogens before they spread amongpeople, give us the best chance to prevent new pandemics, said JonnaMazet, the UC Davis scientist leading PREDICT. Mazet directs the UCDavis Wildlife Health Center within the new One Health Institute atthe School of Veterinary Medicine.

The concept of 'One Health' -- that human, animal and environmentalhealth are inextricably linked and should be considered holistically-- is a core principle of the PREDICT team.

To establish and maintain global pathogen surveillance, we will workdirectly with local governments and conservation organizations tobuild or expand programs in wildlife and human health. Together wewant to stop the next HIV, Mazet said. This collaborative approachis key to PREDICT's success.

The PREDICT team will be active in global hotspots where importantwildlife host species have significant interaction with domesticanimals and high-density human populations. They may include SouthAmerica's Amazon Basin, Africa's Congo Basin and neighboring RiftValley, South Asia's Gangetic Plain, and Southeast Asia. Asactivities in targeted regions come on-line, the team will focus ondetecting disease-causing organisms in wildlife before they spillover into people.

While no one can predict with certainty where the next pandemicdisease will emerge, being ready for early detection and rapidresponse will minimize its potential impact on our social andeconomic well-being, said Murray Trostle, deputy director of theAvian and Pandemic Influenza Preparedness and Response Unit of USAID.

UC Davis will bring on emerging-disease authority Stephen S. Morse ofColumbia University Mailman School of Public Health as director ofPREDICT. Morse said that, historically, pandemics -- epidemics thatspread around the world -- occurred perhaps every 30 to 40 years.But in our modern world, the chances of novel diseases or even a newpandemic emerging are higher than ever, because of how we live andthe extent to which we travel, Morse said. Our human settlements androadways push deeper into forests and wild areas where we now raiselivestock and poultry; and we transport ourselves, our animals andour food farther and faster around the globe.

Those conditions enable the spread of microbes, especially virusesand bacteria, from animals to humans. Among the 1,461 pathogensrecognized to cause diseases in humans, at least 60 percent are ofanimal origin.

Notable outbreaks of these animal-to-human diseases, or zoonoses(pronounced ZO-oh-NO-sees), include:

New therapy for vasculitis will help patients avoid infertility and cancer

Sat, 17 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have identified that Rituxan, a drug previously approved for the treatment of non-Hodgkin's B cell lymphoma and rheumatoid arthritis, can treat severe ANCA-associated vasculitis as effectively as cyclophosphamide, the current standard therapy. The news will be presented October 18 at the annual meeting of the American College of Rheumatology in Philadelphia.

The reason this is a big deal is that this is a disease where people would come in and be told 'listen, we are probably going to be able to get on top of your life-threatening disease by using cyclophosphamide, there is the potential for major side effects down the road from this drug,' said Robert Spiera, M.D., an associate attending rheumatologist at Hospital for Special Surgery in New York. This study provides strong evidence that Rituxan works as well as cyclophosphamide, at least in terms of getting patients into remission, and over that acute hump of being very ill. And, we can treat patients without the likelihood of causing infertility or causing secondary cancers, which have been a concern with the use of cyclophosphamide.

Hospital for Special Surgery was one of nine centers involved in the Phase III trial, which was led by Ulrich Specks, M.D., a professor of medicine in the Department of Pulmonary and Critical Care Medicine at the Mayo Clinic, and John Stone, M.D., MPH, director, Clinical Rheumatology, Massachusetts General Hospital.

Vasculitis, an inflammation of the blood vessels, can damage tissues and organs and, in severe cases, lead to death. Specifically, the study examined something known as ANCA-associated vasculitis that includes Wegener's granulomatosis and microscopic polyangiitis. The reason this is such a significant study is that this is an uncommon but devastating group of diseases, said Dr. Spiera. Prior to the use of cyclophosphamide treatment, 70 percent of patients who were diagnosed with severe forms of ANCA-associated vasculitis could be expected to be dead within three years. In the 1970s, doctors discovered that cyclophosphamide was extremely effective at combating the disease and could put people into remission. In the ensuing decades, however, doctors recognized that these drugs came with a price.

If you followed patients long enough, you found they had a higher risk of leukemias, lymphomas and solid tumors, said Dr. Spiera, who is also an Associate Professor at Weill Cornell Medical College. People would sometimes develop terrible infections. Women, almost reliably, would become infertile, as did many men. So, although it was a dramatically effective drug at reducing remissions in these patients, it came at a price.

In the current study, nine centers enrolled a total of 197 patients with severe Wegener's granulomatosis or microscopic polyangiitis, two of the more common types of ANCA-associated vasculitis. Patients were given steroids and randomized to receive either the standard treatment with cyclophosphamide or Rituxan given at a dose of 375 mg/m2 weekly for four weeks. Investigators used the standard tools to assess disease status and remission. The study was rigorously designed and was double-blinded, meaning that neither patient nor doctor knew which drug individuals were getting.

At the time of the data analysis, 84 of the 99 (85%) patients in the Rituxan arm and 81 of the 98 patients (83%) in the cyclophosphamide arm had completed six months of follow-up. Investigators found that the treatments were equally effective in putting patients into remission and that, in fact, the treatment outcomes looked slightly better in patients receiving Rituxan (64% vs. 55%). This difference, however, was not considered statistically significant (P=0.21).

These results show that the Rituxan worked at least as well as cyclophosphamide, Dr. Spiera said. If anything, there was almost a hint of it maybe looking a little better, and even in the short term, it looked safer in some respects. This study shows that there is strong evidence that Rituxan may be an alternative to cyclophosphamide in this disease. It might help manage flares in patients who have gone into remission, and it could be a consideration as first-line therapy, especially in women of child bearing potential who have a good chance of losing their fertility if treated with cyclophosphamide.

Until this study, there was only anecdotal evidence that Rituxan would be beneficial in patients with vasculitis. ANCA-associated vasculitis is one of the few rheumatic diseases that is equally represented in men and women. It can occur in people of all ages. Rituxan, manufactured by Genentech, is currently approved in the U.S. to treat non-Hodgkin's lymphoma and rheumatoid arthritis.

NIH prepares to launch 2009 H1N1 influenza vaccine trial in people with asthma

Fri, 09 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) The National Institutes of Health is preparing to launch the first government-sponsored clinical trial to determine what dose of the 2009 H1N1 influenza vaccine is needed to induce a protective immune response in people with asthma, especially those with severe disease. The study is cosponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Heart, Lung, and Blood Institute (NHLBI), both part of NIH.

People with severe asthma often take high doses of glucocorticoids that can suppress their immune system, placing them at greater risk for infection and possibly serious disease caused by 2009 H1N1 influenza virus, says NIAID Director Anthony S. Fauci, M.D. We need to determine the optimal dose of 2009 H1N1 influenza vaccine that can be safely administered to this at-risk population and whether one or two doses are needed to produce an immune response that is predictive of protection.

The study plan has been submitted to the Food and Drug Administration for review. With FDA allowing it to proceed, the clinical trial will be conducted at seven sites across the United States that participate in NHLBI's Severe Asthma Research Program.

This program already has a well-characterized group of participants with mild, moderate or severe asthma who may be eligible for this new study. These groups are largely distinguished by the amount and frequency of glucocorticoids needed to control asthma symptoms. People with mild disease may not need glucocorticoids, or may require low doses of inhaled glucocorticoids; those with moderate asthma need low to moderate doses of inhaled glucocorticoids; and those with severe asthma need high doses of inhaled glucocorticoids and frequently use oral glucocorticoids as well.

Individuals who already have been infected with 2009 H1N1 influenza or have received a 2009 H1N1 influenza vaccination will not be eligible for the study.

The results of this study will have immediate implications for individuals with severe asthma as well as those who have milder asthma, says NHLBI Director Elizabeth G. Nabel, M.D.

Early results from other clinical trials of 2009 H1N1 influenza vaccines in healthy adults have shown that a single 15-microgram dose of 2009 H1N1 influenza vaccine without adjuvant is well tolerated and induces a strong immune response in most participants. The same vaccine also generates an immune response that is expected to be protective in healthy children ages 10 to 17 years. Ongoing trials are comparing the immune response to one and two doses of 15- or 30-micrograms of vaccine given three weeks apart in various populations.

The Centers for Disease Control and Prevention has recommended that certain at-risk populations receive the new H1N1 vaccine as a priority before the general population. These target populations include pregnant women, health care providers and individuals with underlying chronic medical conditions, including asthma.

People who have severe asthma may be particularly at risk for infection with the 2009 H1N1 influenza virus. A report published in 2004 suggested that some people who took high doses of glucocorticoids to treat their asthma may receive less protection from influenza vaccines against some strains of influenza. Early in the 2009 H1N1 flu outbreak a CDC review of hospital records found that people with asthma have a four-fold increased risk of being hospitalized with infection compared to the general population.

The study will enroll approximately 350 people with mild, moderate and severe asthma. Participants will be organized into two groups: those with mild or moderate asthma and those with severe asthma. Half of the participants in each group will receive a 15-microgram dose of vaccine, and the other half a 30-microgram dose. Three weeks later, each participant will receive a second dose of the same amount. The strength of the immune response induced by the vaccine will be determined in blood samples by measuring the level of antibodies against 2009 H1N1 flu virus.

Safety data will be collected and examined throughout the course of the study by trial investigators and by an independent safety monitoring committee. Participants will be monitored for any side effects they may experience because of the vaccine, as well as asthma attacks that occur during the study period.

The vaccine to be used in the trial, manufactured by Novartis, contains inactivated 2009 H1N1 influenza virus and therefore cannot cause anyone to become infected with the virus.

The trial will be conducted at the following locations:

NIH launches 2009 H1N1 influenza vaccine trials in HIV-infected pregnant women

Fri, 09 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) The first clinical trials to test whether the 2009 H1N1 influenza vaccine can safely elicit a protective immune response in pregnant women launched yesterday, and a trial to conduct the same test in HIV-infected children and youth will begin next week. The International Maternal Pediatric Adolescent AIDS Clinical Trials Group is conducting the studies, which are sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), both part of the National Institutes of Health.

These studies are important because HIV infection and pregnancy both increase the risk for a poor immune response to the normal 15-microgram dose of seasonal influenza vaccine given to the general population, says NIAID Director Anthony S. Fauci, M.D. Moreover, children, young people and pregnant women are at higher risk for more severe illness from the 2009 H1N1 influenza virus than other groups, and HIV-infected individuals in these populations may be particularly vulnerable.

Because of the increased vulnerability of these populations, these trials are testing whether doses of licensed 2009 H1N1 influenza vaccine that are higher than doses being tested in other groups can safely elicit protective immune responses in HIV-infected children, youth and pregnant women, adds Lynne Mofenson, M.D., chief of the Pediatric, Adolescent and Maternal AIDS Branch in NICHD.

One trial will enroll 130 HIV-infected pregnant women ages 18 to 39 years who are in their second or third trimester (14 to 34 weeks) of pregnancy. The other trial will enroll 140 children and youth aged 4 to 24 years who were infected with HIV at birth.

Thirty-five sites and eight sub-sites across the United States and Puerto Rico are eligible to conduct the trials. Each volunteer will receive two 30-microgram doses of 2009 H1N1 influenza vaccine 21 days apart. (In contrast, the NIAID studies of 2009 H1N1 influenza vaccine in HIV-uninfected children, youth and pregnant women are testing doses of 15 and 30 micrograms.)

Safety data will be collected and monitored closely by the study investigators and an independent safety monitoring committee. The strength and longevity of the immune response elicited by the vaccine will be gauged in several ways.

The study team will take blood samples from the pregnant women after each dose and three and six months after delivery to measure the concentration of antibodies the women produce against 2009 H1N1 influenza virus and how strong that antibody response remains over time. After the women give birth, study staff will sample umbilical cord blood to measure the concentration of maternal antibodies against the H1N1 virus that were transferred to the infants through the placenta. The study team also will collect small blood samples from the infants at 3 and 6 months of age to measure their level of maternally derived antibody protection from the virus over time. The infants will not receive vaccine.

Similarly, in children and young people, the strength and longevity of the immune response will be gauged by testing blood samples taken 21 days after the first dose, 10 days after the second dose, and six months after entering the study.

The vaccine, manufactured by Novartis Vaccines and Diagnostics, contains inactivated 2009 H1N1 influenza virus, so it is impossible to become infected with the virus by receiving the vaccine. The vaccine does not contain adjuvant, a substance added to some vaccines to improve the body's response to vaccine.

Research on seasonal influenza vaccine and vaccines for other diseases in HIV-infected and other populations suggest that higher doses of vaccine tend to elicit stronger immune responses. These stronger responses, in turn, increase the concentration of protective antibodies in the bloodstream, which likely is beneficial to both the vaccinated individual and, if pregnant, to her fetus. This is the rationale for testing whether higher doses of licensed 2009 H1N1 influenza vaccine elicit a protective immune response in HIV-infected individuals and whether that protection is transferred to the fetuses of vaccinated pregnant women.

NIAID announces vaccine adjuvant discovery contracts

Thu, 08 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has awarded six new research contracts to discover and characterize novel adjuvants, substances that can be added to vaccines to enhance the protective immune response they induce.

The goal of these awards is to find safe new adjuvants that will boost the effectiveness of vaccines, says NIAID Director Anthony S. Fauci, M.D. Adjuvants can be used not only to enhance the immune response to a vaccine and thereby offer better protection but also to extend the vaccine supply if needed, enabling more people to be vaccinated with fewer doses.

Currently, the only vaccine adjuvant approved for use in the United States is an aluminum mixture known as alum.

NIAID has awarded a total of approximately $60 million over five years for these contracts. The awardees will identify novel compounds with the potential to be vaccine adjuvants. All compounds will be tested in animal models and human cells to determine how well they stimulate the immune response. The investigators also will examine and describe the cellular reactions the compounds induce.

The goal of these awards is not only to identify new adjuvant candidates but also to describe how these candidates work, says Helen Quill, Ph.D., chief of NIAID's basic immunology research branch. We would hope that these adjuvant candidates will become part of a robust pipeline leading to the development of many different vaccines.

The awardees of the adjuvant contracts will work to identify and characterize novel adjuvants that trigger receptors of the inborn, or innate, immune system. These receptors recognize and bind small molecules that are unique to harmful microorganisms. Binding stimulates an immediate innate immune response, a broadly protective reaction. The innate immune response also is required for the development of the highly specific antibody and T-cell responses that characterize long-term immunity.

The investigators also will seek to identify the cellular receptor for each of the novel adjuvant candidates, determine how it triggers the innate immune response, and then make changes to the adjuvant to improve its ability to induce the innate immune response. Although a number of innate immune receptors already have been described, many more likely exist and are expected to be uncovered in the course of these projects.

The award of these contracts is an integral part of NIAID's long-range plan to expand the adjuvant pipeline, says Daniel Rotrosen, M.D., director of NIAID's Division of Allergy, Immunology, and Transplantation, which oversees these awards. A first round of NIAID contracts, awarded in 2003, limited the discovery of novel adjuvants to those that stimulated the only group of innate immune receptors known at the time. With this second round of awards, we intend to increase the number of adjuvant candidates by expanding the research scope to include all known innate immune receptors.

The institutions receiving contracts for 2009 are

Lessons learned from H1N1 virus pandemic

Thu, 08 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) A comprehensive study has revealed, for the first time, the impact of swine flu on the health of the general public in Australia and New Zealand.

The lessons learned in Intensive Care Units (ICUs) across the two countries on the impact of the H1N1 (swine flu) virus are being shared with countries in the Northern Hemisphere to help them prepare for their upcoming flu season.

The three-month study, conducted at the height of the pandemic between June and August, reveals that 722 patients were admitted to ICUs and that at the peak of the epidemic up to 20 per cent of ICU beds were occupied by patients with swine flu infection.

The study was co-coordinated by the Monash University-based Australian and New Zealand IntensiveCare Research Centre (ANZIC-RC). The study involved all ICUs in Australia and New Zealand with the affected patients being treated in 109 of these units. The study was conducted utilising the resources of the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG).

Dr Ian Seppelt, a specialist in Intensive Care Medicine and based at Sydney's Nepean Hospital, saidthe impact of the virus on ICUs across Australia and New Zealand was dramatic.

Intensive Care Units specialise in the management of patients with life-threatening illness and thesurge of patients with H1N1 placed substantial strain on staff and resources. The most severely affected patients had pneumonia affecting both lungs that was caused by the virus. The number of patients admitted to ICUs with this complication represented a 600 per cent increase compared toprevious years, Dr Seppelt said.

Clinical Associate Professor Steve Webb, from the Intensive Care Unit at Royal Perth Hospital, wasanother key researcher on the project and said the information, which surfaced from the study willbenefit other countries about to head into their winter flu season.

Unlike previous 'seasonal' influenza strains, which impact heavily on elderly people and people withsevere coexisting medical conditions, the H1N1 virus affected a different profile. Critical illness due toswine flu was most common in infants and middle aged people; with pregnant patients, the overweight,and indigenous patients particularly affected. Overall, about one-third of patients admitted to anICU because of swine flu had no underlying health problems. Associate Professor Webb said.

Professor Rinaldo Bellomo, Foundation Chair of the ANZICS CTG and Director of Intensive CareResearch at Austin Health, Melbourne said the results of the study would be shared with health authorities in other countries to assist them better prepare for their flu season.

We have come through our flu season and our assessment of the impact of the H1N1 strain will assist them prepare for any outbreak. The H1N1 virus has taken hold in many countries already, but many countries in the Northern Hemisphere will benefit from the lessons we have learned, Professor Rinaldo Bellomo said.

Fortunately a vaccine is now available to prevent the complications of swine flu and it is important thatall members of the community and especially those with risk factors, consider being vaccinated, hesaid.

Research ensures 50 million vaccinated against deadly brain infection

Tue, 06 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Research at the University of Liverpool has supported the vaccination of more than 50 million people against a zoonotic brain infection that affects thousands of children across Asia every year.

The infection, called Japanese encephalitis (JE), is found in pigs and wading birds and transmitted by mosquitoes in areas of Southeast Asia and the Western Pacific. The World Health Organisation (WHO) estimates that JE affects approximately 50,000 people a year and kills around 15,000. Those that survive the infection can be left brain damaged.

Scientists at Liverpool, in collaboration with Asian governments, the WHO and the Program for Appropriate Technology in Health (PATH), are improving understanding of the disease and developing immunisation programmes to control it, with the support of funds from the Bill and Melinda Gates Foundation.

Children in poor rural communities are particularly vulnerable to the infection, but as a result of improved diagnostics and clinical management, vaccinations against the disease have now reached more than 50 million children and the programme continues across Asia.

Professor Tom Solomon, Head of the University's Brain Infection Group, said: Japanese encephalitis invades the central nervous system and can cause seizures, paralysis and in severe cases, death. Approximately 50 per cent of people who survive the infection are left with physical and mental illness, which could include personality changes. It affects children between the ages of one to 15, but adults, including tourists to the region, can contract the disease also.

Although we knew this disease was important, five years ago it was virtually unrecognised due to the difficulty in diagnosing cases. It causes disability more often than it causes death, but with no standard method of quantifying the disability, it was difficult for governments to make decisions on introducing vaccines. We have been developing ways of diagnosing JE and measuring the outcome of the infection, and these methods are now being used in many countries across Asia.

Previously scientists used highly specialised laboratories to grow cultures of the virus, but these facilities were not widely available across Asia. The Liverpool team, and partner institutions, have developed simple blood tests that allow medics to detect antibodies of the disease, a procedure that can be performed in hospitals and regional labs to provide accurate diagnosis.

Scientists have been working to enhance disease detection by developing surveillance guidelines, which helps medics build a database of all patients that enter hospitals with symptoms of the infection. The system allows authorities to monitor the number of people infected so that appropriate measures can be taken to protect against the disease. The team have also developed a standard method of quantifying the disabilities caused by JE. This gives a profile of the disease and shows how to characterise the disabilities children may have after the infection has left the body.

As a result of these new measures many governments across Asia are beginning to effectively control JE through vaccination.

Vitamin D's role in preventing asthma studied in pregnant women

Thu, 01 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) A group of pregnant women who have asthma or allergies will get extra vitamin D as part of a study to determine if the vitamin can prevent their children from developing asthma.

Washington University School of Medicine in St. Louis is part of the multi-center trial in collaboration with Boston University and Brigham and Women's Hospital in Boston and Kaiser Permanente Medical Center in San Diego.

Children born to one or both parents with asthma or allergies have a higher risk of developing asthma than children whose parents don't have asthma or allergies. Recent studies have shown that vitamin D plays a role late in pregnancy in developing lungs and that higher levels of maternal vitamin D may be associated with lower rates of asthma in their children. However, researchers don't know if increasing or correcting those vitamin D levels prior to or during pregnancy can prevent the disease.

We want to find a definitive answer to that question, says Robert C. Strunk, M.D., a Washington University pediatric asthma and allergy specialist at St. Louis Children's Hospital. If we could simply supplement women during pregnancy and decrease asthma prevalence in children, that would be a huge impact on child health.

Strunk, lead investigator of the trial, said asthma has doubled in U.S. children over the last two decades. About 6.7 million American children suffer from asthma, according to the Centers for Disease Control and Prevention, making it the most common chronic childhood illness. About 90 percent of all cases are diagnosed before age 6.

Vitamin D deficiency is also prevalent in the United States, occurring in healthy children and adults despite fortification of foods and intake of multivitamins. Pregnant and lactating women and their children are at high risk for vitamin D deficiency, although most pregnant women take prenatal vitamins. Researchers say the shift from outdoor activities and less time spent in the sun is one factor.

The Vitamin D Antenatal Asthma Reduction Trial (VDAART), a five-year research study funded by the National Institutes of Health, will enroll women between 10-18 weeks of pregnancy and randomly divide them into two groups. One group will receive a typical prenatal vitamin with 400 units of vitamin D and a 4,000-unit vitamin D supplement. The other group will receive the same prenatal vitamin plus a placebo.

The trial seeks to enroll 870 women nationwide. Washington University School of Medicine seeks to enroll 290 women from its obstetrics and gynecology clinics and one outside clinic.

During the course of the study, patients will attend regular visits with their obstetrician, provide blood and urine samples and answer questionnaires about diet, pregnancy, sunlight exposure, physical activity, health and medications. Their children born during the study will be evaluated for asthma and recurrent wheezing at ages 1, 2 and 3.

What's very attractive about this study is how simple it is, said George A. Macones, M.D., the Mitchell and Elaine Yanow Professor and head of Obstetrics and Gynecology at the School of Medicine and a co-investigator on the study. We hope that supplementing mothers with extra Vitamin D during pregnancy will help to reduce risks of asthma in children and will improve children's health over the long term.

HIV vaccine regimen demonstrates modest preventive effect in Thailand clinical study

Thu, 24 Sep 2009 04:00:00 PST

( from http://www.rxpgnews.com ) In an encouraging development, an investigational vaccine regimen has been shown to be well-tolerated and to have a modest effect in preventing HIV infection in a clinical trial involving more than 16,000 adult participants in Thailand. Following a final analysis of the trial data, the Surgeon General of the U.S. Army, the trial sponsor, announced today that the prime-boost investigational vaccine regimen was safe and 31 percent effective in preventing HIV infection.

These new findings represent an important step forward in HIV vaccine research, says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, which provided major funding and other support for the study. For the first time, an investigational HIV vaccine has demonstrated some ability to prevent HIV infection among vaccinated individuals. Additional research is needed to better understand how this vaccine regimen reduced the risk of HIV infection, but certainly this is an encouraging advance for the HIV vaccine field.

We thank the trial staff in Thailand and the United States for their years of effort in successfully conducting this study and the study participants and the people of Thailand for their long-standing support of HIV vaccine research, Dr. Fauci adds.

The Thai Phase III HIV vaccine study, also known as RV144, opened in October 2003. The placebo-controlled trial tested the safety and effectiveness of a prime-boost regimen of two vaccines: ALVAC-HIV vaccine (the primer dose), a modified canarypox vaccine developed by Sanofi Pasteur, based in Lyon, France, and AIDSVAX B/E vaccine (the booster dose), a glycoprotein 120 vaccine developed by Vaxgen Inc., and now licensed to Global Solutions for Infectious Diseases (GSID), based in South San Francisco, Calif. The vaccines are based on the subtype B and E HIV strains that commonly circulate in Thailand. The subtype B HIV strain is the one most commonly found in the United States.

Led by principal investigator Supachai Rerks-Ngarm, M.D., of the Thai Ministry of Public Health's Department of Disease Control, the study was sponsored by the U.S. Army in collaboration with NIAID, Sanofi Pasteur and GSID. The trial, conducted in the Rayong and Chon Buri provinces of Thailand, enrolled 16,402 men and women ages 18 to 30 years old at various levels of risk for HIV infection. Study participants received the ALVAC HIV vaccine or placebo at enrollment and again after 1 month, 3 months, and 6 months. The AIDSVAX B/E vaccine or placebo was given to participants at 3 and 6 months. Participants were tested for HIV infection every 6 months for 3 years. During each clinic visit, they were counseled on how to avoid becoming infected with HIV.

In the final analysis, 74 of 8,198 placebo recipients became infected with HIV compared with 51 of 8,197 participants who received the vaccine regimen. This level of effectiveness in preventing HIV infection was found to be statistically significant. The vaccine regimen had no effect, however, on the amount of virus in the blood of volunteers who acquired HIV infection during the study.

The Thai study demonstrates why the HIV vaccine field must take a balanced approach to conducting both the basic research needed to discover and design new HIV vaccines and, when appropriate, testing candidate vaccines in people, says Margaret I. Johnston, Ph.D., director of NIAID's Vaccine Research Program within the Division of AIDS. Both avenues provide critical information that will continue to help us better understand what is needed to develop a fully protective HIV vaccine.

NIAID and the collaborating partners are working with other scientific experts to determine next steps, including additional research of the RV144 vaccine regimen and the need to consider the impact of these new findings on other HIV vaccine candidates.

Individuals who acquired HIV infection while participating in the Thai trial have been provided access to HIV care and treatment, including highly active antiretroviral therapy based on the guidelines of the Thai Ministry of Public Health.

ART therapy for babies, mothers safely reduces HIV transmission

Wed, 22 Jul 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Giving daily antiretroviral syrup to breastfeeding infants or treating their HIV-infected mothers with highly active antiretroviral drugs is safe and effective in preventing mother-to-child HIV transmission through breast milk, a study led by University of North Carolina at Chapel Hill investigators has found.

This is an exciting development, said Charles van der Horst, M.D., a professor in the UNC School of Medicine and the study's lead investigator. We may be able to spare mothers in the developing world a horrible choice by offering them an effective method for preventing transmission of HIV during breastfeeding.

These findings, from investigators at UNC-Chapel Hill, UNC Project-Malawi in Lilongwe, Malawi and the U.S. Centers for Disease Control and Prevention (CDC), were presented July 22 at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town, South Africa (Abstract .WELBC1 - Late Breaker C 16:30 - 17:30 Session Room 2).

Approximately 420,000 infants are infected with HIV annually, half through breast milk. HIV-infected women in resource-constrained areas face a terrible dilemma: provide the many health and nutritional benefits of breast milk but face a 20 percent chance of transmitting the virus to their baby or choose costly formula, which relies on an unsafe water supply and carries a higher risk of morbidity and mortality, and avoid transmitting HIV.

The Breastfeeding, Antiretrovirals and Nutrition (BAN) study is the only large-scale, randomized trial comparing infant prophylaxis or maternal treatment to an enhanced standard-of-care arm in the prevention of HIV transmission through breast milk. The study was conducted in Lilongwe, Malawi at a single site. Investigators randomly assigned at total of 2,367 mother-infant pairs to one of three treatment arms. For both the interventions, the probability of HIV-infection was significantly lower than in the enhanced control arm.

Of the randomized infants, 4.9 percent were found to be HIV positive at birth. Among infants who were HIV-free at one week old, 6.4 percent on the enhanced control arm were infected by 28 weeks, compared to 3.0 percent of the infants on the maternal treatment arm and 1.8 percent of the infants who received daily nevirapine syrup. Upon examining the probability of HIV infection or death by 28 weeks postpartum, 7.6 percent of the infants on the enhanced control arm were HIV-infected or died compared to 4.7 percent of the infants on the maternal treatment arm, and 2.9 percent of the infants on the infant prophylaxis arm.

The BAN study results give global and national policy makers the choice of which intervention (maternal or infant antiretroviral intervention) to implement based on the conditions and resources in their particular setting. We hope to see these results translated quickly into program and policy.

Falling birth rates shift rotavirus epidemics

Thu, 16 Jul 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Fewer births in states such as California may be delaying the annual onset of a common intestinal virus in the southwest, according to epidemiologists. The timing of infectious outbreaks in other locations such as the northeast remains more or less unchanged.

Rotavirus is a leading cause of diarrhea among children, both in the developed and developing world. In the United States, the virus causes about 60,000 hospitalizations each year and kills about 40 children below the age of five.

It is an imperfectly immunizing infection, said Virginia Pitzer, postdoctoral researcher in the Center for Infectious Disease Dynamics and the department of biology, Penn State. So you can get infected multiple times throughout your life.

Up until the late 1990s, annual rotavirus epidemics in the U.S. followed a predictable pattern. Infections appeared in the southwest and peaked in December or January, then spread to the northeast, where they peaked in March. In recent years epidemics in the southwest have begun later than usual.

Pitzer and her colleagues initially looked at environmental factors such as solar radiation, precipitation and temperature but these could not explain the shifts in outbreaks of new infections. Unlike other viruses that die out and are replenished each year with new strains from outside the United States, rotavirus infections tend to linger in the summer months.

In general, the pattern of spread of rotavirus outbreaks from the southwest to the northeast is not consistent with any climatic factors, explained Pitzer, whose findings appear today (July 17) in Science. For instance, temperature tends to be high in the southwest but it also tends to be high in places like Florida, where epidemics occur much later.

Instead, Pitzer and her colleagues looked at human birth rates and the potential link to the timing of rotavirus epidemics. While birth rates are typically high in the southwest and low in the northeast, census data indicates a recent decline in the southwest, particularly in California.

Statistical analysis suggested a negative correlation between birth rates and the timing of the epidemics between 1991 and 2006.

Each time there was a decline in birth rate, whether from state to state or year to year, infections tended to happen later, explained Pitzer.

A mathematical model using information on the epidemiology of rotavirus and birth rates from states confirmed the statistical correlation and predicted that given the declining birth rate in California, rotavirus epidemics in the state would gradually shift from December to February.

Since infants often have diarrhea and can be very infectious when they get rotavirus, they are the ones who tend to drive the epidemics, said Pitzer, who is also associated with Fogarty International Center at the National Institutes of Health through the Research and Policy for Infectious Disease Dynamics program. Thus, you can get outbreaks of rotavirus happening a lot sooner when and where there are more infants being born.

Vaccines introduced in 2006 further confirm Pitzer's model. Since vaccination reduces the number of infants vulnerable to symptomatic infections, the effect is analogous to a decline in birth rate.

With the effects of vaccination factored in, the model accurately predicted a small decrease in the incidence of severe diarrhea during the 2006-2007 season, and a larger decline and delay during 2007-2008, providing validation for our model, said Pitzer.

Researchers add that high levels of vaccination could further limit the intensity of new epidemics and lead to a period of years with very few cases of severe diarrhea caused by rotavirus.

The important message here is that vaccination can have a big impact in controlling rotavirus infections, explained Pitzer. Even those not vaccinated can benefit from those vaccinated because it lowers the overall prevalence of the infection in the population.

Falling birth rates shift rotavirus epidemics

Thu, 16 Jul 2009 04:00:00 PST

Common chemotherapy drug triggers fatal allergic reactions

Mon, 08 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO -- A chemotherapy drug that is supposed to help save cancer patients' lives, instead resulted in life-threatening and sometimes fatal allergic reactions.

A new study from the Research on Adverse Drug Events and Reports (RADAR) pharmacovigilance program at Northwestern University Feinberg School of Medicine identified 287 unique cases of hypersensitivity reactions submitted to the FDA's Adverse Event Report System between 1997 and 2007 with 109 (38 percent) deaths in patients who received Cremophor-based paclitaxel, a solvent-administered taxane chemotherapy.

Adverse event reports generally only represent from 1 to 10 percent of actual incidence, so the number of hypersensitivity reactions and deaths is likely significantly higher. The severe allergic reactions are believed to be caused by Cremophor, the chemical solvent - a derivative of castor oil -- that is used to dissolve some insoluble drugs before they can be injected into the blood stream.

Two patients who died from an allergic reaction had early-stage breast cancer, which had been surgically removed, and were being treated with Cremophor-containing paclitaxel to prevent the cancer from coming back. Both of these patients had received medications before the chemotherapy to reduce the risk of hypersensitivity reactions.

The study was led by Charles Bennett, M.D., RADAR program coordinator and a professor of hematology/oncology at Northwestern's Feinberg School, and Dennis Raisch, a professor of pharmacy at the University of New Mexico.

The deaths of women with early-stage breast cancer are particularly disturbing because without the adverse reaction, they could have likely had 40 years of life ahead of them, Bennett said.

RADAR investigators also found that 22 percent of all fatalities occurred in patients despite patients having received premedication to prevent hypersensitivity reactions, while another 15 percent of such patients experienced life-threatening respiratory arrest.

The report was presented at the 45th Annual Meeting of the American Society of Clinical Oncology held recently in Orlando, Fla.

Cremophor-containing paclitaxel has been associated with hypersensitivity reactions, with responses ranging from mild skin conditions to more severe effects, including anaphylaxis and cardiac collapse. Current U.S. product labeling for Cremophor containing paclitaxel includes a black-box warning alerting physicians and patients of potential toxicity and recommending the use of corticosteroids and other medications before chemotherapy administration to reduce the risk of hypersensitivity reactions.

The results of our review suggest that physicians should be vigilant in monitoring the safety of their patients undergoing chemotherapy treatment, said Bennett, who also is the A.C. Buehler Professor in Economics and Aging at the Feinberg School and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Patients receiving Cremophor-based paclitaxel should be given medications to prevent hypersensitivity reactions, but what is sobering, as the study has shown and as the black-box warning indicates, women suffer anaphylaxis despite receiving steroid premedication, Bennett said. Physicians should be diligent in reporting adverse events to regulatory agencies to better monitor the impact of Cremophor on patient safety. Physicians may also want to consider exploring other alternative chemotherapy options that do not include Cremophor.

In addition to the two women with early-stage breast cancer who died after treatment with the Cremophor-based paclitaxel, four other women with early-stage breast cancer experienced life-threatening anaphylaxis reactions. Each of them had received prior medications to prevent the reactions.

The fatal outcomes observed in patients with early-stage breast cancer were particularly striking as this is a patient population with a good prognosis that is generally treated with curative intent, said Raisch.

For the report, Bennett and Raisch reviewed adverse event reports submitted to regulatory agencies in the U.S., Europe and Japan. The most common cancer diagnosis for these patients with allergic reactions was lung cancer followed by breast cancer and ovarian cancer.

First mouse model for auto-inflammatory diseases reveals role for innate immunity

Sun, 07 Jun 2009 04:06:31 PST

( from http://www.rxpgnews.com ) Researchers at the University of California, San Diego School of Medicine have developed the first mouse model for auto-inflammatory diseases, disorders that involve the over-activation of the body's innate, primitive immune system. Their study, published early on-line in Cell Immunity on June 4, suggests that the innate – not adaptive – immune system drives auto-inflammatory diseases. The findings could open new therapeutic directions for research into disorders such as gout or inflammatory bowel disease.

"Auto-inflammatory diseases are a relatively new classification of diseases that are different from autoimmune diseases or allergies," said Hal Hoffman, MD, associate professor of medicine at UC San Diego School of Medicine. Hoffman studies a group of rare, inherited auto-inflammatory conditions called Cryopyrin-Associated Periodic Syndromes (CAPS), which includes Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS).

Autoimmune diseases arise from an overactive response of the body's adaptive, or acquired, immune system against substances and tissues normally present in the body. Allergies are also a product of the adaptive immune system, but in response to environmental substances. Both involve the action of lymphocytes such as B cells and T cells. The older innate immune system, on the other hand, recruits immune cells to sites of infection and inflammation, but doesn't confer long-time protection. Pathogens evoke an inappropriate response that doesn't involve antibodies or lymphocytes.

With CAPS, Hoffman had earlier discovered that mutations of the NLRP3 gene caused the auto-inflammatory disease symptoms because the gene causes alterations in the protein called cryopyrin. Cryopyrin regulates the release of interleukin-1, an important mediator of fever and systemic inflammation during the body's innate immune response, and alterations in cryopyrin lead to over-production of Il-1.

Mutations in the NLRP3 gene are thought to result in inappropriate activation of a multi-protein complex called an inflammasome, leading to excessive Il-1β release and manifestation of CAPS disease symptoms. Treatment with Il-1β inhibitors reduces the inflammation and symptoms in auto-inflammatory diseases; however, NLRP3 may have other effects in addition to increased Il-1β.

"Patients treated with the Il-1β inhibitors got much better, but still exhibited some symptoms," said Hoffman.

In order to examine the role of inflammatory mediators and adaptive immune responses in CAPS, the researchers developed two NLRP3 mutant knock-in mouse models. (In "knock-in" models, genetic information is inserted into a particular part of the genome; in contrast to "knock-out" mouse models, in which genetic information is removed.) These mice had systemic inflammation and poor growth, similar to some human patients.

By mating these mice to mice with various gene mutant backgrounds, the scientists showed that CAPS requires an intact inflammasome, is only partially dependent on Il-1β and is independent of T cells. Their findings may help lead to more effective treatments for CAPS syndromes.

"The data shows that CAPS are true inflammasome-mediated diseases and that the adaptive immune system is not necessary for this disease," said Hoffman.

"In the larger picture, our findings also suggest that innate and adaptive immune systems don't necessarily always 'cross talk' or communicate with one another."

According to the researchers, given the importance of IL-Β and the inflammasome to innate immunity, NLRP3 knock-in mice may be applied to the study of many diseases along the autoinflammatory-autoimmune spectrum.

Obesity does not worsen asthma, but may reduce response to medications

Wed, 03 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Being overweight or obese does not make asthma worse in patients with mild and moderate forms of the disease, according to a study by National Jewish Health researchers, although it may reduce the response to medications.

With both asthma and obesity on the rise in recent years, there has been much interest in the possible link between these two conditions, said lead author E. Rand Sutherland, Associate Professor of Medicine at National Jewish Health. By studying a well characterized group of patients with asthma, we were able to determine that increased weight is not associated with more severe asthma. Although benefits can be obtained with weight loss in other diseases, these findings suggest that an improvement in asthma may not necessarily result from weight loss.

The findings also suggest that patients and physicians should be aware that obese asthma patients may not respond well to corticosteroids, the most successful controller medication for asthma, which can affect dosing decisions and choices of possible alternatives to steroids.

Previous studies have suggested that obesity predisposes people to developing asthma, to suffer more severe asthma symptoms, and to respond less to medications. However, the exact mechanism for these links has been unclear, and the studies have generally relied upon patients' reports of their diagnosis and symptoms rather than using more precise tools to characterize patients.

Dr. Sutherland and his colleagues decided to examine the issue in a well characterized group of 1,256 patients who had participated in NIH-sponsored studies. They divided them into patients with a body mass index of less than 25 (lean) and greater than or equal to 25 (overweight and obese). They found that lean asthma patients had slightly greater forced expiratory volume in one second , or FEV1 (3.05 liters vs 2.91 liters), and slightly greater ratio of FEV1 to forced vital capacity (83.5% vs. 82.4%), both common measures of lung function. They also found slightly greater use of rescue inhalers among overweight patients (1.2 puffs per day vs. 1.1 puffs per day) and slightly higher scores asthma-relate quality of life questionnaires (5.77 vs. 5.59).

These differences were small and are unlikely to be of any real clinical significance, said Dr. Sutherland.

Response to medications, however, did show an effect of increased weight. Among a subgroup of 183 people, lean patients taking inhaled corticosteroids alone showed a 55% greater reduction in exhaled nitric oxide, a measure of inflammation. Lean patients taking a combination inhaled steroid and long-acting beta agonist increased their FEV1 by 80 more milliliters. There were no differences, however, between these patients in the number of asthma exacerbations.

The data suggest overweight and obese people respond less well to controller medications for asthma than do their lean counterparts, said Dr. Sutherland. These data come from already-completed studies designed to answer other questions, however, and ongoing studies are being conducted to more definitively determine the effect of increased weight on treatment response in asthma.

Indiana U. research at the American College of Sports Medicine conference

Sat, 30 May 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Note: Information about the high-speed accelerometers study presented on Saturday is embargoed until the time of the 10:30 a.m. PDT presentation. Information about the other studies is not embargoed

CAFFEINE SHOWN AS EFFECTIVE AT REDUCING EXERCISE-INDUCED ASTHMA SYMPTOMS AS AN ALBUTEROL INHALER

An Indiana University study found that the ingestion of caffeine within an hour of exercise can reduce the symptoms of exercise induced asthma (EIA).

A large dose -- 9 milligrams of caffeine per kilogram of body weight -- was as effective as the use of an albuterol inhaler, which is commonly used to treat or prevent exercise-induced asthma. Smaller amounts of caffeine -- for example, 3 and 6 milligrams of caffeine per kilogram of body weight -- also reduced the wheezing, coughing and other symptoms of EIA.

Timothy Mickleborough, an associate professor in the Department of Kinesiology and co-investigator of the study, said no additional benefit was found when caffeine was combined with an albuterol inhaler.

Mickleborough and his research colleagues have been investigating the efficacy of a number of nutritional factors, and his research to date has shown that a diet high in fish oil and antioxidants and low in salt has the potential to reduce the severity of EIA and perhaps reduce the reliance on pharmacotherapy. This is especially important since prolonged use of daily medications can result in reduced effectiveness, and there is growing concern about the potential side effects of inhaled corticosteroid use.

*Background: The caffeine study involved 10 asthmatic subjects who also had EIA, in a randomized, double-blind double-dummy crossover study. They ingested 3, 6, or 9 milligrams of caffeine per kilogram of body weight or a placebo an hour before running on a treadmill. Pulmonary function tests were conducted 15 minutes before the a eucapnic voluntary hyperpnea challenge (a surrogate for an exercise challenge) and then again 1, 5, 10, 15 and 30 minutes afterward.

For someone weighing 150 pounds, 3 to 9 milligrams of caffeine per kilogram of body weight equals around 205 to 610 milligrams of caffeine. Earlier research has found that caffeine can reduce the symptoms of EIA. This study extends this earlier work and is the first to examine any synergistic effect of caffeine use along with an albuterol inhaler.

The study, Comparative and Synergistic Effects of Caffeine and Albuterol on The Severity of Exercise-Induced Bronchoconstriction, was presented at the American College of Sports Medicine conference during the Respiratory Session on Friday morning. Co-authors include lead author Timothy A. VanHaitsma, now at the University of Utah; Martin R. Lindley, Loughborough University, United Kingdom; and David Koceja and Joel Stager, IU's Department of Kinesiology.

Mickleborough can be reached at 812-855-0753 and

New vaccine strategy might offer protection against pandemic influenza strains

Mon, 18 May 2009 04:00:00 PST

( from http://www.rxpgnews.com ) A novel vaccine strategy using virus-like particles (VLPs) could provide stronger and longer-lasting influenza vaccines with a significantly shorter development and production time than current ones, allowing public health authorities to react more quickly in the event of a potential pandemic.

Ted Ross, Ph.D., an assistant professor at the University of Pittsburgh's Center for Vaccine Research, will present his laboratory's latest data on the efficacy of VLP vaccines for potential pandemic strains, such as H5N1 and 1918 influenza, today at the 109th General Meeting of the American Society for Microbiology in Philadelphia.

Virus-like particles look just like a live virus, but they are hollow shells without a genome inside and they cannot reproduce, Ross explained. Because they look like the virus, they evoke a more robust immune response against the real thing.

Ross and his colleagues have already made VLP vaccines that have been tested in early clinical trials and appear to provide complete protection against both the H5N1 avian influenza virus and the 1918 Spanish influenza virus.

There is a debate in the influenza community about priming the human population for potential pandemic strains such as H5N1 or 1918, Ross said. Some researchers advocate adding these strains to the annual flu vaccine. They might not match the next pandemic flu strain exactly, but could provide some of protection.

Others contend that it might be premature, as well as costly, to vaccinate people against a virus that may never emerge, he said.

The current injectable vaccine for seasonal influenza is a trivalent, inactivated vaccine. It consists of three different influenza strains that are grown in eggs and then inactivated, or killed, by chemicals that break them into tiny pieces. Because they no longer look like the circulating virus, conventionally made vaccines strains do not elicit as strong an immune response as VLP vaccines. Because it is made with live, attenuated virus, the inhaled, mist-based vaccine can elicit a strong immune response but can also increase the risk of side effects.

VLPs can be quickly and easily produced in several ways, including growing them in cell cultures or in plants. Also, if the genes in the disease virus are identified, then researchers can generate particles for a vaccine without an actual sample of the agent.

The sequence for the recent H1N1 'swine flu' virus was online and available to scientists long before physical samples could be delivered, Dr. Ross noted. It would have been possible to produce VLPs in quantity in as little as 12 weeks while conventional vaccines require physical samples of the virus and production can take approximately nine months.

One VLP-based vaccine already is on the market, namely the human papilloma virus (HPV) vaccine.

New procedure alleviates symptoms in people with severe asthma

Mon, 18 May 2009 04:00:00 PST

( from http://www.rxpgnews.com ) A new drug-free treatment for asthma has been shown to be effective in an international study of patients with severe, uncontrolled asthma. The results showed statistically significant improvements in quality of life and reductions in asthma attacks and emergency room visits for patients who underwent the treatment.

Conducted at 30 sites around the world, including Washington University School of Medicine in St. Louis, the trial tested a procedure designed to reduce the ability of the lung's airways to contract and interfere with breathing. The findings will be presented May 18 at the international conference of the American Thoracic Society in San Diego.

An acute asthma attack is characterized by contraction of muscle tissue in the airway walls in response to irritation, infection or inflammation. Although drugs can lessen the constriction of the breathing passages in many patients, some patients can't control their asthma symptoms even with high doses of medications. The new treatment uses a device to heat the walls of the lung's air passages to reduce the amount of muscle tissue and potentially inhibit narrowing of the airways.

One of the reasons I find this treatment exciting is that many patients with severe asthma are already taking the best drug therapy we have and are still experiencing debilitating symptoms, says the study's lead U.S. investigator, Mario Castro, M.D., a Washington University pulmonary specialist at Barnes-Jewish Hospital. This device provides a meaningful new treatment for such patients.

The device is the Alair Bronchial Thermoplasty System, developed by Asthmatx Inc., which funded the study. None of the trial's investigators has financial interest in the company.

The study, the Asthma Intervention Research 2 (AIR2) Trial, a randomized, double-blind, sham-controlled trial, follows the earlier AIR Trial, completed in 2005. AIR compared bronchial thermoplasty to standard medical care for moderate to severe asthma. That trial showed use of the device reduced asthma exacerbations and provided more symptom-free days than standard care.

But past research has shown that almost any medical procedure has the potential for a placebo effect or to cause a benefit not related to actual treatment. So the larger AIR2 trial compared patients who had bronchial thermoplasty with patients who had a sham procedure. In the sham procedure, all the instrumentation looked and sounded the same, but no heat was applied to airway tissue. In all, 297 patients participated in AIR2, two-thirds receiving the bronchial thermoplasty procedure and one-third getting the sham treatment. All patients were followed for one year.

During the post-treatment period, the treated group had an average 32 percent reduction in the rate of severe exacerbations and 84 percent fewer visits to the emergency department for respiratory symptoms compared to the sham group. Further, the treated group missed fewer days of work or school due to asthma symptoms, had more symptom-free days and needed rescue medication (fast-acting bronchodilators) less often than the sham group.

The researchers also determined how well patients responded using a standard quality of life questionnaire, which measured the physical and emotional impact of asthma. For both groups, the quality of life score rose, but the treatment group reported a greater improvement. Starting at an average score of 4.3 on a scale of one to seven (seven indicating high quality of life), the treated group experienced an average increase of 1.35, while the sham group saw an increase of 1.16. The difference in scores between the groups was statistically significant.

Although we were expecting the sham group to improve, the amount of their improvement surprised us, says Castro, professor of medicine and pediatrics in the Division of Pulmonary and Critical Care Medicine and director of the Asthma Center and Pulmonary Function Laboratory. Nevertheless, it was clear that the treatment did benefit most patients who received it.

Patients were sedated during the procedure, which involved inserting the catheter of the Aliar device deep into the main air passages of the lungs. The catheter has an expandable wire array at its tip. When deployed, the wires touch the airway walls and deliver heat. The thermoplasty treatments took place in three sessions, three weeks apart, and each session targeted a different area of the lungs.

During this treatment period, some patients in both groups experienced upper respiratory tract infections and a worsening of asthma symptoms such as wheezing, chest discomfort and cough. The treated group had somewhat more of these side effects during the treatment period but fewer during the post-treatment period compared to the sham group.

Patients considering the procedure will want to balance the possible risk of adverse events with the potential benefit, Castro says. There's no one answer for every patient. Each person feels differently about the impact of their asthma and what they might be willing to do to alleviate it. That's going to have to be a personal decision in consultation with their physicians.

The AIR2 trial is no longer recruiting participants, and before the thermoplasty procedure will be available to patients outside of the trial, the U.S. Food and Drug Administration (FDA) must approve the device for use in the treatment of asthma. Asthmatx has submitted it for FDA review, and a ruling is expected by fall of 2009.

Alzheimer's, asthma, cancer, malaria and TB focus of new Singapore grants

Tue, 28 Apr 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Over 50 research grants totaling $24 million in U.S. dollars have been awarded to Singapore universities, research institutes and hospitals to fund studies related to asthma and other immune system disorders, infectious diseases, aging and cancer.

The extramural grants were awarded by the Biomedical Research Council (BMRC) of A*STAR (Agency for Science, Technology and Research), the government agency driving Singapore's transformation into an international powerhouse in the biomedical and physical sciences.

In addition to extramural research grants, A*STAR sponsors the research institutes at Singapore's Biopolis and Fusionopolis.

The common dust mite, Blomia tropicalis, which can have an immense impact on quality of life and even be life threatening when it causes allergies in patients with chronic diseases such as cancer, is the focus of three grants awarded to Chua Kaw Yan, Ph.D., of the National University of Singapore's Department of Pediatrics.

One of Dr. Chua's studies will examine the mechanisms of an oral vaccine against the predominant allergen, the Blo t 5 protein, in B. tropicalis, which is responsible for 60-70% of allergy cases in Singapore, including asthma, allergic rhinitis and eczema.

Optimizing the potency of a genetic vaccine against the dust mite will be the focus of her second grant, while the third project will be directed at creating a modified or recombinant protein to foster immunity against Blo t 5.

Immunotherapy remains the only truly disease-modifying treatment for asthma and allergic rhinitis, said Dr. Chua. Traditional forms of immunotherapy use natural sources of allergens and have numerous disadvantages, such as the presence of undefined material, huge variability in sample composition, and contamination of allergens from other sources.

We therefore hope to use the major allergen, Blo t 5, to develop a novel and effective therapeutic vaccine for immunotherapy, she added.

Grants also were awarded to support research using genomics, proteomics and bioimaging to investigate the mechanisms of infection in tuberculosis and malaria, which cause deaths as well as serious illness despite widespread efforts to prevent their transmission.

In their studies of Mycobacterium tuberculosis (MTB), which infects an estimated two billion people worldwide, National Cancer Centre of Singapore (NCCS) scientists will sift through a bank of DNA samples extracted from drug-resistant MTB strains to identify novel mutated genes conferring resistance to Isoniazid, the main drug now used to treat tuberculosis.

In Singapore, the incidence rate of tuberculosis has increased for the first time in 10 years, leading to concerns over increased transmission of the MTB bacteria.

Ann Lee, Ph.D., who heads the NCCS research team that will investigate MTB, said: The identification of additional genes associated with Isoniazid resistance is important for the development of comprehensive molecular strategies that are potentially more efficient than current susceptibility testing methods, and could aid in giving more appropriate treatment to patients and decrease the spread of resistant strains. In addition, the discovery of new genes may reveal novel targets suitable for the development of alternative therapeutic options.

At Nanyang Technological University (NTU), a research team led by Peter Preiser, Ph.D., was awarded a grant to conduct basic research on the pathology of malaria, which infects as many as 600 million people worldwide and kills over 1 million yearly.

Novel lung cancer vaccine shows promise in fighting early-stage lung cancer

Mon, 06 Apr 2009 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO - An experimental vaccine that triggers the patient's immune system to identify and attack specific tumor cells is showing new promise for the treatment of early lung cancer. Thoracic surgeons at Rush University Medical Center are researching the vaccine called MAGE-A3 Antigen-Specific Cancer Immunotherapeutic, which is designed to kill cancer cells without harming normal cells. Rush is one of only five hospitals in Illinois offering the vaccine.

The MAGRIT (MAGE-A3 as Adjuvant Non-Small Cell LunG Cancer Immunotherapy) study is a randomized, double-blind and placebo controlled trial that will enroll patients with MAGE A-3-positive, non-small-cell lung cancers. The experimental vaccine targets MAGE-A3, a protein expressed in certain cancer cells but not in normal cells. Thirty-five percent of non-small-cell lung cancers have this protein which also is present in some melanomas and head and neck cancers.

The principle is that you can possibly teach a patient's immune system to eliminate cancer cells that express certain proteins such as the MAGE-A3 protein, said Dr. Anthony Kim, thoracic surgeon and principal investigator of the study at Rush. In a trial of early-stage lung cancer patients whose tumors expressed MAGE-A3, preliminary results showed that the vaccination reduced the risk of recurrence and the need for repeat surgery.

The vaccination may be a promising alternative treatment solution for lung cancer patients that may not be ideal candidates for chemotherapy. Many surgically treated lung cancer patients are not able to tolerate the side effects of chemotherapy.

Surgery is the standard treatment for patients with early-stage lung cancer, but approximately 50 percent of patients who have surgery ultimately die of lung cancer.

Adding the tumor vaccine to surgery has the potential to boost the survival rate by 10 percent, which was the figure that was observed in the initial phase of the MAGE-A3 trial, said Kim. This is a potential alternative for patients that otherwise would not undergo chemotherapy treatment either because of their tumor stage or other co-morbidities such as their age or other medical problems.

A total of 182 patients with non-small-cell lung cancers were included in the early phase of the study sponsored by GlaxoSmithKline, which is developing the vaccine therapy. All the patients had cancers expressing MAGE-A3, the tumor-specific antigen. After having surgery to remove the tumors, 122 patients were randomly assigned to treatment with the MAGE-A3-targeting vaccine and 60 patients received placebo vaccines. The preliminary research shows that the treatment was well tolerated by patients and the MAGE-A3-treated patients seemed less likely to have recurrences and die from their disease than the placebo-treated patients. Further studies need to be completed to test the safety and efficacy of the vaccine.

Patients were given five injections every three weeks at the beginning of treatment and then eight injections every three months later for a total of 27 months. Earlier phases of the study indicate the immunotherapy treatment was well tolerated by patients.

Environment plays role in complex heart defect

Mon, 30 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) A congenital heart disease that often leads to death in newborns is significantly more common during the summer, leading researchers to believe that the environment, and not just genes that affect the heart, may play a role in causing mini-epidemics of this disease.

A cardiac surgeon from Cincinnati Children's Hospital Medical Center presents this research today at the annual American College of Cardiology Meeting in Orlando, FL. The study is a finalist in the ACC's Best Poster Awards Competition.

Hypoplastic Left Heart Syndrome is one of the most complex cardiac defects seen in newborns and remains probably the most challenging to manage of all congenital heart defects. In a child with HLHS, all of the structures on the left side of the heart (the side which receives oxygen-rich blood from the lungs and pumps it out to the body) are severely underdeveloped. This results in the left side of the heart being completely unable to support the circulation needed by the body's organs.

The most common treatment for HLHS is staged reconstruction, in which a series of operations, usually three, are performed to reconfigure the child's cardiovascular system to be as efficient as possible despite the lack of an adequate left ventricle. Current management at major pediatric heart centers has resulted in survival rates of 75 percent or better.

Pirooz Eghtesady, MD, PhD, a cardiothoracic surgeon at Cincinnati Children's, led a study of nearly 1,500 newborns from 38 children's hospitals in the United States who had left-sided congenital heart diseases. Dr. Eghtesady and his colleagues found a seasonal occurrence of HLHS, but not other left-sided diseases, over a 10-year period, 1996 to 2006. Seasonal differences in HLHS occurred each year, with peaks between April and July and low points in January.

Strong seasonality is a clue that environmental factors may play an important role in this disease, as we see, for example, with such common childhood illnesses as asthma and croup, says Dr. Eghtesady. The study augments some prior epidemiologic studies and points the finger at the possibility of additional factors. It also opens the window for genetic studies to consider candidate genes not directly related to cardiac maldevelopment, such as those involved in immune responses, which really have not been considered in the past.

One potential environmental factor being studied by Dr. Eghtesady and colleagues is recurrent maternal exposure to the common agent strep throat, which is also responsible for the devastating condition known as rheumatic heart disease. Numerous studies have indicated that an immune reaction against strep in rheumatic heart disease can lead to injury on the left side of the heart, which is the side also affected in HLHS. Dr. Eghtesady's preliminary study suggests that many mothers whose newborns had left-sided heart injury had a significant history of problems related to strep throat.

Cincinnati Children's is involved in an ongoing clinical trial looking at maternal history of strep exposure compared to mothers with normal hearts and mothers affected by other cardiac defects. Researchers at Cincinnati Children' also are studying whether there are antibodies in the blood of mothers exposed to strep similar to ones found in patients with rheumatic heart disease

NF-κB mediated bioluminescence- sensitive and early indicator in auto-immune diseases

Wed, 25 Mar 2009 16:06:56 PST

( from http://www.rxpgnews.com ) Current research describes a new method to track the development of autoimmune diseases before the onset of symptoms. The related report by Zangani et al, "Tracking early autoimmune disease by bioluminescent imaging of NF-κB activation reveals pathology in multiple organ systems," appears in the April 2009 issue of The American Journal of Pathology.

Autoimmune diseases such as lupus, multiple sclerosis, rheumatoid arthritis and diabetes are caused when the immune system attacks the body's own cells. Normally, immune cells are prevented from attacking normal cells; however, in patients with autoimmune disease, this "tolerance" is lost. The immediate causes of autoimmune diseases remain unknown, partially due to the inability to detect disease before the onset of symptoms. Early detection of autoimmune disease is critical for assessing new treatments.

The molecule NF-κB is activated by inflammation, which plays a key role in autoimmune disease development, making NF-κB a prime candidate to track autoimmune activity. Researchers at the University of Oslo led by Drs. Ludvig Munthe and Bjarne Bogen in collaboration with Rune Blomhoff engineered NF-κB such that it would emit light when activated. Using a mouse model of systemic autoimmunity with features of lupus, they found that NF-κB activation signals were present in affected organs several weeks before the clinical manifestations of disease. The light signal intensity correlated with disease progression. NF-κB tracking may therefore provide a new tool in the evaluation of early autoimmune therapies.

The article from Zangani et al "indicate[s] that NF-κB mediated bioluminescence is a very sensitive and early indicator of inflammation and disease", allowing precise identification of incipient disease sites for biomedical and pathogenetic studies. In future studies, Drs. Munthe, Bogen, and colleagues will utilize this new model "for studies on early intervention, e.g. drug treatment, to prevent or treat autoimmune disease", and for studies of the development of B cell lymphoma.

Biotech company cofounded by BIDMC scientists targets natural killer T-cells

Thu, 19 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) BOSTON -- NKT Therapeutics, Inc., a Newton-based biotechnology company cofounded by Beth Israel Deaconess Medical Center (BIDMC) researchers Steven Balk, MD, PhD, and Mark Exley, PhD, has announced that it has closed an $8M Series A venture financing co-led by venture capital firms SV Life Sciences (SVLS) and MedImmune Ventures.

The company will work to develop therapies based on natural killer T-cells, with their first program focusing on treatments for asthma.

Doctors Balk and Exley [together with the company's third cofounder Brian Wilson, MD, PhD, of Massachusetts General Hospital] have extensive expertise in the applications of immunotherapeutic agents to human disease, explains Mark Chalek, Chief of Business Ventures at BIDMC. Their research has helped to establish the important role of NKT cells in the regulation of many immune responses.

Although NKT cells represent approximately .01 percent of the body's total lymphocyte population, they serve as a central regulator of the immune system, playing a critical role in health and disease, according to Balk, a member of the Division of Hematology/Oncology at BIDMC. By regulating the innate arm of the immune system, NKT cells help to destroy threatening pathogens and cancers, he explains. And by regulating the immune system's adaptive arm, they help to modulate antibody and cell-mediated immunity, which offers sustained protection over time.

Balk and Exley have been studying natural killer T cells since 1996. They were the first investigators to identify the NKT human subset, functionally define these immune cells, and demonstrate that they had defects in cancer patients. The scientists were also the first team to describe the cells' anti-viral roles and to characterize related populations of cells in liver and bone marrow, as well as to demonstrate their roles in various disease states.

NKT cells are a very potent source for good in some types of immune response, but in other instances can cause problems, adds Exley, who is also a member of BIDMC's Division of Hematology/Oncology. By selectively activating or depleting NKT function we plan to develop drugs that can target a wide range of diseases, from asthma and autoimmune disorders to cancers and infectious diseases. Asthma is one of the conditions in which NKT cells create an adverse immune response. Therefore, by downregulating NKT activity, we hope to create successful asthma treatments.

I am very excited to lead the development of this very promising technology whose broad potential for addressing major health care needs is underscored by this successful financing, adds Robert Mashal, MD, President and Chief Executive Officer of NKT Therapeutics.

NKT Therapeutics has licensed an extensive intellectual property portfolio from Beth Israel Deaconess Medical Center (BIDMC), Dana Farber Cancer Institute, and Massachusetts General Hospital. Stan Mah of BIDMC's Technology Ventures Office (TVO) had the lead role in organizing licensing on behalf of all parties.

Studies show children can complete treatment for peanut allergies and achieve long-term tolerance

Sun, 15 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) DURHAM, NC -- A carefully administered daily dose of peanuts has been so successful as a therapy for peanut allergies that a select group of children is now off treatment and eating peanuts daily, report doctors at Duke University Medical Center and Arkansas Children's Hospital.

It appears these children have lost their allergies, says Wesley Burks, MD, Chief of the Division of Pediatric Allergy and Immunology at Duke. This gives other parents and children hope that we'll soon have a safe, effective treatment that will halt allergies to certain foods.

Long-term tolerance in children with peanut allergies was documented for the first time by the presence of key immunologic changes, according to researchers at Duke and Arkansas Children's Hospital who presented their findings at the American Academy of Asthma and Immunology meeting in Washington, DC today.

Tests of several immunologic indicators suggest the body builds tolerance quickly.

At the start of the study, these participants couldn't tolerate one-sixth of a peanut, Burks said. Six months into it, they were ingesting 13 to 15 peanuts before they had a reaction.

About four million Americans have food allergies, and allergies to tree nuts and peanuts are the most common. Life-threatening reactions can occur from exposure to even a trace amount of peanuts, and nearly half of the 150 deaths attributed to food allergies each year are caused by peanut allergies.

Duke and Arkansas Children's Hospital began enrolling patients in studies five years ago to determine if incremental doses of peanut protein could change how the body's immune system responds to its presence. The doses start as small as 1/1000 of a peanut. Eight to 10 months later, the children are ingesting the equivalent of up to 15 peanuts per day. The children stay on that daily therapy for several years and are monitored closely.

Nine of the 33 children participating in the study have been on maintenance therapy for more than 2.5 years. After a series of food challenges, four of those children were taken off the treatment and continue to eat peanuts. Some have been off treatment for more than a year. Doctors keep tabs on any potential changes in their immune system via skin, blood and immune studies.

One of the tests used in the study looks at immunoglobulin E (IgE), a protein the body makes in response to peanut allergens. If you have it, you're likely allergic, if you don't, you aren't, explained Burks. Children in this study generally started with IgE levels greater than 25. At the end of the study, their peanut IgEs were less than 2 and have remained that way since we stopped the treatment, he said.

Because the pool of children now off treatment is so small, Burks says it's hard to say whether these children simply outgrew their allergies or if the therapy did something to enhance that outcome. The next step is a blinded study in which children on treatment are compared to a control group. First year results were presented at the meeting by Stacie M. Jones, MD, a pediatric allergist at Arkansas Children's Hospital. So far, the oral immune therapy appears to be working.

We see initial desensitization effects of the treatment are real, Burks says. Those children are now able to eat up to 15 peanuts with no reaction, but the children not on treatment have symptoms early on in the study.

Despite the news, Burks insists this research is still ongoing and cautions parents and professionals against trying any version on their own. In my clinic, I would do the same things I've always done. Once diagnosed with a food allergy, I would recommend they avoid the food. We have to wait for the studies to show the treatment is safe, and to see desensitization start to work. We also want to know the therapy works long term.

Burks also cautions that some people are too sensitive to peanut allergens to be able to undergo the therapy.

African-Americans aware and accepting, but often do not receive, the HPV vaccine

Wed, 04 Feb 2009 05:00:00 PST

( from http://www.rxpgnews.com ) CAREFREE, A.Z. - Although only 25 percent of eligible African-American adolescents have received the HPV vaccine, a new survey presented at the American Association for Cancer Research conference on the Science of Cancer Health Disparities, suggests they have a positive view of the treatment and might respond to more education.

The Pennsylvania Department of Public Health is funding research to develop ways to increase the rate of HPV vaccination among those at highest risk. HPV vaccination prevents cervical cancer by inoculating against the human papillomavirus.

The consensus among those surveyed in our study was that it would be a good, beneficial option, said Ian Frank, M.D., professor of medicine in the Infectious Diseases Division of the University of Pennsylvania.

The HPV vaccine, approved for use in the United States as Gardasil and manufactured by Merck and Co., has been shrouded in controversy since it was released in June 2006.

Frank said the controversies break down into four basic areas. Following approval, Merck pushed for mandatory vaccination, which is generally opposed by citizens in the United States who believe health care decisions should not be forced. Others were concerned about the long-term efficacy of the vaccine or its possible side effects.

Most famously, some groups insisted that if adolescents were aware that they could inoculate themselves against the human papillomavirus, which is spread through sexual contact, they would be more likely to have early sexual relations.

I doubt that whether or not she is at risk for cervical cancer is on an adolescent's mind in the heat of the moment, said Frank.

Frank said the African-Americans who participated in the survey conducted by his research group were aware of these controversies, but they did not outweigh their positive views of the vaccine as an option.

Researchers surveyed 71 females for the study; 94 percent were African-American and the mean age was 15.3 years. Approximately 60 percent of them had had their first sexual encounter when they were 14 years old.

Of those who had not received the vaccine, 43.9 percent said they were very likely or likely to do so soon. A majority believed it was a good or very good idea and they generally viewed the vaccine as safe, effective and a wise choice.

Forty-five caregivers of adolescents also participated in the study, all of whom were African-American, 94 percent were female and 47.9 percent had a high school diploma.

The caregivers agreed that the vaccine was safe, effective and a wise choice, but two-thirds of them could not recall their health care provider ever mentioning the HPV vaccine.

Many of these caregivers, most of whom were women, reported feeling overwhelmed by the challenges of raising an adolescent girl, but they wanted to protect their daughters from health and emotional risks, said Frank. This suggests they would respond positively to an increased effort to inoculate.

Ireland Cancer Center researcher finds most triple-negative breast cancers express muc-1 target

Fri, 12 Dec 2008 05:00:00 PST

( from http://www.rxpgnews.com ) CLEVELAND: Research out of the Ireland Cancer Center of University Hospitals Case Medical Center has found that the vast majority of triple negative breast cancers express the MUC-1 target. This first-of-its-kind finding, presented today at the San Antonio Breast Cancer Symposium, has paved the way for an upcoming vaccine trial for patients with early stage triple negative breast cancer that could potentially prevent recurrence of this aggressive type of breast cancer.

Joseph Baar, MD, PhD, Director of Breast Cancer Research at the Ireland Cancer Center, and colleagues analyzed 53 tumors and determined that 92 percent of them expressed MUC-1. These findings support their theory that this MUC-1 protein on breast cancer cells could be a target for a novel vaccine using the patient's immune system to target and kill cancer cells.

Dr. Baar has received a prestigious grant from the National Cancer Institute and the Avon Foundation to begin the vaccine trial in January 2009 for women with early stage triple negative breast cancer to see if this vaccine can raise their immune response against MUC-1. If it does, then a later study would be undertaken to determine whether the generation of such an immune response leads to an increase in patients' relapse-free survival rates, thereby preventing recurrence. The vaccine will be administered following standard therapy of surgery, radiation and chemotherapy.

This vaccine trial has the potential to rev up patients' immune response to the MUC-1 protein and shut down the tumor's ability to grow, says Dr. Baar. Women with this aggressive triple negative breast cancer have an increased risk of recurrence and we are hoping to provide them with protection against the return of this deadly disease. Our findings that have been presented at the San Antonio Breast Symposium provide us a strong basis for this trial.

Triple negative breast cancer is a highly aggressive form which comprises 10-15 percent of newly diagnosed early stage breast cancer. Most triple negative tumors are high grade and have a high incidence of recurrence and metastases (spreading to other organs). Unlike other types of breast cancer, there is no standard follow-up treatment for triple negative breast cancer to prevent recurrence.

This is an important study because there has traditionally been nothing to offer women with triple negative breast cancer beyond standard therapy, says Stanton Gerson, MD, Director of the Ireland Cancer Center. This vaccine trial has the potential to lay the groundwork for a new standard of care for women with this aggressive form of breast cancer.

K-State researcher finds correlation between childhood obesity and asthma

Fri, 12 Dec 2008 05:00:00 PST

( from http://www.rxpgnews.com ) MANHATTAN -- A Kansas State University graduate student has found a correlation between childhood obesity and asthma.

Sara Rosenkranz, doctoral student in human nutrition, Manhattan, conducted research that found that healthy children with higher levels of body fat and lower levels of physical activity had greater amounts of airway narrowing after exercise.

Kids who are overweight and inactive are having -- even at the age of 8 to 10 years old -- a negative response to exercise challenge tests, which might be contributing to the increase that we've been seeing over the past several decades in asthma prevalence as well as obesity prevalence, Rosenkranz said.

Rosenkranz worked with other K-State faculty and students to recruit 40 children in the 8- to 10-year-old age range to participate in exercise studies. All of the children were healthy, meaning none of took medication or had a diagnoses or history of acute or chronic disease, including asthma.

For Rosenkranz's project, the children completed pulmonary function tests, an exercise test that doctors often conduct to determine if children have asthma, and body composition tests.

The children also took questionnaires to determine if they were active or inactive compared to the standards of their age, gender and ethnicity.

After the exercise challenge, the researchers measured the children's FEV-1, which determines if the individual's airwaves narrow post-exercise. The researchers found that the higher the body fat and the lower the level of activity of the child, the more likely they were to have asthma-like symptoms following exercise. In fact, these specific children had FEV-1 measures that many consider to be classified as exercise-induced asthma.

It was pretty interesting. There's that whole idea that it's possible to be fit and fat in adults, but that really hasn't been looked at closely in kids, Rosenkranz said. That's what spurred the idea for this research.

At the completion of the project, a follow-up letter was sent to the parents that showed their child's pulmonary test results and body fat percentage, which also had the corresponding fat group based on the child's age, gender and ethnicity.

It's important for parents to know what's going on with their children at a young age so that they can help do something to maybe stop a downward cycle, Rosenkranz said. It's especially important for those kids who already are overweight and are very physically inactive.

For many of the students that had higher levels of body fat and lower levels of activity, Rosenkranz said it is possible that they had the early stages of asthma and they didn't know it.

They might not know it because they might not be doing anything that could ever trigger it, she said.

When an asthma diagnosis is made, Rosenkranz said it is important that the child remain active to prevent airway problems.

Before the study, little was known about the role body composition and physical activity have in airway health in children, Rosenkranz said. When considering childhood obesity, pulmonary function wasn't often considered, she said.

At K-State, we just started working with the childhood population, she said. We've been working more with college-age students because that's a handy group to have access to, but with kids, it's a whole new world and there's not much information out there.

Immunology Center will continue to drive standard methods, better science

Thu, 11 Dec 2008 05:00:00 PST

( from http://www.rxpgnews.com ) The Rochester Human Immunology Center (RHIC) has been awarded a $4 million renewal of its grant from the National Institute of Allergy and Infection Disease (NIAID). The renewal enables RHIC to continue leading the field of immunology in a worldwide effort to standardize how researchers use complex technologies like flow cytometry that are central to the discovery of new treatments.

When standardization is achieved, researchers will be better able to compare data collected worldwide, with the results of many studies combined into massive datasets to guide the construction of hyper-accurate computer models of the mechanisms of disease. Such simulations will yield scientific conclusions that are dramatically more valid and reproducible in areas like infectious disease, transplantation and cancer, researchers said. The resulting sophistication in understanding of the human immune system, and of how it responds to influenza, HIV or smallpox for instance, will guide the more precise design of near-future vaccines.

Since its founding four years ago, the RHIC has proven that it can drive the development of standard operating procedures, having helped more than 39 investigators and teams standardize their testing, and lending expertise that helped lead to the winning of 22 major grants. As an internationally known resource, the RHIC is part of working groups seeking to standardize methods for analyzing flu viruses and HIV in partnership with the Division of Microbiology and Infectious Diseases at NIAID, the HIV Vaccine Trials Network and the New York Influenza Center of Excellence.

Standardizing test methods to achieve comparable results goes far beyond being able to compare apples to apples, said Sally Quataert, Ph.D., director of Core Facilities for the University of Rochester School of Medicine and Dentistry, and co-principle investigator for the grant renewal. Validated methods assure researchers that their experimental results are good science, and truly meaningful. Standard methods also directly contribute to translational science, where the results of studies are more readily affirmed by regulatory bodies, and with fewer conflicting studies.

Prior to 2004, Quataert was director of Immunobiological Laboratory Services at Wyeth Vaccines Research in Rochester for seven years. Her industry background prepared her to apply Good Laboratory Practice (GLP) standards to academic studies, making them more likely to withstand scrutiny by the U.S. Food and Drug Administration as sound evidence that new treatments are safe and effective. If applied internationally, such standards would make drug candidates discovered at universities much easier to license to industry, with potential to increase the number of new drugs becoming available.

Also recently joining the RHIC executive committee was Tim Bushnell, Ph.D., director of the Flow Cytometry Core at the University of Rochester Medical Center. Bushnell's active role in the International Society of Analytical Cytology (ISAC) has positioned RHIC, not just to develop expertise, but also to take a leading role in the groups that are shaping related standards worldwide.

Flow cytometry is a method of counting and sorting cells that have been labeled by fluorescent markers which correspond with physical and chemical qualities of the cell. Modern flow cytometers can analyze thousands of cells in real time to unravel the complex interactions driving disease processes. The devices beam laser light into a stream of liquid which carries the cells to be analyzed. Detectors catch the patterns of fluorescent light that bounce off single cells as they pass through the laser. The cells have been prepared with fluorescent dyes that absorb the laser light and emit light at lower frequencies in scatter patterns that reveal information about the cell.

Modern instruments have multiple lasers and fluorescence detectors, with 18 fluorescence detectors now commonplace in larger research institutions. Increasing the number of lasers and detectors enables more precise identification of target cell populations by their characteristics. Four years ago, the RHIC had eight-color flow cytometry, but has since upgraded to 11- and 18-color cytometers with support from the Medical Center and its Clinical Translational Science Institute (CTSI). Researchers receive training on flow cytometry and other key discovery techniques and gain access to a growing suite of RHIC equipment. With the renewal of the NIAID grant, the center will continue to develop and standardize immunological methods.

Beyond general leadership and standard setting, the center will take the lead in the next five years in helping the field to make better use of three cutting-edge technologies of immense importance. The goal is to advance technologies to maturity so that they can be applied widely, with the new standards communicated through publications, the RHIC Web site and symposia.

The first technology is arrayed image reflectometry, which promises to be very useful in large-scale analysis of immune responses against multiple disease-causing proteins like those encountered during influenza outbreaks. Immune system proteins can be coated with a thin film that prevents light from reflecting off of them, but that become more reflective as the proteins bind to disease-related proteins. When several proteins to be tested are attached to a biochip, a great many proteins can be analyzed for little cost.

The grant renewal will also bring together RHIC experts in cytometry and in a second new technology: quantum dot nanostructures. These microscopic machines have optical qualities that can be harnessed to measure cellular qualities via flow cytometry with more precision than fluorescent dyes. Like dyes, the dots can be designed to inhabit certain regions of the cell, or cling to certain proteins, so that their number and characteristics can be measured. Dyes are an older technology, limited in number and with overlapping emission spectra, which means they interfere with each other. RHIC teams will seek to establish new Q-dot production methods to replace and extend dye capability. As RHIC machinery gets more complex, it will become increasingly able to pick apart and to build accurate immune cell models.

Thirdly, the team will seek to design better gating procedures. Flow cytometry separates cell types by brightness into groups, and gating is the process by which researchers select which cells go into each group. The current process in many labs is arbitrary, tedious and has poor reproducibility between operators because research teams select patterns of cell characteristics by eye. The field of flow cytometry is in desperate need of high-speed automation to process the mountains of data generated by the tests, and when gating the results, researchers said. The current process is greatly slowing the pace of discovery as research teams do double duty with lab work and time-consuming computational work.

One unique capability that drove the RHIC renewal was that the Medical Center has a world-leading core of biostatisticians along with leading immunologists. Led by Hulin Wu, Ph.D., chief of the Department of Biostatistics and Computational Biology, the biostatistics team within RHIC will seek to establish statistically-rigorous, automated gating protocols for flow cytometry analysis that will greatly increase the reproducibility of data and the speed of flow cytometry lab by lab.

Allergies could be a blessing in disguise, against cancers

Sat, 15 Nov 2008 14:06:24 PST

( from http://www.rxpgnews.com ) Washington, Nov 12 - Sneezing, coughing and itching may just help prevent cancer affecting colon, skin, bladder, mouth, throat, uterus and cervix, lung and gastrointestinal tract, according to a new study.

These cancers involve organs that are exposed to the external environment, said Paul Sherman, professor of neurobiology and behaviour at Cornell University, who led the study.

He and colleagues analysed 646 studies on allergies and cancers published over the past 50 years, putting together 'the most comprehensive database yet available' on allergies and cancers.

The study revealed 'a strong relationship' between allergies and cancer in environmentally exposed tissues, Sherman said.

This relationship seldom exists, he noted, between allergies and cancers of tissues that are not directly exposed to environment, particularly breast and prostate cancers, myelocytic leukemia and myeloma, said a Cornell report by Susan Lang.

The study has been co-authored with Erica Holland, a medical student at the University of Massachusetts, and Janet Shellman Sherman, a Cornell research scientist.

'Sherman believes that allergy symptoms may help protect against cancer by shedding foreign particles from the body. Some of those particles, he said, might be carcinogenic or carry carcinogens.

Asthma is linked to higher rates of lung cancer. Unlike other allergies, however, asthma reduces the ability to expel mucus, while other allergies facilitate mucus expulsion and are correlated with lower rates of lung cancer.

These findings are scheduled for publication in the December issue of The Quarterly Review of Biology.

Researchers aim to over-stress already taxed mantle cell lymphoma cells

Mon, 10 Nov 2008 05:00:00 PST

( from http://www.rxpgnews.com ) AUGUSTA, Ga. - Cancer cells are already stressed by the fast pace they require to grow and spread and scientists believe a little more stress just may kill them.

Think about an assembly line in a factory that is working five times faster than normal, said Dr. Kapil Bhalla, director of the Medical College of Georgia Cancer Center. There is a lot of stress but you need workers to keep going. Some of them fall out, some get bent out of shape.

His research team believes they can disrupt the over-stressed assembly line of mantle cell lymphoma and possibly similar cancers such as pancreatic, liver and breast, by taking away support needed for rapid protein turnover and by clogging up the mechanism for eliminating poorly made ones.

Mantle cell lymphoma, an aggressive cancer of the lymphatic system that mostly occurs in middle age, responds initially to chemotherapy and antibiotics, but often returns, said Dr. Bhalla. Patients have a median survival of three to four years. This cancer affects b lymphocytes, immune cells which make antibodies to fight infection. Ironically, in the process of rearranging genes to make antibodies to a specific invader, mistakes happen, and a would-be protector becomes cancer.

MCG researchers found that to keep their fast pace, these now-malignant cells need increased activity of heat shock protein 90. Cancer cells require hsp90 for keeping their proteins in active conformation to do their job. That is what cancer is addicted to, said Dr. Bhalla, Cecil F. Whitaker, Jr., M.D./Georgia Research Alliance Eminent Scholar in Cancer and Georgia Cancer Coalition Distinguished Cancer Scholar. Hsp90 is one of the more common molecular chaperones, which help proteins get made, moved, folded and function. Its levels and activity are upregulated in response to stress.

They also found that the usually busy endoplasmic reticulum of these cells, which is supposed to be making normal antibodies, is stressed by making hyperactive, cancer-associated proteins. Stepped-up protein production also means more misfolded proteins that the proteasome must deal with. It's all stressed-out machinery, Dr. Bhalla said.

To help push cancer cells over the edge, the researchers are inhibiting hsp90, so the cells lose the molecular chaperone function required to maintain their fast pace. This also puts more stress on the endoplasmic reticulum. Independently hsp90 inhibitors are known to selectively kill cancer cells. But researchers also are clogging up the proteasome, the machinery for chopping up misfolded proteins, recycling some products and eliminating what's left. Much like a sink won't work with a clogged garbage disposal, mantle cell lymphoma cells will start backing up. When a cell detects excessive misfolded proteins, it first has a protective response, but if the problem persists, it commits suicide.

With support from a five-year, $1.5 million grant from the National Cancer Institute, the researchers are using hsp90 and proteasome inhibitors to study protective versus lethal endoplasmic reticulum stress as a way to get rid of mantel cell lymphoma cells. The laboratory studies are being done in human mantle cell lymphoma cells as well as an animal model the researchers developed.

The drugs they are using already are in early clinical trials for a variety of cancers but have not yet been packaged together, Dr. Bhalla said. We kill cancer cells and a lot of them with this strategy. Still, at least one more inhibitor may get added to the mix. After the rather brutal attack at the cancer's molecular underpinnings, the immune system comes in to essentially mop the floor, but researchers have found cancer cells can still get a pass from an enzyme called IDO. A team of MCG researchers led by Dr. David Munn is exploring IDO's therapeutic potential in cancer. Fetuses use IDO to avoid rejection by the mother's immune system and tumors appear to use it as well. Dr. Bhalla suspects an IDO inhibitor, already under study for lung cancer and other tumors, likely will get a shot at mantle cell lymphoma as well.

New hope for HIV treatment: Cells exhausted from fighting HIV infection can be revitalized

Mon, 10 Nov 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Researchers at the University of Toronto and the University of California, San Francisco, have revealed new hope for HIV treatment with the discovery of a way to 'rescue' immune cells that are exhausted from fighting off HIV infection.

The team lead by Drs. Mario Ostrowski, of the University of Toronto's Faculty of Medicine, and Douglas Nixon, of the Division of Experimental Medicine at the University of California, San Francisco, has discovered that a molecule called Tim-3 is present at high levels on poorly functional immune system cells which are 'exhausted' from fighting HIV infection. The researchers found that blocking the activity of Tim-3 on these cells improved their function and allowed them to rejoin the battle against HIV.

In the typical course of HIV infection, an initial burst of very high levels of the HIV virus is brought partially under control by the infected person's immune system, specifically by an immune system cell called a CD8+ killer T cell. In the majority of cases without antiretroviral drug treatment, the immune system is eventually overwhelmed and progression to AIDS occurs, said co-principal author Brad Jones, a PhD candidate in Immunology at the University of Toronto.

Progression to AIDS is associated with a breakdown in those CD8+ T immune system cells. In a typical viral infection, those cells rapidly multiply, kill off virus-infected cells and stimulate other cells in the immune system. But over time, in the battle to fight off HIV infection these CD8+T cells become less functional and enter into a state known as 'exhaustion.' The mechanisms that lead to this exhausted state are not well known, said Jones. We felt that if we could understand these mechanisms then we may be able to intervene and re-energize the immune system. The research team theorized that this exhausted state may result from the Tim-3 molecule sending a signal to shut down CD8+ T cells in HIV-infected individuals.

The researchers observed that Tim-3 expression on T cells, in particular the CD8+ T cells, associated remarkably strongly with clinical parameters of HIV disease progression in a diverse group of HIV-infected individuals. From these results we predicted that the Tim-3 pathway might be manipulated to potentially confer clinical benefit and serve as a promising new target for clinical intervention to decrease the severity of HIV infection, said co-principal author Lishomwa Ndhlovu, MD, PhD in the Division of Experimental Medicine, University of California, San Francisco.

To test this, we produced a molecule capable of blocking the Tim-3 signal and studied the effect that this had on CD8+ T cell function in vitro, said Mario Ostrowski, MD, Associate Professor in the Department of Immunology, University of Toronto. We observed that blocking the Tim-3 pathway rescued those cells and restored their ability to fight off infection.

This discovery, published in the November 24th issue of the