Protein Inhibitor May Bring a Topical Treatment for HPV

/PRNewswire/ -- Human papillomavirus (HPV) causes cervical cancer, the second most common cause of cancer death for women, and is a common cause of anogenital and some head and neck cancers. Thanks to research being done at Tufts University School of Medicine, patients infected with cancer-causing HPV may someday have an alternative to surgical and harsh chemical treatments. In a study funded by the National Institutes of Health and published online in advance of print in The FASEB Journal, the researchers report on the development of a protein-based inhibitor that could provide a topical treatment for HPV.

"Currently, there is no cure for HPV, and the available treatment options involve destroying the affected tissue. We have developed a protein inhibitor that blocks HPV protein expression in cell culture, a first step toward a topically-applied treatment for this cancer-causing virus," said senior author James Baleja, Ph.D., associate professor of biochemistry at Tufts University School of Medicine (TUSM) and member of the biochemistry program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.

"Vaccines are helping to lower the incidence of HPV, but vaccines will not help the millions of women and men who currently have an infection, especially those who have high-risk and persistent infections. Social and economic challenges make widespread administration of a vaccine difficult, particularly in developing countries. A topical treatment for HPV could provide an economical option," he continued.

HPV affects approximately 20 million people in the United States, making it the most common sexually transmitted infection. There are more than 100 types of HPV of which more than 40 are sexually transmitted. These include two high-risk types, HPV-16 and HPV-18, which cause the majority of cervical and anogenital cancers, and some portion of head and neck cancers, particularly oral cavity and oropharynx cancers. Cervical cancer is diagnosed in nearly 500,000 women each year, killing 250,000 annually. In the United States, it was estimated that 12,000 women in 2010 would be diagnosed with cervical cancer, while 10,100 women and men in the United States get vulvar, vaginal, penile or anal cancers each year. In addition, some portion of the head and neck cancers in the United States (11,300 men and women each year) is attributable to HPV. Other types of HPV, or low-risk HPV, can cause genital warts or are infections that clear on their own.

In their efforts to inhibit HPV, Baleja and his team zeroed in on the viral protein E2, which controls viral activities including DNA replication and the activation of cancer-causing genes. Using structure-guided design, the team developed a protein called E2R that prevents E2 from functioning normally. When the researchers applied E2R to a cell model of HPV biology, viral gene transcription was halted. Because HPV infects epithelial cells, the outermost layer of the skin and the mucous membranes, protein inhibitors such as E2R could be applied in a topical form.

Baleja and colleagues used biophysical tools including circular dichroism spectroscopy and x-ray crystallography to test the structure and stability of different inhibitors. The most stable inhibitor was then tested in mammalian cells and was found to inhibit the E2 protein of HPV-16, the high-risk strain that is most commonly associated with cancers. The data in this study suggest that the inhibitor may also be effective against another high-risk virus, HPV-18, as well as a low-risk virus, HPV-6a, which causes warts.

Additional authors on the paper are first author Kakoli Bose, Ph.D., formerly a postdoctoral fellow in the Baleja laboratory at TUSM and now with the Advanced Centre for Treatment, Research and Education in Cancer at the Tata Memorial Center in India; Gretchen Meinke, Ph.D., senior research associate in the Bohm Laboratory at TUSM, and Andrew Bohm, associate professor in the Department of Biochemistry at TUSM and member of the biochemistry program faculty at the Sackler School of Graduate Biomedical Sciences.

This research was funded by the National Cancer Institute, part of the National Institutes of Health, and by the Lifespan/Tufts/Brown Center for AIDS Research (CFAR), a joint research effort between Tufts and Brown Universities and their affiliated hospitals and centers. CFAR is funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Bose K, Meinke G, Bohm A, and Baleja J. The FASEB Journal. "Design and characterization of an enhanced repressor of human papillomavirus E2 protein." Published online April 11, 2011. DOI 10.1096/fj.10-176461

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Emergency Visits Are Increasing, New ACEP Poll Finds; Many Patients Referred By Primary Care Doctors

/PRNewswire/ -- More than 80 percent of emergency physicians responding to an ACEP poll said emergency visits are increasing in their emergency departments, with half reporting significant rises, and more than 90 percent expecting increases in the next year. Almost all (97 percent) reported treating patients on a daily basis who were referred to them by primary care doctors, going against a widely-held assumption that people are choosing to go to the emergency department instead of seeking primary care.

At the same time, 97 percent of emergency physicians also report treating Medicaid patients on a daily basis who could not find any other doctor to accept their health insurance. If the new health care reform legislation provides insurance coverage that reimburses doctors at Medicaid rates, this could exacerbate a lack of access to medical care.

"This poll confirms what we are witnessing in Massachusetts — that visits to emergency rooms are going to increase across the country, despite health care reform, and that health insurance coverage does not guarantee access to medical care," said Dr. Sandra Schneider, president of the American College of Emergency Physicians. "Emergency medicine provides lifesaving and critical care to millions of patients each year and yet only represents 2 percent of the nation's health care expenditures. Emergency physicians command the resources of a hospital to provide the best care for patients, but we must be prepared for increasing numbers of patients, not fewer, especially given our growing elderly population."

ACEP conducted the poll from March 3 to March 11, 2011. E-mails were sent to 20,687 emergency physicians, and 1,768 responded. The survey has a theoretical sampling error range of plus/minus 2.23.

While 79 percent of responding emergency physicians said their emergency departments use resources efficiently, nearly half of respondents (44 percent) said the fear of lawsuits was the biggest challenge to cutting emergency department costs. More than half (53 percent) of emergency physicians reported that fear of lawsuits is the main reason for ordering the number of tests they do.

"Emergency departments need more resources, not fewer, and medical liability reform would help reduce overall costs by reducing the need for defensive medicine," said Dr. Schneider.

Two-thirds of emergency visits occur after business hours, when doctor's offices are closed and patients have nowhere else to turn. Visits to ERs reached an all-time high of nearly 124 million in 2008, according to the Centers for Disease Control and Prevention (CDC) and are expected to rise nationwide.

Physicians responding to the poll attribute the overall increase in emergency patients to patients without health coverage (28 percent) and a growing elderly population (23 percent) are seen by physicians as the most important reasons for the overall increase in ER patients.

An overwhelming 89 percent of physicians believe the number of visits to the emergency department will increase as health care reforms are implemented with 54 percent of them expecting to see a significant increase.

"Emergency visits have increased at twice the rate of the U.S. population, and less than 8 percent of those patients have nonurgent medical conditions, meaning the vast majority need to be there," said Dr. Schneider. "At the same time, hundreds of emergency departments have closed. The new health care reform law does not address these problems and with the elderly population and more emergency departments forced to shut down, this crisis will only get worse."

More than 1,400 (82.5 percent) responding to the poll said that lives were saved every day in their emergency departments. "Emergency medicine is critical at any hour of the day. It must be there when you need it," said Dr. Schneider.

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Free Oral, Head and Neck Cancer Screenings at Emory

Oral Head and Neck Cancer Awareness Week

In support of Oral, Head and Neck Cancer Awareness Week, Emory Healthcare will be offering free oral head and neck cancer screenings at the Emory Clinic on Friday, April 29 from 1-4 pm, and on Wednesday, May 4 from 8 am to noon.

According to the American Cancer Society, head and neck cancers represent the sixth most common form of cancer in the United States, with more than 50,000 cases diagnosed annually, and over 12,000 deaths.

Screenings on Friday, April 29, will take place in the Oral Surgery Department of Clinic B, 1365-B, Clifton Rd., 2nd floor. Screenings on Wednesday, May 4, will take place in the ENT Department, 1365-A Clifton Rd., 2nd floor. Screenings are first come first served.

Study Suggests an Alternative to Foot Amputation for Some Diabetic Patients

/PRNewswire/ -- A recent study published in the March issue of Foot & Ankle International (FAI), the official scientific journal of the American Orthopaedic Foot & Ankle Society (AOFAS) describes a possible amputation alternative for patients with neuropathic ulceration of the first metatarsophalangeal (MTP) or big toe joint. The findings are noteworthy as diabetes is the leading cause for non-accident/injury leg and foot amputations among US adults, with more than 60,000 lower extremity amputations performed annually. In addition, neuropathy (nerve damage or loss of feeling) of the foot occurs in 60-70% of diabetic patients.

The study's alternative operative treatment to amputation includes debridement and resection arthroplasty with temporary external fixation and VAC dressing. Nicholas Smith, corresponding author of the study says, "While the study includes only a small sample, it does represents the largest group followed in literature. Given that patients are very satisfied with the outcomes and that we achieved an equally positive end point compared to more radical amputation, we are hopeful that this option will be considered for select patients in the future."

The retrospective study examined 16 patients (the largest group followed in the literature) who underwent resection arthroplasty with external fixation for first MTP ulceration. The patients were studied post-operatively for an eight year period. The purpose of the study was to obtain information on long-term outcomes for all patients who underwent the procedure. Ten out of 16 patients were ulcer free at the conclusion of the study and required no further surgery. The remaining six patients required a secondary procedure which required amputation.

Treatment includes complete debridement of the infected tissue, application of external fixator with pins and wires, and 6 to 8 weeks of antibiotics with use of negative pressure wound therapy (NPWT) for the postoperative treatment of open wounds

The findings are noteworthy for diabetic patients with foot ulcerations. The authors of the study feel the procedure warrants consideration in the treatment of deep forefoot ulcerations, yet concede that if the ulceration fails to heal, amputation may be the only viable option.

For more information on diabetic foot as well as resources on foot and ankle care, visit the AOFAS website, www.aofas.org. The site also features a surgeon referral service that makes it easy for patients to find a local orthopaedic surgeon specializing in foot and ankle care.

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UGA researchers develop non-invasive early diagnostic test for gastric cancer

Early detection of cancer may eventually become as easy as taking a home pregnancy test, according to new University of Georgia research.

Two studies recently published in the journal PloS ONE identified for the first time that certain proteins excreted in urine can indicate the presence of gastric cancer.

The researchers initially studied stomach cancer because it is the number two cancer killer in the world.
They hope that with further study, the detection of abnormally abundant proteins in urine will lead to diagnosis of many types of cancer and other diseases, said Ying Xu, lead author of the study and Regents-Georgia Research Allianceeminent scholar of bioinformatics and computational biologyin the UGA Franklin College of Arts and Sciences.

“In theory, the methodology that we developed should be applicable to other cancers,” said Xu, who also is a professor of biochemistry and molecular biology and director of the UGA Institute of Bioinformatics.

Xu and his colleagues, Celine Hong, Juan Cui and David Puett of the Institute of Bioinformatics, identified a protein called endothelial lipase that differed significantly in its abundance in urine samples of stomach cancer patients versus healthy people. Xu said the computational capability presented in the study for predicting which of the abnormally abundant proteins in diseased tissues can be excreted into urine is a key breakthrough in cancer detection. Using samples from already known excretory and non-excretory proteins, the study found that the classification system was more than 80 percent accurate.

Of the 21 urine samples of healthy people, only two did not have the protein. In the 21 urine samples of stomach cancer patients, only one sample was considered to have a relatively high level of the protein; levels in the rest were low or absent. “We are suggesting from this relatively small urine sample set that healthy people should have this protein in their urine,” Xu said.

The researchers are currently working on a larger urine sample set of 200 gastric cancer patients and 200 healthy people. “If the EL protein still has the 10 to 15 percent miscalculation rate as with the 21 versus 21 samples, I think we have found a good diagnostic marker for stomach cancer and potentially other cancers,” said Xu.

Now that the researchers have identified a protein marker, Xu says they should be able to develop a method where urine can change the color of a piece of paper to indicate the presence or absence of the protein, similar to the way a home pregnancy test works. The researchers hope to find multiple protein markers for each cancer to increase the accuracy of the test.

Although the test is not yet 100 percent accurate, it can lead at-risk patients to seek a more comprehensive exam, said Xu. Current procedures such as endoscopy are invasive, uncomfortable and may be avoided by many people. “A person could go get a urine test, and if the marker protein is present, then they are generally stomach-cancer free,” said Xu. “If the protein is not present, we might suggest that they get their stomach checked.”

The researchers began by studying a set of 1,500 proteins known to be excreted in urine and identified a list of features that distinguish them from proteins that are not excreted into urine. Identifying these distinguishing features allowed them to develop a classification system that could predict which proteins in cancerous tissues are excreted into urine.

Xu and his colleagues then used microarrays—chips that are about the size of a stamp that contain nearly twenty thousand human genes—to identify which proteins varied in abundance in the cancerous versus non-cancerous tissues. Messenger RNA (mRNA) molecules extracted from the sample tissues are converted to complementary DNAs (cDNAs) and hybridize with their complement genes on the microarray and light up as spots when the corresponding mRNAs are abundant. The researchers then identified proteins corresponding to those genes that appeared at significantly different levels in the cancer and non-cancer samples. From there, the researchers were able to determine which of the abnormally abundant proteins were secreted into the blood and then excreted in urine using the classification method they developed.

The UGA researchers work in conjunction with a team of researchers led by Fan Li of Jilin University in China, where Xu spends two months a year working with medical doctors and researchers on sample collection and carrying out microarray experiments. This long-term collaboration has led to the establishment of the Jilin University/University of Georgia Joint Research Center for Systems Biology. The researchers are currently collecting tissues from patients with different types of cancer to identify more protein markers that can be detected in urine.

The study was supported by the UGA President’s Venture Fund, the Office of Vice President for Research, the Georgia Cancer Coalition, the Georgia Research Alliance, Jilin University and the National Institutes of Health.

To learn more about the UGA Institute of Bioinformatics, see http://www.bioinformatics.uga.edu/. To learn more about the Franklin College of Arts and Sciences department of biochemistry and molecular biology, see http://www.bmb.uga.edu/.

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Streptococci and E. coli Continue to Put Newborns at Risk for Sepsis

Bloodstream infections in newborns can lead to serious complications with substantial morbidity and mortality. What’s more, the pathogens responsible for neonatal infections have changed over time. In recent years, however, antibiotic prophylaxis given to at-risk mothers has reduced the incidence of early-onset group B streptococcal infections among their babies.

A new nationwide, multi-site study aimed at determining current early-onset sepsis rates among newborns, the pathogens involved, and associated morbidity and mortality demonstrates that the most frequent pathogens associated with sepsis are group B streptococci (GBS) in full-term infants and Escherichia coli in preterm infants.

The study, which included nearly 400,000 newborns, also found that infection rates in newborns increased with decreasing gestational age and birth weight. The overall rate of infection was 0.98 per 1,000 live births; 0.41 per 1,000 live births involving GBS and 0.28 per 1,000 live births involving E. coli.

The study appears online April 25 and in the May 2011 issue of Pediatrics.

GBS emerged as the leading cause of early-onset sepsis and meningitis in newborns in the 1970s. In 2002, the Centers for Disease Control and Prevention recommended universal screening of women at 35 to 37 weeks of pregnancy followed by chemoprophylaxis for women with GBS colonization.

Sepsis occurs when pathogenic bacteria enter the blood stream, causing systemic infection. In infants less than 72 hours old, sepsis is considered of early onset.

“Infections occur in almost one case per thousand live births,” says Barbara Stoll, MD, lead investigator for the study. Stoll is the George W. Brumley, Jr., Professor and Chair, Department of Pediatrics in Emory University School of Medicine. “With approximately 4 million births a year in the United States, this equates to a substantial burden of disease. We estimate that approximately 3,000 infants a year develop early-onset sepsis. With current mortality rates, approximately 300 to 350 deaths per year are associated with neonatal sepsis. So, it’s not inconsequential.”

The study also shows that opportunities for prevention of neonatal GBS infections continue to be missed. “Missed opportunities for prevention of GBS include failure to screen all women who deliver at term, failure to provide antibiotics to all colonized women or to those who delivered preterm with unknown colonization status and false negative GBS screens among women who deliver with GBS infection,” says Stoll.

“Our findings suggest that accurate point-of-care diagnostic tests at the time a woman comes in for delivery would enhance our ability to identify at-risk women.”

In addition, the gap in linking electronic medical records between a woman’s obstetrician and the hospital where she delivers can also impede prevention. “A community health record that links the medical record in a physician’s office with the hospital where the woman gets care could enhance identification and therapy for at-risk women,” says Stoll. “If a woman has been screened for GBS and is known to be colonized, that information should be available to the health care team taking care of her at the time she is in labor.”

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Centers for Disease Control and Prevention.

By Robin Tricoles

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FDA approves the first vaccine to prevent meningococcal disease in infants and toddlers

The U.S. Food and Drug Administration today approved the use of Menactra in children as young as 9 months for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135. Menactra already is approved for use in people ages 2 through 55 years.

Meningococcal disease is a life-threatening illness caused by bacteria that infect the bloodstream (sepsis) and the lining that surrounds the brain and spinal cord (meningitis). Neisseria meningitidis is a leading cause of meningitis in young children. Even with appropriate antibiotics and intensive care, between 10 percent and 15 percent of people who develop meningococcal disease die from the infection. Another 10 percent to 20 percent suffer complications such as brain damage or loss of limb or hearing.

Although the rates of meningococcal disease are low in the United States, infants and toddlers are more susceptible to getting this serious illness. Meningococcal disease is particularly dangerous because it progresses rapidly and can cause death within hours. Early symptoms are often difficult to distinguish from influenza and other common illnesses.

“The highest rate of meningococcal disease occurs in children under one year of age. With today’s approval, Menactra can now be used in children as young as 9 months of age to help prevent this potentially life-threatening disease,” said Karen Midthun, M.D., director of FDA's Center for Biologics Evaluation and Research.

The safety of Menactra in children as young as 9 months was evaluated in four clinical studies in which over 3,700 participants received the vaccine. The most common adverse events reported in children who received Menactra at 9 months and 12 months of age were injection-site tenderness and irritability. Occurrence of fever was comparable to other vaccines routinely recommended for young children.

Menactra is given as a two-dose series beginning at 9-months, three months apart; and the study results showed the vaccine produces antibodies in the blood that are protective against the disease.

Menactra was originally approved on Jan. 14, 2005, for use in individuals ages 11 years through 55 years and was approved in October 2007 for children as young as 2 years. Menactra is manufactured by Sanofi Pasteur Inc. of Swiftwater, Pa.

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UGA compound offers new hope for treatment of painful adult shingles

Researchers at the University of Georgia and Yale University have discovered a compound with the potential to be more effective than existing agents in treating the very painful blisters known as shingles—a condition that affects up to 30 percent of Americans, mostly elderly, and for which no specific treatment exists.

Most adults remember the fever, itchy blisters and possibly tiny scars they experienced as children when they had chickenpox, which is caused by the varicella-zoster virus, or VZV.Unfortunately, that memory can come back—with a vengeance—when they are older. The VZV virus from childhood chickenpox hides in the nerves, emerging most frequently in adults over the age of 60 as a blistering rash on one side of the body. The rate of complications, including nerve pain that can persist for months or years after the shingles attack is gone, also increases with age.

The novel and effective anti-shingles agent called L-BHDA may change that. Rights to the shingles treatment have been licensed to Bukwang Pharmaceutical Company for preclinical investigations by the University of Georgia Research Foundation, Inc. and Yale University.

“We need new options for medications with increased potency and specificity that can treat VZV, including strains that may be resistant to existing drugs,” said medicinal chemist Chung (David) Chu, Distinguished Research Professor of Pharmaceutical and Biomedical Sciences at UGA, one of the inventors of L-BHDA.

A collaboration between Chu and co-inventor Yung-Chi (Tommy) Cheng, the Henry Bronson Professor of Pharmacology at Yale, has resulted in an extensive portfolio of antiviral compounds that target such diseases as HIV, shingles, hepatitis and cancers.

Chu, who is head of the Drug Discovery Group in the UGA College of Pharmacy, said that although there are generic antiviral drugs to reduce the duration and pain of shingles, and a variety of pain medications and topical creams to relieve long-term pain, “They are only moderately effective.We need more effective anti-VZV agents.

“L-BHDA has the potential to be more effective than existing agents,” said Chu. He noted that the new compound has been tested in the laboratory and demonstrated in mice models by a group of researchers headed by Jennifer Moffat, associate professor of microbiology and immunology, State University of New York Upstate Medical University.

A vaccine to prevent shingles, available to older adults since 2006, can cut the likelihood of a shingles attack in half. However, according to a recent study in the American Journal of Preventive Medicine, only a small percentage of older people receive the shot, principally because of cost, lack of insurance reimbursement and shortage of supply.

It is likely that immunization against chickenpox during childhood also protects against shingles, because the vaccine uses a weakened strain of the virus. However, the vaccine was only introduced in 1995, and there are not enough data to provide a definitive answer.

“Dr. Chu and Dr. Cheng have been working diligently to fill a much needed gap in the treatment options for such a prevalent disease,” said Rachael Widener, UGARF technology licensing manager. “Before the chicken pox vaccine became widely used in the mid-1990s, older, unvaccinated individuals would have their immunity boosted naturally.

“Now, with less exposure to chicken pox, shingles is becoming more prevalent,” said Widener. “This, combined with the aging baby boomer population, underscores the need for more directed treatment. We are hopeful that L-BHDA will allow patients to get well sooner and feel less pain, and will lessen their chances of complications.”

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FDA approves Rituxan to treat two rare disorders

The U.S. Food and Drug Administration today approved Rituxan (rituximab), in combination with glucocorticoids (steroids), to treat patients with Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA), two rare disorders that cause blood vessel inflammation (vasculitis).

Vasculitis in patients with WG and MPA can lead to tissue damage. WG mostly affects the respiratory tract (sinuses, nose, trachea, and lungs) and kidneys, while MPA commonly affects the kidneys, lungs, nerves, skin, and joints. Both of these diseases affect people of all ages and ethnicities, and both genders. The causes of these disorders are unknown, and both are considered orphan diseases because they each affect less than 200,000 people in the United States.

“This new indication for Rituxan provides the first approved therapy for these two orphan diseases,” said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research.

Rituxan is an antibody that is manufactured through biotechnology methods. The drug works by greatly reducing the number of specific immune cells in the blood, known as B cells.

The safety and effectiveness of Rituxan was demonstrated in a single controlled trial, in which 197 patients with WG or MPA were assigned at random to receive either Rituxan plus glucocorticoids once a week for four weeks or oral cyclophosphamide plus glucocorticoids daily to induce remission. After six months, 64 percent of patients treated with Rituxan had complete remission compared to 53 percent of patients treated with cyclosphosphamide.

Retreatment with Rituxan was not formally evaluated; therefore, the safety and efficacy of retreatment with subsequent courses of Rituxan has not been established. More data are needed to determine the safety of more than one course of Rituxan and long term safety of use of Rituxan in patients with WG and MPA. These questions will be further evaluated in a required post-marketing study.

Rituxan carries a Boxed Warning for infusion reactions, which can occur during infusion or within 24 hours afterwards. Other Boxed Warnings for Rituxan include rashes and sores in the skin and mouth (severe mucocutaneous reactions); and progressive multifocal leukoencephalopathy, a brain infection that generally is fatal. Rituxan is not recommended for use in patients with severe, active infections.

The most common side effects in study participants with WG and MPA included infection, nausea, diarrhea, headache, muscle spasms, and anemia.

Rituxan, which has been marketed since 1997, is also indicated for the treatment of patients with non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.

Rituxan is manufactured by San Francisco-based Genentech, a member of the Roche Group.

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FDA approves Actemra to treat rare form of juvenile arthritis

The U.S. Food and Drug Administration today approved Actemra (tocilizumab), given alone or in combination with methotrexate, for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in children ages 2 years and older.

SJIA, or Still’s disease, is a rare, potentially life-threatening disorder in children that causes severe inflammation throughout the body. SJIA is distinguished from other forms of juvenile idiopathic arthritis (JIA) by the prominence of systemic and inflammatory features, including spiking fevers; rash; swelling and inflammation of lymph nodes, liver, and spleen; and high white blood cell and platelet counts. The prevalence of JIA is an estimated 1 to 2 per 1,000 children, and SJIA affects about 10 percent of all JIA patients.

Actemra is an interleukin-6 receptor blocker approved by the FDA on Jan. 8, 2010, for treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to other approved therapies.

“This new indication of Actemra provides the first approved therapy for children with this rare disease,” said Badrul Chowdhury, M.D., Ph.D., director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

An international, multicenter controlled trial demonstrated the safety and effectiveness of Actemra, in which 112 patients received either Actemra infusions or placebo infusions every two weeks. Study participants included patients with SJIA aged 2 to 17 years old who had inadequate response to or who were unable to take nonsteroidal anti-inflammatory drugs and corticosteroids.

Eighty-five percent of those receiving Actemra responded to treatment, compared with 24 percent of patients receiving placebo. Response was defined as at least 30 percent improvement in the American College of Rheumatology’s JIA efficacy variables, along with absence of fever in the preceding seven days. In the long-term, follow-up period of the trial there were three cases of macrophage activation syndrome (MAS) among SJIA patients receiving Actemra. MAS is a potentially fatal complication of childhood systemic inflammatory disorders, thought to be caused by excessive activation and proliferation of certain immune cells.

Actemra carries a Boxed Warning for serious infections. Patients treated with Actemra who develop a serious infection should stop Actemra treatment until the infection is controlled. A Boxed Warning is a brief, concise summary of the information that is critical for a prescriber to be aware of, including any restriction on distribution or use, which is included in a black box at the beginning of the drug label.

Changes in certain laboratory test results such as liver tests, blood counts, and cholesterol are not uncommon with Actemra and should be monitored with regular blood tests. The most common side effects in trial participants with SJIA included upper respiratory tract infection, headache, sore throat, and diarrhea.

Actemra is marketed by San Francisco-based Genentech Inc., a subsidiary of the Roche Group.

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Doctors Recommend Different Treatments for Patients Than for Themselves

A patient who can't decide between two available treatments asks his doctor: "What should I do?" Another patient, torn between the same two treatments, asks: "Doctor, what would you do if you were me?"

Will those two patients get the same answer? That question, posed by researchers from Duke University and the University of Michigan in a national survey of physicians, found doctors often recommend different treatments for patients than they would choose for themselves.

The study, from professor Peter Ubel and post-doctoral associate Andrea Angott of Duke University's Fuqua School of Business and professor Brian Zikmund-Fisher of the University of Michigan, appears in the April 11 edition of the Archives of Internal Medicine. Funding for the study was provided by the American Cancer Society, the National Science Foundation and the National Institutes of Health.

In the study, the researchers conducted a randomized experiment asking some physicians to make a recommendation to a patient seeking advice, while other physicians were asked what they themselves would choose as a patient facing the same health care decision.

Doctors frequently advised patients to pursue treatments with higher rates of side effects and lower mortality rates, while choosing treatments with lower rates of side effects and higher mortality rates for themselves.

"Our research found that people felt living with a colostomy or being paralyzed was better than dying. From that perspective, the ‘right' decision is to take the risk of side effects and reduce the chances of dying," Ubel said.

However, emotions brought on by potential significant side effects often push people away from the "right" decision. Doctors -- free from the side effects of treatment -- can make more objective treatment recommendations to their patients.

"When making recommendations to patients, physicians can push aside any emotions that would lead them astray," Ubel said. "But those emotions may loom large when a doctor is deciding for him or herself. In other words, the act of giving advice to others may reset the balance between emotion and reason."

Ubel noted, "Many physicians are biased by their own backgrounds, valuing things that patients don't necessarily value, or they can even be influenced by financial and professional conflicts of interest that can skew judgment."

As a result, you might not always get the objective advice you seek, Ubel said. "Instead, the advice you get could depend on whether your doctor is thinking about what you should do, or instead thinking about what he or she would do in your situation."

A detailed report on the research is available at http://archinte.ama-assn.org/.

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FDA approves new treatment for large brain aneurysms

The U.S. Food and Drug Administration has approved the cPAX Aneurysm Treatment System for surgery on brain aneurysms that are difficult to manage because of their size and shape.

An aneurysm is a bulge in the wall of a blood vessel, which can rupture as it increases in size, causing hemorrhage or death. Brain aneurysms often produce no symptoms until they grow and press on nerves in the brain, or until they begin to leak blood or rupture.

Aneurysms can be repaired in two ways: surgeons can close the base of the aneurysm with a surgical clip, or use a technique commonly known as coiling, in which surgeons use a catheter to thread metallic coils through a blood vessel in the groin and into the blood vessel in the brain that contains the aneurysm. Surgeons then fill the aneurysm with the detachable coils, which block it from circulation and cause blood to clot, effectively destroying the aneurysm.

Aneurysms larger than 10millimeters are difficult to treat with clipping or coiling. The cPAX Aneurysm Treatment System is indicated for use in those brain aneurysms.

“Like coiling, the cPAX Aneurysm Treatment System is a form of endovascular repair,” said Christy Foreman, director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health. “But instead of tiny metallic coils, it uses a special polymer material to fill the space within the aneurysm.”

The cPAX polymeric filler material can be secured in the aneurysm in one of two ways, either by insertion through openings in a permanent stent, which is a tiny metal scaffold placed along the vessel wall, or by using a temporary balloon catheter to block off the opening to the aneurysm and keep the filler material from coming out of the aneurysm as it is being delivered.

By filling the bulging space within the aneurysm with implant material, the blood flow through the aneurysm is stopped and any remaining space around the implant material clots. When filled with implant material and blood clot, and the risk of rupture of the aneurysm decreases.

The cPAX Aneurysm Treatment System was approved on April 1, 2011, under a Humanitarian Device Exemption (HDE). The HDE makes medical devices available to patients with rare medical conditions that affect fewer than 4,000 people a year. The approval for this HDE was based on safety data from two studies of 43 subjects.

The cPAX device system is indicated for use in adults ages 22 and older and should not be used in patients with an active infection or in those in whom anticoagulation and antiplatelet therapy is contraindicated.

The cPAX Aneurysm Treatment System is manufactured by Neurovasx Inc., Maple Grove, Min.

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Expansion of HIV/AIDS Vaccine Program Announced by GeoVax Labs, Inc.

/PRNewswire/ -- GeoVax Labs, Inc. (OTCQB/OTCBB: GOVX), announced today that it is expanding its preventative HIV/AIDS vaccine development effort in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH) and the HIV Vaccine Trials Network (HVTN). Specifically, the HVTN plans to clinically test a novel vaccine product developed by GeoVax scientists that expresses human granulocyte-macrophage colony stimulating factor (GM-CSF) in combination with inactivated HIV proteins. The novel vaccine consists of a recombinant DNA vaccine co-expressing human GM-CSF and non-infectious HIV virus-like-particles. The DNA vaccine is used to prime immune responses that are subsequently boosted by vaccination with a recombinant modified vaccinia Ankara (MVA) vectored vaccine. The MVA expresses the HIV virus-like-particles, but does not express GM-CSF. The regimen builds on the GeoVax DNA/MVA vaccine that is currently in Phase 2a clinical testing through the HVTN.

GM-CSF is a cytokine (growth stimulating protein) that serves to expand and mature cells that initiate immune responses and has undergone extensive testing in humans for cancer vaccines. The GM-CSF-adjuvanted vaccine was added to GeoVax's portfolio because of the outstanding ability of the simian prototype vaccine to induce immune responses that prevented simian immunodeficiency virus (SIV) infection. In nonhuman primates, the GM-CSF enhanced vaccine achieved protection against SIV in 70% of the animals. Protection was measured against 12 weekly rectal challenges using a dose of SIV which is estimated to be 30 to 300 times higher than the typical exposure dose of HIV in mucosal transmission in humans.

"For years, the HIV vaccine field has been working with vaccines that elicited immune responses that primarily controlled immunodeficiency virus challenges in infected animals, but did not actually prevent infections. The ultimate goal is to prevent infections. The co-expression of GM-CSF with the SIV proteins is a vaccine design that appears to be a large step towards reaching this goal," said Dr. Harriet Robinson, Chief Scientific Officer at GeoVax. "In our trials in nonhuman primates, GM-CSF enhanced the quality of the SIV-specific antibody response. Antibody is present in blood and tissues and has the potential of blocking SIV before it infects cells. The GM-CSF-adjuvanted vaccine induced the production of antibodies characterized with increased tightness of antibody binding. The tightness of antibody binding, known as avidity, can be expressed as an index. Animals with indices above 40 were protected from infection, whereas animals with lower indices were infected with the number of challenges to infection correlating with their index."

"We are very pleased that the HVTN will be conducting trial HVTN 094 of our GM-CSF adjuvanted vaccine product, which we expect will begin late this year," said Dr. Robert McNally, CEO of GeoVax. "The HVTN, funded by the NIAID, is the largest worldwide clinical trials network dedicated to the development and testing of HIV/AIDS vaccines. We are looking forward to working with an excellent team of HVTN trial investigators."

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FDA Permits Marketing of First Test to Help Diagnose Dengue Fever

/PRNewswire/ -- The U.S. Food and Drug Administration today allowed marketing of the first test to help diagnose people with signs and symptoms of dengue fever or dengue hemorrhagic fever, a leading cause of illness and death in the tropics and subtropics.

The dengue virus is transmitted to humans by the bite of an infected Aedes mosquito. As many as 100 million people worldwide are infected by the virus each year, according to the U.S. Centers for Disease Control and Prevention (CDC).

Symptoms of dengue fever include high fever, severe headache, severe pain behind the eyes, joint pain, muscle and bone pain, rash and mild bleeding involving the nose or gums, and easy bruising.

Most reported dengue cases in the continental United States occur in people returning from travels to tourist destinations in Latin America, the Caribbean and Southeast Asia. Dengue is also endemic in the U.S. in Puerto Rico, the Virgin Islands and some U.S.-affiliated Pacific Islands. Recently, dengue outbreaks have occurred in Hawaii, Texas, and Florida.

The DENV Detect IgM Capture ELISA test detects antibodies to dengue virus in blood samples from patients who have signs and symptoms of dengue. The test will be available for use in clinical laboratories and will assist in the diagnosis of dengue, which can improve patient care and management.

The DENV Detect IgM Capture ELISA test is based on technology patented by the CDC and manufactured by Seattle-based Inbios Inc.

"Cases of dengue fever or dengue hemorrhagic fever can be potentially fatal for people who do not recognize the symptoms," said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics Device Evaluation and Safety in FDA's Center for Devices and Radiological Health. "This test will now aid health care professionals in their effort to more effectively diagnose dengue."

The FDA reviewed data for the test via the "de novo" pathway, an alternative path to market for devices that are low to moderate risk and may not require premarket approval (PMA), but are of a new type, and therefore may not be able to be cleared in a "510(k)" premarket notification.

People who believe they have dengue should immediately contact a health care professional. There are no FDA-licensed vaccines to prevent dengue and no medicines specifically approved to treat the infection.

The test should not be used in people who do not show signs or symptoms of dengue. Diagnostic testing for dengue is complicated by the fact that an IgM antibody response to the dengue virus infection is not detectable until 3-5 days after the onset of fever, which can produce a negative test result even though a person has dengue. During this "IgM negative window" the dengue virus is present in the bloodstream.

There are currently no FDA-cleared or approved tests for direct detection of dengue virus.

This new test shows cross-reaction with other closely related viruses such as those that cause West Nile disease. However, in most patient testing situations found in the United States, a positive test result in a patient with signs or symptoms consistent with dengue should be considered presumptive evidence of dengue.

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FDA approves Horizant to treat restless legs syndrome

On April 6, the U.S. Food and Drug Administration approved Horizant Extended Release Tablets (gabapentin enacarbil), a once-daily treatment for moderate-to-severe restless legs syndrome (RLS).

RLS is a disorder that causes a strong urge to move the legs. This urge often occurs with unpleasant feelings in the legs. People who have RLS describe feeling pulling, itching, tingling, burning, or aching in their legs, and moving the legs temporarily relieves these feelings. The urge to move often happens when a person is inactive, and the symptoms typically are worse in the evening and early morning.

“People with restless legs syndrome can experience considerable distress from their symptoms,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “Horizant provides significant help in treating these symptoms.”

The effectiveness of Horizant was studied in two 12-week clinical trials in adults. The trials showed that people taking the medication had an improvement in their RLS symptoms, compared with people taking an inactive pill (placebo).

Horizant will be dispensed with an FDA-approved Medication Guide that explains the drug’s uses and risks. Horizant may cause drowsiness and dizziness and can impair a person’s ability to drive or operate complex machinery.

Horizant contains gabapentin enacarbil that becomes gabapentin, a drug used to treat seizures in people with epilepsy, when absorbed into the body. All drugs used to treat epilepsy carry warnings that they may cause suicidal thoughts and actions in a small number of people. Horizant will have the same warning.

Horizant was developed by GlaxoSmithKline of Research Triangle Park, N.C., and Xenoport of Santa Clara, Calif.

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FDA approves new treatment for rare form of thyroid cancer

The U.S. Food and Drug Administration today (April 6) approved vandetanib to treat adult patients with late-stage (metastatic) medullary thyroid cancer who are ineligible for surgery and who have disease that is growing or causing symptoms.

Thyroid cancer is a cancerous growth of the thyroid gland, which is located in the neck. Medullary thyroid cancer involves specific types of cells that are found in the thyroid gland and can occur spontaneously, or be part of a genetic syndrome.

About 44,600 new thyroid cancer cases were diagnosed in the United States during 2010, and about 1,690 people died from the disease, according to the National Cancer Institute. Medullary thyroid cancer is estimated to represent 3 to 5 percent of all thyroid cancer; its estimated incidence in the United States for 2010 is about 1,300 to 2,200 patients, making it one of the rarer forms of thyroid cancer.

Common symptoms of medullary thyroid cancer may include coughing, difficulty swallowing, enlargement of the thyroid gland, swelling of the neck, a lump on the thyroid, and changes in a person’s voice or hoarseness.

Vandetanib targets medullary thyroid cancer’s ability to grow and expand. There are currently no FDA-approved treatments for this type of cancer. Vandetanib is administered orally on a daily basis.

Vandetanib’s safety and effectiveness were established in a single, randomized international study of 331 patients with late-stage medullary thyroid cancer. Patients in the study were selected to receive vandetanib or placebo (sugar pill).

The study was designed to measure the length of time a patient lived without the individual’s cancer progressing (progression-free survival). Patients who received vandetanib had a longer period of time without disease progression when compared to patients receiving placebo. Median progression-free survival was 16.4 months in the placebo arm and at least 22.6 months in the vandetanib arm. It is too early to determine the median progression-free survival in patients treated with vandetanib or to tell whether they will live longer (overall survival) compared to patients treated with placebo.

“Vandetanib’s approval underscores FDA’s commitment to approving treatments for patients with rare and difficult to treat diseases,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research.

Common side effects occurring from vandetanib use include diarrhea, rash, nausea, high blood pressure, headache, fatigue, decreased appetite, and stomach (abdominal) pain. Serious side effects reported during the study resulted in five deaths in patients treated with vandetanib. Causes of death included breathing complications, heart failure, and a bacterial infection in the blood (sepsis).

Vandetanib was shown to affect the electrical activity of the heart, which in some cases can cause irregular heart beats that could lead to death. Vandetanib is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals about these serious heart-related risks. Only health care professionals and pharmacies certified through the vandetanib REMS program, a restricted distribution program, will be able to prescribe and dispense the drug. Patients will also receive an FDA-approved Medication Guide informing them of the potential risks.

Vandetanib is marketed by AstraZeneca Pharmaceuticals LP of Wilmington, Del. There is no trade name established for this drug at this time.

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