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February 26, 2010

Recent Cancer Screening Changes Leave Many Confused

Filed under: Health — Tags: — admin @ 9:22 am

The world of cancer screening has been upended in the past two weeks.

Not only did the U.S. Preventive Services Task Force (USPSTF) just raise the age at which it recommends women get their first mammogram from 40 to 50, but the American College of Obstetrics and Gynecologists (ACOG) decided that adolescents should be spared the inconvenience and possible risks of cervical cancer screening, and wait until they reach the age of 21 for such testing. Both groups also recommended screening less frequently.

Add to that the long-simmering debate on the value of PSA testing for prostate cancer and the fact that both the American Cancer Society (ACS) and the American College of Radiology have condemned the new USPSTF recommendations, it’s no wonder patients and even experts feel like they are suffering from a bad case of medical whiplash.

Was the timing of the announcements anything more than coincidence? Are the changes a reflection of new science, attempts to influence the current raging health-care debate or just medical business as usual?

The timing, by most accounts, was purely accidental.

“I think it’s a coincidence that this [the mammogram recommendation] came out when it did, right in the middle of the health-care reform discussion. It’s a good panel, one that was dedicated to getting the right answer to what should be done about this,” said Dr. Robert J. Barnet, senior scholar in residence at the Center for Clinical Bioethics at Georgetown University, in Washington, D.C.

Added Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La: “This is nothing new. Cancer screening guidelines have been changing as more scientific knowledge accumulates.”

And much of the new knowledge does suggest that over-screening does happen, often resulting in false-positive results, which lead to more biopsies and more angst. This is true of breast, cervical, prostate and other forms of cancer, experts concur.

“There’s appropriate screening and there is the appropriate population that should be getting that screening, and there is the appropriate screening interval,” said Dr. Otis Brawley, chief medical officer of the American Cancer Society. “We can violate all of those things.”

Meanwhile, false-positive results from mammographies are more common in younger (age 40 to 49) women than in the upper age bracket. And the age cut-offs for screening may be artificial.

“We like to lump people into big decades of life, so the risk of a 40-year-old woman and the risk of a 49-year-old woman [for breast cancer] are different,” Brooks noted. “The risk at 40 is much less than the risk at 49.”

“Younger women are at higher rates of false-positives, which results in more biopsies, more procedures being done and women getting callbacks for extra mammograms,” he added. “This creates anxiety for something that’s not anything bad.”

Also, there’s increasing evidence that some cancers will never turn into anything dangerous and, therefore, don’t warrant treatment.

“Our definition of cancer was given to us by German pathologists in the 1840s after they looked at biopsies from autopsy specimens,” Brawley explained. “Now, 170 years later, we’ve progressed in terms of imaging, in terms of medical diagnostics into what I call the genetic and molecular biologic age, but our ability to define cancer has not progressed beyond the light microscope. What we need to be able to do eventually is say that ‘this cancer is never going to progress,’ it is not going to spread and invade other organs in the body. But right now we don’t have the molecular tools to predict their behavior.”

“Not only do we need to find small tumors, we need to know more about the biology of those tumors,” added Dr. Michael V. Seiden, president and CEO of Fox Chase Cancer Center in Philadelphia.

Until those tools are developed, imperfect screening is going to lead to over-diagnosis and unnecessary treatment.

Still, there’s no question that the revisions do fit into a larger and rapidly changing health-care picture.

“Where I think the question was solely focused on ‘can you prevent cancer death?’ … 10 years ago or 20 years ago, I think there has been a much more open dialogue about the burden of screening, the cost burden, the anxiety burden, the false-positive burden,” Seiden said. “As screening techniques become more sensitive, you do a better and better job of capturing people with cancer but you also do a better job of capturing people with tumors they might not have died from. So, all of a sudden the incidence of pre-malignant breast disease, the incidence of low-grade prostate cancer, starts doubling and the death rate drops, but only very, very modestly.”

While the USPSTF stated that cost considerations had nothing to do with the new breast cancer recommendations announcement, ACOG did mention costs in its announcement regarding changes to cervical cancer screening.

“In this country, health care is an enormous issue and it is the single greatest driver of the national debt,” Brooks said. “There’s nothing wrong with raising financial questions in a public health setting.”

“It’s my belief that the task force just set the date [for its announcement] and wasn’t really paying attention to the politics. In truth, I don’t know but . . . part of the way of controlling costs is the rational use of medical care, not the rationing of care,” Brawley said. “For most women in the U.S., to get a Pap smear on an annual basis means that we’re going to spend three times more on cervical cancer screening than we need to spend and we’ve actually gotten evidence that screening tests every five years is going to save as many women as every three years [but] we’ve gone every three years to be safer.”

According to Brawley, ACOG’s new cervical cancer guidelines “look amazingly” like the 2002 American Cancer Society guidelines.

The ACS does not agree with the new USPSTF guidelines for breast cancer screening, however.

“Our view is that breast cancer screening saves lives and women aged 40 and above should get a high quality mammogram and clinical breast exam on an annual basis,” Brawley said.

Ochsner Health System’s Brooks is not changing his advice to women. “I tell women at age 40, if she wants to begin screening with mammography, it’s fine,” he said. “I haven’t changed what I’m recommending in my practice but I try to explain to women what the rationale behind it is.”

February 22, 2010

Smokers Double Their Risk for Heart Disease

Filed under: Health, Heart — Tags: — admin @ 9:21 am

A new study offers yet more proof that smoking is a major risk factor for death from heart disease and cancer.

Researchers followed 12,152 American and European male and female smokers, formers smokers and nonsmokers for three years. During that time, current smokers were 4.16 times more likely to die of cancer, 2.26 times more likely to die of heart disease and 2.58 times more likely to die from any cause than were former or nonsmokers. Current smokers were also more likely to suffer a heart attack or stroke.

There were no significant differences between former smokers and nonsmokers in the risk for dying from heart disease or any cause, but former smokers were more likely to die of cancer than those who’d never smoked.

“The analysis provides further strong evidence that people with heart disease who continue to smoke take a very high risk of increasing their chances of death in the short term,” principal investigator Dr. Deepak L. Bhatt, chief of cardiology at the Veterans Affairs Boston Healthcare System, said in a news release from the American Heart Association.

“This study provides impetus for a smoker to stop,” he said. “The benefits of risk reduction accrue relatively quickly when someone stops smoking, although the lingering cancer risk is still there.”

January 31, 2010

How long does hepatitis B vaccine protection last?

Filed under: Health — Tags: , — admin @ 2:53 am

The hepatitis B vaccine – given to protect against infection by a virus that can cause severe liver damage and cancer – may protect for more than two decades, according to a new study.

In 1981, Dr. Brian J. McMahon, from the Alaska Native Medical Center, Anchorage, and his colleagues gave more than 1500 Alaska Native adults and children over age 6 months three doses of hepatitis B vaccine. Before the hepatitis B vaccine was licensed for U.S. use in 1981, as many as one in 12 Alaskan Natives were infected.

In 2003, the team checked with almost 500 of those given the shots and had a response to them at the time to see who was still showing evidence of an immune system response. Blood tests found that more than half – 60 percent — were still considered immune to the virus.

To test whether the other 40 percent were immune, they were given a booster dose of the vaccine, to simulate infection. Most of those people – more than 80 percent – showed a response.

Overall, the researchers estimate that more than 90 percent of the original group was protected. There were no long-term hepatitis B infections in the group, which also suggests a high level of protection, they note in a report in the Journal of Infectious Diseases.

They conclude, “in light of the strong evidence we present here, hepatitis B vaccine booster doses are not currently indicated.”

January 25, 2010

Nicotine Patch Plus Lozenge Best for Quitting Smoking

Filed under: Health — Tags: , — admin @ 2:51 am

The first head-to-head comparison of different quit-smoking products finds that a nicotine patch combined with a nicotine lozenge had the most success.

More than other methods, including antidepressants, this combination best mimics the actual highs and lows of smoking to help smokers kick their habit, experts said.

“The study shows that, yes, one therapy came out on top, the patch and the lozenge [together],” said Dr. Jonathan H. Whiteson, co-director of the Joan and Joel Smilow Cardiopulmonary Rehabilitation and Prevention Center at NYU Langone Medical Center in New York City.

“The reasoning behind it is that the patch supplies a steady supply of nicotine replacement and the lozenges give a boost of nicotine which you can use when you have an extra craving. It gives people control,” said Whiteson, who was not involved in the research.

“If you combine these different types of nicotine replacement you’re going to get the best bang for your buck,” added Megan E. Piper, lead author of the new study and an assistant professor at the Center for Tobacco Research and Intervention at the University of Wisconsin, Madison. “But also remember that in this study people got a lot of counseling. It was that combination that resulted in a 40 percent quit rate [at six months out].”

In fact, coupling the patch with the lozenge was the only intervention that performed better than a placebo, reported the study, which appears in the November issue of the Archives of General Psychiatry.

The study adds insight to a field that’s long suffered from too little research. “As each medication comes out, it is tested against a placebo,” but not against other methods, Piper explained. “There just hasn’t been the funding or the availability of a program to do something like that.”

This research was funded by the U.S. National Institutes of Health. Medication was provided free by drug maker GlaxoSmithKline. Several of the study authors reported financial ties to different pharmaceutical companies.

For this study, 1,504 adults who had smoked at least half a pack a day for the past six months and wanted to quit were randomly assigned to a placebo or one of five different quit-smoking interventions: nicotine lozenge, nicotine patch, bupropion (Wellbutrin, an antidepressant), nicotine patch plus nicotine lozenge, and bupropion plus nicotine lozenge. All groups received six individual counseling sessions with a case manager.

The nicotine patch, which has been available for more than two decades, is currently the most widely used pharmacotherapy to help people quit smoking.

However, only the combination of the nicotine patch and the lozenge performed significantly better than placebo six months after the person smoked their last cigarette, the team found.

People taking the patch-lozenge combination were also more likely to have sworn off cigarettes after one week and were more likely to have attained one full day without smoking, the researchers said.

The 40 percent (at six months) success rate reported here will decline as time goes on, Whiteson noted. He added, however, that in the smoking cessation arena, “even the 30 percent range is very good.”

Another expert said the study raised some key concerns. “The question is, how many of them had to continue on the lozenge in order to stay off cigarettes? I always tell people not to do the lozenge alone because it mimics the very thing that smoking does, which gives you a spike. Then, when you reach a trough, you pick up a lozenge — or cigarette,” said Dr. Len Horovitz, a pulmonary specialist with Lenox Hill Hospital in New York City. “Once they stopped everything, could they do without the spikes and troughs [of the lozenge], which mimics physiologically everything the cigarette is doing? Smoking is a two-pronged problem. There’s nicotine dependence and a behavioral aspect to it.”

Dr. Elliot Wineburg, assistant clinical professor of psychiatry at Mount Sinai School of Medicine in New York City, felt the study suffered from some limitations, namely lack of individual attention to individual smokers’ habits.

“The authors said that they gave the patients lozenges according to the company’s [instructions],” he said. But this doesn’t take into account how much people smoke or how strong their cigarettes are. “They don’t even look into the amount of nicotine a person takes.”

January 11, 2010

Radiation After Surgery Lowers Chances of Melanoma Recurrence

Filed under: Health — Tags: — admin @ 3:36 am

Patients whose melanoma has spread to one or more lymph nodes face a decreased risk of the deadly skin cancer returning if they have radiation treatment following the removal of the nodes, a new Australian study shows.

In a paper to be presented Monday at the American Society for Radiation Oncology annual meeting in Chicago, lead researcher Dr. Bryan Burmeister, a radiation oncologist at Princess Alexandra Hospital in Brisbane, reported the hopeful findings from the five-year study.

“Results of this trial now confirm the place of radiation therapy in the management of patients who have high-risk features following surgery for melanoma involving the lymph nodes,” Burmeister said in a news release. “In some institutions, radiation treatment is routine protocol, while in others, the protocol has been either for patients to just be observed or receive some type of adjuvant chemotherapy or immunotherapy. I encourage patients with melanoma to talk to their doctors about whether radiation should be added to their treatment plan.”

External beam radiation involves the use of a beam (or beams) of radiation directed through the skin to the cancer and the tissue in its immediate vicinity. This targeted radiation destroys the tumor while helping to mop up nearby cancer cells that might remain after surgery. The therapy is usually painless and performed on an outpatient basis.

Burmeister’s study followed 217 patients with melanoma, a deadly skin cancer, between 2002 and 2007. All had at least one lymph node removed after doctors determined that the cancer had spread into the nodes. The surgery, called a lymphadenectomy, is standard treatment for metastasized melanoma.

About half the patients underwent postoperative radiation treatment, while the other half followed-up with their physicians to see if their cancer had returned. By the end of the study, 19 percent of the radiation patients had experienced a local nodal relapse of their melanoma, compared with 31 percent of patients who did not undergo postoperative radiation treatment. Overall survival was not affected, however.

Melanoma starts in the melanocytes, which are cells found in the top layer of skin that are responsible for producing the pigment melanin. Melanoma can arise anywhere there is pigmented tissue, including the eyes, sinuses, anus and a woman’s vulva.

According to the Memorial Sloan-Kettering Cancer Center in New York City, skin melanomas often look asymmetrical, have a ragged or blurred border and are dark in color. But rare forms of melanoma contain no pigment and can appear as pink nodules on the skin.

The disease is less common than other skin cancers, but if untreated, melanoma can spread and be difficult to cure. In the United States, more than 67,000 people annually are diagnosed with melanoma, and more than 8,000 will die, according to the American Cancer Society.

Given the severity of the disease, U.S. melanoma experts said they found the study intriguing.

“This is the first randomized study that tested the question whether postoperative radiation therapy offered any advantage in terms of loco-regional control to patients with loco-regionally advanced melanoma,” said Dr. Nancy Lee, a radiation oncologist at Memorial Sloan-Kettering. “The authors are to be congratulated for finally completing an important study in our field. This is particularly important as [local] recurrence can be devastating and often is difficult to salvage with additional therapy.”

Dr. David Fisher, of Boston’s Massachusetts General Hospital, praised the study but said he wanted more data on overall survival.

“This is an important study, since decisive data on the value of adjuvant radiation therapy have been lacking,” said Fisher, director of the melanoma program at Mass General. “It will be important to learn additional details, but the study appears to provide important supportive evidence for adjuvant radiation therapy.”

December 13, 2009

Task Force Finds Insufficient Evidence for Screening for Newborn Jaundice To Prevent a More Serious Chronic Condition

Filed under: Health — admin @ 9:14 am

According to a new recommendation from the U.S. Preventive Services Task Force, there is insufficient evidence to assess the balance of benefits and harms of screening infants for hyperbilirubinemia to prevent chronic bilirubin encephalopathy. Hyperbilirubinemia is a condition marked by a high level of bilirubin in the blood, which is often apparent as yellow-colored skin and eyes (jaundice). This recommendation and the accompanying summary of evidence will appear in the October issue of Pediatrics.

About 60 percent of all infants have jaundice, and it generally clears up without any medical treatment. Some infants are more likely to have severe jaundice and higher bilirubin levels than others. In some infants, hyperbilirubinemia may lead to chronic bilirubin encephalopathy, a rare but devastating neurological condition. The brain damage associated with chronic bilirubin encephalopathy, or kernicterus, may result in cerebral palsy, auditory processing problems, gaze and vision abnormalities, and cognitive problems. The number of children who develop chronic bilirubin encephalopathy is unknown and difficult to determine.

“There is inadequate evidence that screening all full-term and near-term infants for elevated bilirubin leads to improved health outcomes,” said Task Force Chair Ned Calonge, M.D., who is also chief medical officer for the Colorado Department of Public Health and Environment. “More research is necessary to understand how often chronic bilirubin encephalopathy occurs, its risk factors, and whether screening is associated with a reduction in chronic bilirubin encephalopathy.”

There is evidence that screening using risk factor assessment or bilirubin level measurement can identify infants at risk of developing hyperbilirubinemia, but there is no known screening test that will reliably identify all infants at risk of developing chronic bilirubin encephalopathy. Not all infants with chronic bilirubin encephalopathy have a history of hyperbilirubinemia, and not all infants who have extremely high levels of bilirubin develop chronic bilirubin encephalopathy.

In assessing the potential benefits and harms of screening infants for hyperbilirubinemia, the Task Force looked for evidence that screening reduced the number of new cases of chronic bilirubin encephalopathy. No studies have directly addressed whether screening, either risk-factor assessment or bilirubin testing, reduced the number of new cases of chronic bilirubin encephalopathy. The current evidence on screening has evaluated the effectiveness of screening to identify infants for treatment intended to reduce high levels of bilirubin.

The Task Force found that the evidence is currently insufficient regarding whether treating infants with high levels of bilirubin results in fewer children developing chronic bilirubin encephalopathy. There is a critical gap in the evidence regarding the relationship between screening infants without symptoms of hyperbilirubinemia and the desired outcome of reducing cases of chronic bilirubin encephalopathy. When the Task Force finds insufficient evidence to make a recommendation, it does not mean a clinician shouldn’t provide a service but that the evidence is lacking, and if a service is offered, patients should understand the uncertainty about the balance of benefits and harms. The Task Force recognizes that clinical or policy decisions involve more consideration than their recommendations alone, and clinicians and policy makers should understand the evidence but individualize decision-making to the specific patient or situation.

Efforts have been made by clinicians to eliminate this rare disorder by applying measures to screen for and aggressively manage high bilirubin levels. Universal screening for jaundice is widespread in the United States, and clinicians and parents should continue to work together to decide whether to screen in the face of insufficient evidence. Clinicians must remain aware that screening and resulting treatment of hyperbilirubinemia have potential harms such as weight loss, gastrointestinal problems, and disruption of the mother-infant bonding.

The Task Force is the leading independent panel of experts in prevention and primary care. The Task Force, which is supported by the Agency for Healthcare Research and Quality (AHRQ), conducts rigorous, impartial assessments of the scientific evidence for the effectiveness of a broad range of clinical preventive services, including screening, counseling and preventive medications. Its recommendations are considered the gold standard for clinical preventive services.

The recommendations and materials for clinicians are available on the AHRQ Web site at http://www.ahrq.gov/clinic/uspstf/uspshyperb.htm.

December 7, 2009

When Pounds Go, Sleep Apnea May Improve

Filed under: Health — admin @ 3:13 pm

People with sleep apnea who are also obese may triple the chances of eliminating their sleep problems by losing weight, a new study suggests.

Losing about 10 percent of their body weight was enough to bring on total or near-total remission, said Gary Foster, head of the Center for Obesity Research and Education at Temple University in Philadelphia, and lead author of the study.

“It’s been clear that obesity increases the risk of sleep apnea but less clear that if obese people or people with type 2 diabetes lost weight, it would result in significant improvements in their sleep apnea — and it did,” said Foster.

People who are overweight or obese are much more likely to have obstructive sleep apnea, a condition in which a person’s breathing stops or becomes very shallow, sometimes several hundred times a night and sometimes for as long as a minute, according to the American Sleep Apnea Association.

“The soft palate in the back of mouth falls down and blocks the airway,” said Dr. Mitchell Roslin, chief of bariatric surgery at Lenox Hill Hospital in New York City. “When you get to people with serious levels of obesity, it’s virtually impossible to find those without [this type of] sleep apnea.”

The condition can lead to cardiovascular problems, including stroke, and can raise the risk for dying prematurely.

“It really has tremendous detrimental effects on the cardiovascular system,” Roslin said.

The study involved 264 obese men and women who also had type 2 diabetes and obstructive sleep apnea. They were randomly assigned to an intensive behavioral program intended to encourage weight loss or to a less intensive set of group sessions that mainly addressed the issue of diabetes management.

After a year, those in the intensive program had lost an average of about 24 pounds, compared with slightly more than a one-pound average weight loss for the others.

Those who lost the weight also saw a substantial reduction in the number of sleep apnea episodes they experienced, with more than three times as many people in the intensive group experiencing complete remission (13.6 percent versus 3.5 percent).

“The greatest benefit was seen in men and those with severe apnea,” Foster said.

Any amount of weight loss brought on an improvement, but those who lost about 10 percent of their original body weight saw the greatest effect. “Any weight loss is good,” Foster said.

Most experts recommend 10 percent as the weight loss needed to improve sleep apnea.

However, the study also found that people whose weight remained stable experienced a worsening in their sleep apnea. Just why that occurred remains unclear.

“This is one of the first and certainly the largest study ever conducted so we’re at the point in the field, unfortunately, where we’re just describing the effect,” Foster said.

The study, published Sept. 28 in the Archives of Internal Medicine, does seem to confirm what common sense and experience have shown.

“We’ve seen that when patients gain five to 10 pounds, their sleep apnea is much worse. If they lose five to 10 pounds, the sleep apnea is much better,” said Dr. Hormoz Ashtyani, director of pulmonary critical care and sleep medicine at Hackensack University Medical Center in New Jersey. “It’s usually not a resolution, but it’s a significant improvement.”

November 24, 2009

Life Expectancy at All Time High; Death Rates Reach New Low, New Report Shows

Filed under: Health — admin @ 7:29 am

U.S. life expectancy reached nearly 78 years (77.9), and the age-adjusted death rate dropped to 760.3 deaths per 100,000 population, both records, according to the latest mortality statistics from the Centers for Disease Control and Prevention (CDC).

The report, “Deaths: Preliminary Data for 2007,” was issued today by CDC’s National Center for Health Statistics. The data are based on nearly 90 percent of death certificates in the United States.

The 2007 increase in life expectancy – up from 77.7 in 2006 — represents a continuation of a trend. Over a decade, life expectancy has increased 1.4 years from 76.5 years in 1997 to 77.9 in 2007.

Other findings:
Record high life expectancy was recorded for both males and females (75.3 years and 80.4 years, respectively). While the gap between male and female life expectancy has narrowed since the peak gap of 7.8 years in 1979, the 5.1 year difference in 2007 is the same as in 2006.
For the first time, life expectancy for black males reached 70 years.
The U.S. mortality rate fell for the eighth straight year to an all-time low of 760.3 deaths per 100,000 population in 2007 — 2.1 percent lower than the 2006 rate of 776.5. The 2007 mortality rate is half of what it was 60 years ago (1532 per 100,000 in 1947.)
The preliminary number of deaths in the United States in 2007 was 2,423,995, a 2,269 decrease from the 2006 total.
Heart disease and cancer, the two leading causes of death, accounted for nearly half (48.5 percent) of all deaths in 2007.
Between 2006 and 2007, mortality rates declined significantly for eight of the 15 leading causes of death. Declines were observed for influenza and pneumonia (8.4 percent), homicide (6.5 percent), accidents (5 percent), heart disease (4.7 percent), stroke (4.6 percent), diabetes (3.9 percent), hypertension (2.7 percent), and cancer (1.8 percent).
The death rate for the fourth leading cause of death, chronic lower respiratory diseases, increased by 1.7 percent. Preliminary death rates also increased for Parkinson’s disease, chronic liver disease and cirrhosis, and Alzheimer’s, but these gains are not statistically significant.
There were an estimated 11,061 deaths from HIV/AIDS in 2007, and mortality rates from the disease declined 10 percent from 2006, the biggest one-year decline since 1998. HIV remains the sixth leading cause of death among 25-44 year-olds.
The preliminary infant mortality rate for 2007 was 6.77 infant deaths per 1,000 live births, a 1.2 percent increase from the 2006 rate of 6.69, though not considered statistically significant. Birth defects were the leading cause of infant death in 2007, followed by disorders related to preterm birth and low birthweight. Sudden infant death syndrome (SIDS) was the third leading cause of infant death in the United States.

November 19, 2009

Chemo Plus Palliative Care Reaps Benefits

Filed under: Health — admin @ 7:29 am

Providing palliative care at the same time that advanced cancer patients are undergoing treatment improves their quality of life and mood, a new study shows.

It included 322 patients randomly selected to receive either usual cancer care or a palliative care program consisting of four weekly educational sessions followed by monthly sessions until they died or the study ended. The palliative program was designed to encourage patient self-management and empowerment.

The study appears in the Aug. 19 issue of the Journal of the American Medical Association.

The patients’ quality of life, symptom intensity and mood were assessed at the start of the study, at one month, and then every three months until death or study completion.

The palliative care program “demonstrated higher quality of life, lower depressed mood, but limited effect on symptom intensity scores and use of resources in intervention participants relative to those receiving usual cancer care,” Marie Bakitas of the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues wrote in a journal news release. “The intervention had no effect on the number of days in the hospital and ICU, the number of emergency department visits, or anti-cancer treatment because the proportions of participants in each group receiving these therapies were similar.”

Regarding patients’ symptom intensity, the researchers wrote that “there may be little room for improvement because usual care participants also reported relatively low symptom intensity scores compared with patients with advanced cancer in other studies. It may be unrealistic to expect to reduce symptoms further in the setting of progressive disease.”

November 9, 2009

Diagnostic Technique Shows Promise for Primary Sjögren’s Syndrome

Filed under: Health — admin @ 7:28 am

For the thousands of Americans who will be evaluated this year for the autoimmune disorder primary Sjögren’s syndrome, their doctors will likely test for two antibodies that are often associated with the condition. The problem is today’s standard blood tests detect the more strongly associated antibody, called SSB, only about half the time, making the meaning of a negative result uncertain.

But these numbers could one day improve. Scientists at the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health, report online in the journal Autoimmunity that a rapid, automated test now under development called LIPS identified the SSB antibody correctly three out of four times and with perfect accuracy. It also detected a second antibody, SSA, about as well as today’s standard assays in the group’s initial study of 82 people, 57 of whom had well-characterized primary Sjögren’s syndrome.

“This is just step one in our work to improve antibody detection for Sjögren’s syndrome,” said Peter Burbelo, Ph.D., lead author on the paper and a scientist at NIDCR. “With further refinements, the percentages will only get better.”

Burbelo and colleagues also reported using LIPS to profile additional antibodies of interest that may be related to other largely unrecognized manifestations of the syndrome. These first-pass antibody profiles have the potential to help scientists define for the first time a range of clinical subtypes of primary Sjögren’s, which could greatly improve diagnoses and possibly better target treatment.

Primary Sjögren’s syndrome is a chronic autoimmune disorder that affects about 4 million Americans, 90 percent of whom are women. Scientists have long thought the syndrome is triggered when white blood cells mistakenly attack the body’s moisture-producing glands, typically causing chronic dry mouth, dry eyes, and arthritis.

But other Sjögren’s-related health problems continue to be reported in the medical literature, including lymphoma, thyroid dysfunction, painful peripheral neuropathy, and gastrointestinal problems. These seemingly phantom symptoms remain poorly defined, diagnostically controversial, and suggest a more systemic and yet-to-be-defined underlying pathology.

That’s where LIPS enters the picture. Short for luciferase immunoprecipitation technology, LIPS is a traditional bait-and-bind diagnostic assay. The bait is any recombinant laboratory-made antigen, or segment of a protein known to elicit an antibody response, that is then fused to an enzyme similar to the light-producing luciferase that produces the flash in fireflies.

According to Burbelo, this hybrid antigen is incubated in solution with a drop of a person’s serum. If the antibody of interest is present, it will bind to the bait. Thereafter, the entire antibody-antigen complex attaches to small beads that are then measured by its firefly-like light emission. The greater the intensity of the light flash, the more target antibody there is bound to the antigen.

What makes LIPS different from other antibody tests is its extreme sensitivity, or ability to correctly detect an antibody of interest. Burbelo said this stems from selecting mammalian cells and its biological machinery as the recombinant cloning vector to make the antigens. They more closely resemble human cells than the non-mammalian sources typically used today to make test antigens, such as the bacterium E. coli.

“Antibodies must see the natural three-dimensional shape of an antigen to recognize it,” said Burbelo. “With today’s tests, the assumption is an antigen’s three-dimensional shape will be retained once it’s produced and affixed to plastic. But typically that’s not the case. Antibodies will recognize a stretch of amino acids here and maybe there. They won’t see other pieces of the protein that have degraded and lost their natural conformations.”

“With LIPS, more of the three-dimensional shape is retained, and that heightens the sensitivity,” he continued. “For example, an ELISA [Enzyme-Linked ImmunoSorbent Assay] typically has a dynamic range of between 5 and 15,000 units of signal. A unit of signal is the measure of light intensity. In other words, how bright is the test’s green or red signal? With LIPS, we see samples that range from zero to sometimes over a million units of signal.”

This zero-to-million diagnostic window allows Burbelo and colleagues to more objectively measure any antibody response associated with an autoimmune disorder. It also suggests LIPS may have the potential to detect most developing autoimmune disorders before they become symptomatic, more closely monitor the ups and downs of a patient’s antibody counts over time, and track the immunological outcome of an autoimmune treatment.

To date, Burbelo and colleagues have published intriguing data involving LIPS and a range of autoimmune conditions, from type I diabetes to herpes simplex virus. In the current study, they began by applying their new tool to the Sjögren’s-associated antibodies, SSA and SSB. But they did so with a diagnostic twist.

“Traditionally, the SSA antigen consists of two proteins — Ro52 and Ro60 — that are conjoined and anchored on the plastic diagnostic assays,” said Mike Iadarola, Ph.D., an NIDCR scientist and senior author on the study. “We teased apart the two proteins to present their full three-dimensional shape and were able to measure the antibody response to each separately.”

The group found that 42 of the study’s 57 previously diagnosed Sjögren’s patients had antibody reactions against a segment of the Ro52 antigen that does not elicit a response in today’s ELISA tests, a sign of the LIPS assay’s greater sensitivity. Overall, LIPS detected antibody responses against each protein in about 60 percent of patients, roughly equal to an ELISA, but with a far greater dynamic range and perfect specificity.

The scientists then decided to test for other conditions not traditionally linked to Sjögren’s syndrome but that occasionally — and bewilderingly — have been reported in some patients. “We hypothesized that if we made antigens for the thyroid, stomach, and peripheral nervous system, LIPS could pick out the subset of patients with antibodies against these tissues,” said Iadarola.

And it did. The scientists found 14 percent of their Sjögren’s patients had antibodies against the thyroid antigen, 16 percent had antibodies against an antigen associated with autoimmune gastritis, and four percent had antibodies linked to an autoimmune attack of the eye’s peripheral nerve.

These findings suggest that LIPS may be used as a substitute for more invasive and expensive procedures typically used to diagnose these peripheral conditions. “Again, this study is just a start,” said Burbelo. “All of these tests can be performed on the automated robotic machine in my laboratory, and we can do thousands a day. There’s more data to come.”

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