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December 20, 2009

Scientists Discover How Chemo Can Make Women Infertile

Filed under: Women — admin @ 9:15 am

Italian researchers say they have identified the mechanism by which chemotherapy can rob a woman of her ability to have children.

Intriguingly, the scientists also found that another anti-cancer drug might counteract the negative effects of the chemotherapy drug cisplatin.

The finding, demonstrated in mice and reported in the Sept. 27 online edition of Nature Medicine, raises the hope that there might be a way to protect a woman’s fertility while she undergoes treatment for cancer but, the authors stressed, this is still a long way off.

“The extension of these findings to patients and the design of clinical trials is likely to require the development of targeted drug delivery strategies to avoid any potential interference with anti-cancer systemic therapy,” explained study author Stefania Gonfloni, of the department of biology at the University of Rome.

“I think it’s a great idea. They found a pathway that can be used as a marker to detect which drug would produce cell death as a result of chemotherapy, and they found a repair effect of a drug,” said Dr. George Attia, an associate professor of reproductive endocrinology and infertility at the University of Miami Miller School of Medicine. “[But] it’s very basic science research. It’s still early.”

Because chemotherapy affects the egg cells of the ovary, women often end up with ovarian failure and infertility as a result of cancer treatment.

“We frequently deal with women of childbearing age, and there’s a lot of concern about fertility preservation although as women get older, the chemo induces menopause,” said Dr. Igor Astsaturov, an assistant professor of medical oncology at Fox Chase Cancer Center in Philadelphia. “The standard approach now is egg collection [storing eggs for later use].”

Chemotherapy can also cause genetic defects in offspring. In particular, cisplatin, which was studied in this trial, causes specific types of chromosomal damage.

Cisplatin is primarily usually used to treat ovarian cancer, Attia noted.

In this study, Gonfloni and her colleagues showed that cisplatin promotes the death of oocytes, or female germ cells, by way of the c-Abl enzyme, a protein that, when mutated, can also cause chronic myeloid leukemia (CML).

But targeting the enzyme with imatinib (Gleevec), a drug used to treat CML, protected the oocytes from the ill effects of cisplatin.

“These results raise the possibility of protecting ovarian function during cancer treatments, thereby preserving the fertility in female cancer survivors,” Gonfloni added.

But how to use one drug without compromising the other?

“First, we have to show that imatinib can be used to prevent chemotherapy-induced ovarian toxicity without interfering with anti-cancer treatments,” Gonfloni said. “In other words, we have to prove that tumor-bearing laboratory animals can be cured with a combined cisplatin and imatinib treatment, while at the same time preserving fertility,” she explained.

“Then, for any clinical implications, it will be very important to prove the same protective effect of a specific dosage of imatinib on human oocytes cultured and challenged with chemotherapeutic drugs in vitro,” she added.

And preserving fertility is not always the right thing, Astsaturov said.

“Chemotherapy induces menopause in some hormone-dependent cancers. It has a beneficial effect because it’s withdrawing the stimulants for the cancer cells. Menopause is contributing to the cure,” he said. “It’s still debated whether we should preserve menstrual function at all costs.”

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 30, 2009

Herb Shows Potential for Rheumatoid Arthritis

Filed under: Uncategorized — admin @ 9:30 am

An ancient Chinese herbal remedy called “thunder god vine” helps reduce inflammation in people with rheumatoid arthritis, a new study shows.

The remedy is an extract of the medicinal plant Tripterygium wilfordii Hook F (TwHF) — known in China as “lei gong teng” — and has been used for centuries to treat a variety of inflammatory diseases.

The study compared reduction in joint swelling among people with rheumatoid arthritis who took either the herb or an anti-inflammatory drug.

Rheumatoid arthritis causes chronic and painful inflammation of the joints that, over time, can lead to joint damage and loss of function.

The 121 participants in the study all had at least six swollen joints. One group took 60 milligrams of TwHF root extract three times a day, and the others 1 gram of sulfasalazine (Azulfidine), a prescription anti-inflammatory drug, twice a day.

After 24 weeks, about 65 percent of those taking the herbal extract showed at least a 20 percent improvement in their joints, based on American College of Rheumatology criteria, a standard measure of the effectiveness of arthritis treatments. About 33 percent of those taking sulfasalazine improved to that degree.

A report on the findings is published Aug. 18 in Annals of Internal Medicine.

“This study is a reminder of the potential importance of supplements and herbs in the management of arthritis,” said Dr. John H. Klippel, president and chief executive of the Arthritis Foundation.

Even so, the study involved a relatively small number of people, Klippel noted. Clinical trials for pharmaceuticals typically involve many more participants studied over several years, he said.

“The findings are encouraging, but [TwHF] is not likely to be recommended by rheumatologists based on the findings of this one study alone,” Klippel said.

And, though sulfasalazine used to be very popular as an arthritis treatment, the drug is not used that often today in the United States, according to Dr. Stephen Lindsey, head of rheumatology at Ochsner Health Systems in Baton Rouge, La.

Methotrexate (Rheumatrex, Trexall) is the drug most often used today, he said.

“I would be optimistic that an herbal medicine would play some role in improving rheumatoid arthritis,” Lindsey said. But he added that he “would be a little bit wary since the medicine they compared it to is a fairly mild, anti-rheumatoid agent and not the standard drug used in the U.S.”

Other alternative remedies, he said, have proven helpful for arthritis, including fish oil, though some of them have not held up to more rigorous studies.

Participants in the new study were allowed to continue taking oral prednisone or nonsteroidal anti-inflammatory drugs, but anyone who was taking disease-modifying anti-rheumatic drugs (such as methotrexate), which slow the progression of the disease, had to stop taking them about a month before the study began.

Researchers did not see a statistically significant difference in joint damage on X-rays, Klippel said. But he said that probably was because six months wasn’t long enough for noticeable changes.

The study also had a high dropout rate, with 62 percent of those taking TwHF and 41 percent of the others continuing to the end. According to the study, 17 people taking sulfasalzine and 8 taking TwHF dropped out because of adverse effects — most often gastrointestinal symptoms, including nausea and diarrhea.

Lindsey noted that people should always remember to tell their doctor if they are taking an herbal supplement.

“Just because something is herbal doesn’t mean it’s going to be cheap or safe,” he said.

November 29, 2009

Antioxidants Abound in Cereals, Popcorn, Whole-Grain Snacks

Filed under: Antioxidants — admin @ 7:30 am

Eating a bowl of your favorite cereal every day is a great source of natural antioxidants, new research shows.

Joe Vinson, a professor of chemistry at the University of Scranton, in Pennsylvania, and his team have found that nearly all whole-grain breakfast cereals and many common, grain-based snacks contain substantial amounts of polyphenols, a form of antioxidants that is thought to have major health benefits. Vinson was scheduled to present his findings Tuesday at the American Chemical Society annual meeting, held in Washington, D.C.

“Cereals have a plethora of [good things],” said Vinson, who tested more than 30 brands and types of breakfast cereals found in supermarkets. “They all have polyphenols.”

Whole grains are the main source of polyphenols in breakfast cereals, and since nearly all cereals contain at least some whole grains, it stands to reason that consumers should consider making cereals a regular part of their diet, said Vinson, adding that he received no food industry funding for his study.

“Early researchers thought the fiber was the active ingredient for these benefits in whole grains — the reason why they may reduce the risk of cancer and coronary heart disease,” Vinson noted. “But recently, polyphenols emerged as potentially more important. Breakfast cereals, pasta, crackers and salty snacks constitute over 66 percent of whole grain intake in the U.S. diet,” he added.

“We found that, in fact, whole-grain products have comparable antioxidants per gram to fruits and vegetables,” Vinson said. “This is the first study to examine total phenol antioxidants in breakfast cereals and snacks, whereas previous studies have measured free antioxidants in the products.”

Polyphenols occur naturally in plants and are the most abundant antioxidant. They have anti-inflammatory properties, and scientists believe they may reduce the risk of cardiovascular disease, cancer and other illnesses.

Nutritionists have recommended regular consumption of green tea, red wine, fruits, nuts and a few other food categories for their antioxidant content. Vinson found that cereals containing whole-grain corn or oats contained the most polyphenols, roughly 0.2 percent by weight per box. Wheat-based cereals contained an average of 0.07 percent polyphenols, and rice cereals contained the lowest amount, at 0.05 percent.

Raisin bran had the most polyphenols — 3 percent by weight; however, Vinson attributed the concentration to the raisins — like other dried fruits, a known rich source of antioxidants.

Another high-ranking cereal was a wheat-based blend containing the polyphenol-rich spice cinnamon. Vinson declined to name the brands he tested, but he encouraged people to add nuts, raisins and various spices like cinnamon to their cereal to boost their polyphenol content.

As for snacks, Vinson found that popcorn had the most polyphenols (2.6 percent), followed by whole-grain crackers (0.45 percent). Sadly, most processed tortilla chips — Vinson’s favorite — contained negligible amounts of polyphenols.

Registered dietician and nutritionist Eva To, who practices in White Plains, N.Y., said she found the study fascinating, but she had some concerns.

“Whole-grain cereal is a great replacement for high-fat breakfast food or as a replacement for no breakfast at all, since breakfast is the most important meal of the day,” said To, who specializes in obesity and diabetes management. “But moderation is the key. Many cereals contain ingredients that may not be very good for you, such as excessive sugar.”

Also, she added, “cereals are easy to binge on. It is very important to follow the serving size suggestions.”

To Vinson, the benefits of eating more cereals may outweigh the negatives.

“We always think of fruits and vegetables as the primary sources of polyphenols,” he said. “But many people, especially students, don’t eat enough of them. Here we have a product that is very familiar in the diet and that people like to eat. We can push kids to eat more whole grains.”

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 14, 2009

Life Expectancy in U.S. Hits a New High

Filed under: Uncategorized — admin @ 7:28 am

Life expectancy in the United States has reached almost 78 years, a record high, federal health officials said Wednesday.

Not only has life expectancy increased, but the death rate has dropped to an all-time low of 760.3 deaths per 100,000 people, according to the new report from the U.S. Centers for Disease Control and Prevention.

“It is difficult to say for sure why this trend continues,” said report author Robert N. Anderson, chief of the Mortality Statistics Branch, at CDC’s National Center for Health Statistics. “We are making improvements in medical care and prevention. There are lots of factors that could be in play,” he noted.

“If you look at all the demographic groups, we are making improvements across the board,” Anderson said. “Life expectancy has been increasing for the last 50 years or so, and the mortality rate has been coming down steadily as well.”

Anderson noted that life expectancy in the United States is still lower than in many other industrialized countries, including Canada and Japan.

The report is based on data from nearly 90 percent of U.S. death certificates.

According to the report, life expectancy in 2007 increased to 77.9 years, up from 77.7 years in 2006. Life expectancy has increased 1.4 years since 1997.

Other findings in the report include:
Life expectancy is at an all-time high for both men and women (75.3 years and 80.4 years, respectively).
The gap between male and female life expectancy has narrowed since a peak of 7.8 years in 1979 to 5.1 years in 2007 (the same as in 2006).
Life expectancy for black men has reached 70 years for the first time.
The death rate fell for the eighth straight year to a new low of 760.3 deaths per 100,000 people. That’s 2.1 percent lower than the 2006 rate of 776.5. The 2007 death rate is half that of 60 years ago (1,532 per 100,000 in 1947.)
In 2007, the number of people who died in the United States was 2,423,995. That’s a 2,269 decrease from 2006.
Heart disease and cancer accounted for almost half (48.5 percent) of all deaths in 2007.
From 2006 to 2007, deaths for eight of the 15 leading causes of death dropped. There were fewer deaths from influenza/pneumonia, homicide, accidents, heart disease, stroke, diabetes, high blood pressure and cancer.
However, deaths from the fourth leading cause of mortality, chronic lower respiratory diseases, increased 1.7 percent. Death rates also increased for Parkinson’s disease, chronic liver disease and cirrhosis, and Alzheimer’s.
In 2007, there were 11,061 deaths due to HIV/AIDS, a 10 percent drop from 2006, the biggest one-year drop since 1998. HIV remains the sixth leading cause of death among those aged 25 to 44.
The death rate for infants was 6.77 per 1,000 live births in 2007, up 1.2 percent from 2006, but the increase was not statistically significant, the researchers noted. The leading cause of infant mortality was birth defects followed by problems related to preterm birth and low birth weight. Sudden infant death syndrome (SIDS) was the third leading cause of infant death.

Dr. David L. Katz, director of the Prevention Research Center at Yale University School of Medicine, said he is less concerned with increased life expectancy and more concerned with how people are living longer.

“It’s certainly the wrong season for a Grinch, so I would prefer not to be one, and to simply add a hallelujah in response to these convincing data that life expectancy in the U.S. has reached an all-time high,” Katz said. “But I fear this glass may be half empty. I need to know both why, and how, we are living longer.”

Obesity, diabetes and chronic disease rates are at an all-time high in the United States, Katz noted.

“I suspect we may be living longer not because of improvements in health, but thanks to the ability of high-tech, high-cost medicine to forestall death despite a growing burden of chronic disease,” he said. “That means we may be adding years to life while reducing the life and vitality in those years, a very dubious bargain.”

Modern medicine may help humans live relatively long lives, Katz said. “But to prosper, we must do a far better job of cultivating health at its origins. There is much more to living well than not dying.”

November 10, 2009

End-of-Life Advice Not Always Welcome

Filed under: Uncategorized — admin @ 1:35 pm

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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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