New report in the Journal of Leukocyte Biology suggests that zinc activates a key protein on T cells needed to fight infections

Everyone knows that vitamins “from A to zinc” are important for good health. Now, a new research study in the August 2009 print issue of the Journal of Leukocyte Biology (http://www.jleukbio.org) suggests that zinc may be pointing the way to new therapeutic targets for fighting infections. Specifically, scientists from Florida found that zinc not only supports healthy immune function, but increases activation of the cells (T cells) responsible for destroying viruses and bacteria.

“It has been shown that zinc supplementation significantly reduces the duration and severity of childhood diarrhea, lower respiratory infections, and incidence of malaria in zinc-deficient children,” said report co-author, Robert Cousins, Ph.D., who also is the director of the Center for Nutritional Sciences within the Food Science and Human Nutrition Department at the University of Florida. “Age-related declines in immune function have also been related to zinc deficiency in the elderly.”

Scientists administered either a zinc supplement or a placebo to healthy volunteers to assess the effects of zinc on T cell activation. After isolating the T cells from the blood, scientists then simulated infection in laboratory conditions. Results showed that T cells taken from the zinc-supplemented group had higher activation than those from the placebo group. Specifically, cell activation stimulated the zinc transporter in T cells called “ZIP8,” which transports stored zinc into the cell cytoplasm where it then alters the expression of a T cell protein in a way needed to fight infections.

“As the debate over zinc supplementation in healthy individuals continues,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, “studies like this help shed light on how zinc may enhance the ability of our immune systems to fight off foreign invaders. Equally important, this work points toward new possible targets for entirely new drugs to help augment immune function and prevent or stop infections that might be resistant to traditional antibiotics.”

The Journal of Leukocyte Biology (http://www.jleukbio.org) publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.

Details: Tolunay B. Aydemir, Juan P. Liuzzi, Steve McClellan, and Robert J. Cousins Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN- expression in activated human T cells. J Leukoc Biol 2009 86: 337. http://www.jleukbio.org/cgi/content/abstract/86/2/337

Federation of American Societies for Experimental Biology

Disturbed calcium signaling may play a critical role in brain cell degeneration

University of Utah School of Medicine researchers and their colleagues at University of Texas (UT) Southwestern Medical Center have found strong evidence that abnormal calcium signaling in neurons may play an important role in the development of spinocerebellar ataxia type 2 (SCA2), a disorder causing progressive loss of coordination, speech difficulty, and abnormal eye movements. Their findings are published in the July 27, 2009 issue of Journal of Neuroscience.

SCA2 is an inherited neurodegenerative disease that predominantly affects neurons called Purkinje cells in the cerebellum, the region of the brain that controls voluntary muscle movements, balance, and posture. It is one of a group of genetic disorders characterized by ataxia, or loss of muscle coordination.

“We have known for some time that, at a molecular level, SCA2 is caused by glutamine repeat mutations in the ataxin-2 gene, but the exact mechanism of Purkinje cell degeneration is not well understood,” says Stefan-M. Pulst, MD, University of Utah professor and chair of neurology, member of the Brain Institute at the University of Utah, and contributor author on this study. Pulst’s group also discovered the ataxin-2 gene in 1996.

The glutamine repeat mutations found in SCA2 are also found in other neurodegenerative diseases, including Huntington disease (HD) and spinocerebellar ataxia type 3 (SCA3). It is commonly assumed that these disorders share a common pathogenic mechanism. Ilya Bezprozvanny, PhD, associate professor of physiology at UT Southwestern Medical Center, and his group had previously uncovered evidence that deranged calcium signaling played an important role in the pathology of HD and SCA3, so they thought that abnormal calcium signaling might also be involved in SCA2.

Calcium signaling refers to the movement or release of calcium ions as a form of cellular communication. Bezprozvanny and his colleagues demonstrated that the mutant ataxin-2 gene strongly associated with an intracellular calcium release channel, increasing the sensitivity of the channel to activation. They also found that enhanced calcium signaling contributed to the death of Purkinje cells in cell culture, but this effect could be attenuated by dantrolene, a stabilizer of intracellular calcium signaling. Bezprozvanny and his colleagues then approached Pulst, who had developed a mouse model of SCA2, in order to test whether these results could be replicated in genetically modified mice.

The authors discovered that dantrolene was effective in alleviating motor coordination deficits in mice with a mutant ataxin-2 gene. After being fed dantrolene for a period of nine months, these mice were found to have motor coordination that was similar to normal mice and they did not suffer any significant adverse effects from long-term treatment with the calcium signaling stabilizer. The scientists also discovered that, beyond the positive effects on coordination, feeding dantrolene to mice with a mutant ataxin-2 gene reduced the death of Purkinje cells in the cerebellum.

“We were all elated to find that dantrolene had a pronounced effect in our mice,” says Pulst. “It prevented deterioration in motor function and Purkinje cell death. ”

Dantrolene is approved for use in humans for the treatment of muscle spasticity. “Although it showed effects in mice with ataxia, it could have major side effects in human patients with ataxia because it may cause sedation and muscle weakness. Therefore, this drug should be evaluated in controlled clinical trials before wide-spread use in SCA2 patients,” cautions Pulst.

Taken together with their previous studies on HD and SCA3, the research group now has evidence that deranged calcium signaling contributes to the pathogenesis of at least three inherited ataxias. This strongly suggests that abnormal neuronal calcium signaling may also be involved in other neurodegenerative diseases caused by glutamine repeat mutations.

It is estimated that SCA2 affects as many as one or two in every 100,000 people. “Neurodegenerative diseases like HD and SCA2 are progressive and have no known cures at this moment,” according to Pulst. “Calcium signaling stabilizers such as dantrolene or similar compounds may provide a new avenue for investigation in the laboratory and in clinical trials to limit disability and disease progression.”

University of Utah Health Sciences

Surgeons from Hospital for Special Surgery in New York have identified a drilling technique that improves the outcome of surgery to reconstruct the anterior cruciate ligament (ACL). The news will be presented during the annual meeting of the American Orthopedic Society for Sports Medicine, June 9-12, in Keystone. Colo.

“We found that the anatomy was better reproduced with the anteromedial portal drilling technique compared to the transtibial technique,” said Asheesh Bedi, M.D., a fellow in sports medicine and shoulder surgery at Hospital for Special Surgery who was involved with the study.

In recent years, an improved understanding of the anatomy of the ACL has allowed surgeons to refine techniques to reconstruct the ACL. Investigators at Hospital for Special Surgery (HSS) set out to compare the outcomes of surgeries using two common techniques. “The goal in repairing the ACL is to recreate the normal anatomy, and there are a variety of different techniques to prepare tunnels for ACL reconstruction that have evolved over time,” said Dr. Bedi. “The focus of the study was to compare two very common techniques in terms of their ability to reproduce the native ligament anatomy and restore the stability of the knee after reconstruction in a cadaveric model.”

The investigators used ten matched cadaveric knees to directly compare the transtibial and anteromedial portal drilling technique. The researchers found that the transtibial technique could not reproduce the position of the ACL, whereas the anteromedial portal drilling technique could better restore the native anatomy. The transtibial technique also presented additional concerns. “In preparing the femoral tunnel using the transtibial technique, the tibial tunnel is inadvertently re-reamed as much as 30 percent and can lead to significant time-zero tunnel expansion,” Dr. Bedi said. The transtibial reconstruction also performed inferiorly to the medial portal on a number of biomechanical parameters of stability assessed with computer navigation.

“This study clearly demonstrates that restoring the anatomy of the ACL and the stability of the knee is far superior when the femoral socket is reamed through the anteromedial portal rather than the tibial tunnel, as has been traditionally done by most surgeons,” said David W. Altchek, M.D., attending orthopedic surgeon and co-chief of the Sports Medicine and Shoulder Service at HSS. “HSS is an international leader in this innovative solution toward further improving patient outcomes in ACL surgery.”

According to Dr. Bedi, the work has translated into modified techniques in the operating room at HSS, where more than 800 ACL surgeries are performed each year. Tears of the ACL are quite common, with between 70,000 and 80,000 reported each year in the United States.

Other researchers involved in the study are Volker Musahl, M.D., Volker Steuber, M.D., Daniel Kendoff, M.D., Answorth A. Allen, M.D., and Andrew D. Pearle, M.D., all with the Sports Medicine and Shoulder Service at HSS.

About Hospital for Special Surgery

Founded in 1863, Hospital for Special Surgery (HSS) is a world leader in orthopedics, rheumatology and rehabilitation. HSS is nationally ranked No. 1 in orthopedics and No. 4 in rheumatology by U.S. News & World Report (2008), and has received Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center. In 2008 and 2007, HSS was a recipient of the HealthGrades Joint Replacement Excellence Award. A member of the NewYork-Presbyterian Healthcare System and an affiliate of Weill Cornell Medical College, HSS provides orthopedic and rheumatologic patient care at NewYork-Presbyterian Hospital at New York Weill Cornell Medical Center. All Hospital for Special Surgery medical staff are on the faculty of Weill Cornell Medical College. The hospital’s research division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases. Hospital for Special Surgery is located in New York City and online at www.hss.edu.

Structural muscle damage may be present in patients who have statin-associated muscle complaints, found a new study in CMAJ (Canadian Medical Association Journal) http://www.cmaj.ca/press/cmaj-181-E11.pdf (www.cmaj.ca).

Statins are one of the most widely prescribed medications in the world, given their importance in reducing the risk of cardiovascular disease. Many patients on statins develop muscle weakness and pain. In some cases, muscle biopsies show underlying structural injury, even in patients without elevated levels of circulating creatine phosphokinase.

The study, by researchers from the University of Bern, Switzerland and the Tufts-New England Medical Center in Boston, Massachusetts, looked at muscle biopsies from 83 patients, 20 of whom had never taken statins. They found significant muscle injury in patients who had taken statins, including several who had discontinued medication before the biopsy.

“Although in clinical practice, the majority of patients with muscle symptoms improve rapidly after cessation of therapy, our findings support that a subgroup of patients appears to be more susceptible to statin-associated myotoxicity, suffering persistent structural injury,” write Dr. Annette Draeger from the University of Bern and coauthors.

They note there is a need to evaluate alternative treatment strategies for patients with significant muscle symptoms.

Researchers did what others thought was not possible by finding a small molecule to stop ’slippery’ protein from binding to another, causing Ewing’s Sarcoma

Washington, DC In a discovery that rebuffs conventional scientific thinking, researchers at Georgetown University Medical Center (GUMC) have discovered a novel way to block the activity of the fusion protein responsible for Ewing’s sarcoma, a rare cancer found in children and young adults.

In the paper published online July 5 in Nature Medicine, they report discovering and successfully testing a small molecule that keeps the fusion protein from sticking to another protein that is critical for tumor formation. The researchers say this interaction is unique and is especially surprising since the Ewing’s sarcoma fusion protein is extremely flexible, which allows it to change shape constantly.

“Most targeted small molecule cancer drugs inhibit the intrinsic activity of a single protein, but our agent stops two proteins from interacting. This has never been shown before with a cancer-causing fusion protein and represents a potentially novel medical therapy in the future,” says the study’s lead investigator, Jeffrey Toretsky, MD, a pediatric oncology physician and researcher at GUMC’s Lombardi Comprehensive Cancer Center.

The study could provide a model upon which to design treatment for other disorders caused by the interaction between two proteins, and may be especially useful in cancers caused by translocations of genes, such as sarcomas and leukemias, the researchers say. Agents in use now that work against fusion proteins inhibit a single protein to stop intrinsic enzymatic activity; one example is Gleevec, used for chronic myelogenous leukemia (CML). The Ewing’s sarcoma fusion protein, known as EWS-FLI1, lacks enzymatic activity, “and this difference is why our work is significant,” Toretsky says.

In the United States, about 500 patients annually are diagnosed with the cancer, and they are treated with a combination of five different chemotherapy drugs. Between 60-70 percent of patients survive over time, but with side effects from the treatment. Few additional treatment options are available for patients whose cancer progresses, Toretsky says.

Ewing’s sarcoma is caused by the exchange of DNA between two chromosomes, a process known as a translocation. The new EWS-FLI1 gene is created when the EWS gene on chromosome 22 fuses to the FLI1 gene on chromosome 11, and its product is the fusion protein responsible for cancer formation. It is a so-called disordered protein, which means it does not have a rigid structure. A number of cancer-causing proteins are disordered.

In their 15-year search for a new treatment for Ewing’s sarcoma, Toretsky and his colleagues were the first to make a recombinant EWS-FLI1 fusion protein. They used it to discover that the fusion protein stuck to another protein, RNA helicase A (RHA), a molecule that forms protein complexes in order to control gene transcription. “We believe that when RHA binds to EWS-FLI1, the combination becomes more powerful at turning genes on and off,” says the study’s first author, Hayriye Verda Erkizan, PhD, a postdoctoral researcher in Toretsky’s lab.

Then, from a library of 3,000 small molecules loaned to Georgetown from the National Cancer Institute, the researchers searched for a small molecule that would bind on to EWS-FLI1. They found one, and further discovered the same molecule, NSC635437, could stop EWS-FLI1’s fusion protein from sticking to RHA.

This was a wonderful discovery, Erkizan says, because the notion long accepted among scientists is that it is not possible to block protein-protein interactions given that the surface of many of these proteins are slippery - much too flexible for a drug to bind to.

They tested the agent in laboratory cell culture, and with the help of GUMC’s Drug Discovery Program, the researchers designed a stronger derivative compound they called YK-4-279. In this study, they tested YK-4-279 in two different animal models of Ewing’s sarcoma and found that the agent significantly inhibited the growth of tumors. There was an 80% reduction in the growth of treated tumors compared to untreated tumors.

Toretsky says that while the agent needs to be “optimized,” these results serve as a proof of principle that inhibiting protein-protein interaction can work as a novel therapeutic that will target only cancer cells.

“We may be able to use this strategy to attack proteins we thought to be impervious to manipulation,” he says.

The study was funded by grants from the National Institutes of Health, Children’s Cancer Foundation of Baltimore, MD, Go4theGoal Foundation, Dani’s Foundation of Denver, the Liddy Shriver Sarcoma Initiative, the Amschwand Sarcoma Cancer Foundation, the Burroughs-Wellcome Clinical Scientist Award in Translational Research, and the GUMC Drug Discovery Program.

Toretsky and co-authors Milton L. Brown, Aykut ren and Yali Kong are inventors on a patent application that has been filed by Georgetown University related to the technology described in this paper. The other authors report no related financial interests.

About Georgetown University Medical Center

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through Georgetown’s affiliation with MedStar Health). GUMC’s mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis — or “care of the whole person.” The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, the world-renowned Lombardi Comprehensive Cancer Center and the Biomedical Graduate Research Organization (BGRO), home to 60 percent of the university’s sponsored research funding.

An HIV/AIDS vaccine called SAV001H, developed in Canada has passed safety tests in animals with the next step to begin human trials in the U.S. Trials of the new vaccine on animals have reportedly resulted in good anti-body reactions with no adverse effects. The vaccine was created by Dr. Chil-Yong Kang and his team at The Canadian University of Western Ontario partneted with Sumagen Canada, a subsidiary of the Korean pharmaceutical company.

The vaccine has been submitted for approval to the U.S. Food and Drug Administration to begin human toxicology tests and two phases of clinical trials in the United States. Numerous trials have been carried out by pharmaceutical companies to develop vaccines since the AIDS virus was recognized in 1983, but no commercialized vaccine has been successfully developed so far. While Other scientists have used fragments of viruses for HIV/AIDS, this vaccine was made by using entire HIV viruses subjected to a barrage of chemicals and gamma rays designed to render them safe. Whole virus has been difficult to manufacture in large quantities safely, but Kang believes his team has overcome those challenges by genetically engineering the virus. According to a 2008 United Nations report on the global AIDS epidemic, 33 million people were living with HIV in 2007.

ChattahBox News

Using cells grown in a lab, new treatments eliminate risks of traditional procedures

People with ankle injuries who do not respond successfully to initial treatment may have a second chance at recovery, thanks to two new procedures developed to restore the injured area, according to a study published in the July 2009 issue of the Journal of the American Academy of Orthopaedic Surgeons (JAAOS).

The study reviews emerging techniques that have proven successful in treating injuries to the talus, the small bone, which is located between the heel bone and the lower bones of the leg. The talus helps form the ankle joint.

Although most injuries to the talus can be successfully treated using traditional “first-line” therapies involving removal of dead tissue (called “debridement”) and drilling, about one-fifth to one-quarter of people with ankle injuries need additional “second-line” restorative treatment to heal successfully, said lead author Matthew Mitchell, MD, an orthopaedic surgeon in private practice in Casper, Wyoming.

The two new techniques rely on cells grown in a lab, and eliminate the need for ostetomy (cutting the bone of the tibia) in some cases, he said.

• Autologous chondorcyte implantation, or ACI, involves removing cartilage cells from the knee or the ankle and growing them in a lab. Once grown, the cartilage is transplanted to the talus. ACI usually involves an ostetomy in order to implant the cells.
• In matrix-induced autologous chondrocyte implantation, or MACI, cells are grown on a special backing material, or “matrix,” and then transplanted to the talus. In the authors’ experience, an osteotomy is not necessary to implant the cells.

Of these two techniques, the newer MACI technique may offer the most benefits to the patient, according to Dr. Mitchell.

“Both ACI and MACI show a lot of promise, but I think the advantage of MACI is that an osteotomy is not necessary in order to successfully implant the matrix,” he said. “You only need to make an incision to place the graft, which decreases the morbidity of the procedure quite a bit.”

“In my experience so far with this emerging technique in Australia, the results have been as good as, or better than, other restorative techniques,” he added. MACI is currently considered investigational by the FDA in the United States.

Traditional restorative techniques involve removing a cartilage donor plug from the knee and implanting it over the ankle injury, or “lesion.” This requires an operation on the knee and cutting the bone (osteotomy) of the tibia to accomodate the graft.

As a result, these traditional techniques involve potential problems, including:

• pain in the donor knee
• tissue damage in the donor knee
• tissue damage in the ankle as a result of osteotomy

“In most individuals, results are favorable with reparative techniques, such as debridement and drilling,” said Dr. Mitchell. “The lesions that are problematic and which don’t respond well to reparative treatments are lesions that are larger, and those which are fairly deep, as well as lesions which have a cyst-like structure. Whether or not an ankle “lesion” requires additional treatment after an initial reparative procedure often depends upon several factors, including: size, depth and structure of the legion.

“Once you’ve performed a reparative technique and the patient still doesn’t heal properly, then we would move on to a second-line restorative treatment,” he said.

American Academy of Orthopaedic Surgeons

Undiagnosed celiac disease associated with nearly quadrupled mortality

ROCHESTER, Minn. — Celiac disease, (http://www.mayoclinic.org/celiac-disease/) an immune system reaction to gluten in the diet, is over four times more common today than it was 50 years ago, according to findings of a Mayo Clinic study published this month in the journal Gastroenterology (http://www.gastrojournal.org/).

The study also found that subjects who did not know they had celiac disease were nearly four times more likely than celiac-free subjects to have died during the 45 years of follow-up.

“Celiac disease has become much more common in the last 50 years, and we don’t know why,” says Joseph Murray, M.D., (http://www.mayoclinic.org/bio/13032852.html) the Mayo Clinic gastroenterologist who led the study. “It now affects about one in a hundred people. We also have shown that undiagnosed or ’silent’ celiac disease may have a significant impact on survival. The increasing prevalence, combined with the mortality impact, suggests celiac disease could be a significant public health issue.”

In patients with celiac disease, the presence of a protein called gluten from wheat, barley or rye triggers an immune system attack, damaging the villi in the small intestine. Villi are fingerlike projections that increase the intestine’s surface area for nutrient absorption. Celiac disease symptoms may include diarrhea, abdominal discomfort, weight loss, anemia, unexplained infertility, loss of teeth or even premature or severe osteoporosis.

The Mayo Clinic research team tested blood samples gathered at Warren Air Force Base (AFB) in Wyoming between 1948 and 1954 for the antibody that people with celiac disease produce in reaction to gluten. They compared those blood test results with those from two recently collected sets from Olmsted County, Minn. One matched the ages of those from the 1948 testing at the time of the blood draw, and the other matched their birth years. Researchers found that young people today are 4.5 times more likely to have celiac disease than young people were in the 1950s, while those whose birth years matched the Warren AFB participants were four times more likely to have celiac disease.

“Celiac disease is unusual, but it’s no longer rare,” says Dr. Murray. “Something has changed in our environment to make it much more common. Until recently, the standard approach to finding celiac disease has been to wait for people to complain of symptoms and to come to the doctor for investigation. This study suggests that we may need to consider looking for celiac disease in the general population, more like we do in testing for cholesterol or blood pressure.”

Dr. Murray says the study findings highlight the need for increased awareness of celiac disease, both among physicians and patients. “Part of the problem is that celiac disease symptoms are variable and can be mistaken for other diseases that are more common, such as irritable bowel syndrome,” he says. “Some studies have suggested that for every person who has been diagnosed with celiac disease, there are likely 30 who have it but are not diagnosed. And given the nearly quadrupled mortality risk for silent celiac disease we have shown in our study, getting more patients and health professionals to consider the possibility of celiac disease is important.”

In addition to Dr. Murray, authors of the study, which was conducted in collaboration with the University of Minnesota Medical School and the Medical Follow-Up Agency, Washington, D.C., include Alberto Rubio Tapia, M.D.; Robert Kyle, M.D.; Edward Kaplan, M.D.; Dwight Johnson; William Page, Ph.D.; Frederick Erdtmann, M.D.; Tricia Brantner; W. Ray Kim, M.D.; Tara Phelps; Brian Lahr; Alan Zinsmeister, Ph.D.; and L. Joseph Melton III, M.D.

VIDEO ALERT: Additional audio and video resources, including excerpts from an interview with Dr. Dr. Joseph Murray describing the research, are available on the Mayo Clinic News Blog (http://newsblog.mayoclinic.org/2009/06/29/celiac-disease-prevalence-and-mortality/). These materials are also subject to embargo, but may be accessed in advance by journalists for incorporation into stories. The password for this post is 0701Murray.

About Mayo Clinic

Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. Doctors from every medical specialty work together to care for patients, joined by common systems and a philosophy of “the needs of the patient come first.” More than 3,300 physicians, scientists and researchers and 46,000 allied health staff work at Mayo Clinic, which has sites in Rochester, Minn., Jacksonville, Fla., and Scottsdale/Phoenix, Ariz. Collectively, the three locations treat more than half a million people each year. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education, visit www.mayo.edu. MayoClinic.com (www.mayoclinic.com) is available as a resource for your health stories.

An otherwise effective treatment for cystic fibrosis places patients at a high risk of sensorineural hearing loss, according to new research published in the July edition of Otolaryngology-Head and Neck Surgery.

Cystic fibrosis is an inherited chronic disease that affects the lungs and digestive system of about 30,000 children and adults in the United States (70,000 worldwide). A defective gene and its protein product cause the body to produce unusually thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections; and obstructs the pancreas and stops natural enzymes from helping the body break down and absorb food.

Researchers reviewed the medical records of cystic fibrosis (CF) patients at Children’s Hospital Boston over a 13 year period, and found that seven of 50 CF patients (14%) suffered from sensorineural hearing loss. Of that group, 43 percent of those that had received aminoglycosides intravenously had received more than 10 courses of the treatment; patients who were treated more than five times with nasal irrigation of aminoglycosides were also at risk of sensorineural hearing loss.

Because CF patients are prone to suffer from infections of the pulmonary and sinonasal systems, aminoglycosides are commonly administered to CF patients because of the potent effect they have on bacteria. The treatment is considered so effective that it outweighs the well-known side-effects, which include hair cell loss, and thus hearing loss.

The authors contend that CF patients should have routine hearing evaluations that specifically target the detection of sensorineural hearing loss, especially when repeated courses of systemic or intranasal aminoglycosides have be used in treatment. They also note that further investigation through a prospective study is warranted in order to replicate these results.

Otolaryngology Head and Neck Surgery is the official scientific journal of the American Academy of Otolaryngology Head and Neck Surgery Foundation (AAO-HNSF) and the American Academy of Otolaryngic Allergy (AAOA). The study’s authors are Alan G. Cheng, MD; Patrick R. Johnston, MMath; Jeniffer Luz, BS; Ahmet Uluer, DO; Brian Fligor, ScD; Greg R. Licameli, MD, MHCM; Margaret A. Kenna, MD, MPH; and Dwight T. Jones, MD.

The American Academy of Otolaryngology Head and Neck Surgery (www.entnet.org), one of the oldest medical associations in the nation, represents nearly 12,000 physicians and allied health professionals who specialize in the diagnosis and treatment of disorders of the ears, nose, throat, and related structures of the head and neck. The Academy serves its members by facilitating the advancement of the science and art of medicine related to otolaryngology and by representing the specialty in governmental and socioeconomic issues. The organization’s vision: “Empowering otolaryngologist-head and neck surgeons to deliver the best patient care.”

A minimally invasive procedure to treat tendonitis in the rotator cuff of the shoulder provides immediate symptom relief to the patient, according to a study published in the July issue of Radiology. The study found that ultrasound-guided nonsurgical therapy significantly reduces pain from calcific tendonitis of the rotator cuff and restores lasting mobility after treatment.

“With this treatment, we were able to establish a single inexpensive and effective treatment for calcific tendonitis of the rotator cuff. This has never happened before,” said co-author Luca M. Sconfienza, M.D., from the Unit of Radiology, IRCCS Policlinico San Donato, University of Milan School of Medicine in Milan, Italy. “Symptoms improved in patients treated with our procedure compared to non-treated patients.”

Calcific tendonitis is a condition that causes the formation of small calcium deposits within the tendons of the rotator cuff in the shoulder. It is most common in adults in their 40s. In most cases, the deposits become painful and can restrict mobility of the shoulder. In minor cases, physical therapy or anti-inflammatory medications may be sufficient to address the problem until the calcifications break apart spontaneously. In severe cases, patients may require shockwave treatment or open surgery to remove the calcium. Open surgery requires a hospital stay and rehabilitation and, on rare occasions, may result in major complications, such as tendon rupture.

“This treatment could completely replace other treatments that are affected by several limitations and complications,” Dr. Sconfienza said.

Ultrasound-guided percutaneous (through the skin) therapy represents an effective and inexpensive alternative to surgery that is less stressful for the patient. For the 20-minute procedure, the shoulder is anesthetized and, with ultrasound guidance, a radiologist injects a saline solution into the rotator cuff to wash the area and break up the calcium. A second needle is used to aspirate, or withdraw, the calcium residue. Recovery time is about an hour.

“People with calcific tendonitis should know that with a simple, one-time ultrasound-guided procedure, they could recover completely from the terrible pain constantly affecting their shoulder,” Dr. Sconfienza said.

For the study, Dr. Sconfienza, senior author Giovanni Serafini, M.D., from the radiology unit at Santa Corona Hospital in Pietra Ligure, Italy, and colleagues used ultrasound-guided percutaneous therapy to treat 235 shoulders in 133 women and 86 men (mean age 42) with calcific tendonitis. An additional 68 patients (31 men and 37 women) did not receive treatment and acted as a control group. All of the patients had shoulder pain that was unresponsive to previous medical treatment. Follow-up was conducted after 1 month, 3 months, 1 year, 5 years and 10 years.

The results showed that treated patients exhibited a considerable reduction in pain and significant improvement to mobility of the affected limb after 1 month, 3 months and 1 year compared to non-treated patients. Five and 10 years after the procedure, the condition of non-treated patients had improved to the point that reported outcomes were similar to those of the treated group.

While few institutions currently offer this therapy, Dr. Sconfienza says that, theoretically, the procedure could be performed in any hospital or clinic that has ultrasound equipment with a superficial probe.

“There are millions of people in the world affected by calcific tendonitis,” Dr. Sconfienza said. “This treatment can provide quick and inexpensive relief for all of them.”

“Rotator Cuff Calcific Tendonitis: Short-term and 10-year Outcomes after Two-Needle US-guided Percutaneous Treatment: Nonrandomized Controlled Trial.” Collaborating with Drs. Serafini and Sconfienza were Francesca Lacelli, M.D., Enzo Silvestri, M.D., Alberto Aliprandi, M.D., and Francesco Sardanelli, M.D.

Radiology is edited by Herbert Y. Kressel, M.D., Harvard Medical School, Boston, Mass., and owned and published by the Radiological Society of North America, Inc. (http://radiology.rsnajnls.org/)

RSNA is an association of more than 43,000 radiologists, radiation oncologists, medical physicists and related scientists committed to excellence in patient care through education and research. (RSNA.org)

For patient-friendly information on ultrasound and interventional radiology procedures, visit RadiologyInfo.org.