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Vertebroplasty Shows Promise for Vertebral Compression Fracture Treatment

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Vertebroplasty, an interventional radiology treatment for vertebral compression fractures, provides patients with significant pain relief and lasting benefit, according to a 5-year follow-up study of 884 osteoporosis patients.

The procedure calls for the injection of medical-grade bone cement into a fractured vertebra, and acts like an internal cast on the fracture. It is particularly effective for painful vertebral compression fractures that do not respond to analgesics or intolerable narcotics. The average pre-treatment pain score on the 11-point Visual Analog Scale was 7.9 +/- 1.5, and it dropped significantly to an average of 1.3 +/- 1.8 after the vertebroplasty treatment.

The Oswestry Disability Questionnaire (ODQ), which measures a patient’s ability to manage everyday life, was completed by patients before, and one month after vertebroplasty, and showed greatly improved mobility—from an average of 69.3 percent +/- 13.5 to 18.8 percent +/- 6.9.

"These data provide good news for physicians and osteoporosis patients. Many osteoporosis patients with compression fractures are in terrible pain and have a greatly diminished ability to perform basic daily activities, such as dressing themselves," said Giovanni C. Anselmetti, M.D., interventional radiologist at the Institute for Cancer Research and Treatment in Turin, Italy. While vertebroplasty can improve a patient’s quality of life, the procedure is generally reserved for people for whom conventional medical management was ineffective.

"Osteoporosis patients who have persistent spinal pain lasting more than three months should consult an interventional radiologist, and those who require constant narcotic pain relief should seek help immediately," noted Anselmetti. The treatment was completed in all patients without major complications and with good clinical results. The data add to the body of evidence in the United States for the minimally invasive treatment’s safety, effectiveness and low-complication rate. The treatment is widely available in the United States at all major institutions and many smaller institutions and is generally covered by health insurance.

The study also showed that vertebroplasty does not increase the risk of fracture in nearby vertebra. "Vertebroplasty is already known to be a safe and effective treatment for osteoporotic vertebral fractures. Osteoporosis patients remain susceptible to new fractures, which often occur in the contiguous vertebra to an existing fracture. Our large-scale study shows that vertebroplasty does not increase the risk of fracture in the level contiguous to previously treated vertebra and that these new fractures occur at the same rate as they would in osteoporosis patients who did not have vertebroplasty," added Anselmetti.

The research was presented at the Society of Interventional Radiology’s 33rd Annual Scientific Meeting.

Obese Women Experience More Aggresive Breast Cancer

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Obese women with breast cancer have lower rates of survival, and suffer a more intense form of the disease, according to recently-published research.

"The more obese a patient is, the more aggressive the disease," said Massimo Cristofanilli, MD, associate professor of medicine in the Department of Breast Medical Oncology at The University of Texas M.D. Anderson Cancer Center. "We are learning that the fat tissue may increase inflammation that leads to more aggressive disease."

606 women with breast cancer were observed by Cristofanilli and colleagues, and classified by body mass index into three groups—normal/underweight (24.9 or below), overweight (at least 25 but less than 30), or obese (more than 30). At five years, overall survival was 56.8 percent among obese women, 56.3 percent among overweight women and 67.4 percent among normal weight women. The 10-year survival rate was 42.7 percent among obese women, 41.8 percent among overweight women and 56.5 percent among normal weight women. Researchers found that the rate of inflammatory breast cancer was 45% among obese women, compared with 30% in overweight women, and 15% in women with normal weight.

Obese or overweight women also displayed a higher risk of breast cancer recurrence. Obese women (50.8%) reported a recurrence after 5 years, compared with normal weight women (38.5%). After 10 years, the rate of recurrence was 58% in obese women and 45.4% in women with normal weight.

"Obesity goes far beyond just how a person looks or any physical strain from carrying around extra weight. Particular attention should be paid to our overweight patients," Cristofanilli said.

Drugs commonly used to treat cancer patients, such as tamoxifen, said Dr. Cristofanilli tend to increase weight gain during treatment – an effect physicians should note carefully. "We have actually become quite good at managing acute side effects such as nausea in our chemotherapy patients and it goes away within a couple of days," Cristofanilli said. "Following the nausea, our patients tend to overeat, which further increases their risk of weight gain. We need to implement lifestyle modifications interventions and develop better methods to follow these patients closely."

Clinical Cancer Research, March 15, 2008

Lung Damage Evident 25 Years After Workers Exposed to Legal Limits of Asbestos-Like Material (Vermiculite)

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Workers who processed vermiculite tainted with asbestos-like fibers 25 years ago show high prevalence of scarring and thickening of the membrane that lines the chest wall, including people exposed below legal levels.

In 1970 workers who had handled "Libby vermiculite" (so named after the Libby, Montana mine where the tainted fibers were first noted), exhibited a cluster of bloody pleural effusions. The Libby mine at one time produced up to 80 percent of the vermiculite used around the world.

513 former workers at a plant that processed Libby vermiculite were checked by researchers in 1980, and pleural changes or interstitial fibrosis were found in 2.2 percent of them. A team led by James Lockey, M.D., the principal investigator of this report, found that the unadjusted prevalence in the still-living members of the original cohort was 28.7 percent for pleural changes and 2.9 percent for interstitial fibrosis. The findings are published in the second issue for March of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

"I expected to see a higher rate of x-ray changes, but was surprised at the percentage," said. Dr. Lockey. "We found that even low levels of exposure to asbestos-like fibers can cause thickening of the membrane that lines the chest wall."

280 workers of the 431 workers stlll living were interviewed for the follow-up study, to determine their lung health and work history, as well as their exposure level and the number of years worked. Chest X-rays were reviewed by professional radiologists for pleural plaques, thickening and interstitial changes.

A significant trend of increasing changes with increased exposure was detected by researchers analyzing workers with pleural changes. Those with the highest exposure levels had an average of 6 to 16 times the risk of pleural changes compared with those minimally exposed. Equally important, changes were significant at levels permitted by law.

The findings indicate that "a significant number of workers exposed at the current limit would experience pleural abnormalities," wrote Gregory Wagner, M.D., of the National Institute for Occupational Safety and Health, in an accompanying editorial. Furthermore, regulations governing legal exposure limits to hazardous materials apply only to specific fibers, not to all types of fibers that have similar and predictable biological effects.

"When humans are exposed to any mineral fibers that are long, thin and durable in human tissue and can reach the pleural membrane, these fibers can cause health problems," said Dr. Lockey. "Six types of asbestos are currently regulated, but other existing types of fibers that share similar characteristics are not."Perhaps most importantly, the research highlights the need to anticipate the health implications of occupational exposures.

"The initial Lockey investigation found a relatively modest prevalence of pleural abnormalities," wrote Dr. Wagner. But the current study "found over 10 times that level, despite the fact that contaminated vermiculite had been removed from the production process by 1980."

Consumers encountered minimal risk from most products containing Libby vermiculite, said Dr. Lockey, but advised that any home improvements that involve contact with vermiculite insulation should be left to professionals.

Source: American Journal of Respiratory and Critical Care Medicine, March, 2008 (second issue).

Appendix Removed Via the Mouth in First of its Kind Surgery in US

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Surgeons have performed one of the first removals of an appendix via the mouth in the United States. The surgery was part of a clinical trial designed to test techniques for minimally invasive surgery.

The surgery was performed on Jeff Scholz, a 42-year old California resident, at US San Diego Medical Center by Santiago Horgan, M.D., professor and director of UC San Diego’s Center for the Future of Surgery, and Talamini, president elect of the Society of American Gastrointestinal and Endoscopic Surgeons. UC San Diego Medical Center is first U.S.-based hospital to perform this procedure. India is the only other country to report such an operation.

"Only one small incision to insert a small camera in the belly button was required to complete the surgery versus three incisions required for a laparoscopic procedure," said Horgan. "The patient was discharged 20 hours after surgery and is now reporting minimal pain which is a goal for all of our patients."

"I had to have my appendix removed and the opportunity to participate in something so innovative sounded enticing. A day after surgery, I have little pain, a ‘2’ on a scale of 1 to 10," said Scholz, a resident of La Jolla. "My father had the conventional appendix removal. I didn’t want the standard issue scar on the abdomen."

The procedure, called Natural Orifice Translumenal Endoscopic Surgery (NOTES), involves passing surgical instruments, and a tiny camera, through a natural orifice, such as the mouth, to the desired organ. By avoiding major incisions through the abdomen, patients may experience a quicker recovery with less pain while reducing the risk of post operative hernias.

Horgan and Talamini used FDA-cleared EndoSurgical Operating System (EOS) developed by USGI Medical, Inc. to perform the procedure. EOS was passed through the patient’s mouth and into the stomach where a small incision was made in the stomach wall to pass the instrument through to the appendix for removal.

In addition to Horgan and Talamini, the surgical team included: John Cullen, M.D., Garth Jacobsen, M.D., Karl Limmer, M.D., John McCarren, M.D., Bryan Sandler, M.D.and Thomas Savides, M.D.

Source: University of California, San Diego Health Sciences

Alzheimer’s Disease Connection to Stroke Explained

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The risk of Alzheimer’s disease is nearly doubled among people who have had a stroke, and researchers at Columbia University Medical Center have found a process in the brain that explains the connection.

There is an increase in the production of the toxic amyloid beta (Aß) peptides after a stroke that are believed to cause Alzheimer’s disease. Results in this study showed that Aß production rises when there is an increase in production of a peptide called p25, which occurs in rodents and humans following a stroke. The Columbia team identified a pathway, known as p25/cdk5, whereby higher levels of p25 led to enhanced activity of a molecule called cdk5, which in turn led to a rise in the production of Aß

By reducing the activity of cdk5, by either an inhibitor or by genetic manipulation, lead author Karen found a decrease in Aß production in the brain, demonstrating that the p25/cdk5 pathway may be a treatment target for Alzheimer’s disease. Specifically, inhibitors of cdk5 are particular candidates for therapeutic development.

"This finding connects the dots between p25 and increased production of amyloid beta, and this p25/cdk5 pathway could explain why the risk of Alzheimer’s disease is significantly higher following a stroke," said Dr. Duff, professor of pathology (in psychiatry and in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) at Columbia University Medical Center and the New York State Psychiatric Institute. "However, we still need to verify that this pathway is actually set in motion after a stroke; right now the data is still circumstantial."

Dr. Duff’s laboratory is currently working on experiments to verify this pathway’s involvement using human post-mortem tissue of stroke patients. The specific pathway investigated was shown to be most active in young mice, as compared to older mice suggesting that p25/cdk5 may not be implicated in late-onset Alzheimer’s disease, the most common form of this neurodegenerative disease.

The research was published in the March 13, 2008 issue of Neuron.

Active Tuberculosis Prevented by New Drug that Kills Latent Bacteria

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A new chemical that can prevent active tuberculosis in people infected with the latent form of the bacterium has been discovered by researchers. The drug could also shorten the recovery time needed, and suggests new ways of combating bacterial infection, increasingly resistant to traditional antibiotics.

"With each new case of antibiotic resistance, doctors are losing ground against Mycobacterium tuberculosis and other infectious diseases," explains the study’s senior author Dr. Carl Nathan, chairman of Microbiology and Immunology and the R.A. Rees Pritchett Professor of Microbiology at Weill Cornell Medical College. "This new approach fights the pathogen in a way that’s different from conventional antibiotics. For what may be the first time, we have found compounds that only kill M. tuberculosis when they are not dividing. This lack of replication is a characteristic of latent bacteria, which are tough to eradicate with existing antibiotics and ultimately play a huge role in the epidemic’s spread."
The World Health Organization reports 1.6 million worldwide die from the lung infection annually. It is also estimated that as many as one-third of the world’s population is infected with latent or non-replicating M tuberculosis. The latent bacteria begins to replicate in 5% – 10% of these people, resulting in active disease, while experts opinion states that each person with active TB is estimated to infect 9 and 20 other people.
"That means that killing latent M. tuberculosis is one of the keys to curtailing or eliminating TB as a disease," Dr. Nathan says. "Antibiotic research has typically focused on killing rapidly dividing bacteria. But with antibiotic resistance rising, that no longer seems like a winning strategy. The long duration of treatment required for curing TB may reflect the fact that some of the bacteria remain non-dividing even during clinically active disease."
It can take 6 months to wipe out most non-dividing bacteria using present drugs, but if this difficult regime is stopped too early, drug-resistant bacteria can appear. The focus of the Weill Cornell researchers was a bacterial enzyme called dihydrolipoamide acetyltransferase (DlaT).
"DlaT’s main job is to help M. tuberculosis get energy from nutrients. But when the bacterium is under stress, it also uses the enzyme to defend itself against oxidative damage from human immune cells, such as macrophages," explains study lead author Dr. Ruslana Bryk, assistant research professor in the Department of Microbiology and Immunology at Weill Cornell Medical College.
DlaT is vital to initiating active TB disease, the team discovered. "So we screened 15,000 compounds to find chemicals that might inhibit DlaT," Dr. Bryk says. The researchers discovered one such compound from a class of chemicals called rhodanines. Their collaborators at deCODE Chemistry then synthesized over 1,000 different variants until the Weill Cornell team found several that can enter and selectively kill non-dividing M. tuberculosis.
"We believe that these DlaT inhibitors probably target additional mechanisms that non-dividing M. tuberculosis needs to survive, and we are currently investigating that possibility," Dr. Nathan says. "We also believe that these compounds work in synergy with human immune responses and the chemical environment inside the host to kill latent bacteria."
The inhibitors described in the paper are surely not the only ones with the ability to kill non-dividing M. tuberculosis selectively. "This was really a proof-of-principle effort to show that targeting non-dividing bacteria was feasible," Dr. Nathan explains. "In recent work supported by the Bill and Melinda Gates Foundation, we have since found additional compounds that appear to kill non-dividing M. tuberculosis selectively."
"As a parent, a citizen and an occasional patient, I worry about losing the hard-fought gains we’ve made against infectious disease," Dr. Nathan says. "When traditional antibiotics work, treating TB, pneumonia and other bacterial diseases seems routine. When they don’t work — as is happening now with growing frequency — these infections become emergencies. The growing crisis of microbial resistance demands innovative new approaches. We hope this work will encourage more scientists that such innovations are worth seeking."
The new findings are published in the March 12, 2008 online issue of the journal Cell Host & Microbe.

Teen Pregnancy May Be Reduced by Sex Education in Schools, Says Study

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Sex education may reduce teen pregnancy without increasing the amount of sexual intercourse among teens, or the incidence of sexually transmitted diseases among them, according to new research.

"It is not harmful to teach teens about birth control in addition to abstinence," said study lead author Pamela Kohler, a program manager at the University of Washington in Seattle.

Which approach will postpone sexual experience? Instruction on birth control, or advice on how to say No. That’s the longstanding debate between sex educators and parents. The findings of a study analyzing the response from 1,719 teens, heterosexual and aged between 15 and 19, and the 2002 national survey, found that one in four teens received abstinence-only education, 9%—primarily those living in rural areas and the poor%—received no sex education at all, while the remaining two-thirds received comprehensive instruction with discussion of birth control.

Predictably, those teens receiving comprehensive sex education were 60% less likely to become pregnant or impregnating someone than those receiving no sex education at all. The one in four teens receiving abstinence-only education were 30% less likely to become pregnant than those receiving no sex education at all, although this number was dismissed as statistically insignificant by the researchers because so few teens fit the categories researchers analyzed.

The findings support comprehensive sex education, Kohler said. "There was no evidence to suggest that abstinence-only education decreased the likelihood of ever having sex or getting pregnant." Don Operario, Ph.D., a professor at Oxford University in England, said the study provides "further compelling evidence" about the value of comprehensive sex education and the "ineffectiveness" of the abstinence-only approach.

Still, the study does not show how educators should implement comprehensive sex education in the classroom, said Operario, who studies sex education. "We need a better understanding of the most effective ways of delivering this type of education in order to maximize audience comprehension and community acceptability."


The study appeared in the April, 2008 issue of the Journal of Adolescent Health.

Insulin Research May Lead to Longer, Healthier Life

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Insulin can affect aging and lifespan, a previously unknown outcome which could provide a means of gene manipulation capable of lengthening lives and making people healthier.

In a recent paper, researchers from the Joslin Diabetes Center note that Insulin inhibits a master gene regulator protein called SKN-1, whose activity increases lifespan. SKN-1 also controls what is called the Phase 2 detoxification pathway, a network of genes that defends cells and tissue against oxidative stress—damage caused by elevated levels of free radicals (byproducts of metabolism)—and various environmental toxins. This new research result was validated in experiments on the digestive system of C.elegans, a microscopic worm often used as a model organism.

"We’ve found something new that insulin does and it has to be considered when we think about how insulin is affecting our cells and bodies," said Dr. T. Keith Blackwell, senior investigator at Joslin and author of the paper. "This has implications for basic biology since under some circumstances insulin may reduce defense against the damaging effects of oxidative stress more than we realize."

Enhancing the activity of SKN-1 may lead to increased resistance to chronic diseases and influence longevity, said Dr. Keith, and the work could be important as it relates to diabetes and the many problems associated with the disease, particularly vascular and renal complications.

"The major implication is that we have found something new that affects lifespan and aging, and an important new effect that insulin and/or a related hormone called insulin-like growth factor-1 may have in some tissues," said Blackwell. "The implications go far beyond diabetes."

A gene regulator protein called FOXO is important in diabetes metabolism, tumor suppression and stem cell maintenance, a fact known since the 1990’s. FOXO controls a number of genes involved in stress resistance, and studies in C.elegans demonstrated that diminished insulin signaling increased activity of a FOXO protein called DAF-16, leading to greater stress resistance and longer life.

The Joselin research adds to knowledge about insulin and its effects on gene pathways, while putting SKN-1 next to FOXO as a second master gene regulator that is inhibited by insulin signaling. According to the paper, insulin’s effect on SKN-1 occurs independently of its effect on DAF-16.

The paper was published in the March 21, 2008 issue of Cell.

Many Gulf War Veterans’ Health Problems Traceable to Toxic Chemicals

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The high incidence of illness in Persian Gulf War veterans can be traced to their exposure to toxic chemicals such as nerve agents and pesticides, say researchers at the University of California, San Diego School of Medicine.

Symptoms reported by deployed personnel include fatigue, muscle pain, memory problems, trouble sleeping, rash and breathing problems. These personnel had a higher rate of chronic, multi-symptom health problems than non-deployed personnel, or those deployed elsewhere.

"This evidence suggests that exposure to this certain class of chemical may be linked to elevated risk of health problems," said Beatrice Golomb, M.D., Ph.D., associate professor of medicine at the UC San Diego School of Medicine.

"Health issues among Gulf War veterans have been a concern for nearly two decades. Now, enough studies have been conducted, and results shared, to be able to say with considerable confidence that there is a link between chemical exposure and chronic, multi-symptom health problems," said Golomb. "Furthermore, the same chemicals affecting Gulf War veterans may be involved in similar cases of unexplained, multi-symptom health problems in the general population."

Chemicals known as acetylcholinesterase inhibitors (AChEis) and organophosphates (OP), nerve gas chemicals, sarin and pesticides were included in the study, together with carbamate pyridostigmine bromide (PB) pills originally given to service members to protect against potential nerve-agent exposure. (Note: As a result of an earlier RAND corporation report by Golomb outlining the risks of using such pills, military policy has been changed.)

The study linked exposure to each of these chemicals with the chronic, multi-symptom health problems in 25 to 33 percent of returning Gulf War veterans.
"There is evidence that genetics have something to do with how a body handles exposure to these chemicals," said Golomb. "Some people are genetically less able to withstand these toxins and evidence shows that these individuals have higher chance of suffering the effects of exposure."

Specifically, illness is linked to lower activity of enzymes that detoxify AChEis, due to genetic variants The enzymes known to be involved are paraoxonase (PON) for OPs, including sarin, and butyrylcholinesterase (BChE) for PB.

Source: Proceedings of the National Academy of Sciences (PNAS), March 18, 2008, vol. 105, no. 11, pp. 4295-4300

Concerns Voiced Over Long-Term Effects of Synthetic Progestins

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In a study done at the University of Oregon, the widely used synthetic progestin medroxyprogesterone acetate (MPA) decreased endothelial function in premenopausal women. The finding, researchers said, raises concerns about the long-term effects of MPA and possibly other synthetic hormones on vascular health in young women.

The vascular endothelium lines the inside of blood vessels. In recent years, it has been found to be a dynamic organ that serves an important role in the prevention of atherosclerosis. "The logical conclusion of this study is that over a long period of time it would not be good to have exposure to an agent that is reducing blood vessel flexibility, because it could be associated with the development of heart disease or related problems," said co-author Dr. Paul F. Kaplan, a long-time Eugene gynecologist and senior researcher in the UO’s human physiology department. He stressed, however, that a longer, larger study is needed.

MPA is the active ingredient of Provera, used to treat abnormal uterine bleeding, induce menstrual cycles and relieve symptoms of menopause. Depo/Provera, an injectible long-lasting contraceptive in common use by many young women, contains MPA as an active ingredient. MPA was also used in the Women’s Health Initiative (WHI) including a clinical study on hormone replacement. This was stopped because of health concerns in post menopausal women. Millions of women use hormone therapies with a variety of progestin types for contraception.

The UO study is among the first to target the impact of MPA in premenopausal women. Fourteen women, 19-27 years old, participated in the study after exams to screen out various health conditions. The five-member UO team—led by Jessica R. Meendering, a former UO doctoral student now a professor of exercise science at the University of Nebraska in Omaha—studied the effects of the sex hormone estradiol by itself and in combination with MPA on endothelial function of the brachial artery. The health of the endothelium in this artery has been shown to be a telling proxy for the coronary arteries and a good predictor of cardiovascular risk.

When researchers gave an oral version of MPA to determine its impact, they found that it wiped out the positive effects on endothelial function that estradiol had provided. MPA reduced the function by reducing the brachial artery’s ability to dilate—grow bigger in diameter—in response to the stress of changing blood flow, Kaplan said.

Source: Journal of Physiology: Heart and Circulatory Physiology