A chemotherapy drug packs a one-two Punch

Cancer can be wily, and those who treat the disease have amassed a wide array of weapons with which to fight it and kill tumors. Radiation therapy and various forms of chemotherapy were all thought to be separate but equal treatments. Now, however, new research is beginning to show that it's not just killing the cancer cells that matter. How they're killed may turn out to be just as important and could play a role in marshalling the body's immune response.

New research by Rockefeller University associate professor Madhav Dhodapkar, head of the Laboratory of Tumor Immunology and Immunotherapy, shows that one form of chemotherapy - a drug called bortezomib - kills tumor cells in such a way that it may allow the immune system to recognize them. In a first edition paper published online by the journal Blood, Dhodapkar, postdoctoral fellow Radek Spisek, and their colleagues show that unlike radiation or other chemical therapies, bortezomib can kill multiple myeloma cells in culture in such a way that it elicits a response by memory and killer T cells. The results suggest the drug has the potential to enhance patients' immunity to tumors, helping their bodies fight the disease more effectively.

Multiple myeloma is a cancer of immune cells in the bone marrow. Dhodapkar's experiments show that when treated with bortezomib in tissue culture, multiple myeloma cells die in such a way that a heat shock protein, called hsp90, migrate to their surface. When another group of immune cells, called dendritic cells, encounter hsp90 on the dying tumor cells, the protein acts as a signal for their activation. The dendritic cells then ingest them for presentation to memory and killer T cells, a progression that - in humans - could potentially lead to enhanced immunity. "If you could directly target the drug to these cells," Dhodapkar says, "it may be sufficient enough to create a vaccine. The exposure of heat shock proteins on dying cells represents an immunogenic form of cell death."

When the researchers tested other standard treatments for multiple myeloma, such as radiation or the corticosteroid dexamethasone, the therapies failed to increase levels of hsp90 on the surface of dying cells, and so couldn't activate dendritic cells to the degree that bortezomib did. And their findings aren't limited to a single cancer: After treatment with bortezomib, dying lymphoma and breast cancer cells experienced the same increase in hsp90.

How well this research will translate to increased survival rates depends on how applicable these tissue culture studies are to the actual immune system response in people. So Dhodapkar plans to determine whether the enhanced T-cell effect he witnessed in tissue culture holds true in patients treated with this drug. If it does, the next move will be to directly target tumors in patients. "A simple experiment that hasn't been done yet is simply injecting bortezomib directly into tumors. By directly targeting the tumor, rather than injecting the drug intravenously, we may be able to take better advantage of bortezomib's distinct properties," he says.

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Smoking alters brain 'like drugs'

Smoking cigarettes causes the same changes to the brain as using illicit drugs like cocaine, a study suggests.

US researchers compared post-mortem brain tissue samples from smokers, former smokers and non-smokers.

Their findings, published in Journal of Neuroscience, suggested smoking causes changes to the brain which are evident years after someone has quit.

A UK expert said the changes might explain why smokers found it hard to stop - and why they then relapsed.

The researchers from the National Institute on Drug Abuse (Nida) looked at samples of human brain tissue from the nucleus accumbens and the ventral midbrain - brain regions that play a part in controlling addictive behaviours.

Eight samples were taken from people who had smoked until their deaths, eight from people who had smoked for up to 25 years before their death and eight non-smokers.
All died of causes unrelated to smoking.

Relapse
The scientists looked at levels of two enzymes - protein kinase A and adenylate cyclase. Both translate chemical signals, such as dopamine, which exist outside the cells, into a form that can be understood inside.

Smokers were found to have higher levels of these enzymes in the nucleus accumbens, a part of the brain that processes information related to motivation and reward, which virtually all illicit drugs act upon.

But levels of both enzymes were also found to be high in the area of the midbrain that responds to dopamine, which acts as a "reward chemical" in smokers and former smokers.
The same changes had previously been seen in the brains of rats given repeated injections of cocaine and morphine.

Writing in the Journal of Neuroscience, the team led by Dr Bruce Hope, said: "The present study confirms that drug-induced neuroadaptations [brain changes] observed in animals can also be observed in humans."

The researchers suggest that the differences seen in both smokers' and non-smokers' brains "may contribute to long-lasting alterations in nicotine-induced reward and addiction in humans".

The researchers say this suggests that the changes persist long after smoking has ceased and could contribute to drug relapse.

Dr John Stapleton, of the National Addictions Centre at King's College London, said: "It would be surprising if taking large doses of a drug such as nicotine many times a day over many years did not result in lasting changes in the brain.

The new results may take us closer to understanding these changes.
"The key question remains as to whether such changes are partly responsible for the intractable nature of smoking and relapse after many months or years of stopping."

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Shoulder Problems and Injuries

Minor shoulder problems, such as sore muscles and aches and pains, are common. Shoulder problems develop from everyday wear and tear, overuse, or an injury. They can also be caused by the natural process of aging.

Your shoulder joints move every time you move your arms. To better understand shoulder problems and injuries, you may want to review the anatomy and function of the shoulder. The shoulder is a ball-and-socket joint with three main bones: the upper arm bone (humerus), collarbone (clavicle), and shoulder blade (scapula). These bones are held together by muscles, tendons, and ligaments. The shoulder joint has the greatest range of motion of any joint in the body. Because of this mobility, the shoulder is more likely to be injured or cause problems. The acromioclavicular (AC) joint, which lays over the top of the shoulder, is also easily injured.
Shoulder problems can be minor or serious. Symptoms may include pain, swelling, numbness, tingling, weakness, or changes in temperature or color. Shoulder injuries most commonly occur during sports activities, work-related tasks, projects around the home, or falls. Home treatment often can help relieve minor aches and pains.

Breast Cancer May Be Prevented

A few hours of daily exercise may help prevent breast cancer and also help those who are suffering to cope, said studies.

In one study, researchers surveyed 15,000 women and found that those who indulged in over six hours of strenuous exercise a week and have no family history of breast cancer may be 23 percent less likely to develop the disease than women who don't exercise at all. Another study showed that a 12-week group exercise programme might lift moods and boost physical functioning in women with early-stage breast cancer.

The researchers, however, don't promise that exercise will prevent breast cancer completely. They don't blame breast cancer on a lack of exercise either. Many factors affect cancer risk. But, they do report that exercise appears to have benefits in protecting against cancer for women of all ages. "We have found that exercise likely offers protection against breast cancer regardless of a woman's stage in life," researcher Brian Sprague, of the University of Wisconsin Paul P.

Carbone Comprehensive Cancer Center, said in an American Association for Cancer Research (AACR) news release. "The take-home message for women should be that it is never too late to begin exercising," said Sprague.

U.S. offers drugmakers advice on obesity drugs

As more Americans struggle with growing waistlines, U.S. health officials on Wednesday set out their own tips for drugmakers seeking to develop products for people trying to shed pounds.

The U.S. Food and Drug Administration's draft guidelines -- more than 10 years in the making -- aim to help companies develop and test new drugs and devices for treating obesity.

About a third of U.S. adults, or more than 60 million people, are obese and another third are overweight, government statistics show. Nearly a fifth of U.S. children also weigh too much.

The FDA proposed that companies should prove their products can help people lose weight and keep it off for at least a year. It also urged them to study people with a body mass index of at least 30 or those with a BMI of at least 27 with diabetes, heart disease or other weight-related conditions.

BMI is determined by dividing weight by height. People with a score of 25 to 29.9 are considered overweight and those at 30 or higher are considered obese.

"In general, patients should have or be at significant risk for weight-related morbidity and mortality," the FDA said.
The proposed guidelines come as more companies look to enter the U.S. weight-loss sector, which some analysts have said remains untapped.

Overweight individuals are at risk for other, potentially life-threatening problems. In addition to diabetes, high-blood pressure and certain cancers are also possible.

Drugs usually aim to help people lose weight by curbing their appetite or preventing fat absorption. Some devices, such as Allergan Inc.'s Lab-Band, are used in surgical procedures to limit stomach size.

Last week, GlaxoSmithKline Plc won U.S. approval to sell an over-the-counter version of Roche AG's prescription obesity drug, Xenical, called Alli.

Sanofi-Aventis is also awaiting the FDA's ruling on its Acomplia drug, which the agency earlier this week postponed until July.

Although the guidelines are non-binding, drugmakers often rely on them when developing products. Companies may take other approaches as long as they meet legal standards, the FDA said.

They could also help prompt more manufacturers to develop weight-loss solutions.
"There clearly are not enough effective drugs" for overweight patients, Dr. Richard Kahn, chief scientific and medical officer for the American Diabetes Association, told Reuters.

DIABETES

"Diabetes is a family disease. Not only does it tend to run in families, but the eating habits and needs of one family member directly affect those of other family members," says Jacqueline M. Kerr, M.D., a family practitioner who works closely with the Seton Ease Community Health Center. More women than men have the disease. The American Diabetes Association estimates approximately 6.5 million women are diabetics, and half of them do not know it.

"For adult-onset diabetes the best cure is prevention, reducing risk through developing good eating habits while you are young," she says. Not only can you help prevent diabetes development in middle age, but it can create a lot of complications with childbirth.

"For adult-onset diabetes the best cure is prevention, reducing risk through developing good eating habits while you are young," she says. Not only can you help prevent diabetes development in middle age, but it can create a lot of complications with childbirth.

A recent study indicates women are twice as likely to die from diabetes than from breast cancer, and that people with diabetes run a much higher risk of dying from other illnesses such as flu and pneumonia.

Giving daily insulin is a life-saving treatment for many diabetics, but most still must adhere to strict dietary practices to successfully control the disease. Insulin use mush be balanced to match food intake, and if either insulin or food intake fall out of balance, the patient suffers.

"The key to successful treatment is to make sure patients are supplying their body's energy needs on a regular basis," says Dr. Kerr, who employs a nutritionist's expertise to help teach individuals how to manage food. "Many of us are guilty of eating too much for our body's daily needs and packing most of our daily caloric intake into one meal, generally dinner. That doesn't work well at all for diabetics, who must space out meals to keep energy levels adequate throughout the day." At Seton East, Dr. Kerr treats many working poor Hispanic patients with diabetes.

"It is unclear whether there is an ethnic genetic connection between being Hispanic and developing diabetes, whether there is a cultural/lifestyle connection or whether being a low-income family is a contributor," she says. "What is clear is that people who are 20 percent or more overweight are more likely to develop it."

Dr. Kerr believes there are many barriers to good diabetes management in low-income neighborhoods.

"Regular exercise is a problem if the neighborhood is unsafe and you don't have transportation to a safe area. People who don't read well don't get information from labels. Low-income families eat a lot of canned foods, which may have too much salt and a lot of hidden fat. Unless you stick to seasonal produce, fresh vegetables can be expensive. To be successful in managing diabetes, the patient has to be willing to manage all of these problems, not just food," she adds.

Dr. Kerr follows diabetic patients regularly and changes their medication as their conditions improve.

"Despite barriers, we've had a lot of success stories. An added benefit is that family members usually trim down and shape up, too. The best thing that can happen to you is to have someone who loves you stick to your regime."

Dramatic rise in accidental drug-overdose deaths

Unintentional fatal drug overdoses in the United States nearly doubled from 1999 to 2004, overtaking falls to become the nation's second-leading cause of accidental death, behind automobile crashes, the government reported.

The number of accidental drug overdose deaths rose from 11,155 in 1999 to 19,838 in 2004, according to the Centers for Disease Control and Prevention.

The report was based on death certificates, which do not clearly detail which drugs played the greatest role. But CDC researchers said they believe sedatives and prescription painkillers like Vicodin and OxyContin were the chief cause of the increase.

OxyContin has been blamed for hundreds of deaths across the country in recent years, becoming such a scourge in Appalachia that it is known as "hillbilly heroin."
Deaths from falls climbed between 1999 and 2004 at a more modest rate, from 13,162 to 18,807, the CDC said. Motor vehicle crashes accounted for 40,965 fatalities in 1999 and 43,432 in 2004.

The South had one of the lowest fatal drug overdose rates in the nation in 1999, but it doubled by 2004. The South now ties the West for having the highest rate -- about 8 per 100,000 population.

"This is the first study really to describe the large relative increases in poisoning mortality rates in rural states. Historically, the drug issue has been seen as an urban problem," said Dr. Len Paulozzi, a CDC epidemiologist.
The federal report, issued this week, noted that accidental drug overdoses remain most common in men and in people 35 to 54. But the most dramatic increases in death rates were for white females, young adults and Southerners

Other findings:
• The death rates for men remained roughly twice the rate for women, but the female rate doubled from 1999 to 2004 while the male rate increased by 47 percent.

• The rate for white women rose more dramatically than for any other gender group, to 5 deaths per 100,000 population.

• The rate of overdose deaths among teens and young adults, ages 15 to 24, is less than half that of the 35-to-54 group. But it rose much more dramatically, climbing 113 percent in the study years, to 5.3 deaths per 100,000 population.

About 50 percent of the deaths in 2004 were attributed to narcotics and hallucinogens, a category that includes heroin, cocaine and prescription painkillers like Vicodin and OxyContin.
Earlier research suggests that deaths from illegal drugs appear to be holding steady.
"There is a misperception that because a drug is a prescription medicine, it's safe to use for non-medical reasons. And clearly that is not true," said Dr. Anne Marie McKenzie-Brown, a pain medicine expert at Atlanta's Emory Crawford Long Hospital.


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Heart drug backfires may make death in next 5 years

A drug widely used to prevent excessive bleeding during heart surgery appears to raise the risk of dying in the five years afterward by nearly 50 percent, an international study found.
The researchers said replacing the drug -- aprotinin, sold by Bayer AG under the brand name Trasylol -- with other, cheaper medications for a year would prevent 10,000 deaths over the next five years.

The findings were more bad news for Trasylol: The same scientists found the drug raised the risk of kidney failure, heart attacks and strokes in a study published last year. Most of the deaths in the new study were related to those problems.

Bayer rips researchersBayer said in a statement that the findings are unreliable because Trasylol tends to be used in more complex operations and the researchers' statistical analysis did not fully account for the complexity of the surgery cases.

Nevertheless, the drug company said it will ''work with regulatory agencies and external experts in the field to further evaluate the findings.''

Dr. Dennis Mangano of the nonprofit Ischemia Research and Education Foundation, lead author of both studies, said: ''I believe that for the vast majority of coronary bypass patients the drug should not be used.'' But he said the drug should remain on the market because some very high-risk patients may benefit from it.

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Problem of Digestive System

Your body has a few main ways to respond to an ever-changing, wide variety of invaders and irritants. Sneezing ejects the intruders from the nose, coughing from the lungs and throat, diarrhea from the intestines, and vomiting from the stomach.

Nausea is the sensation of having an urge to vomit. Vomiting is forcing the contents of the stomach up through the esophagus and out of the mouth.

Vomiting is a complex, coordinated reflex orchestrated by the vomiting center of the brain. It responds to signals coming from:

*The mouth, stomach, and intestines
*The bloodstream, which may contain medicines or infections
*The balancing systems in the ear (motion sickness)
*The brain itself, including unsettling sights, smells, or thoughts

An amazing variety of stimuli can trigger vomiting, from migraines to kidney stones. Sometimes, just seeing someone else vomit will start you vomiting, in your body's effort to protect you from possible exposure to the same danger.

A number of medicines are effective at preventing vomiting. Your doctor is unlikely to prescribe these because, in most situations, the vomiting is an important part of getting well. In some situations, however, preventing the vomiting makes life much better.
also it is important to stay hydrated. Try steady, small amounts of clear liquids, such as electrolyte solutions. Other clear liquids, such as water, ginger ale, or fruit juices also work unless the vomiting is severe or a baby is vomiting.

Smoking and Asthma

Smoking is unhealthy for everyone, but especially for someone with asthma. If a person smokes, their lungs may not work as well as they should. The person might cough, wheeze, and have shortness of breath. Smoking causes the airways to become swollen, narrow, and filled with sticky mucus - the same problems that cause breathing trouble in people with asthma. For this reason, if a person with asthma smokes, they're more likely to have more frequent and severe flare-ups.

Being a smoker is an obvious risk, but just being around people who smoke - and breathing in secondhand smoke - can cause problems, too. Parents can help kids and teens with asthma by protecting them from the effects of tobacco smoke.

The Dangers of Secondhand Smoke
Secondhand smoke is a well-known asthma trigger. If you smoke, consider quitting, especially if your child has asthma. Secondhand smoke can damage the lungs by leading to long-term breathing problems or worsening existing breathing problems.

Kids with asthma who live in households with smokers:

• may have flare-ups more often
• are more likely to have to go the emergency department with severe asthma flare-ups
• are more likely to miss school because of their asthma
• must take more asthma medicine
• have asthma that's harder to control, even with medication
  

Even children who don't have asthma are at risk of problems if their parents smoke. These kids are more likely to get upper respiratory infections and develop lung conditions, including asthma. Just being exposed to smoke from 10 cigarettes per day may put children at risk of developing asthma, even if they've never had any breathing problems before.

And here's the best reason of all to quit smoking: Children whose parents smoke are more likely to smoke themselves when they get older.

You don't have to quit on your own. Talk to your doctor about possible strategies - from support groups to medication. If you do continue smoking, don't smoke in the house or car.

Exposure to Smoke Outside the Home
Even if no one in your household smokes, your child will still encounter secondhand smoke. Try to help him or her avoid it as much as possible. If your child has asthma, let friends, relatives, and caregivers know that tobacco smoke may cause an asthma flare-up. Some other ways you can prevent your child from having to breathe in smoke include:

• Don't allow guests to smoke in your house or car.
• Avoid smoky restaurants and parties. Choosing the nonsmoking section is not adequate protection.
• Ask friends and relatives not to smoke around your child.
• Choose caregivers who don't smoke or, if they do, ask them not to smoke around your child.
• Encourage family members who smoke to quit.

Sending an Antismoking Message
No one wants their child to start smoking, but it's especially important to discourage this behavior in children who have asthma. If your child has asthma, smoking may actually undo the effect of any controller medication he or she is taking. Your child may also need to use rescue medications more often, visit the doctor or the emergency department more often, and miss school more often because of flare-ups.

A child with asthma who smokes may sleep less at night and be less able to participate in sports or other physical activities. And of course, there are the long-term health consequences, such as heart disease, emphysema, and cancer.

Make sure your child understands that secondhand tobacco smoke is a trigger for asthma and that hanging around people who smoke might make him or her more likely to have a flare-up. You might even want to give your child tips on how to say no if offered a cigarette. You can lay the groundwork for that moment by taking these steps:

• Teach your child the facts about smoking and the short- and long-term damage it can do.
• Talk about how expensive cigarettes and other tobacco products are.
• Discuss how smoking gives people bad breath, smelly clothes, and yellow teeth.
• Tell your child he or she isn't allowed to smoke.

If your child already smokes, you're not alone. More than 2 million 11- to 17-year-olds start smoking each year. Nearly half of them will become regular smokers. In fact, 90% of smokers start before they're 21.

Still, despite the obvious risks, your child may not respond to an antismoking message. Though the long-term consequences are clear, preteens and teens often feel invincible. Instead, let your child know about the immediate consequences: Smoking will cause more asthma flare-ups and make his or her asthma more difficult to control. When asthma isn't controlled, it gets in the way of what kids want to do, such as playing sports or going out with friends.

Black Cancer Death Rate Higher

Black Americans are more likely to die of cancer than whites, the American Cancer Society reports.

Black men are 35% more likely to die of cancer than white men; black women are 18% more likely to die of cancer than white women.

Why? The American Cancer Society (ACS) says it boils down to one main reason: Less access to health care and health information for blacks than for whites.

"Access to insurance and health care, as well as health education, play an important role in one's health -- but a lot of African Americans do not have access to these tools," Durado Brooks, MD, director of prostate and colorectal cancers for the ACS, said in a news release.

The findings come in the newly released ACS publication Cancer Facts & Figures for African Americans 2007-2008.
There is some good news for blacks.

As it has since the early 1990s, the overall cancer death rate for black Americans continued its decline of about 1.7% a year. That's faster than the 1% decline for white Americans.

The ACS notes, "Still, some key statistics in the report show a continuing racial divide":

• Prostate cancerProstate cancer is 2.4 times more deadly for black men than for white men.
• Breast cancerBreast cancer is 1.4 times more deadly for black women than for white women.
• Colon cancer and breast cancer rates are declining more slowly for blacks than for whites.
• By the time black Americans find out they have cancer, their cancer is at a later stage than for newly diagnosed white Americans. There are fewer treatment options for later-stage cancer.
• For all major cancers, black Americans are less likely than whites to survive five years after diagnosis -- even when their cancers are diagnosed at the same stage.
  

Black Americans, the report states, have "less access to appropriate and timely treatment" than do white Americans.
This appears mostly due to social and economic factors:

• The income of nearly one-in-four black Americans is below the poverty level. One-in-10 white Americans lives below the poverty line.
• 20% of black Americans and 11% of white Americans lack health insurance.
• 19.4% of black Americans and 10% of white Americans don't have a high school education.
  

"This report makes clear there is a need for more focus on improving socioeconomic factors and providing educational opportunities that can help further lessen cancer's unequal burden on African Americans," Brooks said.