In the first national study of human drugs in fish tissue, new research finds that fish caught near wastewater treatment plants serving five major cities had residues of pharmaceuticals in them, including drugs used to treat high blood pressure, cholesterol, allergies, depression and bipolar disorder.

The study has prompted the U.S. Environmental Protection Agency (EPA) to expand similar research to more than 150 locations.

“The average person hopefully will see this type of a study and see the importance of us thinking about water that we use every day, where does it come from, where does it go to? We need to understand this is a limited resource and we need to learn a lot more about our impacts on it,” said Bryan Brooks, the study’s co-author and a Baylor University researcher and professor who has published several studies about environmental pharmaceuticals.

While Brooks and other researchers have found that even small concentrations of pharmaceutical residues can harm frogs, fish and other aquatic species, a human would have to consume hundreds of thousands of fish dinners to get even one therapeutic dose, Brooks told the Associated Press.

Brooks and his colleague Kevin Chambliss tested fish obtained from rivers where wastewater treatment plants release treated sewage in Chicago, Phoenix, Dallas, Philadelphia and Orlando.  For comparison, they also tested fish from the pristine Gila River Wilderness Area in New Mexico, an area isolated from human pollution sources.

Previous research has confirmed that fish absorb pharmaceuticals because the rivers in which they live are contaminated with trace amounts of drugs that are not removed in sewage treatment plants. A large portion of this contamination is derived from unmetabolized residues of pharmaceuticals that people have taken and excreted. Unused medications dumped down the drain also contribute to the contamination.

Researchers tested fish for 24 pharmaceuticals and 12 chemicals found in personal care products, and discovered trace concentrations of seven drugs and two soap scent chemicals in fish at all five locations.  Although the amounts varied, some of the fish had combinations of many of these compounds in their livers.

In contrast, the researchers did not detect any of these chemicals in the reference fish caught in New Mexico.

A similar investigation by the Associated Press had found trace amounts of pharmaceuticals in drinking water provided to at least 46 million Americans.

The EPA has called for further research on the human impact of long-term consumption of trace amounts of medicines in their drinking water, particularly in unknown combinations.  Preliminary laboratory studies have shown that cells in humans failed to grow or became unusually shaped in people exposed to certain pharmaceutical combinations found in drinking water.

“This pilot study is one important way that EPA is increasing its scientific knowledge about the occurrence of pharmaceuticals and personal care products in the environment,” An AP report quoted EPA spokeswoman Suzanne Rudzinski as saying.

The completed and expanded sampling for pharmaceuticals and other chemicals in fish and surface water is part of the agency’s National Rivers and Stream Assessment, she added.

The current study was funded by a $150,000 EPA grant.

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• EPA
• Baylor University

On Tuesday, Xytex International, a U.S. sperm bank, announced a stimulus package for customers who are hurting during this economic crisis.

Xytex is offering up to $200 off per vial of sperm to clients wishing to start or add to their family, but need a little help.

“We’re all feeling the effects of the economy and, especially for families seeking reproductive options, every dollar counts,” Xytex spokeswoman Danielle Moores told AFP.

Xytex is offering deals on the “select” donors, rather than the usual “standard” donor.

“Select donors are a new level of donor which we introduced to try to help our clients who are interested in third-party reproduction but, with the tough economy, are having a little bit of trouble purchasing a regular donor,” Moores told AFP.

The select donors are men who Xytex has “many, many vials because they’re very successful donors or able to stop in several times a week or — for whatever reason, we have a huge inventory,” explained Moores.

Xytex considers this the effect of supply and demand.

“Select donors haven’t reached the end of their shelf-life, they’re just over-produced,” Moores said.

The select donors run between $250 to $350, with a savings now between $135 and $235.

Xytex is also offering deals on ART donors, which is “assisted reproductive technology.”  These can run between $290 and $390.

“These are vials that are available for patients who are undergoing either IVF or intracytoplasmic sperm injection (ICSI), which can be very costly procedures,” said Moores.

“For ICSI, you really only need one sperm which is injected into the egg. So we can offer these donors at a lower cost because there’s a lower quality commitment, but it works for these patients because they need fewer cells anyway,” Moores said.

“It’s a way to offer another option at a slightly better price to help someone undergoing IVF or ICSI to have a family,” she said, stressing that while prices have been cut, Xytex has not scrimped on its usual rigorous medical, psychological and genetic screenings for donors.

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On the Net:

• Xytex International

Enjoying to relaxing music could restore loss vision in patients who suffered a stroke, UK research implies.

60% of stroke patients experience “visual neglect,” a condition defined by visual impairment following the attack.

The capacity to follow objects in their eye line on the side opposite to the damage caused by the stroke is lost. It happens because of harm caused to the areas of the brain critical for the incorporation of vision, focus and activity.

The Proceedings of the National Academy of Sciences study proposes the theory that music can help this correct itself.

The current study investigated three patients who had lost half their vision.

They worked on everyday jobs while listening to music they enjoyed, music they did not enjoy, and without any music. All three could label highlighted shapes and things in their affected side of vision much more easily while they were listening to music that they enjoyed.

The researchers think that the pleasant music creates optimistic emotions, which produce more competent indications in the brain, increasing its capability to understand stimuli.
 
Brain scans correlated the theory that listening to music triggered areas connected to encouraging emotional responses, which reinforced the patients’ performance on the tasks.

Lead researcher Dr David Soto, from Imperial College London, said: “Visual neglect can be a very distressing condition for stroke patients. It has a big effect on their day-to-day lives. Our findings suggest that we should think more carefully about the individual emotional factors in patients with visual neglect and in other neurological patients following a stroke.”
 
“Music appears to improve awareness because of its positive emotional effect on the patient, so similar beneficial effects may also be gained by making the patient happy in other ways.”

Joanne Murphy, of the Stroke Association said: “This is very interesting research that indicates that a positive emotional state can help a stroke survivor with an obstacle such as visual neglect.

We would welcome further research into this and other conditions which could help benefit the 150,000 people affected by stroke each year.”

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• Proceedings of the National Academy of Sciences
• Imperial College London

Scientists at the University of Liverpool have demonstrated how a single-celled organism, living freely in the environment, could be a source of Salmonella transmission to animals and humans.

Salmonella are microscopic living creatures that can contaminate almost any food type, causing diarrhea, abdominal pain and fever. Scientists know that Salmonella ““ which can also cause typhoid fever ““ has evolved unique mechanisms to prevent the body’s immune system from functioning effectively, but until now it was not understood how it survives so successfully in the environment.

Scientists at Liverpool, in collaboration with the Institute for Animal Health, have shown that Salmonella use a secretion system to protect themselves inside amoeba ““ a single-celled organism living on land and in the water. The research suggests that amoeba may be a major source of Salmonella within the environment and could play a significant role in transmission of infection to man and animals.

Salmonella uses a system, called SP12 type III, which acts as a bacterial machine inside organisms and causes disease in humans, animals and plants. The system employs a ‘syringe-like’ mechanism to inject bacteria into cells that would normally release compounds to rid the body of harmful substances. This system changes the structure of the cell and prevents these compounds from coming into contact with pathogens and destroying them.

Dr Paul Wigley, from the National Centre for Zoonosis Research, based at the University’s Leahurst campus, explains: “Salmonella has managed to survive extremely successfully in the environment, finding its way into our food and causing illness, despite the body’s best efforts to fight it off. We found that it uses a system which operates in the human immune system as well as inside amoeba living in the environment. This system essentially protects Salmonella within cellular compartments, called phagosomes, where it can survive and multiply.

“Its ability to survive in amoeba is a huge advantage to its continued development as it may be more resistant to disinfectants and water treatment. This means that we need to work to understand ways of controlling amoeba in water supplied to animals and prevent it acting as a ‘Trojan Horse’ for Salmonella and other pathogens.”

The research, supported by the Society for Applied Microbiology, the Department for Environment, Food and Rural Affairs (DEFRA), and the Higher Education Funding Council for England (HEFCE), is published in Applied and Environmental Microbiology.

The Salmonella Pathogenicity Island 2-Encoded Type III Secretion System Is Essential for the Survival of Salmonella enterica Serovar Typhimurium in Free-Living Amoebae in Applied and Environmental Microbiology Vol. 75. Authors: Benjamin Bleasdale, Penelope J. Lott, Aparna Jaganathan, Mark P. Stevens, Richard J. Birtles, and Paul Wigley.

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• University of Liverpool
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Results of the first human clinical studies confirm that a new yogurt fights the bacteria that cause gastritis and stomach ulcers with what researchers describe as almost vaccine-like effects, scientists in Japan will report here today at the 237th National Meeting of the American Chemical Society.

Researchers have long known that yogurt, a fermented milk product containing live bacteria, is a healthy source of calcium, protein, and other nutrients. Some brands of yogurt are now made with “probiotics” “” certain types of bacteria “” intended to improve health. The new yogurt represents a unique approach to fighting stomach ulcers, which affect 25 million people in the United States alone, and is part of a growing “functional food” market that now generates $60 billion in sales annually.

“With this new yogurt, people can now enjoy the taste of yogurt while preventing or eliminating the bacteria that cause stomach ulcers,” says study coordinator Hajime Hatta, Ph.D., a chemist at Kyoto Women’s University in Kyoto, Japan.

The new yogurt is already on store shelves in Japan, Korea, and Taiwan. The study opens the door to possible arrival of the product in the U.S., the researchers suggest.

A type of bacteria called Helicobacter pylori (H. pylori) or over-use of aspirin and or other nonsteroidal anti-inflammatory drugs, causes most stomach ulcers. H. pylori ulcers can be effectively treated and eliminated with antibiotics and acid suppressants. However, that simple regimen is unavailable to millions of poverty-stricken people in developing countries who are infected with H. pylori. New research also links childhood H. pylori infection to malnutrition, growth impairment and other health problems. As a result, scientists have been seeking more economical and convenient ways of dealing with these bacteria.

In the new study, Hatta and colleagues point out that H. pylori seems to rely on a protein called urease to attach to and infect the stomach lining. In an effort thwart that protein, or antigen, Hatta turned to classic vaccine-making technology. They injected chickens with urease and allowed the chickens’ immune systems to produce an antibody to the protein. The researchers then harvested the antibody, called IgY-urease, from chicken eggs. Hatta and colleagues theorized that yogurt containing the antibody may help prevent the bacteria from adhering to the stomach lining.

To test their theory, the scientists recruited 42 people who tested positive for H. pylori. The volunteers consumed two cups daily of either plain yogurt or yogurt containing the antibody for four weeks. Levels of urea, a byproduct of urease, decreased significantly in the antibody group when compared with the control group, indicating reduced bacterial activity, the researchers say.

“The results indicate that the suppression of H. pylori infection in humans could be achieved by drinking yogurt fortified with urease antibody,” Hatta states. The antibody was eventually destroyed by stomach acid, but not before having its beneficial effect.

Although the yogurt appears less effective than antibiotics for reducing levels of H. pylori, it is a lot easier to take than medicine and can be eaten daily as part of regular dietary routine, Hatta says. The antibody does not affect the yogurt’s overall taste and does not cause any apparent adverse side effects, he notes.

But anti-ulcer yogurt is not for everyone, Hatta cautions. He notes that people who are allergic to milk or eggs should avoid the product. Although the yogurt contains egg yolk, which tends to have lower allergen levels than egg white, an allergy risk still exists, he adds.

Pharma Food International Company, Ltd. a Japanese firm that does research and development on the functional food ingredients, including the anti-ulcer yogurt, provided partial funding for the study.

The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With more than 154,000 members, ACS is the world’s largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

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Image Caption: A new type of yogurt fights the bacteria that cause stomach ulcers. Manufacturers sell it in Japan under the name “Dr. Piro” and in Korea as “Gut.” Credit: PharmaFood International Co., Ltd.

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• American Chemical Society
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The recent death of actress Natasha Richardson is highlighting the delayed dangers of traumatic head injuries.

Richardson was injured during a ski trip in Canada. Shortly after the accident, the actress reported feeling fine. Later that night, she began to complain of a headache when at her hotel. She was taken to a hospital where she died on Wednesday.

On Thursday, an autopsy revealed that Richardson had experienced a blow to the head, which resulted in bleeding between the skull and the brain’s covering, called an epidural hematoma.

Doctors refer to Richardson’s experience as a “lucid interval,” during which patients report no complications until symptoms later emerge.

“Once you have more swelling, it causes more trauma which causes more swelling,” Dr. Edward Aulisi, neurosurgery chief at Washington Hospital Center, told the AP.

“It’s a vicious cycle because everything’s inside a closed space.”

Swelling often results in dangerous pressure that forces the brain to press down on the brain stem where vital functions such as breathing are controlled. In order to reverse the effects of swelling, doctors can remove a portion of the skull or drain the blood.

“This is a very treatable condition if you’re aware of what the problem is and the patient is quickly transferred to a hospital,” said Dr. Keith Siller of New York University Langone Medical Center.

“But there is very little time to correct this.”

Aulisi said it is crucial for patients who have experienced head trauma to seek a CT scan, which can show whether or not internal bleeding is ongoing.

“If there’s any question in your mind whatsoever, you get a head CT,” Aulisi advised. “It’s the best 20 seconds you ever spent in your life.”

Image Courtesy UPI

Researchers at the University of Pittsburgh School of Medicine have begun testing a vaccine that might be able to prevent colon cancer in people at high risk for developing the disease. If shown to be effective, it might spare patients the risk and inconvenience of repeated invasive surveillance tests, such as colonoscopy, that are now necessary to spot and remove precancerous polyps.

Colon cancer takes years to develop and typically starts with a polyp, which is a benign but abnormal growth in the intestinal lining, explained principal investigator Robert E. Schoen, M.D., M.P.H., professor of medicine and epidemiology at the University of Pittsburgh. Polyps that could become cancerous are called adenomas.

In a novel approach for cancer prevention, the Pitt vaccine is directed against an abnormal variant of a self-made cell protein called MUC1, which is altered and produced in excess in advanced adenomas and cancer. Vaccines currently in use to prevent cancer work via a different mechanism, specifically by blocking infection with viruses that are linked with cancer. For example, Gardasil protects against human papilloma virus associated with cervical cancer and hepatitis B vaccine protects against liver cancer.

“By stimulating an immune response against the MUC1 protein in these precancerous growths, we may be able to draw the immune system’s fire to attack and destroy the abnormal cells,” Dr. Schoen said. “That might not only prevent progression to cancer, but even polyp recurrence.”

According to co-investigator Olivera Finn, Ph.D., professor and chair of the Department of Immunology at Pitt’s School of Medicine, MUC1 vaccines have been tested for safety and immunogenicity in patients with late-stage colon cancer and pancreatic cancer.

“Patients were able to generate an immune response despite their cancer-weakened immune systems,” she noted. “Patients with advanced adenomas are otherwise healthy and so they would be expected to generate a stronger immune response. That may be able to stop precancerous lesions from transforming into malignant tumors.”

About a dozen people have received the experimental vaccine so far, and the researchers intend to enroll another 50 or so into the study. Participants must be between 40 and 70 years old and have a history of developing adenomas that are deemed advanced, meaning they are greater than or equal to 1 centimeter in size, are typed as villous or tubulovillous, or contain severely dysplastic, or abnormal, cells. After an initial dose of vaccine, the participants will get shots again two and 10 weeks later. Blood samples will be drawn to measure immune response at those time points as well as 12 weeks, 28 weeks and one year later.

People who develop advanced adenomas undergo regular surveillance with colonoscopy so that recurrent polyps, which are common, can be removed before matters get worse, Dr. Schoen said.

“Immunotherapy might be a good alternative to colonoscopy because it is noninvasive and nontoxic,” he noted. “And, it could provide long-term protection.”

Colorectal cancer is the third leading cause of cancer death in the United States. In 2008, the American Cancer Society estimated that there were more than 108,000 new cases of colon cancer, nearly 41,000 cases of rectal cancer, and almost 50,000 deaths due to both diseases.

Pitt’s colon cancer vaccine is sponsored by the National Cancer Institute and The Nathan S. Arenson Fund for Pancreatic Cancer Research. Its adjuvant component, which enhances the immune system’s ability to respond to the target protein, was developed and provided by Washington, D.C.-based Oncovir, Inc.

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On the Net:

• University of Pittsburgh School of Medicine

Sales of prescription drugs in the United States rose a paltry 1.3 percent last year, as patients sought cheaper generic versions of their medications or went without treatment altogether due to the economic slowdown.

The data reflects a continuation of a slowdown in U.S. sales of prescription drugs in recent years. In 2007, prescription drugs sales in the U.S. rose 3.8 percent.  In 2006 the number was roughly 8 percent.  However, even those years were less than the double-digit annual percentage sales growth seen in previous decades.

The troublesome news comes from information supplied by IMS Health Inc., which compiles pharmaceutical industry market data.

“Dispensed prescription volume in the United States grew at a 0.9 percent pace” in 2008, a Reuters report quoted the IMS as saying.

Previous IMS reports placed the dispensed volume growth at  2.8 percent in 2007 and 4.6 percent in 2006. 

In its current report, IMS predicted that U.S. prescription drug sales would climb 1 to 2 percent in 2009.  However, the company did not provide an updated sales forecast in its media advisory.

Lipid drugs, those that lower “bad” LDL cholesterol and triglycerides or raise “good” HDL cholesterol, were at the top of the list last year of dispensed U.S. retail prescription drugs on a volume basis, according to IMS.  These were followed by codeine and other drugs containing the narcotic painkiller, anti-depressants and two types of blood pressure medications known as ACE inhibitors and beta blockers.

“In terms of overall prescription sales through both retail and non-retail channels, antipsychotics led all therapy classes,” followed by lipid regulators, a popular class of ulcer and heartburn drugs known as proton pump inhibitors (PPIs) and anti-seizure medicines, IMS told Reuters.

In parallel with slowing sales growth in the United States, three large drugmakers are bracing for patent expirations on some of their top selling drugs in 2011, leaving them vulnerable to competition from lower-cost versions.

The firms include Pfizer Inc. with its $12 billion-a-year Lipitor cholesterol drug, Bristol-Myers Squibb Co with its Plavix blood clot prevention drug, and Eli Lilly & Co with its Zyprexa schizophrenia treatment.

Some analysts worry that U.S. sales of prescription drugs could suffer even more if President Obama and the Democratic-led Congress decides to require drugmakers to negotiate prices of their branded products.

The United States is currently the only major industrialized nation without price regulations for prescription drugs, making the country the world’s most profitable market for medicines.

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• IMS Health Inc.

David Mackay, chief executive of Kellogg, will speak to Congress on Thursday about issues he believes the U.S. food safety system must immediately address, Reuters reported.

Kellogg lost $70 million after it had to recall millions of packages of peanut butter crackers and cookies during the recent salmonella outbreak.

Mackay is pushing for an appointed food safety authority within the Department of Health and Human Services devoted to keeping such incidences from happening.

While the HHS’s Food and Drug Administration regulates food safety, some experts say drug issues get most of its attention.

The Kelloggs CEO also called for new requirements that all food companies have written safety plans, annual federal inspections of facilities that make high-risk foods and other reforms.

Mackay is expected to tell a House Energy and Commerce subcommittee hearing that the recent outbreak illustrated that the U.S. food safety system must be strengthened.

“We believe the key is to focus on prevention, so that potential sources of contamination are identified and properly addressed before they become actual food safety problems,” he said.

Contaminated food cases like the recent peanut outbreak have shaken the public confidence in food safety and renewed calls for FDA changes.

Ingredients supplied by Peanut Corp of America were linked to a salmonella outbreak that began in September and caused over 3,491 products that contain peanuts to be pulled from shelves.

Peanut Corp has since declared bankruptcy.

Some 700 people have become ill after eating contaminated peanut products, according to government statistics.

Kellogg recalled items such as its Keebler and Austin brands of peanut butter crackers. Mackay said they were forced to pull more than 7 million cases of products due to the Peanut Corp contamination.

Congress and the White House have both supported stricter food safety regulations.

The Obama administration blamed the recent outbreak partly on outdated food safety laws and underfunding and understaffing at the FDA. President Obama has since organized a panel to improve food safety laws.
 
Critics say more FDA funding is needed for inspections and basic research.

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Health policy experts estimate the price for providing universal health care to Americans could reach $1.5 trillion over the next ten years, more than double the $634 billion President Barack Obama has set aside to overhaul the U.S. healthcare system.

Some 48 million people in the United States are uninsured, and the problem is expected to worsen as the cost of coverage rises.
 
Nevertheless, administration officials have avoided providing a detailed cost estimate for Obama’s reform proposal, saying it would depend upon how Congress would work out the details.

“It’s impossible to put a price tag on the plan before even the basics have been finalized,” an Associated Press report quoted White House spokesman Reid Cherlin as saying.

“Here’s what we do know: The reserve fund in the President’s budget is fully paid for and provides a substantial down payment on the cost of the reforming our health care system.”

The potential for surging healthcare overhaul costs concerns some Democrats and Republicans alike, as Congress works to prepare a draft of next year’s budget.

The U.S. currently spends $2.4 trillion annually on health care, more than any other developed nation, one-third of which goes for tests and procedures rather than treatment and prevention, according to experts.

“We shouldn’t just be throwing more money on top of the present system, because the present system is so wasteful,” Senator Judd Gregg (R-NH), the ranking Republican on the Senate Budget Committee.

The health care plan Obama proposed during his presidential campaign would have cost nearly $1.2 trillion over a decade, according to an estimate last fall by the consultancy firm Lewin Group.   And that proposal would not have covered all the uninsured, something most congressional Democrats seek to do.  

Lewin Group senior vice president John Sheils said $1.5 -$1.7 trillion would be a plausible estimate for a plan that covers all Americans, or roughly 4 percent of the total projected health care costs over the next decade.

The cost of providing healthcare coverage to the uninsured is “a difficult hurdle to get over,” Sheils told AP.

“I don’t know where the rest of the money is going to come from,” he added.

Some of the top supporters of universal healthcare estimate the cost at roughly $1.5 trillion.

“Honestly … we can’t do it for the $634 billion the president put in the reserve fund,” said John Rother, an AARP public policy director, at an insurance industry meeting in Washington last week.

“In all likelihood, it will be over $1 trillion,” he said, estimating the cost would be about $1.5 Trillion.

Economist Len Nichols, who oversees the health policy project at the New America Foundation, told AP that universal coverage will cost $125 billion to $150 billion a year.

However, earlier this month Peter Orszag, the White House budget director, told the House Budget Committee that Obama’s $634 billion fund is “likely to be the majority of the cost.”

About half of that money would come from spending reductions, while the other half would come from increased taxes.
 
However, the cost “will depend on the details of whatever is finally done … as we move through the legislative process,” Orszag said.

The total costs are an important issue since the expansion of health coverage is intended to be a permanent reform, meaning future generations of Americans will fund the changes.

“We are dealing with huge numbers,” former U.S. comptroller general David Walker said, according to the Reuters report.

“We need to have a much better sense of what we are talking about doing, and whether or not it’s affordable and sustainable over time, said Walker, now head of the Peter G. Peterson Foundation, which promotes fiscal responsibility.

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Surgery at Loyola Makes it Possible to Attach Prosthesis with Magnets

To look at Matthew Houdek, you could never tell he was born with virtually no left ear.

A surgery at Loyola University Health System made it possible for Houdek to be fitted with a prosthetic ear that looks just like the real thing.

Ear-nose-throat surgeon Dr. Sam Marzo implanted three small metal screws in the side of Houdek’s head. Each screw is fitted with a magnet, and magnetic attraction holds the prosthetic ear in place.

It takes only a few seconds for Houdek to put his prosthetic ear on in the morning and take it off when he showers or goes to bed. It doesn’t fall off, and it’s much more convenient than prosthetic ears that are attached with adhesive.

“I’m extremely happy with it,” said Houdek, 25, who lives in Chicago. “It turned out better than I expected.”

Houdek was born with a deformity called microtia (small ear). About 1 in 10,000 babies are born with this condition, in which one or both outer ears are under-developed or absent. On his left side, Houdek was born with just an ear lobe and a bump.

When Houdek was about 4 years old, a surgeon reconstructed a new ear from his rib cartilage. At first, the ear was the right size. But it did not grow as Houdek grew up. “As I got older, it became more of an issue,” Houdek said.

The silicone prosthesis was made by Gregory Gion, a facial prosthetist based in Madison, Wis. The flesh-colored silicone prosthesis looks almost identical to Houdek’s natural ear — right down to the small blood vessels. Houdek said everyone loves it. “And my mom almost cried when she saw it.”

Like many people with microtia, Houdek also was born without an ear canal, a condition called congenital aural atresia. Marzo opened a new ear canal and lined it with a skin graft from Houdek’s leg. Houdek now has partial hearing in his left ear.

“With a hearing aid, his hearing should be very good,” Marzo said. Marzo is an associate professor in the Department of Otolaryngology at Loyola University Chicago Stritch School of Medicine

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On the Net:

• Loyola University Health System

A small government study suggests that the narcolepsy drug modafinil “” a so-called “smart drug” increasingly being used to enhance cognitive abilities “” may be more addictive than doctors thought, the Associated Press reported.

A study involving 10 healthy men found that the prescription drug Provigil (generic name: Modafinil) caused changes in the brain’s pleasure center, very much like potentially habit-forming classic stimulants.

College students often use Modafinil as an illegal study aid to increase their academic endurance.

Experts believe the new study may end the myth that the drug is safe for healthy people.

Provigil hit the market in 1999 as a treatment for excessive sleepiness for narcoleptics. Cephalon, the company’s flagship product, reached sales of over $1 billion in 2008.

An Air Force study that found the drug improved the performance of sleep-deprived fighter pilots resulted in Modafinil’s reputation as a brain enhancer. It quickly caught on with college students, who buy and sell it illegally to stay alert while studying.

A report in the journal Nature quoted several scientists who believe that healthy people should have the right to boost their brains with pills like Provigil.

However, other experts promoted caution.

“The new study goes to show that we need a little caution and a little humility when we’re messing around with our brain chemistry,” said brain scientist Martha Farah of the University of Pennsylvania, one of the contributors to the commentary.

Farah noted that even after all the years of Provogil being on the market, doctors are still learning things about it that are relevant to its safety.

The study involved men between 23 and 46 years old who received either a dummy pill or Modafinil. PET scans showed that the drug increased dopamine, the brain’s “feel-good” neurotransmitters.

Studies in mice and monkeys suggest that Modafinil, which was once thought to be safer than conventional stimulants because it was believed that it did not engage the brain’s dopamine system, does indeed show a link with addiction.

The researchers claim to have recorded evidence that a typical dose of modafinil affects dopamine in the brain as much as a dose of Ritalin, a controlled substance with known dependence capabilities.

However, Modafinil acts slowly when swallowed and is difficult to inject, making it less likely to be abused, according to Dr. Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist..

It often draws higher street prices than Ritalin, but Volkow said that might change when generics become available in 2012.

Side effects from Modafinil include severe rashes and other issues such as headache, nausea and anxiety. Cephalon doesn’t support the drug’s use as a cognitive enhancer.

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On the Net:

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• Nature
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A new study shows that stethoscopes carried by ambulance crews are not always cleaned as often as they should be and may be exposing some patients to drug-resistant bacteria, the New York Times reported.

The report examined the stethoscopes used by emergency medical services workers in New Jersey, noting that a significant number carried methicillin-resistant Staphylococcus aureus, bacteria known as MRSA that are resistant to standard drugs.

The report was published in the current issue of Prehospital Emergency Care.

The researchers said that some of the ambulance workers did not even recall the last time the instruments had been cleaned.

It’s still unclear how big a threat MRSA on a stethoscope posed to a patient, according to the study’s lead author, Dr. Mark A. Merlin of Robert Wood Johnson Medical School.

However, he said that as incidents of infection by the bacteria become more common, and with the possibility that it will become more resistant to antibiotics, it is important to reduce its spread.

Ambulance crews arriving at an emergency department over a 24-hour period were asked by researchers to have their stethoscopes tested. They were also asked when the instruments had last been cleaned.

The report showed that among the 50 stethoscopes reviewed, 16 had the bacteria.

Experts say a simple alcohol swab is usually enough to kill the bacteria.

The report noted that the concept of cleaning an entire ambulance after every patient is not practical yet doesn’t require very much energy.

“Cleaning a stethoscope is not labor-intensive, does not require much time, and does not require any special equipment beyond currently stocked items.”

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• Prehospital Emergency Care
• Robert Wood Johnson Medical School

Old age is typically faulted for causing us to misplace car keys, forget a name, or lose our train of thought. 

However, according to new research, the common signs of aging may reveal themselves long before our twilight years, reported UK Dailymail. 

Scientists suggest that our mental capacities reach their peak at 22 years of age and start the declining process at the age of 27. 

Two thousand men and women aged 18 to 60 agreed to participate in the study for a seven year period under observation of researchers.  The participants, who were healthy and well-educated for the most part, had to recall words and story detail, spot patterns in letters and symbols, as well as decipher visual puzzles. 

Tests comparable to these are commonly used to diagnose mental discrepancies and deterioration, like that of dementia. 

Research at the University of Virginia indicated that in 9 out of 12 assessments, superior performance was marked at an average age of 22, as recorded in the academic journal Neurobiology of Aging.  

At age 27, signs of performance began to significantly decrease in comparison to peak scores at age 22, as revealed in three tests that gauge reasoning, speed of thought and spatial visualization.  The average age of 37 indicated decline in memory.  In other tests, lower results were evident by the age of 42.

Professor Timothy Salthouse commented that the findings propose that earlier treatments designed to prevent or reverse age-related conditions may be needed, prior to retirement. 

“Results converge on a conclusion that some aspects of age-related cognitive decline begin in healthy, educated adults when they are in their 20s and 30s,” he wrote. 

The report offered some positive news in light of this research.  It conveys that abilities contingent on accumulated knowledge, such as presentation of vocabulary or common information, continue to grow until at least 60 years of age.

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On the Net:

• University of Virginia
• Neurobiology of Aging

Preliminary results show that a shortened course of radiation therapy for prostate cancer called stereotactic body radiation therapy (SBRT) provides good PSA response for early-stage prostate cancer and has the same side effects as other treatments, according to a March 15 study in the International Journal of Radiation Oncology*Biology*Physics, the official journal of the American Society for Radiation Oncology (ASTRO). Study authors caution that further follow-up will be necessary to establish that SBRT is as effective in the long term as other proven treatments.

Radiation therapy is an effective way to treat localized prostate cancer. Proven successful treatments include brachytherapy (seed implants) where radiation sources are placed directly into the prostate and external beam radiation therapy where doctors give small daily doses of radiation to the prostate, five days a week, for eight weeks to give enough radiation to kill the cancer cells while sparing nearby healthy tissue.

External beam radiation therapy can be a very effective and minimally invasive treatment. However, the length of treatment can be burdensome for some patients, particularly those who live very far from a treatment facility. Doctors have been investigating ways to shorten the course of the treatment through a technique called stereotactic body radiation therapy, where radiation oncologists give a higher dose of radiation every day for five days. Growing biologic evidence also suggests that delivering radiotherapy in this fashion might be more effective for prostate cancer than conventionally protracted courses.

In this study, researchers from Stanford University treated 41 men with low-risk prostate cancer with SBRT. After a median follow-up of 33 months, no man in the study has seen his cancer return. Men in the study reported side effects, including urinary and rectal problems that were no better or worse than with other prostate cancer radiation treatments.

“There is great enthusiasm in reducing the length of treatment for prostate cancer while also possibly improving its effectiveness, and these early results are very promising for men with early-stage prostate cancer,” Christopher King, Ph.D., M.D., an associate professor of radiation oncology at Stanford University School of Medicine in Stanford, Calif., said. “However, it can often take as long as 10 years to see late side effects and recurrences, so we will have to monitor these men closely and cautiously pursue these treatments further before we can confidently say that SBRT is as good as other proven prostate cancer treatments, like external beam radiation therapy, brachytherapy or surgery.”

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On the Net:

• American Society for Therapeutic Radiology and Oncology
• International Journal of Radiation Oncology, Biology, Physics

A new report issued by the consumer safety group Campaign for Safe Cosmetics finds that dozens of commonly-used children’s bath products sold in the United States contain carcinogens.

The watchdog group commissioned an independent laboratory to test 48 best-selling children’s products for the presence of 1,4-dioxane.  Additionally, 28 products were tested for the presence of formaldehyde, a by-product of a preservative added to products to prevent bacteria growth and extend shelf-life.   

The 1,4-dioxane chemical is used as a foaming agent in some products, while formaldehyde is used for embalming corpses and as glue in chipboard.  Both chemicals are “completely unregulated” in the U.S., the report said, while 1,4-dioxane is prohibited in Europe and the use of formaldehyde is restricted, according to Stacy Malkan of the Campaign for Safe Cosmetics.

In total, 23 of the 28 products tested for formaldehyde were found to contain the chemical, 17 of which contained both 1,4-dioxane and formaldehyde.

Among the 17 containing both cancer-causing chemicals were popular products such as L’Oreal Kids Extra Gentle 2-in-1 shampoo, Johnson’s Baby Shampoo and Pampers Kandoo foaming hand soap, which contained enough formaldehyde to spur a skin reaction in highly sensitive people, the report said.

Previous studies of workers exposed to formaldehyde have linked the chemical to cancers of the nasopharynx, nasal sinuses, brain and possibly leukemia, according to the U.S. National Cancer Institute.
 
The report said that 32 or the 48 products tested contained the chemical 1,4-dioxane, to which exposure even in trace amounts gives “cause for concern,” the report said.

Indeed, both the Environmental Protection Agency (EPA) and Department of Health and Human Services have identified 1,4-dioxane as a “probable human carcinogen”, and have said the chemical causes cancer in animals .

“If chemicals are causing cancer in animals, we really shouldn’t be putting them on babies’ heads,” an AFP report quoted Stacy Malkan of the Campaign for Safe Cosmetics as saying.

However, not everyone agreed with the new report. 

The Personal Care Products Council, a U.S. trade association for the cosmetic and personal care products industry, dismissed the findings as “patently false,” saying the Campaign for Safe Cosmetics was “preying upon parental worries.”

“The levels of the two chemicals the group reportedly found are considered to be ‘trace’ or extremely low, are well below established regulatory limits or safety thresholds and are not a cause for health concern,” the organization told the AFP.

“When present, these chemicals would likely be found at very low levels precisely because companies have gone to great lengths in the formulation and manufacturing processes to ensure that the products are safe and gentle for children and also protected from harmful bacterial growth.”

Malkan said the report was cause for concern, since “children are more vulnerable to the toxic effects of chemicals.”

“I don’t think parents need to be alarmed but I feel outraged because there’s no need for these products to contain carcinogens.”

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On The Net:

U.S. National Cancer Institute
 

A new study finds that a person’s neck thickness may provide as many clues about their risk of developing heart problems as their waist measurement.

Researchers from the Framingham Heart Study found that even those with relatively small waistlines seemed to be at greater risk of heart problems if they had larger necks.  The study defined risk as having higher blood glucose levels or lower levels of “good” cholesterol.

The researchers examined more than 3,300 study participants with an average age of 51, and found evidence that health depended not on how
fat a person was, but where their fat was located, said professor Jimmy Bell of the MRC Clinical Sciences Center.

In this study, the average neck circumference was 34.2cm for women, and 40.5cm for men, and as neck circumference grew, so did the risk factors for heart problems.

For every 3cm increase in neck circumference, men had 2.2 milligrams less of good cholesterol per deciliter of blood (mg/dl) and women 2.7mg/dl.

Good cholesterol, also known as high-density lipoprotein (HDL), takes cholesterol away from the cells and back to the liver, where it is broken down.

Measurements of less than 40mg/dl in men and 50 mg/dl in women are believed to increase the risk of heart disease.

The researchers found that neck size made no difference to levels of low-density lipoprotein (LDL), also known as “bad cholesterol”, which can cause harm.  However, it did affect blood glucose levels such that for every 3cm more of neck circumference men had 3.0mg/dl more and women 2.1mg/dl of LDL.

Normal fasting blood glucose levels are below 100 mg/dl, and higher levels are believed to be an accurate indicator of future heart problems.

And while the risk was higher independent of waistline, it was compounded for those who had both a larger waist and neck circumference.

The scientists speculated that a thick neck may be a “crude measure” of upper body fat, something associated with heart risks.

“What you don’t want is fat around your liver or heart, and this can happen even if you look fine on the outside. Dieting isn’t what you need to shift this – it’s exercise,” a BBC News report quoted professor Bell as saying.

The results were presented to a meeting of the American Heart Association.
 

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On The Net:

AHA

“HappyHR” aims to elevate fitness enthusiasm, health knowledge through technology

Counting calories that burn through activity is a constant quandary.

One can only run on a treadmill so long, watching intently as the pedometer reads out the number of calories melted during a session of exercise. Not to mention the question of how many calories are burned through basic daily movements and even during sleep.

But technology ““ and youthful ambition ““ is presenting a round-the-clock solution for those consumed with this calculation.

A group of Georgia Tech students has crafted a device that allows individuals to constantly compute the amount of calories they burn ““ even as they sleep.

“It’s a completely converged device,” said Garrett Langley, 21, a senior in the School of Electrical and Computer Engineering (ECE) who spearheaded the project. “It’s a single unit that provides complete fitness monitoring and management.”

Dubbed HappyHR, the instrument is a personal monitor that allows users to measure and compare day-to-day physical and caloric activity. The name is a reference to the euphoric feeling that follows an intense round of exercise ““ the “happy hour.”

The small, rectangular-shaped instrument straps to the wrist or ankle, gathering data related to heart rate and exercise. The information is then transferred via Bluetooth to a PC, where the statistics can be analyzed through Web-based software.

Although the device focuses on calorie counting, Langley envisions more thorough health applications including respiratory and glucose monitoring.

This tool began as a senior design project for Langley, who viewed a marketplace that was lacking such technology coupled with a results-hungry populace eager for more health information. An aspiring entrepreneur, he also found that it provided an organic way for him to develop a business.

An avid runner, Langley himself was frustrated at the challenge of quantifying fitness results.

“I saw that there was a huge gap in the market,” he said. “There are simple $30 pedometers, and there’s nothing in between that and $400 health monitors.”

Comparatively, HappyHR should carry a $100 price tag if it becomes commercially available.

Shortly after conceiving the idea, the development process became an interdisciplinary endeavor incorporating several colleges at Georgia Tech.

Fellow electrical engineering student John Hamilton, biomedical engineering students Stephen Mann and Nathan Kumar and industrial design student Stuart Lawder all contributed their expertise to actualizing Langley’s concept.

The result: a deft and subtle device that resembles a compact MP3 player more than fitness monitoring technology.

The project, and the fortitude behind it, has impressed Steve Chaddick, Tech alumnus and chairman of the ECE Advisory Board. Chaddick has served as a mentor to Langley and his team, lending his advice to both the design and business plan process.

“It’s a terrific opportunity to promote what I believe in engineering education,” Chaddick said. “We should be teaching the “Ëœwhy’ before the “Ëœwhat,’ so to speak. It’s been very satisfying for me personally.”

Langley is finalizing the HappyHR prototype and beginning discussions with manufacturers. His goal is to make HappyHR commercially available some time this fall.

“Ideally, this could change the way America stays in shape,” Langley said. ” ‘Stay fit and be happy’ is the slogan. This is going to motivate people to exercise more and be happier.”

Don Fernandez GATech

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On the Net:

• Georgia Tech

‘It is imperative that these barriers hampering adoption of personal health records be addressed’

Interest in personal health records as an electronic tool to manage health information is increasing dramatically. A group led by a UCSF researcher has identified cost, privacy concerns, design shortcomings and difficulties sharing information across different organizations as critical barriers hindering broad implementation of electronic personal health records.

The barriers are discussed in a paper appearing in the March-April 2009 issue of the journal “Health Affairs.”

“It is imperative that these barriers hampering adoption of personal health records be addressed. We do not have the ‘best of breed’ yet, but I do believe that if we encourage nimble innovative solutions, we can achieve the ideal personal health record,” said James S. Kahn, MD, professor of clinical medicine at UCSF’s Positive Health Program at San Francisco General Hospital.

The paper notes that costs may be offset by improvement in health activities and reduced administrative costs. The difficulty of making personal health record data portable for patients as they change health organizations is a key factor limiting wider and more rapid adoption.

“Personal health records controlled by patients that are interoperable with other systems so that they can take their records with them are also essential for empowering patients and ensuring their control over their own health care. Exploring other technologies such as mobile phones as an easier entry point for consumers to access their records could play an important role as well,” said Kahn.

The authors posit a dynamic relationship as patients’ behavior influences personal health record acceptance and personal health record adoption influences consumers’ behavior.

“For instance, a personal health record could interact with patients through automated mechanisms such as alerts or reminders and improve medication adherence. Consumer-to-consumer interactions through social networking sites could provide group support for healthy behavior changes such as tobacco abatement,” said Kahn.

Kahn has directed the development of the Health Care Evaluation Record Organizer (HERO) at Ward 86, UCSF’s outpatient HIV/AIDS clinic at San Francisco General Hospital, a public hospital where many patients are in a safety net situation.

“In addition, we need to recognize that some established personal health record vendors may not respond to all patient needs. We are actively trying to understand how personal health records can be used in a safety net setting in a public hospital,” added Kahn.

Co-authors include Veenu Aulakh, program director at the California Healthcare Foundation and Adam Bosworth, president and CEO of Keas Inc., in San Francisco.

Funding from the Commonwealth Fund and the National Institutes of Health supports Kahn’s work.

By Jeff Sheeh, UCSF News Office

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On the Net:

• University of California – San Francisco
• Health Affairs

A patient record software that uses a three-dimensional computer model of the human anatomy has been developed by physicians at Thy-Mors hospital in Denmark in cooperation with IBM.

The new software is expected to help doctors have a better overview of a patient’s history and save hospitals considerable time spent searching through records systems. 

“If you just need to know about the heart, you can click and get straight to the record and get the piece of information that you need,” Kurt Nielsen, the hospital Director, told Reuters by telephone on Tuesday.

“You can get a quick overview of the health history of the patient,” he said.

The software is designed to work with different types of electronic patient records and pulls information from these complex systems to display in a user-friendly interface.

Arrows indicate treated areas on the model of the body, and a mouse click on a specific arrow or body part automatically retrieves the pertinent medical information from the record, including past and current medication and diagnoses.

“We’re going to use it. In the pilot we tried to use it on real patient record systems, and now we will have a clinical pilot. It can be adapted everywhere where you have electronic patient record systems,” Nielsen said.

IBM and business partner Nhumi Technologies will collaborate in the commercialization of the technology and plan to start marketing the tool in the Netherlands, Switzerland and Scandinavia and in other countries through partners.

The doctor-patient dialogue is a tool that is expected to improve by allowing physicians to illustrate relevant parts of the body in the model.

“This we believe is an added important benefit. We think that some of the time saved by the hospital will be used for better dialogue with patients,” said Nhumi Technologies sales director Peter Lundkvist.

IBM researchers worked with Thy-Mors staff from May to December last year to understand better their needs, Lundkvist said.

Last year, Thy-Mors, in West Denmark, was selected as a development partner because the hospital was preparing to purchase a new electronic patient record system.

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On the Net:

• IBM
• Nhumi Technologies

British researchers reported that men will be hit harder than women by the recessions gripping economies around the world, as job insecurity threatens an inherent sense of masculinity and damages mental health, Reuter’s reported.

Even though more women than men are losing their jobs in Britain because of the credit crunch, men who think they may be fired or laid off are likely to become more stressed and depressed than women, according to the Cambridge University study.

The study found that the effects of job insecurity would take a greater toll on men’s health than that of their female counterparts as the economic slowdown continues.

Dr. Brendan Burchell from the University of Cambridge’s sociology department, who compiled the study, said it was partly due to the macho issue concerning men being “the breadwinner” in a family.

“Men, unlike women, have few positive ways of defining themselves outside of the workplace between when they leave school and when they retire,” Burchell said.

However, despite several decades of more equal employment opportunities for men and women, men retain traditional beliefs that their masculinity is threatened if their employment is threatened, he added.

A poll released earlier in the year showed that women, more than men, reported being worried about the possibility of losing their jobs.

Though men may put on a braver face, the study found that job insecurity causes more symptoms of anxiety and depression in men than in women.

When unemployed men move into insecure jobs, they showed no improvement in psychological health, according to data from 300 current British employees, combined with a survey of thousands of people by the Economic and Social Research Council charting the effects of social and economic change since the early 90’s.

By contrast, even finding an insecure job helped to restore psychological health for most unemployed women.

The long-term decline in mental health can also be even more harmful to people who are under threat of losing their jobs than for those who are actually made redundant, Burchell said.

“Given that most economic forecasts predict that the recession will be long with a slow recovery, the results mean that many people — and men in particular — could be entering into a period of prolonged and growing misery,” he added.

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On the Net:

• Cambridge University

More and more information is being gathered about how human genes influence medically relevant traits, such as the propensity to develop a certain disease. The ultimate goal is to predict whether or not a given trait will develop later in life from the genome sequence alone (i.e. from the sequence of the bases that make up the DNA strands that store genetic information in every cell of the body).

Now, writing in the journal Current Biology, a Cell Press publication, a group of researchers form the Netherlands put this goal to a test using eye color. The group around Manfred Kayser of the Erasmus University Medical Center Rotterdam showed that it can be predicted with an accuracy of over 90% whether a person has blue or brown eyes by analyzing DNA from only 6 different positions of the genome.

Human eye color, which is determined by the extent and type of pigmentation on the eye’s iris, is what geneticists call a ‘complex trait’. This means that several genes control which color the eyes will ultimately have. Over the past decades a number of such ‘eye-color genes’ have been identified, and people with different eye color, will have a different DNA sequence at certain points in these genes.

Such differences are known as single nucleotide polymorphisms (SNPs). Manfred Kayser and his colleagues analyzed the DNA of over 6000 Dutch people whose eye color had been scored. They determined the sequence at 37 SNPs in 8 eye color genes for each of these and found that the eye color of a given individual can be predicted with over 90% confidence already with the best 6 SNPs from 6 genes, as long as the person’s eyes are blue or brown. For the intermediate color, shown by about 10% of the people tested, the accuracy is lower at about 75%.

The implications of this study are two-fold. For one, it is a proof-of-principle that complex traits can be predicted from the genome sequence alone, provided that genes with strong effects on the trait exist and are known. This can have implications for predicting disease risks based on DNA, before the disease breaks out. In addition, these findings have direct relevance in the forensic sector. Consider a case where the only trace of the suspect is a DNA trace but the DNA profile generated does not match that of known suspects or any in the Criminal Database.

There currently is in fact one such open case in Germany where the DNA of a single woman was found at dozens of crime sites over several years. Using the approach of the new study, the eye color of a suspect”” and in principle also other traits such as hair color “” can be predicted, thus helping to find unknown suspects. Needless to say, there are also caveats, one of them is that the prediction was only tested for individuals of Dutch European descent, and, although expected, it needs to be shown that similarly high prediction accuracies are obtainable in other populations across Europe.

Also, the reliability of such DNA-based eye color prediction test currently depends on an accurate knowledge that the unknown person whose DNA was tested is of European descent, since the used SNPs are associated with eye color but have no direct functional implications as far as known. Inferring highly accurate information on European ancestry from a DNA sample is not trivial, although such research is underway as well.

The researchers include Fan Liu, Kate van Duijn, Johannes R. Vingerling, Albert Hofman, Andr© G. Uitterlinden, A. Cecile, J.W. Janssens, and Manfred Kayser, of Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.

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On the Net:

• Cell Press
• Current Biology

A Swedish study published on Friday suggests that people who begin exercising at the age of 50 can still benefit from physical activity, although the effects may take 10 years to start showing, Reuters reported.

Researchers from Uppsala University said that men who began exercising after the age of 50 had the same life expectancy after 10 years as men who had exercised throughout their life.

The study followed 2,205 Swedish men for more than 20 years from the age of 50, who were placed into low, medium and high activity groups.

Around 50 percent of the volunteers reported a high level of exercise, corresponding to at least three hours of sport or heavy gardening each week.

The researchers wrote in the British Medical Journal that a third of the men said they exercised moderately, such as taking walks and cycling, while the rest did little or no exercise.

For those who waited until later in life to start physical activity, exercise made no difference in premature death rates for at least a decade, the study found.

Liisa Byberg, a researcher at Uppsala University in Sweden, told Reuters Health that hitting the half-decade mark doesn’t mean it’s too late to start physical activity.

“It has been shown that young people benefit from exercise but this is the first time we have been able to show that old people can also benefit as well,” she said.

The authors wrote that increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity.

During the first five years of the study, death rates were highest among the sedentary group and lowest among the most active volunteers. However, after 10 years, people who began exercising at 50 had similar death rates to people in the high activity group.

“This reduction is comparable with that associated with smoking cessation,” the report said. Byberg said that while there is an effect, there is a bit of a delay.

“These results are very interesting,” said Professor Alan Maryon-Davis, president of the Faculty of Public Health. “It shows that it is never too late to start exercising. I think this period is very important for men and what is probably happening here is that the exercise during these years is strengthening their cardiovascular system.”

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On the Net:

• Uppsala University
• British Medical Journal