Even ancient Egyptians suffered hardening of the arteries, CT scans show

CT scans of Egyptian mummies, some as much as 3,500 years old, shows evidence of atherosclerosis or hardening of the arteries, which is normally thought of as a disease caused by modern lifestyles, researchers said today. "Atherosclerosis is ubiquitous among modern-day humans and, despite differences in ancient and modern lifestyles, we found that it was rather common in ancient Egyptians of high socioeconomic status," said co-author Dr. Gregory Thomas, a cardiologist at UC Irvine. "The findings suggest that we may have to look beyond modern risk factors to fully understand the disease."

"Perhaps atherosclerosis is part of being human, as we are observing the footprint of the same disease process in people who lived thousands of years ago," added co-author Dr. Michael I. Miyamoto, a cardiologist at the UC San Diego School of Medicine."The possibility that humans throughout time might share the same predisposition to the development of certain afflictions was poignantly illustrated to us" by the study, presented at the American Heart Association meeting in Orlando.

The study was conceived by Thomas after he read the nameplate of Pharoah Merenptah in the Museum of Egyptian Antiquities in Cario. The nameplate says that, when he died at age 60 in 1203 BC, Merenptah was plagued by atherosclerosis, arthritis and dental decay. Because atherosclerosis is characterized by calcium in plaques, Thomas reasoned that some evidence of the disease might still be present even after so long. He organized a team of cardiologists and Egyptologists who scanned a series of 20 mummies in the Egyptian Museum during the week of Feb. 8, 2009. The scanning was performed on a Siemens machine permanently installed at the museum.

Among the 16 mummies who had identifiable arteries or hearts, nine had calcification clearly seen in the arteries or in the path where the arteries should have been. The disease was clearly age-related. Seven of the eight who were over the age of 45 when they died had calcification, compared to only two of eight that were younger than 45. Men and women were affected equally. The most ancient of the mummies afflicted with atherosclerosis was Lady Rai, who had been a nursemaid to Queen Ahmose Nefertiti. She died at the age of 30 to 40 around 1530 BC, about 300 years prior to the time of Moses and 200 years before King Tut. Other mummies examined died as recently as AD 364.

The findings should, perhaps not have been surprising. The high-status Egyptians ate a diet high in meat from cattle, ducks and geese, all fatty. Because mechanical refrigeration was not available, salt--another constributing factor in heart disease--was widely used for preservation. Maybe the question that should be asked is why they didn't have higher levels of disease.

-- Thomas H. Maugh II

Top: Mummy of Esankh (male, Third Intermediate Periodm 1079-712 BC) undergoing scanning.

Middle: Mummy of Djeher (male, Ptolemaic Era, 304-30 BC) entering scanner.

Bottom: Mummy of Esankh undergoing preparation for CT scanning.

Credit: Dr. Michael Miyamoto

Gene therapy strengthens monkeys' muscles, may eventually work for human diseases

Injecting a gene into thigh muscles of a monkey's leg greatly increased muscle mass and strength, a finding that could have potential application in a variety of human diseases that involve muscular weakening, researchers reported this week in the new journal Science Translational Medicine. The effects have now persisted for as long as 15 months and no side effects have been apparent, according to the researchers from Ohio. Clinical trials in humans are expected to begin next year.

Researchers have long sought ways to boost muscle mass and tone. Androgen steroids and glucocorticosteroids are the most obvious approach, but both have long-term consequences that render them less than desirable. Many researchers have thus turned to gene therapy, but results have been mixed so far.

Physiologist H. Lee Sweeney of the University of Pennsylvania has been working with a gene that is the blueprint for a protein called insulin-like growth factor 1, or IGF-1. Sweeney injected the gene for IGF-1 into one back leg of rats and found that the muscles in that leg became as much as 30% bigger than those in the untreated leg, even without exercise. But Sweeney has since switched his studies to focus on a chemical called follistatin, which promises to be more useful.

Work on that chemical was pioneered by molecular biologist Se-Jin Lee of Johns Hopkins University, who had been studying another chemical called myostatin. Muscles in young animals continue to grow until they reach maturity, at which time the body begins producing myostatin, which blocks the growth process. Researchers have been looking for chemicals that would block the activity of myostatin, thus allowing the muscles to continue their growth. Lee discovered another naturally occurring chemical called follistatin that is the strongest blocker of myostatin activity known. Lee found that giving follistatin to mice caused them to bulk up substantially. Genetically engineering mice to produce extra amounts of follistatin and to not produce myostatin led to exceptionally muscular mice whose muscle fibers were more than double the size of normal mouse muscle fibers.

In the new study, Dr. Jerry R. Mendell, director of the gene therapy center at Nationwide Children's Hospital in Columbus, Ohio, and his colleagues inserted the gene for follistatin into a defanged cold virus, which they used to insert the gene into thigh muscles in the legs of healthy macaque monkeys. Eight weeks after the treatment, the monkeys' leg muscles were 15% bigger and as much as 78% stronger. The effects persisted for the full 15 months that the monkeys were studied and no obvious side effects were observed.

The treatment would not cure muscle diseases such as muscular dystrophy or amyotrophic lateral sclerosis, which are caused by genetic defects, Mendell said. But  it could strengthen the weakened muscles, allowing victims of those disorders to use them for longer periods.

The results in the monkeys should be sufficient to persuade the Food and Drug Administration to allow clinical trials of the technique in humans, Mendell said. He hopes to begin such studies by the middle of next year. The first patients will be people with inclusion body myositis, a rare condition that weakens the muscles of adults over the age of 50.

Mendell conceded that the therapy could be abused by athletes seeking to improve their muscle strength. But he noted that, if it is approved eventually, it will be closely regulated and will likely be very expensive. Athletes, he said, are more likely to stick to cheaper and more readily available steroids.

-- Thomas H. Maugh II

Photo: Gene therapy in the legs of monkeys like this macaque in Bangkok made the legs up to 78% stronger. Credit:  David Longstreath / Associated Press

Medical marijuana: A refresher on the 'medical' component

When it comes to medical marijuana, the nation's doctors seem to be softening their stance even as local officials harden theirs. All things considered, perhaps a refresher on the treatment and research realities is in order.

Today's story on medical marijuana by staff writer John Hoeffel begins: "The American Medical Assn. on Tuesday urged the federal government to reconsider its classification of marijuana as a dangerous drug with no accepted medical use, a significant shift that puts the prestigious group behind calls for more research."

And Tuesday's story begins: "As hundreds of medical marijuana dispensaries have opened this year in a startling rollout across California, unnerved local officials have started to push back aggressively. Many cities and a few counties have banned them. Others have imposed emergency moratoriums. And some have started to sue dispensaries to force them to close. So far, the state's courts have sided with local officials."

Now back to marijuana's uses and potential. This article from health journalist Judy Foreman offers an overview of marijuana's safety and effectiveness in treating pain, cancer and other conditions. It notes, "There is a growing body of studies, much of it supportive of the drug’s medical usage, though some of it cautionary.’’ For more, check out a 2008 L.A. Times Health section story by freelancer Jill U. Adams.

And here's a nice explainer, via the National Pain Foundation, on how the drug affects pain. Plus a look at the issue from ProCon.org. It poses the question: "Should marijuana be a medical option?"

"Medical" is the operative word for this element of the debate.

— Tami Dennis

A new magazine celebrating the nursing lifestyle

Nurses work long hours, sometimes for little pay, and are often under-appreciated for their caregiving work. But some recognition is being thrown their way, via a new magazine.

Called Scrubs (as in the uniforms most nurses wear), it's being touted as the first lifestyle magazine for nurses. That's right, nurses have a lifestyle, and this new magazine, debuting Nov. 15, celebrates that.

"There are many things nurses have in common," says Michael Singer, who came up with the concept for the magazine. Some of those shared issues are working crazy hours, being in careers that are physically and emotionally demanding, and constantly being in a caregiving role. "We also found that nurses were doing so many incredible things but were really under-appreciated in so many ways," he adds. "So many nurses go out of their way to help patients, and that was a real source of inspiration for us. We felt like there were stories that really needed to be told."

Singer is chief executive of the Chatsworth-based company Strategic Partners Inc., also the magazine's founding sponsor. The company designs, manufactures and distributes medical and nursing apparel and footwear.

Stories in the premiere issue include an article on makeup strategies for 12-hour workdays, how to prepare fast and inexpensive gourmet meals, profiles of people who have switched careers to become nurses, and how to cope with stress. Cyclist and cancer survivor Lance Armstrong pens a piece on a particular nurse who was integral in his recovery. A companion website offers fresh content.

One thing readers won't see are stories with a clinical bent--editorial director Catherine Ettlinger (formerly editor in chief of Elle and the U.S. prototype of Marie Claire) says that's addressed on other nursing-related websites, magazines and journals. "We’re going to cover all categories from food to fashion, fitness and nutrition, the balance of work and family, all of that."

While the magazine is primarily geared to women, Ettlinger says the smaller cadre of male nurses will be addressed. Scrubs will also speak to the nursing profession's ethnic population.

The magazine plans on publishing thrice yearly, and will be available in nursing apparel stores nationwide.

"I came into this not knowing very much about nursing," Ettlinger says. "I'm finding these nurses are so smart and such compelling human beings, and they're so compassionate and caring. It's really been a pleasure meeting them."

-- Jeannine Stein

Prescribing drugs 'off-label': an ethical prescription

More than one in five of the prescriptions U.S. doctors write for 160 common drugs is for a use other than that approved by the Food and Drug Administration. The practice is perfectly legal, though patients are largely in the dark about what "indications" or uses the FDA has approved for different prescription medications. (You can, however, always check the FDA-approved product labels for a prescription drug here.).

These "off-label uses" have not been scrutinized by the FDA for safety and effectiveness. It's not legal for drug companies actively to promote a drug for "off-label" purposes. But the practice means big money for drug makers, and some do it anyway (just last month, Pfizer agreed to plead guilty to promoting off-label uses for some of its medications and was fined $2.3 billion by the Justice Department, according to the Justice Department website).

So, while it's legal, the practice is controversial.

That leaves doctors, who often feel immense pressure to offer something--anything--to relieve a patient's suffering, in uncharted ethical waters. In some cases, the "off-label" use of a drug might be just the treatment the patient needed. But it might just as likely be a waste of time and money--or worse, pose unpredictable dangers to the patient. When "everybody's doing it" (and, yes, even physicians say stuff like that sometimes), what's a physician to do?

In a commentary in the latest issue of Archives of Internal Medicine, three writers from the National Institutes of Health make it pretty simple: do a little research before writing off-label; think twice before offering something that's new to the market, carries risks of dangerous side effects or is very expensive; in most cases, acknowledge uncertainties to the patient; and share what you've learned with other doctors, especially if the patient did poorly on the medication.

In some cases, a welter of clinical trials has established the safety and effectiveness of a drug's off-label use, and professional societies have recommended the practice: Though the FDA has never approved the use of beta blockers for congestive heart failure, for instance, they are formally acknowledged by cardiology groups as standard in the treatment of the condition.

When there's not a lot of evidence, when the drug in question has been in wide use for less than three to five years or when the drug is being prescribed quite differently from its FDA-approved use (at higher doses, for longer times, or as part of a cocktail of drugs, for instance), a doctor should consider the treatment "suppositional," write the commentators. And in those cases, a doctor should tell a patient explicitly why she is proposing the drug, what the medical community knows about the risks of its use and what alternatives exist (and you can look here for a list of drug therapies the FDA has approved for various common conditions).

Finally, whenever a doctor prescribes a drug off-label without solid evidence that it works, he has a responsibility to help build a body of evidence about the drug's safety and effectiveness. If it proves ineffective or the patient suffers notable side effects, the physician should make a report to the FDA's MedWatch system, the NIH writers assert. Beyond that, physicians should press drug makers, their specialty associations and the FDA to organize registries that track how well a drug fares in off-label treatments.

-- Melissa Healy

As genetic medicine races ahead, docs are left behind

Genetic tests that can help predict and refine a patient's response to drug therapy may be the first big thing in personalized medicine. But the vast majority of physicians don't know how to use them, a new survey finds.

Individual genetic variations can affect how a patient will respond to many antidepressants, pain medications, cardiovascular medicines and certain drugs that treat cancers and gastrointestinal ailments. In all, roughly one in four American patients take medications whose effectiveness could be tweaked or predicted by a pharmacogenetic test. And purveyors of genomic testing services and devices are rushing to provide tests for them all.

A survey of more than 10,000 U.S. physicians undertaken by the American Medical Assn. and the pharmacy benefits manager Medco Healthcare Solutions Inc. found that just more than  one in four had had any type of education in the use of genetic testing to guide medication decisions. And only 1 in 10  felt he or she had the necessary training and knowledge to put pharmacogenetic testing to good use in treating patients. Some 13% had ordered or recommended a genetic test for a patient in the last six months. But twice that many said they would do so in the next six months. 

Genes that regulate liver enzymes can have a particularly powerful influence on a patient's response to a medication. Scientists believe that one such enzyme may be responsible for governing the way patients respond to some 30% of all drugs used today. In oncology, a test can help predict if breast cancer patients will respond to the drug tamoxifen. And cancer drugs in the development pipeline are expected overwhelmingly to be administered with the guidance of genetic tests. Genetic tests also can help reduce unwanted side effects; the blood thinner warfarin, for instance, can cause blood clots or serious bleeds in some patients with an identified genetic variance, and physicians are increasingly testing those on a blood-thinning regimen in an effort reduce such risks.

"It's clear there's wide acceptance" on physicians' part for the role that genetic testing can play in guiding medication decisions, said Dr. Robert Epstein, Medco's chief medical officer, who briefed physicians and researchers on the survey at the annual meeting of the American Society for Human Genetics on Thursday. But the AMA and other groups must step up efforts to educate physicians in the use of these tests, added Epstein. "With the number of new drugs coming to market with a companion diagnostic, it's paramount that this education takes place."

--Melissa Healy

Extra pounds, and attitudes about them, can affect doctor-patient relationships

Doctors can be fairly significant, one would think, in helping people combat obesity-related health problems. But a good working relationship usually begins with respect. And that might be a stumbling block.

In a new study, researchers at Johns Hopkins University School of Medicine report on their questioning of  238 patients -- and their physicians -- from 14 medical offices about their encounters. The patients for whom doctors said they had little respect just happened to have higher body-mass index scores. 

Here's the news release. The study is to appear in the November issue of the Journal of General Internal Medicine.

And here's a recent L.A. Times column from Dr. Valerie Ulene suggesting that doctors might be at least partly to blame for those weight problems: What the doc doesn't say: You're overweight

Plus, an article exploring the effect of a physician's excess weight on patients: Does a doctor's weight matter?

Apparently, attitudes about weight can affect both sides of the doctor-patient relationship.

-- Tami Dennis

Photo: Daniel Acker / Bloomberg

 

Docs decide the time is right to recommend an erectile dysfunction drug

Just in case anyone out there was unconvinced that erectile dysfunction is best treated by popping one of those well-advertised pills, the American College of Physicians has officially proclaimed the superiority of drugs such as Viagra, Levitra and Cialis over hormone treatment.

Published in the Annals of Internal Medicine, the new clinical practice guideline finds that for most men who complain of erectile dysfunction, one of the phosphodiesterase Type-5 inhibitors -- sildenafil, tadalafil, and vardenafil -- is a more effective treatment than pills, creams, gels or patches containing testosterone.

The physicians group limited themselves to comparing ED drugs with testosterone therapy alone. They did not consider alternative treatments for erectile dysfunction that they said are rarely recommended by primary-care physicians, including psychotherapy, pump devices, suppositories or injections.

While oral or gel testosterone were a little more effective than a placebo in the studies reviewed by the guideline's authors, the so-called PDE-5 inhibitors improved erections in 73%-88% of cases (compared with 26%-32% of cases in which a placebo improved the quality of a man's erection). The practice guideline found little research evidence to recommend one of the five ED drugs over another, leading the authors to recommend that doctors base their prescribing decisions on a drug's cost, ease of use, side effect profile and the patient's preference.

The guideline's drafters did find evidence that for sildenafil (Viagra) and vardenafil (Levitra), slightly higher doses (50 milligrams. and 20 milligrams, respectively) tended to yield the best results. (For tadalafil -- Cialis -- they found no dosage consistently superior).

Talking about the drugs' side effects, the physicians who wrote the practice guideline complained that the research evidence in this area was "limited and inconclusive," and called for more to be done. They noted common side effects -- headache, flushing, stuffy nose and upset stomach -- but wrote that future trials need to flesh out which medications are most likely to result in the more serious side effects of visual disturbance, myalgia, nausea, diarrhea, vomiting and chest pain.

There's plenty of money riding on this recommendation. Given the aging population, increased life expectancy and rising rates of diabetes and cardiovascular disease, the Annals article cites a projection estimating that by 2025, 322 million men will suffer from ED. If all American men sought medical help for ED today, the cost could be $15 billion.

Which brings us to the question of whether the guideline's authors are receiving money from the makers of ED drugs. Of the seven authors, one disclosed that he has received grants for research from Pfizer, maker of Viagra. A second author had received research funding from a variety of drug manufacturers, but none that produce ED drugs.

-- Melissa Healy

Rx for health: Take two new books and call me in the morning

We check out and bag our own groceries at the supermarket; we park our own cars and bank online rather than bothering a teller; we fix our own computers. Small wonder, then, that we are increasingly called upon to make a preliminary diagnosis of our own medical problems before deciding whether to call the doctor.

For this last DIY challenge, at least, there are two big honkin' new health and medical manuals just out. Health-conscious patients and parents might want to have them on the bookshelf.

The Merck Manual Home Health Handbook--a consumer-oriented version of the standard Merck Manual that sits on most physicians' desks--has just been updated for a third time. Its 2,306 pages of text are written in everyday language by 300 medical experts from across the world. And it's available--of course--as an iPhone app as well.

The manual is organized in 18 sections that outline and describe disorders of every major system in the body, four sections that deal with specific health issues relevant to men, women, children and older people, a section on injuries and poisoning. It ends with a single section on "special subjects," which includes a description of common imaging tests and chapters on medicinal herbs and nutraceuticals and complementary and alternative medicine.

The manual, which lists for $39.95, seems best used after someone has been given a diagnosis--not so much as an exhaustive guide to treatment options but as a general overview, helpfully illustrated in many cases. But it will also tell you how to preserve a severed body part for possible reattachment at the hospital, how to perform the Heimlich maneuver for choking victims and how to spot signs of elder mistreatment--among many, many other things.

And if you're thinking of becoming a scriptwriter for "House," this is the manual for you, since it describes every arcane syndrome and disorder imaginable.

The American Academy of Pediatrics on Tuesday issued its revised and updated edition of "Caring for Your Baby and Young Child, Birth to Age 5." Intended as a comprehensive guide for parents and guardians, the AAP's 800-page tome outlines normal developmental milestones, describes common pediatric illnesses and injuries and what to do about them, outlines the schedule and purpose of childhood vaccinations and advises on temper tantrums. The newest edition also includes new chapters, reflecting new research on sleep, allergies (including food allergies), autism, multiple births, asthma and sickle-cell disease.

The AAP's guide sells for $22.00. And sure, you could find most of this stuff on the American Academy of Pediatrics' (or other less reputable) website. But for the 45 seconds it will take the parent of a young child to fall asleep once his or her head has hit the pillow, isn't a book a lot nicer than a laptop?

-- Melissa Healy

Doctor group calls for warnings on new prescription drugs

The nation's leading group of general internal medicine physicians has taken the U.S. Food and Drug Administration to task over drug safety and urged the agency to adopt a raft of new consumer safeguards for prescription drugs.

The American College of Physicians recommended that the FDA place limits on the advertising of newly approved drugs to the public, and require that prescription drugs that are new to the market bear a symbol alerting consumers to that fact. The internists also urged the agency to improve its system of detecting drug-safety problems once a newly approved drug is in broad circulation, and said the agency must do a better job of monitoring the safety of drugs manufactured abroad.

The first years of a prescription drug's availability can be boom times for manufacturing giants, who generally "roll out" a new FDA-approved drug with a flashy and expensive marketing campaign aimed at doctors they hope will prescribe the drug and patients they hope will ask for it by name. Those efforts often make new drugs "blockbusters" soon after they reach the general patient population.

The problem: The general patient population is generally less healthy, more diverse, less careful about following use instructions and on more other medicines than were the subjects the drug companies used in their preapproval clinical trials. As a result, safety and effectiveness problems are sometimes detected only when a drug goes into wide circulation. The result is that, when drugs are withdrawn from the market over safety concerns, it is typically in the first couple of years they're on the market.

That's a perspective lost on many American consumers, who tend to reach for their wallets when they see a label proclaiming a product "New!" Advocates of stricter warnings say that an FDA new-drug symbol should serve as a warning that the product still has a limited track record of safety in a general population.

The example generally cited as Exhibit A  in support of such proposals is Vioxx, the arthritis pain reliever withdrawn from the market by Merck after post-marketing reports and company studies found the drug greatly increased stroke and heart attack risks. The withdrawal, however, came after an aggressive marketing campaign had made the drug one of the bestselling pain pills on the market.

But limits on the advertising of new drugs, as well as a "new drug" symbol, would likely require a go-ahead from Congress, and both initiatives would face stiff resistance from drug manufacturers and advertising interests. Both have charged that advertising restrictions on drugs that has passed FDA muster would trample free-speech rights and deny patients the right to inform themselves of a legal medical option.

-- Melissa Healy