AA501927-E47F-4C86-B3C5-1AF8CE6F41AC.jpg
Alan Felzer, right, and his daughter Karen Felzer, holding her son 11-month-old Emmet Harrington, look at a laptop computer in their house in Claremont, Calif., Saturday, Sept. 27, 2008. Felzer, who suffers from ALS (amyotrophic lateral sclerosis) or Lou Gehrig’s Disease, and his daughter Karen helped lead a patient and care giver web study on the effectiveness of lithium on treating ALS. (AP Photo/Stefano Paltera)

E31395AC-22AE-404A-9068-A3CB0ADB5469.jpgDC1F8338-39A4-4E20-B379-5C3C4BB3668C.jpg

(AP) — November/December 2008, by Marcus Wohlsen — Until last year, Alan Felzer was an energetic engineering professor who took the stairs to his classes two steps at a time. Now the 64-year-old grandfather sits strapped to a wheelchair, able to move little but his left hand, his voice a near-whisper.

Felzer suffers from ALS, also known as Lou Gehrig’s disease. The fatal neurological disorder steals the body’s ability to move, speak and ultimately to breathe. But rather than succumb to despair along with his illness, Felzer turned to the Web to become his own medical researcher — and his own guinea pig.

Dozens of ALS patients are testing treatments on their own without waiting on the slow pace of medical research. They are part of an emerging group of patients willing to share intimate health details on the Web in hopes of making their own medical discoveries.

Some doctors caution that such patient-led research lacks rigor and may lead to unreliable results, false hopes and harm to patients.

“The Internet is a wonderful tool, but you know, it’s buyer beware,” said Dr. Edward Langston, immediate past chairman of the American Medical Association’s board.

In Felzer’s case, the experiment’s results illustrate the obstacles that stand between patients and self-discovered breakthroughs. The drug he tried did no good. But he and his family felt they had little time and little to lose in trying.

“ALS is such a short illness,” said Felzer’s wife, Laura. She helps her husband communicate using sign language with his one good hand when his slow, halting words become difficult to understand. “You want to do what you can as fast as you can.”

The U.S. Food and Drug Administration has approved only one drug to treat ALS symptoms. It only works for some patients, and its effects are limited. As a result, Internet forums for ALS patients brim with links to the latest research offering any hint of promise. After Alan Felzer was diagnosed last year, his 33-year-old daughter, Karen, dived into the forums and found new hope.

In a recent small study, Italian scientists reported that every ALS patient given the drug lithium, commonly used to treat bipolar disorder, saw the disease’s progress slow substantially.

Many ALS patients began trying lithium on their own. They persuaded their doctors to prescribe it “off-label” — a use not approved by federal drug regulators. Off-label prescribing is a common practice, researchers say, when patients are facing a terminal illness.

Despite the risks, Langston of the AMA pointed out that doctors often stumble upon treatments, and patients could possibly do the same. “If patients are willing to share their experiences, that may in fact occur,” he said.

Felzer began taking lithium in January, and his scientifically minded family reached out to other ALS patients. “All those people are taking it anyway,” said Alan Felzer, whose smile remains bright and his gaze sharp even as the rest of his body fails him. “So it only made sense to keep track of what was happening.”

The task of leading the ALS-lithium project fell to Felzer’s daughter, Karen, a U.S. Geological Survey earthquake researcher. Her partner in the effort was Humberto Macedo, a 42-year-old computer systems analyst, father of six and ALS patient in Brasilia, Brazil.

The study grew naturally out of the strong reliance of ALS patients on one another for information, Macedo said.

Working online, Karen Felzer and Macedo recruited nearly 200 patients worldwide to take a specific lithium dosage and answer standard surveys to gauge their symptoms. They began running their study through a Web site called PatientsLikeMe.com, using it to attract volunteers and track their progress.

On the site, patients share detailed information about their symptoms and the drugs they are taking. The site focuses on conditions that have stubbornly resisted medical science, such as ALS, Parkinson’s and multiple sclerosis.

The site’s founders hope professional and amateur researchers alike will dip into the resulting pool of data and emerge with insights that lead to better treatments.

“My ultimate frustration that drove this site into existence was an overall feeling that there was a lack of transparency and speed or urgency” by the medical system, said Jamie Heywood, who co-founded PatientsLikeMe months before his own brother died of ALS.

Heywood too hoped that lithium was the breakthrough he and others had been seeking.

But after six months, none of the 87 people who stuck with the study showed any letup in the disease’s progress, said Karen Felzer. She now doubts the Italian study’s results.

“It’s obvious to everyone it’s not the miracle drug we thought at first,” she said. She also thinks other tests of lithium for ALS should be halted to spare patients the drug’s possible side effects, such as tremors, weakness and difficulty breathing. Her father stopped taking the drug, though Macedo is continuing.

However, other reseachers say professional lithium studies should go forward. Dr. Merit Cudkowicz, a Harvard Medical School professor, is set to begin one in December with 84 patients. Her study will stick to the so-called gold standard of research, in which each patient will be randomly chosen to take the drug in question or a placebo. Neither patients or researchers will know who got the drug to avoid introducing bias.

Because the patient-led lithium study lacked those tight controls, it is unreliable as a measure of safety and effectiveness, Cudkowicz said. With an incurable disease, she said, “You don’t want to be throwing something away that works because of a bad study.”

On the Net:

* Patient-led ALS lithium study: http://alslithium.atspace.com/
* PatientsLikeMe: http://www.patientslikeme.com/

Harvard Medical School, December 3, 2008 — Although aging puts people at greater risk for serious eye disease and other eye problems, loss of sight need not go hand in hand with growing older. Practical, preventive measures can help protect against devastating impairment. An estimated 40% to 50% of all blindness can be avoided or treated, mainly through regular visits to a vision specialist.

Regular eye exams are the cornerstone of visual health as people age. Individuals who have a family history of eye disease or other risk factors should have more frequent exams. Don’t wait until your vision deteriorates to have an eye exam. One eye can often compensate for the other while an eye condition progresses. Frequently, only an exam can detect eye disease in its earliest stages.

You can take other steps on your own. First, if you smoke, stop. Smoking increases the risk of several eye disorders, including age-related macular degeneration. Next, take a look at your diet. Maintaining a nutritious diet, with lots of fruits and vegetables and minimal saturated fats and hydrogenated oils, promotes sound health and may boost your resistance to eye disease. Wearing sunglasses and hats is important for people of any age. Taking the time to learn about the aging eye and recognizing risks and symptoms can alert you to the warning signs of vision problems.

Although eyestrain, spending many hours in front of a television or computer screen, or working in poor light do not cause harmful medical conditions, they can tire the eyes and, ultimately, their owner (see below). The eyes are priceless and deserve to be treated with care and respect — and that is as true for the adult of 80 as it is for the teenager of 18.

5 common eye myths dispelled

1. Myth: Doing eye exercises will delay the need for glasses.

Fact: Eye exercises will not improve or preserve vision or reduce the need for glasses. Your vision depends on many factors, including the shape of your eye and the health of the eye tissues, none of which can be significantly altered with eye exercises.
2. Myth: Reading in dim light will worsen your vision.

Fact: Although dim lighting will not adversely affect your eyesight, it will tire your eyes out more quickly. The best way to position a reading light is to have it shine directly onto the page, not over your shoulder. A desk lamp with an opaque shade pointing directly at the reading material is the best possible arrangement. A light that shines over your shoulder will cause a glare, making it more difficult to see the reading material.
3. Myth: Eating carrots is good for the eyes.

Fact: There is some truth in this one. Carrots, which contain vitamin A, are one of several vegetables that are good for the eyes. But fresh fruits and dark green leafy vegetables, which contain more antioxidant vitamins such as C and E, are even better. Antioxidant vitamins may help protect the eyes against cataract and age-related macular degeneration. But eating any vegetables or supplements containing these vitamins or substances will not prevent or correct basic vision problems such as nearsightedness or farsightedness.
4. Myth: It’s best not to wear glasses all the time. Taking a break from glasses or contact lenses allows your eyes to rest.

Fact: If you need glasses for distance or reading, use them. Attempting to read without reading glasses will simply strain your eyes and tire them out. Using your glasses won’t worsen your vision or lead to any eye disease.
5. Myth: Staring at a computer screen all day is bad for the eyes.

Fact: Although using a computer will not harm your eyes, staring at a computer screen all day will contribute to eyestrain or tired eyes. Adjust lighting so that it does not create a glare or harsh reflection on the screen. Also, when you’re working on a computer or doing other close work such as reading or needlepoint, it’s a good idea to rest your eyes briefly every hour or so to lessen eye fatigue. Finally, people who stare at a computer screen for long periods tend not to blink as often as usual, which can cause the eyes to feel dry and uncomfortable. Make a conscious effort to blink regularly so that the eyes stay well lubricated and do not dry out.

Physician’s First Watch, December 2, 2008 — Breathing exercises help improve asthma patients’ quality of life, although they have little effect on the disease itself, according to a study published online in Thorax.

Some 180 adults with mild-to-moderate asthma and impaired disease-related quality of life were randomized to three sessions of either physiotherapist-directed breathing exercises or nurse-delivered asthma education (control).

The primary outcome — asthma-related quality of life — initially improved in both groups, but by 6 months, patients in the breathing group saw significantly greater improvement. The authors estimated that six patients would need to be treated for one to show significant improvement over controls at 6 months.

Physiological outcomes, such as inflammation and airway hyperresponsiveness, did not differ between the groups.

The authors conclude that breathing exercises “may help patients whose quality of life is impaired by asthma, but they are unlikely to reduce the need for anti-inflammatory medication.”

……………………………………………………………………………………………………………

Research links epilepsy drug to autism

LONDON, Dec 1 (Reuters) – Pregnant women taking the Sanofi-Aventis epilepsy pill Epilim may raise their child’s risk of developing autism, British researchers said on Monday.

Their study published in the journal Neurology showed children whose mothers took Epilim during pregnancy were seven times more likely to develop the condition compared with babies whose mothers did not take an epilepsy drug.

The preliminary findings on the drug, known generically as valproate and sold as Depakine in the United States by Abbott Laboratories, bolster previous research linking the drug to problems during pregnancy.

But a researcher not involved in the study cautioned the link to autism was preliminary and said women should consult their doctors if they are concerned, noting seizures during pregnancy can endanger both mother and fetus.

“It raises a question that should be pursued,” Michael Goldstein, a vice president of the American Academy of Neurology who practices at Western Neurological Associates in Salt Lake City said in a telephone interview.

“Women should not panic but instead talk to their neurologist before becoming pregnant to determine whether medicine is needed and what the best medicine is.”

Other studies have shown that the drug is more likely to cause birth defects than other epilepsy drugs, the researchers said.

Sanofi spokeswoman Jennifer Wilson said the drugmaker welcomed the preliminary results from the study it partially funded and was committed to improving treatments for women with epilepsy, particularly during pregnancy.

The company also agreed with the researchers acknowledgements of the study’s limitations, including the relatively small sample size for each of the groups. Gus Baker and colleagues at the Liverpool and Manchester Neurodevelopment Group looked at 632 children, about half of whom were exposed to epilepsy drugs while in the womb.

Of the children whose pregnant mothers took an epilepsy drug, 64 were exposed to Epilim, 44 to GlaxoSmithKline Plc’s Lamictal, 76 to Novartis AG’s Tegretol and 65 to other epilepsy treatments.

Tests at one, three and six years of age showed that nine children had developed autism, and another showed signs of the disorder whose symptoms range from severe social avoidance to repetitive behaviours and sometimes mental retardation.

Seven of the autistic children had mothers who took an epilepsy drug while pregnant, including four on Epilim and another on a combination of the Sanofi drug and Lamictal, the researchers said.

None of the children in the study had a known family history of autism and the raised risk for the mysterious condition was not seen with the other epilepsy drugs, the researchers said.

No one knows what causes the disorder affecting about 1 in 150 children but doctors agree there is a genetic component. They also theorize that something in the environment — and possibly conditions in the womb — can trigger the condition. (Reporting by Michael Kahn; Editing by Maggie Fox and Jon Loades-Carter)

………………………………………………………………………………………………………..

Can Naltrexone Reduce Amphetamine Abuse and Dependence?

The answer might be yes.

Journal Watch Psychiatry, December 1, 2008 — Amphetamine abuse and dependence, which commonly involve reoccurrences and relapses, constitute a major public health problem. Effective pharmacologic interventions are greatly needed. Amphetamines, similar to cocaine, achieve their clinical effects and induce craving via dopaminergic systems involving mesolimbic and ventrotegmental areas, the substantial nigra, amygdala, and nucleus accumbens. Furthermore, µ-opioid receptors are colocalized on dopaminergic neurons, and craving in chronic cocaine abusers is associated with binding of µ-opioid receptors in the limbic area on PET scans. The opioid antagonist naltrexone has been found to limit subjective amphetamine effects in abusers and in healthy nonusers and to decrease cravings in abusers. In a double-blind study funded by the Swedish government, investigators randomized 80 amphetamine-dependent subjects to 12 weeks of treatment with naltrexone (50 mg/day) or placebo.

Treatment fidelity and amphetamine use were monitored via urine tests; 25 naltrexone recipients (62%) adhered to medication continuously. In both the intent-to-treat group and the group of 55 completers (26 placebo recipients and 29 naltrexone recipients), naltrexone was associated with significantly lower amphetamine use and lower cravings compared with placebo. Tolerability was good, and few adverse effects were seen.

Comment: This welcome preliminary study points out how treatments targeting µ-opioid receptors might have diverse anticraving effects. These receptors now have been shown to affect craving for substances as diverse as stimulants, alcohol, and opiates. Because only 16% of positive urine samples showed evidence of methamphetamine use, we do not know naltrexone’s effectiveness for abuse of this drug, and thus additional studies are necessary. Also, more data (e.g., on response and clinical utility) would be helpful. Still, with its benign adverse-effect profile, naltrexone seems likely to become a useful tool for clinicians treating patients with amphetamine abuse.

* Joel Yager, MD

………………………………………………………………………………………………………

Ginkgo biloba for prevention of dementia: a randomized controlled trial.

University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
November 2008
CONTEXT: Ginkgo biloba is widely used for its potential effects on memory and cognition. To date, adequately powered clinical trials testing the effect of G. biloba on dementia incidence are lacking. OBJECTIVE: To determine effectiveness of G. biloba vs placebo in reducing the incidence of all-cause dementia and Alzheimer disease (AD) in elderly individuals with normal cognition and those with mild cognitive impairment (MCI). DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow-up of 6.1 years. Three thousand sixty-nine community volunteers aged 75 years or older with normal cognition (n = 2587) or MCI (n = 482) at study entry were assessed every 6 months for incident dementia. INTERVENTION: Twice-daily dose of 120-mg extract of G. biloba (n = 1545) or placebo (n = 1524). MAIN OUTCOME MEASURES: Incident dementia and AD determined by expert panel consensus. RESULTS: Five hundred twenty-three individuals developed dementia (246 receiving placebo and 277 receiving G. biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow-up were low (6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person-years in participants assigned to G. biloba and 2.9 per 100 person-years in the placebo group. The hazard ratio (HR) for G. biloba compared with placebo for all-cause dementia was 1.12 (95% confidence interval [CI], 0.94-1.33; P = .21) and for AD, 1.16 (95% CI, 0.97-1.39; P = .11). G. biloba also had no effect on the rate of progression to dementia in participants with MCI (HR, 1.13; 95% CI, 0.85-1.50; P = .39). CONCLUSIONS: In this study, G. biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI. Trial Registration clinicaltrials.gov Identifier: NCT00010803.

Comment: These results show clearly that Ginkgo biloba in its most common formulation and dosage is of no benefit in preventing dementia. These results also are consistent with those of a meta-analysis of 35 smaller trials.

— Thomas L. Schwenk, MD

By Kevin Davies for PharmaWeek, December 4, 2008 — Pediatric oncologist Alan d’Andrea has enjoyed a distinguished academic career over the past two decades. As a postdoc at the Whitehead Institute in the late 80s, he almost single-handedly cloned the erythropoietin receptor. At the Dana Farber Cancer Institute, his interests pivoted toward Fanconi anemia (FA), a rare genetic cancer disorder where patients are prone to solid tumors, leukemias, and bone marrow failure. d’Andrea’s group has helped define some of the disease’s 13 known mutated genes and the underlying biochemical pathways. Now, as co-founder of The DNA Repair Company (DNAR), d’Andrea is hoping that his insights into the mechanisms of DNA repair’s six major pathways will help pharma identify patient responders and improve drug safety.

PharmaWeek recently caught up with d’Andrea in his Dana-Farber digs to learn more about the commercial prospects of analyzing DNA repair.

Alan, what was your motivation behind The DNA Repair Company (DNAR)?
I can give you a couple of different renditions. Conventional chemotherapy and radiation kills cancer by causing DNA damage – that’s how most cancer chemotherapy works. Even in the post-Gleevec, post-targeted therapy days, still, 18 of the 20 major anti-cancer drugs cause DNA damage. Cancer cells become resistant to chemotherapy and radiation by amplifying their DNA repair pathways. So the idea here [of DNAR] is, if we could get a fresh tumor sample and profile its DNA repair – which pathways are on or off – we might be able to predict the best drug(s) or radiation treatment for that patient. It’s another example of personalized medicine.

At the same time, other starting companies were saying, ‘We don’t know what’s important, so let’s just transcriptionally profile everything.’ But we think DNA repair is important. So that was the impetus behind the company, to pull together people I viewed as the five or six major leaders in DNA repair and ask them: Do you have biomarkers? Do you have antibodies that would be a sign as to whether your pathway is working? I co-founded DNAR with Michael Yaffe at MIT, who has intellectual property (IP) in DNA damage response pathways, while most of my work has been on FA and homologous recombination. So we said, let’s put all this together.

Our long-term goal is to screen for small-molecule inhibitors of these pathways. We’re interested in Chk1, PARP inhibitors, etc. The original intent was to develop a drug screening company, and eventually, things may move in that direction. But to get started, it made more sense to say, there’re a lot of conventional drugs out there already. Can we better define which patients will respond?

The personal story is a fun one – for the last 15 to 20 years, I’ve been working on this rare genetic disease, FA. Children with FA are born with a DNA repair defect. I wrote a tiny review for Nature Genetics in the early days on forging a novel pathway when the second FA gene was cloned. Well, there are now 13 FA genes! It’s astounding, and it’s been a fun ride for us. Studying this disease entailed working with pediatricians, getting samples – we have a clinical lab here running the diagnostic test for FA, and we’ve been a repository for collecting a lot of FA cell lines. So I was able to establish IP in the context of the FA pathway, which I tried to license to Big Pharma, but nobody was all that interested because it’s such a rare disease. That’s when the idea of starting our own company came about, after we reached a critical mass of IP here at Dana Farber.

How did former Human Genome Sciences CEO Bill Haseltine [Chairman of the Board] get involved?
Ah, that’s an interesting story. Thirty years ago, as an undergraduate at Harvard, I wrote my thesis while working at the [then] Sydney Farber Cancer Institute with Bill, who was a new assistant professor. He’d been a postdoc with [Nobel laureate] David Baltimore, working on retroviruses. Bill had two or three people in his lab; he was just getting started. He got very interested in DNA damage and repair – the Maxam-Gilbert protocol was, you take a piece of DNA and you damage it with alkylating agents. Bill always had a passion for DNA sequencing, and we got the protocol from Allan Maxam before it was published – I was probably one of the first people in the world sequencing DNA with this method. I kept up with Bill as a friend over the years; he worked on HIV and ultimately started Human Genome Sciences. Three or four years ago, Mike [Yaffe] and I visited him – he was very interested in the idea [of DNAR] and agreed to help.

What’s the status of the company today?
We have venture backing from Mohr-Davidow Ventures; they have particular expertise in diagnostics and personalized medicine. We have about 12 employees and research space in the Photonics Center at Boston University, but we’re moving to a bigger space in Cambridge. Also, we’re currently raising a B round of financing.

At DNAR, we’re generating small panels of antibodies against different DNA repair proteins and protein modifications. These are useful in screening particular tumor types for DNA repair activity, and thereby predicting drug and radiation sensitivity. So the clinical validation here requires the use of these antibody sets in analyzing archival tumor samples, which we obtain from collaborators around the country. We often get tumor sets from 50-100 patients with a particular tumor type. These are clinically annotated, meaning that we know how they responded to particular drugs. Next, we apply the DNAR antibodies to these samples to see if our antibody profile does correlate with the patient’s response, with the idea of coming up with predictive tests.

Is there a paradigmatic example of this approach that you can give?
There’s actually a practical example in play. Most of the validation for our company has been external. Steve Jackson [Cambridge University] started a company called Kudos, which has a real drug: a PARP inhibitor that blocks base excision repair. A certain subset of breast tumors have a deficiency in one of the six repair pathways – homologous recombination (HR) repair; they’re hyper-dependent on base excision repair instead. So predictably, a PARP inhibitor is an excellent drug here. It’s a classic example of synthetic lethality. The initial thought was that this drug could be used as a sensitizer, in combination with other chemotherapeutic agents. But astoundingly, for this subset of patients where the repair profile is known – deficient in HR, heavily dependent on base excision repair – the PARP inhibitor works as a single agent. So that has bred a fair amount of excitement for our company. Maybe our panels can actually predict small groups of patients with very distinct DNA repair profiles – they might respond to drugs in trials as single agents, allowing us to stratify subsets of patients for new drugs coming along. All drug companies, when they start a drug in the clinic, want to use it as a monotherapy rather than part of a combination, as this might increase the chances of getting positive results. So we’re hopeful that our panels could prove useful to big pharma companies in launching new drug trials.

Could you use your panels as a service like Genomic Health’s Oncotype Dx, where physicians would send clinical samples to you?
We looked at the Genomic Health model very closely. They did a couple of things very well – they set up a centralized lab, rather than send a kit out to pathology labs around the country. They also asked a very discrete clinical question: What’s one of the most vexing problems in breast cancer treatment? In other words, tamoxifen versus no tamoxifen? I think Genomic Health was wise, not necessarily going after the biggest market, but instead going after a problem that was particularly troubling to clinicians managing breast cancer.

Right now at DNAR, we’re going after tumor types – breast, ovarian, colon – and subsets of patients who will respond to conventional therapies. We’re looking for panels of antibodies that aren’t just prognostic, but predictive of drug response. So it’s less of a crapshoot using this drug set. It also says, here’s a subset of patients who will not respond – because it’s as important to disqualify patients from the drug as to qualify them.

DNAR’s other mission is partnering with bigger companies who have PARP inhibitors or DNA repair inhibitors, with the idea that we can find subsets of patients who are most likely to respond to these drugs, and stratify them for clinical trials. Let’s get them into Phase I trials, so the trial isn’t simply a toxicity test; you’re trying to enroll patients who might actually respond. The whole success of Velcade at Millennium was having a few multiple myeloma patients in their Phase I trials. You want to stack the deck.

Do you have any ongoing Big Pharma collaborations?
We do, but I’m not sure I’m allowed to reveal them yet. We’re hopeful that over time, these same pathways and biomarkers will be useful in screening drugs. That’s an important component of this: Why have a company doing immunohistochemistry when there are 5-10 times as many companies doing transcriptional profiling, looking at nucleic acids? I’d argue that the logic of having a pathology-based company is, you’re actually looking at a pathway and if you find a marker, it can also be pharmacodynamically useful for developing drugs around that pathway.

Are you looking for additional partners?
When I go to ASCO or clinical oncology meetings, I talk to small companies that have drugs – Chk1 inhibitors, PARP inhibitors – and who may be modulating DNA repair pathways. I then try to set up relationships with DNAR. In terms of the competitive landscape, there are several other companies coming up in the DNA repair area, but I haven’t seen any as focused as we are.

Who are some of the other key management team players?
Dan Paterson, our president, used to work at Dana Farber; he has a lot of knowledge of clinical trial networks, and he’s a business guy. Our chief scientific officer, David Weaver, is himself a highly regarded expert in DNA repair, while Brian Ward, our executive vice president, previously worked at Myriad and Genomic Health – he’s the development guy, trying to get these ideas into a nice little packaged kit. That’s the race with all this! Some postdocs from my own lab are now working at DNAR. Each scientist has a different tumor assignment; they collaborate with experts in academic medical centers for samples and clinical information. I think it’s working well.

The New York Times, by Catherine Saint Louis — Keeping skin healthy as decades pass can be as easy as remembering this adage: Accept the things you cannot change. Have the courage to change the things you can. Be wise enough to tell the difference.

Ah, that is the hard part. When $89 anti-aging creams promise to lift saggy faces in just minutes, and some sunscreens claim to offer all-day protection, truth can be scarce. But dermatologists say there are simple and inexpensive ways to stave off premature aging and its attendant wrinkles and loss of collagen. Some of the following advice is backed by independent clinical research, while other practical tips come from board-certified dermatologists.

“I’m big on simplifying everything,” said Dr. Jeffrey S. Dover, an associate clinical professor of dermatology at Yale University School of Medicine. So he counsels his patients to “cleanse, treat, prevent” daily. Wash your face with your scrub, gel or foam of choice; slather on a sunscreen every morning to forestall further sun damage; and reverse the signs of photoaging by applying a prescription retinoid nightly like Renova or Retin-A, which is now available generically as tretinoin. “Retinoids take months and months to work,” said Dr. Dover, a co-author of a forthcoming book called “The Youth Equation.” “It’s not going to reverse 30 years of lying on the beach overnight.”

Still, diligent application of a topical retinoid has been shown to stimulate new collagen, lighten dark spots and even out complexions, said Dr. Bruce Katz, clinical professor of dermatology at the Mount Sinai School of Medicine. “It doesn’t do a heck of a lot,” said Dr. Katz, director of the Juva Skin and Laser Center in Manhattan. “But it does do something.”

Despite the fact that it has been proved for more than a decade that alpha-hydroxy acids (like glycolic acid) in topical forms can increase skin thickness and improve wrinkled and sun-damaged skin, most consumers hunting for an anti-aging cream on drugstore shelves don’t realize it.

The reason? Marketing muscle, Dr. Katz said. With cosmetic pharmaceuticals like the alpha-hydroxy acids, Dr. Katz explained, “multiple companies were behind them, but they didn’t have a lot of money invested, so there wasn’t a major motive to market.”

One potential downside is that alpha-hydroxy acids “thin out the epidermis, making it a little more sensitive to being sunburned,” but not nearly as sensitive as it is to Retin-A, he said. So he recommends that people who wear either product be sure to keep sunscreen on during the day as well.

Stress might also make you more susceptible to ultraviolet light. One study found that when mice were exposed to it, those who were stressed (by the smell of a predator) developed tumors at week 8, compared with week 21 in unstressed mice. “Can’t say the same for humans,” said Dr. Francisco Tausk, a professor of dermatology and psychiatry at the University of Rochester School of Medicine. Still, he said, “it’s quite suggestive. If you have chronic stress, and you’re exposed to a carcinogen such as ultraviolet light, you are more susceptible” to cancer.

No need to go white-faced wearing zinc oxide anymore, just to protect against short UVB rays and longer UVA rays, said Dr. Amy Derick, a board-certified dermatologist in Barrington, Ill. Recently, the Food and Drug Administration has approved more broad-spectrum sunscreen products with Mexoryl SX, a European formula that is now widely available here and much less visible on the skin, she said. Dr. Derick also recommends Neutrogena sunscreens with Helioplex, which has a form of stabilized avobenzone for prolonged UVB/UVA effectiveness that won’t leave consumers feeling as if they’re “wearing a white mask.”

Several studies have shown that antioxidants also protect the skin from light, scavenging free radicals, said Dr. Derick, explaining, “antioxidants hook onto the free radicals generated by UV light and basically negate them.” She recommends applying vitamins C and E in the form of a serum.

Finally, don’t neglect your noggin. Last month, an epidemiological study of 51,704 melanoma cases nationwide showed that melanomas of the scalp and neck are disproportionately fatal. Dr. Anne Lachiewicz, lead author and a medical graduate of the University of North Carolina at Chapel Hill, said that after controlling for age, sex, tumor thickness and ulceration, the study found that 14 percent of people who developed scalp and neck melanoma died from them, compared with 6 percent of those with melanoma on their extremities, “where they might be more likely to notice a new and changing lesion.”

So dermatologists should inspect scalps for melanomas, and beachgoers should wear wide-brimmed hats.

Medscape, by Robert Lowes — By selecting former Senator Tom Daschle (D-SD) to head the Department of Health and Human Services, President-Elect Barack Obama has found a point person for sweeping health-care reform who also shares his bipartisan — read realistic — approach to politics.

The Senate must confirm the appointment.

Since leaving the Senate after losing to Republican challenger John Thune in 2004, Daschle has buffed both his healthcare and bipartisan credentials. He and 3 other former Senate majority leaders — Republicans Bob Dole and Howard Baker and Democrat George Mitchell — formed the Bipartisan Policy Center in 2007 to tackle healthcare reform and other social issues. Daschle also joined the law and lobbying firm of Alston & Bird as a special policy advisor, with healthcare as one of his strong suits. That’s where his old rival Bob Dole also works on healthcare issues as a special counsel.

Besides serving as HHS secretary, Daschle will head the Obama administration’s policy-making group on healthcare. His goal will be turning Obama’s healthcare campaign promises into a detailed legislative blueprint. Not surprisingly, he’s being called Obama’s healthcare czar.

Clues on what Daschle might want to achieve in his 2 new roles can be gleaned from a book that he coauthored titled Critical: What We Can Do About the Health Care Crisis. In the book, published earlier this year, Daschle proposes creating a national agency that would oversee the healthcare system in the same way the Federal Reserve oversees the country’s financial system.

While speculation brews about Daschle’s effect on the massive healthcare sector, Obama already has come under criticism for choosing a cabinet member with an arguable conflict of interest, something Obama promised not to do. Daschle not only works for a firm that represents healthcare companies (although he is not a registered lobbyist), but also serves on the board of the Mayo Clinic. Republican National Committee spokesperson Alex Conant said in a statement, “For voters hoping to see new faces and fewer lobbyist connections in government, Daschle’s nomination will be another disappointment.”

Proponents of making healthcare more accessible and affordable, however, are applauding Obama’s pick. “The appointment of Senator Daschle as Secretary of the Department of Health and Human Services is the best news possible for those who want to achieve meaningful health care reform,” said Families USA Executive Director Ron Pollack in a statement posted on the group’s Web site. “Senator Daschle has a deep commitment to securing high-quality, affordable health care for everyone in our nation. His new leadership position confirms that the incoming Obama Administration has made health care reform a top and early priority for action in 2009.”