Faculty Bibliography

Because of the public fear of bird flu, there has been a lot of pressure on Roche to produce more supply -- even political pressure to break the patent on Tamiflu and allow the drug to be sold generically before the patent expires. Tamiflu is the newest of the neuramidase inhibitors, drugs that work by blocking the transmission of the influenza virus from cell to cell. As a drug to treat the fear of, rather than the effect of bird flu, Tamiflu can easily be misused

Nervous anticipation is creating emotional and physical wrecks among some of us who live in the big cities or obsessively watch the ever-alert cable TV news shows. President Bush has pounded Sen. John Kerry as being weak on terrorism and inconsistent on Iraq. Kerry has warned voters that a second Bush term could lead to another Vietnam while reminding us that Osama bin Laden is still a haunting threat. Both candidates, via ads, speeches and the debates, are megaphoning their danger/safety messages via the media's hype apparatus. The message -- be afraid -- is getting out. A front-page headline in this newspaper last week pointed out that even the voting process is stirring fears: 'Election warning causes anxiety.' Fear traces its roots as a protective mechanism to the animal kingdom. The fear center of all animal brains, humans included, becomes activated in response to perceived danger signals. The body is thrown into a 'fight or flight' mode. Unchecked, however, this stress creates far more heart disease, stroke and suicide victims than does terrorism

Both Vioxx and Celebrex are members of the class of drugs known as Cox-2 inhibitors, which act against an enzyme that causes inflammation but theoretically spare another that protects the stomach lining. The drugs had been promoted as stomach-safe, and heavy advertising had helped Celebrex become the top-selling arthritis drug in the country (although its stomach-protective benefits have never been proved). More than 20 million prescriptions were written for Celebrex last year alone, according to IMS Health, a pharmaceutical information company. It was true that the National Institutes of Health had just suspended an Alzheimer's prevention study after it was discovered that study participants taking naproxen (Aleve) for three years appeared to have a 50% increased risk of heart disease. This was still no reason that a patient couldn't take an occasional Aleve or its prescription counterpart. I tried to explain that daily use of nonsteroidal anti-inflammatory drugs -- be they the Cox-2 inhibitors or the more common ibuprofen or naproxen -- could put stress on the heart after several months or years by causing the organ to retain fluids and by raising blood pressure. But my patient no longer seemed to be listening. He'd been convinced by the drug representative to use Celebrex to replace Vioxx, and he'd even reported on how well it had worked. But now, disappointed by the sudden news, he no longer had faith in the earlier sales pitch. With Vioxx banned and Bextra, Celebrex and now Aleve seemingly down for the count, I instructed my office staff to beware of the Mobic representative. (Mobic is a nonsteroidal drug that has some of the properties of Celebrex but is not a full-fledged Cox-2 inhibitor.)

Most of my patients will do fine without one, but knowing that there's a scarcity has clouded people's reason. The flu is blamed for approximately 36,000 deaths every year and 200,000 hospitalizations, but most of these patients are very sick to begin with. Among those who are hospitalized for the flu, it is pneumonia or bronchitis, not the flu, that more than half the time makes patients the sickest and can kill them. My usual flu vaccine supply, like that of most of New York's private practitioners, originates with Chiron Corp., the company whose license was suspended in Britain for having contaminated stock. Most of the remaining vaccine (from Aventis) went to corporations, hospitals and supermarket chains. Health is seeking submissions from physicians for its Doctor Files column, a monthly feature that explores the art of medicine. The column seeks to illuminate the human aspect of medicine, including the doctor-patient relationship. Submissions, which should be 700 to 800 words in length, can be sent by e-mail to health@latimes.com, or by regular mail to Doctor Files, Health, Los Angeles Times, 202 W. 1st St., Los Angeles, CA 90012. Submissions cannot be returned

This realization is a silver lining to the Vioxx recall. It gives doctors a chance to revisit the issue of pain and arthritis and to compare the actual versus the intended use of a medicine. In this patient's case, I was more concerned about the long-term effects of the drug on her kidneys and liver than her heart. With extended use, nonsteroidal drugs such as Vioxx -- along with Celebrex (a competitor to Vioxx), naproxen and ibuprofen -- are associated with gradual, progressive damage to the tubules of the kidney. Despite the patient's esophageal reflux, she didn't have proven gastritis or ulcer, so I was reluctant to automatically switch her to Celebrex. I might have done so previously, but the Vioxx recall had made me more wary of all the newest arthritis drugs, regardless of what the drug reps said to try and influence me

Afterward, she and I held to the slim chance of a cure. She hurried to show her latest art work at a local gallery, at the same time receiving chemotherapy. The medication made her vomit, and when she became dehydrated she carried intravenous fluids with her. She was a striking sight in my office waiting room, leaning against her IV pole as if it were a cane while talking on her cellphone to friends. I gave her morphine to make her comfortable. The drug lowers blood pressure even as it relieves advanced suffering. I tended to use high doses when a patient's life was all about pain, when he or she was lethargic from the effects of cancer and oblivious to all but the suffering. In Holland, active euthanasia is legal, which means that a dying patient can ask a physician to inject him or her with a deadly drug. This process gives the physician a new power, choosing the exact moment and the cause of a patient's death. It also requires that the physician decide when a patient's quality of life has been so compromised that death is in all ways preferable

Mr. 'Enrand' came to me with depression, weight gain, high cholesterol and elevated blood pressure. Each of these abnormalities was mild, but they were likely to get worse if left untreated. Eight months after relinquishing my control, I took Enrand's blood pressure and discovered it was back to normal without medication. The scale indicated that he had lost 30 pounds during that time. His cholesterol was back below 200. Now he was sleeping through the night without Valium. Now that Enrand had passed through his midlife crisis and the crippling anxiety accompanying it, I realized that he'd been doing the doctoring. He'd learned to treat -- not illness -- but the fear that ran through the heart of it

I had ordered a CT scan on 'Mr. Azziz' during a routine physical because he was a smoker. I had always reassured smokers that the test was routine, that a CT scan was more sophisticated than an X- ray in analyzing a smoker's lungs. But knowing that a CT scan or other state-of-the-art test could tell the future made many patients anxious, worrying about the results. I decided to show the CT scan to my office mate, a prominent pulmonologist. He crisply snapped the scan up onto his view box. This type of precision and ease at looking at potential cancers could frighten a patient if he saw it. The report already had the words 'suspicious for a bronchogenic neoplasm' written on it. Like the lung doctor, the radiologist who had interpreted the X-ray was pronouncing sentence on a man he'd never met. The technology told your future and could take away your hopes and plans with a single verdict

What isn't clear to the public is that drugs like Celebrex are largely safe when taken for shorter periods at lower doses, which is the way they're generally intended to be used for common joint inflammation. The increased risk to the heart is due to taking them at high doses over a prolonged period of time. Celebrex diminishes an enzyme that prevents clotting, which is associated with heart attacks. The prolonged use of Aleve, and perhaps all non-steroidal anti-inflammatory drugs, can lead to fluid retention and elevated blood pressure, itself a risk factor to the heart. Yet these drugs are being overprescribed by doctors and overused by patients who consider them safe and effective. Public expectation regarding Celebrex and Vioxx was ramped up by direct-to-consumer advertising, a process that is not adequately overseen by the Food and Drug Administration. The public was told that these so-called Cox 2 inhibitors protect the stomach in a way that other non- steroidal drugs, all of which can cause bleeding ulcers or gastritis, don't. Thinking of Celebrex as a wonder drug, the public naturally feels betrayed now that it understands that the stomach- sparing qualities, though they may exist, were not actually proven, and now that it knows about the elevated heart risk, which FDA scientists suspected from the outset. The FDA that engages in that analysis will have to be a much stronger and more effective agency than the one in place now. In an editorial in the Nov. 30 issue of the Journal of the American Medical Association, deputy executive editor Phil Fontanarosa discussed the creation of a new office of drug safety to ensure a more independent and extensive evaluation of drugs than the FDA can provide. It would seem that a better first step would be to try to strengthen the FDA itself, to make it a more effective regulatory agency less dependent on drug company money and political appointments