The music of the night

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(This article appeared in the Winter 2008-2009 issue of NYU Physician.)

To cure sleep apnea, an ancient instrument may be best medicine of all.

Puff-cheeked and red-faced, with beads of sweat across his forehead, Kazim Yildiz, 42, is steadily vibrating his lips, much like a baby blowing bubbles. He is playing a didgeridoo, believed to be the world’s oldest wind instrument. Traditionally crafted from a branch of a eucalyptus tree, the cylindrical wooden tube is indigenous to Australia, where it’s been used in traditional Aboriginal ceremonies for thousands of years.

Now, modern medicine has found a new use for this ancient artifact. With practice, the didgeridoo produces an eerie, reverberating bellow. But to those afflicted with sleep apnea—a potentially serious sleep disorder in which breathing repeatedly stops and starts—the sound is music to their ears.

“In people with sleep apnea, the airway intermittently collapses during sleep,” explains Dennis Hwang, M.D., a researcher in the Division of Pulmonary and Sleep Medicine. “We believe that learning to play the instrument strengthens the muscles of the upper airway and reduces the airway collapsibility during sleep.”

Yildiz, an information technology expert at Merrill Lynch, is part of a 10-person study being conducted at NYU to determine whether playing the didgeridoo regularly can help to cure their disorder. Sleep apnea (Greek for “without breath”) affects as many as one in five middle-age adults, who literally stop breathing for moments while they are asleep. These stoppages cause the brain to wake up, which allows breathing to resume, but the pattern may leave him sleepy and irritable during the day. Loud snoring is a common symptom of sleep apnea, although not everyone who snores has the disorder.

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Two Alzheimer’s drugs show promise

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(This story was #18 in Discover magazine’s top 100 stories of 2008.)

Two unconventional treatments for Alzheimer’s disease show promising early results. Both Rember (methylthioninium chloride) and Dimebon (dimebolin hydrochloride) appear to slow the mental decline associated with the illness.

No effective medicines exist for Alzheimer’s, which is estimated to afflict more than 4 million people in the United States alone. The disease is characterized by a decline in cognition and function and usually strikes after age 60. Most Alzheimer’s treatments have targeted amyloid, the main protein component of the associated plaques that form in the brain; Rember is the first to target the tangled, abnormal fibers of a protein called tau. At an Alzheimer’s conference in Chicago, the drug, made by TauRx Therapeutics, was reported to slow the progress of mild to moderate Alzheimer’s disease by 81 percent over the course of a year. In a phase 2 trial of 321 people with mild to moderate disease, those on the drug stayed at about the same cognitive level for up to 19 months, while those on the placebo got worse. A final trial is expected to begin in 2009.

The second drug, Dimebon, is an allergy drug used in Russia 20 years ago. A Lancet article in July reported that over 26 weeks of treatment, Dimebon significantly improved memory, thinking, and overall functioning in 68 Alzheimer’s patients, compared with a 66-member control group. Although researchers don’t know exactly how Dimebon does this, it may work by protecting mitochondria—the powerhouses of cells—from injury, says Rachelle Doody, the study’s lead author and a neurology professor at Baylor College of Medicine in Houston. A phase 3 trial for the drug began recruiting participants in June.

Microbiology: Straight from the gut

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(I first heard about gut transplants when I was interviewing Michael Zasloff of Georgetown University for a different piece. The idea that you can transplant someone’s entire intestines blew my mind. None of the Nature editors had ever heard of it, either. The implications–that you can study how bacteria colonize a gut after birth–really make this story compelling. And yes, I got to see some gruesome stuff. I’ll never quite forget the startlingly yellow poop Stuart Kaufman raved about. You can download a pdf of this article.)

The human body teems with microbes. Apoorva Mandavilli meets the surgeons who have a rare opportunity to watch an ecosystem being established as they transplant guts from one person to another.

Dirty business: gut transplants give bacteria and scientists new choices.

Stephanie is the first to admit that she never had the guts for life. She was born with familial adenomatous polyposis, a genetic disorder in which thousands of polyps form in the colon. By the age of 22, much of the organ had to be removed. Four years later, a massive benign tumour choked off the blood supply to her small intestine, so doctors cut out all but a metre of it. For the next six years, she was fed by a tube every night until the feeding left her liver badly scarred and fighting recurring infections. “I was given a month to live,” she says.

That’s when doctors referred Stephanie to Georgetown University Hospital in Washington DC. There, on 17 April 2006, surgeons cut out her stomach and what was left of her small and large intestine and replaced it with new organs from a donor who had died days earlier in Tennessee. “Oesophagus to anus, her entire gastrointestinal tract was in the garbage can,” says Tom Fishbein, who directed the surgery. “She got a brand new one.”

All organ transplants are complicated, but there are only a handful of centres in the United States that have the  expertise to transplant  a small intestine, the seven metres of coiled tissue connected up to the stomach at one end and the large intestine at the other. The technique is complicated because the gut is teeming with trillions of bacteria and other microbes, plus the bulk of the body’s lymphocytes.

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FDA says cold medicine is not for children under 6

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(This article was #18 in Discover Magazine’s top 100 stories of 2007.)

In October, Food and Drug Administration (FDA) advisers recommended against the use of most nonprescription cold and cough medicines for children under age 6, citing the lack of evidence of safety or efficacy in this age group. Prior to the announcement, most manufacturers had already voluntarily restricted sales of medicines formulated for children less than 2 years old.

The FDA review of the medications began after a report by the Centers for Disease Control in January found that, between 2004 and 2005, more than 1,500 children under the age of 2 had wound up in emergency rooms after taking over-the-counter cough and cold medicines. In another development that prompted the review, Baltimore city officials filed a citizen petition with the FDA in March, noting that the remedies do not help children under 6 years of age and may in fact harm them.

There are roughly 800 products on the market containing antihistamines, decongestants, anticough agents, and other chemicals intended to treat colds and coughs in children. Like many pediatric medicines, they have been tested only in adults and are simply packaged to deliver smaller doses to children.

In September, the FDA also required that, by November 2007, drug companies stop making unapproved prescription drugs containing the narcotic cough suppressant hydrocodone for use by children younger than 6. Manufacture of all other unapproved hydrocodone products must halt by December 31.

Held to ransom

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(This Opinion column ran on Nature’s news site on March 26, 2007. You can download a pdf of the original post.)

A pharma giant’s decision to withhold new drugs from Thailand will only hurt patients, says Apoorva Mandavilli.

Is there ever a good enough reason to deny life-saving medicines to an entire country’s citizens? I say no. But it seems pharmaceutical giant Abbott begs to differ.

The Chicago-based company decided on 14 March not to introduce in Thailand any of its seven new drugs — including an antibiotic, an important AIDS drug called Kaletra and medicines to treat blood clots, kidney disease and high blood pressure. Without this crucial registration, the drugs cannot be imported to or sold in that country.

It seems to me that Abbott is, in effect, holding millions of Thais’ lives hostage to force their government to respect its patents. This is good business?

The price of drugs varies from place to place.

What’s shocking to me is that the company is making no bones about the fact that its decision is retaliation against Thailand’s decision in January to issue ‘compulsary licenses’ allowing some locals to import or make cheap copies of Abbott’s new version of Kaletra. “This matter is about intellectual property and the integrity of the patent system,” Abbott spokeswoman Melissa Brotz said in a statement.

Lofty words, but I’m reminded more of a schoolyard fight.

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Premature medication

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(This Opinion column ran on Nature’s news site on December 22, 2006. You can see the original post here.)

Handing out experimental drugs to desperate patients is not a good idea, says Apoorva Mandavilli.

At first glance it seems only kind and right to let people with serious illnesses take whatever medicines they want. Some have campaigned so hard for this that the US Food and Drug Administration agreed on 11 December to let patients buy experimental drugs direct from the manufacturer when there are no other options available.

But this could have some terrible consequences.

Yes, the humanitarian argument for giving access is compelling. And yes, on an individual basis, it seems cruel to deny a medicine to someone who is suffering. But if the drug hasn’t been properly tested, how do we know it won’t aggravate the illness or, worse still, prove fatal to the people who take it? It may even actively discourage companies from investing in proper trials for those drugs where the only customers are desperate patients.

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Your first dose…

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(This is the post I wrote launching Spoonful of Medicine, Nature Medicine’s blog. You can see the original post here.)

Hello everyone!

Welcome to ‘Spoonful of medicine’, where we hope to enlighten, entertain and occasionally exasperate you with our comments on biomedical research and public health.

We hope you’ll be active participants as well, letting us know when we’ve made sense and, of course, when you think we’re stark, raving mad. We hope the proportion is at least slightly more of the former.

Initially, at least, most entries will be posted either by me, Apoorva Mandavilli, or by my colleague, Charlotte Schubert. I am the news editor and am responsible for pretty much everything you read in our news section. You can read more about me here.

Charlotte edits the News & Views section, which involves much editing of copy written by scientists. She’ll say hello soon… you can read more about her here.

Let the games begin…

Seeking care

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(This is a sidebar to The coming epidemic, an article about the AIDS epidemic in India, and part of a special package on Indian science called Nature Outlook: India.)

When you’re trying to manage an AIDS epidemic and you have limited resources, preventing infection is the logical priority. But where does that leave those who are already infected?

Treating people with AIDS is not easy. At the very least, it requires trained medical staff and the resources to make sure patients take the drugs on time. Nobody knows that better than the doctors at Tambaram Hospital.

Built in 1928 as a sanatorium for patients with tuberculosis, the government centre is 45 km outside Chennai and has more AIDS patients than any other Indian hospital. There are often more than 900 inpatients for its 776 beds, so some have to sleep on the floor. Every hallway is flooded with patients who look skeletal, with shrunken limbs and sallow skin. Outside the wards, hairy black pigs roam beneath drying laundry, accompanied by the rancid smell of sewage.

The hospital was one of eight government centres that together were meant to roll out antiretroviral drugs (ARVs) to 100,000 people over five years. In the first year, which began April 2004, it treated fewer than 1,000.

“From the outside, you may think it is a low number, but for people working here, there are a lot of problems,” says S. Rajasekar, the hospital’s deputy superintendent. Despite repeated requests, he says, the centre has the same resources it did in 1993, when it had just two HIV-positive patients. In 2004, it saw 14,991 new patients and had 140,000 hospital visits from HIV-positive patients. “With just 25 doctors,” says Rajasekar. “Amazing, right?”

By June 2005, government centres, including Tambaram Hospital, had doled out ARVs to 8,000 people. In the same time, since April 2004, small private and non-profit clinics reached an estimated 30,000 sufferers. But these clinics are in a constant struggle for survival.

One such centre is the Naz Foundation’s orphanage in New Delhi. Of the 24 children there — ranging in age from 19 months to 17 years — 10 are on ARVs. Despite one child dying two years ago, only the oldest one knows that she is HIV positive. To spare the children from stigma, their status has also been kept secret from their teachers and neighbours.

One child’s monthly supply of ARVs can cost about Rs900 (US$20). The home was funded by the Gere Foundation until March 2005, but since then money has come almost entirely from small, private donations. “Care is something no traditional donor wants to fund,” says the centre’s director, Anjali Gopalan. “They see it as a black hole, as one donor told me. There’s no return on the dollar.”

Scrambling to treat their patients, doctors at some clinics use medicines that are past their expiry date; others bring free drugs they are given in the United States or elsewhere. Staff at the YRG Care Clinic in Chennai last year began asking people to donate just $10 each. “It’s always beg, borrow, steal, donations, fundraise. That’s how we get funds for care,” says Suniti Solomon, who runs the YRG. “We cannot save the millions out there. The government has to do that.”

ArtMedicine: Science diagnoses art

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(This article appeared on Medscape in February 2001.)

The bulge in the left breast is large and distinct. The nipple and areola appear swollen and the skin nearby looks dimpled–puckered. It takes Dr. James Stark exactly 2 seconds to make his diagnosis.

“That woman’s got breast cancer,” Stark whispers to his wife as they stand in Florence’s Church of San Lorenzo. He has just diagnosed the subject of Michelangelo’s 500-year-old sculpture called Night.

Over the years, art historians have suggested that the breast is malformed because Michelangelo was unfamiliar with female anatomy, or that it is the result of a sculpting error. But until June 1999–when Stark visited the chapel–no one had diagnosed the prominent lump.

“I’ve been . . . [diagnosing breast cancer] for 25 years. I looked at the breast for 2 seconds and I just knew,” says Stark, medical director of the Cancer Treatment Centers of America and associate professor of medicine at the Eastern Virginia Medical School. For the next 1 1/2 years, Stark and Jonathan Nelson–a scholar in Renaissance art and a visiting professor at the Florentine campuses of New York University and Syracuse University–thoroughly investigated Stark’s theory. Skeptical at first, Nelson has since become convinced that Michelangelo knew the woman had a fatal disease.

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