High dose asthma inhalers linked to cataracts

12:15 18 September 03

NewScientist.com news service

Using high doses of steroid asthma inhalers significantly increases the risk of developing cataracts, suggests a new UK study.

People who used high doses of inhaled corticosteroids for a long time increased their chance of developing the eye disorder by nearly 70 per cent compared with those not on the drugs.

Researchers compared the medical records of around 15,000 people with cataracts, with 15,000 people without cataracts from an electronic database run by British general practitioners.

"People with cataracts were quite a lot more likely to be exposed to steroids - in particular high doses were quite strongly associated with increased risk," says Liam Smeeth, an epidemiologist at the London School of Hygiene and Tropical Medicine, who led the study.

"We need to strive to use the lowest doses we can while still controlling airways disease," he told New Scientist. But he cautions: "Don't stop using your inhaled steroids. If you are worried and on a high dose go and see your doctor."

"Astonishingly high"

Nita Odedra, eye health officer for the UK's Royal National Institute for the Blind, says the link between asthma inhalers and cataracts was known. But she says the new work show "it's an astonishingly higher risk than previously thought".

She agrees patients should discuss lower doses with their doctors. But some people will need the higher doses to control their asthma. "It's the difference between staying alive and having a cataract, which is treatable."

Smeeth and colleagues found that people on the highest doses of inhaled steroids had a 69 per cent increased risk of developing cataracts, while people on the lowest doses had no raised risk at all. All the subjects were over 40 - cataracts are rare below this age.

Of all the 15,000 subjects, 11.4 per cent of those with cataracts had used a steroid inhaler, compared with 7.6 per cent of the control group. Smeeth notes that only 117 of the cataract group and 43 of the control group were on the highest doses. "It is really a very high dose indeed."

Collagen fibres

Cataracts are caused by the clouding of the lens within the eye. Odedra says using steroid drugs is associated with a particular type of cataract - a posterior subcapsular cataract - which forms nearer the back of the eye. This affects the visual axis and has potentially "devastating effects" for sight.

She says steroids enter the blood and lymphatic systems and can affect the way that collagen fibres are arranged. "If it affects the way fibres are arranged in the lens, it will cause an opacity leading to a cataract," she told New Scientist.

Over half of all people over 65 are likely to develop cataracts, according to the US National Eye Institute in Bethesda, Maryland.

Journal reference: British Journal of Ophthamology (vol 87, p 1247)

Shaoni Bhattacharya

Heart-stopping drugs reduce surgery risks

10:40 18 September 03

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A new way of stopping the heart during bypass operations could reduce damage to the heart and improve patients' chances of a full recovery.

More than a million people a year have open-heart surgery to unblock or bypass clogged arteries, or repair damaged valves. The heart is usually stopped for about one hour while they are under the knife because it is impossible to operate on a moving target. But the standard method of achieving this - flooding the heart with potassium ions - can cause permanent damage.

Now Geoffrey Dobson and Michael Jones of James Cook University in Townsville, Australia, have developed an alternative. It has only been tested on animals so far, but experts say the results, due to appear in the Journal of Thoracic and Cardiovascular Surgery, look promising.

"By keeping potassium levels normal they are preventing injuries to the muscle cells and to the vessels that carry blood to the heart," says Peter Macdonald, a cardiologist at St Vincent's Hospital in Sydney.

Electrical wave

In resting muscle cells, the distribution of ions across the cell membrane generates an electric potential. The waves of electrical activity that sweep across the heart, telling muscle cells to contract, are generated when channels in the membrane open, allowing ions to flow across the membrane and depolarise the cells. Flooding the heart with potassium ions freezes its cells in this depolarised state.

Dobson and Jones instead freeze the heart in the resting state using two drugs: adenosine, which opens some of the channels that transport potassium ions in and out of the cell, and lignocaine (known as lidocaine in the US), which blocks sodium ion channels.

"There are two ways to stop a heart cell. Let it run out of gas - that's the potassium infusion - or to not even turn it on. That's what Dobson has done," says Jakob Vinten-Johansen, a cardiovascular physiologist at Emory University in Atlanta, Georgia, who now collaborates with Dobson.

When rat hearts were perfused with potassium for two hours, only half started beating again afterward. Yet when Dobson and Jones perfused rat hearts with adenosine and lignocaine for four hours, they all started again, although the hearts retained only around 70 per cent of their previous pumping ability.

Body temperature

Dobson and Vinten-Johansen found that a single five-minute infusion of the drugs was all it took to stop the heart of an anaesthetised dog for an hour. It started beating again spontaneously, and appeared to work just as well as before.

What is more, the heart was kept at body temperature, whereas in open heart surgery the body is usually cooled to help prevent damage. "The injection seemed to put the heart in a state of suspended animation, something you'd never see with potassium," says Vinten-Johansen.

But even if the technique is adopted by surgeons, it will not prevent all the side effects of open-heart surgery. The heart-lung machines used while the heart is stopped cause a variety of problems, such as damaging blood cells.

In some cases, surgeons now use "off-pump" surgery, in which the heart is kept beating but a small area is mechanically immobilised. But this is not yet suitable for most operations.

Rachel Nowak, Melbourne

First human clone embryo ready for implantation

18:32 15 September 03

NewScientist.com news service

The first human cloned embryo could be implanted into a surrogate mother's womb before the end of the year, US fertility expert Panayiotis Zavos claimed on Monday.

The attempt follows months of "practising" in the lab on hundreds of hybrid embryos made by fusing human cells with empty cow eggs, Zavos told a press conference in London.

If the human pregnancy proceeds and goes to term, the baby will be a girl, he adds.

"We've created the first human embryo for reproductive purposes," says Zavos, director of the Andrology Institute of America and associate director of the Kentucky Center for Reproductive Medicine and IVF.

Zavos says that the frozen human embryo should have been implanted in July, but the surrogate mother developed complications which meant that the attempt had to be postponed. But it's still "on the agenda this year", he says.

"The announcement has no scientific merit - its pure hype," says Bob Lanza, scientific director at Advanced Cell Technology in Worcester, Massachusetts.

Human-cow embryos

Zavos says he created the human cloned embryo by fusing an empty human egg with a granulosa cell, an exclusively female cell which nourishes and protects oocytes as they grow in the ovary.

The embryo, which was frozen after growing to a ball of eight to 10 cells, was created after Zavos had experimented for months with hybrid embryos made by fusing human cells with empty cow oocytes.

To make female hybrids, he fuses the empty cow oocytes with granulosa cells from women. And to make male hybrids, he fuses the empty cow oocytes with differentiated forms of fibroblast skin cells taken from men.

He claims to have attempted this with 600 to 700 cow eggs, and successfully created around 200 human-cow embryos. "Our replication and duplication is remarkable," he said. "We have a 40 per cent success rate".

"It's teaching us how to refine the system to a point where we can use it in humans," said Zavos, adding that he planned to disclose more at the American Society for Reproductive Medicine's annual meeting in Texas in October. He says that he has submitted his results for publication to the online journal, Reproductive BioMedicine.

Creating monsters

Zavos rejected any suggestion that the hybrids were unethical. "We're not interested in creating monsters," he says. "We have no intention of taking them above the blastocyst stage of about 100 cells, and no intention of transferring any to term."

He says that his team had pioneered a refinement to the fusion process, the electrical "jolt" which unites the human cell with an empty egg. He says that his system now uses two "jolts", separated by about five hours, and he was also testing chemical stimulants which trigger fusion.

Zavos stresses that once thawed in preparation for implantation, the human embryo will be thoroughly tested for chromosomal and other defects before insertion. If it proves defective, he will abandon the procedure.

But Lanza says: "It's dangerous and scientifically irresponsible to attempt human reproductive cloning, with or without chromosome testing. We've seen abnormalities and defects in almost every species cloned to date. There is no reason to think humans would be any different."

Zavos refuses to reveal the country where the procedure would take place, but says it would not be the US, the UK, France or Germany.

But he denied attempting anything unlawful. "We're not lawbreakers, we're law-abiding, and intend to stay that way," he says.

Andy Coghlan