Mutant mice shed light on nicotine addiction/Survival of the smallest babies

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Mutant mice shed light on nicotine

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29181993B243

November 05 2004 at 10:00AM

 

Washington - Genetically altered mice that are unusually sensitive to

nicotine may help scientists nail down exactly how people become addicted to

smoking, United States researchers said on Thursday.

 

Specific doorways into brain cells, called receptors, in the newly

created mice could hold the key to nicotine addiction, they said.

 

Studying the mice may help in the development of better drugs to help

people quit smoking, the researchers wrote in Friday's issue of the journal

Science.

 

" Nicotine addiction, the largest cause of preventable mortality in the

world, leads to 94 million smoking-related deaths annually, " wrote the

researchers, led by Andrew Tapper of the University of Colorado and Henry

Lester of the California Institute of Technology.

 

'Most scientists believe that's a key reason why nicotine is so

addictive'

Scientists have known that a family of receptors called nicotinic

acetylcholine receptors were involved in addiction to smoking.

 

Lester and colleagues created mice with a mutation in the " Alpha 4 "

portion of the receptor that were unusually sensitive to the effects of

nicotine.

 

Brain cells communicate using a neurotransmitter or message-carrying

chemical that jumps across gaps between the neurons called synapses.

 

One such neurotransmitter, acetylcholine, activates certain cells to

release another neurotransmitter called dopamine, associated with

pleasurable sensations.

 

Once finished, acetylcholine is rapidly broken down by an enzyme

called acetylcholinesterase.

 

But nicotine mimics acetylcholine and is not broken down by

acetylcholinesterase.

 

" So it persists at the synapse for minutes rather than milliseconds,

and excites the post-synaptic neurons to fire rapidly for long periods,

releasing large amounts of dopamine, " Lester said in a statement.

 

" Most scientists believe that's a key reason why nicotine is so

addictive. "

 

If a way can be found to stop nicotine from latching on to brain

cells, tobacco addiction might be curable.

 

" It's a complicated pathway that still must be broken down into

individual steps before we can understand it fully, but I personally believe

that nicotine addiction will be among the first addictions to be solved,

because we already have so many tools to study it, " he said.

 

 

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Survival of the smallest Jeremy Laurance

November 07 2004 at 05:28PM

 

Each year thousands of babies are born at the limits of viability and

medical science enables many to live. But now the courts are being asked to

sit in judgment: should doctors always intervene to save a life? The writer

reports from the front line of neonatal care.

 

In Nursery 6 of the Elizabeth Garrett Anderson hospital in central

London, England, a baby is gasping for breath. The consultants are clustered

around the tiny scrap of humanity which is festooned with tubes and wires

and checking her vital signs displayed on a screen above her incubator.

 

She was Born at 28 weeks and weighed only 560g.

 

She grew rapidly at first but now, seven weeks later, progress has

faltered. The specialists are worried and think it may be because she is

fighting against the ventilator, using up calories she needs to grow.

 

Her tiny chest pumps 80 times a minute

Her tiny chest pumps 80 times a minute.

 

Doctors in the neo-natal unit of a modern hospital operate at the

limits of medicine and their new-born patients cling to the edge of life.

The babies have lost the protection of the womb so, with warmth, oxygen and

nutrients, the doctors try to substitute for its life-giving force. But

there are problems.

 

Bill, his head covered in a bandage, is only nine weeks old but has

already had three operations.

 

Twins Ryley and Roman, born at 24 weeks, close to the limit of

viability, are still on ventilators 10 weeks later. Raven, aged 13 weeks,

has a hole in her heart that has been patched but faces further major

surgery before she is a year old. She was given a 25% chance of survival the

day before her birth at 30 weeks.

 

The futures of scores of families hang in the balance among the

incubators, their flashing lights and their beeping alarms.

 

Her positive attitude reflects that of the unit

This is medical technology at its most sophisticated but is it

achieving miracles or creating ethical dilemmas?

 

In the past month the parents of two grieviously ill babies have taken

their doctors to court to compel them to do everything in their power to

prolong their lives.

 

Charlotte Wyatt and Luke Winston-Jones suffered from terminal

conditions and medical teams felt it was kindest to keep them comfortable

and let them die.

 

But Darren and Debbie Wyatt and Ruth Winston-Jones argued in court for

more aggressive treatment to be provided to keep the babies alive for as

long as possible.

 

The courts ruled it would be wrong to compel doctors to keep them

alive and that it was acceptable for them to withdraw care when no more

could reasonably be done.

 

The judgments have been welcomed as wise and humane, and accepted by

the parents, but they have raised wider questions about the practice of

intensive care at the limits of life.

 

In September a BBC Panorama programme questioned whether too many

premature babies were being saved to face a life of disability. Is

everything being done that should be done for babies born before their time?

Or is too much being done merely because it is technologically possible?

 

Ryley and Roman were born only a day or two beyond the 24-week

abortion limit. Ten weeks on they in incubators in the cramped Elizabeth

Garrett Anderson neo-natal unit, part of University College Hospital,

London.

 

Pink and plump, they are growing well thanks to the top-quality care

they have received since being transferred from the East Surrey hospital in

Surrey, which took 12 hours.

 

But, like all babies who are extremely premature, they face problems.

 

They have had surgery to correct heart defects and both have had

infections. Ryley has thin bones and developed renal failure for which a

kidney specialist is being consulted. Both have chronic lung disease caused

by the long period that they have been on ventilators.

 

In addition, there is a " significant risk " that they might have a

neurological impairment, the doctors say.

 

The good news is that there is nothing on the brain scans yet to

suggest damage but it is still early days and, as every parent of a

premature baby knows, progress is never smooth.

 

Heather Andrews, the twins' mother, aged 20, is cheerfully positive

about the outlook.

 

" When they told me there would be good days and bad days, they weren't

joking. First one gets an infection, then the other has a setback. It is

like living in a dream; you can't take it in, " she says.

 

She went into labour one Sunday night in Crawley, Surrey, where she

lives with her partner, Wayne Baines, 21, and daughter Chloe, four, and was

taken to the East Surrey hospital. She was not asked outright whether she

wanted the babies resuscitated if they were not breathing when born.

 

" They just said they were trying to get the babies out and it was a

case of how they were going to do over the next few days. "

 

In any case, her views are clear. " I think it's wrong when doctors

won't resuscitate a baby even though there is nothing wrong with it. If it's

a year on and they are making no progress and the baby is struggling, then

maybe.

 

" But to not even give them that one chance is disgusting. "

 

Her positive attitude reflects that of the unit, which is committed to

saving lives, not - as some other units do - counting the cost.

 

From the moment you enter the warren of little nurseries linked by a

winding corridor, you sense the atmosphere of optimism and hope.

 

Nurses squeeze past each other, dripping expressed breast milk through

tiny tubes into infant stomachs and checking monitors attached to scrawny

chests.

 

Alarms beep constantly as traces record heart rate, breathing, oxygen

level and blood pressure, while ventilator pipes gently vibrate. And amid

the tubes and wires and screens are what appear to be ancient, miniature

human beings.

 

Premature babies lack the subcutaneous fat that develops in the last

month of pregnancy and gives full-term babies the chubby, glossy look of the

newborn. Their skin hangs loose in wrinkles and folds, as their lives hang

by a thread.

 

Every feature of their existence presents a challenge. The consultant

ward round is dominated by discussion of " creatinine levels " , " neuronal

migration " and " immunoacids " .

 

Feeding is more complicated than getting milk into the stomach; many

underdeveloped babies are intolerant of food and have to receive nutrients

direct into a vein.

 

No one could question the commitment of the doctors to saving all who

can be saved. Even so, most die when ventilation is withdrawn. Sometimes

parents, struggling to comprehend their loss, object.

 

" We do have a baby now whom we think is inevitably going to die and

the parents don't want us to withdraw care, " says one consultant.

 

" We don't know when it will happen and the time parents have with

their baby is precious. We don't want to go to court. "

 

" If you rush them, it may be something they regret for the rest of

their lives. It takes time to adjust, " says another.

 

A striking feature of the ward is the number of babies with major

medical problems who are not premature, or only slightly so.

 

A full-term baby with a heart defect transferred from a hospital 320km

away will require heart surgery.

 

Another, born at 33 weeks, is about to go home after major surgery.

 

This is a key point for Jane Hawdon, consultant neo-natologist and

head of the unit. In the debate about the dangers facing premature babies

and the limits of viability, the risks of a normal birth have been

forgotten, she says.

 

A mother of three, the youngest of whom was born seven weeks premature

and cared for at the unit, she fizzes with energy and enthusiasm, having

experience as both parent and doctor.

 

" What people don't realise is the casualty rate of having babies, full

stop. I spent all my pregnancies petrified because I have seen the

unexpected. I never assumed everything was going right until I saw it going

right. "

 

She and many of her colleagues were critical of the Panorama

programme, which highlighted the risk of disability in babies who are

extremely premature and asked whether a 25-week limit should be set below

which attempts at resuscitation would not be made, as is done in the

Netherlands.

 

Hawdon rejects this. " We assess cases on an individual basis and we do

what we can for them with conscience and rationale. If you go to a special

school for handicapped children, you will find a tiny number were born

pre-term.

 

" The rest will have syndromes and congenital disorders that have

developed in full-term babies. It depends from which end of the telescope

you are looking. "

 

For the parents, struggling with uncertainty, this positive approach

is received with gratitude.

 

Despite the cramped conditions, several said they preferred the homely

atmosphere of the Elizabeth Garrett Anderson unit to that of the more formal

concrete and glass of the new Great Ormond Street hospital, the famed

children's hospital.

 

Nevertheless, the risks to premature babies born very early are high.

International research shows survival rates are continually improving, but

up to 50% of those born before 29 weeks have some kind of educational or

behavioural problem later on, compared with one in six of those born at term

(37-42 weeks).

 

For John Wyatt, research director at the unit, this can be seen two

ways.

 

" Is the glass half full or half empty? Isn't it amazing that half of

these babies have no problems by school age?

 

" There is a tendency to concentrate on the negative in this debate. We

believe here that a baby who has a realistic chance of benefiting from

intensive care should be offered it. There is a resistance to using

arbitrary cut-offs. "

 

The medical team is, however, discussing the introduction of a new

threshold of not resuscitating babies at 22 weeks. It claims to have a 50%

survival rate for those born at 23 weeks - better than many other units.

 

The debate revolves not only on attitudes to disability, but also on

attitudes to parenthood.

 

" If parents are prepared to look after a handicapped child, who are we

to make a judgment about that? There is enormous prejudice against

disability in this society, " says one consultant.

 

" You may be a parent for a few hours or a few days. That is a

privilege, " says another.

 

Every parent hopes that the days turn into weeks and the weeks into

years and that their baby will thrive.

 

Frances Bennett, 42, the mother of Bill, has already taken his twin

brother Lenny home, two months after they were born seven weeks premature.

 

But while Bill remains in his incubator facing the possibility of more

surgery, his mother feels she cannot celebrate. " Not until they are both

home, " she says.

 

Yet for Eric and Olenka Schwer, aged 35 and 27, that moment has come.

Raven is their first baby and today she is going home, 13 weeks after they

were told she had a one-in-four chance of survival.

 

Sitting in the tiny parents' room, Raven lying on her father's chest,

Olenka says: " It was scary but we had hope. We had bad days, but we were

lucky. "

 

A young doctor checking the brain scan of a 28-week gestation infant

in the intensive care unit next door, said:

 

" Should we be doing everything we can? That is the million-dollar

question. We do what we feel is possible, based on the facts - the

gestation, the size, whether there was an infection in the mother.

 

Different parents have different attitudes.

 

" If you have someone who has had 10 pregnancies and no live births,

they are in their mid-40s and this is their last chance, you can see where

they are coming from. " - The Independent

 

 

 

a.. This article was originally published on page 23 of Tribune on

November 07, 2004

b..

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c.. Related Stories More Medical Stories

a.. Premature babies might be at risk of ailments

b.. Infection tests may reduce premature births