What is Living in my Mouth?

The last time you opened wide, did you ever imagine that you were opening the door to what is essentially home to thousands of bacteria? Living inside your very own mouth! Yes, hundreds of varieties of critters, eating for free every time you visit your favourite restaurant. The ultimate uninvited dinner guest.

Many of these bacteria are fairly benign and exist in your mouth without doing any harm at all, but there are some that have the capacity to do some impressive damage.

In the interest of keeping your attention, I'll dedicate another chat to my favourite villains and their superpowers.

One particular kind of bacteria that is both common and relatively abundant among oral flora is the mutans streptococcus group. These common bacteria are particularly good at existing in the oral environment. When you eat carbohydrates, so do they, which is significant because these carbohydrates are metabolized into acid. This acid can lead to cavities in unsuspecting teeth. This acid works to demineralize teeth, stripping the outer enamel layer of it's strengthening minerals. This usually happens slowly over time as the demineralization front moves deeper into the tooth, through the outer layer of enamel, then even faster through the porous dentine* layer to the core or "pulp" of the tooth where nerves and blood vessels reside. Bacteria can then move through the extent of the carious lesion and may result in a necrotic pulp. Hello root canal!
(* - Think of dentine as a layer made of drinking straws in parallel embedded in plaster.)

So, the formula for cavities can be thought of as: acid-producing bugs + carbohydrates + teeth. But that's not the whole picture. There are many factors that determine an individual's susceptibility to cavities, or in dental-speak, "caries". They include the relative amounts of acid-producing, (acidogenic) bacteria**, how often carbohydrates are consumed, and the rate of salivary flow, to name just a few.
(** - Such as the Streptococcus mutans group of bacteria.)

Some individuals have the good fortune of having relatively low numbers of pathogenic bacteria, whereas others have gobs of them. This means their mouths are charged and ready to produce lots of acid when given the right fuel (carbohydrates). One interesting study examined a population in Africa that, based on their high mutans strep counts, would have been considered a high-risk group for caries. However, the incidence of caries in this population was disproportionately low because of their diet, which was free of simple carbohydrates.

But jumping on the Atkins bandwagon is not necessarily the answer! If carbohydrates are consumed, say, three times a day with each meal, then there are really only three major "acid-attacks" to worry about. However, sipping tea with sugar throughout the day and then sucking on a few sugary after-dinner mints means a multiplicity of fuel blasts for the acid-producing bacteria! Here, frequency becomes an appreciable problem if you have the right type and amount of bacteria in your mouth.

This frequency problem is often the culprit when a patient with low salivary flow rate presents with a mouthful of cavities. "Xerostomia", or "dry-mouth", can be a side-effect of prescription drugs, smoking, radiation, chemotherapy or result from some diseases. These individuals have less saliva sloshing around to rinse the surfaces in their mouth and wash the acidogenic bacteria and their carb-fuel away. The bacteria can stick around longer, colonize and expand their communities into an acidogenic machine!

To temper their xerostomia, patients may try drinking juices or sodas frequently throughout the day or sucking on candies or mints. Unfortunately, sugar is virtually ubiquitous and many patients end up exacerbating, rather than diminishing, their high caries-risk. Drinking sugar-free liquids frequently, enjoying candy and food with sugar-substitutes, and using a saliva-substitute (a gel-like slop or mouthrinse that can be applied to the inside of the mouth and lasts for hours) may be a better solution.

So wait a minute… who invited these bacteria anyway?

Figure 2: Next time you kiss someone, remember this image, which is an electron microscope close-up of the chains of bacteria (cocci) that live on your teeth.

A newborn's mouth is initially sterile, but can become home to new flora as they pass through the birth canal (I'm not going to pretend I'm not grossed-out by this), get kissed by bacteria-laden relatives, and put their fingers, toes, objects galore, into their mouths (see references 1,2,3 below). One study examining the pattern of infectivity of common acidogenic bacteria from mother to child found that there may even be a "window of infectivity". The bacteria studied colonized the child's mouth at a median age of 26 months (reference 4, below).

Oral bacteria differ among sites in the mouth, even among sites on the same tooth, and the flora shifts as the infant begins to sprout teeth at around 6 months. There is a change in structural environment as hard tissues are exposed (tooth enamel) and bacteria that welcome the change can expand and proliferate in this new environment. Other bacteria that enjoyed the gummy environment may decrease in number and the population balance shifts.

How do these bacteria stick around with spit sloshing around and a big muscular tongue?

The resident microbes don't work alone. Together they form a biofilm, aka plaque, which begins with the interplay of electric charges. Certain bacteria can "stick" to oral structures through electrical interaction. Once their anchorage is established, they can bind to other bacteria floating around in the mouth through interesting appendages similar to the tentacles of an octopus. As this web of interacting bacteria builds, it's capacity to hold more bacteria increases and the plaque thickens as more microbes are added. Disrupting this biofilm with food, saliva, a toothbrush and floss is critical in dismantling the microbial community's ability to proliferate and harm teeth and gums. Floss becomes especially important since some sites are more protected than others from mechanical removal, such as between the teeth and along the gumline.

These bacteria are not your friends! They eat your French rolls without your permission! I suggest you blow them away with a nice toothbrush and floss.

Christa Favot

Herpes Simplex Viruses: Cold Sores and Genital Herpes

Most people have heard of Shakespeare's 'Romeo and Juliet', and the majority know that it is a tragedy based on a love story, but you could probably be forgiven for missing the subtle reference it contains to one of mankind's most common infections:

O'er ladies ' lips, who straight on kisses dream,
Which oft the angry Mab with blisters plagues,
Because their breaths with sweetmeats tainted are:
Act 1. Scene IV

The blisters that Shakespeare refers to are in fact cold sores produced by the herpes simplex virus (HSV) which comes in 2 types, HSV-1 and HSV-2. Type 1 herpes is carried by over 80% of the population; it's the culprit responsible for causing recurrent cold sores, and most people pick it up in the first few years of life, usually in the form of a loving kiss from a parent or sibling. HSV-2, on the other hand, affects between 5 and 10% of the population (including many individuals who are also infected with HSV-1), and is more often associated with genital herpes, although either virus can cause a similar disease at both anatomical sites.

Part of the reason that herpes infections are so common, and so easy to transmit, is that up to 30% of people previously infected with HSV go on to periodically shed the virus in their saliva or genital secretions (depending upon the site of infection) without suffering any symptoms. These individuals are known as 'asymptomatic shedders' and can transmit the infection to other susceptible individuals but without showing any obvious signs of the disease themselves.

Shedding, and recurrent lesions, occur because once a person is infected with herpes they carry the virus for life. This is because HSV has evolved a clever strategy, called latency, that enables it to escape from the immune system by hiding inside nerve cells. Then, in about 15% of people carrying it, the virus periodically reawakens producing recurrent, painful, infectious sores on the affected part of the body.

The herpes virus itself (left) consists of a tiny particle one five-thousandth of a millimetre across. It's so small that 100 million of them could fit on a pinhead. Each particle consists of a core, containing the viral DNA, wrapped in a protein-studded coat known as the envelope. These proteins are the viral equivalent of velcro and help HSV to lock on to, and invade, its target cells. Viruses are the ultimate parasite and comprise little more than infectious packets of genes. To reproduce they hijack healthy cells and turn them into viral production lines that churn out millions of new viral particles, which is how the infection spreads.

WHAT HAPPENS WHEN YOU ARE FIRST INFECTED WITH HSV ?
The first time someone encounters HSV, known as primary infection, they don't develop a classic cold sore like lesion, which is why many people often don't realise that they have been infected. Instead, most cases of primary herpes affecting the face present with a nasty sore throat, a sore mouth (which can occasionally ulcerate), swollen neck glands, and a temperature. Similarly, primary infection in the genital region usually produces a painful, red, ulcerating crop of lesions that can spread over a wide area and may involve the perineum and anus. Genital infection can also be associated with temporary numbness in the affected area, swollen glands in the groin, difficulty passing urine, and a temperature. Occasionally, primary infections such as these can also trigger viral meningitis.

WHY HSV INFECTION LASTS A LIFETIME
As HSV spreads through infected tissues it also penetrates nerve fibres which inadvertently provide the virus with the neurological equivalent of a getaway car. Indeed, as the immune system moves in to control the infection, the virus conceals itself within nerve cells and slips away from the scene by hitching a ride on a special transport system that nerves use to move materials from one end to the other.

In this way the virus is carried to the nerve 'cell body' in a swelling called a ganglion located close to the spinal cord. In the case of infection on the mouth or face this ganglion is known as the trigeminal ganglion, and in the case of genital herpes the 'sacral' ganglia are involved. When it reaches the cell body, the viral DNA is added alongside the nerve cell's own DNA in the nucleus. It remains there, hidden within the nerve cell and in an inactive state, for the lifetime of the infected individual. The purpose of this process is to provide a reservoir of virus within the body which can periodically be 'reactivated' to spread the infection to other susceptible individuals.

SO WHAT CAUSES YOU TO DEVELOP A COLDSORE ?
A number of things can trigger the virus to reactivate including being stressed or run down, menstruation, drugs that suppress the immune system, and skin damage including burns caused by the sun, heat, or chemicals.

In some way these 'stimuli' reawaken the virus and it begins to make new particles from the recipe stored in the viral DNA hidden in the nerve cell. These newly-assembled viral particles are then shipped back down the nerve fibre to the region of the skin that it supplies - for instance around the lips. The virus 'buds off' from the nerve ending and infects the surrounding epithelial (skin) cells, producing a painful cluster of pale blisters which are crammed with herpes simplex virus and highly infectious.

When this process first begins to happen, and before the blisters appear, most people notice a mild tingling sensation on the patch of skin supplied by the affected nerve cell. Soon after they form the blisters break open, releasing their infectious cargo, leaving a red raw patch - the cold sore - which measures about half a centimetre across and takes about 7 to 10 days to heal up.

How often the virus reactivates varies from one person to the next but, as a general rule, recurrences tend to occur most often during the year following infection, and then they tail off.

Significantly, cold sores and genital lesions remain infectious until they have crusted over, so contact should be avoided during this time because the virus can be transmitted to other parts of the body, and to other people, especially between the mouth and the genitals. Cold sores and genital lesions also create a breach in the skin's natural defences, producing portals of entry for other infections, like HIV, so extra care should be taken to minimise the risk of any exposure.

Between 5-20% of the population of western countries are affected by genital herpes, and the prevalence is increasing, making this one of the commonest sexually transmitted infections. Traditionally, most genital infections were caused by HSV-2, but more recently there has been a large increase in the number of cases caused by HSV-1, mainly due to changing sexual practices, and particularly oral sex.

COMPLICATIONS OF HERPES INFECTION
Apart from cold sores and genital disease, herpes simplex viruses can also cause more serious infections, although fortunately these are relatively rare.

The most important are HSV meningitis (a form of aseptic meningitis), HSV encephalitis (HSV infection of the brain), neonatal herpes (HSV infection in the newborn acquired from the mother around the time of birth), corneal ulceration, scarring, and visual impairment following eye infection, and more severe generalised infections amongst those with weakened immunity. Such patients include people with HIV, and those on immunosuppressive drugs (for instance transplant patients), who tend to suffer worse recurrent disease, and are also more likely to develop drug-resistant forms of the virus.

DIAGNOSIS
Herpes affecting the face (orolabial herpes) is usually diagnosed clinically - that is, the diagnosis is made solely on the basis of the symptoms. But in the case of suspected genital herpes, HSV affecting the eyes, or more severe skin outbreaks, it can be useful to confirm the diagnosis by means of a variety of laboratory tests which are outlined below.

Traditionally, herpes infection is confirmed by taking a swab from an active lesion, growing the virus in the laboratory, and then using colour-coded antibodies to pinpoint whether HSV-1 or HSV-2 is the culprit. This method can be useful in confirming the presence of asymptomatic shedding of the virus.

Another way, which is faster but yields less information, is to use an electron microscope to look for viral particles in fluid collected from the blisters.

More recently, however, many laboratories have moved to using a highly accurate DNA test which can rapidly pick up the presence of the virus in a sample, and at the same time tell whether it is HSV-1 or HSV-2. This approach is particularly useful in the diagnosis of viral meningitis, or encephalitis, caused by herpes infection. In these instances a sample of cerebrospinal fluid (CSF), the watery substance that bathes the brain and spinal cord, is collected by lumbar puncture, and analysed.

Doctors also sometimes take a blood sample, particularly in people with a history of possible herpes infection but no active lesions, in order to look for herpes antibodies. The benefit of this kind of blood test is limited, but it can sometimes be used to confirm whether a patient has been infected with herpes previously, and which type of virus they are carrying.

MANAGEMENT
Herpes causes a lifelong infection and there are currently no treatments capable of removing the viral DNA from the nerve cells that carry it. This means that treatment focuses on reducing the intensity of a primary infection, and the frequency and severity of subsequent viral reactivations.

COLD SORES
Prevention :
If you are prone to cold sores try to avoid the things that trigger recurrences - - When skiing or sunbathing use high-factor sun creams to avoid sunburn.

• Try to avoid becoming run down.
• Eat a healthy diet including plenty of fresh fruit and vegetables.

Treatment :
Uncomplicated orofacial herpes (cold cores) responds well to topical aciclovir cream (Zovirax), which is available over the counter. It is extremely safe (including during pregnancy) and can reduce the duration and severity of a recurrence. It should be applied as soon as the tell-tale symptoms heralding a cold sore appear. Warning signs usually include localised pain, or a tingling sensation on the lip. But remember, cold sores remain infectious until they have crusted over.

GENITAL HERPES
Genital infection with HSV also places partners and babies at risk, meaning that appropriate counselling, contact tracing, and exclusion of other co-existent infections play an important part in the management of this condition. For this reason, patients with genital herpes should be referred to a genitourinary (GU) medicine clinic for appropriate investigation and follow up. With any sexually transmitted disease it is always important to exclude the presence of other infections which may have been picked up at the same time as HSV, especially chlamydia which is very common, highly infectious, often symptom-free, and (left untreated) can lead to infertility.

Prevention :

• Always use barrier methods of contraception (e.g. a condom).
• If you have a partner with known genital herpes, try to avoid intercourse whenever they experience a recurrence.
• Avoid oral sex when you, or your partner, have a cold sore - the virus is readily transmitted from the mouth to the genital area, and vice versa.
• Like cold sores, genital lesions remain infectious until they have crusted over.

Treatment :
Initial (primary) infection with genital herpes can be extremely painful and very distressing, but prompt presentation to a doctor can help through the administration of antiviral drugs, and pain relief.

General measures to reduce discomfort :

• Bathing with saline - soaking the affected area in salt water can reduce pain.
• Analgesia - simple painkillers such as paracetamol provide effective relief.
• Topical anaesthetics - these can be very effective but should be used carefully owing to the risk of potential sensitisation to the agent.

ANTIVIRAL DRUGS
The drugs aciclovir, valaciclovir and famciclovir have all been shown to be effective at reducing the severity and duration of infection and, in general, they are more effective the earlier they are started. Ideally they should be introduced within 5 days of the start of the episode and continued for at least 5 days, or while new lesions are forming, whichever is the longer. On the grounds of cost, oral aciclovir is usually the drug of choice.

These antiviral drugs work by blocking the ability of the virus to copy its DNA, preventing it from growing. The agents themselves are active only in virally-infected cells, so healthy cells are not affected.

The drug molecules resemble one of the building blocks used to make new DNA but, critically, they lack a certain chemical group which is required for a DNA chain to continue growing. So when the virus inserts one of these drug molecules into its DNA, the DNA chain is prematurely terminated, stopping the virus from growing.

In general, oral agents are extremely well tolerated, have few side effects, and are more effective than topical agents. Trials have also shown that combining oral and topical medications is no better than oral medication alone.

IMMUNOCOMPROMISED PATIENTS
Patients with HIV, or other immune-disabling conditions such as organ-transplant recipients, are at increased risk of developing severe (and sometimes life-threatening) infections. They should receive prompt antiviral therapy which should be continued until fresh lesions have stopped appearing, and the existing lesions have crusted over. Lesions which are not responsive to therapy might be due to drug-resistant forms of herpes. Under these circumstances it may be necessary to switch to another class of antiviral drugs, and to collect samples of the virus for drug susceptibility testing.

RECURRENT GENITAL HERPES
Most HSV recurrences occur in the year following infection, and then the frequency of reactivation tends to tail off. But for some patients recurrences remain a problem and they may require regular use of antiviral agents.

For patients with infrequent herpes reactivations the condition can be controlled effectively by using oral antiviral medications, chiefly aciclovir, whenever they experience a recurrence. When used in this way, known as episodic therapy, antivirals have been shown to reduce the duration of symptoms by 1-2 days, and the clinical severity of the outbreak.

But patients with more frequent recurrences (6 or more per year) often benefit instead from 'suppressive therapy', which means taking antiviral medications every day to prevent the virus from producing clinical symptoms. In other words, whenever it tries to reactivate, the virus is immediately switched off by the antiviral agent. Again, aciclovir, valaciclovir, and famciclovir have all been shown to be effective at preventing recurrences, but this course of action must be balanced against the inconvenience and costs of taking regular medication. Again, on cost-grounds, aciclovir is usually the agent on choice.

Most doctors advise stopping suppressive therapy after a year in order to re-assess the activity of the disease, and to reduce the risk of developing viral resistance to the antiviral drugs. Because the clinical course of the condition varies between patients, treatment is tailored to the requirements of the individual, and based upon the severity and frequency of their symptoms.

GENITAL HERPES IN PREGNANCY
Genital herpes can be dangerous for the newborn, but the risks can be minimised by careful medical management. All women who develop new genital herpes during pregnancy should be referred to the genitourinary medicine clinic in order to exclude the possibility of other infections, and for advice on treatment. Aciclovir has been used extensively during pregnancy, it is well tolerated, and in over 20 years of use there have never been any reports of foetal toxicity or birth defects. It is not contraindicated in cases of primary genital herpes occurring during pregnancy.

All women with first-episode genital herpes lesions at the time of delivery are advised to deliver by caesarian section because the risk of transmitting the infection to the newborn under these circumstances is 40%. But caesarian is not recommended for women who contract HSV during the first or second trimesters, or for women with a past history of genital herpes but without any signs of recurrence, because the local infection will have cleared by the time of delivery, and protective antibodies will have been produced against the virus. These antibodies will be passed to the developing baby before it is born, greatly reducing the risk of transmission. The baby should, however, be monitored closely when it is first born for any signs that it may have picked up the infection, in which case treatment with intravenous aciclovir should be started immediately.

EYE INFECTIONS
Herpes infection involving the eye usually presents as single, sore, red eye which is extremely sensitive to the light. Often the virus attacks the cornea producing a dendritic ulcer which doctors can see by adding some coloured drops and examining the eye with a slit lamp. If these ulcers are allowed to recur (like the ocular equivalent of recurrent cold sores) they can lead to corneal scarring, opacity, and blindness. They should be treated aggressively with pain relief and aciclovir (or a topical equivalent), which can also be used to prevent recurrent lesions.

MENINGITIS AND ENCEPHALITIS
HSV can occasionally trigger aseptic (viral) meningitis. Patients usually complain of a severe headache, neck stiffness, nausea, fever, and a dislike of bright lights. Unlike meningitis caused by a bacterial infection there is usually no skin rash. Anyone with these symptoms should see a doctor urgently. Cases of HSV meningitis usually resolve rapidly with intravenous aciclovir therapy, and without long term consequences.

A very rare manifestation of HSV is encephalitis in which the brain tissue itself becomes infected by the virus. There are very few warning signs, but patients with encephalitis tend to become confused and drowsy. Without prompt treatment with intravenous antivirals (usually aciclovir) the condition is often fatal, and even when treated rapidly often causes long term neurological problems including memory loss and epilepsy.

ON THE HORIZON
Scientists are currently trying to identify the chemical signals responsible for providing the wake up call which causes the latent (inactive) viral DNA to reactivate and produce recurrent disease. Pinpointing these cellular messengers, or the means that the virus uses to detect them, would provide scientists and drug manufacturers with new targets to aim at in their search for novel antiviral agents capable of preventing reactivation, shedding and transmission of herpes infections.

But with no solution presently on the horizon, we will just have to cross our fingers, and possibly our legs, and hope that the answer is not too far away.

Chris Smith

Bio-plastics: Turning Wheat And Potatoes into Plastics

In the past, fields of wheat and rows of potatoes were seldom destined for anything more than a rumbling tummy. But bio-products have come a long way since people first branched out into weaving hemp into clothes and pulping papyrus into scrolls. Today the line between Mother Nature and man made has never been more blurred. Animals are re-engineered into living drug factories, crops fuel our cars and now plants are increasingly being repackaged as the epitome of the synthetic world – plastic. Wheat, maize, vegetable oils, sugar beet and even the trusty spud are finding new life as water bottles, car fuel lines and laptops.

Wheat, maize, vegetable oils, sugar beet and even the trusty spud are finding new life as water bottles, car fuel lines and laptops.

Bio-plastics harness the natural structures found in crops or trees, such as slightly modified forms of the chains of sugars in starch or cellulose, that share the ability to be easily reshaped that has made conventional oil based plastics so useful. Bio-materials scientists are also constantly tweaking these natural structures to try and better replicate the durability and flexibility of conventional plastics.
Global business is now turning to bio-plastics for an increasing number of applications, as consumers and governments demand cleaner alternatives to petroleum based technologies and their reckless production of the greenhouse gas CO2.

Worldwide players, such as DuPont and Toyota Motor Corp, are making vast investments in new technologies and processing plants with the hope of cornering a multi-billion pound industry.

The "BC" at Bangor University in North Wales has 18-years experience of working with large companies and Non-Governmental Organisations (NGOs) to find sustainable and viable bio-based alternatives to man-made materials.

BC director Paul Fowler points out that “practically anything that you can find as polyethene you can find as a bio-plastic. You are talking about a whole range of everyday products - cups, combs and wrappers, everything you can think of is out there. There are inroads being made all the time - on the one hand there is research into trying to get biological alternatives to replicate the properties of conventional plastics and on the other hand people are looking at the natural properties of these plants and trying to find an application for them. Most of the manufacture is happening in the US and continental Europe. The UK is a producer of wheat starch and biotimber but the only major bioplastic producer is Innovia Films in Cumbria, which produces cellulose films.”

Innovia Films has an annual turnover of £400m, employing 1,200 people worldwide and producing more than 120,000 tonnes of film – used in packaging to protect food. Japan is also forging ahead, from the leading role in bioplastic production played by Toyota to its recent passing of a triumvirate of laws pushing forward environmental initiatives.
In South Korea too there is a rapid drive to replace conventional plastic packaging with polylactic acid bio-plastics.

Fowler says bio-plastics also offer an opportunity to get a double return for the energy used in their manufacture – first as a useful item and secondly as a fuel source. “My view is that we should burn them at the end of their life to recover energy, which could be then used to produce new materials,” he said. “In the first instance you have a valuable resource can use, be it as packaging or a shopping bag, and then you are also getting some energy back at the end of it. The biggest advantage of such bio-materials is the reduction of CO2 emissions in their production over petrochemical-based plastics.”

He also suggests that burning bio-plastics would also avoid the problems caused by them breaking down and producing methane, which is 25-times more potent as a greenhouse gas than CO2.

The BC is currently looking at developing naturally-derived alternatives to phthalates, which are plasticisers added to PVCs to make them more flexible in products such as electrical cable flex. It follows concerns that phthalates are metabolised in the body into substances that can mimic the body's own hormones, including those concerned with fertility. The centre is also developing bio-resins, natural alternatives to synthetic resins such as phenol and formaldehyde.

What types of bioplastic are there?
The common types of bio-plastics are based on cellulose, starch, polylactic acid (PLA), poly-3-hydroxybutyrate (PHB), and polyamide 11 (PA11). Cellulose-based plastics are usually produced from wood pulp and used to make film-based products such as wrappers and to seal in freshness in ready-made meals.

Thermoplastic starch is the most important and widely used bioplastic, accounting for about 50pc of the bio-plastics market. Pure starch’s ability to absorb humidity has led to it being widely used for the production of drug capsules in the pharmaceutical sector. Plasticisers, such as sorbitol and glycerine are added to make it more flexible and produce a range of different characteristics. It is commmonly derived from crops such as potatoes or maize.

FOMA(TM) N701iECO phone made of PLA bioplastics reinforced with kenaf fibres developed by NEC, UNITIKA and NTTDoCoMo © Paul Fowler

PLA is a transparent plastic whose characteristics resemble common petrochemical-based plastics such as polyethylene and polpropylene. It can be processed on equipment that already exists for the production of conventional plastics. PLA is produced from the fermentation of starch from crops, most commonly corn starch or sugarcane in the US, into lactic acid that is then polymerised. Its blends are used in a wide range of applications including computer and mobile phone casings, foil, biodegradable medical implants, moulds, tins, cups, bottles and other packaging.

PHB is very similar to poylpropylene, which is used in a wide variety of fields including packaging, ropes, bank notes and car parts. It is a transparent film, which is also biodegradable. Interest in PHB is currently very high with companies worldwide aiming to expand their current production capacity. There are estimates that this could lead to a price reduction below five euros per kilogram but this would still be four times the market price of polyethylene in February 2007. The South American sugar industry has commited to producing PHB on an industrial scale.

PA 11 is derived from vegetable oil and is known under the tradename Rislan. It is prized for its thermal reistance that makes it valued for use in car fuel lines, pneumatic air brake tubing, electrical anti-termite cable sheathing and oil and gas flexible pipes and control fluid umbilicals. These are often reinforced with fibres from the kenaf plant, a member of the hibiscus family traditionally used to make paper, to increase heat resistance and durability.

At the cutting edge of bioplastic technology lie polyhydroxyalkanoate (PHA) materials. These are derived from the conversion of natural sugars and oils using microbes. They can be processed into a number of materials including moulded goods, fibre and film and are biodegradable and have even been used as water resistant coatings.

What are the benefits of bio-plastics?

- Reduced CO2 emissions.
One metric ton of bio-plastics generates between 0.8 and 3.2 fewer metric tons of carbon dioxide than one metric ton of petroleum-based plastics. Electronic giant Sony uses PLA in several of its smaller components, including one of its new walkmans, but in future hopes to use PLA-based polymers to reduce its carbon dioxide emissions by 20pc and non-renewable resource input by 55pc compared to oil-based ABS.

- Rising oil prices
Despite currently costing more to produce than conventional plastics bio-plastics are becoming more viable with increasing and instability in oil prices, which are in turn triggering spikes in conventional plastic costs, illustrated in a sharp upturn two years ago. Dwindling oil supplies means that man will eventually be forced to turn to a sustainable basis for plastics.

- Waste
Bio-plastics reduce the amount of toxic run-off generated by the oil-based alternatives but also are more commonly biodegradable. The US’s second largest biopolymer producer Metabolix, of Cambridge, Massachusetts, claims that its plastics are biodegradable in composting bins, wetlands and the oceans. On the flip side not all bio-plastics are biodegradable and there are a growing number of conventional plastics that can naturally break down. The downside of their biodegradability is the methane that can be released as the bio-plastics decompose is a powerful greenhouse gas.

- Benefit to rural economy
Prices of crops, such as maize, have risen sharply in the wake of global interest in the production of biofuels and bio-plastics, as countries across the world look for alternatives to oil to safeguard the environment and provide energy security.

- Enhanced properties
In some fields engineered bio-plastics are now beating oil-based alternatives at their own game. Multinational materials giant Arkema has produced a form of Rislan PA11 that is being used in Europe and Brazil in fuel lines to carry biofuels as it is better able to withstand the corrosive effects of biofuels than oil-based alternatives such as polyamide 12. Rislan is widely used in oilfield applications as well as automotive brake lines. Elsewhere innovations in PA11 production are helping increase car passenger safety and reduce the risk of accidents by inhibiting spark ignition in the fuel lines. US car giant General Motors has replaced its non-conductive fuel-pump modules for new North American car models as it felt it was the best material for the job. In the US chemical multinational DuPont says it has developed a bioplastic derived from corn sugar that has superior stiffness and strength to its naturally based competitors. Global electronics corporation NEC has produced a kenaf-reinforced laptop casing, made of 90pc PLA, which helps reduce overheating by conducting heat better than stainless steel coupled with high temperature resistance and increased strength.

Who are the flagwavers?
Bio-plastics are not being produced by a group of hippies brewing up in their garage. Some of the world’s largest companies including multi-billion dollar chemicals company DuPont, car manufacturer Toyota, UK-based Innovia, US food processing behemoth Cargill and electronics giants NEC and Fujitsu are pouring money into driving the technology and production forward.

NEC and its partners Unitika and NTT DoCoMo produce mobile phone and laptop casings based on plant-derived bio-plastics, mostly PLA. NEC plans to expand its green credentials by substituting more than 10pc of the oil-based plastics in its electronic products with bio-plastics by 2010.

Toyota Motor Corp uses mainly PLA bio-plastics, derived from sweet potatoes corn and sugar beet, reinforced with kenaf to produce components for its cars such as the Prius and Lexus. It hopes to grow its bio-plastics division into a four billion yen business by 2020 and capture two thirds of the global market for petroleum free plastics.

Fujitsu introduced its FMV BIBLO notebook PC series two years ago, which it has manufactured using a material called Ecodear, a combination of 50 pc PLA and an oil-based plastic. Fujitsu is now developing a castor oil derived PA 11 plastic with Arkema, which is more flexible and will help expand its use of bio-plastics in notebook computers. The material can withstand repeated bending thanks to scientists weakening the interaction of the chain molecule in PA 11 and relaxing the stereoregularity of their organisation. The improved durability means its prototypes of PC cover components consist of 60-80 percent of the new bioplastic, an unprecedented achievement to date. Fujitsu is also using high density fillers to increase strength and extend its use into notebook covers and other applications requiring high impact resistance. The new material is expected to cut carbon dioxide emissions by 42pc compared to oil-based nylon 6/6.

DuPont in particular is continuing to expand the market for bio-plastics and plans to continue to offer hybrid bio/conventional plastic materials until the market matures, which could eventually cost less than the oil-based alternatives. DuPont has teamed up with sugar giant Tate & Lyle to build the world’s largest aerobic fermentation plant in Loudon in Tennessee in the US for the production of bio-PDO, with a capacity of 45,000 metric tonnes a year.

The largest commercial producer of bioplastic in the US is NatureWorks, owned by Cargill. The company’s plant in Blair, Nebraska uses corn sugar to produce PLA plastics packaging material and its own Ingeo-brand fibres.

What lies ahead?
With US President George Bush’s recent pledge to produce 35 billion gallons of renewable and alternative fuel by 2017 - driving the price of maize up 60pc in the past two months - the farmer’s field is fast turning into a high tech bio-battleground.

Mr. Fowler warns that the still fledgling industry will have to fight for space and commercial viability as millions of hectares are given over to corn, rapeseed and sugarbeet for bio-fuel production. "There is a real tension between the use of agriculture for fodd versus plastics and other non-food uses and this whole move to produce new fuels," he said. Whereas only two years ago plant materials were at the cheap end of the market and bio-products such as straw had little value, now it is really much more costly. There would have to be a step change in the extent of the production to match oil-based plastics. The amount of bioplastics produced worldwide is less than 200,000 tonnes a year; contrast that with the more than 30 million tonnes of oil-based plastics. You can see we have a long way to go before they replace conventional plastics".

Nick Heath

Biomimetics: Borrowing from Biology

The idea of looking to nature for inspiration is a notion perhaps most notably associated with the arts, particularly painting and poetry. But Mother Nature isn't a muse exclusive to the artist; she can also inspire scientists, engineers and industrialists.

Nor is the concept of borrowing from biology new to us. More than 3000 years ago the Chinese craved a synthetic silk, and more recently the Wright brothers based the designs for their planes on birds' wings. George Mestral grasped the concept for his invention, Velcro, from the burrs that stuck to his dog’s coat, and the unique, super-efficient cooling system of the Eastgate Centre in Harare, Zimbabwe, is modelled on the system of ducts and passages used by termites to maintain a constant temperature in their mounds. It's on these foundations that the field of biomimetics has been built, and over the last 15 years it's gained momentum rapidly.

Also known as biomimicry and bionics, biomimetics can be defined as "the abstraction of good design from nature" and came about when engineers and medical researchers realised that many of the answers they sought were already available in nature. For example, why spend many years and colossal amounts of money trying to design a new building material from scratch when the chances are there is something in nature that can already do most of what you want? Better still it's likely to have been refined to near perfection during millions of years of evolution.

So, with a little ingenuity and some modifications, a once challenging problem can be elegantly resolved. Exploiting nature and avoiding the pitfalls that have already been ironed out by evolution is precisely what Thomas Speck of The University of Freiberg did when designing the "Technical Plant Stem", a novel material combining features from the stems of the giant reed (Arundo donax) and Dutch rush (Equisetum hyemale).

Inspired by the observation of these plants standing tall, swaying in the wind and yet never appearing to break, this new material combines both stiffness and elasticity with a resistance to breakage and has the potential to be used in the fabrication of a wide range of applications from building materials to snowboards.

This relatively new scientific field of Biomimetics is especially interesting as it brings together researchers from all disciplines to generate solutions to a vast array of problems and appears to be limited only by the imaginations of those involved.

Geckos, glue and sticky tape
Geckos are amazing creatures with the ability to walk up the smoothest of surfaces and even on ceilings, but quite how these lizards achieve their adhesive properties eluded scientists for a long time. One suggestion was that, just like cartoon villains with suction cups strapped to their hands and feet, the geckos used suction to adhere to walls. This was ruled out when these sticky little creatures were still able to cling on tightly in a vacuum. Instead, since even the smoothest of surfaces have microscopic undulations, it was suggested that the geckos used friction to climbs walls, but this couldn’t explain why they are able to walk on ceilings. Another hypothesis was that, like the cockroach, they exuded a glue-like substance from their feet, but this was not possible as their feet are dry and free from the glands required to excrete such a substance.

The answer to this conundrum came about in 2000, when Professor Full and colleagues at UC Berkley looked more closely at the toes of the Tokay Gecko (Gecko gecko). They discovered that each of the gecko’s toes were covered in thousands of tiny "nano-hairs", called setae, each less than one tenth the thickness of a human hair. At the end of each seta were hundreds to thousands of minute mushroom shaped structures called spatulae. The gecko’s super adhesive abilities are achieved because these minuscule structures allow the geckos feet to get so close to the surface, such as a wall, that the molecules of the spatulae and the surface are able to interact electrically. This generates tiny forces, known as van der Waals attractions, that lock the two surfaces together. Although individually they are extremely weak, with billions of molecules interacting with each other the combined force is more than ample for the Gecko to stick to pretty much any surface. If your own hand had the same sticking power, it would be able to hold about 40kg.

Once the mystery of the sticky footed gecko had been solved, the applications of this knowledge to technology were rapidly realised. Within three years a group of scientists from the University of Manchester, lead by Professor Geim, had produced a sticky tape that consisted of microscopic hairs of polyimide which mimicked a gecko’s toes. This sticky tape was believed to be as effective as the real thing, and the researchers were not short of offers from Spiderman wannabes who volunteered to be hung from the lab window by the tape. Unfortunately, the would-be spidys' dreams were never realised, mainly because of the lengthy and expensive process used to produce the tape.

	100g. This toy has been attached to several surfaces before this photo was taken." style="border: medium none ; padding: 0px; width: 202px; height: 356px;" title="Spiderman toy hanging from a glass plate, attached using the tape with a contact area of approximately 0.5cm2 with a carry load of >100g. This toy has been attached to several surfaces before this photo was taken © Andre Geim, University of Manchester">
Figure 1a: Scanning electron microscope image of a 1cm2 section of the Gecko-sticky tape.	Figure 1b: Spiderman toy hanging from a glass plate, attached using the tape with a contact area of approximately 0.5cm2.	Figure 1c: Bunching of the hairs is a problem that reduces the adhesive properties of the tape.

In 2006 BAE systems announced that they were able to generate a gecko-like adhesive using a modified version of photo-lithography, the method used to make silicon chips, that was economically viable and easy to scale-up. This super-adhesive was made using polyamide, like nylon, and like the design from Manchester consisted of mushroom shaped structures. While not as sticky as the gecko’s feet, it could quite comfortably stick an elephant to the ceiling, should you have any call to do so! However, unlike conventional adhesives, the gecko-inspired substance can be reused, easily peeling from the surface to which it was stuck, meaning that a Spiderman suit is now a possibility and no doubt likely to appear on a great number of childrens' (and adults') wish lists. The other advantage is that it doesn’t leave any sticky residues behind, so no more patches of blue fluff where something was once stuck. But there are still advances to be made, and the scientists involved hope to make this adhesive even stickier, so for now we’ll just have to wait and stick to using ladders for our window cleaning chores.

Leaves, Loos and the Lotus Effect
Despite preferring to grow in muddy rivers and lakes, the leaves of the Lotus plant (Nelumbo nucifera) remain clean and free of contaminants, even after emerging from the murky waters. This self-cleaning ability is believed to be why this plant is regarded as a symbol of purity in many Asian religions and has been the inspiration for many biomimetic inventions.

Instinctively you might think that smoother surfaces would be the cleanest, as grooves and ridges would only serve to trap dirt. However, on closer inspection two German scientists, Professors Barthlott and Neinhuis, revealed that the shiny detritus-free surface of the lotus leaf is anything but smooth. Scanning electron microscope images revealed that the leaves were very rough and covered in micro-lumps and bumps of protruding epidermal (outermost) cells, which were in turn covered in wax crystals around one nanometre (1 millionth of a millimetre) in diameter. The wax crystals are hydrophobic (water hating) and so they repel water droplets and help prevent wetting of the leaf surface. The combination of these micro- and nano-scale features greatly reduces the contact area between the surface and water molecules, which is the key to the cleaning process and explains how even a light rain shower is enough to wash the leaves clean.

Figure 2: The Lotus Effect. Water forms droplets on the tips of the epidermal protrusions and collects pollutants, dirt and small insects as it rolls off the leaf.

Instead of sitting flat along the surface of the leaf, the water only makes contact with the leaf at the top of the lumps (figure 2), which forces it into spherical droplets. Then, even with the slightest of angles, instead of sliding down the leaf surface the bead of water starts to roll and tumbles off the leaf picking up dirt particles and small insects as it goes. This process, called the Lotus Effect, is so efficient that even honey and water-based glues will roll straight off the leaves, leaving no trace behind.

So-well has evolution refined this system that even hydrophobic dirt particles, which would ordinarily repel water, are trapped by the rolling water droplet and washed away. This is because the particles on the leaves only make contact at the tip of the wax crystals and so do not adhere very well. This means that the energy required by the water to pick them up is much less than the energy required to stick them to the leaf and so they are washed off.

But this effective method of self-cleansing is not restricted to this sacred plant. It also operates naturally in cabbages, reeds and the wings of butterflies and dragonflies, and it has now been exploited by industry to produce several technologies including a water repellent spray developed by BASF. This agent uses nanoparticles and water resistant polymers such as polypropylene, polyethylene and wax that self assemble into tiny structures which can mimic the Lotus Effect. This spray can be effectively applied to a wide range of surfaces from masonry to textiles and leather. Other products in the same vein include Lotusan, a house paint that combines this effect with other characteristics of water-repellent paints, and a more water-efficient urinal that cleans itself using only a fraction of the water required by a regular facility.

I can't imagine many people wouldn’t be attracted by such technology: houses and windows that would clean themselves with every rain shower, shoes that no longer need polishing, clothes that shun dirt. And the technology can have a positive environmental impact too, dramatically reducing the water required to flush a toilet for example.

Blood clots, arteries and self-healing space craft
Nevertheless, inspirational as nature may be, not all biomimetic innovations are direct copies of their natural world counterparts. Instead, sometimes the concept provides the clue to a more advanced technological solution. Take the blood clotting system for example. When you cut yourself, it is not long before your blood clots to prevent further bleeding and a scab appears. Hidden and protected by the scab your body repairs the damage below and after a short period it is as good as new.

Figure 3a: Micro glass tubes used to contain the resin and setting agent.

So can a similar method be adopted to repair wounds in the skin of a spacecraft? Well yes and no. On the one hand a self-healing system would spare astronauts from having to attempt risky repairs in space, but a repair that worked on the relatively slow time-scale used by the body's clotting system would be of little practical benefit, so it would need to be speeded up.

With this in mind Drs Bond and Trask of Bristol University set about developing a composite material for use in space craft construction that would heal itself in the event of damage. Just as blood passes through tissues in tiny capillaries, the Bristol team have incorporated glass tubes (figure 3a), each only sixty microns (60 thousandths of a millimetre) in diameter, throughout the material (figure 3b). The tubes contain either a resin, or a chemical setting agent which triggers the resin to polymerise and set hard.

This arrangement means that if the material is stressed or cracked, the tubes will rupture, allowing the two "clotting" components to escape and mix. The resulting hard plug will block the breach and restore strength and integrity to the material. Indeed, by including a fluorescent dye to the tubes, it's possible to see the new hardened resin being deposited wherever the material was damaged (figure 3c).

Figure 3b: The glass tubes were set in the composite material in layers.

Although the inclusion of the glass "blood vessels" reduced the strength of the material by 16% and the healed section was only 87% as strong as the original, this piece of research demonstrates that the concept of self-healing materials is feasible and now research is on-going to produce stronger "healants". Also, unlike the mammalian vascular system where blood circulates and is topped up in the event of loss, the present system works only once. So the team are now looking at ways to allow circulation and re-filling of the vessels. And just as our own circulatory system plays a key role in transport and temperature regulation in the body, it may be that the vessels of the space craft could be used to serve similar purposes too, helping to keep down weight and save space.

Another feature of the mammalian response to wounding that would be useful in the vasculature of a space craft is bruising, which can indicate damage below the surface. Often fractures occur inside a composite material leaving no external sign of damage. But if a give-away "bruise" could be generated at the same time as the healant is deposited, it could be used to identify problem areas more speedily.

Figure 3b: Repairs are localised to the areas of damage as observed using a flourescent dye.

The idea of a self-healing spacecraft complete with vascular system may seem a little strange and even more advanced than many sci-fi movies, but with the speed at which these developments are being made it may not be too long before it becomes a reality.

The tip of the iceberg...
Sometimes inspiration can be gleaned from the strangest of places, such as worms inspiring the development of robots that could be used to carry cameras into your intestines, traffic systems modelled on the behaviour of ants, and the skunk cabbage that is revealing secrets of how to keep warm during the winter.

Perhaps the most quirky phenomenon that sparked some research was the observation of bullet-proof pheasants. Occasionally, a pheasant can be hit with shot from a shotgun and yet escape unscathed, possibly due to its feathers absorbing the shot’s energy. This sparked an interest in understanding the properties of the feather protein keratin and its potential use in high-velocity impact protection, such as bullet-proof vests.

Other bio-inspired inventions include the sharkskin swimsuit, worn by 28 of the 33 gold medal winners at the swimming events in the 2000 Sydney Olympics. The swimsuit was designed to channel water over the body in the same way that a shark's skin does, reducing drag. Researchers have also been looking at the humble pine cone for other clothing ideas such as anti-sweat ventilation flaps that open and close in response to moisture when things get a bit sweaty. Penguins are also helping to keep polar explorers warm thanks to synthetic insulators based on their feathers; the breakthrough here is that, unlike down, they don't lose their insulating capacity when they become wet.

Where the next invention or moment of inspiration will come from, is virtually impossible to predict, but nature appears to have an inexhaustible supply of answers. All we need is a little ingenuity an open mind.

Becky Poole

How The Lymphatic System Works

The lymphatic system is an offshoot of the cardiovascular system and comprises lymphatic vessels, lymph nodes, lymph (the fluid they contain) and lymphocytes (immune cells). Lymphatics were first seen by Hippocrates in 400BC as vessels containing ‘white blood’, but the lymphatic system was not properly described until the 1600s, around the same time that William Harvey published his detailed description of the blood circulatory system.

Figure 1 - The lymphatic system ©St. George's, University of London

Whilst our understanding of the blood circulation progressed rapidly, the lymphatic system was regarded as a simple drainage system and largely ignored. It is only in the last 20 years that lymphatic research has really progressed. It's now clear that the lymphatic system is far more than a simple drainage network and instead comprises a complex system involved in many conditions, ranging from cancer to asthma. This article explores the essential role that the lymphatic system plays in tissue fluid regulation. A disturbance in this regulation can cause fluids to accumulate in tissues, leading to swelling or lymphoedema, a condition which presents us with many unsolved puzzles.

The essential role of the lymphatic system in tissue fluid volume regulation
The lymphatic system has several key roles including transporting fats absorbed from the gut, priming the immune system during infections bv carrying material to local lymph nodes and regulating tissue fluid volume.

Tissue fluid (also known as interstitial fluid) forms when water and proteins filter through tiny channels in the walls of small blood vessels, called capillaries, and enter the surrounding tissue.

Figure 2 - Chronic venous disease resulting in oedema. ©St George's, University of London

In general, fluids filter out of the capillary at a rate determined by pressures on either side of the wall. These pressures (‘Starling forces’) are exerted by the fluid and by protein, on both sides of the wall. All the body’s cells are bathed by 10-12 litres of interstitial fluid compared with a blood plasma volume of only 3 litres. In order to keep the volume of fluid in the interstitial compartment constant, excess interstitial fluid and large proteins must be returned to the blood stream. This process is carried out almost entirely by lymphatic vessels.

Excess interstitial fluid first drains into small, thin walled lymphatics (initial lymphatics) and then into larger lymphatics. Larger lymphatics possess valves to ensure that lymph flow is one-way and have muscular walls which can pump the interstitial fluid (now termed lymph) towards lymph nodes. Lymphocytes within lymph nodes police all fluid which passes through them and an immune response may be initiated if a foreign body is encountered (this is why our lymph nodes e.g in the neck, may swell when we are unwell). After exiting the lymph nodes, lymph empties into the blood circulation via connections to veins in the neck.

What is the difference between oedema and lymphoedema?
As the lymphatic system is essential to the regulation of tissue fluid volume, any impairment is likely to lead to a build up of fluid and protein. This can manifest as swelling (oedema). Both oedema and lymphoedema manifest as swelling but the two conditions have distinct causes.

Many of us notice that our feet swell during a long haul flight and this is because the capillary filtration rate is temporarily exceeding the ability of the lymphatics to remove fluid. This however, is normal and will disappear over time. Clinical oedema is caused by a sustained excess of fluid filtering across the capillary wall. The lymphatic system will work harder to remove this excess fluid but eventually it becomes overwhelmed and fails, resulting in swelling. This excess in fluid filtration can occur as a result of a variety of conditions including: malnutrition, renal failure, heart failure and inflammation. The oedema can usually be cured if the underlying cause is identified and treated.

Figure 2 shows a patient with leg swelling caused by chronic venous disease, which is sometimes caused by deep vein thrombosis, varicose veins or chronic heart failure. This condition causes capillary filtration to be increased over a sustained period. The lymphatics are overwhelmed and this leads to an excess of interstitial fluid and oedema (swelling).

Types of Lymphoedema
There are two broad categories of lymphoedema:

Figure 3 - Milroy disease (leg swelling and associated skin changes) ©St George's, University of London

Primary Lymphoedema can be genetically pre-determined but can also develop later in life with no discernable cause. Primary refers to the fact that the lymphoedema is caused by an inherent defect, which may include under-development, in the lymphatic system. For example, there may be too few lymphatics or malfunctional lymphatics which do not pump properly or have faulty valves. Primary lymphoedema is relatively rare. Two examples of primary lymphoedema, in which the genetic abnormality has been identified, are:

A. Milroy disease. This involves lower leg swelling, present from birth (1 in 6000 births) (figure 3). It is caused by mutations in a gene responsible for embryonic lymphangiogenesis (lymph vessel development). As a result, lymphatics fail to develop properly, particularly in the leg.

B. Lymphoedema Distichiasis. This involves leg swelling (figure 4) and is caused by mutations in a lymphatic developmental gene called FOXC2.
As a result, the valves of large lymphatics become incompetent allowing lymph to flow backwards. This impairment in lymph flow is exacerbated in the upright position as the lymph also has to work against gravity. Surprisingly, this condition is associated with a double row of eyelashes (distichiasis) (figure 5), presumably because the lymphatics and the eyelashes have a common developmental origin. The double row of eyelashes is present from birth but the lymphoedema develops only after puberty. The reason for this is unknown but hormonal changes may be a contributory factor.

Figure 4 Leg swelling in Lymphoedema distichiasis	Figure 5 Double row of eyelashes associated with lymphoedema distichiasis

Figure 6 - Lymphoedema caused by Lymphatic filariasis

Secondary lymphoedema is much more common. The word secondary refers to the fact that the lymphoedema is caused by something external to the lymphatic system.

1. The commonest cause of lymphoedema is lymphatic filariasis which affects approximately 90 million people worldwide, mostly in developing countries. Lymphatic filariasis is caused by a nematode worm infestation that is transmitted by mosquitoes. These worms reside in lymphatic vessels and impair lymphatic function mainly in the limbs and scrotum, causing a lymphoedema associated with hyperkeratotic elephant-like skin (Elephantiasis) (figure 6).
2. In Western countries, the commonest cause of lymphoedema is cancer surgery. One example is surgery for breast cancer. In the UK, around 41,000 new cases of breast cancer are diagnosed each year. (N.B Breast cancer in men does occur but it is rare – approximately 300 cases are diagnosed per year). The lymphatics are the main routes for metastases of malignant breast cancer. Axillary lymph nodes (which are the lymph nodes in the armpit which receive lymph from the breast and upper body) are usually removed during breast cancer surgery. This means that they can be examined under a microscope to determine if the cancer cells have spread. In many cases, all axillary lymph nodes are removed (there are between 30 and 50). The removal of such nodes can obstruct lymph drainage, resulting in swelling. Arm swelling is particularly common but swelling can also affect the breast and upper body.

Figure 7 - Breast cancer-related lymphoedema of the left arm ©St George's, University of London

Breast cancer-related lymphoedema (BCRL) affects approximately 25% of breast cancer patients and can be exacerbated by radiotherapy which scars tissue and disrupts lymph drainage. Most women will undergo axillary surgery as part of the breast cancer treatment and will have lymph nodes removed from the arm and approximately one quarter of these women will develop BCRL.

Clinical features and management of BCRL
Breast cancer-related lymphoedema is incurable and the swelling characteristically worsens with time. The swollen arm can feel heavy and painful and the risk of infection and skin cancer is increased. BCRL is also associated with functional and psychological morbidity. Distress may be caused by clinicians whose primary focus is recurrence of the breast cancer and who may trivialise the lymphoedema because of its non-lethal nature. Some women have reported that the appearance of the arm is more distressing than living with a mastectomy. The latter can be easily hidden whereas a disfigured arm is a constant reminder of the breast cancer and a subject of curiosity to others.

Lymphoedema (unlike many cases of oedema) is incurable because underlying causes are irreversible and currently there is no drug or surgical therapies which improve lymph transport. Nevertheless, following an intensive treatment course combining Manual Lymphatic Drainage (a massage technique which encourages lymph drainage), compression bandaging (which limits the swelling) and exercise, the swelling can be reduced and controlled.

Puzzles in BCRL
The traditional and widely accepted view of BCRL is that damage to the axillary lymph nodes prevents lymph from properly draining out of the arm, much like a blocked drain, resulting in the swelling. However, this view explanation is too simplistic as it fails to fully explain certain puzzles which relate to BCRL. These include:

• Why do only approximately a quarter of women who have similar breast cancer treatment develop BCRL and why not all?

• Why can BCRL develop when just a single lymph node is removed and why does swelling not necessarily occur when all lymph nodes are removed?

• Why can the arm seem normal for months or years after surgery and then suddenly swell for no obvious reason? (Swelling has been reported to develop as much as 20 years after surgery).

• Why can certain parts of the arm be more swollen than other parts which may have no swelling at all? For example, sometimes the whole arm can be swollen whilst the hand is spared of swelling (figure 8) even though the hand and arm lymph drains to the same lymph nodes.

Current research into BCRL aims to solve these puzzles in the hope that management of the condition will improve and the swelling may be minimised or even prevented. Unless more can be understood about the mechanisms which cause the swelling, this incurable and debilitating condition is likely to remain a significant problem.

Stephanie Modi