NHS Together

NHS Together is a campaign that, to quote,

"brings together all the health service unions and staff associations together with the TUC.

It's a new campaign alliance of health staff. We want to raise the alarm at what is happening to the NHS and to press the government for honest and open discussion about its reform agenda.

The NHS has been getting better thanks to increased spending and the dedication and commitment of NHS workers to new ways of working.

But progress is under threat:

• Health trust deficits are causing cuts in patient care and staff jobs


• NHS staff support reform that delivers better patient care, but that has been replaced by untested rapid changes with no staff involvement.


• the fragmentation of the NHS threatens the NHS values that bind it together.
  

On Saturday 3 March NHS Together is planning a national day of action with the aim of sending a powerful message in celebration and defence of the NHS.

Here's the NHS Together website where you can find events in your local area.

For our sake, Lucia's, John's and everyone's, please please support it.

(And don't forget to sign the online petition).

To the Government - a Rant

As a youngster, as a student, I was “left-wing” (and still). I was notionally pro-Labour, anti-Conservative (or more accurately anti-Thatcher). Don't you remember wearing a Socialist Workers Party “Stuff the Jubilee “ badge at university in our (pretty pathetic) protest against the establishment? I wore it at school at the age of fifteen with pride. We've grown up since then ...

I received a loan-free university education (so did you), worked for the U.K. government, received another U.K. government discretionary grant to do a Masters and worked again as a VSO volunteer (an unofficial arm of U.K. aid policy as, although not government, it's c. 90% government funded). I am grateful.

I now work for our alliance partner, promoting our common goals (!). I am grateful.

I still firmly believe in the old education policy of giving tertiary education for free ... although when she abolished this, it wasn't enough to make me vote against Thatcher. I never voted. Labour was too right-wing for me. Then, as a long-term ex-pat with no residence in the U.K., I lost the right to vote.

The abolition of free tertiary education was shameful. Anyone with today's student loan burden/debt has my heartfelt sympathy ,,, and I apologise to you for not having voted.

Now the (Labour “left-wing”) government, that notionally I would vote for, threatens my National Health Service.

The NHS would probably treat me, illegally, without questions. It is treating my British Citizen (not her fault) daughter without questions illegally, and my wife and (unofficial) stepson (both non-British thanks to-Mrs Thatcher) illegally without questions. I am grateful.

The staff of the NHS, I praise and bow to you. Thank you also to all the people who have overlooked the illegalities (my embassy, the Foreign and Commonwealth Office, the Immigration and Nationality Directorate, the Department of Health and Social Security, the Department of Education and Science, our GP, our local primary school etc). Thank you especially to the woman in the local Primary Care Trust accounts department. Thank you for your humanity. Thank you for saving Kezia's life. I am very very very grateful.

And, thus, now I have the vote gain, and as a very small token of my appreciation, I will not be party to he reelection of the current administration.

Hi Lucia

Looking at the comments on John`s site, we certainly created a stir!

My next post is even heavier - hopefully tomorrow.

As a YOB you are by definition an "activist" - keep it up ! We, whether sufferers or carers, need to be empowered. I don´t know where to go from here, it is new to me and I/we are still finding our feet .

Take care.

NHS gripes

Lucia relates here how the NHS won't allow the nurse who runs the teenage group at our hospital in her own time to attend a Teenage Cancer Trust national conference as a carer for the group on NHS time.

On Blogging Cancer

There are various kinds of leukaemia and cancer blogs and websites. Obviously we all have our personal preferences to what we read and my cup of tea won't be the same as other leukaemia/cancer sufferers/carers (or anyone else for that matter).

First, on blogs in general – in normal circumstances I haven't got the time to go through all your archives to read the story from the beginning. And you haven't got the time to go through mine – so you're a new visitor and you will say “that's interesting“ to the current post and “can't be bothered” to everything else. We are selective in our reading.

Additionally, too long a list of links is a waste of time (to my thinking, I know John, Alex, Kathryn linked on right will disagree!) – I haven't got the time to visit every site you've listed. I'm much more likely to visit a link in a short list because I know you really go back to these sites again and again so they must be interesting. Equally there are lots of sites about cancer but since alot of the information out there is the same, there's not much point in linking to it. I'm keeping my link list short.

I'm also beginning to feel that perhaps the chronological format is somewhat limiting. For example, the posts I've written on drugs are educational to both myself and I hope other carers/sufferers – gradually they are going to get hidden away in archives. Yes, I know there is a labels list, but you'll have to scroll down and click to get to the post. A Drugs section would perhaps be more useful – for that reason I'm toying with the idea of a “proper” site (such as Patty Feist's Pediatric Oncology Resource Center or Auspicious Dragon) of which the blog is just a part.

Cancer sites and blogs come in a variety of overlapping flavours. But some common categories do emerge.

Charity sites: these come in various flavours. Some support scientific research, some are to support cancer sufferers and carers. The best are very informative (see the link to Leukaemia Research on ALL at right), alot provide only summary information on treatment, drugs etc. This is probably enough for many readers.

Scientific research: most of this is hidden away on overall medical research sites such as Biomed Central. There are some research groups which have sites, but these are generally networking sites for practitioners and researchers with news of meetings, projects etc rather than the actual results of research. What I'll term layman's science i.e. beyond summary information but not as turgid and specialist as scientific papers, is very hard to come by – information on the Pediatric Oncology Resource Center (link on right) is a notable exception.

Sufferers and carers: in general the best are by adult sufferers and the worst are by adult carers of young children.

The very best of the former do not limit themselves to their illness. They have diverse interests and write about these as well as their illness. They are often witty.They are often activists in some way or another (though they may not define themselves as such).They are not self-pitying and do not want your sympathy. They would probably be blogging even if they weren't ill.

Blogs by adult carers of young (alive and deceased) children are, I'm sorry to say, generally abysmal and certainly of little interest to the wider world. Such sites abound on the cancer webring to which this site belongs (link at bottom of page). Sure they are cathartic, sure they provide news to family and friends. But all too often, they are exercises in gushing sentimental self-pity. They are often characterised by horrible sickly sweet wallpaper, horrible gifs of bunny rabbits, angels etc and lots of links to sites of the same type. They may provide some other parents with comfort but I'm afraid they leave me cold. Worse – they make me want to vomit. I know how small children and their carers suffer, I don't need to hear about yours. Give me information and facts to help us get through this. Entertain me.

Teenage cancer sufferer blogs are a sub-category. Generally they are quite good as teenagers have the diverse interests of adults. Ok I might not know the pop-groups they are referring to but they talk about other things as well. And, of course, I'm not really their targetted audience.

There's my two ha'pence worth – like it or lump it.

“I reserve the right to go off topic and talk about anything I damn well like” .

UKALL 2003 - Escalating Capizzi II Update

Kezia had her third dose of IV Methotrexate yesterday as well as Vincristine. Seems to be tolerating the IV MTX alot more than last time - she finished the IV MTX at 80 mg/sq. m in Escalating Capizzi I and is now up to 130 mg/sq. m. Today she's due Peg Asparaginase - can't see any problems there. She's now suffering from photophobia.

The family saw snow for the first time last week - but not enough to make a snowman! Jaime loved it ... but Nanda wasn't so keen, too cold!

National Blood Service Protests - Update

I cannot see anything in the news about yesterday's protests about closing U.K. blood centres apart from this from BBC Birmingham. Anyone got any news?

National Blood Service - the St Valentine's Day Massacre

I read in the news today that there are plans to cut the number of U.K. blood centres from twelve to three. These centres match blood, platelets and plasma to individual patients. Protests at these cuts are planned today by the trade union Amicus. Here's their press release.

From our own experience I think these cuts are probably disastrous. We never know whether Kezia is going to need a transfusion until the analysis results come from the hospital lab. If she does need a transfusion, then a wait of up to three hours entails whilst the requisition is sent to the central Manchester blood centre, matched etc and then transported back to the Royal Manchester Children's Hospital. Then there's the transfusion itself.

Now Manchester blood centre is not one of those proposed to be cut. But say we were being treated in Birmingham, where it is proposed to close the blood centre, then the blood would have to come from London - and we would probably be talking about an overnight stay, occupying one of those beds in such short supply.

African Caribbean Leukaemia Trust

I have just found the African Caribbean Leukaemia Trust (based in the U.K.) and linked it on the right. It seems to be mainly involved in the registration of bone marrow and blood donors of African or Caribbean descent - who knows when we might need one ... but I hope never.

Malaria

John Crippen at NHS Blog Doctor has written about malaria prophylaxis for tourists not being covered by the NHS. I totally agree with you John.

Living in a high malaria zone and having had malaria too many times to remember (first time amost 25 years ago) I think I am somewhat qualified to comment.

Firstly, if you can afford to take a holiday in a malaria zone, then you can afford malaria medication. Secondly, if you don't, you put your once-in-a-lifetime holiday at risk. Five days into your fortnight's holiday you come down with it and, even if it's only a mild attack, your holiday is ruined.

MK Student in the post's comments complains that he is going to do community work in a hospital in Ghana and still has to pay for the medication. I did three years here as a VSO volunteer – VSO rightly picked up the tab for vaccinations and malaria prophylaxis. Any organisation sending people to malaria zones should do this – if they don't, they are irresponsible.

That said I don't take malaria prophylaxis any more – I've been here too long, I cannot take it my whole life. But most people here generally know the danger signs. If you have a fever, unusual aches, anything, you don't think the flu, you think malaria and get tested for it. You have to know how to bring your temperature down with paracetamol and cold showers as well - I've brought myself back from almost unconsciousness by lowering my temperature.

I also ensure I carry malaria treatment medication with me when I travel abroad - my first experience of malaria was six months after geting back to the UK in the early '80s - I sat at home for three weeks getting weaker and weaker trying to shake off the 'flu before heading back to my parents. Immediate hospitalisation and isolation. They even suspected leukaemia at one point! The second time I knew what it was but the doctor coudn't give me a prescription until the test results came back - several days. I believe awareness, diagnosis and treatment have improved alot since the '80s but if I have the medication on hand and the malaria strikes on Sunday night, I am prepared.

Yes, it is the biggest cause of death here, generally through people not treating it properly but public health campaigns, impregnated mosquito nets, changes to treatment regimes and most recently a country-wide insecticide spraying campaign are beginning to work now.

Side Effects

I said I should do a drug side effects post at the end of the Asparaginase post and Jessica left a comment that yes, I really should. So this weekend's offering ...

There are many resources out there dealing with side-effects of specific drugs so I won't try and reinvent the wheel but will talk in a more general way.

First off, most of these drugs are cytotoxins i.e. they are toxic, poisonous – to both bad and good cells. As well as killing the bad cells, they'll kill the good cells. Often they produce useless by-products that can do damage as well.

Many of the side-effects are common to several drugs. Both this and that and that may produce this or that or that side-effect. But there's no guarantee that you/your child will suffer any particular effect. What causes one person's hair to fall out, won't for another person.

So let's start with the common effects that everyone will suffer at some time or another (in no particular order):

Hair loss: everyone's hair falls out. Then it will start to grow back, and then you repeat the drug that caused it to fall out in the first place, and yes, you've got it, it falls out again. Kezia isn't bothered about it, (hey punk!), but for teenage girls it's a bit depressing. In the UK the NHS provides wigs. Lucia (a teenager) has some advice for teenagers on her Teenage Cancer site

Mucosis: sore and/or infected mouth. The degree to which this happens will vary from person to person. Kezia has suffered just a bit – soft foods and antiseptic mouthwash have been enough. H.'s mouth went green and she couldn't eat or drink. If it gets this far, they'll suspend the treatment that has caused it, put you on antibiotics and hydration.

Both of these occur because hair and mouth cells naturally reproduce and die very quickly compared to other cells so if you're killing them off even quicker, their reproduction cannot keep up with their loss.

Nausea and vomiting: they can give you an anti-emetic (anti-nausea) medication for this.

Stomach cramps, diarrohea etc: speaks for itself.

Odd eating habits: increased appetite, decreased appetite, manias for certain foods – at the end of Kezia's induction nothing but chips and roast chicken crisps! The glucocortisoids, dexamethasone and prednisone, are particularly good at increasing appetite leading to weight-gain and puffy faces.

Neural effects: tingling or pins-and-needles in limbs etc. At the moment Kezia has sensitive feet and doesn't want to walk.

Mood swings: depression and euphoria, temper tantrums, unco-operativeness, Irritable Bastard Syndrome, highs and lows. This is especially difficult with young children who cannot verbalise it and cannot rationalise it. As a parent carer you've got to be especially sensitive – what is normal childhood pain-in-the-neck, what is drug-induced, what is both, and then how do you draw the lines?

As an absent father, I don't have to deal with this very much. But Nanda does.

Infections: your white blood counts are low so you don't have the normal protection against infections. At the slightest sign of an infection, a temperature or whatever, into hospital, normal chemotherapy suspended and onto the antibiotics.

You will be warned that THIS WILL HAPPEN right at the beginning. It's normal. It's happened to Kezia now on two occasions.

You may need a blood and/or platelet transfusions. Even if you don't have an infection, if your blood counts are really low, then you'll get a transfusion.

With kids you really have to look out for chicken-pox – if someone at school, comes down with it, then you keep your child at home.

Photophobia: sensitivity to light in the eyes. Kezia has this right now due to the IV methotrexate she's receiving in Escalating Capizzi II (obviously she had it in Escalating Capizzi I as well).

Contracting tendons: we were taught foot exercises to help prevent this. H. got it so bad that even physiotherapy didn't help and they had to put her ankles in plaster to resolve it.

Feeling Shit: ...

So those are (some of) the common side-effects! You think that's bad?

Less common effects ... (this isn't a full list – just a sampler!)

Vincristine: convulsions, optical atrophy with blindness

6-Mercapturine: abnormal liver functions

Dexamethasone: diabetes (Lucia and H.), inhibits growth, intestinal ulcers.

Cytarabine: liver injury

Methotrexate: liver, lung, kidney damage, stoke, seizure, neurotoxicity leading to learning difficulties.

etc etc

P.S. Lucia in the comments to this post describes severe bone pains as a result of dexamethasone. This is so bad for her that it was reported as a Severe Adverse Event (severe reactions are reported) to the UKALL 2003 trial, necessitates morphine when she comes off steroids and changing from dexamethasone to prednisone.

The Daily Grind

As I'm not back in the UK, I cannot narrate the ins-and-outs of the family's daily life there - you'll have to wait for my next visit. I know Nanda is frustrated and bored with daily life. Kezia doesn't want to walk or go in the pushchair which means carrying her – and now at almost three years old that's quite heavy. They get up in Britain's dark and cold winter, Jaime has to be prepared for and taken to school. Then, when there is not a hospital visit, Nanda hasn't got much energy to go to the shops downtown, carrying Kezia, so she shops at our local Co-op about 5 minutes down the road.

On hospital days they never know when the hospital-provided transport will arrive so they have to be prepared and sit and wait and wait ... I don't think there's been a repeat of the transport arriving at 06:50! There's a Breakfast Club at the school from 08:00 so Jaime can go early on hospital days. If there's no hospital visit, pick up Jaime at 15:30.

Hospital visits are always an anxious affair as until the blood test results come through, we won't know if Kezia will need a blood or platelet transfusion, which will be a lengthy affair. The blood and platelets have to be matched exactly and then have to be transported from a central blood bank some distance away. Jaime can stay at the after-school club until 18:00 but even then, with the added factor of waiting for transport back from the hospital, there might not be enough time and Jaime pick-up alternatives have to be organised.

On receiving my January salary I organised a SkypeOut account so I can phone Nanda on her land-line or mobile cheaply. Our January Jaime childcare crisis cost me an arm-and-a leg in international phonecalls. My local telecomms/ISP monopoly says it doesn't have the capacity to give me a fixed land-line at home (and therefore no Internet), so I have had to rely on my mobile and international reimbursable calls from work. Fortunately, we have a free satellite Internet link at work so now when I'm there I can Skype her at the hospital and see if there are any problems.

Me? I get up for work at 06:00 (already light being near the equator), get ready for work, leave around 06:45, a 30 minute commute. Work until 16:00 and, if I don't need to some shopping in town, get home, have shower and do the home's daily inspection before settling down to this or the television until bedtime (around 21:00).

So ... Kezia's sick, Jaime's having a great time, Nanda's bored and frustrated and I'm missing my family. The joys of living with leukaemia!

Have a good weekend!

UKALL 2003 - Asparaginase

Asparagine is an amino-acid produced by normal cells. It was the first amino-acid to be discovered back in 1806 in asparagus – hence its name. One of the twenty most common amino-acids. Because human cells produce their own it is not considered essential in your diet.

It is required for protein synthesis and thence the synthesis of RNA and DNA. Most lymphoblasts, however, cannot produce asparagine and depend on freely circulating (or exogenous) asparagine produced by healthy cells.

If we can wipe up all this freely circulating asparagine, then the lymphoblasts cannot reproduce and cell death (apoptosis) results.

L-Asparaginase breaks asparagine down into aspartic acid and ammonia. It was first discovered in guinea pig serum about 30 years ago and found to suppress the growth of lymphosarcomas in mice. But, as the UKALL 2003 points out, “Clearly it was not a viable option to source this agent from guinea pig serum ...”. However, it is widely found in nature and ideal sources were discovered in the bacteria Escherichia coli and Erwinia crysanthemi.

It has quite a fantastic chemical formula C₁₃₇₇H₂₂₀₈N₃₈₂O₄₄₂S₁₇. With that number of atoms in a molecule, you're unlikely to find a diagram of it!

Early experiments found that the half life E. coli and E. crysanthemi asparaginase was about 10-12 hours which necessitated frequent injections and higher risks of side-effects. However, when attached to polyethylene glycol (pegylated), E. coli asparaginase has a half life of 5.73 days thus necessitating less frequent injections.

The study of Peg Asparaginase is one of the objectives of the UKALL 2003 trial. More specifically, the study aims

To test whether with current dosing/scheduling/product used we achieve:-

a) Adequate Asparaginase levels for the appropriate duration
b) Whether these levels deplete asparagines?
c) What is the rate of anti-asparaginase antibodies?
d) How many of the reactions to pegaspase are inhibitory?

To test the feasibility of routine Asparaginase monitoring.

Various measures on blood samples are performed – levels of asparaginase, levels of asparagine and levels of antibodies to the asparaginase. These will then be correlated to early leukaemic cell kill as measured by peripheral blood blast clearance, Day 8/15 and Day 29 marrow clearance plus the minimal residual disease estimates that form other objectives of the UKALL 2003 trial.

The Peg Asparaginase is administered as an intramuscular injection in this trial as it is thought that this route results in decreased hypersensitivity, although it may be administered intravenously in other protocols. The brand name is Oncaspar.

Numerous possible side-effects. Maybe I'll have to do an entire post on side-effects of all these drugs!

Language Support

Back in 1986-87 I trained as an English as a Second/Foreign Language (ESL/EFL) and underwent a period of six weeks teaching practice at a secondary school in the UK town where the rest of my family are currently living. There is a high ethnic minority population in the town and at that time each school had a level of language support with some schools having staff dedicated full-time to ESL teaching and support.

Jaime is now at a local primary school and slowly learning English. However, I was told there are now only two language support staff in the entire local education authority!

Is this true? Surely, the demographics of the town have not changed that much? Does the entire ethnic minority population read, write, speak and understand English perfectly? Is there no immigration anymore? Or have progressive budget cuts led to cuts in language support staffing?

Probably a combination of all these factors ...

However, I discover from the town council's website that “data collected in 2004 show there to be around 6500 (18.5%) minority ethnic pupils in [the town's] schools of which around 6300 are bilingual. About 1000 (16%) of these are in the early stages of acquiring English”.

So Jaime is one of a thousand. The LEA has an Ethnic Minority Achievement Team (EMAT) to assist schools with English as an Additional Language (EAL – the jargon has changed) teaching. No indication on the website of the staffing levels of the EMAT.

I wonder if Jaime and his teacher are receiving any support from the EMAT? The most recent OFSTED report states that there are very few early stage EAL learners at the school. I didn't manage to see his teacher at Christmas due to the school holidays. But I will be able to in April and we'll be able to see how he's coming along ...

Open Source Medicine V

In writing the last post I had a query about the way 6-Mercaptopurine and 6-Thioguanine and their modes of action were similar and different. Not being a biochemist, not even a scientist, I wrote Patty to ask for some clarification but before she had a chance to reply, I found PharmGKB.

This is database project to pool pharmogenetic and pharmogenomic data to allow researchers open access to others' data on the mechanisms of drugs and the often different reactions that patients have to the drugs due to differences in their genetic make-up.

To quote from a downloadable paper explaining the project (available here – but I couldn't get it to open in Acrobat Reader and had to use KGhostView):

“The ultimate product of this project will be a knowledge base that will provide a public infrastructure for understanding how variations in the human genome lead to variations in clinical response to medications.”

The project uses XML schema for data to be structured with modifications to the schema being made available for review by participating researchers. It provides a Java API for uploading data which conforms to the Open Knowledge Base Connectivity standard (I'll have to do some more research on that). Data can be submitted via web-based forms or directly in XML following the project's schema. Integration with other external databases is another project aim with project data being made available freely. This requires the project to monitor closely the structure of the external databases to ensure efficient and maintainable data transfer. Sorry if that's a bit technical for non-geeks.

The project is based at Stanford University in the USA.

Anyway I found my answer about 6-MP and 6-TG here – not that I really understand it! But basically 6-TG follows a more direct approach to integrating with DNA than 6-MP. Why this should have resulted in higher mortality for 6-TG in the UKALL 1997 trial I really don't know.

Several other of our chemotherapy drugs are also on the site and I'm sure I'll be using the resource again.

Patty adds "From the schemes given, no, biochemically one can't see why. But the body is such a complex system, and although biochemists try to put everything into nice little pathways, the story is rarely that simple. I know that one CCG trial found a lot of liver toxicity with 6TG".

UKALL 2003 - 6-Mercaptopurine

Also more commonly known simply as 6-MP, this is given orally at various stages of the first year of treatment and then daily throughout the maintenance phases.

Again I am indebted to Patty Feist (link on right) for her explanation of its mode of action. It appears to have three modes of action. In the liver 6-MP is converted to a corresponding ribonucleotide (i.e. links to a ribose sugar – see the post on cytarabine). This inhibits the conversion of a compound called inosinic acid to adenylic acid which is needed to make the DNA base adenine.

In its second mode of action it also inhibits the conversion of inosinic acid to xanthylic acid that is necessary for the synthesis of guanylic acid necessary for the synthesis of the DNA base guanine.

Finally, it also works by being incorporated into nucleic acids as thioguanosine deoxyribose, rendering the resulting nucleic acids (DNA, RNA) unable to direct proper protein synthesis. Thus in this case we're changing the base rather than the sugar as is the case with cytarabine. (See this abstract)

Some people have different levels of TPMT (thiopurine methyltranserase - the enzyme that metabolizes 6-MP) activity that controls the first two modes of action (but not the third). This is controlled genetically (good explanation of this here). In fact, 1 in 300 individuals cannot break down 6-MP at all. In the UKALL 2003 protocol this is tested at diagnosis and later on, if found necessary due to adverse reactions.

In an earlier clinical trial UKALL 1997 the related drug 6-Thioguanine (6-TG) was found to increase remission death rates in comparison with 6-MP and so is no longer used. However, it would seem to be still used in other protocols (e.g the CCG 1961 protocol that Patty Feist's son was on).

It will be taken at night (see this paper on chronotherapy), at least one hour after a meal and with no recent intake of milk (see this abstract) as a compound in milk converts the 6-MP into useless by-products

See this link on Gertrude Elion, the discoverer of 6-MP and 6-TG.

UKALL 2003 - Escalating Capizzi II

Kezia had her second dose of intravenous methotrexate today. The dose will have been increased to 80 mg per square metre. Next appointment is 15 February with an increase to 130 mg per square metre if she hasn't reached toxicity. Currently suffering with tingling feet and doesn't to walk much.

Just heard from A. H. has had her third dose of IV MTX and is beginning to get mucositis (sore mouth).

UKALL 2003 - a Very Small DNA Primer

As most of these drugs are messing with the DNA that forms the nucleus of a cell and preventing it from reproducing or splitting, I think I should say a little bit about DNA before I continue this series of posts about the drugs Kezia is taking.

The nucleus of a cell is its “brain”. It controls everything. Birth, Life, Death. The DNA consists of four chemical compounds known to our scientists as A (adenine), T (thymine), G (guanine) and C (cytidine). And they are known as bases.

Each of these chemical bases is connected with a sugar named in chemistry a deoxyribose (whose structure I showed in the Cytarabine post). If we can fool the bases to combine with a defective sugar (for example, a molecule out of place as in Cytarabine) or otherwise mess with DNA's structure (as in Daunorubicin), then the DNA won't function correctly and the cell won't reproduce before dying. Equally, if we deprive the cell of something the DNA needs to reproduce (as in the case of Vincristine), then the cell won't be able to reproduce.

Because these drugs are messing with DNA etc indiscriminately, they effect both healthy and cancerous cells. What are really needed, are drugs or treatments that only target cancerous cells – hence the interest in Dichloroacetate (that we blogged about here – and Dr Crippen at our favourite NHS Blog Doctor only picked up yesterday – beat you John!). Copy of the original research paper as a pdf is here.

Happy Birthday

Happy Birthday Lucia!

Christmas in the UK - Final Part

Final part I promise!

Jaime, in six weeks in the UK, was beginning to get into Gadgets! Primary school in the UK is teaching him computers ... I expect he'll want a Play Station etc etc soon

Christmas presents included a host of “kits” - a Meccano (now M&S) plane, a wooden dinosaur etc etc – I approve of this, encourages your mechanical skills. schematics, reading etc etc. Hey I grew up with all this and I'm sure it did me good!I But they all say 2 years and up – what? They challenged me at 44! You expect a 7 year old to deal with this!

Hence the photo below when he wanted and learned to manipulate my digital camera!

We went out for a walk on New Year's Day up the Spodden Valley next to the abandoned asbestos mill, known as Taylors, now owned by the multinational Federal Mogul. When my brother's dog, Lady, was alive we'd take her out for walks up here – a rural idyll in the midst of decaying industrial Lancashire

Much of the woods are now taped off-limits due to asbestos-waste dumping (and there's big legal things going on) but the main footpath is still open. Not really a place for Nanda, Jaime and Kezia to go alone but ok during the day for the family.

Kezia looks like the Red Dwarf serial killer in Nicholas Roeg's film “Don't Look Now” - the scariest “horror” film I've ever seen. All suspense, no (well, not much) gore!

UKALL 2003 - Vincristine

Another drug derived from a natural source – the Madagascan Periwinkle Caranthus roseus. The plant has been in use in traditional medicine for centuries treating anything from diabetes to wasp stings to eye infections. When scientists began looking at it in the 1950s, they discovered over 70 alkaloids among which was vincristine.

Microtubules form part of the structural network, or cytoskeleton, of a cell's cytoplasm. They are made of a protein called tubulin. They form various structures and have various functions. One of these is the formation of a structure called a mitotic spindle (mitosis = cell division). This segregates chromosomes correctly during cell division so that each daughter cell receives the correct number of chromosomes. In the picture below the mitotic spindle is green and the chromosomes are blue.

Vincristine binds to tubulin and prevents the formation of microtubules and, in particular, the mitotic spindle. Thus the cell dies without being able to divide.

Unlike our other chemotherapy agents so far, this is not working directly on the cell nucleus and DNA but within the cell's cytoplasm surrounding the nucleus.

It has, like all our drugs, many side-effects. Particularly, noticeable are neurological effects – Kezia developed tingling feet making her unwilling to walk. Others report similar effects.

If given intrathecally (in the spine), it is fatal. For this reason the UKALL 2003 protocol gives the following warning:

“All medical staff involved in the care of patients with leukaemia MUST be aware that the inadvertent administration of vincristine by the intrathecal route is invariably FATAL. Vincristine should NOT BE AVAILABLE when an intrathecal needle is in situ. This protocol has been written to provide separation of intrathecal methotrexate administration from intravenous vincristine administration in time. An additional precaution is that the two drugs should not be administered in the same place.”

UKALL 2003 - Cytarabine (Ara C)

Cytarabine, more commonly known as Ara C, is administered over four consecutive days in four blocks during Augmented BFM Consolidation, and two blocks each in Delayed Intensification I and II (in Regime C of UKALL 2003). It is administered through the Hickman Line and is generally done at home as four consecutive days visiting the hospital is a bit much for both patients and carers. You'll be given a choice of learning to do it yourself or have a community nurse visit. However, the latter is a bit infeasible if a dose falls on a weekend so I would really recommend learning to do it yourself. The hospital will train you and check you are proficient as well as providing written instructions to take home.

It's really best to have two people present when administering it so the second can both check the first is doing it right, and comfort the child. We have a two-person safety rule at work for any electrical or mechanical maintenance – the second person can catch any potentially dangerous slip-ups and assist if there are difficulties – the same is true here.

The process consists of cleaning the line with saline, injecting the drug, injecting Hepsal (Heparin Sodium – an anti-clotting agent to stop the line getting blocked) and finally saline again.

The story of the development of Cytarabine is fascinating – I will try and summarise here but go to Patty Feist's page for a more in-depth account A Tale from the Sea to Ara C. Thanks also to Patty for the graphics here.

The story starts in 1945 when a young scientist, Werner Bergmann, was collecting sea sponges (Cryptotethia crypta) on the coast of Florida. He boiled them up in acetone and instead of finding a steroid as expected, discovered a new substance similar to the DNA building-block, the nucleoside thymidine. Bergmann named the new compound Spongothymidine.

The two diagrams below demonstrate the very slight difference between the two molecules. The blue portion is known as the base, and the red part is a sugar. The base of each is the same, thymine, whilst the sugars differ slightly. In thymidine the sugar is known as deoxyribose and in spongothymidine it is arabinose.

Deoxyribose sugars (plus base) form the backbone of DNA, and ribose sugars (plus base) form the backbone of RNA. So arabinose is unlike either of them.

Early research in chemotherapy concentrated on changing the base but with the discovery of spongothymidine the focus moved to changing the sugar. John Evans and Seymour Cohen bound the sugar arabinose to another of the four DNA-bases, cytosine, making Cytosine arabinoside or Ara C, and tested its anti-cancer properties with positive results.

Here's how it works (another Patty page here).

In a cell Cytosine riboside (an RNA molecule) is converted to Cytosine deoxyribose (a DNA molecule) with the help of an enzyme. The enzyme needs to bind to the riboside and strip off an oxygen atom from the OH group (on the bottom right of the sugars in the diagrams below) to make the deoxyribose. However, if cytosine arabinoside is present, the enzyme binds to it through mistaken identity but as that OH group is on the top-right of the sugar instead, it cannot find it and cannot convert it to deoxyribose. Without the cytosine deoxyribose, new DNA cannot be made and the cell will die.

Other anti-cancer drugs are now being developed from marine organisms. Patty discusses Ara G and Clofarabine in the treatment of childhood leukaemia. Other anti-cancer drugs derived from marine organisms and currently under trial include Yondelis and Apledin derived from marine tunicates and Kalahide derived from a nudibranch (a sea slug).

This just goes to show how important biodiversity conservation is – new substances, of great scientific use, are still being found in plants and animals around the world. If we lose these, before discovering what they have to offer us, we have lost an incredible resource.

Open Source Medicine IV

Some more Open Source medicine and science links:

Science Commons: this is the central "clearing house" of everything to do with Open Source science and scientific research.

BioMed Central: an independent publishing house committed to providing immediate online open access to peer-reviewed biomedical research.

PLoS One: the Public Library of Science is a non-profit organisation of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource that publishes peer-reviewed research online. Two links here - one to the library and one to the organisation.

Directory of Open Access Journals: aims to increase the visibility and ease of use of open access scientific and scholarly journals thereby promoting their increased usage and impact. It aims to be comprehensive and cover all open access scientific and scholarly journals that use a quality control system to guarantee the content. A one stop shop for users to Open Access Journals.

A good article on Open Access research by John Wilbanks of the Massachusetts Institute of Technology pusblished in the British Medical Journal is here.

I think I'll start a Links section dedicated to Open Source medicine and science.

Christmas in the UK - Part 3

It's about time I finished with the holiday stories as we're almost at the end of January.

My maternal cousin, J. and her family were back from France (where they live) for Christmas. They were staying with her sister/my cousin P. and her family for the holidays, and, of course, they live not far from mum, my Aunty L., in Staffordshire.

As I haven't seen any of them in some 23-odd years, and as J. has been particularly kind since Kezia's birth, and all of them since Kezia's illness (I gather that Aunty L. has rung one or twice a week since we first arrived back in the UK in May), we set up a “family reunion”. P. and P. wanted to take advantage of my visit to get away over the New Year weekend but they have seen our cousins and aunty a lot more recently than myself.

We arranged for them all to come up on the 30^th, come to the house and then proceed to a local country pub for lunch.

My Aunty L. converted to the Church of the Latter Day Saints (Mormons to you and me) many years ago. I have a couple of work friends (occasional sub-contractors) who have come out here on occasions and who live in Salt Lake City. One's a Mormon, one isn't. The latter B.R. is perhaps the only American I know who understands cricket and I've spent happy hours watching it over beer when he's visited! Non-Mormons are very distinctly a minority in Salt Lake City and the Mormon lifestyle is a constant source of humour to them, an example being the Sunday morning traffic jams as all the Mormons head back to town to attend their local temple meetings!

My other friend K. is the brother of the notorious, and imprisoned, Mormon fundamentalist and polygamist Tom Green (look him up in Wikipedia) – the Mormons haven't permitted polygamy for over a century and, having excommunicated him, obviously don't consider him a Mormon. Anyway, K. has stayed in the fold and drinks Coca-Cola but not coffee - caffeine being prohibited but as coke didn't exist back then it was not put on the original proscribed list ... my Aunty L. didn't agree with this doctrinal interpretation.

B.R. and K. have worked together and been friends for many years. As with other distinct social or religious groups (Jehovah's Witnesses, Catholics, cancer sufferers, homosexuals ...), the Mormons have developed their own humour and comic traditions. For cancer jokes see the Furry Monkey.

Anyway, I digress ... but at least Aunty L. will ensure Kezia will get baptised so we don't have to worry on that score! Aunty L. - you've been very kind to us and it's much appreciated!

Anyway, the whole tribe descended at about 11:30 – Aunty L., cousin P., her spouse and their two daughters, cousin J, her spouse and their daughter. The house could hardly contain us all and we had to spill over into the kitchen. Blimey, my cousins have changed – we've all grown up and my old teenage attitude, “Oh it's sissy to be friends with your female cousins”, was instantly dismissed as I face two grown-up women with all their own life experiences. A short game of football in the front garden with two of my cousins' children and Jaime and then I ordered a taxi for us and we all set off for lunch.

I won't say much about lunch as the photos below say it all – a good time was had by all!

The Tribe

Angus and Kezia at the bar - introducing her young!

Aunty L. hiding behind her fan.

Aunty L. comes out of hiding
.

Cousin J. and her daughter M.

Cousin P. and her daughters

Finally Kezia looks at the camera and I get the flash right

Open Source Medicine III

Much medical literature is unavailable, particularly to medical personnel in countries such as ours, due to its high cost. These two sites - FreeBooks4Doctors and Free Medical Journals - aim to promote the free publication and dissemination of scientific medical information and research online.

UKALL 2003 - Escalating Capizzi II

Finally Kezia started Escalating Capizzi II today with a dose of intrathecal methotrexate. So I guess her neutrophil and platelet counts were good. Tomorrow intravenous methotrexate and vincristine. The IV methotrexate is particularly nasty with its side effects but I'm pleased we've started - only 16 weeks give or take until we start the alot less intensive maintenance phases.

She was meant to start this phase last week but her counts weren't adequate. Not surprising really as she had been hospitalised with a temperature the previous Wednesday to Friday. Nothing really to be worried about but it did bring on a small family crisis over Jaime's childcare when they're in hospital. Anyway, with the great help of the social services, we have put in place some alternative childcare arrangements for the next time this happens.

A New Link - Patty Feist

I have just discovered an awesome site about ALL run by Patty Feist in Colorado. She attempts to answer many of the more technical aspects in layman's terms (as we are trying to do here). Her collection of links to other ALL sites (both technical and support) she is involved with is also amazing. I've only just touched on it. I know this will be a resource I will be using alot in future posts. She also runs the Childhood Cancer Webring - link at bottom of page. Please take a look!

UKALL 2003 - Dexamethasone 2

I've refrained from tackling this until now as I really didn't understand even a twinkling of the science behind Dexamethasone's anti-cancer properties. After much reading I discover that not even the scientists fully understand the mechanisms.

In my last post on Dexamethasone I attempted to explain its anti-emetic (nausea, vomiting) properties. However, talking to our consultant J. over the holidays, it seems the justification for its use in the treatment of leukaemia is its anti-cancer properties – the anti-emetic effects are a beneficial side-effect.

Right, I'll try and explain what is known about its anti-cancer properties. There appear to be several mechanisms at work:

• It appears to trigger programmed cell death (apoptosis). Both good and leukaemic cells.

• They inhibit the production of interleukins which are signalling chemicals which stimulate a variety of cell behaviours. The IL-2 interleukin (there are 33 of them) is produced by T-lymphocytes. The IL-2 then binds itself to the T-lymphocyte signalling it to grow and differentiate. (This self-signalling is termed autocrine). Clearly, inhibiting the production of leukaemic T-cells (or T-cell blastogenesis) is one of our goals.

• It can also (seemingly) increase the ability other chemotherapy drugs to destroy leukaemic cells

It can also prevent white blood cells from reaching sites of infection. Hence (as with most chemotherapy drugs) there is an increased risk of infection when taking it. Strangely, as the WBCs cannot reach the infection, the white blood count may be seen to go up.

I should also add that one of the lesser known and rarer side effects of the glucocortisoids is induced diabetes - this is what H. suffered from - she got over it but insulin injections in the stomach were no fun. I guess no more dexamethasone for her!

Next in the series is Cytarabine - this is kind of cool!

Update: in the comments Lucia also reports having suffered from diabetes so they have switched her to prednisone.

Christmas in the UK - Part 2

Christmas Eve was a bit of a blur. I was totally knackered. What I do remember follows:

• Nanda had opened and repacked all the presents under our Asda Christmas Tree. This is kind of par-for-the-course as Nanda has done this every Christmas since I've known her and I end up doing a kind of cat and mouse/hide and seek game with presents. I think it's partly cultural and partly personal – traditionally Christmas Eve after Midnight Mass is the big time here (because of colonially/catholic imposed practices), it being a poor African country you don't buy presents for all and sundry (well, anyone for that matter) and personal Nanda is totally materialistic! Whilst in the UK Christmas presents are opened on the morning of the 25^th. I commented as she knew I would but this year I didn't make a fuss. Too tired.

• My brother and sister-in-law came round early evening. We talked for a while but, I confess, I had to say I need to crash, I'm shattered, bye.

Christmas (25^th) morning arrived and, as my surprise presents hadn't arrived, we had a leisurely breakfast before opening the presents which had already been opened. (Sorry to harp on at this – it really annoys me!).

At 11 we went around to P. and P.'s. for Christmas dinner. Fortunately, Nanda had been unable to open their presents to Kezia and Jaime in advance so there were big surprises. Best for us as parents was a kids' size table and two chairs so they can sit up to table for meals!

P.'s son S. came round (I really love him). Here's a picture – Cheers S. Thanks for everything!

A wonderful traditional Christmas dinner followed - turkey, stuffing (three types!), roast spuds, brussel sprouts, gravey, Christmas Pudding (flambed on the table), mince pies, crackers (not the edible kind), silly paper hats etc etc. My brother made it all! Thanks! (If any of our non-UK readers want some explanation, please ask!).

After dinner Jaime and Kezia had had enough and wanted to take off home with their new presents – ungrateful bastards. So we walked around the corner with table and chairs on our heads.

Cancergiggles

Cass at Cancergiggles (link on right) has passed away. Our deepest condolences.

Open Source Medicine II

See these links on the anti-cancer drug Dichloroacetate which is both cheap and cannot be patented but for which private sector research funding cannot be found.
DCA 1 and DCA 2

Karaoke

The song for Christmas was Patience by Take That.

Snapshots

We bought hair clippers so that Nanda can cut Jaime's hair at home. Here he tries them out.

Kezia phoning home.



Missies Senegal sitting on their new chairs at their new table.



Nanda in her new wig.



Nanda in her new wig and Funk Hat.



Kezia in the Funk Hat.

Charity and Benefits

Our social worker at the RMCH, T., working for Clic Sargeant, has been marvellous. She's arranged us bits of money here and there ... every bit has helped.

A.& H. suggested we should apply to the Samantha Jones Trust, a young peoples cancer charity, for a computer – so I could communicate with Kezia, Nanda and Jaime by VoIP and save on our telephone bills. So T. tried for us.

H.'s application was successful. Lucia, I know was successful ... but ours wasn't. Ours wasn't - as they figure she's only 2 ½ and doesn't know how to operate a computer ... T. tells me they have a policy of no computer grants to under 5 year olds.

Operating a computer is not important – she needs to see and talk to her dad, I need to see and talk to her.

Anyway, a friend here, another T. has given us a laptop with a wireless card which I took over to the UK, I bought a webcam at Christmas, and hopefully we'll all talk by the Internet soon and save lots on phone bills!

SJT – look I know you're only meant to benefit the patient ... but surely father talking to patient daughter comes under that ...

Nanda has “no recourse to public funds” as a condition of her visa. Therefore Kezia cannot get any benefits (e.g. Child Benefit and Disability Living Allowance). If I had been resident in the UK for six months, she could. That she has been resident in the UK for over six months doesn't count. I think this is pretty stupid particularly in the case of Child Benefit which aims, I believe, to umm ... benefit the child!

Never mind.