Wednesday, January 31, 2007

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!

Tuesday, January 30, 2007

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.

Friday, January 26, 2007

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 30th, 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

Thursday, January 25, 2007

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.

Wednesday, January 24, 2007

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.

Tuesday, January 23, 2007

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.

Monday, January 22, 2007

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 25th. 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 (25th) 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.

Friday, January 19, 2007


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

Tuesday, January 16, 2007


The song for Christmas was Patience by Take That.


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.

Wednesday, January 10, 2007

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.

Tuesday, January 9, 2007

One Phase Over, Next Phase to Start

Kezia and Nanda are just back from the hospital following the final dose of Vincristine in Delayed Intensification I. No problems today. Phew!

Next phase, Escalating Capizzi II, starts on the 17th. Not even our consultant J. could tell me where/why "Capizzi". Can anyone out there elucidate?

Monday, January 8, 2007

Open Source Medicine

I haven't gotten round to talk about this subject yet but when I was in the UK, I picked up a copy of the New Scientist and there was an interesting article about what could be termed open source medicine.

Apparently, a drug used to cure Hepatitis C called interferon-alpha in its pegalated form (see this post for meaning of this) is far too expensive to treat the majority of sufferers as the process of pegalation has been patented by parmaceutical giants Hoffman-La Roche and Schering Plough. The patented version involves attaching the PEG molecule to the surface of the interferon.

So researchers in London decided to find a way to produce a cheap version of the drug allowing far more sufferers to be treated. They discovered a way of inserting a PEG molecule inside the interferon molecule and found it works as well as the drug created with the patented process. Clinical trials are to start in 2008.

The first part of the article is here but you have to subscribe for the full version.

Christmas in the UK - Part 1

Don't know where to start! Fuckin' brilliant on the whole!

Got back yesterday (Saturday) at 08:30 after having left UK home at 07:30 on Friday. Lots to talk about – but most importantly, Kezia, Jaime and Nanda are well. I'm a bit down down now, especially when last night Nanda told me that Kezia is expecting me to walk through the door at any moment. She doesn't understand I've come back here, and probably won't visit for the next four months.

Took lots of photos, of varying quality – will post some shortly over the next few days.

So where do I begin? As I don't have the writing skills to produce creative literary constructs that wander back and forth through time, I guess I'll start at the beginning ...

My brother-in-law woke me up at 03:45 (on the 23rd) even though I'd said to not pick me up until 04:30. Well, better early than late, and I could take a shower, a cup of coffee and the first cigarette calmly without the rush we had in November taking Jaime over.

Everything ran smoothly on the journey out ...

... except we arrived in Lisbon late. My friend L., from the travel agency, asked me to look after a young woman who then missed her onward flight to London. She managed to get on my later flight as, I guess, the before Christmas Eve flights were not in great demand.

We got to Heathrow. No luggage! Watched the carousel go round and round until they put the next luggage from a Rome flight on the same carousel. I was anxious to catch my bus to Manchester, she, never having travelled abroad before, was anxious about her luggage. I managed to persuade her that we should fill in lost luggage claims which I helped her with. Took her through customs and there were people to meet her.

Caught the bus without my suitcase. And arrived at Manchester Chorlton Street at 05:40 on Sunday 24th. Took a taxi up to Manchester Victoria railway station - it's empty, closed, no-one around, eery! Discover there's no onward train until 09:15! Shit! A distance of 15 miles and I have to wait 3 hours when I've come so far! I walk up to the Shude Hill Bus Station and find out the first bus is at 06:55! Phew! It's fuckin' freezing! I've only got a T-shirt and a fluff on. It's fuckin' freezing!

So I make it home at about 08:00 and they're still in bed.

Luggage - I eventually got it one week later on New Year's Eve. There seem to be varying accounts for the luggage chaos that ensued this Christmas. The version I got from Alitalia (who run baggage-handing services at Heathrow) was that the computerised baggage-handling system crashed and they had to take down every single baggage ticket number by hand and manually enter it into their computers. Thus, although my suitcase probably arrived on the 24th December, it didn't get to me until the 31st.

Better late than never!

To be continued ...