Monday, May 29, 2006

St Pierre

The venue for my daughter's wedding was just over the old Severn Bridge into Wales. Well, I say Wales, but when I went to school Monmouthshire was part of England, but it became Gwent and part of the Welsh Principality. The old Severn Bridge was built in 1966. Diane and I walked over it in November that year, but the more direcct route into Wales (and the M4) takes the new Severn Bridge, built in 1996.

The church of St Peter was built around 1100 AD, although there was probably an even older Saxon church there. It was restored by the Victorians (at the cost of £1000) but incorporated a wooden chancel screen from 1400 and two stone coffin lids from the 13th century. The manor of St Pierre is first mentioned in 1340, but the house was built in 1475 and has been added to and improved ever since.

Ownership of the estate changed hands many times, and in 1946 it fell into the hands of the National Association of Boys Clubs. When they moved elsewhere it was eventually established as St Pierre Golf and Country Club. It became the site of the Welsh Open in 1971 and the Dunlop Masters was played there the same year. In 1973 it was acquired by Whitbread Hotels and in 2005 it became part of the Marriott chain. In 1996 the Solheim Cup was held there and in 2000 the Welsh Masters.

Today the house is a hotel and leisure center with two 18 hole golf courses, swimming pool, gym and tennis courts. There are 143 rooms many of them as appartments and small cottages. A very pleasant place to spend a few days.


This really has been a cold spring in England. We have our first blue geraniums out in the garden, the pink ones have been out for a couple of days. We have blue tits and their fledgelings in our nesting box, the lilac is well advanced, small Bramly apples have formed on the trees; but it has been the wettest May since 1983 and one of the coldest. Last year we had a week in May when the temperature touched 80 degrees. This year it has been mainly in the fifties.

Everything is very green. The trees are in full leaf and growing quickly. The oil seed rape is glowing luminous yellow in the fields. We certainly have bright and sunny days; but a North wind is blowing.

I wonder if Nature is confused by this weather? The vigorous growth of vegetation seems like an overreaction. The grass needs cutting twice a week. Plants we had forgotten about are growing stronger than we ever remember them. The Christmas Cactus that we moved into the greenhouse is flowering six months early.

I've put on a thick pullover and gone back to thick woolly socks. If Nature isn't confused, I certainly am.

Sunday, May 28, 2006

Harry Potter

I have just watched the DVD of Harry Potter and the Goblet of Fire. I thought it very well done. My usual complaints that the music was too loud, muffling the dialogue, and everything was too dark to see properly applied, but I turned the subtitles on and was able to follow it.

The young actors have much improved since the first film, Ralph Feinnes was excellently evil, but Michael Gambon is still a disappointment after Richard Harris. Brendan Gleeson was fun. Spotting the uncredited actors was interesting. No John Cleese this time, but veteran comedian, Eric Sykes put in an appearance at the beginning and the new Dr Who, David Tennant played the part of the villain, Barty Crouch Junior.

Saturday, May 27, 2006

Fludarabine and prednisolone

This is the comparison of two phase II trials at MDACC showing no benefit from adding prednisolone to fludarabine. Posted by Picasa

Steroids 3

After a long interval, I want to complete this subject with an essay on how steroids are used in CLL.

First, it goes without saying that where steroids are used in autoimmune diseases, they are also used in autoimmune disease associated with CLL. Thus for AIHA and ITP, and for paraneoplastic pemphigus steroids are used in a conventional way starting with a dose of 1 mg/kg and tailing off once the complication is controlled.

But steroids are also used as a treatment for CLL, either alone or in combination with chemotherapy or antibody therapy. Early studies showed no benefit from adding steroids to chemotherapy. The British CLL2 trial, for example, compared chlorambucil 20 mg/sq m for 3 days every 4 weeks with the same dose plus prednisolone 40mg/sq m for 5 days ever 4 weeks. There was no significant difference in response rates (74% v 80%) or in overall survival. After this study the recommendation was made that steroids only be used in patients with anemia or thrombocytopenia for the first or second course as anecdotally it was thought that such an approach afforded some protection from the potential marrow damaging affect of chlorambucil.

At the MD Anderson Cancer Center they don’t do comparative trials, but they compare successive phase II studies. The combination of fludarabine at 30 mg/ sq m/d for 5 days combined with prednisone at 30 mg/sq m/d for 5 days every 4 weeks was certainly no improvement on fludarabine alone, and may well have been worse, although with historical controls such a comparison lacks authority.

The use of high dose methylprednisolone with a dose of 1g/ sq m/ d for 5 days – about 30 times the dose that was used with chlorambucil in CLL 2 – was a development from the Royal Marsden Hospital, in London. They found that most patients responded to this, even those who were resistant to chlorambucil or fludarabine.

How does high dose methylprednisolone work? It seems to have a direct lympholytic effect that does not depend on the presence of steroid receptors, and does nor depend on the presence of p53.

Recently, two trials of high dose methylprednisolone (HDMP) and monoclonal antibody have begun. In Britain the combination of Campath and HDMP is being trialled, and in America HDMP plus rituximab. The logic of using Campath with HDMP is that both agents are effective in CLL with a crippled p53 pathway, the commonest cause of drug resistance. Rituximab is ineffective in these patients, but perhaps the combination is more effective. Both these studies are phase II trials, so we will not discover whether either combination is better than single agent treatment.

The suggestion has been made that steroids will render the effector cells used in ADCC ineffective. Although theoretically this seems to be a problem, in practice it does not seem to matter. Perhaps the other methods of killing that antibodies invoke synergize with the effects of the high dose steroids.

It is important to remember that high doses of steroids have major side effects. In diabetics there will be immediate loss of control of blood sugar and sometimes in pre-diabetics the existence of this precursor condition will be revealed. It is important therefore to monitor blood sugar. There is likely to be a change in psyche. Some patients are unable to sleep, others weep in an uncontrolled manner. Others are on a permanent high. Appetite is markedly increased. Blood pressure often goes out of controlled. Some patients will suffer bony collapse – crush fractures of the vertebrae are a possibility, and necrosis of the femoral head (hips) both occur, though usually only after repeated doses and with other auxiliary factors.

Infections are a real possibility. Reactivation of herpes infections such as zoster, herpes simplex and CMV, infections with Pneumocystis, Listeria monocytogenes, Aspergillus and other fungi, are a real possibility and therefore patients on these regimens need to be carefully monitored by doctors with experience of these complications.

In conclusion, steroids clearly have a role in CLL, but that role is not clearly defined. Apart from their use in the autoimmune complications, they are useful in displacing cells from relatively inaccessible sites like bone marrow and lymph nodes, and in high doses for their lympholytic effect which is active even in drug-resistant cases.

Friday, May 26, 2006

Sean Bean

For the past couple of days I have been attending the wedding of my eldest daughter in Wales. They decided to be married at the golfing resort of St Pierre near Chepstow. It was well organized by the hotel staff and I can give them a hearty recommendation. But the most remarkable thing about the couple of days occurred because the actor Sean Bean was making a film there.

My 87-year old mother doesn't get around very well these days, and seeing her struggling with a few stairs, the actor gallantly gave her his arm. It really made her day. At breakfast the next morning next morning she had to endure some gentle ribbing about baked Beans and whether the tomatoes weren't too Sharpe for her, but as she was sitting in the lobby afterwards, the actor came up and greeted her again. I guess she'll be talking about this for the rest of her life.

Sunday, May 21, 2006

Monoclonal antibodies in CLL

On May 4th this year the UKCLL Forum held a meeting in London. The topic was "Monoclonal Antibodies in the Treatment of CLL" I have written a report of the meeting and the first part is reproduced here.

Monoclonal antibodies were one of the first attempts at targeted therapy. Two monoclonal antibodies, rituximab (anti-CD20) and Alemtuzumab (anti-CD52) are currently widely used in the treatment of CLL. Lumiliximab (anti-CD23), and HuMax (a fully humanised anti-CD20) are in clinical trials. Although the response to single agent Rituximab in previously treated patients is only 13%, in untreated patients it is 51%. The response in untreated patients to single agent Alemtuzumab is even better at 87% and patients whose disease shows deletions of p53 respond well even though this defect defeats most other therapeutic agents, but Alemtuzumab also kills T cells and engenders immunodeficiency. Used in combination with chemotherapy, the response to rituximab approaches 100%, though the use of chemotherapy detracts from the specificity of the targeting.

According to Professor Martin Glennie, University of Southampton, CD20 is in many respects the ideal target. Compared with most other antigens on the surface of CLL cells antibodies that target it are much more effective killers. It is believed that rituximab kills in three different ways: 1] antibody dependent cellular cytotoxicity (ADCC) in which macrophages, NK cells and possibly granulocytes recognise the Fc portion of cell-bound antibody through their FC receptors, and this invokes killing and ingestion of the CLL cell; 2] complement dependent killing (CDC) – either tumbling the complement cascade right up to the membrane-attack-complex that punches a hole in the CLL membrane or, more likely, opsonizing the cell so that a derivative of the third component of complement, C3b, sits on the cell surface to be recognized by the C3b receptor of macrophages; 3] direct killing by cross-linking adjacent CD20 molecules into lipid rafts which sends a signal through the cell to self-destruct, either through apoptosis or through some other, as yet unclear, process. It is probably true that all three mechanisms play a part in real life, but experiments have revealed two quite distinct types of anti-CD20s. Most are rituximab-like and kill by ADCC and CDC – these are known as type I anti-CD20s – type II antibodies like B1 the original antibody produced in Boston, and the one used in Bexxar, kill by a mixture of ADCC and direct killing. The acute reactions seen after rituximab are cause by the release of C3a, an anaphylactoid, after the fixation of complement, but these also act as chemo-attractants for effector cells.

Dr Glennie also spoke about HuMax, a fully humanized anti-CD20 developed in his lab and currently undergoing clinical trials. This is a type I antibody, but it has certain advantages over rituximab. It is directed against a slightly different portion of the CD20 molecule from rituximab, and a slower off-rate (it stays on the cell longer) so that it is more effective at killing cells with lower quantities of CD20 on the surface.
Dr Josee Golay from Bergamo, Italy stressed the importance of complement in rituximab killing. In animal models lacking complement no killing occurred. Other models emphasize the importance of effector cells, both NK cells and macrophages being required. She went on to stress the importance of the interaction of various killing mechanisms. Fixation of anti-CD20 leads to the upregulation of the chemokines CCL3 and CCL4, which attract and activate a number of cell types including mononuclear phagocytes, NK cells, T cells and granulocytes through interaction with their CCR1 and CCR5 receptors. Which killing mechanisms are predominant depends on which tumor is being attacked and in which body compartment – blood, marrow, spleen or lymph nodes.

Dr Ron Taylor from the University of Virginia, Charlottesville also stressed the importance of complement fixation in rituximab-induced killing and added the information that complement could be consumed. Post-rituximab-infusion sera lacks complement activity, principally through consumption of the C2 component of complement. Although this might be overcome by the infusion of fresh plasma or of recombinant C2, a more important barrier to successful immunotherapy was also revealed. Antigen shaving is another mechanism for antigenic modulation. Antigenic modulation was seen as a potential barrier to antibody therapy in the 1980s. Fixation of antibody led to movement of the antigen in the lipid cell membrane – patching and capping – which in turn led to pinocytosis (internalization) of the antigen/antibody complex so that the cell became naked of antigen. One of the reasons that CD20 was chose was that it is not subject to antigenic modulation. However Dr Taylor has shown that after exposure to quite small amounts of antibody CLL cells are cleared from the circulation, to shortly reappear, this time bereft of surface CD20. The antigen had not been internalized, but phagacytosed by macrophages. It appears that the capacity of macrophages to ingest antibody coated tumor cells is soon exhausted and thereafter as the antibody binds to the macrophage Fc receptor, the most that can be accomplished is the stripping of the immune complex from the tumor cell – antigen shaving – and its ingestion by the phagocytic cell.

The choice of 375 mg per square meter as the dose of rituximab was quite arbitrary, dependent on the amount of antibody available and the number of patients needed to be treated. It may be that most of this antibody is wasted. Dr Taylor suggested that smaller doses given fairly frequently might be more effective. A dose between 20 and 60 mg was suggested, given once or twice a week

On a clear day

Last night I watched an interesting movie. Entitled "On a Clear Day" it won a Scottish BAFTA for best film last year. It stars Peter Mullen as a redundant Glasgow shipbuilder who decides to swim the English Channel. It uses this plot device to explore his relationships with his wife (played by Brenda Blethyn) and the other characters. He keeps the swim secret from his wife, just as she keeps secret from him the fact that she is training to become a bus driver.

Three of his workmates and fellow swimmers at the local baths also feature. One has retained his job but at the expense of his manhood; he is now required to clean the bosses' lavatories. The other two have women problems. The young guy (played by Billy Boyd, who was Merry or Pippin in Lord of the Rings and was also in Master and Commander) looks up to our hero as a father, recognising him as a strong and principled character whom he wishes to emulate, but is afraid to ask out the young girl who serves at the local sweet shop. The older chap was once married but his wife left him for a jam salesman and he has steered clear of women ever since lest history repeat itself. There is also a Chinese Chippy (fish and chip shop owner - not carpenter) who never says a word and cowers when the potato delivery man regularly drops the sack on the floor of the shop, splitting the sack and spilling the spuds. When he speaks it is a surprise because he has a broad Glaswegian accent and is highly intelligent.

But the main broken relationship is with his thirty-something son. He had been a twin but his brother had been lost in a swimming accident when he was a child. The son now has twin boys himself, but his father has pushed both son and grandchildren out of his life. The son feels rejected and thinks his father blames him, whereas in fact the father blames himself and keeps his family at bay to protect them from him.

The channel swim (22 miles in the busiest shipping lane in the world) becomes the talisman for all these people. If he succeeds it will restore all of their lives. The swim is their collective Redeemer.

Here is a movie that won't break box office records, didn't cost a mint to make, doesn't display spectacular scenery or exotic locations, but will reward you more on seeing it than almost any Hollywood spectacular. The acting was fine; the sound balance was perfect - despite the Scottish accents I could hear every word.

It won't be appearing at a cinema near you, but if it comes on cable try to catch it, or try and find it on DVD.

Thursday, May 18, 2006


Today was my day at a major London Teaching Hospital. Practically the whole team had decamped to America with management consultants to inspect the transplant set-ups at Dana Farber and the Hutch. So it was rather lonely there.

One particularly difficult case was a patient with ATLL, the strange and intractible T-cell leukemia caused by the HTLV-1 virus. She was Jamacian and an illegal immigrant, but she had been in the UK for 17 years and had a son who was a student in College. The leukemia was in her brain and she has perhaps 6 months to live. She could go home, but she has given up her lodgings since she has been in hospital. Social Services, who have the responsibility of finding the homeless somewhere to live don't want to know. Two adjacent areas each claim that she is the responsibility of the other. My suggestion was to contact the Pastor of her local church and ask them to care for her for her last few months, on the Christian principle of "I was a stranger and you took me in." Failing that I suggested that they contact the MP in whose constituency the hospital is and who also happens to be a Government Minister, and complain that a valuable transplant bed in the biggest marrow transplant center in the UK is being blocked by an illegal immigrant that nobody wants to own.

Another problem was a 59 year old patient with CLL who had been in hospital for nearly a year since his low intensity mini-transplant. His problem was chronic graft versus host disease. He receives phototherapy for his skin GVHD and this is improving but he still has diarrhea and abnormal liver function. On large doses of steroids to control his GVHD his CMV had reactivated and for this he takes gancyclovir. I asked how common was severe GVHD in the mini-transplants. The answer was 15% unless they also need donor lymphocyte infusions, when it rises to 30%.

Apparently the patient looks like Gollum from Lord of the Rings. For light relief, I informed the meeting that Andy Serkis, who plays Gollum, also played Bill Sykes in the BBC's early Oliver Twist and the gorilla in King Kong. "That was before he had his marrow transplant," opined some wag.

I also learned that once you have had Hepatitis B, the virus remains in your liver for life, ready to be awakened by immunosuppression. I caught Hepatitis B from a needle stick injury when I was a Fellow. Another good reason why I don't ever want a bone marrow transplant. Or fludarabine.

For relief from the doom and gloom I picked up this story from the Internet:
A man came across a striking brass rat in an antique store and decided it would look great on his desk. He paid $100 for it but was surprised when the proprietor insisted it was non-returnable. He said, "It's been returned twice already, and I don't want to see it again." Leaving the store, the man saw a couple of rats scurrying around the corner; several more were near his car. As he drove, rats appeared from the gutters and side streets until he was nearly overwhelmed. In panic, he threw the brass rat over a bridge railing into a river, and witnessed the army of live rats follow into the depths. The man hurried back to the store, but the owner cut him short, saying, "Look, I told you there would be no returns." The man quickly replied, " Oh no, that's fine. I was just wondering if you had a brass lawyer."

Tuesday, May 16, 2006

The Constant Gardener

I have just watched the Constant Gardener on DVD. Now this was a movie worth watching, and beautifully transferred to the screen by Fernando Meirelles. Le Carre's books are all about betrayal, and frequently he mixes sexual betrayal with betrayal of country, friends, class, whatever. There were stunning perfomances from Ralph Fiennes and Rachel Weisz, and good supporting roles for Bill Nighy, Pete Postlethwaite, Danny Houston and Juliet Aubrey. The photography is spectacular. There are no green screens, and the single car chase is sinister rather than exciting. * The plot is just the Maguffin; probably preposterous and hardly likely to be true. Pharmaceutical firms may do some dreadful things, but hanging out so far that they are likely to get caught by a idealistic girl is unlikely in their risk averse culture. But that is beside the point, in this sort of literature you need a evil-enough villain, and now the communists have gone, the white South Africans have been defeated and the Moslems blow you up if you attack them, who is there left but big Pharma? It's also hard to believe that you could buy the British government for 1500 jobs in Wales. A peerage perhaps. But the enemy is frightening, fearful and foreboding. Fiennes is just right for the part. Diffident, gentlemanly, polite and dogged. He bears his suspicions of his wife's infidelity with grace and when he discovers her utter faithfullness he breaks down and weeps with both shame and joy. Rachel Weisz is the best pregnant performance since Fargo, but this shameless display fitted so well with her fearless character. All in all a film worthy of the awards it garnered.

Ministry of Unintended Conseqences

If I were Prime Minister I would set up a Ministry of Unintended Consequences. One of New Labor's trumpeted achievements was the incorporation of Human Rights Legislation into UK law. It sounded good at the time, but it has had the unintended consequence of empowering the judges to frustrate the will of Parliament.

Wicked men from other countries, many of them illegal immigrants, commit crimes in the UK, and are recommended for deportation after they have been released from prison. In many cases pure indolence on behalf of the prison authorities and the immigration department has prevented this from happening, but where they do try and carry this out judges rule that it would infringe the human rights of the individual to send him back to Somalia. It's too dangerous for him. It doesn't seem to occur to the judge that it's a dangerous place because it's full of people like the man we want to deport there.

Human rights legislation is unworkable without a written constitution, something Britain lacks. Our rights are founded on the Common Law and legal precedent. The European Convention of Human Rights might fit with the Napoleonic code, or in countries with an elected judiciary, but judges are supposed to interpret the law as parliament intended, they get above themselves when they interpret it as they think Parliament ought to have intended it.

They need to remember the sovereignity of the people in all this is paramount.

This is not the first time that government action has had unintended consequences. Targeting funding to elective surgery had the unintended consequence of starving acute illness of funds. Setting up unitary local authorities had the unintended consequence of reducing the size of social services departments, ending sub-specialisation in social workers, delaying the discharge of elderly patients from hospital, causing a back-up of emergency patients in Emergency Rooms, thus delaying elective surgery. In schools, in hospitals, in prisons, in road building, in energy policy, in Iraq; whatever the government attempts has unintended consequences. What would my minister do? He would say don't legislate, don't interfere; small government is best.

Reading novels

I have 115 unread novels on my bookshelves. Even if I buy no more (and I shall certainly but the new Discworld) it will take me more than two years to complete them. Perhaps I should be a bit more choosy in what I read.

I am currently comparing Kathy Reichs and Patricia Cornwell, the queens of gory fiction. Both have female protagonists who are experts in forensic pathology, which was always the best attended of undergraduate lectures at medical school.

“Reichs is not just ‘as good’ as Cornwell, she has become a finer writer” says the Daily Express on the back cover. One is tempted to ask how they would know. It is certainly not true. Cornwell at least writes mostly in sentences; Reichs writes in phrases. She even has sentences comprising a single word. Really! Many paragraphs consist of a single sentence, sometimes without a verb.

Here’s an example picked at random:

“Flashbulb memory. Gran, shuffling to bed with her Dearfoam slippers and her chamomile tea.

My gaze shifted to the body.

Parent looked small and pitiful on the perforated steel. So alone. So dead.

Stab of sorrow.

I pushed it down.”

I am tempted to put it down.

Although both ‘Blow Fly’ and ‘Monday Mourning’ are a similar size and weight, Cornwell fits over 300 words on the page; Reichs fewer than 200. This is not to say that Cornwell doesn’t go for the one-word, verbless sentence, but she holds it in check and uses it for effect. Reichs comes over as in a breathless panic, and Tempe Brennan, her heroine, as an empty headed woman ruled by her emotions. Scarpetta, who I guess is the prototype for this type of fiction, has become world-weary. No, I think it is Cornwell who is bored with it all; all the characters are tired of life. They have been around too long. Like the regular actors in a TV soap they need killing off and burying under the patio and some fresh blood introduced (pun intended).

What did I get from reading them? A snippet of information about carbon dating and the strontium content of teeth, which I guess I would not have picked up otherwise.

The success of this kind of book is that it sticks to a formula. Every book is the same. We know that Brennan will never settle down with Ryan, that there will always be trouble between Scarpetta and Benton; that Chardonne, like Moriarty before him, will keep escaping. And why not? Dick Francis wrote the same short book about 20 times and each one was a best seller.

Sunday, May 14, 2006

FA Cup Final

The FA Cup Final was a football match worth watching. I have been to Wembley - I watched West Bromwich Albion beat Preston North End in 1954. My father was the Secretary of the Aldershot Town FC supporters club, and as all league clubs were allocated small numbers of tickets for the final, he was able to obtain a ticket. He had been at the 1953 final when Blackpool came back from the dead to beat Bolton Wanderers 4-3. This was Stanley Matthews' final. Some regard Matthews as the greatest footballer ever better even than Pele. He was known as the wizard of the dribble. He played on the right wing and had the beating of every full back. On this great day he provide crosses from the right to enable Stan Mortenson to score three goals. No-one has scored a hat-trick in a Cup final since. Matthews went on playing top football until the age of 53!

The other great winger of that era was Tom Finney who played for Preston North End. In 1954 we thought that Finney might repeat Matthews's feat and win a medal. Alas West Brom won. I was taken to the match by Mr Calton, my headmaster. My father had obtained a ticket for him too. Astute readers will realise that this was the year that I took the 11+ exam. I hope that the bribe wasn't necessary.

Yesterday's match began with defences on top, with very little activity in the first twenty minutes. Then in eleven minutes came three goals. First, West Ham, the underdogs, struck. Ashcroft, the mid-season signing from Norwich, put through a well-timed pass to the overlapping full back, Scolari, who centered immediately. It was the goalkeeper's to deal with, but needing a shout, Jamie Carragher in attempting to clear, shinned the ball into the net with his trailing leg. Minutes later, a shot from Etherington was blocked by Raina, but the goalie lost control of the rebound and Ashcroft punced to slide it home.

West Ham looked to be cruising, but Steven Gerrard, the Liverpool captain, as so may times before, rescued his side. A cross pitch pass cut out both full back and center back, allowing Djibril Cisse to steal in and volley home Liverpool's first.

Peter Crouch is a skinny giant who wins everything in the air. He nods down a high ball for Gerrard to equalize with a screamer from the edge of the penalty area. Within a few minutes West Ham are ahead again. Kanchesky atempts a cross from the left, but he overhits it. Raina misjudges it and it flies over his head and into the net; 3-2.

Time passes. On the stroke of 90 minutes, just as the announcer lets us know there will be 4 minutes of overtime for injuries, Stevie Gerrard lets loose abeauty from even further out and it scorches into the net; 3-3. West Ham are stunned. The cup was theirs. But as teams prepare for extra time it is West Ham who are on their feet and eagar; Liverpool are in agony, cramps and crocks everywhere lying spreadeagled on the pitch.

Overtime: only one incident: a West Ham corner bounces off the back of o0ne of their players. Liverpool cannot clear and the pull falls to Harewood, the West Ham forward who is barely able to stand with a sprained ankle, but all the substitutes have been used and he must soldier on half crippled. Harewood swipes at the ball, but it trickles feebly past the post.

And so to the penalty shoot out. Raina, responsible for two and possibly all three of West Ham's goals become a hero. Only 40 year old Teddy Sherringham's nerve holds for the Hammers. Raina saves three and Liverpool win the cup.


I finally got around to watching Narnia. Was it worth the wait?

I have to say that I was disappointed. It was given the Lord of the Rings treatment and turned into a cinema blockbuster, but I think this was a mistake. The book is a smaller, less complex opus than TLOR - it can easily be read in an afternoon. It is much more a domestic story that doesn't need the opening out to the plains and mountains of New Zealand. The BBC made a television version of it some years ago that in many ways was better, though I couldn't really enthuse about that. Much better to read the book.

To get down to specifics. First, the music was too loud for the speech - and with CS Lewis the words are important. Second, the acting was nothing to write home about. On the whole the children were adequate - Lucy a bit more than adequate, Peter a bit less. Tilda Swinton, who got rave reviews, was, in my view, poor as the White Witch. She was neither frightening nor evil - just some second rate crook with a stick that turned people into statues. Mr Tumnus was good, but the beavers didn't really work and although Aslan was well visualized he never captured the essence of being 'good, but not safe'. Third, the CGI was OK, but after TLOR rather commonplace.

Of course you can't extinguish the wonderful story, even with a below par film. In the BBC series it all went rather downhill for the later books and I don't hold out too much hope for the other six in the manifetation. I would predict that they don't all get made.

But don't let me put you off reading CS Lewis. Try 'Out of the Silent Planet', 'A Gruef Observed' and 'The Problem of Pain'.

Thursday, May 11, 2006

Food for thought

One of the strangest sights I ever saw occurred during the Manchester Uunited versus Charlton Athletic football match last week. Rio Ferdinand, the United and England center-back, collapsed to the ground apparently injured. The referee called on the United physiotherapist who supplied Ferdinand with a packet of McVitie's Chocolate Digestive biscuits to eat. It seems that the cause of his distress was that he was hungry, poor thing.

I wondered at the time whether this was an advertising stunt. Would we see in days to come advertisments for McVitie's biscuits showing Ferdinand revived on the field by their miraculous confectionary? But reflecting on it, I have seen tennis players at Wimbledon eating bananas between sets. Is their something wrong with the diets of modern atheletes?

The current popular injury among English footballers is a fractured metatarsal. So far the following have suffered: Michael Owen, David Beckham, Ledley King, Gary Neville, Ashley Cole, and Wayne Rooney (twice). The boots are blamed. Not for them the heavy leather clod-hoppers, smeared with dubbin, and soaked in the bath to shrink them to their feet; todays carpet slippers with studs don't protect the feet. But we don't see the same injury in Spain or Italy.

Perhaps the answer lies in the diet. The only food item that impacts on bones is Vitamin D. This vitamin is found in dairy food and is also manufactured in the skin when it is exposed to sunlight. One serious possiblitity being looked at by experts is that cows in Britain don't get enough sunshine. In Spain or Italy the sun always shines, but the murky skies over Britain deny the cows the opportunity to make vitamin D. Added to this the curent crop of youngsters never got their school milk the way we did. When she was education minister Margaret Thatcher thought this was an extravagance and took it away (Margaret Thatcher-milk snatcher).

So England may fail to win the World cup next month because of Mrs Thatcher and the murky skies of the North West where little Wayne grew up.

Sunday, May 07, 2006

The Citadel

I have been reading the autobiography of AJ Cronin. It was written in 1952, and I guess that as an author he is not read much today. Yet Dr Finlay's Casebook was a weekly television duty when I was younger and The Citadel, not only a wonderful film starring Robert Donat, but also a book that almost evrybody read that went through over 30 impressions.

It becomes apparent that both Dr Finlay and The Citadel are intensely autobiographical. There really was a Dr Cameron and a Janet at Tanochbrae.

Cronin was a rather unobservant Catholic and his wife a strict Presbyterian, yet they had a long and happy marriage. He gives a picture of what medicine was like during the early part of the 20th century. Lobar pneumonia ran its course without antibiotics and was expected to be fatal. Scarlet fever was an epidemic to strike terror into families. Syphilis an incurable scourge bringing madness to the next generation. Doctors sold tea and sympathy for pennies, wise words and good advice for nothing or strychnine tonics and bogus diagnoses for guineas.

Just as now they got paid more for injections.

For those who made it in this Darwinian struggle there were servants, fine clothes, a Rolls or a Bentley, a gentleman's club and invitations to sup with the high and mighty. For those who failed, there was scraping a living in a lock-up surgery, a dismal two room Bayswater flat and cheap whisky.

Cronin knew both lifestyles, but Providence intervened to deflate his ego whenever he got to thinking that his success was down to him, and the daily degradation that he saw around him caused him to remember his roots.

Life has certainly changed in the last 60 years and all of us in the Western world are affluent and well taken care of, but when I read this book I remembered why I became a doctor.

Friday, May 05, 2006

Diagnosing ITP

A low platelet count is an indication for treatment in CLL according to the NCI guidelines. However, this is only true if the cause is bone marrow suppression. There are two other fairly common causes in CLL: immune destruction (ITP) and hypersplenism (a big spleen).

The diagnosis of ITP is not easy. There is not a simple test like the Coombs test for AIHA that you can do. It is not easy to measue how long the platelets survive. Often the answer can only be determined by a bone marrow aspirate and biopsy. What you see in ITP are increased numbers of megakaryocytes (the cell that makes platelets). Thes often appear immature - their nuclei are not lobulated and there are no platelets budding off their cytoplasm.

This picture needs to be differentiated from MDS, another cause of thrombocytopenia, in which increased non-lobulating megakaryocytes may also be seen. It requires examination by an experienced pathologist who understands bone marrow - not someone whose day-to-day work is examining vasectomy specimens and breast cancer.

Tuesday, May 02, 2006

Bob Dylan

I have been reading Bob Dylan's 'Chronicles'.

This is not a celebrity autobiography ghosted by a professional writer. Dylan can write. The style is engaging.

Bob Dylan was an early favorite of mine. I never thought much of his voice or harmonica playing, but his words were new and courageous and his tunes catchy. In the book he tells us that he never wanted to be a leader of the protest movement of the 1960s. He was a perfomer and a song writer - who cared what he thought about politics. Too bad that modern celebrities don't follow his example. Actors who have appeared in a TV series or singers who have made a hit record are supposed to have been endowed with superior wisdom on the merits of teh death penalty or the Iraq invasion. Says who?

I suppose he could be accused of name dropping, but after all he is more famous than most of the names he drops. His narrative is full of facts and sometimes the minute detail is tedious, but in a funny sort of way he paints a picture of what it was like to be a young singer in New York. Folk singing was an arcane art that shied away from commercial records. Dylan admires all types of music from Sinatra to Neil Diamond to Woody Guthrie and Leadbelly and even Beethoven. There is no clear timeline in this book. We skip from the young man who hitched across from the mid-west to New York admiring the humdrum with wide open eyes, to the married man with five children trying to find something new in a recording studio in New Orleans. Its line is thematic not chronologic.

I guess he's a grandfather now. The fresh-faced youngster of the record sleeve is long gone. The tone of the book is experience, but now and then the innocent ingenue appears