Cui Bono: For Whose Benefit?

So Irish citizens - men, women and children - are to be crucified on a cross of gold, to shore up the failing Euro.

These huge loans are not for Ireland's benefit.

Ireland needs export-driven industry, creating jobs, the means to repay debt, and to move back to a sustainable prosperity.

But Ireland is small country on the periphery of Europe; exporting is more expensive than in Germany. For this and other reasons the Euro is an over-valued currency in Ireland. A new Irish Punt would be valued much below the Euro.

Ireland cannot export successfully and remain in the eurozone. The Euro blocks Ireland's route to recovery.

Meanwhile German industry exports with increasing success. If Germany restored the Deutschmark it would be valued way above the exchange rate of the Euro. Like China, Germany has an undervalued currency. This has encouraged the development of the huge trade imbalances which caused the crisis.

Some are saying that the value to Germany of an undervalued currency exceeds the costs of loans to states crippled by the Euro, so Germany will fight to keep the Euro until this calculation reverses.

Unless the German Constitutional Court declares such Euro rescues are unlawful. I understand the court's judgement is expected in February.

In the meantime we should recognise reality: the European Union, and specifically the Eurozone, is the Deutsches Wirtschafts Reich - the German industrial empire.

Too Clever By Half

Being too clever can complicate diagnosis. Most often it is a problem for the able young doctor, not yet case-hardened, not yet clear that common things are common, and that an unusual presentation of a common disease is more likely than a rarity.

But over-clever errors can afflict us all, no matter how learned and experienced we may be.

This happened to me after nearly a half-century in practice.

Elwyn was 54 years old. He had a hill farm with a flock of sheep. He was tall, slim and fit, and a non-smoker.

So it was a surprise when he was sent to the hospital as a suspected myocardial infarction.

Soon after getting up that morning he had a sudden severe chest pain, which stopped him. He sat down, in pain, and feeling nausea. He felt his heart thumping and became short of breath. The pain subsided after several minutes but the palpitations and breathing difficulty continued.

He had no significant past medical history; and no heart disease in the family.

He had an electrocardiogram on arrival, which showed some anomalies, but not the changes of acute myocardial infarction.

On examination he looked grey, sweaty and ill. He was sitting up, visibly short of breath, and became distressed at any attempted to lie flat. From the foot of the bed I could see pulsation in his carotid arteries.

His pulses were increased and collapsing, at a rate of 100/minute, regular. Blood pressure was over 250 systolic, with no clear diastolic cut-off down to zero.

The immediate suspicion was that he had suffered some sort of acute failure of the aortic valve, so I was surprised to find a forceful apex beat in the right place - in the 5th. left interspace, in the mid-clavicular line. Leaking valves put a volume load on the heart, causing dilation.

The stethoscope revealed a loud diastolic murmur of aortic regurgitation, as expected.

But listening at the apex of the heart I heard a second, low-pitched, diastolic murmur. Austin Flint's name is associated with an apical mid-diastolic murmur, and this was my first thought. But listening further I hear an early diastolic snap, followed by a decrescendo murmur, increasing again before a loud first sound. These are the classical signs of mitral stenosis.

I demonstrated these signs to the house physician and two students, who agreed with me. Well, I suppose they would.

But it didn't make sense. A double valve lesion must mean a heart damaged by rheumatic fever, probably in child-hood, and long-standing valvular disease. But this man had no such history, and was in good health until a few hours before.

An associated mitral stenosis might explain the undisplaced apex beat.

I was perplexed. I called my cardiological colleague. By good fortune he was in the cardiac laboratory; bring down the patient for an echo-cardiogram.

I watched fascinated. The root of the aorta was dilated, and the valve stretched, the cusps not meeting. There was massive reflux of blood into the left ventricle during diastole. The left ventricular cavity was dilated.

The mitral valve was normal, but it could scarcely open in diastole before the flood of reflux had filled the cavity, pushing the mitral valve cusps back and together. The phonogram showed this was the cause of the opening snap I had heard. The diastolic murmur was functional: high left atrial pressure and atrial systole forcing blood through a closed valve into the full ventricle.

And the heart had not dilated because it was all so acute. Over the next few hours it would, with rapidly increasing left ventricular failure.

Elwyn needed emergency surgery. He was transferred to the cardiac surgeons in another hospital that afternoon, who operated that evening. They put in aortic arch and aortic valve prostheses.

The pathologist reported the resected aorta showed cystic medial necrosis, a recognised degenerative condition.

Elwyn did well, but I didn't see him again - he was followed up by the cardiologist. I heard later he decided the farm was too much for him.

As a young doctor studying for a higher examination I had spent many hours practising with the stethoscope. I had become - yes, I'll admit it - proud of my skill with that challenging instrument. On this occasion I had fallen.

Had I not been so clever when I listened I would have got the right diagnosis.

The Vital Reaction

Carbon dioxide, CO2, or O=C=O, is a gas at the temperature and pressure of our environment.
Water, H2O, or H-O-H, is a liquid.
Both compounds are relatively stable in chemical terms, and abundant in our biosphere and in the kosmos.

Carbon dioxide is soluble in water, and in solution the two compounds may combine to form carbonic acid:

CO2 + H2O <---> H2CO3

This reaction is incomplete: at equilibrium carbon dioxide, water, and carbonic acid exist together in significant proportions in the solution. Of course, removal of one component will pull the reaction in that direction. So, for example, adding calcium hydroxide leads to the precipitation of solid calcium carbonate, eventually trapping all the carbon dioxide. This process cleared huge quantities of carbon dioxide from the atmosphere of the young earth.

The formation of carbonic acid is an important process in geochemistry and physiology, but a second and much more difficult reaction of carbon dioxide and water is perhaps the most important chemical reaction in our biosphere.

The vital reaction is the combination of carbon dioxide and water to produce formaldehyde and oxygen:

CO2 + H2O ---> H2C=O + O2

Formaldehyde is the simplest carbohydrate - compounds which have molecular formulas which reduce to multiples of hydrated carbon, (C.H2O)n.
Under normal conditions this reaction does not proceed at all. The reason is that the products - formaldehyde and oxygen - together contain much more energy than the starting materials. Energy from radiation - photon energy - can drive the reaction. Radiation from stars can cause the production of formaldehyde in surrounding gas clouds. In our biosphere photosynthesis traps solar radiation energy to fix carbon dioxide to produce carbohydrates. Photosynthesis does not produce formaldehyde, which is very toxic to cells, but glucose and other carbohydrates, which are polymers of formaldehyde. Let me explain.

Two molecules of formaldehyde can combine to form glycol aldehyde:

H2C=O + H2C=O ---> H2COH.HC=O

Glycol aldehyde still has the reactive HC=O aldehyde group, so it can react again with formaldehyde to produce glyceraldehyde:

H2COH.HC=O + H2C=O ---> H2COH.HCOH.HC=O

Glyceraldehyde also keeps an aldehyde group, so it too can react further with formaldehyde. In theory the process can go on and on, producing huge molecules. In biology it stops usually at six - glucose, galactose, fructose, and other sugars.

The photosynthetic reaction may be written thus:

(C.H2O)5 + CO2 + H2O ---> (C.H2O)6 + O2

The stages of the reaction are complicated, but overall 1 formaldehyde unit is added to ribulose, a 5-fold formaldehyde polymer, producing the 6-fold polymer glucose, and molecular oxygen. The reaction is driven by radiation energy from the sun.

Glucose is a remarkable molecule. It will form a 6-membered ring structure, by the interaction of the aldehyde and the hydroxyl group on carbon 5 in the chain. The resulting ring has 5 carbon and 1 oxygen atoms. Excellent diagrams can be found here.

Glucose is an important biological fuel, releasing energy as it is broken down in stages, eventually releasing the carbon dioxide and water from which it was made. Glucose is also a starting material in the biosynthesis of many other compounds, and it can polymerize into chains of glucose molecules, notably cellulose, the dominant biological product on earth.

Glucose molecules may combine together in one of two ways. The first is the 1-4-beta linkage. Cellulose is a high molecular weight polymer of glucose units linked in this way. The resultant chain molecules have abundant hydroxyl groups, which are in a configuration favouring intermolecular linkages, excluding water. In this way the insoluble long fibres of cellulose are made and are woven to form the cell walls of plants.

Wood is cellulose impregnated with lignins: complex organic molecules which waterproof, stabilise and protect the cellulose.
Chitin, the tough outer shell of insects, is a similar polymer of a simple derivative of glucose - N-acetyl-2-glucosamine.

The second linkage, 1-4-alpha, produces polymers which tend to form branching coils rather than fibres, more soluble in water, and used as biological energy stores: starch in plants, and glycogen in the muscle and liver of animals.

Starches and glycogen are easily broken down to release glucose: the necessary enzymes are common in the biosphere.
Cellulose is much more difficult to digest, and few organisms have enzymes to do this. Those which do are mostly bacteria or fungi, and animals able to digest cellulose usually rely on bacteria in the gut to start the process for them: wood-boring insect larvae, for example. Cattle and other ruminants have complex stomachs in which bacterial enzymes ferment cellulose from plant structures reduced by grinding teeth, often given a second grinding by 'chewing the cud'.

In our biosphere the rarity of cellulases is remarkable, given the energy potentially available from the digestion of cellulose. In consequence woods are biologically stable, and forests are possible.

But here's another spooky fact. At 19% the concentration of oxygen in the atmosphere is near the maximum if cellulose is to be stable. At 25%, for example, fire might well be so frequent and so extensive that forests could not survive. At 33% cellulose would degrade rapidly on exposure to air, and fire would spread explosively.

Life and the planet must interact to maintain the environment most favourable for life, in ways which we do not understand.

Next time you look at a tree, remember that most of what you see is polymerized formaldehyde, the virtual first product of that remarkable reaction of carbon dioxide and water, energetically unfavourable but vital; which biology achieves with aplomb, and which chemists strive to emulate.

And next time you see wood burning, remember you are seeing the release of energy formed by nuclear fusion reactions in the solar core, many years ago.

Diagnosis is Dangerous

Diagnosis is dangerous. A mistaken diagnosis means wrong advice and management; and failure to identify the realities and respond correctly.

A diagnosis also tends to inhibit thought, especially if a senior doctor has made it.

When there is uncertainty we may speak of a provisional diagnosis, or a working diagnosis, but, being human, all too often those warning adjectives are forgotten.

The obvious diagnosis is especially risky, quickly made, an easy case, time for tea. But the obvious may conceal the real, perhaps much more sinister.

Here are two examples: the first shows the dangers of a wrong diagnosis, the second the danger of the obvious.

Jane was in her early 60's. I was asked to review her at home. Her general practitioner met me there, with a bulky folder of notes.

At the age of 25 she had lost vision in her left eye, but recovered after several weeks. The doctor had recognised retrobulbar neuritis, an inflammation of the optic nerve. In about half of cases retrobulbar neuritis is a first sign of multiple sclerosis; equally, in about half of cases it is not.

During the next two or three years she had seen doctors on several occasions with recurring, transient minor symptoms: numbness and tingling in one or other hand, headaches, an episode of difficulty in writing, and another of double vision. None of these episodes had lasted more than a day, and none had left any disability.

But a diagnosis of multiple sclerosis was made, and discussed with her. To be fair, multiple sclerosis is often a difficult diagnosis, but easier now we have MRI brain scanning.

Over the years she had lived in the expectation of progressive disability and an early death. Her minor symptoms continued, but no demonstrable physical disability developed. She had never married, and lived in a small flat on invalidity benefits. She was active in charities for disabled people, indeed she held a national post in one.

She had received little formal medical treatment, but was on a complicated vegetarian diet, and a number of mineral and vitamin supplements, including regular injections of vitamin B12.

On examination she was tense and talkative, rather obsessive about herself, wearing blue-tinted spectacles, but well nourished and apparently healthy. I found no physical abnormalities, in particular I found no signs of nervous system disease.

As a rough guide, a rule of thirds applies in multiple sclerosis. At 15 years from diagnosis, one third will be dead, one third will be disabled, and one third will be living reasonably normally. Jane was well some 40 years from diagnosis. Either her multiple sclerosis was exceptionally benign, or the diagnosis was in error.

Reviewing her case notes I concluded that the diagnosis was wrong: the original evidence was inadequate, and her subsequent course was not compatible with multiple sclerosis. [Yes, I had the benefit of hind-sight.]

But what to say to her? The belief she had multiple sclerosis had dominated her life for many years; could I kindly say it was all a dreadful mistake? I chose to say her case was exceptionally benign, and the disease had burned out. That might just have been the truth.

I learned later that my assessment had been reported with approval to her many friends, but she had continued much as before - perhaps the best outcome.

Pat was the second case, in her forties, mother of three, working part-time in a local hotel. She had been admitted the day before for a minor operation on her varicose veins. She should have gone home the same day, but persistent vomiting had set in after the operation. It had continued and my surgical colleague asked me to see her.

The consultation request was on my desk when I returned from my Friday morning out-patients' clinic. I had an hour for lunch and the 12 mile journey to another hospital where I was due at 2 pm.

Pat complained of nausea, but the sickness had subsided and she had been able to have some toast and tea. She was anxious to get home.

There was an obvious cause for her nausea: she was taking Distalgesic for pain control. Distalgesic combines paracetamol with dextropropoxyphene, which is a synthetic opiate, prone to cause nausea in susceptible people. It was a familiar problem with this drug.

So the prescription was easy: stop Distalgesic, take simple paracetamol if needed. Go home.

A week later my surgical colleague told me she had gone home, but had returned the next day because the nausea and vomiting had increased, despite stopping the Distalgesic.

Blood tests had shown her serum calcium value was 4.6 mmol/L - seriously increased above normal. Vomiting is a symptom of such a high calcium value. A chest X-ray showed her ribs had multiple translucent areas - the appearance of malignant secondary deposits.

Finally a proper clinical examination found a large hard lump in her right breast. Biopsy confirmed Pat had breast cancer, widely disseminated, a terminal disease.

Opportunity is fleeting; experience fallacious; judgement difficult.

The Four Horsemen of Apocalypse

Another Armistice Day - a cold grey November morning of commemoration, 92 years on from the armistice ending the first of the great European catastrophes of the twentieth century.

My intention was to explore the disastrous wars of the twentieth century, which bled Europe near to death, and unleashed untold suffering on the world. It is the sequence of classical tragedy writ large: koros, hubris, ate, nemesis.

Koros - success, satiety, disdainful self-satisfaction;

Hubris - arrogance; smug, contemptuous pride;

Ate - reckless, self-confident stupidity;

Nemesis - punishment, retribution, downfall.

This grim sequence repeats and repeats again in the histories of humanity, great and small. When will we ever learn?

Do we not see the same grisly sequence revealed in our present banking crisis?

But let me be content to offer a simple calculation, to show the magnitude of the disaster into which Europe sleep-walked in 1914.

John Keegan, in his history of the first world war, estimates that the war cost 10 million deaths. Most of these were young men, disproportionately the brightest and best, the seed-corn of the next generation.

Imagine a parade of those 10 million. Let them march past in ranks of 10, 3 ranks to a platoon, 4 platoons to a company, 4 companies to a battalion. Let them march in quick time, at the rate of a battalion a minute; 48 ranks, 480 men, each minute.

That means 28,800 march past in 1 hour.

And the parade would last 347 hours, more than two weeks, marching day and night.

And that was just the beginning. God help us.

PS And let the ranks be spaced at 5.28 feet - that is 1000 ranks per mile. Then the parade would be a thousand miles long, approximately London to Munich, or London to Inverness and back.

Athos 6: Aphroditi, Dawn-Bearer

Karakallou Monastery on Mount Athos; Tuesday, 2nd. September 2010; 0630.

I was waiting in the courtyard west of the church; my two companions had been at the morning service since 0500. I could hear the rise and fall of the chants, punctuated once by the clashing of the censor. Candles were visible, dimly through the windows.

It was still dark, the monastery obstructing any view of the eastern horizon, and signs of sunrise.

The air was clear and cool. At the zenith the half-moon reflected moonshine enough to see details of the buildings, and bats flying round the church.

A brilliant morning star shone down about twenty degrees west of the moon. Pure white, no twinkling, a tiny disk to the naked eye. The planet Venus, in glory.

My companions emerged from the church. Knowing Ilias is interested in astronomy, I drew his attention to the moon and Venus. He became excited, pointing and calling 'Aphroditi, Aphroditi!'. His voice echoed round the courtyard: a strange name to be heard in such a place.

Aphroditi shining into Karakallou, unseen by the monks buried in the church.

He explained to me that Aphroditi is the morning star, Hesperos the evening star: two names for Venus in opposite chords of her orbit. She may also be called Eosphoros, 'dawn-bearer'. In Latin she is Lucifer, light-bearer.

[Lucifer became a name of Satan. This association may be more apt now we know that Venus is hellish. She has a dense atmosphere of carbon dioxide, a surface hot enough to melt lead, and the brilliant white we admire is sunlight reflected from clouds of sulphuric acid. But she retains her great beauty at our distance.]

In Tolkien Venus becomes The Flammifer of Westernesse, the Silmaril on the ship bearing Earendil, doomed forever to be the herald of dawn and a sign of hope to mortal men.

But these musings were interrupted by the procession of monks coming from the church, black hooded heads bowed, eyes unlifted, black cloaks blowing in the breeze: comparison with the bats still flying was inevitable. With my companions I joined the end of the procession into the refectory with icons in bright paint on every wall, to sit at the pilgrims' table. After a lengthy grace, a monk reading a holy text timed the 10-minute breakfast of pasta, with feta cheese and - surprisingly - red wine.

And then, alas, time to pack up and leave this beautiful place.

On the road from Karakallou, these Ricinus plants graced the wall retaining one of the monastery's vineyards.

The Eleventh Month

November - that should mean the ninth month.

Today is a nicely palindromic date: 01-11-10 in DD-MM-YY format. Enjoy it while it lasts - it will be a century before it happens again.

Today is bright, autumn golds brilliant in the low sun. But this will prove exceptional. You will not be disappointed if you expect November in England to be as Thomas Hood described so memorably.

No sun, no moon,
No morn, no noon,
No dawn, no dusk, no proper time of day;
No warmth, no cheerfulness, no healthful ease,
No comfortable feel in any member;
No shade, no shine, no butterflies, no bees,
No fruits, no flowers, no leaves, no birds:
November!