Dhondy

Eleven percent higher mortality, 23% higher incidence of fatal and non fatal strokes and 24% higher incidence of cardiovascular death in patients who took beta-blockers, compared with those who took either a Ca-channel blocker or ACE inhibitor.

Ninety percent of hypertension doesn't have an underlying cause, and is often inherited in a polygenic pattern. The other 10% have an underlying pathology such as kidney disease, either parenchymal or renovascular, or hormonal excesses such as Cushing's or phaeochromocytoma. These may be inherited occasionally, but are much more likely to be acquired. The National Institute of Clinical Excellence (NICE) in the UK recommends starting treatment with an ACE inhibitor such as perindopril in people below 55, and with a calcium channel blocker such as amlodipine for those above 55. If hypertension is not controlled on monotherapy, they recommend adding the other agent. A diuretic can be used as a second or third agent. Beta blockers are no longer recommended for hypertension, unless they are being used concurrently for another indication such as angina. Data from a recent trial called ASCOT show that they are clearly inferior to the first three agents.

Why die wondering? Ask your consultant for a lung function test with reversibility. While you are waiting for it, get a peak flow meter, and record your reading several times a day. See if you are a "morning dipper". That's asthma.

Was reading an old article in NEJM, when I was reminded of Saint's triad. Saint exhorted us to look for three completely unrelated conditions in obese women presenting with abdominal pain- hiatus hernia, gallstones and diverticulosis. Tummy pain in women in particular, and obese women, specially, can be caused by a combination of two or more of the above three conditions. If you follow Occam's razor, find pathology in one of the above, say the gallbladder, you risk missing out on the other two. There is absolutely no correlation between the three, yet Saint's triad has stood the test of history. Hickam, another physician, chipped in with, " A patient can have as many conditions as he bloody well likes."

OK, lucaspa, you have demonstrated that I know fack-all about Occam's razor. Now can we have some more inspiring stories of breakthroughs in Medicine/science please?

Try this. More challenging. Of all the numbers ending with 1,3,7 or 9, which has the greatest proportion of primes?

Time for more proximate stuff. The human genetic code is stored in DNA, packed as a double helix. The purpose of genes is to carry the information for the synthesis of proteins. This information is transferred from the nucleus to the cytoplasm through the agency of messenger RNA (mRNA), which is a single helix, and is a complementary copy of the helix of DNA from which it is synthesized. In the 1990s, scientists tried to get petunias to display the colour violet, by introducing mRNA for a protein that produced violet colour in other flowers. To their surprise, these petunias turned white. Not only were these flowers destroying the mRNA that were introduced, but they were also inactivating their own colour producing genes. The problem was cracked by Craig Mello, working at Mass. University with a roundworm called C.elegans. Mello made several attempts to silence a certain roundworm gene by introducing mRNAs into the roundworm. No luck. Then suddenly, with one batch of mRNA, it happened. The targeted gene was silenced, and stopped producing the putative protein. The effect spread remarkably fast through the worm, from tissue to tissue. Mello was stunned. He discussed the finding with friend and colleague Andrew Fire at Stanford, who noticed that Mello had inadvertently included some double stranded RNA (dsRNA) into the batch that he had introduced into the roundworm. The pair observed to their amazement that ds RNA were 10 to 100 times effective in silencing genes than single stranded RNA. The two published their paper on RNA interference in a 1998 issue of the journal Nature. It explained the petunia phenomenon, but many other things, such as the ability of human cells to neutralize RNA viruses. It is now thought that this is a pretty ancient characteristic of most living cells, including humans, plants and animals, and plays a role in silencing invading viruses, but also jumping genes or transposons, which can often cause cancer. Mello and Fire's discovery paved the way for further scientific work on such RNA, called small interfering RNA (siRNA), which are being used to silence certain genes in human and animal cells, and thereby elicit their function. It shouldn't be long before such research translates into therapeutic applications. Mello describes the morning of 13th October in 2006, when his phone started flashing at 4:30 AM. His wife asked him not to pick it up, as minutes earlier, somebody has made a "prank call" to the efffect that her husband had won the Nobel Prize. When Mello told his missus that it was the day that the Nobel Prize in Medicine was traditionally announced every year, she was completely gobsmacked. For their work on RNA interference, The Nobel prize for Physiology and Medicine was awarded to Andrew Fire and Craig Mello in 2006.

C'mon, that should be really easy to answer. Any number ending with 2,4,6,8 or 0 will always be divisible by 2, and hence can't be a prime. Similarly, numbers ending with 5 will always be divisible by 5. That leaves numbers ending with 1,3,7 and 9.

Crossing the eye is essentially an exaggeration of the physiological movement of convergence, as happens when you focus on an object very close to you. The musles involved are the medial recti, which are innervated by the oculomotor (III) nerve. On the other hand, following an object with your gaze requires conjugate movement of both eyes, achieved by abducting one eye with its lateral rectus, innervated by the abducent (VI) nerve, and adducting the other eye with the medial rectus, innervated by the oculomotor nerve. The way this conjugate movement is achieved is through a bundle of fibres on either side of the brainstem, called the medial longitudinal fasciculus (MLF), which connects the abducent nucleus of one side to the oculomotor nucleus of the other side. Thus, when the lateral rectus of one eye contracts, the medial rectus of the other eye has to contract with it. Hence we can't disconjugate this movement, i.e. move them in opposite directions. This may be lost in internuclear ophthalmoplegia, a condition affecting the MLF, as is found in brainstem stroke occasionally, but much more commonly in multiple sclerosis. Under this condition, conjugate movement in one direction is lost.

If you accept that The Priniciple of Parsimony is, of necessity, based on existing knowledge, then you will understand what I meant when I cited the example of the role of H.pylori in peptic ulcers. When Warren and Marshall made their groundbreaking discovery, the following were the existing beliefs: 1. Ulcers are caused by an excess of acid or by a breakdown in the protective mechanism of the gastric mucosa, caused by a reduction in prostaglandin synthesis due to drugs such as NSAIDs. 2. Bacterial infection could have no role to play in this, as bactreria simply could not survive in the acid environment of the stomach. 3. Reduce the acid, and the ulcers would heal, and stay healed. Now, statement 3 was implicitly based on statement 1. If you felt that acid caused ulcers, William stipulated that you followed that up by deducing that reducing acid would heal ulcers. Agreed? William would have been wrong. In 75% of cases of gastric ulcers and >90% of duodenal ulcers, acid was not sufficient to cause ulcers, and reducing acid, while healing some ulcers, would inevitably be followed by a recurrence of ulceration at some stage, unless you got rid of H.pylori by triple thearpy. Anyway, let's move on. The purpose of this thread was not to have a philosophical discussion about the correct application of Occam's razor, but to inspire ourselves as a community, with tales of scientific breakthroughs that went completely against the perceived wisdom of that age. Discoveries so unintuitive, they were considered almost heretical at first. I'll try and think of some more. Can I start with Barbara McClintock? This lady has always been one of my biggest heroines because her work was so ahead of her times. In the early 1940s, working on heritability in maize on Long Island Sound (between Connecticut & Long Island), she found that colours of maize kernels changed rapidly, with variegation is single grains of maize, indicating rapid transitions in genetic material. This mottling effect defied Mendel's basic principles of genetics because individual grains were multicoloured rather than a single colour. From this simple discovery, McClintock thought of the concept of transposons, which are genes that move from one location to the other on the chromosome, and either inhibit or stimulate an active gene. In the case of maize, the position of transposons might inhibit or block pigment production in some cells. For example, if the transposon moved to a position adjacent to a pigment-producing gene, the cells were unable to produce the purple pigment. This resulted in white streaks or mottling rather than a solid purple grain. Now consider that this discovery was made before the genetic code & the structure of the DNA double helix was known, and you begin to realize the enormity of her genius. The importance of her discovery was not realized till the advent of the concept of onco-genes (cancer causing genes) & genetic engineering in the late 70s and early 80s. Oncogenes may be activated by the random reshuffling of transposons to a position adjacent to the oncogene. Similarly, transposons may be useful in genetic engineering with eukaryotic cells, by positioning transposons to activate certain genes. The most common example of this is found in genetically modified crops. So it was that in 1983, fully 40 years after Barbara McClintock first described "jumping genes", she was awarded the Nobel Prize for Physiology & Medicine in recognition of her genius.

Then how would you describe it, pray, dear mademoiselle/sir? Do edify this poor yokel.

Oh, delete the bloody thing if it bothers you that much. It's not as if it's gonna win the Pulitzer for me, is it? ;-)

This is "everything goes" section isn't it? Have a look at the desription of the subsection. And now you can bugger off to your sad existence, my friend.

Tick tock...tick tock...Have you ever thought what happens at 5 PM everyday? If you were in space, listening to the earth with a giant stethoscope, you could hear approximately one third of the men and women who are in the same time zone, push back their chairs as they finish work for the day. The discerning diaphragm might also pick up the familiar sound of MS Windows shutting down, the keys turning in their mortice as the doors are locked for the final time. The spying eye high in space would suddenly see an entire longitude plunge into darkness as the office lights are turned off. The stethoscope would pick up the cheery babble of people as they said goodbyes for the day, relieved to be going back to their home and hearth. And then...silence. The profound silence of deserted buildings and empty carparks. Why does it have to be 5 PM? Well, because 5 PM comes between 4 PM and 6 PM. The civilized society views the world in thirds. This third is mine, the other third is yours. A pack of bread has twelve loaves, to be had in fours. People like to have a beginning, a middle, and an end. No surprise then, that the day has 24 hours, divided into three equal eights. Eight for sleeping, eight for working, eight for fun. If 5 PM was 4 PM, you would have to start at 8 AM. Too early. Too dark in many parts of the world. Finish at 6, and you have the mortification of getting home at seven. There's a kind of watershed feeling about seven. It's the peak hour. TV channels start their best shows at 7, Classic FM put in the connoisseur's hour, Channel 4 start the news and the latest feed about Big Brother...you don't want to be getting home at seven. It's got a kinda... missed the boat sort of feeling. Therefore it has to be 5. Or does it? I always view 5'o clock with some satisfaction, but for somewhat different reasons. For me, it's the start of the grace hour, the unpaid hour I put in when I can, freed from the burden of having to work for a living, having to fulfil my obligation to my employers. It's got the refreshing whiff of going the extra mile, of claiming the high moral ground, of the satisfaction of making my colleagues feel slightly guilty as they slam their doors on their way home. Five PM is a familiar hour on Saturdays. As you tune the radio in to Five Live, you hear that same unmistakable voice reading out the football scores as it has done for the last 20 years...Manchester City 1, Aston Villa nil....Bolton nil, Charlton nil...Hibernian 1, Dundee 1.... As if anybody cares about Hibernian and Dundee. Really! But you can see where he is coming from, can't you? It's 5 PM and he has to live the tradition. There will be crushingly boring accounts of the five-nations rugby coming up, with lurid descriptions of how France mauled Italy in their backyard, but you don't switch off. You can't. It's 5 PM. And it's Saturday. Switching off takes a break.

OK, here's another example of failure of Occam's razor in medicine. We all grew up reading that bugs couldn't survive for long in the acid environment of the stomach, right? Surely, that was one of the reasons why the colon was chockful of the little buggers, while the stomach had none. The idea therefore that little rod shaped bacteria called H. pylori could cause gastritis and peptic ulcer was completely counter-intuitive to the scientific community. When Barry Marshall, Aussie medic extraordinaire, in conjunction with the older, seasoned Robert Warren mooted this idea, he was subject of much ridicule from his peers. In fact, Barry had to drink a solution teeming with the bugs, and develop an endoscopy proven ulcer, before people woke up and realized that he was onto something. The Nobel Prize in 2005 brought some consolation, I should think. You may call this a failure of Occam's razor, you may chose to call this a triumph of cussedness over ignorance based on existing knowledge, or lack thereof, but it doesn't really matter, it's just a matter of semantics. The old fogeys told off Marshall & Warren because they were making unproven "assumptions" in their view (Marshall observed the bugs on microscopy of gastric biopsies and then took a leap of faith in linking them to dyspepsia and ulceration). The point I am trying to make is that Occam's razor often involves taking the path of least resistance based on existing knowledge, and people use that to create and perpetuate scientific dogma, as in this instance.

The OP is close to the truth. We do often get near cancerous cells during repair of tissues. The body has mechanisms to recognize and cause self destruction of such cells, through apoptosis (programmed cell death). At other times, the body's defence system, comprising NK cells, T cells in conjunction with antigen presenting cells, B cells (which produce antibodies), and macrophages recognize the altered cells and kill them. Under certain condition, the apoptotic process fails, as does the surveillence mechanism, and cancer may eventuate. Edit: Somebody got there before me, I see!

Actually, that's NOT the Razor. William of Ockham actually meant that, when describing a phenomenon, include no unnecessary entities. I did say this in the next line. Occam's razor implies that in reaching a solution, try and make as few assumptions as possible. This is the key to interpreting Occam's razor. This is also called the "Principle of Parsimony". Good example, anyway.

William of Oakham, mispronounced as Occam, used to live not far from where I now stay....but around 700 years ago. His lasting legacy to philosophy, and indeed to problem solving, was the principle called "Occam's Razor", which essentially states that in trying to resolve to a problem, try and reach for the simplest solution that explains all parts of the problem. Occam's razor implies that in reaching a solution, try and make as few assumptions as possible. I have outlined this in bold, as this is the key to interpreting Occam's razor. This is also called the "Principle of Parsimony". Lest people use this blindly, let me quote something I read, "Occam's razor is no substitute for insight, logic and the scientific method". In the words of Einstein, "Everything should be made as simple as possible, but not simpler." Indeed, much of science draws on Occam's razor, and mostly it stands up to scrutiny. There are occasions though, when it lets you down badly, and one must always be aware of such pitfalls. Let me give you three examples, one from medicine, one from genetics, and one from nature to illustrate this better. Until very recently, upto six years ago, hormone replacement therapy (HRT) was considered the panacea for women who had recently reached menopause. It made intuitive sense- it made them look younger, it stopped their hot flushes, it strengthened their bones, and above all, the oestregen component lowered the levels of cholesterol in the blood, thus holding out the promise of reducing heart attacks and strokes in the future. Quite clearly, Occam's razor pointed to a win-win situation for HRT. Why would anybody be worried about using it? Imagine the shock of the medical community therefore, when, a few years ago, a very large controlled study, called the Women's Health Initiative, showed that HRT in fact increased the risk of heart attacks and strokes in post-menopausal women significantly. The finding led to a worldwide drop in prescriptions for HRT. It is now only used in the short term for alleviating troublesome symptoms such as hot flushes. Another example. High alcohol intake has been shown to be a risk factor for head and neck cancer in observational studies. This is thought to be due to acetaldehyde, a carcinogen that is obtained during oxidation of alcohol in the body. There are two allelles for the gene that oxidizes alcohol- one, let's call it B2, converts alcohol to acetaldehyde 100 times faster than the other, say B1. Scientists therefore justifiably postulated that persons who had two copies of B2, would be at a far higher risk of head and neck cancer than those with B1-B1 or B1-B2. In reality though, it turned out that both B1-B2 and B1-B1 had a far higher risk of developing cancer than B2-B2. The reason for this was that acetaldehyde has very unpleasant effects on the body- it makes people feel unwell. The homozygotes for B2-B2 therefore cut down on their alcohol consumption to escape the dysphoric effects of acetaldehyde, while those with genotypes B1-B2 or B1-B1 continued to drink with impunity, and thus became more susceptible to head and neck cancer. The principle of parsimony would have suggested a higher risk for B2-B2 based on the genotype, but it obviously could not account for confounding by alcohol consumption. Finally, let me give you a topical example from nature. If you watch National Geographic, you will know that there is a huge concern about the dwindling number of cheetahs. There are only 10,000 of them left in the wild, they do not mate very easily, and the cubs they produce are often killed by other predators. Scientists were concerned whether, firstly cheetah females had enough males to mate with, and secondly even if there were enough males, whether mating was taking place often enough, a view based on Occam's razor, due to the low density of cheetahs in general, and the behaviour of females studied on camera. Imagine the surprise of nature scientists therefore, when DNA analysis of cheetah cubs recently revealed that female cheetahs were in fact shamelessly polyandrous, with up to half of their litter being sired by different males. That is to say, they were sleeping with every stranger that came along! It is thought that this kind of behaviour offers a survival advantage by allowing genetically variable offsprings to adapt better to vicissitudes and by reducing infanticide by male cheetahs, who are often confused as to the parentage of the cubs! Who would have thought, eh?