Health and Medicine – Page 22

MMR and Statistical Manipulation

Measles virus

When I was still at high school, way back in the late 1970s, there was a health scare that got a lot of media attention. Apparently, there was a perceived risk that the whooping cough vaccine could cause brain damage. The fall off in vaccination for this disease is claimed to have led to the widespread outbreaks of whooping cough in 1979 and 1982, there having previously been almost zero annual cases. At the peak there were some 60,000 cases.

Fast forward to the near present and you will recall similar scare stories about the combined measles-mumps-rubella vaccine, the MMR, and claims by researcher Andrew Wakefield (Lancet, 1998) that MMR could cause autism in some children. It’s a topic guest blogger Michael Marshall covered on Sciencebase in November 2004. It seemed that, at the time, the debate was pretty much over. However, despite repeated demonstrations of the apparent inadequacies of the original research into a link between MMR and autism, the issue is resurrected on a regular basis. Most recently in a cover story in The Observer, which drew much flack, but also left the chattering classes once more in a flap.

Right now, I’m looking at an article from the print edition of The Times offering an answer to the Question of the Week – “Measles or vaccine?” – the article talks of how measles has reappeared and it is apparently all down to many parents’ reluctance to have their children vaccinated with the MMR jab. The article talks of “herd immunity” and how enough children have had a double dose of MMR which should stave off an epidemic. The emergence of herd immunity, of course, will be little comfort for a parent whose child experience any of the potentially severe side-effects of vaccination.

In the article, pictured alongside a blow-up of the measles virus and an image of a nasty-looking hypodermic needle, are two charts, one showing the number of cases of measles in the UK from 1940 to the present day and the other showing the number of deaths over the same period. Incidence of the disease ebbed and flowed during the period up to the early 1970s whereupon cases began to fall rapidly from a peak of 800,000 a year in the early 1960s to just one or two hundred a year by the mid-1970s.

The MMR vaccine was introduced in the US in 1971 and later in the UK, thereafter incidence of measles has pretty much fallen to levels close to zero. It seems that the pre-vaccine drop had another cause, presumably reduced overcrowding, improved nutrition, better hygiene and healthcare. No one knows at what point this fall would have reached a plateau.

In contrast, the second chart of death rates shows an exponential decline in measles deaths since the 1940s, by about 1970 measles deaths were also close to zero. The risk of getting measles is about one in three, assuming no vaccination coverage at all. The risk of serious consequences to this disease, which personally I had in 1972 or thereabouts, is somewhere between 1 in 5000 and 1 in 15,000. Compare that to the risk of death in a road accident. According to Transport2000 , the UK’s national environmental transport body, each of us has a 1 in 17 chance of being killed or seriously injured in a road crash during our lives. Such figures damn the disease statistics somewhat. Of course, vaccination does come with some risks, but adverse reactions, such as seizures with an associated risk of brain damage, exist at the 1 in 10,000 level.

There has been one UK death from measles since 1992 (as opposed to the several hundred each year during the 1940s). The unfortunate victim was apparently suffering an underlying lung disease for which he required long-term immunosuppressant drugs. He was very unfortunate to be exposed to the measles virus, and when he contracted the disease he was very unlikely to have recovered. This is one fatal case. Even with near 100% vaccination, there would still be a finite risk of any random member of the population contracting the disease. Unfortunate, but true. The statistics would not lie surely?

Cacao caffeine myth – Chocolate Myths

TL:DR – Cocoa beans, and so chocolate, can contain a small amount of caffeine despite claims to the contrary.

Caffeine theobromine

A front page item on a social bookmarking site claimed that chocolate does not contain caffeine. The link was tied to an introductory paragraph that said: “There is a persistent urban legend that chocolate contains caffeine. It would seem that this rumor is based primarily on a confusion between two similar alkaloids: caffeine and theobromine. Theobromine is the active ingredient in chocolate and it occurs only in [the plant Theobroma cacao. The two stimulants are related and have similar structures.”

Yes, they most certainly do, theobromine (not in any way related to the element bromine by the way) and caffeine are almost the same chemical structure but in the caffeine molecule the hydrogen atom on a nitrogen atom in theobromine has been swapped for a methyl (CH₃) group. Why is this important? Well, the difference in chemical and biological activity of two molecules that can differ by a couple of hydrogens and a carbon is astounding. More on that later. What about the site’s claims that chocolate does not contain caffeine?

A quick search on PubMed plucked out several papers all of which have carried out analyses of chocolate to demonstrate that it does indeed contain caffeine. As just one example, in 2006, German researchers Stark, Bareuther, and Hofmann of the German Research Institute for Food Chemistry, in Garching, provided a molecular definition of the taste of roasted cocoa nibs (Theobroma cacao) by means of quantitative studies and sensory experiments. In their paper they state: “theobromine and caffeine…were among the key compounds contributing to the bitter taste of roasted cocoa.” Their tests were carried out using solvent extraction, gel permeation chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC) and corroborated earlier findings. The actual quantity of caffeine in chocolate is very small, especially compared with the amount of theobromine.

To quote the UK’s Institute of Food Research on the subject of caffeine in chocolate:

“Chocolate contains bio-active compounds, e.g. caffeine and theobromine. Caffeine is only present in small amounts in chocolate – in fact, one would have to eat about eight 100-gram bars of milk chocolate to consume the amount of caffeine present in a cup of coffee. Theobromine is related to caffeine, and is present in chocolate in much higher amounts, although it has relatively weak stimulant effects. It is possible that in combination, these and other potentially bio-active constituents do influence our liking for chocolate. At present, however, there is no direct evidence to support this.”

Caffeine is a bitter-tasting alkaloid, a natural product, a xanthine, found in several plant species, coffee, tea, and cacao. It is a stimulant, like its close chemical cousin, theobromine. There have been dozens of media articles, purportedly based on solid research, that send out mixed messages regarding the health effects of caffeine on people and whether or not we should expose our bodies to this stimulant.

A quick search of the web for cacao theobromine and caffeine reveals several sites warning of the toxicity of stimulants in chocolate, coffee and other products. But, an NIH page also appears that says something along the line of caffeine content need only be reported if levels are above a certain threshold.

Could World of Warcraft Fight Disease?

Corrupted blood

In September 2005, about 4 million World of Warcraft gamers saw a new and unexpected challenge in the game. Players exploring a new area within the game encountered an extremely virulent, highly contagious disease, known as Corrupted Blood, which had been introduced in an update on the 13th of that month. The disease quickly spread, like the Black Death, to the population centres of the fantasy world, killing many and causing social chaos. But, who, other than the gamers themselves should care about virtual deaths and digital disease?

Well, according to Eric Lofgren of Tufts University School of Medicine, in Boston and Nina Fefferman of Rutgers University, in Piscataway, we all should care because the virtual epidemic could provide a very useful model of how diseases spread, how individuals and groups respond to the presence of a killer disease, and what we might do to control an outbreak, of bird flu or a SARS-type disease, in the real world. Writing in the journal Lancet Infectious Diseases, the team explains how simulation models are very useful in studying the spread of disease, epidemiology. However, validating the models or tailoring them to particular human behaviour patterns is next to impossible. The World of Warcraft incident, known as the Corrupted Blood outbreak, on the other hand, “provided an excellent example of the potential of such systems.” They explain that while data from the Corrupted Blood outbreak were not gathered scientifically at the time and so represent a missed opportunity, there is the potential for deliberately engineering such gameplay into other virtual worlds. “Virtual outbreaks designed and implemented with public-health studies in mind have the potential to bridge the gap between traditional epidemiological studies on populations and large-scale computer simulations,” the researchers say, “these would involve both unprogrammed human behaviour and large numbers of test participants in a controlled environment where the disease parameters are known.”

The use of distributed networks to help solve scientific and medical problems is not new. many Internet users will have heard of the likes of SETI@home. This system is essentially a program you install on your computer which uses idle time to search for signs of extra terrestrial life in downloaded astronomical data.

SETI@home is just one of a group of applications based on BOINC, the Berkeley Open Infrastructure for Network Computing. You can use your Windows, Mac, or Linux machine to help find cures for disease, study climate change, discover pulsars and solve various other problems in earth sciences, astronomy, physics, biology, medicine, mathematics and strategy games. You can find a full list of projects here.

A recent paper in the International Journal of Web and Grid Services (2007, 3, pp 354-368) reviewed the state of the art in such distributed applications the world over. According to Bertil Schmidt of the University of New South Wales, Australia, desktop grid computing, as these kinds of distributed applications are known technically, is a relatively new technology but can nevertheless provide massive computing power for a variety of applications. He points out that the cost is low for the researchers, given that once set loose in the wild, the running costs of the program are themselves distributed to the downloaders’ computer and the costs to the researchers are then only in terms of retrieving results from those machines as and when necessary and analysing the incoming data.

Schmidt explains how BOINC provides “a proven open-source infrastructure to set up such projects in a relatively short time” and surveys the scientific projects, e-science, that have adopted this strategy. “The power and mass appeal of desktop grid computing for implementing task-parallel problems have been demonstrated in projects such as SETI@home,” Schmidt explains, pointing out that as of April 2007, the average performance of SETI@home was around 250 teraflops. A teraflops (sometimes teraFLOPS), is a million million floating point operations (or instructions) per second. The combined average performance of all BOINC-based projects was around 0.5 petaflops spread over more than 400 000 active CPUs, which is more powerful in total than IBM’s BlueGene/L, which peaks at 0.280 petaFLOPS. By comparison, the next generation supercomputer, Blue Gene/P, will run at 3000 teraflops, or 3 petaFLOPS, so this distributed power represents a vast resource for e-science and is as yet only very partially tapped.

Personally, I have the World Community Grid running on my computer. This application allows you to help out in the fight against Dengue fever, AIDS, and phase 2 of the human proteome folding project. At the time of writing, teh project has 318,888 members and is running on 715,025 devices amounting to a total of 107,837 years of computing time so far. You can view the latest stats here.

If you have a fast computer and are not running CPU or memory intensive applications, then you could do even more with any of those e-science projects, allowing the BOINC application to run even when your machine is not idle. You will not only accrue more “credits and kudos” on your chosen project but you could just solve one of the problems facing humanity.

Biomarkers Point to Earlier Treatment for Parkinsons

Medical diagnostics

Parkinson’s disease and Alzheimer’s disease are devastating illnesses. The former steals a person’s control of their body while the latter takes away their mind. There are no cures. But new research into biologic rhythms now underway could help the medical profession find diagnostic tools that spot the early stages of the disease sooner, rather than later.

“Both Parkinson’s disease (PD) and Alzheimer’s disease (AD) have a profound effect on biologic rhythms,” Otto Appenzeller told me, “Both diseases are recognized clinically only after a considerable loss of nerve cells, which might take years. For example, the clinical diagnosis of PD is only possible after about 70% of nerve cells disappear in a specific region of the brain at risk of complete devastation by the time the disease is easily diagnosed by physicians.”

Appenzeller and his colleagues at the New Mexico Health Enhancement and Marathon Clinics Research Foundation and the University of New Mexico in Albuquerque, USA, together with co-workers at the Universita degli Studi di Milano, in Italy, are using spectral analysis of stable isotope ratios to track changes in hair and tooth enamel that could lead to earlier diagnostics for neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease.

Appenzeller points out that there is therefore a great urgency to find “biomarkers” that would betray the presence of these and other diseases before they are clinically diagnosed. Such biomarkers could allow treatments to be started sooner and potentially save nerve cells and so alter the course of the illness. “Since hair (and teeth) preserve a record of biologic rhythms spanning several years, disturbances in these rhythms attributed to PD or AD as gleaned from stable isotope ratios may provide an important hint of disease processes at work in a given subject,” he told me.

The Michael J Fox Foundation for research into PD has recently launched a “request for research proposals” entitled Biomarkers for Parkinson’s disease, for which the foundation has allocated US$1million (about Â£500k). “At present, there are no good drugs available that can save nerve cells from destruction but the pharmaceutical companies are working feverishly in this area,” Appenzeller said.

Wine and Health

It’s that time of the week again, time to crack open a bottle to share and time to wonder about the health effects or otherwise of wine. There have been hints for years that various antioxidant components of wine, and red wine in particular, could be protective against cardiovascular disease (heart attacks and stroke, basically). Although I’ve reported on some of those studies, I’ve always been rather skeptical of the claims they make because fundamentally imbibing large quantities of a volatile organic solvent (VOC) (ethanol) is not really a good idea (think brain and liver damage). More to the point, we need free radicals to help our immune systems ward off pathogens, so couldn’t stifling them cause more problems than they fix.

Anyway, toxicity is always about dose. However, anyone who has suffered the morning after the night before will know all about the toxic side effects and the downside of ingesting ethanol. the downside is far more well documented in fact than any of the purported benefits of the antioxidant congeners.

So well document in fact are the side-effects that governments are considering making health warnings on booze obligatory in the same way that they are for cigarettes in many places. It makes sense, even if some people cry: “Nanny state gone mad!”. At least those who are unaware of the serious risks associated with overindulging in flavoured ethanol solutions will hopefully get the message and make the right choice.

Now, where did I put that corkscrew..?

Copper Blues

Copper antioxidants

Lots of people take multivitamins, mineral supplements, and a vast range of antioxidants? But, do they improve your health and wellbeing above and beyond what you could achieve with a well-balanced diet, plenty of fresh air and exercise? In some instances, the jury is still out, although recent evidence suggests that deliberately taking super doses of vitamin C (ascorbic acid) will not, despite the proclamations of the late, great Linus Pauling, protect you from the ravages of the common cold.

There is also the issue of contraindications, not only are some fat-soluble vitamins and minerals toxic at high dose because they can accumulate in the body, there are some supplements and so-called natural tonics, that can interfere with prescription medicines. It is not a good idea, for instance to take the purported natural antidepressant St John’s wort with prescribes serotonin reuptake inhibitors (SSRIs) used in treating depression. Why this is so remains unclear and becomes an especially problematic puzzle to solve given the increasing evidence that the active ingredient in SJW, hypericin, does not in fact inhibit the reuptake of serotonin in the brain anyway!

Now, researchers in Italy have demonstrated that copper, an essential element in our bodies, interferes with our natural internal antioxidants and those many people ingest in the form of over-the-counter health boosters.

Chemists Luigi Campanella and Maria Costanza of the University
of Rome La Sapienza and colleague Marcelo Enrique Conti in the Development Studies Research Centre (SPES) have used an electrical technique known as cyclic voltammetry, to investigate the oxidising and reducing behaviour of antioxidants in the presence of copper ions. Their results, published recently in the International Journal of Environment and Health (2007, 1, 328-340) could make worrying reading for anyone popping health pills on a regular basis.

Copper ions have antioxidant activity. Indeed, copper is an essential nutrient for humans because it works in the regulation of antioxidant enzymes to protect out tissues from highly reactive oxygen free radicals that would otherwise tear apart the biomolecules from which our cells are composed. However, the electrical tests also suggest that the presence of copper is a double-edged sword, because it can also promote the kind of oxidising reactions that cause such damage. “the final effect [of taking supplemental copper] may not be as positive as expected,” the researchers say, and may also be associated with “the risk of toxic secondary effects.”

If oxidants and antioxidants are not balanced, then our cells are exposed to harmful oxidative stress, biochemical damage, and ultimately cell death. There are numerous protective agents, including superoxidodismutase (SOD), glutathione peroxidase (GSHPx), catalase enzymes and transferrin, ferrithin and ceruloplasmin (these bond to iron and copper ions as the activating metals of radical reactions) and the secondary ones such as all the molecules, including antioxidant vitamins, that are able to stop the reactions started by free radicals. When these agents are overwhelmed, cell damage ensues, and this plays an important role in the beginning of diseases, including cardiovascular disease, cancer and degenerative diseases.

The team points out that further studies are needed to verify the results of their electrical tests at the clinical level. What seems to emerge from the present laboratory study is that copper ions sometimes act as antioxidants and sometimes as pro-oxidants. “These conclusions disagree with the current theories that copper ions show only antioxidant action,” the researchers say.

Getting into the Cochrane Library for free

Cochrane Collaboration

Today, I was following up a press release about a review of clinical trials. The analysis suggests that the cannabinoid receptor antagonist rimonabant could help people quit smoking without gaining weight.

The research was published today in the Cochrane Database of Systematic Reviews, a repository of clinical trials data and analyses that is an invaluable resource for those in healthcare, medical research, patient advocacy groups and patients and their carers, the medical media, and others. Anyway, more on the actual story later this month in the summer issue of Reactive Reports.

Now whenever I have needed access to information held in the Cochrane Library database previously, I’ve simply gone through the usual journalist’s route to get at such nuggets. However, the press release pointed out that Cochrane Library publications are also available entirely free of charge to particular groups and to members of the public depending on where you are.

Guest users can access abstracts for all Reviews in the database, but if you live in any of the following places, there are special access points through which you can get publications for free from the Cochrane Collection (either that or the country tag of your computer’s IP address gives you free access:

Australia
New Zealand
Denmark
England
Finland
Ireland
Norway
Scotland
Spain
South Africa
Sweden
Wales
Saskatchewan
Wyoming

So, now you know how to get into the Cochrane Library for free. Of course, if you are in Michigan, Montreal or Moscow you may have to move house.

Free cure-alls

Free cure-alls As I think I’ve mentioned before, I get a lot of emails from people claiming to have solved all the worlds environmental problems through some perpetual motion device or similar. These are not the usual run of the mill spam messages, they are usually targeted at me as a science journalist and talk of big solutions and the potential for a Time cover, a Pulitzer or some other grand prize. If they were sent by snailmail I suspect the majority would be written in lurid green ink.

Some of these claims seem to reach global proportions as we’ve seen with the Steorn research, which is yet to bear fruit, although on July 4, Steorn announced it was planning to demo its results publicly; they are yet to materialise, in fact they were delayed to July 5, and at the time of writing had still not been shown.

For some of the more intriguing of these emails, I created a new section on SciScoop to cover and discuss just such controversial conjectures. I have also highlighted several odd scientific claims some time ago on Sciencebase too, purely for your amusement.

Anyway, those emails continue to arrive, within the last week or two I have had one claiming the amazing powers of an electrical device that seems to create energy from nothing. It strikes me and several energy scientists I spoke to as being nothing more than the electrical equivalent of Bhaskara’s wheel, although the inventor has every faith in his product. Good luck to him, I hope it works out.

I know several academics who are always more than willing to assist inventors with bizarre claims…for a fee. They delight in showing up the obvious flaws in an argument. I should send a pharmacology professor the most recent message I received, which claims to cure almost every form of cancer, despite cancer being simply an umbrella term for a massively diverse range of diseases. The email told of a very simple, small molecule, there is no targeting, and no clue as to a mode of action. I suspect the research runs along the lines of another unrelated compound that was popular on bad medicine sites about five years ago. I won’t name either compound for fear of giving them some kind of credence here or inspiring anyone to go looking.

Many of these emails claim that the invention precludes understanding, somehow lies beyond current scientific understanding, and often defies well-proven laws of nature.

Science and medicine do occasionally enter the realms of paradigm shifts, big changes to theory arise, but despite the popular perception these do not often, if ever, come in a single Eureka moment; even the eponymous event concerning Archimedes in his bath is almost certainly apocryphal and a brilliant piece of science popularisation. Moreover, no apple fell on Newton’s head, instead years of observations and the development of a new theory gave rise to his theory of gravitation. Likewise, although Einstein is credited with the theory of relativity, there were other theories around and he built his work on the solid experimental results from the latter half of the nineteenth and early twentieth century to gradually evolve Newton’s ideas at the cosmic scale.

It would perhaps be nice to imagine that there is a quickfix to our energy needs, a universal panacea for our ills, a maverick theory that explains life, the universe and everything, free cure-alls for everything, in fact. But, there isn’t. While, I occasionally draft a quick write-up for Sciencebase on the basis of some of the more plausible of those tantalizing emails with extravagant claims, more often, input from well-respected contacts in academia directs me, once again, to the overflowing Controversial Conjectures folder. Such emails are ultimately filed here for posterity. Whether or not the Steorn case turns out to be fit for this slot, we will have to wait patiently to see. As I said, their advertised demo is not yet available for display and their “offices” are closed for technical reasons. The latest word on the Steorn site is that overhead lighting caused device heating problems and Steorn has now decided to postpone the demonstration until further notice.

Anyone care to draw the obvious conclusion from that?

Yoga Stretches Brain Chemical

GABA yoga posture US researchers have used a specialist brain scanning technique, magnetic resonance spectroscopic imaging, which is effectively an MRI scan carried out at the molecular level to reveal the effects of yoga practice on the brain. Specifically, they have investigated how concentrations of the feel-good compound gamma-aminobutyric (GABA), an inhibitory neurotransmitter, change after regular practice of yoga postures.

Eric Jensen and colleagues at Harvard Medical School looked at eight subjects prior to and after one hour of yoga as well as eleven control subjects who read a book rather than undertaking the yoga exercises. Although the samples are very small, they saw a marked difference in GABA levels in the yoga practitioners compared to the readers. Their findings suggest that yoga, and perhaps other forms of exercise, should be investigated as a complementary treatment for depression and anxiety disorders, which are commonly associated with low levels of GABA.

You can read more on this in my write-up over on SpectroscopyNOW.com. Click here for the Sciencebase complementary medicine roundup

Bad Apples, Colds and Echinacea

Echinacea - Photo by Bruce Marlin Recent media reports seem to have strengthened the case for using echinacea to ward off or treat the common cold. But, are they based on valid new evidence?

The LATimes [item no longer available by link] for instance, says researchers carried out an “analysis of 1,600 patients pooled from 14 previously published studies found that echinacea reduced the chances of catching a cold by 58% and shaved 1.4 days off the duration of a cold.”

The researchers who carried out this analysis point out that none of the previous trials was large enough to be valid, but somehow they attempt to give them new credence by mixing together the data from lots more dubious studies. One bad apple can almost certainly spoil the barrel, but throw together a couple of dozen bad apples and that barrel is going to be humming before the day is out, surely?

Meta analyses of solid double-blind, placebo-controlled clinical trials certainly can shed new light on old findings, but what they do not do is create new data points, they are simply a re-analysis of old results pooled.

Craig Coleman of the University of Connecticut whose team carried out the meta analysis, point out that none of the trials analysed individually were big enough to reveal the benefits of Echinacea. Somehow his new analysis of old data demonstrates an almost two-thirds reduction in the risk of catching a cold compared to a person not using Echinacea. But, how could that be, if those earlier trials succumbed to serious wishful thinking and the placebo effect, then the whole argument is in doubt.

Wallace Sampson, an emeritus adjunct professor of medicine at Stanford University School of Medicine is quoted as saying that because the methodologies of some of the earlier studies are so suspect, this casts doubts on the pooled result. Exactly.

The team also reports that of 800 products containing Echinacea they investigated, there are large variations in the quality, which part of the plant was used – flower, stem or root – and how much so-called active ingredient is present. In addition, they suggest that more work is needed to check the safety of the countless formulations available. Their warning echoes other studies that have pointed to toxicity problems associated with long-term use of Echinacea products, although admittedly some of those studies might also be considered invalid because of poor methodology.

So, should we run to our local herbalist on the off-chance that we might catch a cold or if you’ve already caught one quickly down a dose of Echinacea to “shave off” 1.4 days or runny noses and sneezing? I don’t think so, not unless you don’t mind putting up with a whole lot of bad apples.