Oral Health and Pointless Tests
I really like the Fox News Channel, but I sometimes worry about some of the medical advice that they dish out. The other morning I heard a dentist recommend that people should ask for a blood test to measure inflammation. She was saying that everyone should have the test, called C-Reactive Protein (CRP). This is really bad advice that is based on a fundamental misunderstanding of research data.
Yes, there is a link between dental disease and arteriosclerosis. And yes, there is a link between CRP and arteriosclerosis. But there is no good evidence that we should be measuring it on a routing basis.
The CRP Molecule
So what’s the problem about measuring CRP? If it is elevated, then what? There is no point in measuring anything at all unless you can take some action, or it guides prognosis. No good doctor would ever recommend treating a lab value. So if the CRP is elevated that would not just mean that it’s time to have a look at his or her pearly whites, it would mean a total body workup. There are dozens of causes for an elevated CRP. I know a lot about the topic: sixteen years ago I wrote one of the early scientific papers on CRP. It may go up if you have a fat tummy, have arthritis, allergies or if you are depressed, have fibromyalgia or irritable bowel syndrome. It also goes up as you get older, if you are physically inactive, or if you happen to have one of the genetic variants that can push it up.
In fact the questions of whether or not measuring CRP would improve coronary risk prediction is the subject of three papers and two editorials in the July 10, 2006 issue of the Archives of Internal Medicine and the July 4, 2006 issue of the Annals of Internal Medicine. In the July 10, 2006 issue of the Archives of Internal Medicine, a team led by Dr Aaron R. Folsom from the University of Minnesota in Minneapolis reported the results of the Atherosclerosis Risk in Communities (ARIC) study, which assessed the association of 19 novel risk markers with incident CHD in 15 792 adults followed up since 1987-1989.
The participants underwent a physical examination, including assessment of major risk factors, at the beginning of the study and every three years afterward. At four times during the follow-up period, researchers collected blood and DNA samples for analysis. Patients continue to be tracked for the development of CHD. Novel markers included measures of inflammation, endothelial function, fibrin formation, fibrinolysis, B vitamins, and antibodies to infectious agents.
Folsom concluded that:
“C-reactive protein level does not emerge as a clinically useful addition to basic risk-factor assessment for identifying patients at risk of a first CHD event. Routine screening is not warranted for any of the other 18 novel risk factors tested, either.”
Another study from Brigham and Women’s Hospital in Boston did suggest that CRP might be helpful in predicting coronary disease in some women. But in an editorial, George Davey Smith from the University of Bristol in England had this to say:
“There are many reasons for skepticism about the role of CRP as a predictor of CHD: CRP may not be causally related to CHD; it remains more expensive than asking patients about their health, lifestyle, and socioeconomic background; and it adds only modest additional predictive ability over conventional risk factors, even in Cook and colleagues’ (i.e. the Brigham and Women’s) study.”
The moral of the story? Random measurements of CRP have not been shown to be of much value.
And be a bit cautious about medical advice on Fox News.
Asthma, Air and Allergies
After a couple of weeks away I was distressed to see that I was going to be returning to a city which has just been rated as the most challenging place in America for people with asthma.
This is the list according to the Asthma and Allergy Foundation of America:
- Atlanta
- Philadelphia
- Raleigh, North Carolina
- Knoxville, Tennessee
- Harrisburg, Pennsylvania
- Grand Rapids, Michigan
- Milwaukee
- Greensboro, North Carolina
- Scranton, Pennsylvania
- Little Rock, Arkansas
I am pleased to say that I do not have asthma, though I have a strong family history of it. If you live in one of these cities, or any other with a high rate of pollution, there is nothing much to be done apart from:
Staying indoors when the weather is bad
Using an air purifier
Keep to a diet designed to reduce your risk of inflammation
Use homeopathy and tapping therapies to help when necessary.
And sadly, for some people, medicines are the only option. But I always try the other approaches as well.
A Promising New Treatment for Lupus Kidney Disease
Systemic lupus erythematosus (SLE) is an out-of-control, malignant attack on the body by its own immune system. It can be a horrible illness that may affect virtually every organ of the body. One of the worst things is that it can lead to renal (kidney) failure. Until now, the treatments of SLE have been either symptomatic or "disease-modifying." The second is what we really want: to prevent the illness from progressing. But it has been very difficult to do that, and I have seen some real tragedies in my career.
We now have a new approach that highlights a new approach to illness in general. Students are usually taught that there are diagnostic tests for illnesses like SLE or prostate cancer. The idea of using the tests for treatment is fairly new. So one of the proteins that goes up in prostate cancer becomes the target for treatment.
But what about SLE?
SLE is a chronic inflammatory disease in which the body produces antibodies against the nuclear components of its own cells. The most worrying are antibodies to double-stranded DNA (dsDNA). These antibodies can be triggered by genetics, environmental factors like sunlight and some drugs.
The antibodies attack the body’s cells and tissue, resulting in inflammation and tissue
damage. SLE can affect any part of the body, but most often damages the heart, joints, skin, lungs, blood vessels, liver, kidneys and nervous system.
La Jolla Pharmaceutical Company just announced positive interim antibody results from its ongoing double-blind, placebo-controlled randomized Phase 3 trials of Riquent(R) (abetimus sodium). This is a drug candidate for SLE. Analyses of interim antibody data indicate that patients treated with 900 mg or 300 mg per week doses of Riquent had greater reductions in dsDNA antibodies than patients treated with 100 mg per week or placebo. The results showed a significant dose response when comparing all Riquent-treated patients to placebo-treated patients (p < 0.0001), and each Riquent dose group to the placebo dose group (p < 0.0015 for 100 mg, p < 0.0001 for 300 mg and 900 mg).
For people not used to looking at statistics, these are impressive data.
Clearly other analysts feel the same way: the price of the company’s shares went up 40% on the announcement.
We shall keep an eye on the development of this new medicine to see if it fulfills this early promise. At this moment the data are very exciting.
Anti-inflammatories and Colon Cancer
I just had a very good question after I published my list of Twelve Tips to Reduce Your Risk of Colorectal Cancer.
Dear Dr. Petty,
“That’s a great list, but I am wondering why you haven’t included aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs)? I thought that they had been shown to reduce the risk of colon cancer.”
This is an excellent question, and I deliberately omitted mention of anti-inflammatories because the research suggests that they may cause more harm than good.
There is a report in today’s edition of the Annals of Internal Medicine from the United States Preventive Services Task Force, a highly regarded and independent panel of experts in primary care and prevention, that confirms that screening for colorectal cancer is still important and everyone over 50 should have it. But they urge caution on taking preventive drugs, saying that on balance the health risks of aspirin outweigh the benefits when it comes to preventing colon cancer. This advice holds even for those people with a family history of the disease, as long as they have only an average risk of colon cancer. (20 per cent of people who get colorectal cancer also have a close relative with the disease, with proportionally more cases among African Americans than other races.)
They found good evidence that high doses of aspirin (i.e. 300 mg a day or more) and possibly ibuprofen protect against colorectal cancer but this comes with increased risk of intestinal bleeding, stroke and kidney failure.
In low doses – under 100 mg a day – the Task Force says that good evidence supports the notion that aspirin protects against heart disease. However, at this dosage it will have no preventive effect on colorectal cancer.
The US Preventive Services Task Force regularly reviews the available research evidence and issues advice based on what they regard the strength of the evidence to be. They use a grades to help guide practice. For example a grade A recommendation is equal to "strongly recommends", while a B is just "recommends", and C is "no recommendation for or against".
In this case the Task Force has issued a grade D "recommends against" to the routine use of aspirin and NSAIDs to prevent colorectal cancer.
So for now I recommend following the Twelve Tips that I published yesterday.
Deep Vein Thrombosis
I am sorry to hear that the United States Vice-President Dick Cheney has just developed a blood clot in his leg and is being treated with anticoagulants (blood-thinning medications) that he will need to be on for several months.
He experienced some discomfort in his lower left leg this morning, and the diagnosis of deep vein thrombosis was made.
Mr Cheney is now 66 years old and has a history of cardiac problems. He has suffered at least four myocardial infarctions (heart attacks) and has a pacemaker.
He had quadruple bypass surgery in 1988 after his third heart attack.He also had an operation to remove blood clots around his knees in 2005.
Mr Cheney recently returned to Washington after long flights to Japan, Australia, Pakistan and Afghanistan.
As I discussed a few months ago deep vein thrombosis – often shortened to "DVT" – can be associated with long-distance flying because it leads to inactivity and dehydration. Not, as was formerly thought, low oxygen pressure.
Blood clots in the legs are not in themselves life-threatening but they can be dangerous if they become wedged in the lungs (pulmonary embolism) or other organs, which can in severe cases be fatal.
Although the venous and arterial sides of the circulation are often thought of as quite different, it is not that unusual for someone to have problems in both, either because of immobility, metabolic disturbances or low grade inflammation.
With Spring Break and early summer vacations coming up, please don’t forget to keep moving when you are on planes, limit the alcohol and coffee cnsumption, and have plenty of water to drink.
Bon voyage!
Acupuncture and Parkinson's Disease
Over the last 25 years I have used acupuncture to try and help a great many people with Parkinson’s disease. It has certainly helped a lot of the symptoms, but in my experience has not often done much to change the course of the illness. That being said, I have seen a few people who had remarkable improvements that were sustained for months and even years. The best results have usually come when we have used a combination of acupuncture, diet and homeopathy, in addition to regular medications.
So I was very interested to see a study in the journal Brain Research, even though the work used animals, and I’ve had a longstanding aversion to animal experiments.
There is a chemical called MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine) that damages and kills some types of dopaminergic neurons in the brain, so it can produce Parkinsonian symptoms in humans and in some animals.
Mice were injected with MPTP and then some of them received acupuncture every two days in two spots, one behind the knee and one on top of the foot. In humans, these are two of the points that are traditionally considered to be involved in muscle movement. Another group of mice received acupuncture in two spots on the hips that are not believed to be effective for acupuncture. A third group had no acupuncture at all.
By the end of seven days, the MPTP injections had decreased dopamine levels both in the mice that had not received acupuncture, and in the mice that received fake acupuncture, to about half the normal amount. But in the acupuncture-treated group, dopamine levels declined much less steeply, and nearly 80% of the dopamine remained.
The mechanism for such an effect remains unknown. The most likely mechanism is that it is reducing the inflammation in the brain often accompanies and worsens other symptoms of Parkinson’s disease. So acupuncture might maintain dopamine levels by preventing this inflammation. The same team of researchers from South Korea has already reported that acupuncture also prevents loss of dopamine neurons in rats.
The clinical studies in humans have been less encouraging, and more closely reflect my clinical experience. The problem is that by the time most people get to see an acupuncturist, they have already lost huge numbers of dopamine neurons and it is difficult to do very much. If acupuncture is to be helpful, we would probably need to be able to identify someone with Parkinson’s disease extremely early, perhaps even before clinical signs have appeared, and so far we have no reliable way of doing that.
Here Comes the Sun: To Screen or Not To Screen?
I have been worried to see some people – all, I think, without scientific training – proclaiming that there is no need to protect ourselves against the sun because there is no evidence that sulight causes any health problems.
Ultraviolet radiation (UVR) from the sun has been part of the environment since the first cells began to form. When we discuss the effects of UVR on human health and the environment, the range of UV wavelengths is often subdivided into:
- UVA (400–315 nm), also called Long Wave or “blacklight”
- UVB (315–280 nm), also called Medium Wave
- UVC (< 280 nm) also called Short Wave or “germicidal”
The key questions are these:
Can sunlight cause health problems?
Do the benefits of sunlight outweigh their risks?”
UVB is required for the conversion of 7-deoxycholesterol to vitamin D, (the sunshine vitamin!) which is critically important in the maintenance of healthy bones, although there may also be another mechanism by which vitamin D is generated in the body. As we have seen research is making clear that vitamin D has other potential roles in the maintenance of human health. Low levels of vitamin D have been linked to:
- Rickets
- Osteomalacia
- Osteoporosis
- Maintaining the integrity of cell membranes
- Type 2 diabetes mellitus
- Schizophrenia
- Multiple sclerosis
- Pre-eclampsia (hypertension and accompanying problems during the late stages of pregnancy)
- Some types of cancer
- Fibromyalgia-like pains
- Immune deficiency: Africa Americans do not generate enough of a protein needed to ward off tuberculosis. Why? Because the protein needs vitamin D to be activated, and dark skin is inefficient at absorbing and converting UVR. It may also be that we see epidemics of colds and flu in the winter because that is when we have low levels of vitamin D, which allows the viruses to overwhelm our immune defenses.
This does not necessarily mean that taking extra vitamin D will ward off all of these problems.
In the days before the Industrial Revolution, unless we lived in the frozen North, we had no trouble in getting the amount of vitamin D that we needed. In most of the United States, during the summer months, 10-15 minutes outdoors at midday will generate around 10,000 international units (IU’s) of vitamin D in an average fair-skinned person. This is far in excess of the government’s dietary recommendations of 200 IU’s/day in people up to age 50, 400 IU’s up to age 70 and 600 IU’s in people over 70. Not surprisingly many experts – me included – believe and have provided evidence that these daily requirements are much too low. (Have a look at the comments here.)
Of course many of us do not spend much time outside and don’t take in as much in the way of vitamin D containing foods – such as milk and salmon – as we should. I’ve seen evidence to suggest that we in Atlanta are probably at the Northernmost point in the United States were we could hope to get enough sunshine and therefore vitamin D from modest winter exposure to the sun.
Recent data has suggested that if you spend no time at all in the sun, then you may need as much as 4,000 IU’s of vitamin D/day, though that figure has not yet been widely accepted.
Exposure to UVR, whether of solar or artificial origin, also carries potential risks to human health. UVR is a known carcinogen and excessive exposure, at least to the solar radiation in sunlight, increases the risk of cancer of the lip, basal cell, and squamous cell carcinoma of the skin and melanoma, particularly in fair-skinned populations. There is also evidence that solar UVR increases risk of several diseases of the eye, including cortical cataract, some conjunctival neoplasms, and perhaps also melanoma of the eye.
We have good data for the existence of a threshold amount of UV-B exposure that may lead to the formation of cataracts. The amount needed to cause cataracts depends in part on the amount of pigment in the eye, so albino rats get cataracts with much lower exposures to UV-B.
So what to do?
Sunlight has a definite benefit in preventing or treating many clinical problems and it is no surprise that after 3000 millennia we are adapted to make use of the sun’s largesse. What is less easy to understand is why an excess of sunlight can cause so many problems, unless it is our hairlessness and environmental change that has lead to a loss of the ozone layer.
Some years ago it was suggested that sunscreens may themselves cause skin cancer, but the data has shown that to be false. Indeed modern sunscreens almost certainly reduce melanoma risk.
So how do we balance the positive and negative effects of sunlight? A recent review precisely reflects my own thinking:
- We need some sunlight
- Depending on where you live, you need only a few minutes each day
- Sunscreens confer protection on the skin without blocking all the health benefits
- If you have a medical reason for avoiding sunlight, then your health care provider should measure your vitamin D status.
Toxoplasmosis and Behavior
Last August I wrote an article about some extraordinary new evidence implicating Toxoplasma gondii in some psychological and psychiatric illnesses. Latent infection with
Toxoplasma gondii is amongst the most prevalent of human infections and it
had been generally assumed that it is asymptomatic unless there is
congenital transmission or reactivation because a person has an immune system that has become depressed or compromised. That assumption is being completely re-evaluated.
The article generated some extremely interesting correspondence and some spirited discussions.
Here is a very insightful letter from a physician:
Dear Dr. Petty,
I thought about the concept of psychological illness caused by a virus or other organism. I was wondering what would be the mode of dispersion of such a virus. Upper respiratory tract infections, skin and gastrointestinal infections spread by cough, by touch and hand to mouth respectively. How would such a brain virus or protozoal organism promote itself? Of course it could be by the above methods but it seems that there should some way that the specific disease process is connected to a behavior that helps it to spread itself.
Then I got to thinking; diseases have learned physical ways to disseminate themselves, I wonder if a disease could change behavior to promote it’s own dissemination and survival? I imagine that if that were true, people with the flu would be sociable, people with infectious diarrhea would be sociable and hungry, people with AIDS would have increased libido. I haven’t yet seen any data for this. Although I’ve always felt that there was one disease that did alter behavior in a way that is conducive to disseminating itself, and that is rabies. The host goes from being docile, to seeing all others as the enemy. He then attacks them, bites them and thus passes on the organism. A true mind altering virus, although it’s psychology works better with animals than with people. Do you think that there are other diseases that spread purely by behavior, that cause the host to seek out the next host and not just pass the disease from one to another just due to proximity?
This was my response:
What great questions!
And believe it or not, there’s quite a lot of empirical research on these very topics.
There is a whole textbook on the behavioral effects of parasites edited by Janice Moore entitled Parasites and the Behavior of Animals. Here’s an interesting one: rats and mice are hard wired to avoid cats. Millions of years of programming have ensured that Tom’s very presence would send Jerry packing. Cats carry Toxoplasma gondii and if mice or rats become infected with it, usually by eating cat poop, they lose their fear of felines. So now Tom can have lunch at his leisure.
I’ve also talked about the way in which people with creativity and schizotypal personality disorder (i.e. carriers of genetic risk) tend to be promiscuous, while people with schizophrenia have fewer children. Both groups tend to get more sexually transmitted diseases than the general population. It would be tempting to think that toxoplasmosis can be spread that way, however there’s a 32-year old study in German that showed that Toxoplasma was not transmitted by intercourse. However, cytomegalovirus, a common partner to Toxoplasma may be. And both modulate dopamine activity in the regions of the brain involved in salience.
I have done a very detailed literature search encompassing papers written in all the languages that I can read, and have not been able to find any clear evidence of behavior change induced by HIV, influenza or infectious diarrhea: what interesting and important questions to research.
We do have some more data confirming the effects of Toxoplasma infections on the behavior of rats: they become less anxious and therefore do not respond to environmental threats as quickly as uninfected rodents. An antipsychotic medication (haloperidol), a mood stabilizer (valproic acid) and two chemotherapeutic agents – pyrimethamine or Dapsone – have all been shown to prevent the development of Toxoplasma-induced behavioral change.
Another recent study from the Departments of Parasitology, Microbiology and Zoology, Charles University, the Centre of Reproductive Medicine and GynCentrum, in the Czech Republic also speaks to the significance of latent Toxoplasma infections: the presence of the parasite in the blood of pregnant women increases their chance of giving birth to boys. The increased survival of male embryos in infected women may be explained by Toxoplasmosis infections modulating and suppressing the immune system.
If Toxoplasma plays a part in the development of some psychiatric illnesses, yet a high proportion of the population carries it without any problems, one obvious question is what activates it? Environmental stress might, perhaps, cause the Toxoplasma to become reactivated and play a part in the development of specific psychiatric symptoms.
This story is continuing to develop and I am going to watch it closely. If it is confirmed, it could open up some brand new avenues for helping treat and perhaps even prevent some types of psychiatric illness.
Parkinson's Disease, the Intestine and Infections
Early in my career, one of my mentors was the eminent scientist and clinician Robert Mahler. He recently passed away at the age of 81, but in the last two years of his life he was an author on two papers (1, 2) about an ailment with which he struggled for many years: Parkinson’s disease.
Despite the best treatment, he was severely incapacitated by the illness, at one stage needing a wheelchair to get from his car to his office. But his fine mind remained undimmed by the illness, and he was intrigued by reports of an association between stomach ulcers and Parkinson’s disease and of dramatic improvements in the symptoms of some people with Parkinson’s disease who were being treated with antibiotics for gastric ulcers. (Last year Barry Marshall and Robin Warren were awarded the Nobel Prize in Physiology or Medicine for their pioneering work on Helicobacter – a bacterium associated with peptic ulcers.
I mentioned in an earlier post that I have a strong sense that there are more prizes to come on the
interaction between infectious agents, inflammation, genes, the psyche
and the environment.)
Robert was one of the test subjects in a research study and his Parkinsonian symptoms got much better when he was treated with antibiotics. There are now several important pieces of research on the fascinating topic. In some people eradicating Helicobacter may convert rapidly progressive Parkinsonism to a quieter disease, although only a minority of sufferers have evidence of current infection.
There seems to be an interaction between aging, genes and this infectious agent. Clearly not everyone is helped by antibiotic treatment, but this is a whole new line of very promising research.
