Richard G. Petty, MD

Running Scared

One very promising approach to understanding many psychological problems is to look at them from an evolutionary perspective: to see if clinical observations can be re-framed around the evolution of the brain.

Our brains are a hodgepodge of bits and pieces that have evolved over millions of years. We still have regions that evolved in reptiles, as well as the stunningly complex neocortex that has been developing over the last few hundred thousand years. Most of the time the different systems and circuits cooperate, but that cooperation falls apart if people are under the influence of alcohol or dugs, or in different types of neurological and psychological problems. Then the older and more “primitive” regions of the brain take over. That is typically what happens when a drunk wants becomes irritable or wants to fight. It is also what can happen in people who have sustained damage or have abnormal development of the frontal lobes of the brain. Alternatively it may happen if something over-stimulates the primitive regions of the brain.

Colleagues in London have been doing experiments with a computer game that could be immensely valuable for people with panic attacks and some types of anxiety disorders.

Working with healthy volunteers, Dean Mobbs and colleagues at the Wellcome Trust Centre for Neuroimaging at University College, London, used a Pac Man-like computer game, in which subjects were chased through a maze by an artificial predator. If caught, they received a mild electric shock.

At the same time, brain scans measuring blood flow showed that when the predator was a long way off, lower parts of the prefrontal cortex area of the brain were active. This region is associated with complex decision-making, such as planning an escape.

But when the predator moved closer, activity shifted to the periaqueductal gray area, which is responsible for rapid response survival mechanisms such as fighting, flighting or freezing.

This shows us that the brain's response to fear changes as a threat gets nearer: the more impulsive region takes over from the decision-making regions as a threat looms closer. A problem in the balance between the two regions could explain some anxiety disorders. Most sufferers report that they “know” that their fears are illogical, but they react anyway. So the key question is what is it that shifts the balance of activities between the forebrain and midbrain regions of the brain?

This new research is published in the journal Science, and builds on similar findings in animals, including tests on rats that were performed at the University of Colorado in Boulder and published in 2005. In those experiments rats with a non-functioning prefrontal cortex did not cope with stress as well as those with normal brains.

From an evolutionary perspective, maintaining the correct balance between the different regions of the brain that handle fear help animals to avoid or escape predators.

There are some situations where we only have to be wary about potential threats, but other times we need to react without thought. The closer a threat, the more impulsive will be your response. If the threat is large enough and close enough we lose any semblance of free will and just take action.

Just as happens when someone is in the throes of a severe anxiety attack.

New Treatment Options: Knowing What to Use

One of the main reasons that I created this blog is that I want to empower you: I want to give to give you the information that you need to care for yourself and the people around you.

One of the problems with many new treatments is that they promise the earth, sometimes drag people away from things that may help them and then fail to deliver.

This is something that I struggled with in the field of holistic medicine for thirty years. I constantly hear and see fantastic claims that cannot be right and are often based on a complete misunderstanding of how the body functions. On the other hand there are some highly unorthodox methods and techniques that can be amazingly helpful. My job has been to find out which is which!

But it is not only in the field of unorthodox medicine. I have recently heard about something very questionable in the field of psychotherapy. Somebody has invented a new form of therapy that cuts across and ignores decades of research. He is now offering certifications in his method. So long as you have a very basic healthcare qualification, you pay him a few hundred dollars, do an online training and then you can set up shop as a therapist. Many members of the public do not know how little regulation there is for some of these therapies.

Here are some guidelines for checking out a new therapy or remedy:

1. Efficacy
Be suspicious of any treatment or therapist if they:

• Claim that a treatment works for everyone: I have yet to find ANY treatment that works for everyone
• Only use case histories or testimonials as proof. The plural of anecdote id not evidence. If we see or hear about something that looks promising, it is essential to confirm the reports with systematic, independent controlled research. Be aware that if that has not been done, the person selling you the treatment or the therapist claiming to help is essentially experimenting on you. And if they want to experiment they need your consent and the approval of an Institutional Review Board. And don’t buy into the “my work is so brilliant and cutting edge that nobody will publish it in a journal.” It is hard to publish really new work, but we cannot believe what people are saying until it has been subjected to peer review: other experts go through the work with a fine toothcomb to see if it is right.
• Cite only one study as proof. Hundreds of promising studies have turned out to be dead ends when someone else tried to repeat it. You can be a lot more confident if several studies have shown the same thing.
• Cites a study that did not have a control (comparison) group. That is always a first step in evaluating a new treatment.
• Cite a study that you cannot see yourself. We spend a lot of time checking some of the claims made on infomercials and websites. They often talk about some obscure study in a hard-to-find journal written in a foreign language. We go and find the papers and if necessary translate them. We constantly find that the studies quoted contain results that are 180 degrees away from what they claim.
• Only reference themselves. This recently came to light with a form of therapy that comes with a short book. There was not one scientific citation, but loads of self-references, so it looked as if there was something credible behind it.
• Testing a treatment without a control group is a necessary first step in investigating a new treatment, but subsequent studies with appropriate control groups are needed to clearly establish the effectiveness of the intervention.

2.  Safety?
Be wary if:

• A therapist or someone promoting a remedy cannot tell you the exact consequences of not following up with some other treatment. Safety is not only about the safety of a product or a therapy: it is also about the risks of declining a proven treatment
• A therapist tells you stop any other treatment that you are on without discussing the risks of stopping it, and without discussing the situation with any previous therapist. It does not matter whether you were on a medication or having acupuncture. Different treatments interact, and stopping and starting can be risky. If a therapist who does not prescribe medications tells you stop them, be very, very careful. There are precise ways to discontinue most treatments
• A remedy comes without precise directions about how to use it
• Something does not list its contents or ingredients
• A product has no information or warnings about side effects
• If a product or therapeutic approach is described as natural, with the implication that natural means safe. Hurricanes, arsenic and deadly nightshade are all natural!

3.  Promotion
Be very cautious if a therapy or treatment:

• Claims to be based on a secret formula or a secret that has been deliberately hidden from you
• Claims that the particular treatment or therapy is being suppressed or unfairly attacked by the medical or therapeutic communities
• Claims to work immediately and permanently for everyone
• Is described as an “Amazing breakthrough” or a “Miracle.”
• Claims to be a cure for something that other experts believe is incurable. They could be right, but then we have to go back to the first point about efficacy
• Is only promoted through infomercials, self-promoting books, online or by mail order

4. Evaluating Media Reports

• When evaluating reports of health care options, consider the following questions:
• What is the source of the information? Good sources of information include medical schools, government agencies (such as the National Institutes of Health and the National Institute of Mental Health), professional medical associations, and national disorder/disease-specific organizations. Information from studies in reputable, peer-reviewed medical journals is more credible than popular media reports.
• Who is the authority? The affiliations and relevant credentials of "experts" should be provided, though initials behind a name do not always mean that the person is an authority. Reputable medical journals now require researchers to reveal possible conflicts of interest, such as when a researcher conducting a study also owns a company marketing the treatment being studied or has any other potential conflict of interest.
• Who funded the research? It may be important to also know who funded a particular research project.
• Is the finding preliminary or confirmed? Unfortunately, a preliminary finding is often reported in the media as a "breakthrough" result. An "interesting preliminary finding" is a more realistic appraisal of what often appears in headlines as an "exciting new breakthrough." You should track results over time and seek out the original source, such as a professional scientific publication, to get a fuller understanding of the research findings

5. What Are the Financial Implications of This New Therapy or Remedy?

• Is the treatment covered by health insurance?
• What out-of-pocket financial obligation will you or your family have?
• How long will this out-of-pocket financial obligation be?
• Is there any kind of guarantee?
  

Tips for Finding Reliable Information Online
The good news is that the Internet is becoming an excellent source of medical information. The bad news is that with its low cost and global entry, the Web is also home to a great deal of unreliable health information.
In addition to the tips cited earlier, Web surfing really needs some special considerations:
Know the source. The domain name tells you the source of information on the Web site, and the last part of the domain name tells you about the source. For example:
.edu = university/educational
.biz/.com = company/commercial
.org = non-profit organization
.gov = government agency

The same rules do not always apply if you are looking at websites in other countries.
Obtain a "second opinion" regarding information on the Web. Pick a key phrase or name and run it through a search engine to find other discussions of the topic or talk to your health care professional.

Experts who spend time and trouble evaluating reports and then publish their findings online will often answer questions. RichardGPettyMD.blogs.com is one that does, and there are many others.

The Curse of Crystal Meth

I have the dubious distinction of living in a part of the United States with one of the highest rates of methamphetamine abuse in the country. Around here most of the first time users are teenage girls who are trying to lose weight.

In the last few years the spread of methamphetamine abuse across the United States has been as rapid as it has been alarming. Until about six years ago, methamphetamine use was seen mostly in the western and rural United States. Then it jumped over the Mississippi and continued its demonic march to the sea and Georgia has been hit like a ton of bricks.

Not only can crystal met ravage the brains of users, they can get a wide range of physical problems including inflammatory and immune problems throughout the body.

Methamphetamine abuse has now expanded rapidly throughout the rest of the country and across different ethnic groups. According to the 2005 National Survey on Drug Use and Health it is estimated that 10.4 million Americans ages 12 or older have used methamphetamine at least once in their lifetimes for non-medical reasons.

There is a new and important study from the Scripps Institute that has shown that long-term methamphetamine use changes circulating proteins in drug users, causing aberrant immune responses. As a result, increased levels of pro-inflammatory cytokines - proteins that are involved in immune responses - may initiate a previously unrecognized molecular mechanism for the development of cardiovascular disorders including vasculitis, an inflammation of the blood vessels.

It appears that methamphetamine can add sugars (a.k.a. “glycate”) proteins. The researchers found that the immune system responds dramatically to this methamphetamine-induced glycation, which may lead to vascular inflammation. There was a direct relationship between methamphetamine intake and the level of circulating antibodies in animal models. This immune response, coupled with antibodies binding to methamphetamine, might make the drug less biologically available leading to an increased need for higher and higher doses, a problem found among chronic methamphetamine users.

The resulting glycated proteins are called advanced glycation end products (AGEs) that modify the function of proteins and are associated with a number of diseases including diabetes and Alzheimer's disease.

Methamphetamine-AGE proteins not only increased antibody production, but also were strong enough to overcome the drug's natural immunosuppressive qualities. Furthermore, a wide range of cytokines directly linked to AGE exposure were increased in rats that self-administered methamphetamine.

The study also showed that even limited daily access to the drug was enough to produce an over-expression of vascular endothelial growth factor which is a potent signaling cytokine involved in angiogenesis and vasodilatation.

If you know anyone tempted to dice with this vile toxin, ask them to have a look here. 

It's Not the Food, It's the Size of the Plate

I grew up in a culture where the aftermath of the Great Depression and the Second World War meant that every child was expected to eat everything on their plates. That created a bit of a problem when I first moved to the United States: my conditioning led me to try and eat every morsel of those huge American portions. Fortunately I quickly noticed the impact on my waistline.

I love simple but practical and important experiments. I have just read about some very nice research from the University of Calgary in Alberta, Canada that fits the bill. It appears that simply using plates and cereal bowls with markers for proper portion sizes can help obese patients with diabetes lose weight. As a result, some can even decrease their use of glucose-controlling medications, according to a report in the Archives of Internal Medicine.

Between 1960 and 2000, the proportion of U.S. adults who were obese increased from 13.4% to 30.9%.  There is clearly an association between type 2 diabetes and obesity although it is not quite as simple as saying that obesity causes diabetes, at least not until the obesity becomes extreme. But we have known for half a century that calorie restriction may improve blood sugar control in diabetics, partially by contributing to weight loss.

The enormous increase in obesity has closely paralleled the explosion of portion sizes of both food and soft drinks.

The researchers conducted a six-month controlled trial of commercially available portion control plates and bowls in 2004. The plates were divided into sections for carbohydrates, proteins, cheese and sauce, with the rest left open for vegetables. The sections approximately totaled an 800-calorie meal for men and a 650-calorie meal for women. The cereal bowl was designed to allow a 200-calorie meal of cereal and milk. The subjects consisted of 130 obese patients with diabetes with an average age 56, half of whom were randomly assigned to use the plate for their largest meal and the bowl when they ate cereal for breakfast. The other half of the participants received usual care, which consisted of dietary assessment and teaching by dieticians.

At the end of the six-months, 122 patients remained in the study. Individuals using the portion-control dishes lost an average of 1.8 percent of their body weight, while those receiving usual care lost an average of 0.1 percent. A significantly larger proportion of those using the dishes - 16.9 percent vs. 4.6 percent - lost at least 5 percent of their body weight.

In addition, at the end of the six months, 26.2% needed a decrease in their diabetes medications compared with 10.8% in the control group.

These results are important: a 5% weight loss has been shown to be clinically significant in terms of decreasing morbidity and mortality associated with obesity-linked disorders.

Simple, straightforward and very practical.

Try it!

T’ai Ch Ch’uan and Your Feet

One of the worries about getting older is that aging can adversely affect our balance and increases the chance that we can slip and fall. This is even more of a problem in people with loss of sensation in the soles of the feet due to diabetic peripheral neuropathy and other diseases. T’ai Chi Ch’uan has previously been shown to improve balance in healthy elderly adults.

A new study from the Biomedical Engineering Program, Milwaukee School of Engineering, Milwaukee, Wisconsin was just published in the journal Diabetes Technology and Therapeutics. 

The aim of the study was to see if T’ai Chi improved both balance and sensory perception in the soles of the feet in healthy elderly adults and elderly adults with diabetes and sensory loss in the feet. Eighteen elderly people with a mean age of 73.1 years were tested for sensation and balance before t’ai chi training and again after 6 months of weekly sessions. Participants were grouped by their initial scores on tests of sensory perception, in order to calculate the effects of t’ai chi on sensory perception.

Plantar (soles of feet) sensation results showed that all the participants showed significant improvement in sensory ability with the 6 months of t’ai chi training. All groups also had a general improvement in all balance measures, with the greatest improvement seen in those subjects with large sensory losses. Hemoglobin A1c measurements – a standard way of estimating control of blood glucose - also decreased as a result of the intervention.

The study was small, but the effectiveness of t’ai chi training as a method of improving plantar sensation and balance in elderly adults with sensory loss, with and without diabetes, was impressive.

Another one of those things that is supposed to be impossible!

Exercise May Be the Best Anti-inflammatory

It is almost twenty years since I was awarded my research doctorate and some of what I said at the time was controversial: I made a lot about the link between inflammation, diabetes mellitus and cardiovascular disease. Now we know more, and the link is a lot less controversial.

A number of studies have suggested that regular exercise reduces inflammation but it is still not clear whether there is a definite link. And if there is a link, how does it work? One candidate that we have discussed before has been a link between the autonomic nervous system – sympathetic and parasympathetic - and inflammation. When we exercise, the sympathetic nervous system increases our heart rate and improves lung function, while the parasympathetic system helps to slow things down as we stop exercising.

A recent study by kinesiology and community health researchers at the University of Illinois provides evidence that may help explain some of the underlying biological mechanisms that take place as the result of regular exercise. 

The objective of the research was to examine the independent effect of the “tone” in the parasympathetic nervous system by assessing heart rate recovery after exercise, and whether there was a link between heart rate recovery and circulating levels of C-reactive protein (CRP). CRP, which is mainly produced by the liver, circulates in the bloodstream and is a standard marker for inflammation in the body. We also know that CRP levels tend to rise as we get older, and it may one of the factors involved in the increasing rates of cardiovascular diseases, diabetes and Alzheimer’s disease as we age.

This was a cross-sectional study that focused on baseline test results from 132 sedentary, independently living individuals aged 60 to 83 (47 males; 85 females) who had been recruited to participate in the Immune Function Intervention Trial (ImFIT), a randomized longitudinal trial designed by Woods and funded by the National Institute on Aging to examine the relationship between exercise and immune function.

Participants included only individuals who did not take medications that included corticosteroids, which could interfere with immune measurements. Smokers and/or those with severe arthritis, a history of cancer or inflammatory disease, chronic obstructive pulmonary disorder, uncontrolled diabetes mellitus, congestive heart failure, recent illness or vaccination, or a positive stress test were excluded.

The physical fitness of subjects was assessed through a battery of tests that measured such variables as fatigue, blood pressure, oxygen intake and carbon dioxide elimination and heart-rate recovery in conjunction with exercise on a walking treadmill. Tests also were administered to determine the subjects' levels of physical activity, physical fitness, emotional stress and body composition, including bone density and body fat. Blood samples also were drawn to measure CRP levels.

The results were published in a recent issue of the Journal of the American Geriatrics Society.

It is important that they measured body fat. We know that increasing the amounts of intra-abdominal fat lead to an increase in inflammation: a fat tummy becomes a factory for inflammatory mediators.

The most interesting findings related to heart rate recovery following exercise.

The speed at which people were able to get back to their resting heart rate after a strenuous exercise test was inversely related to the levels of CRP. That means that individuals who had better parasympathetic tone had lower levels of inflammation.

And as any gym rat will tell you, one of the best-known ways improve parasympathetic tone is with aerobic exercise. When an unfit person exercises it can take a long time for his or her heart rate to come back to normal. As you get back into doing regular exercise, your resting pulse rate falls and so does the time that it takes for your heart rate to recover after exercise.

Since the study was cross-sectional, i.e. the researchers took a snapshot of the participants' reactions and measurements at a single, fixed point we cannot say anything about cause and effect relationships.

The research confirms the conclusions of previous research that has indicated that high body fat is related to high inflammation and high fitness to low inflammation, though the researchers did not parcel out total body and abdominal fat. But this new research also suggests that physical fitness may be associated with a decrease in inflammation that is independent of body fat, and that it may be mediated by the parasympathetic nervous system: high parasympathetic tone is related to low inflammation.

So the nervous system may be the key player linking fitness, fatness and inflammation.

If this is correct, exercise alone will likely not be the whole answer. We also need to address other factors that modulate the activity of the parasympathetic nervous system including:

• Physical, psychological and social stress
• Adequate good quality sleep
• Diet and nutrition: there may be foods that can increase stress on the autonomic nervous system
• Adequate hydration: dehydration can be a major stressor on the body
• Breathing: shallow breathing and hyperventilation are all known to stimulate the sympathetic nervous system and damp down the calming activities of the parasympathetic nervous system

Sleep and Your Heart

The amount of sleep a person gets affects his or her physical health, emotional well-being, mental abilities, productivity and performance. Recent studies associate lack of sleep with serious health problems such as an increased risk of depression, obesity, cardiovascular disease and diabetes.

There was some interesting research presented at SLEEP 2007, the 21st Annual Meeting of the Associated Professional Sleep Societies in Minneapolis in the middle of June.

One study that caught my eye was conducted by Siobhan Banks of the University of Pennsylvania School of Medicine. The research was based on preliminary analysis of 39 subjects, each of whom participated in a laboratory-controlled chronic sleep restriction protocol. The subjects underwent two nights of baseline sleep followed by five hours of sleep restriction. The results showed a statistically significant decrease in the heart rate variability after just five nights of sleep restriction.

We already know that a reduction in heart rate variability may occur in several cardiological and non-cardiological diseases, and it is usually a harbinger of a poor outcome.

This work may provide the mechanism for why short sleep duration is associated with a heightened risk of heart and other circulatory problems.

The amount of sleep a person gets affects his or her physical health, emotional well-being, mental abilities, productivity and performance. Recent studies associate lack of sleep with serious health problems such as an increased risk of depression, obesity, cardiovascular disease and diabetes.

So if confirmed, the take home message is that sleep deprivation has a negative effect on a person's cardiac activity and that may in turn increase the risk of cardiovascular disease and mortality.

Even Neurons Need Friends

In many neurological diseases, including multiple sclerosis (MS) and some types of neuropathy, myelin - the insulation that covers and surrounds most of the larger nerves - is damaged or deranged.

Scientists at the Weizmann Institute of Science in Rehovot, Israel, working with colleagues in the United States, recently reported finding an important new line of communication between cells in the nervous system that is crucial to the development of myelinated nerves. This new discovery may eventually help us to restore the normal function of the affected nerve fibers.

Nerve cells (neurons) have long, thin extensions called axons. The longest of these axons is in the verves supplying the feet, and they can be over three feet or more in length. The larger axons are covered by myelin, which is formed by a group of specialized cells called glia.

Glial cells move around the axon, laying down the myelin sheath in segments, while leaving small nodes of exposed nerve in between. Myelin provides protection for the delicate axons, and it also allows nerve signals to jump rapidly between the gaps or nodes, increasing the speed and efficiency of the transfer of electrical signals down the axon. When myelin is missing or damaged, the nerve signals cannot skip down the axons, leading to abnormal function of the affected nerve and eventually the now naked nerve may degenerate and die.

In research published in Nature Neuroscience, Elior Peles, Ivo Spiegel and their colleagues in the Molecular Cell Biology Department at the Weizmann Institute and in the United States, provided a new insight into the mechanism by which glial cells recognize and myelinate axons.

They found a pair of proteins that pass messages from axons to glial cells. These proteins, called Necl1 and Necl4, belong to a larger family of cell adhesion molecules. The whole class of cell adhesion molecules does exactly that: they sit on the outer membranes of cells and provide the glue that helps them to stick together. Even when removed from their cells, Necl1, which is normally found on the surface of the axon, and Necl4, that is found on the glial cell membrane, adhere together very tightly. When these molecules are in their natural homes of the axon and glial cell, they not only create physical contact between axon and glial cell, but also serve to transfer signals to the interior of the glial cells, initiating changes needed to undertake myelination.

The scientists found that production of Necl4 in the glial cells rises when they come into close contact with an unmyelinated axon and as the process of myelination begins. If Necl4 is absent from the glial cells, or if they blocked the attachment of Necl4 to Necl1, the axons that were in contact with the glial cells did not myelinate.

This is an exceptionally important discovery. Most of the approaches that we use for treating MS, peripheral neuropathy and other degenerative diseases, can often help with symptoms and may slow but not cure the diseases. But if we can understand the mechanisms that control the process of wrapping the axons by their protective sheath, we may be able to recreate that process in patients.

T'ai Chi Ch'uan and Shingles

Shingles can be a particularly nasty problem, and treatment can be tough. It should be called herpes zoster, and it is caused by re-activation of varicella zoster virus (VZV) that causes chickenpox.

A new study  from the Norman Cousins Center for Psychoneuroimmunology at UCLA, has shown that t’ai chi therapy can stimulate the immune system of patients with shingles to levels comparable to those achieved using a vaccine against VZV.

It was a controlled trial in which the researchers randomized 112 healthy adults aged 59 to 86, who had a history of varicella infection, to Tai Chi Chih (TCC, a simplified, standardized form of tai chi) or health education (HE) for 25 weeks. After 16 weeks of intervention, subjects were vaccinated against VZV. The results of blood tests showed that TCC alone increased immunity against VZV by an amount comparable to that induced by varicella vaccine in the HE group.

It was interesting that the effects of the two were additive; TCC, together with varicella vaccine, produced a substantially higher level of immunity against VZV than vaccine alone, raising it to levels usually observed in adults 30 years younger.

The tai chi group also showed significant improvements in scores for physical functioning, bodily pain, vitality, and mental health.

Regular readers will recall another report from this research group, indicating that TCC reduced the activity of the sympathetic nervous system. The two studies both show that there is something special going on: the practice does not only calm the mind and body, it also regulates parts of the body that are normally beyond voluntary control.

There are clearly plenty of reasons for taking up t’ai chi, though now we shall have to see whether other forms of t’ai chi can achieve the same results.

Diabetes, Inflammation and the Heart

One of the most worrying signs in people with type 1 diabetes is damage to the nerves supplying the heart. This is called cardiovascular autonomic neuropathy, and one of its first signs is a reduction in the normal heart rate variability (HRV).

It has been known for many years that people with both type 1 and type 2 diabetes have low grade inflammation, and inflammation can have profound effects on the activity of the autonomic nervous system.

A study from Sabadell in Spain has tried to sort out these links in a study of 120 people with longstanding type 1 diabetes.

They measured a great many things including tumor necrosis factor, alpha-receptors 1 and 2, IL-6, and C-reactive protein; insulin resistance and HRV in response to deep breathing and the Valsalva maneuver" forcibly exhaling against with mouth and nose closed.

They did indeed find a link between low-grade inflammation and early alterations in the nerve supply to the heart.

This is important information: when we proposed that inflammation might be an important player in diabetes back in the 1980s, it was greeted with disbelief. Twenty years on it looks as if we might have a whole new line of treatment on the horizon, which will include nutrition and exercise as well as supplements and medications.

Glaucoma and Alzheimer’s Disease

There is a fascinating study by colleagues from University College London (UCL) that has just been published in the Proceedings of the National Academy of Sciences that has found a "clear link between what causes Alzheimer's and one of the basic mechanisms behind glaucoma.”



The research could speed up the development of new treatments for Alzheimer's and revolutionize the treatment of glaucoma, the most common cause of blindness in the Western world.

If glaucoma is indeed confirmed as a marker or risk factor for Alzheimer's then the early warning signs it gives could help ensure that patients have more opportunities to delay the onset of dementia.

The researchers discovered that the same "plaque" proteins are a key process in the development of both diseases. Clumps - or plaques - of beta-amyloid proteins that  kill brain cells in Alzheimer's patients, also kill optic nerve cells in the eyes of glaucoma sufferers. A link has bee suspected for some time: around 1.8-2.0% of the population will develop glaucoma, the figures in Alzheimer’s is as high as 25%.

Dr Francesca Cordeiro, who led the team at UCL's Institute of Ophthalmology, said:

“We've seen for the first time that there is a clear link between what causes Alzheimer's and one of the basic mechanisms behind glaucoma."

Glaucoma is a group of diseases of the optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. People with glaucoma gradually lose their wider field of vision. Many do not realize it until they barge into things.

The textbooks will tell you that glaucoma is caused by increased pressure in the eye, known as intraocular pressure. Standard treatments attempt to lower this pressure, but with only limited success. People with normal pressure can also suffer from glaucoma, suggesting it is not the only cause.

The researchers have shown that drugs that prevent the build-up of "plaque" proteins in the brains of people with Alzheimer's disease were successful in treating glaucoma in rats. One such drug, bapineuzumab, is already being used to treat Alzheimer's patients in clinical trials in Britain and the United States.

The UCL researchers showed that the effects on glaucoma were even stronger when combined with two other novel Alzheimer's treatments - "Congo Red" and a drug called a beta-secretase inhibitor.

This is very exciting work and we should know fairly soon whether these new approaches to treatment will help both glaucoma and Alzheimer’s disease.

Clearly this does not mean that everyone with Alzheimer's will develop glaucoma or vice versa. Both problems have multiple causes and can follow quite different trajectories. But links like these are the stuff of medical progress.

Emotions and Recovery from Hip Surgery

A patient's emotional state plays a significant role in his or her recovery from hip surgery according to research from Saint Louis University. This research was particularly interesting because the researchers were not looking for a link.

Orthopedic surgeons typically use two tests to determine if a patient has recovered from hip surgery: one is a clinical measure of hip function and the second is a patient questionnaire that looks at a number of factors that may play a role in the overall success of the surgical procedure. Originally the research was simply designed to see if the two measures, the clinical one that has been in use for decades, the other, a new subjective scale, correlated in some way.

The clinical test found good-to-excellent results, while the self-test taken by the same patients showed significantly worse recovery. The disparity could be explained by a section of questions on the self-test that are not addressed by the clinical test: those dealing with emotional well-being. After post-operative mobility, the patient's emotional status was the most important factor in determining how well he or she thought recovery was going.

It is common for doctors to think that patients are doing well because they have achieved a good technical result. But if the patient is still miserable, depressed and in pain, we should not congratulate ourselves on a job well done.

Yet a great many people are denied the help that they need. For instance they may have already had depression or they may be depressed because of pain and immobility. It does not really matter which came first. If the psychological aspects of the illness or the surgery are not addressed, people are not likely to recover. The same goes for having poor nutrition or poor social supports.

The whole point of Integrated Medicine is to address every aspect of a person: physical, psychological, social, subtle and spiritual.

This study provides further evidence that if we only look at the physical aspects of a problem or an intervention, we are going to miss the boat.

T’ai Chi Chih and the Sympathetic Nervous System

One of the problems about getting older is that the activity of the sympathetic nervous system may increase, bringing with it an increased risk of metabolic problems such as insulin resistance, hypertension and cardiovascular disease.

The sympathetic nervous system  is a branch of the autonomic nervous system. It is always active at a basal level, which is called sympathetic tone. It becomes more active during times of stress. Its actions during the stress response comprise the classical fight-or-flight response.

There is a very interesting study from the Norman Cousins Center for Psychoneuroimmunology at the UCLA Semel Institute for Neuroscience & Human Behavior in Los Angeles.

There were 32 people in the study aged 60 or over. There were 19 people who were T’ai Chi Chih (TCC) practitioners and 13 who were not. The practitioners had completed a 25-week training in TCC the 13 others just had health education classes. T'ai Chi Chih is a simplified  type of T'ai Chi that emphasizes the development of qi, a.k.a. chi.

TCC practitioners performed the breathing and movements for 20 minutes, while HE participants passively rested for the same time. Investigators measured various cardiovascular parameters before and after the task. A subsample of participants returned for a second evaluation and performed videotape-guided stretching for 20 minutes to evaluate the cardiovascular effects of slow-moving physical activity. TCC performance was found to significantly decrease sympathetic nervous system activity as measured by cardiac pre-ejection, blood pressure and heart rate. In contrast, there was no change in sympathetic activity following passive rest or slow-moving physical activity.

This shows us that there is something different about T’ai Chi. Practicing it leads to a decrease in activity of the sympathetic nervous system to levels that are not achieved by performing comparable physical activity alone.

Counterfactual Thinking

Most of us have experienced the “I should have,” “I could have,” “If only I” and “I would have” moments. Times when we lament our missteps. We say to ourselves that we should have invested in a certain stock, should have married Agnes or become a doctor instead of a cab driver. Though it can be positive, for some people this kind of thinking becomes so pervasive that they simply cannot take any action in the present. So anything that we can learn about this process will likely help a great many people.

We refer to this process in which we evaluate how we would do things differently, as “counterfactual thinking.” Though it can be positive, and help us learn from our mistakes, it is a common psychological mechanism that causes us to harbor feelings of disappointment and regret. For some people this kind of thinking becomes so pervasive that they simply cannot take any action in the present. So anything that we can learn about this process will likely help a great many people.

A common research strategy in the study counterfactual thinking, is to have people read stories in which the main character makes decisions that will ultimately doom him or her to failure. Researchers then ask them how they would have done things differently.

But this method may not provide a complete picture of this mental process. New research published in the June issue of Psychological Science, which is a journal of the Association for Psychological Science, shows that our counterfactual thinking may be markedly different when we are actually experiencing failure rather than reading about someone else's.

In a series of experiments, Vittorio Girotto of the University luav di Venezia in Venice, Italy and his colleagues attempted to demonstrate and explain the differences in counterfactual thinking between actors who actually experienced the problem and readers who just read about it.

The experimental subjects were divided into two groups:

• Actors who were asked to participate in a game in which they could win a reward by solving a math problem. They were then asked to choose one of two sealed envelopes: One was said to contain a difficult problem, and one supposedly contained an easy problem. In reality, both envelopes contained a problem that was nearly impossible to solve in the allotted time. Once the actors failed, they were asked to write at least one way in which things would have been better for them.
• In the second group, “Readers” read a story with a protagonist who faced the same choice and ended with the same negative outcome as the subjects did in the actor condition. Like the actors, readers were required to write at least one way in which things would have been better for the protagonist.

The readers and actors were very different in their counterfactual thinking. Readers tended to undo the protagonist's choice to tackle the problem, while actors changed the way in which they tried to solve the problem. So a reader would say, “I should have picked another envelop,” while the actor would ask if he could use a calculator.

These results run counter to previous theories of counterfactual thinking. It was assumed that people who read a story construct the same counterfactuals as people who experienced the events described in the story. It was also believed that actors tend to avoid self-blame at all costs when thinking of alternatives. Instead, the actor-reader differences emerged even in conditions in which actors' decisions made the best decisions that they could. The researchers said,

“Actors and readers produce different counterfactuals because they rely on different information, not because they have different motivations.”

In both cases, “what might have been” thinking can be stressful.

This research confirms something that we have been teaching for years:
Learn to detach from your aims and desires: you need passion and purpose. But you do not need the third “P:” Pain

Liberate yourself from the past: Healing, Meaning and Purpose has a whole section on novel ways to get rid of some of the “stuff” that most of us carry around in our bodies, our minds and our subtle systems.

Men, Exercise and Broken Bones

One of the problems that we all face as we get older is that unless we are careful, our bones can gradually become weaker. This is a particular problem in women, but a growing body of research indicates that men can run into trouble as well. At one end of the spectrum is “osteopenia:” a reduction in bone mineral density, and at the other end of the spectrum is full-blown osteoporosis.

The reason for taking the problem so seriously is that any degree of thinning of the bones can predispose us to so-called “osteoporotic fractures.” Sad to say, serious fractures are common among older people and can have devastating consequences, particularly if a hip is broken. Man people find it difficult to walk again. For years now we have recommended that women should take exercise to reduce the risk of thinning of their bones, particularly after menopause. But now research published in PLoS Medicine indicates that men who participate in sport or other vigorous activity may also reduce their risk of fractures.

Karl Michaelsson and colleagues at University Hospital, Uppsala, Sweden, report research in which over 2000 men who were initially studied in 1970-1973. The amount of physical activity that they took outside working hours was recorded, and then they were questioned again as they aged. Each of the surviving men was questioned again when they were aged 60, 70, 77, and 82. About half of the men were still alive at the end of the study, and the researchers recorded the number of fractures that the men had suffered during the 35 years of the study.

Based on the answers to the questions on physical activity at the start of the study, the researchers divided the men into three groups: those whose lifestyle was considered to be ''sedentary,'' those whose leisure activities included some walking and cycling and those who participated in sports for at least 3 hours a week. These were referred to as the low, medium, and high-activity groups. Over the 35 years, 428 men had at least one fracture and 134 broke a hip. However, there were significant differences between the groups. 20% of the low-activity men had fractures, compared with 13% of those with medium activity and only 8% of those in the high-activity group. Of greatest importance was that the chance of having a hip fracture – the worst type of broken bone in an older person - was dramatically reduced by increased activity.

The researchers conclude that taking exercise reduces the risk of osteoporotic fracture in men. Participating in sports seems to be particularly effective: they calculated that one-third of fractures could be prevented if men could be persuaded to take part in sports regularly.

There is also an excellent summary by Harri Sievänen and Pekka Kannus from Tampere in Finland. As always each entire article is available online.

And I am to get my running shoes this very instant…

Global Warming May Be Fatal

There are several reasons for being concerned about climate change. One is that global warming may cause significant changes in patterns of disease.

An analysis published last month in Occupational and Environment Medicine found that global warming will cause more deaths in summer because of higher temperatures but these will not be offset by fewer deaths in milder winters

The Harvard researchers analyzed city-specific weather data related to the deaths of more than 6.5 million people in 50 US cities between 1989 and 2000.

They found that during two-day cold snaps there was a 1.59% increase in deaths because of the extreme temperatures. However, during similar periods of extremely hot weather death rates went up by 5.74%. An important point is that deaths did not rise as steeply when temperature fluctuations were less extreme.

Deaths from all causes are known to rise when temperatures go up while heart attacks and cardiac arrests are more likely when it is very cold. It was anticipated that global warming would increase deaths during hot temperatures but that this would be compensated for by fewer deaths in the winter.

The authors conclude:

“Our findings suggest that decreases in cold weather as a result of global warming are unlikely to result in decreases in cold-related mortality in the US. Heat-related mortality, in contrast, may increase, particularly if global warming is associated with increased variance of summer temperature."

While all 50 US cities showed similar rises in deaths when temperatures plummeted, more deaths were seen during extreme temperature rises in cities with milder summers, less air conditioning and higher population density.

The authors suggest that this is because the use of central heating is widespread, whereas fewer people have air-conditioning in their homes.

They said:

“Central heating, which constitutes an important adaptive mechanism against cold, is almost universal in the US and this may explain why the US population seemed fully acclimatized to cold.

Making air conditioning universally available may reduce heat-related mortality but would, on the other hand, have a perverse effect by enhancing global warming through carbon dioxide emissions from electricity consumption.”

This advice is very sound.

There are two other points. First, it is sudden changes in temperature that cause the problems: we are quite god at acclimatizing to extremes. But if global warming brings with it more instability in the climate then we will likely see much more of a problem.

Second, and something that is often missed by the naysayers about global warming, is that most of us no longer have a luxury enjoyed by our ancestors: When they endured ice ages and periods of warming, they could simply migrate to a more congenial region.

Most of us are stuck where we are, and that's the big problem when we think about the health consequences of environmental change.

Can a Pain in the Neck Raise Your Blood Pressure?

A chance discovery at the University of Leeds in the United Kingdom may give credence to longstanding claims by chiropractors that treating pain and stiffness by adjusting the neck can also lower blood pressure.

In a study published in the Journal of Neuroscience Jim Deuchars and his team report finding connections between rats’ neck muscles and a specific region of the brain. Their findings indicate that the neck muscles could play a key role in controlling blood pressure, heart rate and respiration. 

They found that nerves run from receptors in the neck muscles to a region in the brainstem called the nucleus tractus solitarius that is known to be involved in the control of autonomic nervous system. It seems likely that signals from the neck could play a key role in ensuring an adequate supply of blood to the brain as we change position, for instance standing up suddenly. If the signaling system fails we may run into problems with low blood pressure (postural hypotension) and difficulties with balance.

Although it is early days, and it is a long way from a rat study to understanding human physiology, the finding may do more than provide a tentative explanation for the chiropractic reports. It may also explain another puzzle: why some people with whiplash injuries get trouble with their blood pressure. On the other hand, there have been a number of studies that have shown that the practice of yoga may help control blood pressure. It had been assumed that it was simply a consequence of generalized relaxation, but perhaps it is more specific than that: could a soft flexible neck be important in maintaining a healthy blood pressure?

The best research studies are the ones that suggest more questions than answers: on that criterion this is a most important study.

Depression, Folic Acid and Bread

A remarkable study was published in the July edition of the Journal of Epidemiology and Community Health, by researchers at the University of York and Hull York Medical School.

They reviewed 11 studies involving 15,315 individuals and confirmed that there is a link between depression and low levels of folate, a vitamin that comes primarily from leaf vegetables such as spinachturnip greens, dried beans and peas, fortified cereal products, sunflower seeds and certain other fruits and vegetables are rich sources of folate, as is liver. and

Last month, the British Food Standards Agency  recommended to Health Ministers that they should introduce mandatory fortification of either bread or flour with folic acid to prevent neural tube defects, which can result in miscarriage, neonatal death or lifelong disability. This new study suggests that the measure may also help to reduce the frequency and severity of depression.

Lead author Simon Gilbody said:

"Our study is unique in that for the first time all the relevant evidence in this controversial area has been brought together. Although the research does not prove that low folate causes depression, we can now be sure that the two are linked. Interestingly, there is also some trial evidence that suggests folic acid supplements can benefit people with depression. We recommend that large trials should be carried out to further test this suggestion."

Recent research from the same team published in the American Journal of Epidemiology has also shown that people with depression, bipolar disorder and schizophrenia commonly have a genetic mutation named MTHFR C677T in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene on chromosome 1. The enzyme that the gene codes for is involved in folate metabolism, and the mutation (polymorphism) means that they process folate less efficiently. Folate is linked to the production of some of the chemicals in the brain, including serotonin, that in some part some the brain elevate mood. The identification of this gene provides a plausible explanation as to why folic acid supplements may help people with depression.

There is also another implication of the finding: it is well known that some diseases are more common in people who have depression, bipolar disorder and schizophrenia, including coronary artery disease ad some forms of cancer.

This same genetic polymorphism has been linked to cancers of the breast and lung, as well as coronary artery disease. It may be that folate is one of the factors involved in both.

Yet another research project!

T’ai Chi Ch’uan and Diabetic Health

Regular readers will know that I am a great fan of t’ai chi ch’uan and qigong. I have been recommending them to people for years and even taught it for a while.

I have also been very interested in metabolic problems, particularly insulin resistance and diabetes.

So I was intrigued to see a study  from Taiwan that was just sent to me.

The trial involved thirty-two people with type 2 diabetes mellitus who participated in three hour-long tai chi sessions once a week for 12 weeks. The conclusions were that practicing t’ai chi might help improve one component of immune function and also improve the control of blood glucose.

The researchers found statistically significant reductions in levels of glycosylated (glycated) hemoglobin in the blood of participants, indicating improved long-term blood glucose control. Glycosylated hemoglobin or HbA1c reflects the average blood glucose over the last 8-12 weeks, implying that the improvement must have been quite swift.

They also found increased numbers of regulatory and killer T cells. This may be important: people with diabetes are at considerably increased risk of getting infections.

It is even more impressive that the study was published in the journal Diabetes Care, that is known for its exacting standards.

If you or a loved one has diabetes, you may want to think about taking up t'ai chi.

Good luck!

The Speech Field

If you think about it, our remarkable ability to receive and decode speech is a biological miracle of the first order. The more so because it appears that we have only learned the trick in the last 50-100,000 years.

I have commented before about the importance of looking at entire brain systems rather than individual spots in the brain or individual brain cells. The brain is supposed to operate as a unified whole. If it doesn’t things are going wrong. Another concept, and one that is not widely known outside of neuroscience community, is that instead of thinking about a stimulus causing a set of neurons to fire, it is better to think about stimuli modulating the activity pattern of neural circuits that are already active.

Think of the appearance f a TV screen when the set isn’t tuned to a particular station. You get a fast moving “snow” effect. It is only when a coherent signal arrives that the “snow” gets itself organized.

Now colleagues from the University of Maryland have published some new data which may help explain how we discriminate speech, and why sometimes it can go wrong.

It appears that a particular resonance pattern in the brain's auditory processing region appears to be the key.

Huan Luo and David Poeppel found that the inherent rhythm of neural activity called "theta band" specifically reacts to spoken sentences by changing its phase. The researchers also noted that the natural oscillation of this frequency provides further evidence that the brain samples speech segments about the length of a syllable.

The findings represent the first time that such a broad neural response has been identified as central to perceiving the highly complex dynamics of human speech. Previous research studies have looked at the responses of individual neurons to speech sounds, but not the response of the auditory cortex as a whole.

In their experiments, the researchers asked volunteers to listen to spoken sentences. One example was, “He held his arms close to his sides and made himself as small as possible."

At the same time, the subjects' brains were scanned using magnetoencephalography. In this imaging technique, sensitive detectors are used to measure the magnetic fields produced by electrical activity in brain regions.

The theta band oscillates between four and eight cycles per second, and it changes its phase pattern with unique sensitivity and specificity in response to the spoken sentences. As a second experiment, when the experimenters degraded the intelligibility of the sentences, the theta band pattern lost its tracking resonance with the speech.

The researchers said their findings suggest that the brain discriminates speech by modulating the phase of the continuously generated theta wave in response to the incoming speech signal.

Second, looking at the time-dependent characteristics of this theta wave suggest that the brain samples the incoming speech in "chunks" that are about the length of a syllable from any given language.

When you hear something, it goes from your ears to your brain where fields begin to sample what you are hearing. From that you decode the message and turn into something that you can understand, and you make the decision on whether or not you need to act.

It’s remarkable what’s going on under the hood!

The Ancient Core of the Modern Brain

Here is a question for biology students everywhere: “Which part of the brain is closest to the surface of the body?”

The answer is the retina of the eye.

We have known for two centuries that some parts of the brain are involved in primary perception.

But some extraordinarily interesting new research suggests that the brain may have started out as a sensory organ.

Hormones are usually divided into three major groups:
Endocrine
Paracrine
Autocrine

They are important in the control of growth, metabolism, reproduction and many other important biological processes.

In human beings, as in all other known vertebrates, the hormonal control signals are generated by specialized centers in the brain such as the hypothalamus. The signals generate a cascade of effects in different endocrine organs throughout the body. Over the years the list of endocrine organs has been growing, now including the heart and intestines. There is a long list of illnesses that can occur if organs escape from these control signals, or do the adolescent trick of ignoring what they are told.

Over the last decade we have been learning that many of our hormones have been around with little structural change for hundreds of millions of years, though they may have different roles in mammals, fish and birds.

It was interesting to learn that researchers from the European Molecular Biology Laboratory (EMBL) have shown that the hypothalamus and its hormones are not purely vertebrate inventions, but have their evolutionary roots in marine, worm-like ancestors.

Writing in the journal Cell they report that hormone-secreting brain centers are much older than expected and likely evolved from multifunctional cells of the last common ancestor of vertebrates, flies and worms.

For the most part hormones mostly have slow, long-lasting effects that complement the faster activity of the nervous system. Insects and nematode worms have simple but effective nervous system and rely more on the secretion of hormones to transmit information, within and between individuals.

Kristin Tessmar-Raible from Detlev Arendt's laboratory at EMBL compared two types of hormone-secreting nerve cells in zebra fish, a vertebrate, and the annelid worm Platynereis dumerilii. The researchers found some astonishing similarities. Not only were both cell types located at the same positions in the developing brains of the two species, but they also looked similar and shared the same molecular composition.

One of the cell types secretes vasotocin, a hormone controlling reproduction and water balance, while the other secretes a hormone called RF-amide.

Each cell type has a unique combination of regulatory genes that are active in a cell and give it its identity. The similarities between the fingerprints of vasotocin and RF-amide-secreting cells in zebra fish and Platynereis indicate a common evolutionary origin of the cells.

Another point in common is that in both species the cells are multifunctional: they secrete hormones and at the same time have sensory properties. The vasotocin-secreting cells contain a light-sensitive pigment, while RF-amide appears to be secreted in response to certain chemicals.

What this tells us is that we are probably looking at the most ancient types of neuron. Most likely their role was to link sensory cues from the marine environment to changes in the animal's body. Over time these autonomous cells might have clustered together and become more specialized, eventually forming complex brain centers like the vertebrate hypothalamus.

If this were just a clever bit of molecular biology and a trip down the memory lane of evolution it would be interesting but nothing more.

Instead these findings force us to think about the development of the brain in a totally new way.

It looks as if the brain did not start out like a little computer for integrating and interpreting incoming sensory information. It began life as a sensory organ and we will likely find that it is not just the retina that has a sensory function.

Rethinking the brain as an organ for sensation and association instead of a computer for analyzing and processing may help explain a number of puzzles about the brain and how we use it.