Archive for June, 2012

More on salt, actually salts

Saturday, June 30th, 2012

What should we make with our CSA-supplied spinach today?

We're in the prime of our CSA delivery season; fresh vegetables started three weeks ago and fruits this week. Many of our meals consist of spinach, lettuce, beets, rhubarb, apricots & cherries, with milk and/or cheese or yogurt. We rarely, if ever, shop for any "prepared foods," always check labels for sodium content, and only eat out, other than our weekly Thai food splurge, for birthdays and other occasions. I'm firmly convinced that less sodium (often termed "table salt," but most typically found in processed foods and restaurant dishes) is better for us.

So when I started reading an article in the ACP Journal Club section of the January 2012 issues of the Annals of Internal Medicine that was titled "Review: Interventions to reduce dietary salt do not reduce mortality or morbidity," I was skeptical. The original article, published in England, was a meta-analysis, a statistical look at a group of research studies. In this case seven randomized controlled trials were lumped together, and according to the Journal Club, the conclusion was as in the article's title.

But the US and Canadian reviewers disagreed. In people with normal, borderline, or elevated blood pressure, 6 of the 7 studies showed variable results and the pooled data did not reveal statistically significant decreases in death rates or medical complications. I went to the original article and the authors actually say, "Despite collating more event data than previous systemic reviews...there is still insufficient power to exclude clinically important effects of reduced dietary salt..."

That translates, to me, as "we don't know yet what happens when millions of people lower their salt intake." The reviewers, being ultra cautious, say, "...we are unaware of compelling evidence showing that consuming less sodium in the general population is harmful."

A free-lance science writer wrote an article in Scientific American in 2011 with the title, "It's Time to End the War on Salt." She argues that the data linking increased salt intake and various diseases is not solid.

Should I believe those statistics?

Yet there are lots of studies showing a strong link between salt intake and blood pressure and others claiming a similar correlation between dietary sodium and cardiovascular disease.

One country that decided to act on these supposed connections was Finland. In the late 1970s a national-level campaign was started to include mass media education, monitoring of urinary sodium excretion and food-industry cooperation using salt substitutes. The average sodium intake was cut by nearly 30% and over the next ~24 years stoke and heart attack deaths went down by 60%. Was this cause and effect? I'm not sure, since other factors may have played a role and the initial average salt intake was quite high.

But a December, 2011, New York Times article, with the striking title, "Sodium-Saturated Diet Is a Threat for All" led me to find another kind of salt that plays a role. I found the July, 2011, Archives of Internal Medicine research report, "Sodium and Potassium Intake and Mortality Among US Adults" and realized I was on the right track with our diet.

It's not just too much sodium chloride, the kind of salt some use at their dining room tables, manufacturers add to processed foods and restaurants to their recipes to add flavor and preserve food. It's also how much potassium you eat (in fruits, juices, vegetables, fish, nuts and meat), that makes a difference. In this case, within reason and assuming you have normal kidney function, more is better.

I'm going downstairs and eat some fruit and perhaps a baked potato and yogurt, all high in potassium and relatively low in calories.

Tuberculosis Part two: Treatment options, Old, New or None

Monday, June 25th, 2012

Robert Koch discovered the bacillus that causes TB

In the era before antibiotics, especially in the late 19th century, tuberculosis, often called the "white plague," was a leading cause of death in the United States. Eastern patients were urged by their physicians to travel to Colorado where the fresh mountain air was supposedly curative. Hundreds of those stricken with TB went to Denver which was sometimes called "the world's sanatorium." Hospital beds were scare and a Jewish woman, Frances Wisebart Jacobs, recognized as the founder of what is today's United Way, spearheaded a movement to fund a TB hospital which eventually became National Jewish Hospital and served patents of any creed with free care for the indigent.

Prior to the advent of antibiotics, TB continued to treated in sanatoriums, where rest, fresh air (and sometimes surgical collapse of a lung or removal of a cavity) were all the therapy available. Extracts from one such patient's diary, begun in April of 1944 and continued through early June of 1946, are available online having been published in the British Journal of the Royal Society of Medicine in 2004. 

Latent TB is usually treated for nine months with a single antibiotic, usually INH like I was given in the late 1970s. Active TB is quite a different matter and for those with drug-susceptible infection, usually requires a four-drug combination given for six months. This may be given as directly observed therapy with a healthcare worker meeting the patent at their home or workplace.

If the patent stops taking the antibiotics too early or if the particular TB bacteria involved are drug resistant (this occurs more frequently in people with HIV/AIDS and those who have had previous TB therapy), or the medications used are of poor quality, multi-drug resistant TB can develop.

A 2002 paper titled "Tuberculosis therapy: past, present and future," while detailing the history of TB treatment, mentions that George Bernard Shaw, in his 1911 play, The Doctor's Dilemma, talked about the early attempts to cure the disease as a "huge commercial system of quackery and poisons." Elsewhere in the play, Shaw mentions "stimulating the phagocytes," referring to white blood cells that can engulf invading bacteria. The modern take on this 1911 quote would be a TB vaccine.

The only one I'm aware of is BCG, an attenuated live viral vaccine produced from the bovine strain of tuberculosis. It's been around since the 1930s and has been given to at least 5 million people globally, but its major benefit has been to prevent spread of TB to sites other than the lungs. At this stage we really need an effective immunizing agent, as our pharmacologic attempts to keep TB in check are becoming less and less effective.

We all need to support efforts to stamp it out.

Workers at the CDC published a 2007 paper titled "Worldwide Emergence of Extensively Drug-Resistant Tuberculosis" (XDR-TB) mentioning that nearly 90 countries have had multi-drug resistant TB (MDR-TB) requiring usage of so-called second-line drugs for at least two years. Now we've gone beyond that as nearly 10% of the 3,520 samples from an international MDR-TB pool were also untreatable with a majority of those drugs.

So we're up to 2012 and The Wall Street Journal's article, "India in Race to Contain Untreatable Tuberculosis." TB already kills more people than any other infectious disease except for HIV. But since the first cases of XDR-TB were reported in Italy in 2007, Iran and now India have also been struck by the strain.

There's an urgent need for an effective vaccine or a totally new approach to TB treatment.


Tuberculosis Part one: How long has it plagued us?

Saturday, June 23rd, 2012

I was reading an article in The Wall Street Journal this morning about "Untreatable tuberculosis in India" and decided to explore the background data before writing about what we're facing now.

I have a personal acquaintance with TB; when I returned to Air Force Active Duty status in 1977, I got a TB skin test. Much to my surprise it was positive.

I'm glad my chest x-ray didn't look like this

My chest x-ray was normal; I had none of the symptoms of active TB: chronic cough with blood-tinged sputum, night sweats, fever and weight loss. So I didn't have active disease and could be treated with only one drug; the infectious disease specialist told me I would take a medicine called isoniazid (INH) for a year.

I found out that about a third of the entire world population has been infected with the human variant of TB, Mycobacterium tuberculosis. In the US, 5-10% of the population will have a positive skin test; in other parts of the world, especially in some Asian and African countries, up to 80% will test positive.

Around the world new TB infection are estimated to occur at the rate of one per second, nine million cases a year with 95% of those living in developing countries. The vast majority of those remain asymptomatic. Of those who have a normal immune system, roughly 5-10% will ever develop active disease. But if you have HIV you have at least a 30% chance of moving on to symptomatic disease & x-ray-positive TB; other studies place the risk even higher, at 10% per year.

Now that milk is pasteurized, most of us in the US don't have to worry about the bovine strain of TB. But that isn't true everywhere, so beware of drinking unpasteaurized milk when you travel abroad.

A detailed online history of TB from the New Jersey Medical School commented that 2-3 million people die of the infection every year; the vast majority of those lived in developing countries. The ancient Greeks called the disease phthisis. It's been with us for millennia; ~4,500-year-old spinal column bits and pieces from mummies in Egypt  were the earliest evidence of human infection that I had been familiar with, but I found an article that doubled that estimate. Bones from an ancient site off the coast of Israel, estimated to be 9,000 years old, not only had the characteristic signs of TB, but also had DNA and bacterial cell wall lipids that could be analyzed by modern techniques.

One of his ancestors had evidence of the earliest TB we're aware of

Researchers from England commented that the tuberculosis we see today came from a human strain of the bacteria, not from a bovine origin. They also said that the DNA was subtly different from that of TB organisms today and felt this meant there has been a very long linkage between this infection and people. But the very earliest animal to have clearcut evidence of TB was a long-horned 17,000-year-old bison with skeletal remains showing the disease.

TB outbreaks still occur in the US. The June 20, 2012 edition of JAMA has a CDC report of cases which occurred in a homeless shelter in Illinois. The majority of the 28 patents involved (82%) had a history of excess alcohol use  and many had longer stays in the men's section of the shelter and socialized in two bars in the area.

The risk factors seen in developing countries: lower socio-economic status and overcrowding, seem to me to have played a role in this US series of patients. Alcohol over-usage has been implicated as a risk factor for TB,  perhaps from repeated prolong close contacts in bars and perhaps from effects on the immune system.

I'll get back to the current issues with TB in my next post.




Thanks for the Memory: part 2: Dementias

Tuesday, June 19th, 2012

It's on the tip of my tongue

In 1990 I needed neurosurgery. The mass which was removed turned out to be benign, but I had a major post-op bleed and was left with a considerable scar on my right frontal cortex. Up to that point I'd had, as I often said, "the fourth best memory in the family."

Afterwards my brain worked well enough. But I had considerable problems moving information from short-term to long-term memory. So when I bought the Harvard Medical School booklet mentioned in my last post, I was intrigued by the research that has been done on the subject and how it applied to me and to others, especially as we age.

Most of us worry about dementia; the Aging, Demographics and Memory Study figures, published in 2007 looking at people 71 or older, estimated there were 3.9 million people with dementia in the US in 2002. Of that group, 2.4 million had Alzheimer's disease. The crucial factor, I thought, was the prevalence, the total number living with a disease, went up with age from 5% of people in the 71 to 79 year old group to 37.4% in those 90 and above. And there are lots more of us living to that age than before.

It's become clear that having a stroke, what used to be termed a "cerebrovascular accident" (CVA), is another major route for developing dementia. A 2010 study in the journal Stroke describes dementia associated with "first-ever stroke" in a French city of 150,000 inhabitants over a 24-year period. Out of nearly 4,000 patents suffering a CVA, 20.4% had dementia. Risk factors for the outcome included age, diabetes, prior heart attack, and atrial fibrillation (an irregular heart rhythm associated with a risk of emboli, blood clots that can be dislodged, travel to the brain and clog an artery).

These figures clearly included those with new-onset dementia, but, because of the study's design, didn't exclude those who may have had the problem prior to their stroke. Nonetheless a history of stroke nearly doubles the prevalence of dementia in people over 65.

Another group with an increased incidence of neurocognitive (thinking/memory) issues includes the roughly 40 million infected with HIV. At least 30% of that group have associated brain function impairment ranging from minor or mild symptoms to full-fledged dementia. With the newer anti-retroviral drug treatments, the incidence (new cases) of HIV-associated dementia (HAD) has markedly decreased, although with people living longer with the virus, overall there are more HAD patients.

There is a roadblock between the circulation and the brain itself, the blood-brain barrier (BBB), which serves, in usual circumstances, to prevent microbes from invading the central nervous system. The human immunodeficiency virus can penetrate the BBB in several ways: one of which is by hitching a ride inside one kind of immune cells called monocytes. This is termed a "Trojan Horse" method.

Another disease, affecting 1.3 million Americans, is termed Lewy Body Dementia (LBD). It's closely associated with the dementia seen in Parkinson's disease. Both have deposits of an abnormal protein that causes difficulties in brain function. In LBD these proteins are found in several areas of the brain; with Parkinson's they are more localized.

Let's get the right pill to help, not hinder

So why is it important to know what kind of dementia a person has?

Some types respond poorly to medications that may help other forms, at least to a limited extent. And LBD patients may be helped by meds that offer less benefit to Alzheimer patients.

It's not always easy, but an experienced neurologist can often sort out which person has which disease.


Thanks for the Memory: Part one

Thursday, June 14th, 2012

keep in touch with your older friends

My wife and I recently talked about the consequences of aging, physical and mental, and I decided to order a booklet from Harvard Medical School titled "Improving Memory: Understanding age-related memory loss." Then we set out on a Monday through Friday visit to old friends (literally, since most were more than 85 years old and at least five were over ninety). We flew from Denver to a city we once lived in and saw ten individuals/couples over the ensuing four days.

I remembered a family occasion fourteen years ago when my Dad and another elderly relative were talking about whether they'd rather be as they were, over ninety and suffering various aches and pains, but mentally sharp, or like another senior at the dinner was, a year or so older and healthy physically, but over the Alzheimer's cliff. They both voted for being creaky, but lucid.

The older friends we visited in three locales on the recent trip reminded me of Dad's discussion back in 1998. Most were a little frail and complained of a variety of back, leg and joint issues, but they were mentally right on target. On the other hand, I wondered if several had at least mild cognitive impairment.

Then we came home and I started reading the booklet. There are seven normal types of memory problems: a tendency to forget thing over time (transience), absentmindedness, blocking, misattribution, suggestibility, bias, and persistence. All of these can be worsened with age  without implying more severe brain issues: Alzheimer's, other dementias or even mild cognitive impairment.

The missing letters may not mean Alzheimers

I had the second of those seven problems yesterday, seeing a new member of my men's book group on the front steps of the house we were meeting in, introducing ourselves by first names and then sitting through a detailed discussion of a book, The Inventor's Dilemna, over the next two hours.

One of the seniors we visited on our trip had always been superb with names and even in her mid-80s is much better than most of us. I never had that talent and, of course, I have even less of it at age 71.

I had made no real attempt to store the other guy's name, didn't give him one of my usual memory-hook mental pictures, and totally forgot it by the time we left. One trick to overcome absentmindedness is using cues. I'm a "visual-verbal" person, and so I tend to superimpose an unusual tie or a mustache or something similar and then repeat  the cue to myself. When I do that, I remember names. In his case, I hadn't done so.

The book from Harvard has ten ways to promote memory health. One was very striking to me: "Get a good night's sleep." I sometimes read late into the night, 11:30 or 12 or even 12:30, and when I do I'm a tad groggy in the morning. That's not something I should do if I want to be at my best the next day.

So, having been in their company for a few minutes to several hours at most, I wouldn't even venture a guess as to whether the older friends we had eaten a meal with, or talked with for five or ten minutes, were mentally totally normal for their age and encountering one of the seven types of age-related memory problems we'll all have to cope with, or, possibly, had more severe issues.

But I will use the ideas in the book from Harvard Medical School.


Aspirin revisited

Sunday, June 10th, 2012

They may be good for your heart, but.....

Some years ago I began to take a baby aspirin a day as a cardiovascular event preventive medication. In my case, it was primary prevention. I've not had a cardiovascular event and don't have major risk factors. Most of my relative lived until their 90s; the only exception was my older brother who smoked three packs of cigarettes a day, gained 50+ pounds after age 40, didn't always take his blood pressure meds and loved foods that I don't consider as "heart-healthy/" When he died of a heart attack at age 57, I couldn't find his car; Dad said, "Look in the parking lot of the closest Kentucky Fried Chicken," and that's where it was.

Now I plan to stop my daily 81 milligram aspirin having read an article in JAMA which studied the incidence of major bleeding episodes (mostly in the brain or in the bowel) of over 185 thousand people who were taking low-dose aspirin compared to carefully matched controls who weren't.

The authors started with a 4.1 million population base in Italy where aspirin taken to prevent cardiovascular events is paid for by a government prescription plan for all at high risk. A six-year period was selected (start of 2003 to the end of 2008) and those over the age of 30 who began taking low-dose aspirin during that time frame were the study subjects. There were nearly 600,000 people considered for the study, but after appropriate exclusions just under a quarter million current aspirin users were carefully matched with control subjects. From a random sample of nearly 850,00 non-aspirin users, matches were found for 186,425.

let's look at the statistics

I was impressed by the thoroughness of the statistical procedure using propensity scores  ( a way to get apples matched with apples, not with zebras or even melons) and a "greedy-matching algorithm" (this link is only for math fiends) as another way to reduce bias. The results convinced me to stop taking my baby aspirin a day. The number of study subjects who had their first major bleed was fairly low (6,907  or 1.85% of all those in the study were hospitalized for a hemorrhagic event) and the absolute difference between aspirin users and controls weren't huge  (5.58 per 1,000 person-years for those taking the drug versus 3.60 per 1,000 person-years in those who didn't take aspirin). But those numbers don't tell the whole story.

Men had considerably more bleeding episodes than women and older subjects had increased rates than younger ones. So as a 71-year-old man, I paid attention. I'm not diabetic, but noted that those who were had a higher risk of bleeding whether they took aspirin or not.

This wasn't a randomized controlled study, but its enormous size and careful methods were striking. The accompanying editorial by an MD, PhD from a university in Vienna looked at previous meta-analyses (lumped-together studies) and said that for a hypothetical large group of patents who took low-dose aspirin for secondary prevention, there was a 6 to 1 benefit-risk ratio. That supports giving the drug to people at high risk of a cardiovascular event.

But when you come to primary prevention, a similar large group of 10,000 could be expected to have 7 fewer cardiovascular events at the cost of 1 major bleed in the brain and 3 elsewhere. The odds are low enough that new guidelines in Europe don't recommend giving aspirin for primary prevention. This new study would certainly support that viewpoint.

I crossed off aspirin on my pill calendar.

Spinal cord injury: Amazing News

Friday, June 1st, 2012

I read an incredible article in The New York Times yesterday; scientists in a Swiss lab have been able to overcome an experimental spinal cord injury in rats, enabling them to walk again. Today I found the original scientific publication and decided it was a major breakthrough, well worth translating into human terms and language.

There may be rocks below

Let's start with the human statistics; there are about 12,000 non-fatal, but severe spinal cord injury (SCI) cases in the United States every year. Half of those SCI lead to chronic paralysis and a quarter of a million people with significant SCI were alive in the US in 2010. Most of those suffered their injury when they were relatively young and 80% of them are male.

Motor vehicle accidents account for roughly 40% of those cases; the next most common cause is termed "falls," but a typical story for a fall would be a young guy who dives into a pool or a water-filled abandoned quarry, not knowing its actual depth, and strikes the bottom or a rock.

I found a thoughtful blog post on diving. The author gave five suggestions of which one is clearly the most important: "Think First." The others included "Steer up," "Hands up and out" and "Control your dive." The last was also crucial, "Don't drink or take drugs and dive."

Let's go back to the rats. The article was published online in Science and is densely packed with medical terminology (I'd suggest you read the NYT article). The rodents had a partial severing of their spinal cords at two different levels, leaving normal tissue in between and connecting the parts of the spine involved. This corresponds to somewhere between 25% and 33% of human spinal injuries. A week after their SCI, the rats began training for 30 minutes a day.

They were fitted with little vests, held upright on their rear legs and given a goal, a piece of cheese to move toward. At the same time their spines were stimulated electrically above and below the spinal areas partially cut and they got a chemical infusion of several drugs that affect nerve cell activity.

The initial voluntary steps began after 2-3 weeks of daily training and, at that point, the time of exercise was gradually increased. Five to six weeks after the initial SCI all the rats could initiate full weight-bearing steps while the combined electrical and chemical stimulation was being applied. Eventually they could climb stairs and avoid obstacles. They also had anatomic evidence of new neuron (nerve cell) connections around the injury and, higher up, in the brain stem.

Control rodents placed on treadmills did not recover the ability for voluntary motion.

A neurologist from UCSF who was not involved in the research study was quoted as saying, "There's a huge potential to refine this model to mimic more humanlike conditions."

A Stanford medical school website captures the essence of what's going on; this is neural plasticity, the building of new wiring patterns in the nervous system.

Is it possible?

A simpler comment would be that this research, if extended and then repeated in human subjects, may possibly bring hope to some of those afflicted with spinal cord injuries and maybe even diseases. Perhaps some who otherwise would have been wheelchair bound will be able to walk again.

It's not at all clear to me that this will work in people who had a SCI some time ago and it doesn't appear to be applicable to those who have a complete transection (total severing) of the cord.

Time, as always, will tell.