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Saturday, June 11, 2005

Checking The Validity of Medical Claims

Persons who use the Internet are likely to encounter various claims about medical topics.  Indeed, the Internet is a powerful and useful tool for obtaining medical information.  Probably anyone reading this knows, though, that there is a lot of utter nonsense out there.  Some of it is not just wrong, but dangerously wrong.  In this post, I examine one example of a medical claim (Tom Cruise's inept remarks about postpartum depression), then use the example to illustrate how to use the Internet to find valid medical information.

In a recent interview on Access Hollywood, actor Tom Cruise criticized his colleague, Brooke Shields, about her use of paroxetine to treat postpartum depression:  
Brooke Shields, with whom Tom co-starred in "Endless Love," recently wrote a book about her own bout with post-partum depression following the birth of her daughter, Rowan. She wrote about the drug treatment that helped her through it.

"Look at her life," counters Tom. "Here is a woman - and I care about Brooke Shields because I think she is incredibly talented - (but) you look at where has her career gone? It has helped her. When someone says it has helped them, it is to cope. It didn't cure anything. There is no science. There is nothing that can cure them whatsoever." [...]

Tom went on to say, "What you can do with vitamins and exercise to help a woman through that, to help someone through that, all right. She doesn't know what these drugs are and for her to promote it is irresponsible. And I wish her well in life. (But) it is irresponsible to do that."
This comment generated a lot of criticism, as illustrated here.  Obviously, people get pretty worked up about some of these topics.  People who put things on the Internet have all kinds of agendas, and it is not always obvious what their agenda is.  So how can a person figure out which claims are valid, and which are not?  Here are some tips:

1. Consider the source.  Although it sometimes is hard to verify the authenticity of a webpage, some sources clearly are authoritative.  The National Library of Medicine, National Institutes of Health, and the Centers for Disease Control and Prevention often are good starting places for medical information.  Access Hollywood is not.  Look at the credentials of the author, if possible.


Would you take medical advice from this man?

2.  Search for more information.  Search engines such as Google can find a lot of information, but they cannot verify that the sources are any good.  Googling "Tom Cruise postpartum" turns up a lot of commentary, mostly negative.  This is a clue, but is not definitive.
I ask you this, sir: Since when are you a woman? When was the last time you gave birth? When was the last time you were married to a woman who gave birth? You ranting, cult-following lunatic, the answer to those questions, in case you didn't notice, was NEVER.

I feel incredibly sorry for women who have to deal with this condition. Small-minded people without any first-hand knowledge of the situation cannot possibly offer their two cents. I hope women continue to get treatment for this and don't take some male actor's opinions to heart.
3. Search again for more information: this time, use a better search tool.  The best, by far, is Medline.  The National Library of Medicine offers free Medline searching here.  If you search for "postpartum depression" you get 1,284 hits.  If you search for "vitamins" you get 171,562 hits.  If you search for "postpartum depression vitamins" you get 4 hits.  Not a single one of those 4 contains any recommendation for treating postpartum depression with vitamins.  If you search for "postpartum depression exercise" you do a little better: there are 10 hits.  One of them, The role of alternative medicine in treating postnatal depression, was published in Complimentary Therapies in Nursing & Midwifery.  This shows that Medline does not leave out alternative sources of information.  As it happens, nurse midwives think women should exercise after childbirth, but even midwives do not seem to put any stock in using vitamins to treat postpartum depression.  

4. Evaluate specific claims: Vague statements often sound good, but can be difficult to test for validity.  Another quote from Cruise provides some material for the method of testing specific claims:
"When you talk about postpartum, you can take people today, women, and what you do is you use vitamins. There is a hormonal thing that is going on, scientifically, you can prove that. But when you talk about emotional, chemical imbalances in people, there is no science behind that. You can use vitamins to help a woman through those things."
We've already looked at the vitamin question, and found no scientific evidence to support his claims.  But it is hard to prove something by not finding contrary evidence.  However, the claim, that there is no science behind the notion of chemical imbalances, can be shown false by finding evidence of chemical imbalances.  A Medline search on the string "biological basis of depression" turns up 339 hits.  Googling "brain imaging mood disorders" turns up this:



Mr. Cruise, your mission, should you decide to accept it, is to explain how these images came about in the absence of a chemical imbalance.

In summary, it is not only possible, but actually quite easy, to find reliable information on medical topics.  Just stay away from experts who jump on sofas.


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Tuesday, June 07, 2005

Another Stem Cell Explainer

I just got back from a conservative blog that I respect, having read a post about the stem cell controversy.

This is a bit of a follow-up to last week's post. As the embryonic stem cell debate started raging, I noticed that some bloggers with traditional views kept emphasizing the value of adult stem cells (ASC), suggesting that ASC could be just as valuable as embryonic stem cells (ESC). I was perplexed by that. Then I learned that, according to some theological principles, in some circumstances it might be acceptable to bend the rules a little bit, so long as there was no other way to do the job. That assumes that the job to be done has some redeeming outcome. Thus, they would not be able to make as strong of an argument against ESC, unless they could show that the use of ASC could accomplish the same therapeutic purpose as could be derived from ESC. It occurs to me that it may be useful to explain why this is unlikely to be the case.

To understand this, it is helpful to look at a specific example. Read the recent Scientific American article about neuronal stem cells; an excerpt follows, but the entire piece is not much longer:
The discovery that new neurons can arise in adult brains--a feat first observed in songbirds--overturned the long-held belief that a vertebrate's complete supply of neurons is created at birth or soon thereafter. In the new work, Fernando Nottebohm of Rockefeller University and his colleagues investigated how latecomer neurons differ from lifelong ones. The researchers injected two types of dye into the brains of 19 songbirds and collected samples from both types of neurons, which are used in two different pathways in the brain. After analyzing genetic information from more than 3,000 cells from each animal, the team determined that one gene (UCHL1) showed remarkably low activity in the newer, or "replaceable neurons": the longstanding ones exhibited 2.5 times the amount of the UCHL1 protein. "Low levels of UCHL1 appear to be a feature of replaceable neurons wherever they occur," says study co-author Anthony Lombardino of Rockefeller University.
The "latecomer" neurons are nerve cells that developed in an adult brain, growing from neuronal stem cells. Even though many news articles claim that stem cells can grow into any cell in the body, the research cited above chows that the progeny of ASC are not the same as the progeny of ESC. The original brain cells were derived from ESC. They had enough of the UCHL1 protein to be fully viable and functional. The ASC still have the gene that codes for the UCHL1 protein. They still have the ability to generate nerve cells.  But the nerve cells produced by the adult stem cells are not as long-lasting as those produced by embryonic stem cells.  This indicates that ASC are not, with current technology, replacements for ESC.

The difference is not in the genetic makeup. The difference is in how the genes are regulated.   When the gene is expressed, it produces the protein. (UCHL1, in this case.) The regulation of gene expression is rather mysterious at this point in time.

It is possible that, given enough research into gene expression, that we could tweak ASC to act like ESC. But given that you would have to get the expression right for all 20,000+ genes, it is doubtful that we ever would be able to do it correctly by artificial means.

Furthermore, if we are going to figure out how to do that, we almost certainly will have to use ESC to see how it happens in ESC.  Trying to reverse-engineer ASC, to get them to act like ESC, without actually having ESC to study, would be extraordinarily difficult, and likely impossible.

The article that Bill cited on his InDC Journal is here, from WaPo. The author expresses hope that there may be a way out of the ASC/ESC controversy.  In the article, the author states (correctly):
What is different about stem cells -- and what gives them their remarkable capacity to proliferate and morph into whatever kind of cell the body may need -- is the specific pattern of activity of their genes. It is all about which genes are working and which are dormant.
Farther on in the article we see a hopeful sign, hopeful in that it indicates that there may be an acceptable way out of the stem cell controversy:
Working with early mouse embryos, the team has found that single blastomeres, when cultivated in dishes with embryonic stem cells, can become what appear to be embryonic stem cells themselves. Chemicals secreted by the embryonic cells apparently flip the right genetic switches in the blastomeres to make them act "stemmy."
The implication is that it might be possible to remove a single cell from a very early embryo, use that cell to generate a line of cells that are like ESC, although perhaps not exactly the same thing ("stemmy").  If the cell is isolated at an early enough stage, the embryo that had the cell removed might develop normally.  If this works, it may be possible to develop cells that are as good as ESC, without having to try to get ASC to act like ESC, and without diminishing the viability of donor embryos.
If this technique were applied to humans, then a single cell taken from an eight-cell fertility clinic embryo could give rise to a self-replicating line of embryonic stem cells without compromising the donor embryo's odds of someday growing into a baby.
The author points out that the research so far is very early, much of it has not yet been published. That means that it has not been subjected to peer review, and has not been replicated independently.

If everything checks out, this could be a way for our society to get off the dilemma. It's a big if, but...we'll see. If it does turn out as we hope, though, there still could be problems. I can foresee three problems in particular.

First, you would have to get couples to consent to having a cell removed from the donor blastomere prior to implantation. Given that the couple just paid $10,000 for the IVF procedure, and they are desperate for a child, and want that child to be normal, are they going to go along with it? Would it be sufficient to tell them that there usually is no risk in rodent blastomeres?  Well...who knows? It would be up to the couple to decide.

Second, after you get the faux-ESC, and develop something that might be therapeutic, you have to implant them into a human to see if they do the job. To do that, at least in the USA, you need to get the FDA to say it is OK. Perhaps that would be no problem. But getting them to agree to human experiments with "stemmy" cells instead of stem cells would be a somewhat like trying to use a drug that is "penicilliny" instead of using penicillin. Sometimes that really is OK, but it always requires a great deal of hand-wringing to decide.

This may be a surmountable problem, but think of yourself as the patient. You are asked to give permission to have these cells injected into your brain. Do you want the "stemmy" cells, or do you want the real thing?

There are over 20,000 genes in those cells, and most -- if not all -- of them have to be regulated properly for the cell to do what it is supposed to do. Perhaps it will turn out OK if a few of them are not quite right, but if you are like the rest of us, you have only one brain to experiment on.

Perhaps I am being too skeptical here, but after all, I am the guy with a bumper sticker that says "QUESTION SKEPTICISM."


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