Vaccination works

Here is the rate of systemic infections caused by the bacteria Streptococcus pneumococcus (aka pneumococcus or strep pneumo) before adn aftern immunization for it. Not cases are only by those serotypes covered by the vaccine. The <5 is the group that actually got the vaccine, but there seems to be a decrease of disease in each age group, presumably because older people get it from kids. The incidence is so high in the elderly because they tend to be frail to begin with

A Cadillac, not a Hyundai

This article points out the lack of incentive for cost-effective medical care

Another question is how to change incentives for developing the technologies in the first place. "In the automotive and consumer-electronics industries, there are incentives to develop good, cheap DVD players or good, cheap cars," Goldman said. "When it comes to medical technology, there is no incentive to develop something that's pretty good but less expensive because the people who are buying it don't pay for it. It's not surprising that everyone wants a Cadillac instead of a Hyundai."

Of course one soluton would be people paying more of their medical expenses, like those who have health care savings accounts do.

Depressed medical students

An interesting article on depression among medical students in last week's NEJM (free full text).

Others have suggested that although the rate of depression among students entering medical school is similar to that among other people of similar ages, the prevalence increases disproportionately over the course of medical school.

I think there are several contributing factors, including:

1. Hard work, much of it not very rewarding (i.e. memorizing biochemical pathways or printing out lab results)
2. Sleep deprivation
3. Disillusionment. Medicine is a funny sort of career. Most people have no real idea what they are getting into when they decide to go to medical school. They work very hard to get good grades in hard classes and good MCAT scores as undergrads, then show up for 2 even harder years which have no relation to what they'll actually do. Then 3rd year, they start "clinical" work, but it is largely focused on inpatients who are generally old, sick and depressing (most people have no idea what a high percentage of medical care goest to the old/sick). They spend most of their time with even more tired (and often bitter) residents. They don't stay in one place long enough to bond, and are separated from all their classmates. Most people are able to find a specialty the can tolerate (or actually like) but if, say, you are destined to be an anesthesiologist and you do medicine and pediatrics as your first rotations, things can look a little bleak.
4. Learning to live independently. I think studies say undergrads spend 25-30 hours per week on school (granted pre-meds probably spend a bit more than average), and live in dorms with janitors and have meal plans. Even then they have trouble getting their laundry done. Now as a medical student you are working 2-3x as many hours and also having to be more responsible for things like buying groceries and paying the rent.

It is no wonder so many medical students are depressed. Of course, in many ways what comes next, residency, is worse.

Where avian flu is

From this months Nature Medicine. Note that the outbreaks in Canada and the Netherlands are not with the H5N1 strain of the virus and are therefore less worrisome.

Origins of BSE/vCJD

(catchy title!-ed)

It is pretty clear that sometime in the recent past, cattle started getting infected with a "prion" that caused BSE or bovine spongiform encephalopathy. Prions are infectious particles that consist only of protein, without any nucleic acid (e.g. RNA or DNA). Needless to say prions are unusual entities. As best can be determined, they are misfolded proteins capable of causing misfolding in other copies of the same protein. There are genetic mutations that can cause the misfolding (which can then spread to the non-mutant copies) or the misfolding can arise spontaneously.

There are sporadic human cases called Creutzfeldt-Jakob Disease (CJD) and there is a very similar disease called kuru among natives of New Guinea who have a ritual of eating the brains of dead people (which could obviously spread the prions). Sheep has a prion disease called scrapie that is similar and involves the homologous protein. BSE (aka mad cow disease) emerged in 1986. BSE can be transmitted to humans, apparently inefficiently, and there have been about 150 cases of what is called varient CJD (vCJD) in Great Britian.

The source of BSE is unknown. The leading hypothesis is that cattle ingested sheep remains contaminated with scrapie. A recent article in the Lancet suggests that human remains may be the actual source. I like this kind of hypothesizing but the article is ridiculous.

The article spends a fair amount of time establishing the feasability of human to bovine transmission and is succesful at that. The basic idea is that many dead bodies in the Indian subcontinent are disposed of in rivers, often directly. Remains (animal and human) are recovered for use in animal feeds and fertilizers and Great Britain was a substantial importer of such products during the pre-BSE time period. The total amount of human remains actually fed to British cattle is probably very small, but this part of the hypothesis is at least plausible.

The weakness is that sheep seem a much more likely source. Scrapie in sheep is endemic in Britian and sheep remains are routinely included in fertilizers and animal feeds, so the total exposure to sheep remains is much, much higher. Scrapie and CJD are both rare, but the likelihood of exposure to the former must be several orders of magnitude higher than the latter. The only thing that might implicate human remains would be evidence that BSE (or perhaps vCJD) is more similar to CJD than to scrapie. Of course if vCJD was the same as CJD it wouldn't be called variant would it?

The best the authors can do is some hand waving suggesting that BSE isn't particularly similar to either scrapie or CJD; not surprisingly, it is similar to vCJD. One problem for the authors in particular and the field in general is that there is no good way to establish "similarity" between different prion disease. For bacteria/viruses you can sequence DNA (or RNA for some viruses) and measure similarity, but prions by definition lack RNA and DNA. The best that can be done is innoculating mice and studying the characteristics of the resulting disease. More recently patterns of digestion by enzymes which breakdown proteins has been used, but neither of these methods is well established and what exactly similarity means is unclear.

This brings the authors to their final argument:

It is well known that sheep products were incorporated into cattle feed. However, there is no satisfactory explanation for why BSE did not appear earlier, since: scrapie has been endemic in Britain for at least 200 years; meat and bone meal containing sheep material had been fed to cattle for as long as 70 years; and scrapie infectivity must have entered cattle feed in substantial quantities.

Sounds convincing until you think about it a little. Basically they are arguing because cattle have been exposed to sheep remains and scrapie in much larger quantities it can't be the cause! Talk about counterintuitive. Isn't it more likely that ovine to bovine transmission is unlikely in any single episode of ingestion, but happened once (or a few times) given all the ingestions than occurred? Sure seems so to me.

To summarize, I appreciate this kind of hypothesis generation and at this point no one can say definitively where BSE came from, but the overall arguments presented at best establish that humans could have been the source. Sheep, however, remain a much more likely cause.

Really, really bad science humor

Specifically jokes Einstein might tell if he was a stand up comic, from Andrew Tobias:

“Have you heard the one about God? So He’s at Caesar’s Palace, standing next to the crap table and the croupier says, “But with all due respect, God, Albert Einstein says you don’t play dice with the universe.‘Yeah,’ says God, ‘Wasn’t Al also wrong about the cosmological constant?’”

And my favorite:

“So anyway, a neutron walks into a bar. And the bartender says, ‘For you, no charge.’”

If you liked these read them all.

Yet more bird flu

I'm watching the ABC special on avian flu.

The program is very tendentious, but I am actually encouraged by what I'm seeing. The government is starting to stock up on olsetamivir, the one medicne that would help and it seems like people, even in the government are starting to realize what a threat this could be.

I've said before, that I don't think things will be as bad as some fear. We have much more sophisticated medical and public health systems than we did 85 years ago during the last pandemic.

Remember, the pandemic won't start until H5N1 is able to efficiently spread between humans (as opposed to currently when it can only spread from birds to humans, and inefficiently at that) and no one knows when (and perhaps if) that will occur. The fact that people are starting to act is a good sign.

More bird flu

Here is a blog devoted to H5N1.

Here is an article about Margaret Chan who is leading the WHO charge:

She realizes the exercise may be painful for some governments but is dedicated to the cause. "I have a lot of passion for global public health -- that is where I am coming from," Chan said.

"One has to be very vigilant, honest and brave. Sometimes you need to make unpopular, difficult recommendations to political leaders which may have a short-term impact on the economy and on certain sectors," she added.

Somehow I'm not reassured that the public health is not afraid to make unpopular, difficult recommendations. I'd feel better if the political leaders were making unpopular, difficult decsions, which I don't think they are.

Finally this article details some of the challenges of vaccination against H5N1:

A vaccine is the best hope to prevent millions of deaths.

But current global manufacturing capacity, at around 300 million regular flu doses a year, is simply insufficient to meet global needs during a pandemic.

Our health care system

Call me crazy, but this doesn't seem like something that would happen in a rational health care system:

It began last year with Lori Mill's toenail — or rather, with Mill's $1,133 medical bill from Virginia Mason Medical Center for a 30-second office procedure on her toenail.

Mill complained about a $418 charge for "miscellaneous hospital charges." When Virginia Mason responded that it routinely adds such a "facilities charge" when patients go to its downtown clinic instead of its other clinics, she got a lawyer and sued.

I'm not sure what the answer is, but this isn't it. (Hat tip to The View through the Windshield)

Mislabeled article

An article in the NY Times about medical students clinical experiences is titled:

Your Intern Today Is Both Sleepy and Bored. Feel Better?

How hard is this? Medical students are students. Interns are MDs (i.e. former medical students) in their first year of training. Several people I knew as an undergrad went on to be NYTimes reporters and presumably most of their reporters/editors go to schools that crank out lots of future doctors so couldn't they get the medical lingo down?

Katrina and avian flu

I'm struck by similarities between Katrina and a probable future avian influenza pandemic.

In both cases, a clear, well thought out and well implemented plan is/would have been vital. In Katrina, wherever the blame lies, lack of communication and confusion about decision making power among different levels of government were major factors. Despite the fact that the flooding of New Orleans seems predictable, no one did anything to evacuate those who didn't have their own transportation or to make sure the shelters at the Superdome and convention center were secured and supplied.

You think Katrina was bad, imagine a bird flu pandemic which will spread from country to country. The UN and WHO will be in the position of the federal government!

You think the Katrina situation was confused, imagine what an avian flu pandemic would be like: poor countries trying to cover-up cases while the outbreak becomes increasingly widespread while the UN/WHO stands by impotently.

A top H5N1 researcher Yi Guan agrees with me

He urged the World Health Organization and Food and Agriculture Organization to take a more direct role to avert the looming pandemic, which he believes will happen if aggressive action is not taken

"The WHO and FAO must set up a joint expert team. They must get into the (affected) countries and compel them to make changes, take drastic action. The U.N. must say that if you don't follow suit, you will be punished," said the scientist.

A plan that included close surveillance, rapid quarantine, stockpiles of antiviral drugs (and hopefully a vaccine) might be enough to halt spread of the virus andprevent a pandemic, but right now it seems unlikely that will happen. The idea of UN punishment as a stick is, unfortunately, almost laughable.

I'd be a lot happier if Congress and the media would focus on what to do about the next predictable crises, not on what went wrong in Katrina. 1,000 dead seems to be the upper limit on the number who died in Katrina. The number who'd die in an epidemic could be 4 or 5 orders of magnitude large.

The article contains more bad news. Guan recently showed that the current avian flu strain probably originated in southern China. The Chinese goverment, sadly predictable, has now shut down much of Guan's research:

. . . his biggest challenge comes in the form of China's Ministry of Agriculture, which forced his Shantou laboratory to stop its surveillance work on H5N1 around the time the Nature article was published.

The ministry criticized the findings saying Guan's laboratory -- which Beijing has designated a key state facility in the study of influenza viruses -- was not up to standard and had not obtained government approval for its research

Homeopathy

Shockingly, a systematic review in the August 27 Lancet concludes that homeopathy is probably worthless:

Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.

(no free full text but citation is Shang et al. Lancet 2005 366:726)

As an accompanying editorial notes, what is surprising is not the finding, but that we are still having this debate. Of course with a President (and, worse, a Senate majority leader who is both a presidential hopeful and a transplant surgeon) advocating teaching of intelligent design, how much can we expect.

As Vandenbroucke notes in his accompanying editorial (page 691 of same issue):

In 1846, John Forbes compared homoeopathy and allopathy, mostly informally, but also with a few shrewd experiments. He found the results of homoeopathy for certain ailments as good as those of his own treatments. Because he considered the theory of increased potency by greater dilutions “an outrage to human reason”, and therefore any effect of homoeopathy impossible, he proposed that his findings should lead to introspection about the effectiveness of the allopathic medicine of his time.

Unfortunately more than 15o year laters, homeopathy is a billion dollar business. I've always said the great weakness of economics was its assumption of rationality, and the dollars spent on "alternative" health care are about the best refutation of that assumption I can muster.

Legislating against genetic discrimination

An interesting commentary on genetic discrimination in the 9/1 NEJM.

Published accounts of reported genetic discrimination in both life insurance and employment surfaced in the 1990s, along with an increasing number of policy recommendations expressing concern about the potential for genetic discrimination and arguing for legislation against it. However, the early reports often involved allegations of discrimination on the basis of disease, rather than a genetic predisposition to disease. Subsequent studies have shown that although there is widespread concern about genetic discrimination, there are few examples of it — and no evidence that it is common.

Greely goes on to argue for banning such discrmination, even if it isn't common. He avoids refuting any arguments against such a ban. I think the biggest objection would be that it could make insurance more expensive for the healthy. For example, those who knew they were at high risk of early death would by disproportionate amounts of life insurance, increasing claims and eventually cost. Of course as the author notes, for most common diseases (diabetes, atherosclerosis) the genetics are complex and have modest effects on risk

Grand Rounds LI

is here. Great pictures and I like the new, journal based numbering system.

The wages of smoking

Occasionally I get patients or parents who refuse to believe that smoking is really harmful to them or their kids; they apparently believe it is all some sort of conspiracy.

I'm not sure this will convince them either, but I got a solicitation for insurance by virtue of being a University of Chicago Alumni. For a 39 year old man like myself seeking 1 million dollars of life insurance, premiums for non-smokers range from $43 to $61 per month for non-smokers and start at $220 monthly for smokers. Or 3-5+ times more. Here is the online quote engine

What I think it even more interesting is that based on $3 per pack, an upper-middle class pack-a-day smoker would pay more for increased life insurance premiums than for the cigarettes.

An experiment of one

One thing I find frustrating about health and fitness as opposed to medicine is the lack of data. If you want to know if, say, angiotensisn converting enzyme (ACE) inhibitors improve mortality after myocardial infarction (MI) there are multiple randomized trials with thousands of participants, meta-reviews of the trials, etc. But if you want to know how to taper before an ultramarathon, the best data available is anecdotes from other runners and occasional expert opinion; if you're lucky you might find a small unblinded study of 20 total athletes.

This weeks Freakonomics column in the NYT magazine deals with Seth Roberts, a psychology professor who has made a habit of conducting experiments on himself.
Most intriguing to me is the diet that has apparently allowed him to lose 40 lbs while eating whatever he wants:

After a great deal of experimenting, he discovered two agents capable of tricking the set-point system. A few tablespoons of unflavored oil (he used canola or extra light olive oil), swallowed a few times a day between mealtimes, gave his body some calories but didn't trip the signal to stock up on more. Several ounces of sugar water (he used granulated fructose, which has a lower glycemic index than table sugar) produced the same effect.

The theory behind this is convoluted, to put it mildly. He first notes that the body has a "set point" of weight it tries to maintain. The idea here is that there are mechanisms that act over long periods of time (weeks to years) that keep your weight more or less steady. This is clear in animals studies and seems to be the undoing of most human diets (losing weight is relatively easy, keeping it off hard).

He second believes that the set point is affected by the relative abundance or scarcity of foods. Evolutionarily, we are probably designed to eat a lot when food is abundant (successful hunt or harvest time) but also go through periods of relative deprivation (winter, tough years). Roberts thinks (and there may be some evidence for this) that you are actually less hungry during times of scarcity.

It is not entirely clear to me why taking in unflavored calories between meals helps, but I guess the idea is that you tend to eat bland food during times of scarcity.

I've wondered if my current diet (fasting 1 day per week) also helps move my "set point" downwards by tricking my body to take in think food is scarce. I've also noted that you are far less hungry than you would think during a fast. When I run in the morning of fast days, my hunger peaks at breakfast and declines during the day. I do have a sort of awareness that I'd like to eat that is distinct from what I'd generally call hunger

TMQ is back

I am not a big NFL fan, but I still enjoy reading Gregg Easterbrook's Tuesday Morning Quarterback each week during the season, which are about 1/2 NFL analysis and 1/2 random, but intelligent musings:

On the Plus Side, Every NHL Goalie Had A Perfect Year

In April, the Associated Press headlined a story about a meeting of National Hockey League officials, GENERAL MANAGERS DISCUSS WAYS TO INCREASE NHL SCORING. Here's a suggestion to increase scoring -- hold games!

It is blog-like if not actually a blog. I am catching up on the preseason editions I've missed, which are available here. Warning: if you get addicted Tuesday afternoon productivity will plummet.

Scott Jurek

has won the Western States 100 mile run an incredible 7 years in a row. This year he topped it off by winning and setting the new course record at the Badwater to Whitney ultra (135 miles from lowest point in the US, Badwater at 280 some feet below see level to Whitney portals crossing Death Valley in July; like many runners, Jurek "unofficially" summited Whitney after winning the race).

He is interviewed at Runners World online. I have never met him, but always had the impression he was a private person who struggled a bit with all the attention and publicity that came his way. He comes across very well in the interview as a modest, but very focused athlete.

I was interested to see he'd like to run Comrades but knows he isn't fast enough to be competitve there:

I'd certainly like to experience Comrades some day, but to win it, you have to be basically a 2:14 marathoner. So I don't see it as a distance where I can be competitive

Medical response to the London bombings

is the subject of several articles in the August 11 NEJM (all free full text!). These are all excellent, well written articles, with expected British understatement and modesty and together give good insight into what the medical response to an attack like this entails

Ryan and Montgomery give us an overview of the emergency response and also detail just what happens to the victims of a bomb attack:

When an explosive device detonates, a small volume of explosive is rapidly transformed into a large volume of gas. A high-pressure blast wave expands outward at the speed of sound and, in interacting with the body, causes primary injuries (mainly at air interfaces such as the lung, ear, and bowel). The resultant blast wind propels solid matter into the patient (secondary injury) or the patient into solid matter (causing tertiary injury). Quaternary injury is caused by heat, flames, or the inhalation of smoke and hot gases. Confined spaces exacerbate such effects: surface reflections amplify and prolong the blast wave, the blast wind is channeled, and heat and gases are contained. The severity of injuries and the resultant mortality are thus greater. The total number of persons endangered is increased by detonation within a rush-hour commuter environment.

Bolden, who was at the British Medical Association building immediately adjacent to where one of the bombs detonated, helped organize his colleagues, some of whom hadn't practiced clinical medicine in years (and even fewer had recent experience with trauma) into an immediate response team"

I have trained for such a situation for 20 years — but on the assumption that I would be part of a rescue team, properly dressed, properly equipped, and moving with semimilitary precision. Instead, I am in shirtsleeves and a pinstripe suit, with no pen and no paper, and I am technically an uninjured victim. All I have is my ID card, surgical gloves, and my colleagues' expectation that I will lead them though this crisis.

Of course, they were able to effectively triage and stabilize patients until help arrives and the wounded can be evacuated to hospitals.

Redhead, Ward, and Batrick describe their experiences at one of the hospitals that received many of the casualties, despite not being a level I trauma center

Patients were triaged on arrival by senior teams and assigned to one of three areas of the emergency department, depending on priority. When the condition of two patients deteriorated during their initial assessment, their priority was adjusted accordingly. After initial assessment and management, critically injured patients requiring surgery were transferred to the operating rooms, where teams of orthopedic, vascular, and general surgeons would work on into the night.

The repeated reassessment of all casualties was important. A senior surgical consultant reviewed all casualties, ensuring that a thorough secondary survey was performed. Orthopedic surgical expertise was fundamental in assessing patients with complex compound injuries and prioritizing cases for surgery. Ear, nose, and throat surgeons evaluated and arranged outpatient follow-up for all patients with audiologic consequences of the blast. Radiologists interpreted trauma x-rays and performed ultrasonography in the emergency department, as well as performing computed tomography. Chaplains, patient-liaison teams, and the mental health staff provided support to distressed patients and their relatives. Medical students acted as "runners" between key areas of the hospital and helped with supplies and blood samples.

Things got even worse when they found out an unexploded device might be located next door, requiring evacuation of parts of the hospital. I'm concerned terrorists may eventually decide to start secondarily targeting EDs and hospitals that care for the wounded in bombings.

Finally Wessely, a psychiatrist, reviews some of the challenges faced by survivors. He notes that immediate psychological intervention is at best useless and may actually be harmful:

There have now been more than a dozen controlled trials in which people who have been involved in accidents and other traumatic events have been randomly assigned to receive or not to receive such counseling. The results have shown conclusively that such immediate psychological debriefing does not work. Those who received it were no better off emotionally than those who did not. Worse, the better studies with the longer follow-up periods showed that receiving such counseling actually increased the likelihood of later psychological problems. In fact, the people who seemed to be harmed by this intervention were those who had been especially upset at the time — precisely those who one might think ought to be treated.¹ So whereas immediate post-trauma counseling may reassure the rest of us that something is being done, it does not actually help those who receive it.

Why it doesn't work is less clear, but probably trauma survivors need help from those they are already close to, not a therapist they've never met before. They also probably need to work through their shock and grief on their own.

He describes the media driven culture of everyone as victim

There is a danger that our stoicism, professionalism, and pride may become diluted over time. Almost immediately, reporters began carelessly describing London as "a city in trauma." Only 24 hours after the bombings, BBC Breakfast News was asking whether people who had only watched the scenes unfold on television would require counseling, and others demanded that counseling services be offered to all Londoners to enable them to "cope with the trauma." Such voices, however, were muted, and the messages coming from most mental health professionals were consistent, balanced, and less dramatic.

and concludes with an admonition we should all heed:

We must be careful to avoid shifting from the language of courage, resilience, and well-earned pride into the language of trauma and victimhood. The bombs made more than enough victims; it is important that we do not inadvertently create more.

Finally, I think the ultimate goal of these terrorists is to breakdown our society by pulling us away from each other. Bolden notes it doesn't seem to be working:

Many soon come to believe that the bombs were the work of religious extremists. I had counted at least eight different nationalities among the victims. My team consisted of Jews, Muslims, Christians, humanists, and agnostics, who all served humanity irrespective of race, color, or creed and regardless of personal danger.

All about marketing

From a BMJ review of increasing patient safety:

In another effort to bring the issues to the forefront, the Institute of Medicine established its quality of care in America committee. In late 1999 the committee’s first report, To Err is Human, was released. Unlike previous reports on quality, which had been directed at elected representatives, healthcare leaders, and professionals, the key audience for this report was the lay public. In effect, it was direct marketing to patients about medical errors. The impact was tangible, with near saturation coverage in the media for almost three days.

Reference: Elwyn and Corrigan BMJ.2005; 331: 302-304.

Diet update

I've posted a few times previously about a new diet I'm trying. It boils down to fasting (that is abstaining from any caloric intake) for one day per week. This works out to about 33 hours for me (finish dinner about 8PM and breakfast at 5AM 2 days later). The idea is that anyone can be good for a limited time and this lifts the requirement of constantly watching what you eat, which leads to frustration, feeling overwhelmed and poor compliance. An initial worry was that I'd overeat during the 6 non-fast days, negating any benefit. While I do notice I eat more the day after a fast, this overall hasn't been a big problem. The fasting reveals how much of eating is triggered by social cues and helps one not eat when one isn't hungry.

The diet has really worked for me as the graph shows. Blue represent daily morning weights (before breakfast) and pink ones highlight post fast days (when I tend to be a few lbs. down, probably from water weight loss) so you can see I'm down about 20 pounds overall. The 4 month period coincides with a lot of running, so that probably played a role as well. Needless to say, I can really see the difference when I look in the mirror, and I also notice how much easier running is, although again that is partially training.

My wife now says I'm getting too think and I had to promise to start weights again after Arkansas.

Grand Rounds L

where L = 50 is here
with the usual collection of interesting posts, including a timely one about making up a home survival kit.

The 4 day work week

An increasing number of physicians seem to be working only 4 days a week, at least the ones I know. One of our former fellows gets a day off a week in his new job and while on vacation in Chicago I had lunch with a residency colleague who has every Wednesday off.

Every three day weekend I get, I think about how nice life would be if that was the rule, not the exception. I think both my friends do 8 half-day clinics a week which is a lot (I do 7) which means they have to fit in a lot of stuff either during or outside clinics, while I have some time for that (I cover inpatient consults 2 half-days but that doesn't fill up the time). Still, I fantasize about, say dropping my kids at school in the morning, going for a longish run, then picking them up and doing something.

Maybe someday

Graft versus Leukemia

First, how do bone marrow transplants (BMTs) work? Most chemotherapeutic agents (i.e. drugs used to treat cancer) act by targeting rapidly dividing cells. They have various mechanisms like interfering with DNA replication, cross-linking DNA strands and disrupting mitosis, but all interfere with cells duplicating themselves. Radiation works in a similar way. Since cancer cells are, by definition, growing out of control they help kill off cancers. But the side effects of chemo and radiation are damage to other rapidly dividing cells in the body, including the hair (cosmetic problem only), the mucosa of the GI tract (nausea, vomiting, mucositis), and cells of the bone marrow. The last is the real limiting toxicity because destroying white blood cells leaves the recipient open to infection (which is why fever and neutropenia has led to so many people getting cancer).

The initial idea behind bone marrow transplants was that by reinfusing someone else’s bone marrow after higher doses of chemo and radiation. By increasing the intensity of treatment you increased the chance of cure. Of course, there are some problems with bone marrow transplants. The recipients immune system can reject the graft, basically fighting it off, like we all do to the few maternal cells that made their way into our circulation in utero or the white cells that come along in a transufion of red blood cells. That this ever happens, even after huge doses of chemo and total body irradiation is incredible to me and it can even happened weeks to months after transplant. The other problem, graft versus host disease (GVHD) is basically the converse. The transplanted white cells (from the donor) recognize recipient cells as foreign and attack them.

At first GVHD was a major problem and a variety of approaches were developed to prevent and treat it (purging of mature T cells from the donor marrow, immunosuppression, etc.). But then something interesting emerged. Patients with GVHD had a higher chance of cure of their cancer (early bone marrow transplants were mostly for leukemia). A number of lines of evidence now show that in addition to replacing the recipients immune system which has been destroyed the infused cells also kill of the cancer. So the best result after a BMT is probably to have a little bit of GVHD: it isn’t too troublesome (patients can die from GVHD) but it helps cure the cancer)

Oncologists are now trying to take advantage of this graft versus tumor effect and expanding it from blood cancers to solid tumors (that primarily arise from internal organs). In general, bone marrow transplants haven’t been very effective for solid tumors, perhaps because higher doses of chemo and radiation aren’t as effective to them. An initial problem with BMTs for solid tumors is that, for reasons that aren’t completely clear, large tumors are strongly immunosuppressive. But there is starting to be evidence that by first reducing the size of the tumor (and thereby its immunosuppressive effect) the graft versus tumor effect may cure (or at least stop/slow the growth) some solid tumors.

In the July 23rd Lancet (yes, I’m behind on my reading again, summer and vacations make it tough to keep up; in my defense I read this a while ago and am just getting around to blogging about it) is an interesting commentary about this and a trial showing some efficacy in patients with metastatic breast cancer.

Remarkably, three patients had delayed graft-versus-tumour effects occurring in association with acute graft-versus-host disease (GVHD) resulting in complete tumour regression, and remain in remission 3·6, 4·2, and 5·9 years after transplantation

Unfortunately there was substantial morbidity among participants.

NOTE: The Lancet makes it impossible to link directly even to abstracts, which require registration to view.

UPDATE: Sorry not to give full references, commentary is Childs Lancet 05 366:273, study itself is Carella Lancet 05 366:318.

Thoughts on Katrina

Less than a week after the hurricane hit, nearly everyone has been evacuated. I can't see that as anything less than incredible. I think it was very hard to watch all the people stuck in NO suffering and the combination of shame and powerlessness made us want to blame someone, but at this point I think the overall relief effort has been incredible. Not perfect, but incredible.
This was a natural disaster of amazing proportions; we forget just how powerful nature is.

That said, there is enough blame to go around:

1. New Orleans for making no attempt to get those without private transportation out. Why not use all these buses? And why not have supplies stored at the Superdome if you are going to tell people to gather there

2. The thugs who lotted/raped/shot at evacuation helicopters etc. I have no problem with those who took food/water, etc. It wasn't like it was ever going to be sold anyway.

One lesson I learned was the importance of keeping order. Initially, I agreed that it was not a good use of police resources to stop looters. But it seems pretty clear that once the social order breads down you get people firing at helicopters trying to evacuate hospitals.

Parenthetically, what could one do with a plasma TV in NO right now? There is no electricity, no cable, and for most people no where to store it. So most of the looting seemed pointless. Similarly, what possible personal benefit could come from shooting at a helicopter? Could one really imagine the helicoptr would instead evacuate the shooter?

3. Whoever didn't get the Superdome and convention center under security control earlier.

4. Whoever had no plan in advance to get people out of the city once the levee was broken. It seems predictable you'd need to evacuate, but there was apparently no plan to obtain buses to get people out

5. The NO police officers who joined in looting and or walked off the job.

6. FEMA for not getting supplies in 24-36 hours earlier. Like the military they seem to never want to hurry up. A convery of supplies to deliver food and water a day earlier would have helped things immensely.