Category Archives: Science

Our Little Medical Marvel

In 2021, we got a pair of kittens from a rescue organization. One of them, Grace, was sheer easy mode. Cute, low maintenance, gentle with her claws and teeth, not a big lap cat, but that’s ok. The other, Horatio, was very sweet and cuddly, a fluffy little orange boy who was underweight for age and ended up being sick all the time – we were at the vet almost weekly for a while there. And the vet finally said “I think we should check bile acids.”

Grace and Horatio shortly after their arrival in our home.

Bile acids aid in digestion, and they are, in essence, recycled by the liver as it processes what comes out of the gastrointestinal tract. A portosystemic shunt is an extra blood vessel (in the simple case) that routes blood around the liver, so the kinds of toxins that the liver is designed to filter keep circulating. Testing for levels of bile acids before and after a meal is a clever way of seeing whether the blood is flowing correctly – if it is, acids secreted in response to the meal will be promptly recycled. If not, they just keep floating around, hinting that other stuff is building up in the blood. In particular, ammonia compounds, and they can cause terrible symptoms – lethargy, vomiting, disorientation. Liver shunt is a developmental defect, and while the effects can be managed with diet and medication, the prognosis is poor. In the right cases (simple, one big vessel, rather than complex, with a lot of little ones) surgery offers a chance at a normal life. The detouring vein is fitted with a ring containing absorbent material that, over time, slowly narrows the errant vessel, and the blood follows the path of least resistance right into the liver, as intended.

We were fortunate that Horatio was diagnosed before receiving surgery – some cats are discovered to have this defect only after they fail to recover from a routine desexing procedure. And Horatio was fortunate that we were easily able to manage his special diet and medication to keep him healthy and growing, and willing to pursue surgical correction. He was also lucky to be a perfect candidate – and we were lucky that he was a perfect little gentleman in the car when we drove him two hours to the hospital at the University of Pennsylvania’s Veterinary School, where our regular veterinarian referred him so he could be treated by veterinarians who had actually done this surgery before.

Horatio was a perfect passenger on the way to the veterinary hospital.

We had a few hiccups getting him onto the surgery schedule, but when the day came, everything went as well as could be hoped. The only real surprise seemed to be that he needed a relatively large ring – a size usually needed only for dogs. We found this pretty charming, because we joke that he’s our little golden retriever: friendly, unflappable, and in love with his tennis ball. The surgery protocol called for a 3-day stay, but after the first day or so, that’s often just to ensure that the animal is getting an appetite back, and Horatio bounced back more or less right away. They invited us to pick him up early, saying, “We’re just sitting around watching him eat!” We got him home, and our other cats accepted him back almost right away (our third cat didn’t love his cone at first but got over it). His incision healed promptly, and his first follow-up bile acids test was normal. All of that is wonderful, but that’s not the marvel.

It’s not unusual (although also not universal) for cats with liver shunt to have bright copper-colored irises. That is also a normal eye color for cats, but in liver-shunt cats whose genetic trait for eye color is lighter, another buildup is probably to blame. Horatio had very arresting, deep, copper-colored eyes.

Horatio at about 7 months old, about a month after diagnosis of liver shunt, clearly showing coppery eyes.

It took a few months, but his eyes did start to lighten, and by about 7 months after surgery (during which he was weaned off his special diet and medications with no ill effects), they were yellow.

Horatio grew to be a handsome adult of about 11 lb, with definitely yellow eyes.

Seeing him now, playing chase with the other cats, hanging out and watching the birds, being a cute lap cat, it’s hard to believe he was ever so frail and sick. And while his coppery eyes were gorgeous, we are more than happy to see this clear evidence, every day, that the surgery worked.

Would you like to use photos of Horatio’s eye-color change? Send me an email and let’s talk!

False Positives and Unintended Consequences

After an appendectomy, the removed appendix is examined to determine whether appendicitis (or some other problem) was present. In a noticeable proportion of people, it is not. This is not a problem, for a good reason: the consequences of untreated appendicitis can be swift and catastrophic. The consequences of appendectomy are, in general, mild by comparison, at least in societies with good sanitation. (There is always risk from surgery.)

This is being revised after trials with intravenous antibiotics have shown very high rates of survival, but appendectomy was introduced before the antibiotic era, many organisms are involved, and we’re losing antibiotic efficacy – plus appendicitis can still progress after IV therapy – so surgery still needs to be in the toolkit. Still, knowing that there are options well worth trying, and with a good track record, is good news for situations where surgery may not be available, practical, or advisable.

[T]ypes of patients in whom appendectomy might be avoided:

  • Patients with an appendiceal abscess, who would be better treated with percutaneous drainage;
  • Patients who have had a recent myocardial infarct;
  • Patients with severe lung disease;
  • Women in the first trimester of pregnancy; and
  • Persons in a remote environment such as Antarctica or on a mission to Mars.

From Evaluating Acute Appendicitis: Does Everyone Need an Operation? (subscription required)

(Mars – or the Antarctic – is hardly the only remote environment of interest; one of the studies was in Navy personnel on a submarine.)

Appendectomy is a classic teaching case on the value of ending up with a few false positives. It’s better to perform a low-complication procedure a few extra times than to have people walking out of the ER and dying when they get home. But as technology changes – in this case, antibiotic treatment options and CT-scan evaluation – it’s always good to re-evaluate even the obvious “tried and true” approaches, partly to see if there’s a better way across the board and also to address the situations where the outcome of surgery was likely to be bad. On the way, we seem to have discovered some properties of the appendix that can help us understand the environment for other GI disease – a new teaching case for this much-maligned “vestigial” organ!

We are probably right to remain suspicious, though. The appendix may well have more tricks tucked into its submucosa.

Thing-a-day 3: “Should I eat ‘Paleo’?”

Sure, but don’t sweat the small stuff.

The Paleo diet is, in its strict form, a narrow selection of foods, specifically sourced, meant to approximate our ancestral diets. The Paleo claim is that we have not evolved quickly enough to adapt to our current food environment, so we must eat more “primally,” as we are adapted to do. The claim is oversold – we have, in fact, adapted quite a bit with our changing diets; our ancestors in the period at issue ate a wide variety of foods, whatever was available where they were, basically (both a reflection of and a continued stimulus for our adaptability); and selective breeding of food animals and plants means that the foods available to us are even less like their Paleolithic ancestors than we are like ours.

From How to Really Eat Like a Hunter-Gatherer

But that doesn’t mean you should avoid the Paleo food pattern altogether. Remember Michael Pollan’s advice, “Eat food, not too much, mostly plants”? It’s kinda like that, only more meat. The general blueprint of Paleo is a fine one: lots of high-density protein, lots of fiber-rich whole foods, and knock back on the refined/processed foods. Really nothing to argue with there. (Strict Paleo goes a lot further – no grains at all, no legumes, limited fruit, no dairy, and no sugar sweeteners, although a little honey is OK. It also encompasses recommendations for how the food is grown or raised.) Probably the worst thing about it is that its meat-heaviness and prominence of some unusual ingredients makes it kind of expensive.

If you already have lactose intolerance or feel crummy when you eat wheat, Paleo can help you organize your options, but if you don’t, those restrictions don’t have much to offer. Similarly, if you’re the kind of person who finds it hard to set limits when there’s a cake in front of you, a Paleo focus, similar to Atkins or any other high-protein/limited-carb approach, can help you build a food pattern that keeps you out of harm’s way. For most people, the most restrictive details of Paleo can be treated as mere suggestions (from a health perspective), and there are now dozens of websites discussing food options and offering inventive recipes, so Paleo can give you good ideas for how to keep home-cooked food interesting, and explore the many options outside the (processed) food industry’s heavily marketed product range.

You’ll have to say goodbye to all this, though, to follow the Paleo food pattern strictly. —Photo: Caitlin Burke

What about fat?

The Paleo food pattern is pretty fatty, and fellow-traveling approaches to idealized diets claim that our primal food pattern had as much as 75% of calories from fat. (It’s doubtful humans routinely had access to that volume of fat, though.) The short version is that if you don’t already have major health issues, like heart disease or a family history of it, and especially if you exercise regularly (every other day to daily), the kind of fat present in the Paleo diet probably doesn’t matter. After all, deep-fried food is not Paleo!

In with eggs – a free-feed food for Paleo eaters! My stepfather raised the turkeys and chickens that produced these. —Photo: Caitlin Burke

The longer answer is that the same rule of thumb probably applies to most of us, too. Fat got a bad rap in the 1950s with high-profile results from studies of heart disease and the fact that it has a lot of calories, gram for gram, making it a juicy target for calorie restriction. The problem is context. In healthy people with no major risks for heart disease, especially if they’re active, fat intake is probably not that important as a risk factor by itself. And that doesn’t even get into the different adaptations of people on different foods patterns around the world (including variations in the bacteria in our guts that help us digest food). Anything can be a problem if you overdo it, but let’s take “healthy” and “active” to mean people getting regular exercise and eating a balance (not surplus) of calories overall.

One problem with “low fat” as an approach, especially as used by the food industry, is that it often goes hand in hand with “more sugar.” This is a one-two punch, because the lower-calorie benefit of the reduced fat can be undermined by the health risk of disproportionate sugar intake, AND fat acts as a “satiety signal,” helping you to feel full, so it may be harder to exercise portion control with lower levels of it. Consider the packaging for Red Vines: Always fat free! Right, because they are basically 100% sugar. Look, I love Red Vines way more than the average bear, but we all know how hard it is to stop eating ’em. (Serious question: Why on earth are candy labels allowed to tout “fat-free food” on the front of the packaging as if it’s a health claim? George Orwell would gasp.)

Many hyped diet plans treat sugar and other carbs like poison, but a bigger problem for our waistlines has been the way the food-processing industry has stripped the fiber out of our foods. Paleo carbs come mainly from whole vegetables, a good source of dietary fiber. —Photo: Caitlin Burke


Exercise almost never gets mentioned enough with any hyped food pattern – some even claim you “don’t need exercise” with their plan (and I know I’ve heard that claim plenty from people on low-carb, high-protein patterns). Loren Cordain, a major, active proponent of Paleo, pushes the point that the ancestors in question probably exercised about three times as much as current US guidelines for recommended levels of exercise.

An hour a day of exercise is not as scary as it might sound – it’s not like our ancestors were killing it in powerlifting-specialized gyms or constantly training for the Paleolympics. A lot of their activity was low intensity – like walking. And if you now exercise much less than that, don’t rush it; ramp up slowly, because it’s safer, and because if you are sedentary now, every little bit helps, so you will still start to benefit right away. No matter what food pattern you choose, ultimately you should aim for average of an hour or so of activity a day (again: low-intensity activity counts), and can benefit from doing something every day. If you exercise daily because you really love to work out, make sure some days are just low-key stuff, to prevent overuse injury.

In Short

Pros: The small-p “paleo” approach is a good framework for shifting a food pattern from less healthy to more healthy. With its emphasis on nutrient-dense, satisfying foods – and its rejection of processed foods – people often find that eating this way makes it easier for them to eat more nutritiously while controlling their calorie intake. The general idea of paleo – plenty of protein, lots of vegetables, minimal processed food – is appropriate for everyone who doesn’t have a protein-metabolism disorder, you know, pretty much everyone. Also, people feel good on Paleo, an effect reported by people on other high-protein, carb-limited food patterns, too. Maybe it’s the energy bump from the protein, maybe it’s getting enough protein in the first place. And sometimes, as a social-site contact of mine remarked, it’s just that “people feel better eating paleo because before that, they had never eaten a meal they prepared themselves.” Whatever food pattern you choose, be sure to exercise, too.

From an older Beef Checkoff campaign.

Cons: Paleo makes a lot of claims for support that are irrelevant (for example, we can’t eat as our distant ancestors did because the foods are simply no longer available) or wrong (we are evolving – coevolving with our environments – because adaptability is how we wildly successful species do it). Fortunately, we can dispense with those claims, because we don’t need to look that far to find good support for the basic idea of eating nutrient-dense food and avoiding processed food. (If you need a good counterexample, though, it’s lactase persistence. Lactose tolerance in adults seems to have developed in no fewer than 4 different ways over recent millennia – a pretty good track record for adaptability.)

Caution: Strict paleo is expensive, the foods can be hard to source, and it can be so demanding of time and effort that some people may find it sucks joy out of eating. Fortunately, in healthy people, this approach is more of an “if it floats your boat” thing than a delicate balance that must be preserved or trouble will ensue. So if it’s making you miserable, relax your approach while keeping the principles of plenty of protein, plenty of vegetables, and limited refined/processed foods.

In 1975 Walter L. Voegtlin, a gastroenterologist, published a book called The Stone-Age Diet. It offered a basic structure for the Paleo movement. (It’s now out of print, with no plans for a reprinting, but can occasionally be found in libraries.)

What to Eat on the Paleo Diet, from the site for Loren Cordain’s books. Cordain published The Paleo Diet in 2002 (updated in 2010), and has published often and widely about this approach since 1997. He also points out that we should be exercising as our ancestors did – probably about triple the level of activity recommended by current US guidelines – a great idea that somehow gets a lot less attention than the diet itself.

Some Like It Paleo, a food blog by a Crossfit athlete in San Francisco. She has a list of resources, pointing to other sites about Paleo in general and featuring recipes.

The Caveman Controversy: Marlene Zuk has made some interesting discoveries about rapid evolution in animals – and has really angered some Paleo proponents with a provocatively titled book.

Debunking the Paleo Diet, by Christina Warinner – a TEDx talk, and those can be variable in quality, but this is a wonderful one – plus, what a great truncation in the link’s name!

Ancel Keys was a major figure in dietary fat in health, who identified animal fat as a risk factor in the 1950s and promoted the Mediterranean diet. His work was a foundation for the US government’s recommendation of low-fat diets.

Culprit in Heart Disease Goes Beyond Meat’s Fat reports on an interesting study showing how complex eating is – it’s not just the saturated fat in red meat that Keys pointed to, it’s what gut bacteria we have to interact with the foods themselves. This is a small detail in a growing literature about the variety of collections of gut microbes across and within populations around the world.

Go Kaleo, by Amber Rogers, a website about breaking the dieting cycle. Lots of good info about food patterns, exercise, and putting it all together in a way that won’t make you crazy.

The 4 Most Important Things about Flexible Dieting, by Armi Legge. A list of considerations for any food pattern you are thinking about, it emphasizes long-term thinking and having a food pattern you like.

Update March 2014: Don’t Fear The Fat: Experts Question Saturated Fat Guidelines – discusses recent thoughts about the cholesterol–dietary fat–carbohydrate story.

LOL Hairy Mammals Like Petting

Nature has published an article about the neurons that appear to be associated with enjoying being petted or stroked. The authors did their research with mice, but they enlisted cats — which are, after all, noted experts in the areas of mice and, of course, of being petted — to explain their work to the general public.

Genetic identification of C fibres that detect massage-like stroking of hairy skin in vivo

Errol Morris on Dunning-Kruger and Other Blind Spots

I have just finished reading A Wilderness of Error, Errol Morris’s recent book, about the trials of Jeffrey MacDonald. For the first half of the book, I remember feeling that painful tension of being persuaded by an argument when you already know it has failed. As I got closer to the end, I actually found myself saying out loud, “This guy is never getting out.” Never ever. I then came to a passage in which a member of the Innocence Project says it seemed like MacDonald was convicted and failed his appeals because he is a jerk.

Decades in prison for a crime you didn’t commit could easily make a saint into a pretty big jerk, but it seems he rubbed people the wrong way from the beginning. He also didn’t seem to have any self-awareness about it – he was able to articulate peevish objections when people complained about his manner or affect but not able to make the leap that the responses he was getting, as unfair as they may have seemed to him, contained useful information for him.

MacDonald’s fate was probably sealed by the wide sales of Joe McGinnis’s Fatal Vision, a book concluding he was guilty, which was promoted in a “60 Minutes” special and ultimately made into a television miniseries. MacDonald’s manner was such that even Janet Malcolm, who went on to write a book critical of McGinnis’s problematic book, actively avoided reading the correspondence she received from MacDonald, finding it overwhelming and claiming that she could not learn anything from the evidence – that it was necessarily unable to inform, because one’s interpretation is inevitably colored by his (or her) preconceptions (a position that is trivially reasonable but ultimately seems to deny the value of having a court system at all, or indeed any other search for understanding).

This thicket of meaning and self-awareness has been at the center of Morris’s interests for quite some time, and he addressed several such deficits in a series of articles at the New York Times, beginning with a neat summation, Something’s wrong but you’ll never know what it is (part 1).

Morris gets this wonderful quote from David Dunning, Professor of Psychology at Cornell University:

Donald Rumsfeld gave this speech about “unknown unknowns.” It goes something like this: “There are things we know we know about terrorism. There are things we know we don’t know. And there are things that are unknown unknowns. We don’t know that we don’t know.” He got a lot of grief for that. And I thought, “That’s the smartest and most modest thing I’ve heard in a year.”

Brilliant. I have it posted in my office at work. I mean, Rumsfeld’s remarks. Anyway, Morris draws Dunning out some more, and it’s well worth reading, as are Morris’s explorations into how this plays out in detective work and medicine.

Here are parts 2 through 5:

The Illness of Doubt: Everyone Poisons Himself in His Own Way
Doctors Everywhere
Belief Is Not a Monolithic Thing
Honest Feedback

Dunning and Kruger published Unskilled and Unaware of It: How Difficulties in Recognizing One’s Own Incompetence Lead to Inflated Self-Assessments in 1999. This is a fascinating paper, and was even a winner of one of my favorite awards, the Ig Nobel prize, in 2000. Yes, it is funny, and it will definitely make you think. And once you start thinking about it, you may find it hard to stop considering what is perhaps the most fundamentally limiting cognitive bias of them all.

Placebo Success

Before the study began, researchers explained to the parents and the kids, aged 6 to 12, that the dose extender contained no active ingredient. After eight weeks, the symptoms of ADHD had grown more severe in kids who took only a half dose, but they remained stable in the groups that received either the full dose or the half dose plus placebo.

It’s very interesting to see this done with ADHD and stimulants, I guess partly because “stimulants” retain their association with recreational and addictive drug use, and “dose extenders” recall some of the ritual replacement people can use when they are trying to break a dependency. Obviously it’s only suitable with drugs with certain kinds of modes of action—it would spur the development of antibiotic resistance to use this method to “stretch” antibiotic supplies in a stressed environment, for example.

Kids in the ADHD study were told that, “the mind and body work together in interesting ways and placebos are known to work sometimes but no one knows why,” while researchers told patients in [another trial, in irritable bowel syndrome] that placebos “have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes.”

I like this approach, because it explicitly brings a broader inclusion of factors in the patient’s well-being into the doctor’s office. I think it has the potential to improve medical care in a number of ways, from reducing harm (potential side effects) to helping patients feel less buffeted about by what’s brought them into the doctor’s office in the first place. It would be interesting to see some of this work combined with what we’re learning about the better outcomes in people who simply comply diligently with medication instructions—no matter what they’re taking.

Read the whole article, It May Be Fake, but Trust Me—It’ll Work, which also talks about the variety of placebo effects and some of the limitations to consider before putting them to use.