On Further Consideration: What I May Be Reading

(by whizbang) Jul 17 2015

GoSetWatchmanThis week Harper Lee's novel, Go Set A Watchman, hit the shelves of booksellers. The internet gave a collective gasp when early reviews revealed that Atticus Finch has racist views in this sequel, set in the 1950s. I know, because I gave one of those digital huffs. I could not believe that Atticus would be this way! I had no desire to read this book.

With further thought, I am reconsidering.

Racism does not have an on/off switch; it resides on more of a dimmer, with a variety of levels in between the extremes. I know* a lot of people who would agree that Tom Robinson got treated unfairly in To Kill a Mockingbird. They would agree that people of African descent should not be abused by others just because of the color of their skin. They also would not want "those people" living next door to them. They would express dismay when a professional sports team fielded an all-black starting line-up. They are racists, but not as extreme as the white jury of Mockingbird.

As I considered the bits included in reviews about "the new Atticus," I realized that he never professed to be a civil rights pioneer in Mockingbird. Readers really have no idea how he feels about African Americans, other than recognizing that Tom Robinson cannot have raped Mayella Ewell. Providing Tom's constitutionally-guaranteed defense does not mean that Atticus wants black people living next door or attending school or voting.

I will likely download and read Watchman in the near future. With current discussions of race, the "new Atticus" may provide more important lessons than our more heroic version.


*I may be related to some of these people.

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A Doctor Deals: Metformin

(by whizbang) Jul 14 2015

Structure of Metformin

Structure of Metformin

The first-line treatment for type 2 diabetes (DM2) is Metformin. First synthesized in the early 1920s, the discovery of insulin a few years later eclipsed these agents, at least for a time. In the latter part of the 20th century medicine rediscovered these drugs, and they entered clinical use. Despite becoming the standard of care for DM2, it took 30 years to figure out how Metformin works!

Human studies show that its major action is reduction of glucose production in the liver. When we eat, nutrients of all types enter the bloodstream and make a first stop in the liver for metabolism. The liver can convert these other molecules to glucose, our circulating fuel for cells, via a process called gluconeogenesis (literally new glucose).  Patients with DM2 have twice the rate of gluconeogenesis in the liver as nondiabetic people. Metformin for 3 months can normalize this process.

Metformin also has beneficial effects on levels of fats in the bloodstream and uptake of glucose by muscles. Unlike many therapies for DM2, patients usually do not gain weight with Metformin; indeed, many experience weight loss.

AMPK-regulated enzymes circled

AMPK-regulated enzymes circled

One documented cellular mechanism involves AMP-activated protein kinase (AMPK), a protein that functions in a number of metabolic processes. These include lipid (fat) synthesis, muscle glucose uptake, and control of a number of enzymes in the gluconeogenesis process (diagram to the right).

Zhou et al showed that Metformin activated AMPK in liver cells, leading to decreased fatty acid and lipid production (which in turn increases the sensitivity of the liver cell to insulin). Inhibition of AMPK blocks Metformin's beneficial effects on gluconeogenesis, so activation of AMPK also provides an explanation for this beneficial effect.

So have we answered the mystery of Metformin? Of course not!

Metformin has one obvious, often troubling, side effect: diarrhea. For myself and a number of friends who take it, the first dose induced events not unlike the clean-out for a colonoscopy (ask your 50+ year-old friends about the joy of colonoscopy prep). Some folks have ongoing diarrhea that limits therapy with the drug; in most patients, like yours truly, the problem eventually resolves (or becomes less problematic).

Why does Metformin cause intestinal problems? We really do not know. Some have suggested that it reduces intestinal absorption of glucose which could contribute to changes in stool pattern. Its effects on the liver may also change stuff downstream in the gut. Some have suggested that these intestinal effects may be beneficial as well, through changes in the microbiome.

For a drug that's a century old, there is still a lot we do not know about Metformin. At least we know it works!


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Another Problem for Puerto Rico

(by whizbang) Jul 01 2015

My recent meeting included a session with the Deans of Puerto Rico's four medical colleges. As we discussed diversity and inclusion, they presented an unexpected issue. Because Puerto Rico is a US territory, its medical schools are accredited by the same groups as those on the mainland. Their students must take the MCAT, National Boards, and Specialty Boards that mainland students do.

These exams are only offered in English.

That means only truly bilingual students can hope to get into medical school and eventually qualify to practice. For the urban population and wealthier people, this is not a huge problem. For the bulk of the island, that level of English fluency is difficult. Medical school thus becomes primarily an upper-class option, perhaps even more so than on the mainland United States.

Then, if you have that sort of fluency, training on the continent provides more options than the island. Once you move to train, it becomes tempting to stay, leading to major brain drain for Puerto Rico.

My school's problems seem less weighty now.


By the way, San Juan is a lovely city. You can visit the Caribbean without a passport. All of your appliances, including your cell phone, will work. OK, some Verizon customers had issues with voice calls, but my AT&T phone worked just fine. No plug adapters required. There's history, tropical beauty, and the ocean. You will eat more rice, beans, and plantains that you imagined possible, but the food is delicious. So is the rum.

So go; you can thank me later.



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What I Am Reading: #GDIGFA Edition

(by whizbang) Jun 26 2015

One of the plenary sessions at this meeting demonstrated the utility of Whole Brain(R) thinking.

Now, I assumed that I tried to use my whole brain most of the time, so I got the book, The Whole Brain Business Book, and read it en route to Puerto Rico. This model overlaps with a lot of other approaches to how we humans perceive the world, but it can provide a useful new frame for the problem.



Four aspects of human pattern preference occupy each quadrant of the diagram. The upper left thrives on logic and facts. The bottom left craves order and process. The lower right focuses on the human-emotional facet of things. The upper right is creative and big-picture. Many, if not most, people have a dominant quadrant. This doesn’t mean that we cannot appreciate the other perspectives; they just come less easily to us.

Many people have more than one quadrant that is relatively strong. The two upper quadrants are often found in inventors, scientists, and other creative yet data-driven types. The bottom half of the diagram, with its order and emotion, often finds professions like nursing supervisors. Those who favor the left side rely on facts, logic,and order, while those on the right tend to be idealistic.

As I read this book, I thought about the pharma booths I saw at recent clinical meetings. Ad agencies certainly know how to pull all of these perspectives into the show. Each booth featured big images, most often people living good lives with their disease (because of this drug, naturally). If not a patient image, some other emotionally charged picture appeared; fish out of water seem to be favored by pulmonary products. A tag line also dominates the big stuff, often with a message appealing to those D (upper right) quadrant folks: “Imagine a world without disease X.” Less prominent, but still big enough to catch the eye, are diagrams and graphs showing study results about the drug to start pulling in the left side of the diagram; after all, you have to get them close enough to take the reprints and package inserts that have the details they need to change their practice!

Like all models, this one cannot solve every problem of interpersonal communications. It explains a lot, if you let it. And Ann Herrmann-Nehdi put on a rollicking work-shop this morning where we all learned a lot.


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(by whizbang) Jun 19 2015

logo-aamc.gif-dataI have finally dug into the latest AAMC dataset on the status of women in academic medicine. The website AWEnow (Academic Women for Equality Now) will be featuring these updates over the coming weeks. Today I posted the overall scores for the nation.

Good news: The overall share of women in leadership has increased over 4 years (3 datasets).

Bad news: At this rate, I will be 94 when women hold half the leadership positions in academical centers.

Go see my pretty graph here!

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How To Fix Youth Hydration

(by whizbang) Jun 12 2015

This week a story about inadequate hydration in US youth has gotten a fair amount of press. As a pediatric kidney doctor, I end up seeing these kids in my clinic, most often for stones. Getting these kids to drink enough liquid to keep calcium from getting together with other stuff to form crystals and rocks is tough. The biggest barriers come from the schools!

The first problem is lack of access to fluid. There are water fountains in the halls, but kids often do not like to drink from them. Also, a mouthful of water every hour or two is far less than most of these children need. We have a stock letter we send to schools allowing our patients to carry water bottles to class.

ToiletLoveThe next issue involves bathrooms. Carmines' law of physiology states, "You drink, you pee, you don't, you die." Our stock school note also asks schools to let our patients use the bathroom when they need to go. Too many schools have really short transition times between classes that do not give students time to use the restroom. Teachers can also be reluctant to allow their pupils to wander about the school unsupervised, even when pursuing a noble activity like urination.

My final issue also involves bathrooms. Too many students tell me that they do not want to go to the bathroom at school. They are often dirty, unpleasant, and sometimes unsafe. If we want our kids to drink enough fluid, then we need facilities where they can "recycle" that liquid. These facilities should be ones we would use ourselves, and not just in an emergency situation.

We evolved on the savannah where access to liquid was often unpredictable, so our kidneys can conserve water well, without immediate damage. Long-term effects of concentrating urine may occur, but kidney stones are a clear, early result. This is more than a matter of telling our offspring to drink more. It's a matter of making them able and willing to pee more.

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Getting Loud and Angry

(by whizbang) Jun 10 2015

I remember when Acquired Immune Deficiency Syndrome (AIDS) first appeared as a case report in the 1970s. This mysterious illness shared epidemiological features with hepatitis B and some other disorders that made a virus the likely culprit. Eventually we discovered HIV and a number of drugs that have turned this former death sentence into a chronic manageable disease. Magic Johnson has been living with HIV for almost 25 years now! The cure is still out of reach, but what progress in 37 years, from “we have a syndrome” to a chronic disease.

How did this happen? We threw a ton of money at AIDS/HIV. Why did we designate so much funding to a disease that the mainstream had little to fear? At risk and affected people knew how to make some noise. Organizations like ACT UP lobbied and protested. Entertainers and politicians showed support with red ribbons.

Funds at the NIH got earmarked. Not all of that money led straight to scientific advances, but with that much moola driving things, things got done. It was almost like the space-shot of the 1980s.

Once upon a time, kidney disease had vocal advocates. When dialysis first became a practical treatment, it was performed on the floor of congress to get kidney failure treatment covered by the newly formed Medicare program.

Unfortunately, since those early days of yore, the focus for kidney disease has been on reducing costs, not improving treatments. Sure, we have incremental changes in equipment for dialysis and new ways to prevent transplant rejection, but really novel stuff? Not exactly.

We also have contracting funding for kidney disease research, Partly this is because chronic kidney disease disproportionately affects the poor, minorities, and other disenfranchised people. Even high profile patients like Alonzo Mourning and Sarah Hyland have failed to motivate congress.

We need more visibility for kidney disease. We need loud and even angry patients demanding research funding so that we can have cures. Dialysis works fairly well, but we can make it better with more research. Transplant is even better, but it is not a cure. We also do not have enough kidneys for every patient, and there are some diseases that repeatedly attack the new kidney, making dialysis the only option. While Medicare covers dialysis for most patients, it may not allow the optimal prescription for everyone. It also cuts off transplant immunosuppression coverage after a couple of years, making patients choose between their medications and other expenses.

In other words, despite our progress, we do not have kidney disease figured out by a long shot. Our patients, friends, and loved ones deserve better. We need to demand it, loudly and, perhaps, with some anger.

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A Doctor Deals: Thoughts from #2015ADA

(by whizbang) Jun 08 2015

Boston revere 220x175

As usual for this time of year, I am at the annual scientific sessions of the American Diabetes Association. For four days I have been hobnobbing with others interested in diabetic nephropathy, learning about new stuff, and hanging out with my spouse in Boston.

This year brought a new perspective. I am now living with diabetes myself.

The diagnosis provided no big surprise. My fasting glucose levels had been “impaired” for about 10 years, a clear indicator that this could happen. I would start a diet, compulsively recording every bite and calorie I ate. This resulted in a few pounds coming off, but as soon as I failed to track food, it came right back. I had generally resigned myself to plus sizes for the rest of my life.

A few months back I established care with a new doctor. Basic lab work showed a somewhat higher glucose than before. Oops. I got back on the wagon to try and fix that by my next labs. I had some additional motivation as well. My daughter got engaged at Christmas, and I really wanted to drop some tonnage before taking family photos. I thought I would get it all fixed.

Unfortunately, I failed. Or at least my pancreas did. My HbA1c, a measure of the amount of hemoglobin with glucose glommed onto it, was 6.8%. Anything above 6.5% means you have diabetes.

Knowing stuff like this does not help

Knowing stuff like this does not help

My brain spent a few minutes in denial. Perhaps if I got more aggressive and lost some more weight, this would go away…? Luckily, I had put on my big girl panties and dealt with it by the time the doctor came in to discuss my next steps.

So this was my first year attending the diabetes meetings as a doctor, a scientist, and a patient living with the disease. In the near future I will write more about dealing with diabetes. It's especially sobering when you know stuff about your pathology...


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Our Private Wild Kingdom

(by whizbang) Jun 01 2015

Nature and science are everywhere, even in a civilized front yard. In addition to the usual insects and lizards, my spouse encountered a shy copperhead and a small turtle while spreading mulch around our front shrubs yesterday. His scariest encounter was with a mallard hen. We saw her walking around the yard earlier, but as he moved toward the front door she flew out of the bushes at him.

We soon learned why:


This lucky duck feathered her nest of ten eggs right outside our dining room window, a mere 5 feet from our front entry. When she sits on the nest, she is really difficult to see. I thought the duck and eggs were gone this morning!

We will keep an eye on progress and update when things happen!

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For Dottie (And Me)

(by whizbang) May 30 2015

Microbiome research makes headlines often, especially when folks start talking about "fecal transplants" (yup, eating shit). There's a whole microscopic world living in our guts that influences all sorts of things about us. We have only just begun to explore this fascinating area of research.

Now a group is raising money to document the feline microbiome, a Kickstarter project dubbed the Kittybiome. For various amounts of money you can sponsor study of a shelter cat, your own cat, or even other goodies. My friend Michelle Banks, an artist who specializes in science-inspired designs, is creating a Kittybiome scarf. Given the lovely silk items I have previously purchased from her site, I decided to kick in enough to study a shelter cat and buy the scarf.

Dottie Hinson Lane

Dottie Hinson Lane

Why am I doing this (besides my need desire for another scarf)? The little lady in the photo is my inspiration. Dottie Hinson Lane, named for the Geena Davis character in A League of Their Own, has suffered from a diarrheal illness this year. Cat diarrhea is at least as annoying as diarrhea in your offspring. The more we learn about the cat gut, the better as far as I am concerned.

We have Dottie's symptoms controlled at the moment. I still want us to learn more about what goes on in those feline guts.

You should consider supporting this project as well; if nothing else, you can score a cool scarf!

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