Monday, December 8, 2014


Off to Holland on the early flight, then a proper train through such places as Utrecht and Arnhem. Last stop: Nijmegen.
I bring the camera, hoping to have some time to poke around Nijmegen, one of the oldest cities in this country, between sessions at the A-T meeting I've been sent here for. Alas, our hotel is several km outside of the city, in a modern university suburb. Neat & tidy, but boring. The area is nicely wooded and surprisingly hilly for the Netherlands. The hotel brochure mentions a 60 minute walk and a 90 minute one, and even a 16km connection to some sort of national trail network with no proposed timing. Hah, guess you can get out for a walk if you want to.
Ah, here's the meeting schedule. Everything's over with lunch on Saturday, and as long as it doesn't rain I'll have that afternoon to stroll around the autumn hills of Holland. Fingers crossed that the weather holds, because it isn't looking good.
I haven't been to an A-T workshop in ages. The APRAT, the local family association, holds a meeting every two years or so, and I do see one or two of my old colleagues at those events, but they're mostly for the families, not for scientists. They talk about daily issues - how to get the help they need, how to deal with school and physical therapy, tricks to keep their kids involved and active and as healthy as possible. They want to know about treatment, and what to expect of the future, but not too much.
This is a clinical meeting set up to talk about all the nitty-gritty and what can be done and what isn't working and what might eventually be a good idea. I'm here to distill all that into a progress report for the families in France. I hope there's good news. Something to say that they haven't been saying for years already.
There's a slide put up showing the increase in life expectancy for the general population over the past century, showing also the life expectancy curve for people with cystic fibrosis. CF is another recessive genetic disease for which the gene was cloned some several years ago but like A-T that did not particularly help in developing a cure for the illness. The CF curve is going up, though, faster than that of the general population. All the increase is linked to better everyday symptomatic care, and to being pro-active and staying ahead of problems before they're intractable.
At lunch, the father of two A-T patients said to me that he didn't think the curve for A-T patients had changed at all, in spite of all our meetings and networks and expertise.
I thought this just couldn't be true. Like CF, A-T patients are treated as their problems come up, with a recent accent on keeping ahead any bug to settle in the lungs and on exercises to keep the functions that one has, or at least lose them more slowly. So we must be doing better even if there's no cure for the fundamental problem. So I asked around, because these are just the people who would know. But the ones I asked didn't really know. Though they did suspect the father was right, and the survival curve, if it had improved at all, had done so very modestly. Not like the CF curve.
It's actually complicated to figure. In the past decade, lots of patients with variant phenotypes, all mild, have been found to have A-T, genetically. They have real deleterious mutations, just not the severe disease course. So the overall survival figures are inflated by the inclusion of these milder cases (or, conversely, the disease is being redefined). If you stick to 'classical' A-T, and people are increasingly careful to preface their talks with that word, then nobody has the numbers.
Any improvement is not very big.
Which is odd, because if we have better antibiotics, or at least a wider variety of them, and we know better how to do physical therapy (and when), and we're better at chemotherapy, then there should reasonably be some improvement. There are more anecdotes today about A-T patients in their 30s and 40s than there ever were - do they not shift anything?
We talk about health risks in heterozygotes. The cancer risk pretty much boils down to breast cancer in women, which is well-studied. The small residual increased risk for A-T parents to die of cancer is spread out over all types and ages, and there's nothing to follow up on there. The question today is how to catch the breast cancers early, and if the standard mammography might be provoking years later the very thing it's meant to detect. Scientifically, that would make sense. But because of the delay between starting screening and detecting a cancer, nobody can say for sure if the radiological screening itself increased the risk. So women are still being referred for mammograms as early as age 40, and we will see in 10 years if we've made a very big mistake. Or not.
There are other health problems in the carriers. Heart disease, diabetes, things that don't appear to have much to do with the gene defective in A-T.
Why heart disease?
Well, most of the known and studied carriers are the parents of patients. These people have a lot of stress, from caring from their chronically ill children, even more so when their kids become adults with less and less autonomy. And they tend to neglect their own health. It isn't because they have just one working copy of ATM. They have Caregiver Syndrome.
I don't know if it's an official syndrome, but it could be.
If you could get the non-parent carriers in a study (the brothers and sisters and aunts and uncles...) and follow them up long enough, you'd probably confirm this. And then all the carriers identified through the breast cancer risk cohorts - they have no A-T patients in their families at all. Do they have these same problems?
Anyway, it's an interesting meeting, which goes past far faster than I can write about it.
Friday evening there's a bus to take us into town, for a quick private tour of the museum and dinner in one of the historical buildings.
At the museum we skip the extensive temporary exhibit of fashionable hats. Ditto the installations of multimedia modern "art" (thank goodness). We tour instead the history of the city with its Roman camps and strategic positioning on a low bluff along one of the major arms of the Rhine delta. This was the northwestern edge of the Roman Empire.
Yeah, who'd'a thunk?
(Well, ok, anybody with a decent idea of European history)

There used to be interesting castles and forts around, but they've mostly disappeared. Often used as sources of ready-quarried stone or free bricks, and prominent buildings remaining from the middle ages were flattened in a mistaken but very efficient bombing run by the Americans in 1944.
The museum closes at 5 sharp, and we're told by our hosts before being ushered outside into the early night that we're welcome to gather even now at the restaurant for drinks, but at any rate please be there by 6:30 for the meal. It's right down the street here, then on the right. Can't miss it: it's the only "old" building on the square. Shops close at 6 if you're going to wander around town.
Shops close at 6? Dinner at 6:30? Thank goodness they pushed the schedule back half an hour - the program says dinner at 6, and I don't think anyone but the Dutch in our group is interested in eating so early.
I head off with my friend Janet, whom I haven't seen in years, since another of these A-T workshops. The buildings are typical brick rowhouses, three stories tall.. The old street surface is brick. The shops on the ground floors are just the same ones now that you find all over France and the UK, just about. Seems you could be anywhere. The eateries are mostly local, though there are a lot of chain restaurants and fast foods coming in. More homogenization.
Janet exclaims There's a Hema! Just the place to get decent(ish) stuff really cheap. Hema hasn't made it to Clermont, or apparently to Lyon where Janet is based, but Paris has them. The deli section has all sorts of cookies and crackers and sweets and jarred condiments and prepackaged meals, just the stuff an English person needs when in France for too long.
Indeed. I must come back here tomorrow.
Dinner is served at long, long tables in an old merchant storehouse and trading center. Very quaint, lots of wood with iron fittings and brick floors and magnificently high ceilings. Wine from Chile and Argentina, not from any of those little countries right next door.
I used to hate these dinners because I didn't know anyone, and you're stuck there until the bus comes to fetch you. Now I know some people at least a little bit, and I know some of the other people they mention so frequently when talking shop. Which is most of the time of course.  Janet I've known since moving to France, Luciana and our hostess Corry here at my sector of table since grad school, so I'm not so ill at ease. I don't work directly on A-T any more, but it's a good bunch, and the evening goes well.
After two and a half hours at table, though, I really would rather go out for a walk around for the last half hour. It's raining lightly, but what the hell.
The streets are deserted. Many of the shops use metal roll-down curtains, so you can't even look in the windows (not to mention the sad grey air that gives the whole street). The fabulous church is all shrouded in scaffolding. I get as far as the museum, where the bus will pick us up, and it isn't there yet. Curious. You'd think it would be there by now.
Perhaps there's a change in plans and the bus will after all be allowed to pick us up in front of the restaurant, and I'm at this very moment missing that announcement...
So I wander back the other way. Some of my colleagues have gotten their coats and gone for a stroll by now too, and here's Janet and Luciana and a young post-doc. Luciana appears to fear waiting in the drizzle, and looking back toward the museum I see our bus has arrived. If we get on now we can get the very very best seats - the front row on the upper deck. We do that, and save the Italian professor's hair from a soaking.
The thing with getting on the bus too early, however, is that you might end up missing it.
I'm not ready to sit still yet, so while the others settle in I go out again. It's just a few hundred feet through the park to the view over the river with its bridges and houses all lit up. And the ruins of the castle are lit up. Nice. I wander back, all the time in the world,, and see the bus close its doors. Somehow that fails to indicate to my sluggish brain that this means it's about to leave. Time has stopped. They're just closing the doors because it's cold out. What I would do - I'm getting cold.
Yeah, and then it starts to move.

Hey! Wait!

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