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Great Escape, The Chase, The Return
Yesterday was one of those days - Tom is off in Boston getting a PET scan. That always makes me nervous. And I had to go talk to my OB/GYN about genetic testing for BRAC 2, a genetic mutation that makes the chances of getting breast cancer higher. My two first cousins have breast cancer, as did the half-sister of my grandmother. Apparently that is enough to make a test at least for the exact thing my cousin has (a singe site test) reasonable to do. To do that I have to know the exact name of the mutation and I hope to get that soon. My cousin has surgery tomorrow, so maybe by early next week someone will have time to get back to me with the details. I think a single site test for the specific mutation is $385 but the full work up if you are not looking for a specific BRAC 2 could be $3,500.
In the middle of what this bit of drama, I found a zebra finch had escaped from the sun room and was flying frantically around the house. No idea when he escaped. I chased him with a net off and on for four hours and it was hopeless. I finally put food and water out where he landed most often in the living room by our chairs and he found it and filled up.
I planned to try to catch him once it was dark, if I could find him in the house and reach him in the dark. But, while talking to Tom and wandering around the house, I just happened to walk/talk from the living room back to the computer room that is next to the sunroom. And I heard a little beep behind me and the the finch flew into the screen door of the sunroom. The finch had, I guess, followed the sound of my voice back to where he belonged. I opened the screen door and he flew right in (and no one else flew out).
And in other news the 8 chicks seem to be doing fine. Hummingbird is back and I'm watching The West Wing while knitting the cabled vest.
Fiber Jewels Row Counter
The only thing that is keeping me sane and on track with the cables on my vest is this neat row counter from Fiber Jewels . It has rings that slip over the knitting needle and numbers to keep track of your rows. There is also a bead on a lobster claw catch to either count rows over 10, or to keep track of a different pattern. This is very nice for this vest which has two different cables that cross of different rows. The lady who makes these is making me one with extra lobster claws/beads so I can track an even more complicated design. She sells on etsy.com which is sort of like ebay, but just for handcrafted items.
This is my new row counter before the lobster claws are added
On the bird front we have bad news and good news. The bad news is that the bad mother hen (the cuckoo maran) when nuts and killed one, maybe two, of the white dorking chicks. We are just sick. We took her chicks away from her and tossed her back with the main flock. The dark brahma has adopted one and the silkie has the other. The brahma is still setting on eggs but we have about given up on any more hatching.
And for the good news, the hummingbirds have arrived.
White Dorking chicks
I'm not sure if any more eggs are going to hatch. 13 remain, but I think they got to cold when their setters abandoned them. But the 4 chicks are, of course, darling. Unlike all other Dorking chicks I've known, they don't have "cleopatra eyes."
This is what I mean by "cleopatra eyes"
Silkie Chicken Drama and Hat
A chick can live for 3 days after hatching without eating or drinking - it is still absorbing (interanlly) the last of its egg sack. But by day 3 the chick is getting very stressed. Our dark Brahma setting hen hatched a silkie banty out 3 days ago and 3 other chicks out yesterday/this morning. She is still sitting on eggs and so far shows no sign of leaving the nest. If she figures the chick is in distress she may very well abandon the eggs in order to teach the chick to eat/drink. That is what the other two hens did. So I took the silkie chick away and introduced it to the Silkie momma who moved inside because she was getting beat up. It took a few hours, but the hen finally bonded with the chick and the chick the hen. I made sure it got a good drink of water and she taught it to eat.
It isn't completely out of the woods, but things are much better than this morning. Look at the size difference!
And I'm knitting a very quick Chinchilla chemo hat . I know the person who needs it may not like the fuzzieness, but it is very soft and light which ought to be great for summer in Texas. Here it is as a work in progress being modeled with a chick
It is hard to tell which one is softer - one is certainly less wiggly than the other!
PI Topper and Chick News
The latest hat is done, it is PI Topper again, but this time made with the right yarn so I think the fit will be fine.
I love this hat!
Another chick was born this morning. Have not gotten a close look at it, but it is possible it is a Sumatran. But the rest have not hatched yet. I'm still mediating chicken wars and dash out everytime I hear a chick in trouble.
It is very hard to take a good picture of dark hens and chicks the color of pine shavings. There are 2 hens, 4 chicks and a lettuce leaf in the picture. The hen on the left is the aggressive one and in this photo she is teaching her batch to eat. The hen beats up on the Silkie on the right.
Baby chick monitor?
Abandoned Eggs
When I went out to check on the chickens late this afternoon, I found the broody Silkie had left her nest eggs. I fussed at her, picked her up with the intent to make her go back to sitting on eggs, and found two chicks underneath her. As best I can tell, based on broken shells, three eggs hatched under the other two broody ens. Two chicks wandered out of their nest boxes sometime today and the broody Silkie decided they must be hers and proceeded to be mama hen to them. Don't know what happened to the third chick. Can't find it.
I've no idea if the eggs she was sitting on are still alive. They were very cool but not cold to the touch and it has been a damp cool rainy day today. I tried to get two other setting hens from the other coop to take an interest and they refused. So I stuck them under the original two broodies and we will see. We weren't expecting hatching until late Thursday/Friday. And Thursday we were supposed to go off island for the last major shopping expedition before ferry rates go up for the summer. That is now up in the air.
As far as I can tell, the eggs that hatched are ours, not the fancy ones that were sent to us. Pics if poultry cooperate tomorrow.
Shedir hat started
This hat (Shedir see page 3) is densely cabled and will take a little long - and many many stitch markers. (One for start of row, one set for first cable pattern, one set for second cable pattern, one set just to make sure I'm making the purl stitches in the right place.)
It has rained here, lightly all day. We were supposed to have heavy rain, and might still for all I know. Tom made osso bucco today and it will gently meld flavors overnight and we have it tomorrow. I'm surprised we have not posted the recipe and will take care of that tomorrow. We dearly love osso bucco (veal shanks) and are so pleased to find a great source for them at a butcher's in Boston's North End. But we don't know too many other people who really like them.
In World of Warcraft news my mid-40s BELF hunter has taken to wearing the Admiral's Hat and has spent the last session slogging through the great out doors to find Flight Points. Travel is harder on the Horde side. But fishing is easier and I just got Nat Pagle's fishing pole and finished his fishing quest (woot!).
Hat Done
The Wavy Lace Cable hat is done and ready to be shipped off tomorrow. I like the way the hat turned out, but had to do a bit of fudging because I was running out of yarn and the hat was getting too long. But the yarn is very nice because its elasticity solves the problem of knitting with a mostly cotton yarn.
Flock Grazing, Hat Progress
Today we took the flocks out to graze and a grand time was had by all. The new coop would normally graze in their fenced in backyard, but that is where the visiting and broody hens are and I wanted them to stay separate. (I don't want our huge rooster to squish a little banty hen.) So with both of us standing guard, we let them out the front gate - where they never are allowed to go since there is no fence. They were very well behaved and fortunately no hawks overflew us to spook them into scattering for all parts of the island.
Even our very oldest hen, Boue, who has gone broody but makes a dreadful chick-raiser and so isn't allowed eggs came out to graze.
Blue is by far the most popular chicken we have. Everyone loves her poofy head feathers and blue ear lobes.
Though the day was warm and sunny, it was starting to get cool when we let the flock out late this afternoon. I listened to the Ipod (amd listening to The Summerland and worked on the Wavy Cable Lace Chemo Hat .
I really like this weird elasticy soft yarn (Esprit) from elann.com,
For dinner we are having broiled Japanese eel, Japanese sticky rice and something with tofu as soon as I figure out a recipe, and a salad.
Fizz Hat
I'm working on a series of chemo hats for a friend of Mama's. The first two experiments were way too big, but I think I'm getting the hang of it. Even though I've knit many hats, most are wool or wool blends, and that won't do for this lady who is in Texas where it is already hot. (Though with AC on, she does need some warmth and lots of breathability.) I've just knit the Head Huggers No-Hair-Day Hairy Chemo Cap .
Tom is in Boston for his infusion, so I'm discovering the joys of trying to take a picture of the back of one's own head. The hat fits snugly and is very light weight. It didn't use anything close to a whole skein of yarn (so I wonder if I did something wrong. Do you suppose the yarn was supposed to be doubled?)
And a close up of the top
I'll wait for feedback on this one, but I certainly have enough yarn leftover to knit it again - either single or double strand. It goes quickly!
The chemo hat project series showed me that I was woefully short of 16" circular needles. I particularly like the Bryspun Flex ones and have gotten sizes 2-9. I'd always thought I'd never use any circs but Addi Turbos, but the Bryspun's are easier on my hands, particularly in short lengths and I love the shape of the tips.
Off to contemplate the next hat!
White Dorkings, Frizzled Sumatrans, Broody Hens
Our favorite chickens are Dorkings - the squat, five-toed, calm bird that the Romans brought to England. There the breed was used as a superior dual purpose (meat and egg) fowl. Though the bird became extinct in Italy, it hasn't changed much in Britain since Roman days and, in our opinion, that long domestication makes it much better with people. The standard color is grey,
and occasionally we can find red (or colored) ones, but the Romans probably had the much rarer white Dorking.
So we were thrilled to find an ad two weeks ago in the newsletter of the Society for the Preservation of Poultry Antiquities (SPPA )
that the VP was selling White Dorkings. Shipping 3 hens and a rooster was prohibitive, but he said he could send fertile eggs in a month or so basically for just the cost of packing materials. That sounded fine because we would have a month to empty out a coop and round up some broody hens. However, the eggs didn't arrive next month (so to speak, I know the tenses are screwy) but last week. We scrambled like crazy to empty out a coop and borrow broody Silkies from the Jacksons.
(A broody hen is one that wants to sit on eggs [or anything vaguely eggs shaped or even on nothing at all] for 3 weeks and only get off the nest once or twice a day to eat and poop. Their body temperature goes up, they fluff up their feathers to retain heat, and they scream and squawk if you try to bother them. Once a hen is broody, it usually stays that way until all hope of hatching the eggs is gone. Though of the 4 silkies we borrowed, 2 went out of broody as soon as they got to our coop.)
Silkies are bantams with fluff for feathers and are noted for setting eggs. Two of our hens had gone broody, so we have four broody hens plus an extra nonbroody Silkie who may decide to help. Which is just as well since 18 eggs showed up. 14 are the White Dorkings but the surprise was 4 Sumatran eggs. Sumatrans are about as far from the long-domesticated Dorkings as a chicken can get! And, to top it off, these Sumatran eggs have a 50/50 chance of hatching out a frizzled Sumatran. Those are so rare I can't find a photo to show you. A frizzled chicken looks like its feathers are all blowing backwards. Here is a link to Philen Farms frizzles . And here are our ladies (Cuckoo Maran and Dark Brahma) and guest broody Silkie setting
and our footloose guest Silkie on vacation
Uncrowned Brioche
Tom baked his usual New York Times style loves (left) but also made a sourdough loaf (not pictured) and a crown brioche (right). The brioche is a wonderful way to use up extra eggs! It had been a long time since he'd made brioche and somewhere in the years our brioche pans had vanished. And it turns out not many places carry full size ones any more. Little ones are used to make desserts like flourless chocolate cakes. But after looking in cooking supply sites and eBay, I finally found classic ones at Amazon.
The pan's shape helps the dough poof up and then you put a little doughball on top to make the crown. Since Tom used a high sided cheese cake pan with a parchment paper collar, ours has a lovely dome but no crown.
4 cups french flour (see note)
Eggs, 6 (or 7)
Water, warm. 1/4 cup
Yeast, 1 package
1/4 cup sugar
Butter, 5/8 lb
Egg yolk, 1-for glaze
Put yeast into 1/4 cup lukewarm water. Let it sit 10
minutes. Put flour into large bowl. Make well in middle.
Put yeast with its water,6 whole eggs, and the sugar into
the well, and start mixing, bringing in the flour from the
sides of the bowl. The mass should be moist and sticky but
not runny, and all the flour should be wet. If there is dry
flour in the pan add either another egg or a tablespoon of
water depending on how much additional moisture is needed.
Knead by hand to smooth and then divide dough into three
parts. Use food processor with dough blade and process each
third separately. Do not let the dough get above body
temperature--let it rest if necessary. After the dough has
become silky and rolls around processor bowl, start adding
butter by the tablespoon, 1/3 of the total butter to each
batch.
After all the batches are processed, combine and knead by
hand a few minutes. Put dough in Saran covered bowl in warm
place and let rise until doubled in bulk. Punch down, knead
briefly, and put back in bowl, covered, in refrigerator
overnight. It will rise ! The next morning, punch dough
down, knead briefly, shape, and put in a warm place to rise
until double in bulk. Glaze with an egg yolk to which a
Tbsp of water has been added.
Place in a 425 F oven for 10 minutes. Reduce temperature to
375 F and bake 30 minutes longer. Turn out to cool for 15
minutes before cutting.
Note: If you can't find french flour, use 3 cup bread flour and 1 cup cake
flour.
Deck Visitor and The Question and Sourdough
That is a male ringneck pheasant on our deck. For reasons I don't really understand, some are released on the island each year. Ostensibly by and for hunters, though I've never heard of anyone hunting one. And the release point isn't that close so it is a bit is a bit surprising for one to turn up here. There are rumors that another group may be releasing females (which may or may not be permitted) so it is possible this one is native born. Whatever, he is a beauty and the chickens stare at him in worried wonder.
Today (Tom is off in Boston for his treatment) is one of those days where 3 or 4 people have asked me how Tom is. I know they want to know but I get the feeling I sometimes handle the question better than other times. I'm uncomfortable just saying he feels fine but really isn't and I think that leads to telling them far more than they really want to hear. It probably is just when I need to vent/talk about it a little. But it may be a bit hard on my audience sometimes. And if I apologize for dumping on them, they feel even worse. Giving and getting sympathy is hard to do gracefully! Oh well. It is a small problem compared to the big picture, I know, but I wish I hadn't made those people a bit uncomfortable.
On a different, fermenting, note we started a real sour dough starter yesterday and I've been feeding it all day. Once it is started and bubbly, it needs a bit more flour and water every couple of hours. To keep the starter from getting too acid, 1/2 of it isdiscarded before you add the next dose of flour. It seemed silly to throw out a perfectly nice but young cup of starter so I sort of made up a sourdough pancake recipe for lunch. Needs work but wasn't bad.
Easter Hens and Sheep
June and her daughter Noa came to visit. They raise Silkies - a kind of bantam - and wanted to see our coops and, since the Jacksons have Silkies, hoped to get one from them. As usual our very elderly silver crested polish hens are the most popular. The two crested polish are all that is left from our very first batch of chicks.
The Jacksons had a Silky they could give away, and some fertile eggs that June will stick under her broody hen. The goats, llamas and sheep were all admired, and the sheep got a snack of apples and pears.
Tom goes back to Boston Wednesday and Thursday for the next infusion. He is continuing to have few side effects from the treatment, and those are mild (a little tired and a little stomach upset) but is feeling fine.
Thai Semi-Dried Salmon
6 oz semi-dried salmon
1 cup coconut cream
1/2 cup coconut milk
2 tablespoon fermented rice; optional
1 teaspoon palm sugar
1 tablespoon tamarind water
1 dash fish sauce
1 teaspoon lemongrass; finely sliced
2 shallots; sliced
1 chili; sliced
1 small green mango; julienned (we omit or substitute green papaya or carrots)
coriander leaves
1 leaf kaffir lime leaf; shredded
2 tablespoon salmon roe; optional
To semi-dry a salmon fillet:
Clean a 6 oz salmon fillet. Mix 2 tablespoons fish sauce, 1 teaspoon sugar, a dash of salt
and a pinch of ground white pepper. Marinate the fish for at least 3 hours
or overnight. Remove fish and set on a cake rack over a tray lined with
foil in a warm, dry place for several hours, until the fish is semi-dried.
Turn once or twice during this process.
Grill semi-dried fish for 2 minutes on each side over very high heat, or
fry in a little oil. Leave to rest for 10 minutes.
Heat coconut cream and milk together. Add fermented rice, simmer one
minute. Season with palm sugar, tamarind water and fish sauce. It should be
creamy, sweet and sour. Flake in fish, add lemongrass and simmer a minute
or two.
Take off heat, garnish with remaining ingredients. Do not let the roe
simmer! Taste and correct seasonings.
Serve with sticky rice, raw vegetables, steamed shrimp and sprigs of Thai
basil.
Rumination 12 - Stable is Good
Rumination 12. Stable is Good
by
Thomas P. Vogl
March 19, 2008
Last week I had a repeat PET scan that reported "stable disease". That is, in the two months that had elapsed since the previous scan little had changed. There were a few new spots in the liver but some of the old spots had faded; there was a new suspicious spot in my neck, too small to classify, but the lymph node in my chest showed decreased activity. So officially, I am "stable", a condition not common with melanoma which is notorious for its aggressive behavior. Overall life expectancy statistics for metastatic melanoma are usually quoted as five to eight months and/or 14% survival after five years. Ah, well, in any case I am still asymptomatic after 15 months so I have nothing to complain about. We'll repeat the scan in May and continue AZD-1152 infusion every two weeks until then.
Scientifically, the interesting question, at least to me (I note a lack of interest on the part of the PI of the study whom I have not seen since I signed up on the dotted line early in January) is the source of the stability. The drug company's take, since they are continuing me on the study, is that it is their drug. Maybe it is, maybe it is a contributing factor, and maybe it is irrelevant. After all, I had an extended period of stability last Spring and Summer without AZD-1152. Since then I have increased my intake of omega-3 fats (fish oil and flax oil), doubled my intake of Celebrex (a COX-2 inhibitor) regarding both of which there are published indications that they may help suppress melanoma; and I have started taking selenium supplement, a known immune system stimulator. My suggestion that we take a look at my immunoglobulin levels and T-cells fell on deaf ears. After all, the study protocol is to determine maximum safe dosage – let's focus on that and not look at anything else – an attitude that I strongly suspect is fostered by the sponsoring drug company that is footing the bill.
Meanwhile, back at the farm, the lab in my basement to process blood samples has had two dry runs and a production run. I sent samples to John Viator at the the University of Missouri on Monday last, so that John can check for melanocytes in the circulation.
My concerns about the design and conduct of clinical trials has been simmering for years. It has been brought to a head by the experience of a friend who also has metastatic melanoma, with a brain metastasis that, mirabile dictu, disappeared and has remained gone for over a month after a short course of Ipilimumab (Ipi). This surprising (to put it mildly) result appears to be the direct reason for a new study protocol for patients with metastatic melanomas in the brain. Yet this patient is being denied further access to Ipi because, since her Ipi treatment a long-standing and very slow growing intestinal carcinoid tumor was discovered and removed.
She has been denied further Ipi treatment, even as a compassionate use patient, because the protocol says 'no other cancer'. If her carcenoid had been known earlier, she would have been denied her successful treatment. Now that her carcenoid is known (and removed) she is being denied further treatment. How Kafkaesque! How absurd can it get?
I call your attention to a recent, highly relevant paper Observational Research, Randomised Trials, and Two Views of Medical Science by Jan P. Vandenbroucke in PLoS Med 5(3): e67 doi:10.1371/journal.pmed.0050067 available on line: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050067 or http://tinyurl.com/3xoxc8 that points out the limitations of the randomized double blind clinical trial and its stultifying effect on scientific discoveries. I found the paper particularly interesting because when I was at the National Academy of Sciences in the mid 1970s the idea of double blind trials was being introduced and much discussed. The issues raised in this paper were on the table at that time and many of us were quite concerned that in the headlong dash to anoint the double blind clinical trial as the gold standard, the baby was being thrown out with the bathwater.
I will stick my neck out and predict that of the 12 patients to be recruited under this new study of brain metastases, (Clinical Trial NCT00623766) only one (+/- 1) will show a positive result. I base this on the fact that a much larger trial of Ipi had less than 10% response rate and there is no sound reason to believe that the response rate for brain metastases will be any different. My friend just happens to be one of the lucky ones whose melanoma is highly sensitive to Ipi. Her other melanoma metastases also went away. The problem is that the management of the drug companies are all looking for blockbuster drugs in line with the success they had with antibiotics for infectious diseases.
Folks, it ain't going to happen with cancer. Cancer is the result of heterogeneous, highly individualized mutations and/or epigenetic changes. One drug will never fit all, even for sub-types of a particular cancer. What the drug companies apparently are just beginning to acknowledge (kicking and screaming) is that they have to focus on finding markers that identify which drug will help which patient, not look for a drug that will help a high percentage of all patients. It is my opinion that this will never happen effectively, nor will we get humane compassionate use of experimental drugs, nor will we get honest, complete and prompt reporting of the results of clinical drug trials as long as the drug companies control the trials. So, I am trying to do my small part by proposing a solution. The letter that follows, is addressed to my Senator, Ted Kennedy who is the Chairman of the Committee on Health, Education, Labor and Pensions, as well as to Congressman Henry Waxman (D-CA) and Edward Markey (D-MA) who introduced the Fair Access to Clinical Trials (FACT) Act (H.R. 3196). I urge you to write to them and to your Congressmen to support my idea or to present yours. In fairness to patients, our trust in the medical community, and to the advancement of medical science, we cannot permit the present system continue.
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Dear :
I am writing to you to propose a solution to the problems arising from patients' lack of access to new drugs under current compassionate use rules and the problem of inadequate disclosure of the results of drug trials by the drug companies.
The public's loss of confidence in traditional medicine and the increasing appeal of alternative medicine and quack treatments for terminal diseases, especially cancer, is a direct consequence of terminally ill patients' inability to receive a sympathetic and fair hearing for compassionate use of experimental drugs from the drug companies that control the process. The continuing stream of press reports that documents drug companies' failure to report fairly and promptly on the results of clinical trials, particularly if they are disappointing results that are likely to reduce the value of the drug companies' stock, exacerbates the problem and decreases the public's and the patients' confidence in medicine. These problems are also documented in medical publications, e.g., the New England Journal of Medicine [NEJM 357:2219 (November 29, 2007)]. The rejection by the Supreme Court of review of the U.S. Court of Appeals the for D.C. Circuit (No. 04-5350) denying access to experimental drugs to the terminally ill, throws the problem back into the legislative arena.
This letter is written to request that you actively address these issues which impact on so many families and to suggest a cost-effective solution.
I recommend that drug companies continue to propose clinical trials to the FDA, as is the current practice. However, instead of the drug companies then taking control of the trials (i.e. choice of Principal Investigator (PI), patients, protocol, etc.), the FDA, after an initial positive review, would, through a Memorandum of Understanding (MoU), task the relevant institute at the NIH to convene a panel of intramural and extramural scientists and clinical investigators to review the trial protocol submitted by the drug company and, as needed, propose changes with respect to end point(s), sample size, statistical methods, etc., to ensure that the study is both clinically relevant and scientifically and statistically sound. (Far too many of the studies appear to have end points designed to influence the drug companies stock price rather than clinical relevance.) The recommendations of this panel shall be binding on the study. (Of course, the drug company would have the option of withdrawing from the study and canceling its application.)
The FDA, in consultation with the NIH and the drug company would then determine the cost of the study, and the drug company shall deposit that amount of money in a pool established solely for that purpose; all funds in the pool to be applied solely to fund clinical trials. Then, the FDA transfers to NIH funds from the pool and NIH (not as at present, the drug companies) selects the Principal Investigators (PI) and institutions at which the clinical trials will be carried out. In effect, NIH sponsors the studies using the pool as the source of funds. Under this arrangement, there is no change in tax burden and at most a negligible increase in cost to the drug company. The drug company's role in the execution of the trials shall be strictly limited to providing the drug for the trials and for any NIH approved compassionate use.
Patient selection as well as decisions relating to compassionate use of the drug shall reside solely within the purview of the PIs in consultation with, and with the approval of, the NIH.
It shall also be the responsibility of the NIH to ensure prompt, accurate, and complete publication of study results. I recommend that further phases of drug study not be permitted to begin until the publication of the results of the prior phase.
To ensure cost neutrality, it would be prudent in initial years for the drug companies to deposit an extra 15% into the pool with the understanding that any balance left in the pool at the end of the year will be returned to the drug companies not on the basis of cost accounting of each study but on the basis of the fraction of the total pool that each company provided. In subsequent years, FDA can adjust this percentage based upon experience in prior years. That way, if one study runs a little over budget and another a little under, the total moneys in the pool will cover the discrepancies. It will also serve to ensure that the money that each company deposits in the pool is clearly understood to be for overall clinical trials and not in direct payment for any specific trial. Any payments to PIs, physicians, and institutions are made by NIH, not by a drug company, in order to ensure the avoidance of any possibility of conflict of interest and to maintain transparency.
A word on my background. I am a retired research scientist who has spent much of his life in biomedical research with over 150 publications in the peer reviewed literature (see http://upislandeggs.com/Tpv-CV.htm). I am also a patient with metastatic melanoma currently participating in a Phase I clinical trial (for my experience with my disease, please see http://upislandeggs.com/Ruminations.htm).
If there is anything I can do to assist you in this matter, please do not hesitate to call upon me.
Sincerely,
Two Yees and Tin the Egg Bound
Willie and his eldest daughter Jennifer came to visit for the weekend. Even though we were supposed to have showers of snow and/or rain, it held off so the sightseeeing wasn't too bad. And, to our surprise, Chilmark Chocolates was open so everyone was delighted. The served the Swordfish Escabeche (see recipe below) on Saturday and roast beef/yorkshire pudding on Sunday.
Jennifer is a grad student in astronomy at Ohio State.
While she was here I taught her how to knit a sock from the toe-up (she knew how to do top-down already) and how to drop spin. I don't think I've ever taught anyone who learns faster than she did. Incredible manual dexterity! She may be back to visit in May, we certainly hope so!
Then last night I went out to get eggs and shut the chicken coops and found a hen in distress. She was huddled on the floor of the coop, instead of up on a perch, and had her head tucked under her wing. That in a young hen is a sure sign of trouble. I brought her in and indeed she was in bad shape. An egg had gotten stuck sideways and she couldn't expel it. This is called egg binding and is a common cause of death in laying hens. Even with lots of olive oil, the egg wouldn't budge so we carefully cracked it and emptied out the contents and then very carefully removed the shell. The danger is that broken shell will puncture something and make the whole situation much worse. She was prolapsed a bit but I tucked stuff back in and we hoped for the best. She (her name is Tin and she is a one year old Dark Brahma) was not eating or drinking so we squirted some water and olive oil down her. This morning she was still very lethargic and not much interested in eating. However by this afternoon she has perked up. We had roast beef sandwiches for lunch and she was very interested in beef scraps and mealworms and finch food and water. Tin is not out of the woods yet - droppings are almost non-existant which is bad but there isn't much else we can do but keep her inside and try to tempt her with easy to digest semi-soft food. I wish we had gotten photos of the egg binding, but there was just no time.
Swordfish Escabeche
2 lb swordfish, thick steak
----MARINADE----
1/2 cup juice, lime, fresh
2 cup water
1 1/2 teaspoon salt
----SAUCE----
1 1/2 teaspoon oregano, toasted (see note 1)
2 bay leaves; deveined, if fresh
4 allspice, whole
1 teaspoon peppercorns, black
1 1/2 teaspoon cumin seeds
1 cinnamon, stick
3 large garlic, clove, peeled
1 teaspoon sugar
3 garlic cloves, minced and toasted (see note 2)
----ASSEMBLY----
1 cup vinegar, red wine
1/4 cup oil, olive
1 bunch scallions, thinly sliced
2 chilies, red, in thin rings; or red bell pepper
1 bunch cilantro (fresh), chopped
Cabled
Here are my experimental cables
A staghorn cable hat
This is the Rivendell hat from Magknits , knit with Debbie Bliss Rialto . Rialto is a superwash merino and is my new favorite yarn.
A cabled earband for Tom, out of yarn in the stash and a pattern from Walker's. Tom wanted a wide band that would cover his ears and not ride up.
And my funky chef's toque (worn one way) and yarn holder (flipped over)
The next project is with a bulky yarn to make sure I can handle a bigger cabled project before I move down to DK and sportweight cabled vests.
I'll be starting MagKnit's Invested and we will see what happens!
Better about Blogging!
I think my new year's resolution needs to be to get back to blogging and walk at least 2 miles a day. I've started the walking, and now the blogging.
Tom's next Rumination ought to be out in a week or so, but in the meantime his melanoma is still "silent" in that it is there, but not causing symptoms. More later.
Wendy told me about a marvelous knitting resource called Ravelry . It is sort of a giant accumulation of mini-blogs about knitting projects and plans. Though just in beta, it may very well hint at what the web is becoming. You can see an intro to the site, sign up to be invited (took me about a week to get added) and maybe look for my projects (not sure about that). My user ID is KatherineL.
I've been knitting cables - or rather learning to knit cables. I've 2 hats and and earband done so far and a peculiar thing that started out as a yarn holding bag and ended up a sort of cabled, felted chef's toque. As soon as it is light I'll take and post some pictures!
And I'm being pretty good about the two miles a day, while listening to Carry On, Jeeves by P.G. Wodehouse. Next up on the listening list is Fluke, Or I Know Why the Winged Whale Sings by Christopher Moore.
Rumination 11. Nothing Ventured, Nothing Gained
Rumination 11. Nothing Ventured, Nothing Gained
by
Thomas P. Vogl
January 24, 2008
It has been an interesting start to 2008. On January 4th I met with Dr. Geoffrey Shapiro who went over with me in some detail the four phase 1 clinical trials he was currently conducting. We agreed that the trial of AZD1152, an aurora B kinase inhibitor, was the best match for me. My reasons for the choice are: the optimum dose had already been established; only the most minimal side effects have been observed in 30 patients; in the one melanoma patient on which the drug has been tried, extended remission has been observed. We agreed to start the study on January 14th.
On January 8th, I went out to Columbia, MO to spend a day with Dr. John Viator to learn how to prepare samples for his experimental test for melanocytes circulating in the blood (there are not supposed to be any). As I knew beforehand, the protocol is very straightforward and the necessary reagents are easy to obtain. I had already bought the centrifuge and the reagents, tubes, and pipettes all arrived last week. I will make the first dry run next week and send samples to John every six to eight weeks for him to run. I really enjoyed my visit because his experiments are so interesting and it is a rare pleasure these days to be able to give my gray matter a really good workout. To top it all off, he has a delightful family with two great kids. What more could one want?
The immediately past week has been an exhausting one. I spent the entire week, from early Monday (getting there through a snow storm) until Saturday morning in Boston, getting prepped for and receiving the first cycle of AZD1152 "chemotherapy". I put that in quotes, because AZD1252 is one of a new class of drugs that is quite different from the classic anti-cancer drugs, both in mechanism of action and in the image of side effects that the term chemotherapy evokes. AZD1152 works not by arresting cell division but by inhibiting the kinase responsible for arranging the chromosomes in proper alignment. Consequently, the daughter cells are either destroyed by normal p53 at subsequent checkpoints in mitosis or, in the absence (or inactivity) of p53 will be destroyed upon initiating the next cycle of division (because of their polyploidy). Experiments have demonstrated that the effect is much greater on cancer cells than on normal cells that also divide rapidly (mucosal, gut lining, and hair follicle cells) but the reason for this delightful effect are unclear. Details below.
On Monday lab tests (which were normal) and another PET scan that demonstrated some increase in the size of the liver tumors and the lymph node in my chest, as well as a new, small, lesion in my sacrum (the bone at the base of the spine). Clearly, it is time to try something to slow the progress of the disease.
Tuesday was devoted to installing a port. This was a minor surgical procedure, under sedation (not anesthesia), requiring three small incisions, two in my right shoulder and one in my neck, that runs a line (tube) from a small bulb resident under my skin below my clavicle up to my jugular vein and down into the right atrium of my heart. Now that it is in place, any drugs that I need infused, including the AZD1152, can be injected through my skin into the bulb. The procedure went very smoothly. The PA (physician assistant) who did it told me he usually does four a day. The sedation does leave one woozy and exhausted for the rest of the day so I spent the day in my room except for a sojourn to an excellent Vietnamese Pho restaurant for a very restoring bowl of noodle soup.
Wednesday and Thursday each were 13 hour days (7:00 am to 8:00 pm) in the CRC (Clinical Research Center) starting with EKGs and blood samples, a two hour infusion of the drug through the port, and blood samples every couple of hours for the rest of the day. The CRC nurses are knowledgeable, delightful, helpful, and busy. I got a lot of reading done in the comfortable recliner chair in which I spent my days. Katherine's iPod provided lovely classical background music for my reading. I also had a brief but informative chat with Dr. Shapiro who was on his way to Amsterdam for a meeting on AZD1152.
Friday was a short day in the CRC. One more EKG and a blood draw. The drug company requires that the EKGs be done on their machine which incorporates software that interprets the traces. Unfortunately, the interpreting software leaves something to be desired and kept reporting that I have a right bundle branch block, sometime first and sometimes second degree. Of course, I have no such thing, which had to be confirmed by a hospital EKG machine which requires different pads glued to me. I am reasonably sure that the problem is my normal bradycardia (slow heart rate) which confused the software's interpretation algorithm. Unfortunately for me – I wanted to go home – I had to stay over until Saturday for one last blood sample. Then I could dash to the airport and arrived back on island at 11:40.
Yesterday (Wednesday) I went back to Boston for a blood draw and a 'how are you feeling'. The chemistry came back disgustingly normal, including the white cell count which is the real issue (leukopenia is a known possible side effect which I happy to avoid).
Since this is a rumination, I feel free to discourse at random. I have been looking for an opportunity to bring some stray thoughts in, but it has not presented itself. Since I think it is important, I'll stick it in here. As most of you know, I am, and always have been, the opposite of a hypochondriac (hyperchondriac does not sound right and the spell checker doesn't recognize it). None the less, I find myself considering (worrying is too strong a word, at least so far) whether every twinge or ache, which I most certainly have cheerfully ignored in the past, may not be symptomatic of a new or enlarged lesion. So far, it has never been, but I cannot prevent the thought from crossing my mind. I would not be surprised that to a greater or lesser degree it happens to everyone in my situation. It is probably just egotism (or a better understanding of pathophysiology), but I feel that I panic far less than most people in my situation. I can notice the reaction in me, but (so far) I can brush it off within a couple of minutes with the help of a few deep breaths and a little objective analysis.
While on the subject of stray ruminations, although the realization did not hit me until several days later, having the port in place is amazingly reassuring and calming,. As I told one of the nurses in the CRC, having the port in was nearly as good as moving to Oregon. With a port, the problems with potassium induced pain that brought on the execution by lethal injection cases now before the Supreme Court go away, because it is potassium in the peripheral veins that cause the excruciating pain; directly to the heart avoids the issue. An air embolism would do as well as potassium. Even though I knew of the Oregon studies that demonstrated that the suicide rate in Oregon among terminal patients decreased after the passage of the Death with Dignity law (http://egov.oregon.gov/DHS/ph/pas/docs/year8.pdf), it was amazing to me how reassuring and anxiety relieving it is to know that, de facto, I retain control of my life. I am confident that I will actually live longer knowing that I have control. It avoids (as they have found in Oregon) seeking to terminate life sooner for fear of not having the control when it is ultimately needed. You have to be there to appreciate it. So, please, I ask you, dear reader, for your own sake when you get to that point in your life, make every effort to pass a Death with Dignity law in your own state now, before it is too late for you. (End of sermon.)
What follows deals with the details of AZD1152. Readers uninterested in scientific esoterica, can stop reading here.
AZD1152 is a small molecule (relative to the size of proteins and other biologic molecules) that suppresses the activity of aurora B kinase. A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation). Phosphorylation usually results in a functional change of the target protein.Two aurora kinases, A and B, control two critical stages of cell division (mitosis): Aurora A is essential for the assembly of the spindles and centromere maturation and separation; aurora B is active for chromosome alignment, segregation, and movement as they separate. [See V. M. Bolanos-Garcia. Aurora kinases, Int. J. Biochem & Cell Biol. 37: 1572 (2005) and M. Carmena & W. Earnshaw. The Cellular Geography of Aurora Kinases, Nature Rev., Molec. Cell. Biol. 4: 842 (2003).]
Because errors in mitosis provide a source of genetic instability that is typically associated with tumorigenesis, and aurora A has been identified as a bona vide oncogene, and aurora kinases are over expressed in a number of tumors, aurora kinase inhibition make an interesting target for anticancer therapy. [See N. Keen & S. Taylor. Aurora-kinase Inhibitors as Anticancer Agents, Nature Rev. Cancer 4: 927 (2004) and R. Carvajal et al. Aurora Kinases: New Targets for Cancer Therapy, Clin. Cancer Res. 12:6869 (2006).] The paper by Keen is exceptionally lucid and well written.
The specifics of AZD1152 pharmacodynamics is described by Wilinson et al. AZD1152, A Selective Inhibitor of Aurora B Kinase, Inhibits Human Tumor Xenografts Groeth By Inducing Apoptosis, Clin. Cancer res. 13:3682 (2007); by Evans et al. The Selective Aurora B Kinase Inhibitor AZD1152 Is A Potential new Treatment for Multiple Myeloma, Brit. J. of Haematology doi:10.1111/j. 1365-2141 2007.06913.x (11 Sept. 2007); and by Yang et al. AZD1152, A Novel And Selective Aurora B Inhibitor, Induces Growth Arrest, Apoptosis, and Sensitization For Tubulin Depolymerizing Agent Or Topoisomerase II Inhibitor In Human Acute Leukemia Cells in vivo And in vitro, Blood 110: 2034 (2007)].
A reference that Dr. Artemis Simopoulos sent to me [Xia et al. Melanoma Growth is Reduced in Fat-1 Transgenic Mice: Impact of Omega-6/Omega-3 essential Fatty Acids, PNAS 103:12499 (15 Aug 2006).] made me decide that increasing my omega-3 intake may help and cannot hurt. From the abstract:
"The results showed a dramatic reduction of melanoma formation and growth in fat-1 transgenic mice. The level of n-3 fatty acids and their metabolite prostaglandin E3 (PGE3) were much higher (but the n-6_n-3 ratio is much lower) in the tumor and surrounding tissues of fat-1 mice than that of WT animals. The phosphatase and tensin homologue deleted on the chromosome 10 (PTEN) gene was significantly up-regulated in the fat-1 mice. In vitro experiments showed that addition of the n-3 fatty acid eicosapentaenoic acid or PGE3 inhibited the growth of B16 cell line and increased the expression of PTEN, which could be partially attenuated by inhibition of PGE3 production, suggesting that PGE3 may act as an antitumor mediator. These data demonstrate an anticancer (antimelanoma) effect of n-3 fatty acids through, at least in part, activation of PTEN pathway mediated by PGE3."
Two interesting articles hot off the press:
Schatton et al. Identification of Cells Initiating Human Melanomas, Nature 451: 345 (17 Jan 2008) describes the greater specific tumorigenic capacity of ABCB5 positive cells compared to ABCB5 negative cells. While they do not classify these cells as stem-cells, the theory that there is a subpopulation of malignant cells that solely have the ability to metastasize has received a significant boost.
Bundscherer et al. Antiproliferative and Proapototic Effects of Rapamycin and Celecoxib in Malignant Melanoma Cell Lines. Oncology Reports 19: 547 (2008). According to this paper, celecoxib's action is independent of COX2 expression by the tumor and nor does it induce cell cycle arrest. Consequently, it would appear that it does not interfere with the action of AZD1152. This makes me give serious consideration to increasing my celecoxib (Celebrex) intake.
Zaw on Myspace
Ruminations collected
Mascarpone Panna Cotta
We have made this a couple of times and it is very popular - and very easy. The recipe below is the standard one and I'll add my adjustments in italics.
For the topping:
12 oz frozen mixed berries, thawed and drained (we like raspberries and blueberries)
3 tb sugar
---------------
For the panna cotta:
vegetable cooking spray
1 tb milk
1 1/4 ts unflavored gelatin
1 1/4 c whipping cream
1/3 c milk
1 tb vanilla
1/4 c sugar (I skimp on the sugar because I'd rather have a less sweet panna cotta)
1/4 c mascarpone cheese
1/4 c sour cream
Chilling time:3-12 hours (I've made this two days in advance with no problems)
Directions Place mixed berries in a small bowl and crush slightly with the back of spoon. Stir in 3 tablespoons sugar. (If the berries are already sweet - or if you can get fresh ripe berries - I decrease the sugar and add some Cointreau or other liquor.)
Cover with plastic wrap and set aside.
Spray four 3/4 cup ramekins with cooking spray. (I use one large serving dish instead of individual ramekins and skip the cooking spray.)
In a small bowl, pour 1 tablespoon milk. Sprinkle gelatin over and allow it to soften (10 minutes).
Meanwhile, combine cream, 1/3 cup milk, vanilla, and 1/4 cup sugar in a saucepan. Bring to a boil over medium high heat, stirring often. Remove from heat, add gelatin mixture and stir until melted. Let the mixture cool. In a medium sized bowl, whisk together mascarpone cheese and sour cream until smooth. Slowly add the hot cream mixture into the bowl, whisking constantly. Pour mixture into prepared ramekins. Chill until cold and set (at least 3 hours and up to 12) Run a small knife around the edge of the ramekins to loosen the panna cotta. If that doesn't work, dip the bottom of the ramekin in hot water for a few seconds. Invert ramekin onto a plate. (I just scoop out a serving of panna cotta into a bowl for each person.) Spoon berry sauce over panna cotta. Serve.
2007 Solstice Letter from Tom and Katherine
December 30, 2007
Dear Friends,
2007 has not been an easy year although it has ended on a positive note – Tom is still with us and firing on all six cylinders. In fact if it were not for the radiology and pathology reports we would think he was good for another twenty years. Most of you have received his Ruminations; if you are interested, the are posted to our website and you can find them at http://upislandeggs.com/Ruminations.htm
In June we had a marvelous trip to Italy, spending about three days each in Milan, Perugia, Assisi, and Pesaro, with a side trip to Gobbio. Tom loves the mountain towns but Katherine is convinced that any walk from the hotel through the town and back to the hotel is uphill the entire way. Italy has not fared well under the Euro and there is much more poverty and belt tightening than when we were last there six years ago. This was reflected in the food; we found many delightful eateries, but one had to look for them and the quality of the ingredients was down, even in the high end restaurants. Much to our surprise, we were very much taken by Assisi, the only community we have ever visited where one felt that religion had a positive influence.
Katherine's mother and sister came to chicken sit and explore the island while we were gone, for which we are most grateful. Being in Italy was great; getting there and back was not, even though we used up many of Tom's airline miles and flew business class both ways. We can confirm that these days, flying is for the birds, but our birds deserve better.
Our friend, Gus Ben David, who has a marvelous private bird and reptile zoo on island (you should come and visit it, he has the largest boa in the US) needed the cage in which he kept Java finches for more exotic birds and gave his flock to us. As a result, our sun room now has a marvelous group of inhabitants, about 20 birds total, half zebra finches and half Java finches, both of whom have started to reproduce. Much fun to watch and hear.
In early Spring, eighty day old chicks arrived and took up residence in our living room in a wading pool. After the first two weeks, 50 of them went home to our friend Glenn, and their egg production, like ours, is perpetually sold out. Our two flocks now number about 70, but quite a few of them are elderly (two are 8 years old!) so we expect to lose a few over the winter.
Katherine's big thing this year has been her active participation in WoW (World of Warcraft) a multiplayer (9,000,000) on line game that she relishes. (Look for Wit and her pet pink battle ostrich on the Echo Isles server.)
The year ended, as it has for the past 28 years, with our annual Winter Solstice party. It is hard to tell whether we enjoy the preparation, particularly the cooking, or the party itself more. We suspect the former holds sway. This year, since it was the day before Christmas eve, the crowd was a little smaller, about 130 people over the course of eight hours (noon to 8:00). We did the prep on Thursday, and cooked Friday and Saturday. On each day we were done by 2:00. so it was an easy run up to the party, Guests brought finger food and deserts. Of the stuff we cooked, 3 gallons of chili, 2 gallons of bean soup, 16 pounds of ham, 2 gallons of wild rice salad with dried fruit, two 34 inch long poached salmon, 4 dozen tamales (from San Antonio), and a huge bowl of spinach salad with grapefruit and pomegranate vanished. A great time was had by all, and you are invited to next year's party on December 21st, 2008.
We wish you, and us, peace, health, joy, and tranquility in 2008.
New England Stuffing
3 cups bread cubes for stuffing, (1/2 herbed, 1/2 cornbread)
4 oz crumbled linguica or other sausage, cooked, skinned, crumbled
3/4 cup apple, diced (mixed varieties)
3/4 cup onion, chopped
3/4 cup walnuts, pinenuts, almonds, chopped
3/4 cup celery, chopped
2 tsp rosemary leaves, minced
3/4 cup beef stock, strong
1/3 cup butter
Combine bread, sausage, apple, onion, nuts, celery and toss well. Heat water and butter until butter melts. Toss with bread mixture. Spoon into a 2 quart casserole dish. Cover and bake at 350 F for about 45 minutes. This recipe scales up very well; increase cooking time until internal temperature reaches 160 F. It also freezes well.
Ruminations 10: Not So Glad Tidings
Rumination 10: Not So Glad Tidings.
by Thomas Vogl
December 15, 2007
The good news is that I feel just as hale and hearty as I did when I wrote Rumination 9 in late September and that there are a number of options now open to me that were not available a year ago. That is how fast melanoma research is moving.
The bad news is that in the repeat scans done November 28th, there is evidence of melanoma in two new places my liver. So the issue is what, if anything, to do now. In advance of meeting with Dr. Hodi (yes, Dr. Norris persuaded me to try again, hopefully with far better communication) I reviewed the literature and the available clinical trials.
Two immediately relevant new items in the literature caught my attention because they may provide clues as to how and why the immune system is, or is not, responding adequately. A recent review article, The Genome and Epigenome of Malignant Melanoma [C. Dahl and P. Guldberg, APMIS115: 1161 (2007)] and an item about Dacarbazine (below). Among interesting points in this review article is the fact that the tumor suppressor PTEN, a gene that is often mutated by cancers, is often inactivated in prostrate cancer (which I had) and in 30-40% of melanomas. They also report that aberrations in the Wnt signaling pathway, particularly APC, is related to colonic polyps (which I have and which run in my paternal family) and methylation of the APC promoter 1A is present in about 15% of melanomas. I will be most interested to find out from Dr. Hodi whether the science is far enough along to have these observations influence choice of therapeutic modalities. The paper quotes Miller et al., [N. Engl. J. Med., 355: 51 (2006)] in reporting a median survival of six months (no standard deviation given), which I have already beaten by a factor of two.
I have recently developed a possibly relevant hypothesis: For the past two years I have been annoyed by an unexplained skin rash that waxes and wanes. It last bothered me in Italy in June and was quiescent thereafter until November. In that interval an infection developed in the root of the molar holding my prosthesis, so the dentist and I are trying to save the tooth, rather than extract it. I have noticed that when the rash is at its worst, the tooth is at its best, and vice versa. The hypothesis is that the rash is a manifestation of a hyperactive immune system that is endeavoring to keep the melanoma in check (and fortuitously controls the tooth infection) and is the underlying cause of the remission this Spring. Unfortunately, I have no idea how to test my hypothesis. Any suggestions, anyone?
As those who have known me over the decades know, my track record for hypotheses that have been validated is pretty darn good (I'm really not trying to blow my own horn, it's just historical, and possibly relevant, fact). When I combine this hypothesis, hunch if you will, with the fact that I am adamant about maintaining as rectangular survival curve as can possibly be achieved, the possible therapeutic interventions are limited to relatively benign drugs that give my immune system a good kick. All the standard therapeutic modalities have serious side effects and do not increase life expectancy. Ditto for some of the newer modalities such as Dacarbazine [P. Lui et al, Cancer Treatment Reviews, doi:10.1016/j.ctrv.2007.06.004].
None the less, I am heartened by the number of, to me, acceptable clinical trials, not available a year ago, that are now on the books or imminent. (For those of you interested in reviewing all of them: http://clinicaltrials.gov/ct2/results?term=melanoma.)
In order of my preference, based on trials I knew about as of December 8, and what I knew about them, the three clinical trials in which I would consider participating are:
The Syntra trial of STA-4783 (Elescomol). Not yet FDA approved, but supposedly nearly there. I would be willing to wait a few weeks for it since it appears to be a very promising therapy.
NCT00094653 "MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX010/MDX-1379 Combination Treatment ..." I find this one very attractive because each arm is a promising approach; it requires me to be HLA-A*02901 positive, and I have no idea whether I am or not -- a lab test will answer that question. (The HLA histocompatibility complex acts as a ligand for some receptors (CD94/NKG2) on the surface of natural killer cells and for a subset of T cells that (hopefully) attack the melanoma cells. Its presence is needed to make the vaccine component of the trial effective.)
NCT00495066 "Compassionate Use Trial for Unresectable Melanoma with Ipilimumab (MXP-010).