Immune System Involvement with Endometriosis

I love doing research, so of course I have found out a few interesting things about endometriosis.

The nutshell version:
Baboons get endo too. It may be an autoimmune disorder. Contrary to popular belief, there is no evidence that the immune system attacks embryos in endo. Weaknesses in the immune system can promote and sustain endometriosis. The immune system of women with endo pumps out too many of certain kinds of molecules. Once those molecules can be more easily isolated in the blood or abdominal fluid of women with suspected endo, the invasive approach of diagnosing endo through laparoscopic surgery could be avoided. Proteins that bind to the molecules and thereby prevent them from attaching to endo cells instead are already in development. This new form of therapy could be used to treat endo noninvasively while keeping a woman's estrogen levels and ability to conceive intact.

The longer, more descriptive story:

*Baboons & Endometriosis*
As a primatologist I think it's interesting to know that baboons get endometriosis too. Apparently 83% of baboons have what's called "retrograde menstruation" which occurs when endometrial tissue from inside the uterus flows backwards through the fallopian tubes and out in to the abdominal cavity. This is one theory for the origin of endometriosis. However, retrograde menstruation occurs in about 80% of human women too and only 10% of women actually have endo. 25% of baboons have it. So, that's not much of a theory.

*Immune System Involvement*
What do I think is happening? Well, affected women could have been born with stem cells that become endometriosis at puberty when they get bathed in hormones, specifically estrogen. That could be the problem. Or, every woman is born with cells that become endometriosis but they are normally removed by the immune system. Affected women might have an immune system that fails to recognize and then kill the endo cells.

It's important to know the cause of endometriosis so that better therapies can be developed. Currently the standard procedure is to treat it hormonally by getting a woman to stop producing estrogen, or at least not so much of it. If a woman wants to keep endometriosis under control, her only option is to prevent ovulation. For women who want to produce a family, that's not much of an option.

"Although endometriosis can be treated using hormonal suppression, there is need for non-hormonal drugs, which can inhibit the development of endometriosis and alleviate pain or infertility without inhibition of ovulation. New molecules that modulate immune function in endometriosis should be the targets for future research" say the authors of an interesting study published in the Journal of Reproductive Biology and Endocrinology.

The article suggests that what actually happens in endometriosis is that cytokines (proteins synthesized by immune cells which promote inflammation) make endometrial cells proliferate (divide and multiply) and implant/adhere to nearby organs (like ovaries, bladder, colon, etc). So, inflammation is definitely the problem and one particular protein called TNF, tumor necrosis factor, is the real culprit.

Given that inflammation is associated with endometriosis, it stands to reason that immunosuppresive therapy (corticosteroids) could provide relief as it does for a wide variety of auto-immune disorders like rheumatoid arthritis. However, baboons who received the drugs didn't show any regression of endometriosis. The authors hope that more specific immunosuppressive drug therapies could be developed so that rather than attacking the entire immune system, only one part of it, perhaps the TNF, could be targeted.

*Endometriosis May be an Autoimmune Disorder*
The article also suggests that endometriosis may be an autoimmune disorder - the immune system produces antibodies that go unchecked. They secrete too many cytokines and too much inflammation, thus the problem. Meanwhile, other cytokines tell the endometrial tissue to vascularize (form new capillaries). What does that mean? Basically a superhighway is built to transport ever more inflammatory cells to the area. It grows like cancer.

*Impaired Embryo Implantation*
I often come across statistics and anecdotes from women trying to conceive with endo that suggest one reason women with endo have trouble getting pregnant is not that the fallopian tubes are blocked as is commonly thought, but rather that the fertilized embryo fails to implant into the uterine wall, i.e. the place where endometriosis is actually supposed to grow. This explains why so many women with this condition experience repeated "chemical pregnancies," miscarriages, and IVF failure.

The article has this to say, however, "The failure of NK cells to scavenge autologous endometrial cells may allow development of endometriosis. It has been hypothesized that natural killer cells in the endometrium can attack the implantation site of the embryo as it tries to attach to the uterine wall and that autoantibodies can play a role in this process. However, a recent review has shown that there is no proven relationship between abortion, recurrent abortion and endometriosis, and at present there is no proof that endometriosis- associated subfertility is caused by impaired embryo implantation."

-- Translation --
One kind of really-important-for-keeping-you-healthy, immune cell (natural killer cell) was thought to prevent the embryo from implanting in the uterus, but this turns out to not be the case. In fact, there is no evidence that failure to implant is the reason women with endometriosis have trouble becoming pregnant.

*The Immune System - What's Really Happening*
So what the heck is going on with endometriosis and the immune system?
T-cells (those immune cells that attack "germs" and what not and are depleted in people who have AIDS) are less toxic to cells they are supposed to kill. So, they don't kill the endometriosis like they are supposed to in affected women (and baboons!). Also, various other molecules that normally work to initiate programmed cell death (apoptosis) and also mark cells for elimination by the immune system - fail. So, endometriosis flies under the radar of the immune system and then fails to respond to the immune system's own form of euthanasia. Lovely. Absolutely lovely.

*New Diagnosis & Treatment Ideas*
The authors of the study I read think that invasive surgery, the gold standard for an official endometriosis diagnosis, could be rendered unnecessary by measuring the levels of two cytokines in abdominal fluid: TNF and IL-6 (interleukin 6). They say, "Endometriosis could be diagnosed if TNF-alpha levels in PF were higher than 15 pg/ml (100% sensitivity and 89% specificity) and if IL-6 levels in serum were above 2 pg/ml (90% sensitivity and 67% specificity)."

Endo can be treated by surgery and by hormonal suppression (progestins, continuous use of oral contraceptives, danazol, GnRH agonists). Danazol is also an immunosuppressive drug (steroid) that in addition to turning a woman into a She-Man, also makes her immune system quiet down. It shuts of TNF and some other cytokines like IL-1 (not 6).

The authors would really like to see other forms of treatment that don't deplete estrogen and therefore retain a woman's ability to not only get pregnant, but still look feminine. I would appreciate that too! Mouse, rat, and baboon models are being used to develop proteins that will give stuff like TNF and IL-6 something else to bond to instead of the endometrial cells. Already, a protein (recombinant human tumour necrosis factor-binding protein-1) has been shown to decrease endometriosis by 64% - in mice. Cool.

More thoughts on ENDO

In the language of the iVillage message boards I have started reading on the recommendation of my SIL, AF arrived today with the expected discomfort. I've been on Aleve and glued to a hot pad all day with periods of nausea that come and go. I thought I could get some work done today, but didn't have the patience to monkey around with spreadsheets.

Earlier this morning I felt better at one point and got out my laptop to download the latest surveymonkey data in the hopes that enough people participated over the weekend to fill up a cell I still need participants for. I got as far as requesting the data so that I can download it when surveymonkey makes it available. It can take them anywhere from a day or two to 15 minutes to make it available for me to download. It takes me an afternoon to get it all into SPSS depending on the number of people.

I was just about to check back with surveymonkey when I got inundated with phone calls. First my mom (who is normally absentee mom) called to tell me she found the perfect post-surgery outfit. I have been looking for something ultra-comfortable around the waist because the gas they pump in for the surgery is decidedly uncomfortable according to everyone who has had the procedure. Then my SIL called just to say hi and pass on warm thoughts. I called the kennel to get the doggy hotel squared away; in haste I reserved their kennel stay for the day of the surgery and the day Mr. Sleyed needs to get back to work, totally forgetting that we are leaving early so I don't have to do the day-before-surgery prep in the car. I have to totally void my digestive system, to put it delicately. I can't eat anything that day either.... so, we are leaving early so that whole business can happen at my home away from home during the lap experience. Fortunately the kennel had space and I was able to straighten out the problem with over-vaccinating our dogs for kennel cough.

Finally I was on the horn to find out how much it will cost us to get the bloodwork done that my FBCD (fancy big city doc) wants me to get done to find out if my hormone levels will allow me to conceive and sustain a pregnancy. Insurance won't cover the tests because they don't cover any infertility diagnosis or treatment. Rat bastards! It's absolutely assinine that they are allowed to get away with that at the same time they cover insanely expensive end-of-life care and conditions people earn through bad habits. Some states actually have passed laws to make insurance companies cover infertility treatments if they provide pregnancy care. Unfortunately WA is not one of those states. My former state of MT is. Weird. This list identifies states with mandated infertility coverage. The cost of the bloodwork is $420.

I would be surprised if they revealed anything abnormal, but I suppose he wants to know the results so that he can help me figure out what the best post-op treatment will be. Getting pregnant is one approach, but if I can't do that w/o some form of treatment (who knows the cost of that???) then I may have to go on BCPs until I go through menopause. Endo isn't something that can go untreated. If BCPs don't work I may have to take Lupron which gives you menopause and all of the side effects early. I don't want to become a She-Man in my early thirties !@&^% Yuck. If I am unlikely to get pregnant according to the tests, and the cost of treatment to try to get me pregnant is too much, well, then I will have to keep my fingers crossed that BCPs will keep my endo from getting worse and also get used to the idea of only ever having fur kids.

With my time spent laid up today I searched blogger for people who have endo and have had or will have laparoscopic surgery. I have found and read quite a few so I know what to expect. This story of one woman's laparoscopy was the most informative. If you want to know what will be happening to me in a few weeks, check it out.

Unfortunately I also read a lot of stories about people never being able to conceive even after the surgery. And - to make me really worry - quite a few have had more than one laparscopy. One even had more than TEN! Zounds! Why? The endo aggressively comes back even after it's surgically removed, and adhesions (scar tissue) forms where the endo was cut/burned away. That can actually make pain worse. So....

Now I am feeling like there is a chance that this surgery may actually make my pain much, much worse in time, and I will have to have another lap to get rid of the pain. Sheeeesh!

Maybe I should call Ruth (who is incidentally a gyno) so she is actually Dr. Ruth, just not the Dr. Ruth.

*********
The BEST thing that happened today -- I received a card in the mail today from my dissertation advisor. There's a chimp holding a beach ball and wishing me well with my surgery on the front, and inside a hopeful messgae about being well enough to get back to monkeying around again soon. It was really so sweet and unexpected that I actually felt some regret for all of the times I complained about her being a horrible advisor. She really came through, in a small albeit symbolic way.

Fair Medical Care?

Is a medical system fair if you have to be proactive and intelligent in order to get better care?

When I called my doc's office a few weeks ago to describe my symptoms, I had a good guess about what the problem was - endometriosis and endometrial ovarian cysts.

For those of you who don't know, endometriosis occurs when the cells that line the uterus grow outside the uterus too. The cells grow and shrink in unison with a woman's menstrual cycle and unlike the cells that grow inside the uterus that get shed each month when a woman doesn't get pregnant, the cells that grow in the wrong place have nowhere to go. Women with endo essentially bleed internally each month. The cells can grow anywhere in the pelvis and often attach to the ovaries, outside of the uterus, on the bladder, bowels, and sometimes even higher up in the lungs. It's really nasty stuff but usually is not cancerous. It is, however, graded like cancer to describe its severity. So, someone could have stage 3 or stage 4 endo. Severity of symptoms is not correlated with severity of endo. It causes pain and cramping (more than the usual menstrual cramps that women get), diarrhea, pain with intercourse, fatigue, and infertility. Not all women who have endo have symptoms.
I do. And - it sucks.

After speaking with my doc's nurse, I got orders to go get "monkey wanded" in the language of the iVillage discussion group I've been reading. That means I get to lay down in a dark room half naked while an ultrasound technician moves a gizmo around in my vagina that looks more like something you'd see in a sex toy shop. She showed me the 7x6x5 cm cyst on my left ovary and pointed out that my uterus is seriously catawampus. It's supposed to be pointed up at about 11 o'clock and straight. Mine is C shaped with the top part of the C pointed at about 4 o'clock. This kind of retroverted uterus is common in women who have endo. The uterus can get mishapen due to adhesions of endo scar tissue that attach the uterus to something else.

I got sent to a specialist the very next day who told me absolutely nothing new. That's because I had already researched my options - go on drugs that put me into early menopause with all of the well-known side effects or have a surgery, either laparoscopic or a laparotomy. Another option is to go on birth control pills or get pregnant because both make the endometrial tissue regress.

All of these are temporary solutions because there is no cure for endometriosis - not even a total hysterectomy and removal of both ovaries will make it go away forever. The only solution is to have all of the endometrial tissue surgically excised - removed completely, down to every last microscopic cell, which is of course, impossible in practice. Getting pregnant or taking drugs to stop ovulation only holds the growth of endo at bay. Surgical removal of the endo results in good prognosis for pain management and fertility. Women with moderate to severe endo (stage 3 or 4), have a 40% better chance of getting pregnant in the year after the surgery compared with not having one.

She wanted me to go on the menopause drugs. No thanks. I'd like to keep trying to get pregnant. Having the surgery may be my only way to achieve that. Besides, going on drugs just postpones that and doesn't remove the endo. I want the surgery I told her.

Then she told me that it would have to be a laparotomy due to the size of my cyst. That would mean a sizable incision and at least 6 weeks recovery time. I told her I want to have the surgery done laparoscopically and explained my situation with needing to finish my dissertation in the next three months. I don't have time for a laparotomy - especially when it could be taken care of laparoscopically, a procedure with a one week recovery and fewer risks. Plus, through my research I found out that the success of surgery is completely dependent on the skill of the surgeon and his/her experience in recognizing endometriosis. If someone was going to open me up to scrape out the junk, I sure don't want a small town hack doing the job.

I insisted on a laparoscopic approach. She called Seattle Reproductive Medicine and got me hooked up with a surgeon who is experienced at laparoscopic surgery for this problem. My surgery will happen in February a few days before my birthday. It will be an outpatient procedure and I should be able to go home the same day.

The only reason I am having the better procedure in more experienced hands is because I was proactive enough to research the options, smart enough to comprehend the medical terminology and weigh it, and confident enough to assert my choice. If it hadn't been for that, I'd be having a laparotomy in Walla Walla.

I am very fortunate to know enough to insist on going elsewhere for medical care - and - am even more fortunate to be able to go to an expert in Seattle and have insurance that will cover 80% of the cost of the procedure. Not everyone is so fortunate.

Too Much Information

Yahoo! Over the weekend I got all of my data into SPSS and cleaned up - i.e. naming variables, computing new ones based on the received data, filling in the blank spaces, adding new data... It took several hours but now BOTH studies are ready to go. I can begin analyzing any time.

I even have 80% of the responses I need for one cell that I inadvertently screwed up by having the wrong experimental treatment condition assigned to it. Given my complicated 2 x 3 x 4(3) design, I think it's pretty decent to have made only two mistakes in assigning treatment conditions. If I had had no other thing going on at the time, I might have been 100% but I was teaching three classes at the time - one for the very first time. It's sometimes difficult to remember exactly how busy I was!

The end is definitely in sight now. It sure will be wonderful to finally get this dissertation bumped off.

There's just one thing. It's about the size of a tennis ball and it has to be dealt with right away. I don't know how everything will turn out, and all I can do is hope for the best but prepare for the worst (which would be a major surgery and some amount of recovery that may mean I won't be able to defend my dissertation this spring as planned). Even if I have to have a major surgery, I am confident that I will still be able to go to Japan this summer as planned. And, if I have to defend after I get back or sometime after the deadline for spring graduation, I will still be able to participate in the next year's commencement ceremony. After all of the nuisance of grad school, I sure don't want to miss out on the hoopla of getting hooded. I will be the first doctor in my family.

When faced with uncertainty, I take great comfort in acquiring information. Hell - I thrive on information acquisition regardless of circumstances! However, I am one of those people health psychologists say thrive on information and feel better with more of it. It's sometimes hard to imagine there are people out there who are the exact opposite - the kind who would prefer to be willfully ignorant because that feels better. Not me. I went so far as to locate papers my new doc has published... Is that overkill?

To prepare for what might happen, I spent time making phone calls and sending out emails to my committee. I actually called my advisor at home (the one I have ranted about before). She was very supportive, which I very much appreciated. I've got a plan now, but I am still trying to figure out what to do about dog care while My Man With Gills is at work. Giant Newfsance, the Baroness von Roughenhausen, is a bit much to deal with even when everything is wonderful. I might need somebody around for a while who can let her out do her business, entertain her, and reel in her enthusiasm so she doesn't injure me (or Max) while I am in recovery. I am hoping I can have "my buddy" taken care of laparoscopicly so that won't be necessary.

I think I am done being scared, for now.

Dog Day Afternoon

Odd things have been happening lately in the canine camp. Katy, the water-loving Newf, who now weighs around 100lbs at 10 months, managed to fit all of herself in the bathtub. No one asked her to climb in; she just volunteered.

Earlier in the week she had to take a bath because she dove into the duck pond at Whitman while crossing the stepping stone bridge from one side ot the other. Crossing this way is something my husband and I have done for YEARS. It definitely marks us as Whitties. One night while walking the pups, my favorite guy decided to try to cross that way with Katy. I looked up skeptically, thinking - oh I dunno - maybe she'd be like Max and refuse to cross. Nope - she did exactly as you'd expect from 100% Newf: DIVE IN!! She swam around a bit and played in the duck muck. She had a grand time - and had a smell to match. Thus, the bath.

Maybe she was asking us for another? In any case, she sure looked adorable.

In other Newf news, she is still badgering the hell out of Max. She chomps at his neck, ears and back while attempting to lay down completely on top of him. Given his 30 pounds vs. her 100, he's justifiably freaked out. He snarls, attempts to bite, and sometimes squeals as if she's injuring him. I always have to pull her off of him. If I find it stressful, I can only assume Max finds it a totally horrible experience.

This all happened after we brought them home from staying at a kennel for 11 days over the holidays. At first she attacked him when I tried to take him outside. Once I got that under control she switched to attacking him after she eats a treat. They get treats at the same time, and she always finishes hers first. When she does she goes over to try to take his. He stands his ground and she just scrounges crumbs. No snarling, no biting. Then when Max is finished with his, she attacks. It's awful.

After one of their brawls they always make up.

Here they are getting snuggly about an hour after their spat this morning over rawhide "cigarettes."

Not a Recent Photo

Inspired by my favorite guy and a holiday spent scanning in old photos, I thought I'd share this one.

I hate spreadsheets!

Before I realized that I had a MAJOR flaw in my data I thought I would be able to get both studies imported into SPSS from Excel and cleaned up by yesterday. Ha ha ha. What a nice thought.

It all started when I saw some numbers that didn't jive. I scanned the spreadsheet and compared columns and rows for THREE hours and for all of those three hours I thought my data was so completely screwed up that if I submitted a dissertation based on it would be fraud. I thought I was screwed. Seriously screwed. Tears of utter agony were shed.

Then, my Hero came home for lunch and helped me figure out the solution.

It involves manually correcting the mistake over 2000 participants. So, for that afternoon and all of today I have been writing down what the correct number should be for all 2000 participants. Over the next several days, I'll be entering them into SPSS manually.

What fun.

But, at least now I can have confidence in my data. And, by doing this I found some other errors that I have now corrected. I need to keep the study up and running a little while longer. So, really I now need 2 more females and about 33 men to fill out the cells that contained the error.

It all sounds so manageable now, but I have been staring at a spreadsheet for about 6-7 hours a day and I hate them.

What's more? My Hero Who Saved My Bacon and I really enjoy playing Scrabble. I tried to sit down to finish a game we started a few days ago - before the Spreadsheet Disaster Now Averted - and as I scanned the board looking for my best play I could see nothing but little boxes filled with data. And Sudoku is ruined for the time being. I love solving sudokus but they look like spreadsheets too! No wonder that my first choice of break activities was to look at a Victoria's Secret catalogue instead!

New Iraq Ambassador a Whittie too!

Who knew? Ryan Crocker, Bush's choice for the U.S.'s next ambassador to Iraq, is a Whitman College alum.

Early in his career with the State Department he perfected his Arabic by going to Jordan to live with Bedouin.

He's worked for the State Dept for years and has been ambassador to many countries in the Middle East, including Lebanon, Syria, and Kuwait. His first post was to Iran, one year after graduating from Whitman.

The Times article suggests that because of his intimate knowledge of the area and its culture, Crocker might be able to make some positive changes with deft diplomacy. However, other opinions suggest that he's not up to the challenge of ending the civil war. Perhaps no one is.

Read the Times article here.

Maximum Dog Drool

Courtesy of my grandpa - the perfect make-believe image of Maximum Katy and I riding along in a Mini. My BIL#2 let me drive his over the holidays and I can easily say that if I had an extra 30 thou sitting around I would totally buy one - in red. I'd want a custom flag for the top too.

The Data Is In!!

I haven't posted in a while because my nose has been to the grindstone dealing with all of my dissertation data. It has taken about 14 months to get it all, but more than 4,000 people later, I finally have all of my experimental cells filled with the minimum number of respondants I need to have enough power for my analyses.

My Excel files require quite a bit of formatting to get them to the point where I can import them into SPSS for the analyses. My data is spread out over four different Excel files in which most of the cells on the spreadsheet are empty. I have to sift through each one to find the spot where my data actually is located. This happened because I had to direct people to different questions based on their responses to previous ones. This means most people skipped over most of the questions, thus the blank cells. I need to get the actual data into the correct location on the spread sheet. If the four Excel files represent the United States, I have to get the data into WA state when it may actually be located over in Minnesota, Ohio, or even MA. The Excel file sare so large that some of my data is so far away I have to go retrieve it from France or China. As I said before, I have a lot of manual and visual scanning to do to find the data amongst the blank cells and then copy and paste it into the right spot. I have 1,000 of these left to do and get about 500 done in a day.

And - that's just the formatting for one study. At least that's the tricky one. The formatting for the other study can be done by writing some code to make Excel make the changes for me.

Formatting is totally mindless so I find myself listening to music or TV while I do it. There really is some ridiculous stuff on daytime TV. Evidently my body is acidic and I need to buy some pills to cleanse myself of all of the toxic things I ingest. What garbage!