Monday, February 27, 2012

Metallothionein Deficiency / Abstract and References

PAIN [The official journal of the International Association for the Study of Pain]
Volume 153, Issue 3 , Pages 532-539, March 2012





Metallothionein deficiency in the injured peripheral nerves of complex regional pain syndrome as revealed by proteomics





Summary
This work, for the first time, revealed molecules central in intractable pain in complex regional pain syndrome (CRPS). Metallothionein, a very strong free radical scavenger and an anti-inflammatory mediator is lacked in the affected nerves of CRPS. This work may shed a light in pathology of this intractable algetic disorder and open a new paradigm in this difficult condition.

Abstract
Complex regional pain syndrome (CRPS) is characterized by persistent and severe pain after trauma or surgery; however, its molecular mechanisms in the peripheral nervous system are poorly understood. Using proteomics, we investigated whether injured peripheral nerves of CRPS patients have altered protein profiles compared with control nerves. We obtained nerve samples from 3 patients with CRPS-2 who underwent resection of part of an injured peripheral nerve. Sural nerves from fresh cadavers with no history of trauma or neuropathic pain served as controls. Proteomic analysis showed that the number and functional distribution of proteins expressed in CRPS and control nerves was similar. Interestingly, metallothionein was absent in the injured nerves of CRPS-2, although it was readily detected in control nerves. Western blotting further confirmed the absence of metallothionein in CRPS-2 nerves, and immunohistochemistry corroborated the deficiency of metallothionein expression in injured nerves from 5 of 5 CRPS patients and 2 of 2 patients with painful neuromas. In contrast, all control nerves, including 5 sural nerves from fresh cadavers and 41 nerves obtained from surgically resected tumors, expressed MT. Furthermore, expression of S100 as a marker for Schwann cells, and neurofilament M as a marker of axons was comparable in both CRPS-2 and controls.

Metallothioneins are zinc-binding proteins that are probably involved in protection against injury and subsequent regeneration after CNS damage. Their absence from the injured peripheral nerves of patients with CRPS-2 suggests a potential pathogenic role in generating pain in the damaged peripheral nerves.


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                        Sunday, February 26, 2012

                        The Cash Cow Blues

                        Dear Readers:

                        It's Sunday, and I'm engaged in quiet rebellion.  In lieu of Priests for Equality's The Inclusive Bible: The First Egalitarian Translation, I just read Wallace Steven's Sunday Morning.  "Complacencies of the peignoir" and so on, an elegant paganism.  Today, the poem, like coffee and oranges, is compensation enough for imagined losses; The general flight of generic birds provides enough permanence to sustain the necessary fiction.

                        Oops.  Still there?

                        Typing is difficult.  Using the shift key, inserting accented vowels, fending off cat paws -- all these things, though, force me to use my left hand, now ice cold, withered, and tad bit purplish. In this precise moment, I am having no spasm, anywhere.  Were my head clear of fuzz, this instant could be categorized as phenomenal.

                        Since, however, my brain is encased in spidery filament, I will just do what I set out to do -- cobble together a few of the details that led to my recent downfall, in particular, the role of honesty and fear of litigation in the practice of medicine.  Let's be very particular and insist on the specificity of January 31, 2012, the day before I ended up in ICU.

                        It wasn't the surgery that occupied me.  It wasn't pain, even, or at least not my normal pain.  It was all about those bleeping spasms, those crushing and twisting events that put my experience of CRPS on a new level of fear.  Terror.

                        If you've been a Dear Reader for any length of time, you know that I'm defenseless against this permutation of CRPS.  The only measure deemed effective against this dystonia/movement disorder involves the drug baclofen.  People with CRPS and severe spasm usually cannot get sufficient amounts of baclofen without depressing respirations, etc., so the party line is that administration of baclofen via a catheter inserted into the spine is the best option.  Large doses can be given without the accumulation of deadly side effects.  Because I currently have infection assumed to be caused by implanted materials, and because my spine is riddled with microfractures due to osteonecrosis, the intrathecal approach isn't appropriate.

                        Which leaves me you know where and without a paddle.

                        I am a cash cow for Dr. PainManagement Dude.  I haven't seen him in 2-3 years.  Instead, I see one of his Nurse Practitioners or Physician Assistants for "pharmaceutical management."  Most of that time, I saw A, a wonderful NP who was mostly up to date on trends within CRPS treatments and research.  She pointed me in the direction of the sub-anesthetic ketamine experiment last year.  She left right after that, and was replaced by M, who left, and was replaced by another NP whom I had only seen once.  


                        Dr. PainManagement Dude told me early on in our relationship that there was no hope for me, no treatments left to try.  The more I tried, the more disgusted he seemed to be.  Finally, I learned to just show up monthly, grovel, pay my bills, and stifle any stray flares of optimism.

                        But on 31 January, I needed his help.  I had used and overused the brains and opinions of my very smart group of docs, and most everyone seemed to think that PainManagement Dude might hold the key to successful use of baclofen.

                        So I wrote him:

                        Dr. PainManagement Dude --

                        Hi -- Hope you are well!

                        I had my left shoulder prosthesis removed and a temporary antibiotic-laced spacer put in -- last week, by Dr. ShoulderMan at The Lone Alp Hospital (in southern Tête de Hergé).  This is a battle we've been waging, without much success, for three+ years now.  I am getting awesome care by everyone -- your office, Dr. MDVIP Go-to-Guy, and, of course, Dr. ShoulderMan.

                        In the course of all this, however, CRPS kept getting worse.  I think I have tried everything available in this area, and traveling just seems impossible now.  There remains a chance that I will give it one more go, if this shoulder infection problem gets solved, with Dr. Scwartzman at Drexel, but it will be years from now, based on his schedule/demand.  My hope has been that if the infection/inflammation could be "cured," then my pain levels would go down, not just in my arms, but overall. I still think that may happen.

                        It has taken me this long to understand how truly difficult CRPS is to treat.  I am slow on the uptake!

                        These are the things I need to ask you about.  Please excuse the more basic ones.  I am avoiding the phone because the spasm/pain situation makes it a waste of time for retaining any information [also, I tend to scream without warning]:

                        Which PA/NP is treating me?  I was so used to A, then adjusted to M, and now cannot remember whom I saw last, cannot find my paperwork. She was great, but who was she!?  [I can see now that this reads as a criticism, but I swear, Dear Readers, that I simply needed a name.]

                        I need some flexibility in scheduling with your office.  You all have been very accommodating, but I know a new "provider" may not be comfortable starting off that way.  Fred is having to take me to Dr. InfectiousDiseaseDude's office 2-3 times a week for blood work and dressing changes, on top of regular "stuff," plus he administers the Vancomycin by PICC line.  We're exhausted.  Anything anyone can do to reduce stress will be appreciated.  Every Monday and Thursday, we will have to be out and about until roughly 11 am, so is there someone we could see at your office between 12:45 and 2:00 pm?  If not, we'll figure it out...



                        The medication situation:  I have enough methadone (10 mg tablets, though, that I break in half) and endocet for about 3 weeks, enough amitriptyline for a few months, but whether I've enough baclofen is anyone's guess, as my need is rapidly changing. Dr. MDVIP Go-to-Guy has been prescribing it through my mail order pharmacy, Medco.  I have had to take more endocet and baclofen than usual in the past two weeks but am planning to taper back over the coming week. [I am annoyingly honest with my health care providers.  A few appreciate it;  Most cringe.]

                        SPASMS: In CRPS, I don't know what doctors call them -- spasms, cramps, dystonia, WHATEVER! I cannot tolerate them at their current intensity and frequency. You probably hear this all the time, but I did not know it could get like this. This is a whole new animal... Right now, I am at my "calmest" point in a week, and the pain with each spasm -- now in my hands (they flinch, involuntarily[?], about every 20 seconds) -- shoots up to 8-9/10, then down to my usual 5-7/10. Both legs can be involved at the same time, to the extent that my foot is pulled toward my head, my hamstring is pulled in a different direction, and now even my left hip joint is involved. The last round of that began at 8 pm and did not decrease enough to make any difference until around 9 this morning.  They spasmed throughout the day.  I had what seems to me a lot of baclofen already, buteven that, obviously, did not work.  I want to take as little as is necessary to relieve this horrid pain.   I think I will need both a short term and a long term solution, unfortunately.  Intrathecal baclofen is the usual long term approach but that probably isn't a good idea in someone already fighting an infection, plus... I just don't want it...

                         

                        I am sure the correct response is to tell me to "come in to the office." I hope there is an alternative.

                        Thank you so much for "fielding" this email! I am trying to stay organized but it's hard.  Please tell me what is not clear and I will try to answer more succinctly.




                        I did not receive a reply from Dr. PainManagement Dude.  Instead, I got this:


                        Hi XXXXXXXXXX,
                        I was the nurse practitioner you saw at your last visit. It was good to meet you!
                        Please discuss with Dr MDVIP Go-to-Guy the amount of baclofen you can take safely and what else can be done to treat the spasms.
                        We require everyone on narcotic pain medications to come visit monthly for medication refills, so please make an appointment before you run out of medication. I have asked B from our office to call you about an appointment.
                        Have A Good Week,


                        ButterMouth, ANP
                        "Have a good week"!?  If only one of us had known how the week/month was about to unfold...
                        Proof of my capacity to "zip it," evidence of my claims of concision?  Here's my response to ButterMouth:


                        Hi ButterMouth,


                        It was good to meet you, too.


                        Thanks for your response.


                        XXXXXXXXXX

                        To any medicos out there:  Please allow your patients to be honest in their communications with you.  Please don't see legal issues under every rock, something sinister behind every inquiry.  Easy for me to say, I know, but then, whose blog is it, anyway?

                        When a person begs for help, please help.

                        February 1, 2012 proved to be a "Terrible, Horrible, No Good, Very Bad Day," in small part due to PainManagement Dude's studied non-responsiveness.  Shoot, he probably could not have changed the outcome... but I might have felt less abandoned, safer, might have had a little hope.

                        What worries him so about having a medical opinion, a suggestion, a possible way to proceed? Did he fear that his response might be posted on my blog?



                        Ridiculous!




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                        Saturday, February 25, 2012

                        Specialists



                        it's been a difficult day.

                        on the other hand, burly firemen and wise-acre EMTs did not traipse across my freshly mopped floors, and no one told me the doctor on call had to approve the benadryl capsule i needed for a dire case of itching.  when there was despair -- somewhere around 1:58 pm -- there were also three cats and sunshine.

                        the wound care nurse came and provided a fast and efficient assessment and dressing change.  like me, like the wound care team at the LTAC, he is reluctant to reapply the wound vac -- it is healing well on its own. he's gonna voice his opinion to th doc on monday.

                        i don't need another machine to trip me up or more wire/cords to touch my arms or legs..

                        i'm feeling some anger.

                        today's amusing anecdote?  the three conscious encounters with the hospitalist who admitted me to the ICU from the emergency department -- obviously, she and i met while i was unconscious. how rude of me.

                        first encounter:  "well, hello!  you are the lovely lady with the two beautiful lovely daughters who came to my emergency room last weekend...oh! what is wrong with these legs?" [reaches out... and yes, grabs one.]

                        second encounter:  "well, hello!  did we get you set up with a cpap machine?  when is your cardiologist coming to see you so we can order that test?" [don't ask me!  don't use cpap, didn't know why my cardiologist should even be consulted.  so i continued eating a yogurt...]

                        third encounter:  this was the day i saved my own life.  in the midst of extreme muddle, it occurred to me to doublecheck on my "usual" meds, especially corticosteroids, as i have adrenal insufficiency.  turns out she'd discontinued ALL my meds.  no steroids for 6 days, shining a light on my increasing weakness, confusion, etc. this despite a duly delivered medication list, a medical alert necklace, and the presence of fred.  also, i'd just had surgery there a week earlier -- one of seven shoulder operations in the last 3 years.  in other words, you'd have to be willful in your ignorance NOT to know what meds i need.  she  cruised in after the nurse paged her in a panic, offering me this explanation:  "i didn't do that!"  panicked eyes.  never saw her again.

                        "the lovely lady with the two beautiful lovely daughters" would've been more understanding, i am sure. and sometimes i do miss my cardiologist -- he once told me that i'd never die so long as he was caring for me.

                        ah, specialists!


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                        Friday, February 24, 2012

                        To My MDVIP Go-to-Guy and His Nurse Sidekick

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                        rough strife

                        howdy hi, there, buckaroos!

                        taking wednesday as reference point, some things are better and nothing is worse, so i'm declaring today a holiday.

                        when i shut my eyes last night, i was afraid.  my body was sending conflicting signals. doom doom THUD doom doom THUD pulsed my temples.  desperate for a cool cloth, or several, the terror of trying to stand up overruled all desire.  i made myself cry to release tension, then i slept.

                        the home-based wound care service hasn't happened yet and forms the basis of my anxiety of the moment.  i am employing the tried-and-true method of doing something to trump the nihilism of worry.  note that something does not entirely mean anything.

                        don't fall for corporate preciosity, dear buckaroos. at the LTAC [long term acute care], the reason they were stringing me along and refusing to discharge moi to marlinspike hall involved convoluted difficulties in arranging for wound care nurses to visit the manor.  insurance minutiae, complicated machinery, documents, manuals... i expected to hear "Best Practices" at any moment...

                        i was cowed by the evidence of the heroic effort being made on my behalf, but against the good judgment of the best medical minds housed within that five-floored, modular facility.

                        a plucky social worker, however, let slip that the problem involved the one home health agency with which the LTAC was contracted:  "the guy who does wound care is on vacation."

                        and so it was that i roared, and after roaring, left.

                        my MDVIP go-to-guy and his able sidekick had offered to help arrange for home health services once i flew the coop.  they're wonderful and they mean well... by which i mean, of course, that the first company they called didn't take my insurance -- and they didn't think to ask.  we live in different worlds, we do.  so, bushy-eyed and bright-tailed, i was up at 4 am yesterday, in anticipation of an "intake assessment" by wound management.

                        i ended up carefully rewetting the gauze crammed in the gaping maw of the incision... and blithely mouthing schtuff about sufficient unto the day, not borrowing trouble, sparrows, and lilies.

                        we've made progress today, but it's 3 something on a friday, when even the highways of tête de hergé (très décédé, d'ailleurs) can cause traffic headaches.

                        there was a fair amount of drainage, but it looked like innocent blood, and did not smell.  it itched like a mofo, but it did not smell.

                        with the exception of cramming gauze into the aforementioned gaping maw, i just copied the work of the LTAC's wound care specialist.  i was a nervous wreck.  i engaged in more negative self-talk than in the whole previous week.

                        maybe i'll get some help over the weekend.  if i infect this wound somehow, i will never forgive myself.  [yay! there is an agency wound care nurse coming tomorrow morning!]

                        the spasms returned, but the pain is less than it would be were i still trapped by a hospital bed, complete with rails, a bed frame,and a flying trapeze...

                        i need to rest now.  various sweetie-pies have told me that things get better after periods of rough strife*.





                        * i love lynne sharon schwartz... and recommend her novel, rough strife.  better than that, though?  disturbances in the field...




                        *To his Coy Mistress
                        by Andrew Marvell
                        [....]
                        Now therefore, while the youthful hue
                        Sits on thy skin like morning dew,
                        And while thy willing soul transpires
                        At every pore with instant fires,
                        Now let us sport us while we may;
                        And now, like am'rous birds of prey,
                        Rather at once our time devour,
                        Than languish in his slow-chapp'd power.
                        Let us roll all our strength, and all
                        Our sweetness, up into one ball;
                        And tear our pleasures with rough strife
                        Thorough the iron gates of life.
                        Thus, though we cannot make our sun
                        Stand still, yet we will make him run. 




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                        Wednesday, February 22, 2012

                        i am home

                        i'm home.

                        i signed out "against medical advice" after being carted by ambulance from the effed-up hospital to the effed-up LTAC facility [a nursing home in disguise].

                        many long and funny stories about such nether worlds are queuing up for future blog post status.

                        a total of 26 days in hospital, ICU, LTAC.  a wound care service arriving early in the morning, since to make my escape, i had to force the disconnection of my gaping shoulder wound from its pal, the "wound vac."

                        i had a second surgery on feb 13 [correcting a boo-boo from the more major one on jan 23] and the decision was made to hook me up to an oreck...

                        don't anyone dare tsk-tsk me over ducking out AMA -- trust me, i was getting weaker and more spastic by the hour.  there were people on my side -- notably the doctor, the floor manager, the social worker -- but they cannot change by fiat the ignorance [wielded on my legs like billy clubs] that reigns among their staff.

                        my favorite RN? i asked her to please look up CRPS.  she snapped, "i will not!"

                        and then told me she was going to have the doctors "evaluate [my] legs, 'cause that ain't right!"

                        so... god bless us all, be kind to one another, but take care of yourself when no one else will.

                        i'm gonna take it verrrryyyyy slow for a good bit.

                        but i am home.


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