Saturday, May 26, 2012

Bits and Pieces: CCSVI and the FDA – Oy Vey!

Sign leaving Brooklyn on Williamsburg Bridge s...
Sign leaving Brooklyn on Williamsburg Bridge saying "Leaving Brooklyn: Oy Vey!" (Photo credit: Wikipedia)
I wonder if any Wheelchair Kamikaze readers are unfamiliar with the phrase "oy vey"? Given how shockingly worldwide the readership of this blog is, I have to imagine that at least a few out there in Internet land aren't familiar with the term, so what the heck, I might as well go ahead and define it.

"Oy vey" is a Yiddish expression, whose literal translation is something along the lines of "oh, pain". "Oy" and "vey" are ancient Jewish words that are roughly equivalent to the modern English word "woe". In the course of a typical day, a Jewish person who was raised in largely Jewish community, even an extremely secular Jewish person like me, may utter the phrase about a dozen times. It's kind of a catchall suitable for any situation that even hints of trouble, and can also be used when confronted with something so comically stupid as to be almost tragic, allowing "oy vey" to punctuate situations from humorous to disastrous.

So, if when watching a New York Mets baseball game the shortstop allows the ball to pass between his legs, a softly expressed "oy vey", accompanied by a knowing smirk and a shake of the head, is likely voiced by a significant portion of the viewership. Of course, if the same mistake is made at a crucial, game changing moment, the correct response would be to throw a shoe through the TV set. However, if one were to receive a phone call with the news that Aunt Ida was rushed to the hospital unconscious and foaming at the mouth after eating an especially dense matzoh ball, an appropriate reaction would be a loud "OY VEY", expressed with a dramatic tenor of overwhelming dismay. It's a very handy phrase, suitable for most any catastrophe, terrific or tiny.

Okay, all of this has absolutely nothing to do with multiple sclerosis (except that a diagnosis of multiple sclerosis is definitely a reason for a booming and heartfelt "oy vey", followed by a string of stronger expletives in whatever language the patient chooses), but the info about to be proffered for your consumption will be MS related, at least most of it. Every now and then some non-MS related bright and shiny thing will distract my attention and find its way into these posts, but it's my blog and I'll digress if I want to.

And now, on with the show…

♦ As the title of this post indicates, the US government's FDA (Food and Drug Administration) recently weighed in on CCSVI, in the form of a "Safety Communication" (click here) that detailed the administration's concerns with CCSVI, the treatment procedure used treat it, and the clinical research studying the condition.

According to the FDA, the statement's purpose is to:

"… alert people with MS to the risks of serious injuries and death associated with procedures to treat chronic cerebrospinal venous insufficiency (CCSVI). Furthermore, the benefits of these experimental procedures have not been proven, and their promotion as a treatment for MS may lead people with the disease to make treatment decisions without being aware of the serious risks involved.

This communication is also intended to notify physicians and clinical investigators planning or conducting clinical trials using medical devices to treat CCSVI that they must comply with FDA regulations for investigational devices."

The FDA communication then goes on to summarize what it sees as problems surrounding CCSVI, including questions about the existence of CCSVI as a condition requiring treatment, the inconclusive research currently linking CCSVI to MS, and the uncertainty over whether treating CCSVI relieves any of the symptoms of MS. The statement then details the sometimes serious complications that have rarely resulted from CCSVI venoplasty. It asserts that CCSVI trials constitute "significant risk studies", requiring clinical investigators to file for an "Investigational Device Exemption" (IDE) before undertaking CCSVI trials, because the catheters, balloons, and other equipment used during CCSVI treatment procedures were not designed specifically for such purposes.

At the same time, the paper also states that "The FDA encourages research to evaluate the relationship between CCSVI and MS and to characterize the safety and effectiveness of treatment procedures. Rigorously conducted, properly targeted research can provide a more complete understanding of the existence of CCSVI and any relationship between CCSVI and MS, which will help people with the disease and their clinicians make the best treatment decisions."

The Society of Interventional Radiologists quickly responded with their own statement (click here), which basically acknowledges that there are questions surrounding CCSVI and supports "the urgent formants of high quality clinical research to determine the safety and efficacy of interventional MS therapies…"

Of course, all of this has created quite the hue and cry among online CCSVI advocacy groups, who point out that the FDA statement overstates the risks involved in undergoing CCSVI venoplasty, given that upwards of 25,000 patients have had the procedure, and only a relative few have suffered from serious side effects. Unfortunately, the vast majority of the patients already treated for CCSVI have been inadequately tracked, in my opinion to an egregiously woeful degree, so no one can say with absolute certainty what the rates of complications are (or, for that matter, how beneficial the treatment actually is). Although some studies have come out asserting the relative safety of the CCSVI treatment procedure, most of these studies only looked at patients immediately following treatment, and did not track them in the months and years afterwards. Had a majority of the patients who have undergone CCSVI treatment venoplasty been adequately tracked, many of the questions and controversies we are now faced with might very well have answers, but that horse has already left the barn.

While the FDA warning does not blatantly misstate any of the facts, the emphasis it places on the nebulous nature of the current state of CCSVI knowledge and what appear to be rare adverse events is somewhat troubling. More troubling, though, is the possibility that, through the use of Investigational Device Exemptions, the FDA could curtail legitimate CCSVI research, by denying such exemptions. While I would like to think that such shenanigans will not take place, given the power of special interest lobbying groups on a wide swath of US government functions, one needn't be a conspiracy nut to imagine such a scenario. The influence of big money on the American body politic is rotting our democracy from the inside out, but that's fodder for a different kind of post. Oy vey.

For now I'll take the role of the optimist, and hope that the attention this FDA document has placed on CCSVI will spur "rigorously conducted, properly targeted" research, just as the paper states. Unfortunately, after the flurry of newspaper articles that were written directly after the FDA warning was issued, American news organizations have once again fallen into an eerie silence regarding CCSVI. It's really quite strange.

♦ Lots of news on the MS drug front. The oral MS drug BG 12 (dimethyl fumarate) has continued to shine in phase 3 clinical studies (click here), and has been submitted to the FDA for approval. BG 12 works unlike any current MS drugs, in that it doesn't modulate or suppress the immune system, but rather boosts enzymes that apparently serve as neuroprotective agents and anti-inflammatories, protecting cells from the damages inflicted by MS. This makes it an extremely interesting drug, especially as its safety profile appears to be quite good. Interestingly, one study looking at the effectiveness of BG 12 as compared to other substances that have a similar mechanism of action (click here) found that a dietary supplement, Protandim (click here), was the most effective of the lot. It's important to keep in mind that this study was done on cells in a petri dish (in vitro) rather than in animals or human beings (in vivo). It appears that the amount of the effective dietary supplements contained in Protandim (Curcumin, Milk Thistle, Green Tea Extract, Bacopa, and Ashwagandha) would be too small to have a dramatic effect on human beings, but it certainly would be possible to take these herbal supplements in sufficient quantities to possibly achieve the effects seen in the study. I've consulted the naturopath who works out of my neuro's office about this, and I'm scheduled to have more conversations in this with her regard next week. Her initial reaction was very encouraging, though, and I'll certainly keep everyone posted on how this develops.

Speaking of natural supplements, ever since I was diagnosed it's been claimed that omega-3 oils (fish oils) were beneficial to MS patients. Apparently, this isn't the case, according to a newly released study (click here). Fish oils do have other benefits, however, so there is still reason to supplement your diet with them.

In Tysabri news, researchers have established the risk factors associated with a higher likelihood of developing PML, the deadly brain infection associated with the drug (click here). While that's good news, another study suggests that patients stopping Tysabri therapy face a high risk of suffering an MS relapse in the six months following cessation of the drug (click here). This is problematic, since patients on Tysabri who test positive for the JC virus, which is responsible for PML, are advised to stop Tysabri therapy, leaving them in a damned if you do, more damned if you don't situation. This has led me to coin a new phrase: one hand washes the other and both hands slap the face. Oy vey.

The investigational drug Lemtrada, formally known as Campath, was shown to reverse disability in 29% of patients taking it in a clinical trial (click here). Campath is a very powerful drug that severely suppresses the immune system, and worries about potentially serious side effects have dogged the drug throughout the clinical trial process. Still, other trials have suggested that Lemtrada may suppress disease activity in RRMS patients even five years after patients stop taking the drug (click here), which hints that the drug could be a game changer, but is also indicative of the profound effects that Lemtrada has on the human body. Wouldn't it be nice if researchers spent as much time trying to figure out the root cause of MS as they do on finding new and better ways to suppress the aberrant immune response associated with the disease, which, after all, is really just a symptom of some still unknown underlying pathology? All who agree say, "Hallelujah!" (I figured I'd throw that in to counterbalance all of the oy vey's)

♦ In the stem cell arena, there've been some very promising developments. In a study sponsored by one of my favorite MS nonprofits, The Myelin Repair Foundation, mesenchymal stem cells (MSC's) were found to reverse the damage done to mice suffering from a Murine model of MS (click here). The researchers then went one step further, and tried to figure out exactly how the MSC's were repairing damaged nervous system tissues. They decided to inject the medium in which the MSC's were grown in into the mice, and found that, just like the MSC's themselves, this substance also reversed nervous system damage, indicating that the mesenchymal stem cells were secreting some substance that is neuroregenerative. Further tests to isolate the substance were done, and lo and behold a molecule known as "hepatocyte growth factor" was found which seems to hold the key to the neuroregenerative and immunosuppressive effects of mesenchymal stem cells, opening up the possibility that treatment with this growth factor alone, without the use of the stem cells themselves, might offer tremendous benefit to MS patients. Of course, this research is in its earliest stages, but at this stage in the game, my disease has progressed to the point that if they were looking for human volunteers, I'd gleefully run any competitors over with my wheelchair to get to the front of the line. Oy vey.

♦ I've run across several very interesting studies that might just hint at the ever mysterious process that drives MS. One study, out of the Greek island of Crete, looked at the rise in MS among the islands' female inhabitants. It found that females that lived in towns or had relocated to urban centers at an early age were most likely to suffer from MS (click here). The environmental factors that changed with urbanization included an increase in smoking, the consumption of pasteurized cow milk, alcohol consumption, and the use of contraceptives. In addition, women in an urban environment were more likely to have their first child at a later age. These trends were observed over a 30 year period, suggesting that environmental factors associated with urbanization are associated with an increased risk of developing multiple sclerosis.

A study out of Scotland, which has some of the highest rates of MS in the world, looked at the incidence of MS in three Scottish regions, Aberdeen city, Shetland, and Orkney (click here). It found that the prevalence of MS had risen sharply in the last 30 years, to the point that 1 in 170 women in Orkney suffered from MS, a shockingly high number, and in fact the highest prevalence rate ever recorded worldwide. Prevalence of MS was higher in women than men and 45% of those affected had significant disability (EDSS scores equal to or greater than 6). Interestingly, the least MS prevalence was seen in subjects from the lowest socioeconomic group, hinting that some genetic environmental interaction in the lifestyle of those of the higher socioeconomic groups was contributing to the disease. This brings to mind the hygiene hypothesis (click here), which states that the ultra-hygienic environment enjoyed by those living in technologically advanced Western societies suffer from higher rates of certain maladies because many of the pathogens and parasites that were present during the evolution of the human immune system were taken out of the equation, leading to a whole host of allergies and "autoimmune" diseases.

♦ We'll end on one of my favorite topics, asinine research. An investigator in Australia has made the startling determination that – get this – mobility is key to the quality of life for MS sufferers (click here). This astoundingly astute super genius has observed, over the course of a two-year study of SPMS patients, that as the ability to walk declined, so did a patient's quality of life!!! CAN YOU FREAKING BELIEVE IT? WHO IN THEIR RIGHT MINDS WOULD HAVE EVER THOUGHT??? This superduper brainiac, an intellectual figure no doubt on the order of Galileo, Newton, and Einstein, came to the earthshaking conclusion that "a clinical focus on the treatment of reduced mobility in MS patients might deliver significant benefits in the future to patients with secondary‐progressive multiple sclerosis." HOLY FRACKING SHIT, DOES THIS MEAN THAT IF I COULD RUN, SKIP, WALK HAND-IN-HAND WITH MY WIFE AND USE MY RIGHT ARM, I MIGHT BE A TAD BIT HAPPIER?!?! WELL FUCK ME!!!

And to think, it only took Dr. Shithead two whole years to come up with this theory. Talk about a game changer! Now, this really has the wheels in my head turning. This revolutionary new way of thinking might apply to a wide range of disabilities, not just those associated with mobility. Might – gasp – BLIND PEOPLE be somewhat more contented if they could SEE? And DEAF PEOPLE, could it be that – wait, I'm trembling with excitement so much that I'm having trouble getting this out – could it be that, dare I say it, HEARING might actually bring them some small measure of JOY? MY GOD! HOW COULD THIS INSIGHT HAVE BEEN MISSED ALL THESE MANY YEARS? OH THE HUMANITY! THIS CHANGES EVERYTHING! Now instead of just sitting motionless like a week old turd, the next time I see my neurologist I'll suggest, nay, I'll insist that he get right on finding ways to make me walk, instead of whatever the hell he's been doing all these years. HAVE FAITH, MY BROTHERS AND SISTERS IN DISABILITY, SALVATION IS HERE!!!

All together now: OY VEY!

Given the mindbending nature of the above scientific study, I'll leave you with the following bit of medical advice. It might not work, but at least it'd be a hell of a lot of fun to try…




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37 comments:

  1. Another wonderful piece! Your discussions of asinine research are outstanding.

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    1. Thank you. I consider myself an expert on all things asinine.

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  2. Hmmmm. I see you were up at 2:18 AM posting this. Some of our best work is done at that hour, I'm with you on that one. Just thought I'd mention that my laughter at your tale of the miscreant researcher was so boisterous that my spouse appeared in my doorway to find out what was going on. And WHERE in the heck do you find these videos, anyway!

    Appreciate the research update, as always. Whenever I'm feeling lazy about researching, I can comfort myself with the knowledge that eventually, you will do it for me. No, seriously, thank you! I myself am watching videos from the LDN Research Trust this morning, run by our friends across the water in GB.
    http://www.youtube.com/user/TheLDNresearchtrust/videos?view=1
    (scroll down to the bottom to find the MS interviews) Who doesn't want to hear those lovely Brit and Irish accents on a rainy morning!

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    1. Yes, I am quite the night owl. Some might even say vampire. Been like that since I was a child, and one of the positives of my having to leave work to go out on disability is that I no longer have to get up in the ungodly morning hours. Noon is a much more civilized time to wake up, IMO.

      I hope the LDN Research Trust is making progress. There's been far too little research done on LDN, as well as other alternative therapies. Thanks for the link, I'll have to watch the videos…

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  3. Fabulous post as always. Also, as the daughter of a hellfire and brimstone preacher, I can tell you that the cadence of your concluding paragraphs showed great promise for you as a preacher man. ;-)

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    1. I always thought those high-powered preachers looked like they were having a blast doing the especially fiery parts of their sermons. Except for the ones that looked like they were about to suffer coronaries, that is.

      I don't think there's really a Jewish equivalent to that kind of preaching, although I'm probably not the best person to ask. The singers in synagogue, called cantors, usually have incredible voices, and in fact Cab Calloway modeled his own vocal style along the lines of those he heard in the synagogues that were in the neighborhood he grew up in. Just an odd piece of trivia I happen to keep locked in my noggin…

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  4. Always an informative read! Thanks.

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    1. You're welcome, it's my pleasure to serve you…

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  5. For the few readers that don't know it already, I would like to point out that none of the words you use in the last 2 full paragraphs are Yiddish! Although wonderfully emphatic and descriptive, not Yiddish.

    Yiddish Words often sound like exactly what they mean. My favorite definition of two Yiddish words are shlimil and schlimazel. The shlemiel is the guy who spills the soup and the schlimazel is the guy who's lap it lands in. I mentioned these 2 words in particular because for me, they all too often perfectly describe my experience of living with MS. Dropping and spilling are just a regular part of my daily activities.

    I love your writing. I don't read all of your posts because they are often very, very, very long. But when I do make the time, I always enjoy what I read. You are smart, cynical and well-informed. You are funny and entertaining and I often refer people to your blog.

    So, my dear Kamikaze-leh, keep up the good work and I will continue to make the time to read what you have written.

    Michael B. Gerber
    Perspective Is Everything

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    1. Thank you, Michael, for your extremely effusive praise. Not sure I'm quite all that, but it's nice to hear. Or, rather, read.

      Yiddish is an incredibly colorful language, which unfortunately is slowly slipping away. A few generations of my family spoken rather fluently, but most of those family members are now no longer with us, and their progeny, such as myself, only know a smattering of Yiddish.

      My own favorite Yiddish expression is "gay cocken effen yom", which translates into "go shit in your hat", and was an expression my grandmother used to utter with great relish…

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  6. And what gets me about Dr. Shithead's research is that we, the Australian taxpayers, would have paid for him to reach these brilliant conclusions. AAAARRRRGGGGHHHHH !!!!!!!

    Judi from Australia

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    1. Hopefully, not much money was spent on this study, but even the time spent is a shame. Many of these academic folks live in a publish or perish environment, though, which does lead to the publication of some, shall we say, "unnecessary" research…

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  7. Thanks for a good read along with a good laugh--as always

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    1. You're very welcome. After my grandmother was through saying "go shit in your hat" in Yiddish, she'd often say that laughter is the best medicine…

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  8. Good piece Marc!

    Re: the FDA. While the "warning" of CCSVI treatent seemed a tad overbearing, there are some legitimate concerns. Some offering the treatment are guilty of overtreating, perhaps utilizing oversized balloons and thus causing more damage thatn necessary, or utilizing stents where simple venoplasty would have sufficed. Plus, I believe this warning was triggered because one doctor started his clinical trial before he had all of the requisite approvals in place. Some caution and due dilligence is required before seeking treatment.

    On the positive side, the FDA seem to be issuing more warnings about the dangers of MS drugs.

    So perhaps they are just doing their jobs. Oy vey!

    PS: I believe I will start on that diet you suggested. L'Chayyim!

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    1. Certainly, the FDA warning did voice some very legitimate concerns. I believe there is a little bit of a turf war behind this warning, as it was triggered by a Dr. who might have had motives other than completely medical for his giving the FDA a heads up. It seems that CCSVI is exposing the seamy underside of modern medicine, complete with bloated egos, huge profits, and fastidiously disciplined turf wars. All of this, I believe, works to the detriment of patients, unfortunately.

      As for the diet I suggested, I guess you're talking about all of the supplements I mentioned. Please consult with a physician or nutritionist before starting large doses of any supplement, because some of them can have powerful effects, and also may be contraindicated by some medications. Don't let your guard down simply because something is "all-natural" or a "herbal" supplement. Such substances can still be potent medicines, and shouldn't be taken haphazardly…

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  9. You give us all great hope by explaining all the new options coming down the pike...... But you give me a really good dose of joy somehow when you get pissed off!! I get so mad too myself, good to remember to laugh, Oy Vey!!

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    1. Heck, MS is such a miserable disease, that without a sense of humor you're sunk. It helps to maintain a sense of the absurdity of it all. Crazy that any of us got this disease, crazy disease, crazy doctors, crazy, crazy, crazy…

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  10. Great post, thank you! Love your voice.
    Olivia

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    1. Thanks, Olivia. I wonder if you'd love my voice if you actually heard me singing. Maybe not, although I was the lead singer of punk rock band back in my misspent youth. That was more screaming than singing, though.

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  11. I was diagnosed with primary progressive in '05 since then I have become an excellent sitter. my wife is really mad because I don't walk the dogs anymore. I've been following Dr.Zamboni since '09. I had the CCSVI procedure done at the Albany medical Center last month. My right jugular was 50 to 70% blocked. RESULTS ..... I do not take my "crack pill" (provigal) for fatigue anymore. I forgot what it was like to be alive all day rather then two-three hours in the morning. I am currently 50-70% better in my heat intolerance...WOOHOO... I found it interesting that the FDA was looking for reports if you have a problem with CCSVI but there was no report if you had success. I will call them Tuesday to tell them of my success

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    1. Good idea to report to the FDA about your success. Congratulations on that as well. It does seem that symptoms such as fatigue and heat intolerance are the ones that CCSVI has the most effect on. Hoping that helps you some with your mobility, as well.

      I too have been dealing with massive fatigue for the last eight months or so, which is kind of strange because I never had that symptom before, and I was diagnosed in 2003. It does suck not being able to stay awake for more than four or five hours at a crack. Being sick just takes up too much time!

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  12. I think you're being grossly unfair to Prof. Krishnan, or as you refer to him, "Dr. Shithead". It's absolutely critical to the advancement of science that "obvious" things be properly tested and confirmed, since many of the more important discoveries in history contradicted prevailing beliefs. "Obvious" can be a very misleading basis for scientific conclusions. Unfortunately, it's often difficult for researchers to get negative or "obvious" research results published, requiring others to repeat these experiments in the name of thoroughness later. The research you mock here appears to have merely been an analysis of data taken from the placebo arm of an existing clinical trial. In other words, another experiment (probably with more obvious value to the non-scientist) paid for the expensive bits, and Prof. Krishnan subsequently analyzed the resulting data to confirm the "obvious" relationship between walking speed and quality of life. More importantly, this relationship is now quantified.

    If Prof. Krishnan had held a press conference and breathlessly announced his breakthrough discovery, your sarcasm would be more justified. But a small blurb on a medical news website seems entirely appropriate for the nature of his results.

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    1. He's just letting off a little steam :) I think he deserves to do that.

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    2. I respect your sticking up for Prof. Krishnan, and I do understand the scientific process. However, doing a study that "finds" that mobility issues negatively impact the quality of life of the disabled is a bit ridiculous. Many of these academics live in a publish or perish environment, thus the publishing of many studies that appear to be obvious at best, inane at worst.

      Of course, my mocking of this kind of study is an outlet for all of the frustrations involved in dealing with MS, but I truly do find it incredible that intellectual capital is spent on such endeavors when there is a pressing need for intelligent men like Prof. Krishnan to tackle vitally important issues. For that matter, I think it's emblematic of the times we live in that while millions suffer and die from heinous illnesses, tremendous resources are devoted to finding "cures" for human annoyances such as balding or some of the other natural effects of aging. Yes, these do cause consternation, but let's get our priorities straight. Cancer, heart disease, diabetes, MS and other such scourges to the front of the line, please, and limp penises and baldness to the back, thank you…

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  13. Unknown (right above my post)---

    You must me joking. If not, ask any MS patient who is struggling to take a step, or cannot step, if just plain walking would improve the quality of their lives. As for speed? That's absurdly laughable that anyone would even try to quantify or qualify this. And if it were an addendum to a existing clinical trial, don't insult us by publishing it. It's comparable to telling someone who is going to have their leg amputated due to cancer that the procedure will result in a weight loss. No shit, Dr. Shithead. Would it be equal to the weight of the leg?

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    1. And Biogen sponsored the study?

      http://www.msra.org.au/mobility-and-quality-life-ms

      Give me a break. But if this pharmaceutical company were in the business of supporting research that looked for a cure, they'd be out of business. Instead, tell the poor schmucks that their quality of life will deteriorate unless... maybe...you take our drug...

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    2. Hell hath no fury like an MS patient marginalized by a ludicrous report.

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    3. Seems that Biogen is all over everything MS these days. It would probably be a good wager that the drug company has some kind of compound in the pipeline aimed at increasing the mobility of SPMS patients. The reality is that all of the current MS drugs are symptom management instruments of one sort or another, as modulating or down regulating an aberrant immune response does not address the underlying cause of MS, which of course is still unknown. It would be nice to see some of the research dollars spent on finding newer and better immunosuppressants instead going to foundational research looking for the mechanism behind the aberrant immune response. It's hard not to be cynical in the face of a system that clearly puts profit over patient in most cases.

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  14. So much mishegas about that last researcher. He's no maven and perhaps, he's a shmendrik. He tried to study the tsuris that is MS but his study told you gornisht. Feh! No worries about your outburst Marc. You're always such a mentsch! Let's keep Yiddish alive or at least Yinglish! You're allowed to rant. After all, its in the name of your blog.

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    1. I'm a little faklemt at your defense of me. Thank you, and L'Chaim (to everyone)…

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  15. Marc,

    Should auld acquaintance be forgot,
    and never brought to mind
    Should auld acquaintance be forgot,
    and auld lang syne

    For auld lang syne, oor Marc,
    for auld lang syne,
    we’ll tak a cup o’ kindness yet,
    for auld lang syne.

    And surely ye’ll be your pint-stowp !
    and surely I’ll be mine !
    And we’ll tak a cup o’ kindness yet,
    for auld lang syne.......


    Happy Ne'yar our Marc, when it swings aroon,
    When its lost dear Marc, can only get refoon.
    Tell them scotland's mine, oot wae auld asinine.
    FDA is such piss, heading for the glesga kiss
    An' well march t'froggies oot ma toon.

    Early new year wishes,
    Happy first footin'

    Ed

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  16. Loved this post, as always, Marc....always appreciate the humor you bring to us...I believe that expression you reference actually translates to "go shit in the ocean", a far less tolerable proposition! Those Aussie researchers remind me of my so-called healthy friends who call me to complain that they simply can't walk as many miles as they use to....and all I'm thinking is what I'd give for one more dance or one more walk on the beach. Thank you for making our journey more tolerable and light-hearted, dear friend.
    Roberta

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  17. Thank you Marc, that was an awesome rant. I cracked up at the end of the first paragraph!

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  18. being born in Brooklyn 54 yrs ago and living amongst poor Jewish neighbors I always thought it meant Go Shit in the River

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