Last week, the FDA approved Biogen’s long-awaited oral MS drug, Tecfidera (formally known as BG 12). Naturally, the news was featured most prominently in the financial sections of newspapers/websites (click here), as an uptick in shareholder value is much more newsworthy than a potentially breakthrough drug that could help hundreds of thousands of patients suffering from a heinous disease. Much was also reported about the drug's yearly price of $54,900, which is actually considered reasonable in the demented world of MS drug pricing. Such are the priorities of our whacked out society. Okay, social commentary over…
Tecfidera’s active ingredient is dimethyl fumarate (DMF – click here), a derivative of fumaric acid, a naturally occurring substance that can be found in mushrooms, lichens, and moss. DMF was first used for medicinal purposes in a highly effective anti-psoriasis drug called Fumaderm, which has been marketed in Germany since 1994. It’s important to note that Tecfidera and Fumaderm are not identical compounds, which must be kept in mind when comparing the actions and side effects of the two drugs. Much might be inferred by reviewing the history of Fumaderm, but trying to make precise, direct comparisons could well in lead to erroneous conclusions. More on that later…
The release of Tecfidera has been much anticipated in the MS community, as clinical trials showed the pill to be significantly more effective in reducing relapses and slowing the progression of multiple sclerosis disability than the current frontline MS treatments (Copaxone, Rebif, Avonex, and Betaseron – all injectables), while its side effect profile appears to be quite mild when compared to many of the other MS disease modifying treatments.
Tecfidera joins Gilenya and Aubagio as the only MS treatments currently in pill form. In clinical trials, Gilenya was more effective in terms of reducing relapse rates, but concerns about potentially serious side effects (dangerously low blood pressure and pulse rates, potential for opportunistic infections) have kept the drug from reaching "blockbuster" status. There are some indications that Gilenya may have neuroprotective properties, and it is currently undergoing trials for use against Primary Progressive Multiple Sclerosis (click here). It is one of the few drugs being tested for the progressive forms of the disease. In trials, Aubagio proved to be just about as effective as the CRAB drugs in reducing relapses, and has exhibited some potential in inhibiting disease progression, but the drug comes with two black box warnings (the strongest issued by the FDA) concerning liver toxicity and the possibility that it can cause major birth defects (click here). Tecfidera’s comparatively mild side effect profile, which is comprised primarily of flushing of the skin and gastric disturbances, its high rate of efficacy, and oral dosing have led to the expectation that it will soon be a leader in the multiple sclerosis drug market.
Tecfidera’s mechanism of action, which is not fully understood (something that is not uncommon, the action of many pharmaceuticals are not fully understood), appears to be threefold. The drug exhibits immunomodulatory, anti-inflammatory, and antioxidant properties, the combination of which theoretically affords the compound its potency. In two large-scale studies, called DEFINE and CONFIRM, Tecfidera reduced relapse rates by approximately 50% over placebo, and reduced the progression of disability by about 30%. By comparison, the CRAB drugs reduce relapse rates by about 35%, and Tysabri cuts relapses about 65%. Whether these drugs impact disease progression has yet to be firmly established.
Much of the excitement surrounding Tecfidera involves the prospect that, in addition to its disease modifying characteristics, the drug may be neuroprotective. Neuroprotection is one of the holy grails of MS research. If the cells of the central nervous system can be protected from the ravages of multiple sclerosis, then the progression of the disease can be inhibited. The notion that Tecfidera may be neuroprotective is based on the fact that one of the drug’s supposed mechanisms of action is the activation of Nrf2 pathways in the human body. Nrf2 (click here) is simply a protein that exists within every human cell, inoperative until it is kicked into action by a Nrf2 activator (think of it like a bottle rocket – until lit, it sits there doing nothing, but once lit (activated) it zooms into action). Once activated, Nrf2 migrates into the nucleus of the cell and bonds to the DNA within, initiating the production of powerful antioxidants. If Nrf2 was a bottle rocket, it’s thought that Tecfidera could initiate the process that lights its fuse.
Antioxidants (the good guys) are the body’s defense against free radicals (the bad guys), cell damaging oxygen molecules that are released during the biological process of turning food into energy, much like noxious exhaust fumes are released by an automobile engine turning gasoline into energy. Once free radicals are released they act like wrecking balls, smashing through cell walls and inflicting injury. The process by which free radicals do damage to the body’s tissues is known as oxidative stress, which is believed to be one of the primary drivers of MS disease progression, as well as a factor in many other diseases (click here). Therefore, by combating oxidative stress through Nrf2 activation, Tecfidera may protect central nervous system tissues from damage by free radicals, which would be a very good thing.
Some Facebook pages and websites, including a previous post on Wheelchair Kamikaze (click here), have mistakenly equated Tecfidera with a nutraceutical product called Protandim (click here). In laboratory tests, Protandim has proven to be a powerful Nrf2 activator, a quality it does share with Tecfidera. However, Tecfidera’s mechanism of action appears to be much more complex and wide-ranging, and not confined only to Nrf2 activation. It also effects cytokines (chemical signals that influence the inflammatory process – click here), and down regulates the immune system. This down regulation of the immune system may in fact be the primary driver of Tecfidera’s effectiveness. According to the official report detailing the results of the DEFINE trial (click here), which appeared in the New England Journal of Medicine, “It is difficult to determine whether the therapeutic effect of BG 12 stems predominantly from immunomodulatory mechanisms or from neuroprotective mechanisms.”
Now back to Fumaderm, Tecfidera’s very effective German anti-psoriasis cousin. Fumaderm's efficacy in treating psoriasis, an autoimmune disease, is well documented, with 50% of the patients taking it achieving at least 70% improvement in their condition. Since Fumaderm’s primary component, like Tecfidera, is dimethyl fumarate, its side effect profile is similar to Tecfidera’s. Through 20 years of use, the most prevalent Fumaderm side effects have been gastric disturbances (stomach ache, vomiting, and diarrhea) and flushing of the skin, which, according to a paper prepared by Britain’s NHS (click here), can lead to discontinuance and/or noncompliance in 30% to 40% of patients. In the Tecfidera drug trials, though, dropout rates were negligible, with no significant difference between those patients taking the actual drug and those on placebo. Gastric disturbances and flushing of the skin were the most commonly reported side effects in the Tecfidera trials, but appeared to be manageable and diminished significantly after one month on the therapy. This discrepancy between the patient experience with Fumaderm versus Tecfidera is likely due to the different chemical makeup of the two compounds (Tecfidera is composed only of DMF, while Fumaderm includes DMF and some other derivatives of fumaric acid), and/or to differences in dosing, as patients on Fumaderm generally take a higher dose of DMF than will be given to Tecfidera users. Still, only real world experience will tell us how troublesome these side effects prove to be.
Another effect seen in both drugs is leukopenia, a reduction in white blood cell counts. This condition is accompanied by lymphopenia, a reduction in specific white blood cells, including B and T cells, which are the targets of many of the current MS drugs (Tysabri, Rituxan, Gilenya, Aubagio). This suppression of immune system cells may play a part in the two drugs' effectiveness, but can be problematic if the cell counts get too low, as this might open the patient up to opportunistic infections, although none were seen during the clinical trials. Tecfidera induced lymphopenia and leukopenia are reversible with cessation of drug therapy.
In its 20 years on the German market, comprising over 170,000 patient hours, Fumaderm has been linked to four cases of PML (click here), the opportunistic brain infection associated with Tysabri. While this may initially seem troublesome, it’s important to keep in mind that these cases occurred over a very long time period, and at least one of these patients was using other powerful immunosuppressive drugs. Generally, opportunistic infections are not seen in patients using Fumaderm.
During the Tecfidera DEFINE trial, white cell and lymphocyte cell counts dropped an average of 10% and 28% respectively, which could very well play a role in the drug’s efficacy. Importantly, though, over the two-year run of the trial, no instances of opportunistic infections were reported. It was noted, however, that 4% of trial patients experienced a more serious drop in cell counts (this info can be found on page 1106, paragraph 3 in the NEJM article – click here). In Germany, Fumaderm patients are required to have blood tests once a month for the first six months they are on the therapy, and then every other month thereafter, to keep an eye on cell counts The FDA guidelines for Tecfidera only call for yearly blood tests, and though I’m no doctor, this recommendation seems a bit questionable. Even though no opportunistic infections were noted in the two Tecfidera trials, why not err on the side of caution? We’re only talking about simple blood tests, which could head off potential problems before they get started.
Some other rare but potentially serious side effects noted in the Tecfidera study were liver and kidney events, although most were mild and reversible. There were no reported incidences of kidney failure. Still, I would think, all the more reason for regular blood tests, especially since so many MS patients are on other drugs that can be liver or kidney toxic.
So, what do I make of all this, as an educated patient? Tecfidera seems to be a very promising new drug for MS sufferers, one which might even help those with progressive disease due to its antioxidant, neuroprotective potential. I will very likely begin Tecfidera therapy sometime in the near future, even though my diagnosis is still uncertain and none of the other MS drugs have helped me. I’m encouraged by the fact that Tecfidera is related to a drug that is very effective in treating psoriasis, and has also anecdotally been noted to have a positive effect on a host of other diseases, including sarcoidosis and alopecia. I definitely show signs of some sort of systemic autoimmune activity, a condition against which Tecfidera’s mechanisms of action suggest might make it effective.
Tecfidera’s clinical trials convincingly demonstrate it to be effective in treating RRMS. Whether you believe MS is an autoimmune disease or not, it’s indisputable that the immune system plays some significant role in the MS disease process, and Tecfidera’s combination of immunomodulation, anti-inflammatory action, and antioxidant activation should provide a potent mix to help tame the disease. We’ll have to see just how troublesome the gastric and skin flushing side effects turn out to be, although, as stated above, in the trials they appeared to drop off dramatically after the first month of therapy.
Personally, if and when I do go on Tecfidera, I am going to insist on blood tests every 4-6 weeks, based on the study data concerning leukopenia and lymphopenia, as well as renal and hepatic toxicity. I’m on so many drugs that I rattle when I move, and I’ve learned to take nothing for granted. I’d suggest patients sharing similar concerns print out the New England Journal of Medicine DEFINE trial article linked to above and show the pertinent sections to their neurologist. The 4% rate of serious lymphopenia has not been publicized, as far as I can tell, and that alone should be reason for regular monitoring of blood counts. Better safe than sorry, especially when using a drug new to the market. Of course, that’s just my humble “I'm not a doctor” opinion…
(Update: for more information on Tecfidera and PML, please see my latest post on the topic, by clicking here)
Sunday, March 31, 2013
Monday, March 18, 2013
(Photo credit: davidyuweb)
The last couple of weeks have been tough. Losing my friend George, The Greek from Detroit, really hit hard. I’ve never before suffered the premature loss of someone with whom I’ve been so close. Of course I’ve lost loved ones, but they’ve either been elderly, in which case there’s solace in the thought that they lived full lives, or folks for whom I’ve felt affection for but not the extremely close bonds shared with someone in my “inner circle”. The fact that George and I bonded over our shared struggle with a debilitating disease, and that his death was directly related to that illness, only serves to focus the despondency.
Mourning is a strange process. For whom am I actually grieving? George is at rest, the despair he felt at the ravages of his multiple sclerosis ended. From that respect, at least, it would seem that those who knew him should be grateful that his long struggle is over. But I mourn for his life that was upended, and his life that could have been. I feel sorrow for all who will miss him, for all of those who held him dear. But most of all, if I’m completely honest, I mourn for me, for the fact that I’ll never again answer the phone and hear, “Kazmo, this disease fucking sucks!”
Of course, I have other friends to talk to, but George’s tremendously emotional manner was contagious, eliciting, at least in me, a license to let rip with all of the foul miseries and mindbending fears that helplessly watching a creeping paralysis devour your body brews in your brainpan. Yes, I still manage to find some good in (almost) every day, but there were days in the past few years when a significant portion of the good I found was talking to George.
Be that as it may, the world doesn’t stop spinning, the sun doesn’t stop rising, and life must go on. So here’s a collection of MS related items that aren’t too glum or weighty, but include a cause to rally around, some mindful artwork, a few helpful MS hints, and even a healthy dose of sex. What better to focus the mind back where it belongs, on the naughty bits. Believe me, George would approve…
♦ First up, a chance to help a fellow MSer and become a mini movie mogul, all in one fell swoop. Jason DaSilva is a young filmmaker whose work has been seen at film festivals around the world. About eight years ago, at the age of 25, he was struck with progressive MS and decided to turn his camera on himself. His new documentary, When I Walk, chronicles the first seven years of his struggle with PPMS in unflinching fashion, showing the effects of the disease warts and all even as it exposes the heart and soul of the man at the center of the storm. When the film opens, Jason is having some trouble walking; by its end he’s using a scooter full-time, his vision is increasingly affected, and the disease is attacking his hands. In between, we experience the physical and emotional roller coaster of MS as Jason searches for answers and possible cures, and though one might think this would make for gloomy subject matter, the film is an inspiring testament to Jason’s courage, the power of love, and the enduring nature of the human heart. Even as Jason’s body betrays him, he manages to find his soulmate, a woman special enough to love him despite all of the trepidation and uncertainties that come with MS. When I Walk had its premiere at the recent Sundance Film Festival, and received rave reviews (click here). Here’s the When I Walk trailer:
So, it would seem all is well in When I Walk land, right? Unfortunately, that’s not the case. Though the film got a big reception at Sundance, it really needs to be seen in cities around the country and around the world. It shows the side of MS that the public rarely sees, not the sanitized version most often portrayed on television and in the news media, but the Full Monty of ever advancing disability and its effects on the body and mind, capturing the jumble of emotions of the human being trapped inside an increasingly faulty body.
The realities of independent filmmaking today requires that filmmakers themselves raise the funds needed to get their works onto movie theater screens around the country, and Jason has started a Kickstarter campaign (click here) in an effort to do the necessary fund-raising. Kickstarter is a website allows individuals to contribute as little as one dollar to a wide variety of artistic, altruistic, or business endeavors. Jason’s goal is to raise $27,000 by April 3, and as of this writing has almost $19,000 to go. He’ll use the funds to do marketing, advertising, and promotion for the film, as well as pay for printing and duplication costs of the film and its trailer.
I don’t think I’ve ever before made a direct plea for financial donations of any kind on Wheelchair Kamikaze, but I was lucky enough to get a chance to preview this film, and it really struck a chord. So please, if you’re able, chip in as little as one dollar to help kickstart When I Walk into a theater near you (click here), and thus help a fellow MSer tell his story and show the world the realities of living with MS and the courage it takes to battle the disease day in and day out. Thanks.
♦ Check out the cover of the March issue of the journal Neurology, one of the top medical journals in the world:
Can you guess what lies at the heart of the striking piece of abstract art on the cover, called “Celebration”? I think you’ll be surprised to know that it’s (drumroll please)…
Artist and MSer Elizabeth Jamison (click here to see a gallery of her work) uses MRI images to make her compelling etchings, and a few years ago I sent her several images from my MRIs and MRA’s (Magnetic Resonance Angiograms), one of which she transformed into the image that is right this moment gracing the cover of a journal sitting in the offices of neurologists all over the world. Pretty nifty, don’t you think?
Elizabeth is herself an inspiration, as the MS that she’s suffered from for over 20 years has progressed to the point that she is now a quadriplegic. Still, she continues making her art, using a surrogate as her hands as she choreographs the artistic process. Her work is gaining attention worldwide, and will be featured in an exhibit in Barcelona next month.
♦ Here in the northern hemisphere, it’s almost spring, and if things go as planned, summer will soon follow. That means the temperatures will be rising, and many folks suffering from MS will be wilting. Heat sensitivity is a hallmark of multiple sclerosis and for many people with MS, myself included, warm temperatures are like kryptonite. Once the temperatures get much above 80°, I can literally feel the energy being drained from my body, and I start losing whatever functionality I’ve so far managed to retain. Strangely, when the temperatures soar, I seem to be negatively affected even if I stay inside my air-conditioned apartment. Defies logic, but it’s the truth. Fun fact: before the advent of the MRI, one of the methods used to diagnose MS was to place the patient in a hot bath and see if their symptoms got worse.
So, what can a patient do to combat these summertime blues? There are many forms of cooling garments, from vests to headbands to scarves, available from a variety of manufacturers (click here). If you are an American person with MS who is in financial hardship, both the Multiple Sclerosis Association of America (click here) and the Multiple Sclerosis Foundation (click here) have programs offering cooling equipment to qualifying clients, free of charge. Don’t be shy, both groups do terrific work, and the heat of the summer will soon be upon us.
♦ Now, finally, the subject you’ve all been waiting for, sex. The Sexuality and Disability webpage (click here) is a comprehensive resource for all things having to do with, well, sexuality and disability. From information on sexual morality to the actual mechanics of sex when dealing with a disabled body to relationship issues to sexual violence, this site is a veritable almanac on sex, sexuality, and relationships for the disabled person. I especially love the modified handicapped icons that grace the site’s front page, which depict a person in a wheelchair and their partner in all sorts of imaginative hijinks. Must’ve been fun coming up those, although some look to be a bit treacherous…
“Don Juan in a Wheelchair” (click here), an article from Salon.com, was written by a man with cerebral palsy, and explores his determination to lose his virginity. The article brought to mind two recent films that deal with similar subject matter, The Sessions and Scarlet Road.
The Sessions is a terrific, touching film starring John Hawkes and Helen Hunt, which tells the real-life story of Mark O’Brien, a severely disabled man who was afflicted with polio in childhood. Because of the weakness in his muscles, Mr. O’Brien had to spend most of his time in an iron lung, except for stretches of three or four hours at a time when he could survive with the aid of a portable oxygen unit. His entire life was spent lying on his back; despite this, he was able to earn a degree in English, and worked as a writer and poet, managing to get out and about on a gurney wheeled around by an aide. The film takes up his story in 1988, when, at the age of 38, he decided he wanted to lose his virginity and contacted a registered sex therapist. The Sessions deals with its delicate subject in a frank, matter-of-fact manner, and is infused with humanity, humor, and beauty. Though hardly pornographic, the film doesn’t dance around the sexual nature its narrative, so if glimpses of nudity and straightforward talk of sexual subjects aren’t for you, this movie probably isn’t your cup of tea. Everyone else, though, can watch The Sessions on Amazon.com’s streaming video-on-demand service for $3.99 (click here). I recommend this film highly. It’s one of the best I’ve seen in a while. (Please note: I have a raging dislike for 90% of American films made after 1980, so this is high praise indeed. BTW, I’m not a snob, but I do have a degree in Film… Okay, maybe I’m a snob…)
Scarlet Road is an Australian documentary that has received much acclaim, but, as far as I can tell, is so far not available for viewing in the USA. The film profiles a sex worker who specializes in catering to the disabled, and looks to be provocative and entertaining. I only wish I could see it. Here’s the trailer…
With that, I’ll bid you a sweet adieu. The show must go on… RIP George Bokos
Posted at 9:47 PM
Thursday, March 7, 2013
About two and half years ago I was hospitalized with very high fevers. It turned out I had a bizarre case of meningitis, which of course was extremely debilitating and terribly frightening, greatly exacerbating my very heat sensitive creeping paralysis. A short time after I returned home from the hospital, I was greeted with a great big gift basket, filled with all kinds of delicious goodies. To my immense surprise, the basket came from a man in Detroit that I had met only a few months earlier, and had exchanged several emails and phone calls with. He was a fellow MS sufferer, and I had little inkling at the time that we would soon develop a long-distance connection that would eventually transcend friendship and approach something akin to brotherhood.
The man who sent that basket was George Bokos, the self-described “Greek From Detroit”, who died early last Sunday morning. Although it seems almost de rigueur to offer such platitudes in this kind of essay, in George’s case the following are the absolute truth: he was one of the kindest, gentlest, most generous and good-natured people that it’s ever been my privilege to know. He was smart and funny, a master of sarcasm. In his own way, for better or worse, he was a force of nature, a tremendously emotional man whose heart was his guiding beacon. His friendship was a gift, his loss a heartbreak, and I will miss him as long as I draw breath.
The burdens and constraints imposed by the miserable beast called multiple sclerosis simply became too much for George to bear, and he exited this life on his own terms. The farewell note he left on his blog (click here), though quite forthcoming, only hints at the anguish he suffered. The disease and its wicked gravity robbed him of all he held dear, leaving him bereft of joy, a man whose sense of self was too enmeshed with his physicality to submit to an existence spent bedridden. The ravages of multiple sclerosis broke his tremendous heart and shattered his beneficent spirit. His decline was precipitous, a cruel freefall that proved impossible to break.
I first met George almost exactly 3 years ago, in the office of the Interventional Radiologist who performed both of our CCSVI procedures. I was there with my wife for pre-procedure testing, and George, having had his procedure the previous day, was awaiting his follow-up examination, accompanied by his mom, Hilda. The doctor, who is an avid amateur photographer, hadn’t yet arrived, and I was talking to the office manager, telling her of my photographic efforts using a camera mounted to the arm of my wheelchair. I’d been writing this blog for about a year, and when Hilda overheard my conversation with the office manager, she exclaimed, “Oh my, are you the Wheelchair Kamikaze?” Stunned, I stammered “Yes”, and in a blink Hilda was upon me, showering me with hugs and kisses, thanking me for writing about my life with MS and whatever part I played in helping to bring CCSVI to the attention of the MS population. The four of us had a brief but lively conversation, and then we were on our respective ways. I was tickled by the encounter, thinking it one of those strange bits of serendipity that life sometimes bestows upon us, completely unaware of the bond that George and I would eventually form.
Unfortunately, neither of us benefited from CCSVI treatment. At the time, my disease was fairly advanced and had already forced me to rely on a wheelchair, but George’s MS was far less noticeable, in fact, almost invisible. In the relatively short three years since, MS delivered an unrelenting series of hammer blows to George. It seemed the more he fought, the worse things became, like a man frantically struggling to free himself from a pit of quicksand only to find his every effort resulting in his getting dragged further down. He was tortured by terrible spasticity in his torso, and spasms so painful that at the end he all he could do was lie in bed on his side. He tried to find relief by getting a baclofen pump implanted, but this, like all of his other efforts to save himself, only resulted in a cascade of increasingly dire problems, a grueling saga he powerfully recounted on his blog (click here) Please note, I know many patients who have had fantastic success with the baclofen pump, and George's experience with it shouldn't be considered the norm.
Through it all, George and I became a two-person support group, usually speaking on the telephone at least once a week, sometimes more. We shared some tears, but much more often laughter, both of us marveling at the mind-boggling absurdities of the hand the fates had dealt us. George had a keen sense of humor, and a quick and sharp wit. Together, we would pick apart our miseries as only can be done by those who share them, reveling in the freedom of not needing to maintain a stiff upper lip in each other’s company. Life with MS is filled with irony and paradox, and though many of our conversations began with a recounting of tales of woe, they almost always ended with us joined in a catharsis of fitful laughter, the two of us trading quips and throwing verbal barbs at MS and all its attendant indignities. He called me “Kazmo”, and it seems incredible that I’ll never again hear that voice on the other end of the line. I will miss him so.
Was George perfect? Of course not, none of us are. At times that big heart of his proved a detriment, and overruled his head. His emotions could get the better of him and effect his decision-making, especially when it came to treatment choices. But who could blame him when faced with so frightening a foe, when so little is known about the progressive forms of MS, and when so many alternative treatments are promulgated and overhyped on the Internet? Fear plays a large role in the life of every MS patient, and George's MS was especially aggressive. Over many years I've learned the hard way that discretion is often the better part of valor, a notion that my friend George had a difficult time putting into practice. But he always meant well and acted with the best of intentions, with malice towards no one.
Unlike me, a man who spent much of my lifetime wrestling with neurotic existential angst despite whatever successes I achieved, George was a man with relatively simple needs and desires, incredibly content with the basic pleasures of a happy family life thriving on the fruits of the prosperous business he worked hard to build. As he says in his farewell note, he was in his bliss mowing the lawn, shoveling the snow, or washing his truck, three activities which I would be only all too pleased to pay someone else to do, and if he was still here I’m sure we’d share a chuckle over that one. As is far too common, George’s long marriage tragically fell victim to his disease, and though he battled to remain productive, eventually he had to give up work as well. Losing his family and business, the very anchors of his life, tore his heart out, and inflicted more pain than the disease alone ever could. He loved his children dearly, and his mom Hilda, herself a delight and my treasured friend, was among the brightest lights of his life. She was with him when he died, and says that “he was so happy to finally give MS a kick in the ass that he had a beatific glow and a smile on his face at the last breath.”
I know the “right to die” is a controversial issue, but let nobody ever say that George ended his life rashly, or on a whim. He was simply done suffering the indignities that the disease piles on, the relentless gnawing away of the man he once was. Suffice it to say that the exit he chose was not an easy one. George Bokos was a man who was true to himself, and he took control of his ultimate fate, one of the few things he still had any control over. Proud of his Greek heritage, George remained a Spartan to the end, but it is not that end for which he will be remembered. Though I write this through tears, I know that in time it is only the laughter we shared that will remain. George was one hell of a guy, a unique individual, a true and dear friend, and my comrade in arms. This world is a richer place for having had George in it; it owed him a better fate.
Rest in peace, you crazy Greek, Kazmo will always love you.