Friday Fight Song 05-05-06 - Coconut

[Eyedeas]

Coconut by Harry Nilsson


Brother needed Hep C tx, he bought it for a dime
His sister had it also, unknowing for some time.
He did a shot of Peg-Intron, and lots of other meds
She did a shot of Pegasys, at last cleared by the feds
He did a shot of the Hep C tx,
Called the doctor, woke him up, and said,

"Doctor, ain't there nothin' I can take,
I say, Doctor, to relieve the Hep C aches?
I say, Doctor, ain't there nothin' I can take,
I say, Doctor, to relieve the Hep C aches?

[TnHepGuy_]

Prior to reading this most recent Pham summary article, I would have said that the findings show that occult is in a certain percentage - but not all - SVR's/spontaneous. But I'm not quite sure what to make of: "<i>However, when the cells, <b>including those apparently negative for HCV RNA</b>, were ex vivo treated with mitogens known to activate different immune cell subsets, e.g., phytohemagglutinin (PHA) to stimulate T cells, pokeweed mitogen (PWM) to induce B and T cells, and lipopolysaccharide (LPS) to activate monocytes and B cells, <b>HCV RNA was detected in all of the individuals.</b> (1), (2), (19)</i>". This is by no means conclusive in-and-of-itself, but it gives pause for thought.

I'm also intrigued by something 'willing' mentioned, in that some form(s) of occult may not be replicatively viable, i.e. - "less evolutionarily fit" 'duds'/"spare parts". This might explain those patients who have unknowingly (to doctor and patient) received transplants of organs/tissues - or even transfusions - from occult origin, yet have not have gone on to become serum positive.


I would also qualify 'willing's' above <i>"SVR=cure" and "persistent post-SVR HCV RNA is real"</i> to read "SVR=real - with all the potential benefits therein" and "persistent post-SVR HCV RNA is real".


TnHepGuy

[cuteus]

willing, again thanks for that summarizing insight, I tend to agree with that observation, that is not present in all SVRs, and hopefully not in the majority either.
Does anyone know the level of damage in the SVRs used in the Pham study?

Tnguy: I just have one question for you, to clarify what is on your mind to me.  Do you believe that there is residual hcv in ALL SVRs, just not found yet? Or do you give merit that eradication is complete in some SVRs?

[jmjm530]

thg says: "In all honesty, Jim. I don't give **** what your doctor says, what my doctor says (who's mind you now somehow seem to be able to read)"
------------------------------------------
Some other may care what my doc say --  what Cuteus' doc says -- and what other doc's say. As far as I'm concerned, it's all part of a mix that helps us learn more.   As far as reading your doctor's mind, I was referring to your post C47, in the "article on occult/persistence..." thread. It seemed to me that  what your doctor says in that post is very similar to the position of both my doc and Dr. Dieterich.  

I've been involved in similar discussions mostly with DD, and more recently with Willing, and things have remained pretty civil, despite different points of view. I'm not trying to convince you one way or another, just putting stuff out there for folks to take or not to take as they like. I give the people here credit to analyze the source of material presented -- whether it be a study, an analysis of a study, or the opinion of my or someone else's doctor.

I'm sorry this has started to get what for me is bordering on out of hand, because I would have loved to have discussed and  pick your brains more as you are indeed a wealth of information and great asset to this discussion group.

All the best

-- Jim

[TnHepGuy_]

<u>Ina</u> - Congratulations for making it clear at 3!!! That is a HUGE accomplishment after all you done to get there. And the finding is greatly correlated with reaching SVR at 6. I hope you are breathing much easier now. And that your health continues to improve post-tx.


<u>willing</u> - I'm not finding the actual link now, but this paper (Carreno V, Castillo I, Rodriguez-Inigo E, Lopez-Alcorocho JM, Bartolome J, Quiroga JA, Pardo M. Hepatitis C virus persists and replicates in the liver of the majority
of sustained responder patients to antiviral treatment. Hepatology. 2005; 42 (S4):284A) is referenced in Pham and certainly seems to say that replication continues to occur in the liver.


TnHepGuy

[willing]

Ina : Wonderful, wonderful, wonderful, wondeful news. I am very happy for you. Yours was truly an amazing battle. Thoroughly enjoy your floating ...

Cuteus,TN,Jim
this is an uncertain/new area : instead of looking for generalizations "is/is-not a cure" it's worth focusing on the details

- there's not much to be gained by comparing credentials of different researchers. However I believe there is a significant difference between simply expressing an opinion and getting a paper published in a peer-reviewed journal. Reviewers don't take kindly to unsubstantiated generalizations.

-<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15368524&query_hl=6&itool=pubmed_docsum">Tsuda, et al 04</a> is as old as the '04 Pham paper. The persistent RNA finding  in the '04 Pham paper has been cited (and confirmed) repeatedly. Only two papers have cited Tsuda: <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15884032&query_hl=12&itool=pubmed_docsum">Basso, et al '05</a> and <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16441471&query_hl=14&itool=pubmed_docsum">Formann, et al '06</a>. Both echo Tsuda's findings on the beneficial effects of SVR but make no statement about persistent RNA. I don't believe anyone has challenged the high-sensitivity PCR technology of the persistent RNA studies.

-as noted in the post below, I don't know whether anyone has yet demonstrated that persistent RNA is associated with mature, infectious virus ( that is, extracted functional virus from a post-SVR cell line and shown its ability to infect new cells). Nevertheless, negative stand RNA has been reported, which strongly suggests replication. However I also believe packaging of HCV RNA in non-infectious form has been reported, which suggests that at least some of detected RNA may be no more than floating "spare parts" (I'll post that cite when I find it again)

- persistence has not been found in all patients. Negative RNA has not been found in all cell types. In patients in whom persistent RNA has been found it has not been found in all tissue types. I haven't counted, but PBMC infections seem much common than liver. For example, none of the Giannini patients had RNA in their liver cells. I don't believe anyone has yet reported negative RNA in liver cells.

- HCV is known to be capable of mutating rapidly away from any threat. Even if the detected RNA is associated with infectious particles they are obviously much less evolutionarily fit.

- IMHO, there's no contradiction in the statements "SVR=cure" and "persistent post-SVR HCV RNA is real"

[Forseegood]

I'll prob be really showing my age here, and maybe alienate some people (like I care about that soooo much, ha ha) but I think there aren't any new good songs because all the good melodies have been taken or something, vast majority of these new bands suck!!!! there hasn't been a lot of good original music in the past years...with few exceptions, White Stripes, some others...most of these bands that I see on Letterman or Leno are just clone bands of much better bands that came out in the 60's, 70s, even 80's...if I'm going to see a clone band of the Red Hot Chili Peppers, Sex Pistols, Led Zepplin, The Eagles or the Beatles...why wouldn't I just put their albums on instead, they are way better...and of couse, I'm a big Sinatra fan so that makes me ancient...ha ha!

[52TELE]

Do you ever notice that there really are no "new" songs that you can adapt to our "situation"? Is it because we are all so old we wouldn't recognize them?  It just wouldn't have the same effect. This one looks like it may have been a little tricky.
I love it. Thank you.

[TnHepGuy_]

You have plenty of papers on occult to reference - and plenty that have been posted in the past. Might I suggest that if you truly have such a great interest in the subject matter that you take the time to save and <b>read</b> each of the studies posted, then quote freely and accurately from them. And if you don't understand them or find conflict among them, call in your esteemed doctor.

In all honesty, Jim. I don't give **** what your doctor says, what my doctor says (who's mind you now somehow seem to be able to read), or what Joe-Blow-From-Idaho's doctor says - it's nothing more than opinion. What I look to is the new set of basic research that comes out, compare that with previous and current research, and then draw conclusions from them.

What you appear to do is look to what gets posted here by others, take a pre-set opinion (eg. - "I certainly don't want occult to turn out to be anything!"), not look at the papers, qualify statements with 'self-proclaimed ignorance', add your doctor as the End-All-End opinion, next tell others here that they are now "in agreement" with you, then try your hardest to get the final word in - but all the time avoiding the "heavy-lifting" that can come with actually slogging your way through the research - which, of course, is very convenient in that you can therefore avoid finding any possible "unwanted" data/answers that may lie there within.



TnHepGuy

[GoofyDad]

eisbein: Congratulations. Time to relax.

cuteus: You joining a threesome? My life is now complete.

forsee: I'm all for improving the educational system - and spending money to do it. My problem is we are focussing on raising the bottom rung, while assuming those on the top rung are doing well enough. They are, relative to the bttom rung, but not neccessarily relative to their potential. I don't like the assembly line approach - from standardized curriculums to shipping 30 kids from class to class in predefined intervals. Children aren't car parts and an education isn't a paint job.

I'll get off my uniformly sized, mass produced soap box now...

[dyce]

Thats great , thats a long time to tx  , my hats off to ya  .

[FlGuy]

Good news indeed.  I hope the good news has positive effect on the post-tx issues you've had.

[cuteus]

joining the threesome in putting on the ritz and the dancing shoes!!!
good place to post that one in, Ina, sneaky one.  But we know the "other" discussion will continue on, somewhere, somehow, when you least expect it, not! no HCV playing Candid Camera with you, right?
Now, we got to help the others climb on the cloud nine!
where are Sandi's dancing fishies? and the cloud nine?
I AM SO HAPPY FOR YOU!!!!! did you tell Dr yet?

[jmjm530]

Congratulations !!! Not that there was ever a doubt especially after you posted those impressively low enzyme numbers last time. How's your rehab going? I decided to stay out of the cholorine pool until I can find myself a HUGE facemask and snorkel (for skin sensitivity) and until my lungs/esophagus have more time to recover from the riba. But I've already started doing some climbing so step by step, my previous fitness level seems to be returning. Don't know if you caught one of my earlier posts, but my doc attributes some of my recent memory problems to "interferon hangover". He says it's quite common and sure clear up within the year.

[jmjm530]

A brief bio:

"Dr. Dieterich has authored numerous journal articles, abstracts, and book chapters on viral hepatitis and AIDS-associated infections of the gastrointestinal tract and liver, and their treatment. He is an internationally-recognized expert on hepatitis C infection and is involved in several research programs evaluating the management treatment of chronic hepatitis C virus (HCV) infection and co-infection with HIV/HCV."

Complete text:

http://www.hivandhepatitis.com/aboutus2.html#douglas

[jmjm530]

"live" in last sentence (second to last paragraph) should read "liver".

[jmjm530]

From Pham: "These results imply that HCV RNA can persist at very low levels in the serum and peripheral lymphoid cells and that an intermediate replicative form of the HCV genome can persist in PBMC for many years after apparently complete spontaneous or antiviral therapy-induced resolution of chronic hepatitis C."

From Dieterich: "There were small pieces of viral RNA which were not capable of replication found in some blood cells not in liver cells"
===========================
I'm not sure Dieterich and Pham are at odds other than what conclusions they may draw from the data. Note that Dieterich specifies "not in liver cells", so obvious he sees some significande here.  Pham, at least in the abstract does not mention virus being found in live cells.

Also, I don't think "non-researcher" applies to Dieterich. His name appears on countless studies.

-- Jim

[dyce]

Nodoubt the tests are to easy in the schools . The olest daughter carries a 4.5 grade average at school and she feels she is not bein challenged near enough. We live in a area where the education is of better  or higher standard but not to far away it is far below par. When I was a student , if you didn't do it , they flunked ya , not now!

[TnHepGuy_]

Thanks for posting the Tsuda study. Assuming that the researchers were using the "rigours protocols" mentioned below, I can't explain why there are such discrepancies between this studies and more recent ones (see: Pham and references) - (though I do remember some earlier research of a finding of no occult being dismissed because the tests used were not considered sensitive enough. I don't know if that's the case in this particular one. Hopefully 'willing' has some insight here.)

"<i>Recently, research assays applying reverse transcription of viral RNA to cDNA followed by two sequential rounds of polymerase chain reaction (RT-PCR) with HCV gene-specific primers, and validating the amplified products by nucleic
acid hybridization (NAH) with recombinant HCV DNA as a probe, were developed.1 These RT-PCR/NAH assays detect HCV RNA positive
(vegetative) and negative (replicative) strands with a sensitivity of <10 vge/mL (<5 IU/mL) and ~100 vge/mL (~50 IU/mL), respectively. Due to their extreme sensitivity, rigorous protocols ensuring the authenticity of HCV RNA amplification have to be followed. In addition, a quantitative, realtime RT-PCR detecting HCV RNA at a sensitivity of ~100
vge/mL was also recently established.1,3 Application of these
new detection methods has uncovered previously unknown
facts about the natural history of HCV infection, including
identification of occult HCV persistence.1</i>"


Also, you may want to print out Pham, show it to your doc and forward it on to Dieterich - and ask them to refute the findings therein. I'd be very interested to hear how they might scientifically dismiss the evidence - especially since Dieterich (doc/non-researcher) now seems to be behind the curve with his statement that "<i>small pieces of viral RNA which were not capable of replication found in some blood cells not in liver cells.  I am still using the word cure. This virus does not integrate into the genome like HBV and HIV so I firmly believe that there is a cure!</i>", when you see Pham's (doc/researcher) work: "<i>In our studies, using the highly sensitive RT-PCR/NAH assays, conclusive evidence was obtained for the presence of replicating HCV in persons who apparently completely recovered from hepatitis C and whose sera were repeatedly negative for HCV RNA by standard assays. We found that more than 80% of these individuals were serum HCV RNA positive at levels usually not exceeding 102 vge/mL and that 30% to 40% of them also carried HCV RNA in circulating lymphoid cells at levels between 10 and 104 vge per 107 cells (see Figure 1). 1,19</i>"


TnHepGuy

[jmjm530]

Dr. Dieterich says: I think that we can safely say cure. There are scientific disagreements about the data that you refer to. There were small pieces of viral RNA which were not capable of replication found in some blood cells not in liver cells. I am still using the word cure. This virus does not integrate into the genome like HBV and HIV so I firmly believe that there is a cure! DTD
---------------------------------------------------------------

Cuteus, thanks for the study and link to Dieterich's Q&A. What Dieterich says echoes pretty much what my doctor and apparently your doctor also believe. Maybe DD, Willing or THG would like to comment on Dieterich's statement in light of some of the studies they recently posted. I still think it comes down to speculation based on current info and while Dieterich sayhs "I firmly believe" he doesn't say it's a fact -- I imagine same with those on the other side. Still a long way to go here.

[GoofyDad]

On the other hand, if we took the survival, or enahncement, to the fittest to the medical playing field where would us heppers be?

Hopefully under the care of the bightest docs, who throughout school were educated to the highest levels they were capable of absorbing? And maybe taking advanced meds designed by scientists who received the same educational benefits?

Driving to work this AM I was thinking about making a bumper sticker: THE ACCUMULATION OF FACTS IS NOT AN EDUCATION

[FlGuy]

I agree with you. Do you have a little 'Darwin' sticker on the back of your car? In a state which uses 180 instruction days to ready students for standarized state tesing I wonder where kids will learn life's relavant lessons. For us, we do that at home.

On the other hand, if we took the survival, or enahncement, to the fittest to the medical playing field where would us heppers be?

[GoofyDad]

I generally lean pretty far left, but on he education issue, I fault "no child left behind" and the whole philosophy of allocating a disproportionate portion of our educational resources to the under acheiving segment of the student population.

Whether our goal is to lead in the global informational economy, or to improve the quality of life for the planet at large, either agenda would be advanced by identifying and focussing resources on our brightest minds.

One would not field a competitive Olympic team with the "no athlete left behind" mentality. Nature doesn't favor the underacheivers in a colony. What we're doing doesn't make sense.

Consider the standardized tests. They aren't designed to reward the schools producing the largest groups of high acheivers, they are there to reward the schools with the fewest kids in the bottom groups. It seems we define a succesful educational system as one that produces average kids accross the board.

America, where no kids fails and we keep lowering our standards until we meeet that goal.

[dyce]

I agree the oldest girl does 4 hours a homework a nite . She wish she could get higher level courses . By the way how are ya ?

[Forseegood]

wow, that's great, great, news, I'm so happy for you, at least you know youre suffering wasn't all done in vain...that's really great...