User talk:Heathhunnicutt/Archive 1

Mumps

 * Might I enquire as to why you reverted my recent edits to Mumps? I'm trying to format the entry in accordance with Citing_sources and Footnotes. Please let me know. -- MarcoTolo 23:56, 19 April 2006 (UTC)
 * Thanks for inquiring. I wanted to correct the following problems with your edits:
 * The RMNPA article was from University of Tokyo, not Russia.
 * The RMNPA progress is relevant to people who may be able to make progress in the near-term, so that is something I would keep.


 * I liked the ref/citation thing. I didn't know enough about it to replicate it.


 * I wondered if the Myramistin article is questionable, but then I did a mesh search on the authors and see they are attributed to a great deal of credible research.


 * I want to keep the compounds broken out in paragraphs. They are not equilavent in their utility to people and lumping them all in one paragraph puts Sp. Platensis on an equal footing with Myramistin, which is a disservice to people who should tak Sp. Platensis.


 * I liked making Research Compounds a subheading of treatments, but suggest making it parallel 'palliative treatmens' as a subheading of treatments. I think the parallel construction would be better.
 * Heathhunnicutt 02:13, 20 April 2006 (UTC)


 * Okay, I've made some changes to my previous edits - let me know what you think.


 * Concerns:
 * The and  references don't, as far as I can tell, reference the compounds applicability to mumps treatment - i.e. while the research is interesting, it seems to be getting a little far afield.
 * RMNPA does look like an attractive development target, but the guideline Wikipedia is not a crystal ball seems like it might apply here.


 * -- MarcoTolo 02:31, 20 April 2006 (UTC)


 * Uhh... Isn't RMNPA the same compound referenced in the first article of that paragraph?  It's just a particular stereoisomer, which other literature also cited nearby indicates is a potential treatment. Heathhunnicutt 02:41, 20 April 2006 (UTC)


 * Yes, that's true. What I'm geting at is the fact that in the first study, the abstract clearly says "this works X times better when treating mumps", while the other two papers ( and ) don't mention anything about mumps (at least in the abstracts), thus linking to them seems a little more abstruse. I haven't done a search on RMNPA - is there enough research to make it an entry of its own on WP? (Yeah, okay, that might be a little too specialized....)


 * Anyway, I'm not saying the two latter refs "absolutely don't belong", just slightly questioning the rationale. Let me know what you think. -- MarcoTolo 03:01, 20 April 2006 (UTC)


 * The first article mentions the benefit of the isomer, so I think it's all part of a reasonable line of inquiry. Might as well save some academic the searching.  Ideally, RMNPA-2 would get its own entry, but right now there is a lot of more pressing stuff to think about -- like working on the MMR page, or finding more references relating to the outbreaks, or what. Heathhunnicutt 19:15, 21 April 2006 (UTC)

Mumps
Moved. Please direct follow-ups to mumps discussion page. Heathhunnicutt 17:13, 22 April 2006 (UTC)

Mumps, Measles and Rubella combined vacciness
On MMR Vaccine you made a nice, grammatical edit under "Formulation." However, you also added the word "attenuated" in front of "virus" when describing the vaccine. I have removed the word attenuated where it is repititious, and added a fact tag asking for a reference.

In particular, what does the word "attenuated" mean in this case? Is Merck referring to the passage of virus through non-human tissue, changing the virus' tropism? Is it exposure to Formalyn? Is it the freeze-drying?

I know you are on the pro-vaccination side of the debate surrounding compulsory vaccination of children. Personally, I think both sides have valid assertions to make. I'm not happy with the article POV on MMR Vaccine, that is why I injected the topic of Formulation -- what the vaccine truly contains.

I think you are so 'pro-' vaccination, that you believe throwing around the word 'attenuated' might help your case. However, the word 'attenuated' sounds ridiculous. Merck called the vaccine's virus 'attenuated' 29 years before they were aware that there were two strains of Jeryl Lynn mumps in it. Now that it's 2006, we can be step-by-step specific about how that vaccine is made an what is in it. Heathhunnicutt 15:49, 3 May 2006 (UTC)


 * Attenuated as distinct from 1) wild or 2) dead or 3) sub-unit. Both subtypes of the strain Jerryl-Lynn wil be attenuated.  We don't have compulsory vaccination of children and I'm not part of a debate about it.  Vaccination against the potentially lethal childhood diseases seems to me a good idea, a view shared by the health services and governments of every country in the world.  I think I was the first editor to introduce the actual contents of MMR, that it is a mixture of three vaccines, prior to that readers were being presented with it as a separate thing from any of its components, something which has happened with an article on MMRV recently again. Midgley 16:56, 3 May 2006 (UTC)


 * Google: MMR attenuated::

MMR vaccine - Wikipedia, the free encyclopedia The MMR vaccine is a mixture of live but attenuated viruses, administered via injection for immunization against measles, mumps and rubella. ... en.wikipedia.org/wiki/MMR_vaccine - 55k - Cached - Similar pages

[PDF] ® II (MEASLES, MUMPS, and RUBELLA VIRUS VACCINE LIVE) File Format: PDF/Adobe Acrobat - View as HTML women should receive live attenuated rubella vaccine (such as that contained in monovalent rubella. vaccine or in MMR II) to reduce the risk of exposure of ... www.merck.com/product/usa/pi_circulars/m/mmr_ii/mmr_ii_pi.pdf - Similar pages

Notice to Readers: Licensure of a Combined Live Attenuated Measles ... Notice to Readers: Licensure of a Combined Live Attenuated Measles, Mumps, ... ACIP recommendations for MMR and varicella vaccines have been previously ... www.cdc.gov/mmwr/preview/mmwrhtml/mm5447a4.htm - 20k - Cached - Similar pages

Measles, Mumps, and Rubella -- Vaccine Use and Strategies for ...   Emphasis on the use of combined MMR vaccine for most indications; ... Live attenuated Edmonston B measles vaccine (distributed from 1963 to 1975) was ... www.cdc.gov/mmwr/preview/mmwrhtml/00053391.htm - 101k - Cached - Similar pages

MMR Information Centre - Immunisation - NHS Health Scotland MMR is a live vaccine and contains attenuated (weakened) strains of measles virus, mumps virus and rubella virus. This gives protection against the diseases ... www.healthscotland.com/immunisation/mmr/ - 26k - Cached - Similar pages

[PDF] MMR™II File Format: PDF/Adobe Acrobat - View as HTML Swallowing MMR™II would render the live attenuated ... MMR™II vaccine isa mixture of live attenuated measles, mumpsand rubella ... www.mmrthefacts.nhs.uk/resources/pdf/MMRII_SPC.pdf - Similar pages

Reactogenicity and immunogenicity of a new live attenuated ... OBJECTIVE: To compare the reactogenicity and immunogenicity of a novel live attenuated measles-mumps-rubella vaccine, SB MMR (Priorix; SmithKline Beecham ... www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9951979&dopt=Abstract - Similar pages

Reactogenicity and immunogenicity of a live attenuated tetravalent ...   With respect to immunogenicity, MMRV and MMR/V demonstrated similar seroconversion ... Vaccines, Attenuated/adverse effects Vaccines, Attenuated/immunology ... www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12450703&dopt=Abstract - Similar pages [ More results from www.ncbi.nlm.nih.gov ]

Morbidity and Mortality Weekly Report: Licensure of a combined ... The attenuated measles, mumps, and rubella vaccine viruses in ProQuad are identical and of equal titer to those in the measles, mumps, and rubella (MMR) ... www.findarticles.com/p/articles/mi_m0906/is_47_54/ai_n15971325 - 36k - Cached - Similar pages

VaccinePlace.com - Search. Know More About Immunizations and ... Attenuated: Weakened; in vaccines, the weakening of a virus or bacteria to disable its ... FAQs (frequently asked questions) about MMR vaccine & autism. ... vaccineplace.com/?fa=explore/general/10 - 18k - Cached - Similar pages

Help? Given that the second reference is the Merck product information on the vaccines you were wrting up the formulation of, may I ask where you got the formulation information from that didn't describe the virus component in that fashion?

Compare and contrast if you will with inoculation which is with a virus, th Smallpox virus, selecting what is known or believed to be the natural Variola Minor strain of Smallpox, IE this is the [intentional induction of immunity] using a non-attenuated virus of the organism concerned in the disease, or the induction of cross-immunity to Variola Major and Minor (and incidentally Camelpox and perhaps monkeypox) with Cowpox virus - not attenuated, not the same disease, which was the specific ground-breaking step by Edward Jenner. You may find the articles linked above interesting.

I see that reference one and reference three in MMR give the information that the viruses are attenuated, the latter giving it in part as part of the actual reference text. Would you care to replace the fact tag with a further footnote link to one or both of those if you feel the latter is needed, please? I'm a little unclear what caused you to think there was a problem, and also to express it in terms of a lack of balance or POV of mine, would you care to enlarge on that?

Dead and sub-unit examples
Sub unit is distinct from split virion, which is another sort of deactivated, not attenuated, vaccine against a viral disease. Infleunza vaccines available in this recent season in the UK have included both varieties. There is in addition an attenuated influenza virus vaccine which is presented as a nasal spray (and clearly contains no microbicidal components) The second viral disease vaccine prepared was Rabies by Pasteur and that is a dead virus vaccine. 17:02, 3 May 2006 (UTC)

Inhomogeneity of Jeryl Lyn strain virus, and when it should be known
"Afzal, et al., "The Jeryl Lynn vaccine strain of mumps virus is a mixture of two distinct isolates", (1993), Journal of General Virology, vol. 74, p. 917-920. Takeuchi, et al., "Variations of Nucleotide Sequences and Transcription of the SH Gene among Mumps Virus Strains", (1991), Virology, vol. 181, No. 1, pp. 364-366."

Is probably what you looked at. There is another interesting account given as part of a patent in teh same obvious Google search (jery lynn strains) which actually states tehre is a third nucleotide sequence.

You may wish to consider

1. The first virus to be completely sequenced was Polio, quite recently. Until then the difference between viral genomes (IE DNA/RNA sequences) would only be shown by differences in their morphology as observed under an electron microscope or by X-ray diffraction - or by differences in their clinical effect.

2. THere is no suggestion the two sequences have different effects (FX: Python: the three sequences ...)

3. Much of th ehuman genome has been described as "junk DNA". THis may be less true than had been thought, but it is clear that there is a substnatial amount of geneti material in organisms which is not expressed. Changes in this are of the utmost inconsequence in anything other than evolutionary timescales. Viruses, being smaller, will be more efficient on this, but I would be unsurprised if the differences in sequence were not in active genes...

4. The genetic code is sufficiently redundant that many single base changes in a codon do not change the meaing of th ecodon - the amino acid specified.

5. Of the product of genes - proteins - it is well understood that many amino acids are equivalent, or insignificantly different,  in effect at many of the locations in many proteins, even enzymes. Haemoglobin for instance had (IIRC) 140 known variants at the time when a classmate of mine was found via our Physiology class to have another as yet undescribed one, serum albumen as another instance is essentially a ball of string, and has evolved/diverged at about the basal mutation rate since most of it just doesn't matter. THus, even an effective change in a nucleic acid codon may not alter what it produces or th eproduct does.

6. Science progresses, and as it does the fine detail of our understnading of the world increases. I think this is A Good Thing, but there are those who use each new discovery to argue that those making it know nothing, since they have demonstrated they were totally wrong about every prior discovery by making a new one. THere is a paradox there of course, but basically it is barking.

Summary: you may be overestimating the interest and significance of nucleotide sequence variants in a strain or three sub-strains - of a virus. SOmething about the phrasing suggested a source which may be unreliable in evaluating ... well, almost anything.Midgley 17:30, 3 May 2006 (UTC)


 * Your replies strike me as surprisingly rude. In particular, your numbered series of assertions sounds erudite but is truly misleading.  You then accuse me of being " a source which may be unreliable in evaluating ... well, almost anything."


 * Regarding your assertions:
 * (1) We all know this, and it is inherent in my original complaint about the traditional term "attenuated."
 * (2) I think you are mistaken. There are published reports of differences in proteomics between JL1 and JL2. Perhaps you are unaware of this: Changes in Mumps Virus Gene Sequence Associated with Variability in Neurovirulent Phenotype and the other such publications.
 * (3) Your statement seems disingenuous. The Mumps genome is a single, linear, RNA-, 16kbase sequence with 7 genes which are known to encode 8 proteins.  Comparing this to the human genome is not merely extreme, but seems deliberately misleading.
 * (4-5) You are really repeating yourself on Freshman Biology, and also mistaken in the sense that there have been observed proteome differences between JL1 and JL2.
 * (6) We agree on this point. This is why I asked you to elaborate on "attenuated."  And by that I did not mean, "Teach us English."  I mean, "by what mechanism have the viruses been attenuated?"  What is the actual meaning, in this specific case, of "attenuated."  We all know that it represents the distinctions you cited: cultivated as opposed to wild, weaker than the wild strain in the following measured ways, etc.


 * The thing is, Midgley, I agree everyone should get vaccinated. I also think it would be nice if we had less-controversial vaccines to choose from.  In the U.S. presently, we are about to be hit with a major Mumps outbreak.  Lots of people will be getting Mumps booster shots.  Considering all the controversy surrounding MMR, there is good reason to make the article more comprehensive and fact-based.  Merely using the traditional word "attenuated" is deeply unsatisfying; nobody is learning anything from that.  I notice the reference I cited uses the term "neuroattenuated."  May I suggest that we adopt that term?


 * I'm sorry I seemed to steal some of your credit. I think it's wonderful that you added the ingredients to the intro on MMR Vaccine!  But let's put more citable science in that article in preparation for making it utterly reasonable. Heathhunnicutt 19:00, 3 May 2006 (UTC)


 * I see you also wrote this in your reply:

I see that reference one and reference three in MMR give the information that the viruses are attenuated, the latter giving it in part as part of the actual reference text. Would you care to replace the fact tag with a further footnote link to one or both of those if you feel the latter is needed, please? I'm a little unclear what caused you to think there was a problem, and also to express it in terms of a lack of balance or POV of mine, would you care to enlarge on that?


 * Yes, I would love to enlarge on that. I like your POV, but I do not like the article's POV.  I got in touch with you via a fact tag because I wanted to obtain a reference from you -- you are a physician interested in the article.  The problem with the article is not extremism of your POV, but rather the anti-vaccine content is greatly out of balance.  As I see it, the initial steps of rectifying this are to improve the on-topic portions of the article. Heathhunnicutt 19:07, 3 May 2006 (UTC)


 * Reply on my talk page - for a while - I can't do two places. The first Google hit I found describes how Mumps vaccine is attenuated.  http://www.who.int/vaccines-diseases/diseases/mumps_vaccine.shtml
 * I mean, on my talk page, I have written a reply. It won't be there for long, the page is too long and will be archived.

Midgley 23:39, 3 May 2006 (UTC)

MMR Vaccine
reply and original moved


 * Attenuated as distinct from 1) wild or 2) dead or 3) sub-unit. Both subtypes of the strain Jerryl-Lynn wil be attenuated.  We don't have compulsory vaccination of children and I'm not part of a debate about it.  Vaccination against the potentially lethal childhood diseases seems to me a good idea, a view shared by the health services and governments of every country in the world.  I think I was the first editor to introduce the actual contents of MMR, that it is a mixture of three vaccines, prior to that readers were being presented with it as a separate thing from any of its components, something which has happened with an article on MMRV recently again. Midgley 16:46, 3 May 2006 (UTC)
 * Your replies strike me as surprisingly rude. In particular, your numbered series of assertions sounds erudite but is truly misleading.  You then accuse me of being " a source which may be unreliable in evaluating ... well, almost anything."
 * Sorry,., I was in a bit of a rush.  The remark about a source definitely doesn't apply to you, I wondered if you had picked something up from a propagandist - IE a source unreliable about things.  Midgley 23:34, 3 May 2006 (UTC)


 * Thanks for that explanation. Heathhunnicutt 01:31, 4 May 2006 (UTC)


 * Regarding your assertions:
 * (1) We all know this, and it is inherent in my original complaint about the traditional term "attenuated."
 * (2) I think you are mistaken. There are published reports of differences in proteomics between JL1 and JL2. Perhaps you are unaware of this: Changes in Mumps Virus Gene Sequence Associated with Variability in Neurovirulent Phenotype and the other such publications.

It is a bit specialist for me - as a jobbing doctor with an interest in it - I think it is actually a bit specialist for most virologists or immunologists. That may suggest it is not really encyclopaedia material ... DOes it have a different immunogenicity, virulence, etc?  THose are potentially relevant for a vaccine.Midgley 23:28, 3 May 2006 (UTC)


 * As a computer scientist with professional experience in bioinformatics, it is the kind of article I've enjoyed reading for the last 9 years. Yes the strains do have different virulence w.r.t. tissue type (histotropism).  See that article's summary.Heathhunnicutt 01:31, 4 May 2006 (UTC)


 * (3) Your statement seems disingenuous. The Mumps genome is a single, linear, RNA-, 16kbase sequence with 7 genes which are known to encode 8 proteins.  Comparing this to the human genome is not merely extreme, but seems deliberately misleading.
 * Well, that is clever of it. What is the result of the two differences in sequence observed?  I didn't look it up again - on my way out to dinner - but in principle two things obtain: 1)theoretically I knew that, and 2)It is smaller than the human genome and therefore any given codon is much les likely to be insignificant, however the principle is a general one that applies to viruses.   Midgley 23:28, 3 May 2006 (UTC)


 * The principle in general does not apply to viral genomes. There is much more junk genomic material in human DNA than (proportionally speaking) in any virus.  In the case of Mumps, the case actually at hand I might remind you, the amount of non-coding, non-regulatory (promoter regions, etc.) material very minimal even for a virus. Heathhunnicutt 01:31, 4 May 2006 (UTC)


 * Put another way:
 * {|border="1"


 * Genome
 * Base Pairs
 * Human
 * 3 000 000 000 000
 * Mumps
 * 15 300
 * }
 * (4-5) You are really repeating yourself on Freshman Biology, and also mistaken in the sense that there have been observed proteome differences between JL1 and JL2.
 * Background.
 * Arguably.
 * Background.
 * Arguably.


 * (6) We agree on this point. This is why I asked you to elaborate on "attenuated."  And by that I did not mean, "Teach us English."  I mean, "by what mechanism have the viruses been attenuated?"  What is the actual meaning, in this specific case, of "attenuated."  We all know that it represents the distinctions you cited: cultivated as opposed to wild, weaker than the wild strain in the following measured ways, etc.
 * Probably best to ask Merck. If I have to, when I come back from holliday, I could evaluate the several references to this Google search:   Again, this may be a little post-graduate, if not PhD level for an encyclopaedia.  Midgley 23:28, 3 May 2006 (UTC)


 * I think it's a bit silly to hide behind the veil of "too advanced information." It's a fact that there are more strains identified in the vaccine than generally spoken of.  This same situation was identified in polio vaccines and you may also want to do a search on that literature concerning neurovirulence in polio vaccine.  What is important is that the information be correct and not misleading, IMO. Heathhunnicutt 01:31, 4 May 2006 (UTC)


 * The thing is, Midgley, I agree everyone should get vaccinated. I also think it would be nice if we had less-controversial vaccines to choose from.  In the U.S. presently, we are about to be hit with a major Mumps outbreak.  Lots of people will be getting Mumps booster shots.  Considering all the controversy surrounding MMR, there is good reason to make the article more comprehensive and fact-based.  Merely using the traditional word "attenuated" is deeply unsatisfying; nobody is learning anything from that.  I notice the reference I cited uses the term "neuroattenuated."  May I suggest that we adopt that term?
 * I finished giving my patients their MMR boosters to avoid that last year, and treated or observed a couple of people who chose not to get them or didn't get them for Mumps. My advice, which you can by all means repeat, is that everyone should ensure they have an adequate level of immunity to Mumps, ahead of the spread of disease, by the best means available to them.  If they live in or visit Exeter I shall be happy to assist them in this.  Midgley 23:28, 3 May 2006 (UTC)


 * "Neuroattenuated" is not a term I am familiar with. I personally would avoid using it on that basis alone, and also on the groujnds that it seems a term likely to confuse, me if not others. Midgley 23:34, 3 May 2006 (UTC)


 * In this case, "neuroattenuated" means that the virus' virulence in human nerve cells (neurovirulence) has been reduced, as compared to the wild strain from which it was derived. Dr. Hilleman passaged the virus through growth media (Chicken Eggs and Human + Bovine Serum Albumin) that selected for strains that were less well adapted to human nerve tissue.  Somehow, his strains were also useful for a live vaccine.  In the study I cited, the researchers used Vero cells (I love linking to that article!) and other growth media to derive (from the "attenuated" strains) new generations that were increased in neurovirulence.  They then sequenced the mutations which led to this adaptation and compared these mutations to the differences between JL1 and JL2.  However, they could not reach a definitive conclusion regarding the comparative neurovirulence of JL1 vs. JL2 because of confounding factors. Heathhunnicutt 01:31, 4 May 2006 (UTC)

Perhaps an appropriate replacement term might be "attenuated neurovirulence". Heathhunnicutt 01:31, 4 May 2006 (UTC)


 * I'm sorry I seemed to steal some of your credit. I think it's wonderful that you added the ingredients to the intro on MMR Vaccine!  But let's put more citable science in that article in preparation for making it utterly reasonable. Heathhunnicutt 18:49, 3 May 2006 (UTC)
 * Don't worry about it, but I'd suggest that attenuation of viruses is a _general_ topic rather than one to replicate into articles on specific vaccines. Midgley 23:28, 3 May 2006 (UTC)


 * I disagree very much -- in each case, there will be specific information about the way in which each virus has been attenuated. That specific information should not be lost.Heathhunnicutt 01:31, 4 May 2006 (UTC)


 * I see you also wrote this in your reply:

I see that reference one and reference three in MMR give the information that the viruses are attenuated, the latter giving it in part as part of the actual reference text. Would you care to replace the fact tag with a further footnote link to one or both of those if you feel the latter is needed, please? I'm a little unclear what caused you to think there was a problem, and also to express it in terms of a lack of balance or POV of mine, would you care to enlarge on that?


 * Yes, I would love to enlarge on that. I like your POV, but I do not like the article's POV.  I got in touch with you via a fact tag because I wanted to obtain a reference from you -- you are a physician interested in the article.  The problem with the article is not extremism of your POV, but rather the anti-vaccine content is greatly out of balance.  As I see it, the initial steps of rectifying this are to improve the on-topic portions of the article. Heathhunnicutt 19:07, 3 May 2006 (UTC)

I'd suggest sticking with "attenuated" in the introduction, and inserting into the article well down the page a note on the effect and nature of the attenuation in these vaccines. The idea of layering of information for different readers or purposes seems to apply here. If there isn't an article on attenuation of (vaccine) virus strains, and perhaps on the RNA "monster" which can arise in the test tube then there ought to be one. I actually favour having three articles, one each on M, M and R and a minimal entry for the mixtures MMR and MMRV. Midgley 08:49, 4 May 2006 (UTC)
 * Attenuated...