The politics of AIDS in South Africa: beyond the controversies
BMJ 2003; 326 doi: https://doi.org/10.1136/bmj.326.7387.495 (Published 01 March 2003) Cite this as: BMJ 2003;326:495All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Dear Nicholas Bennett,
Once again thank you for your kind support ,interest and imput into
large scale clinical trials of antioxidants.
To be honest thats my sole reason for taking part in this debate.
In Reply to:
"Speaking of which: the necessary steps involved in organising a clinical
study of the kind proposed are relatively simple, providing one has the
infrastructure in place. Superficially it looks likely to get through an
Institutional Review Board and then all you would need would be funding
and a patient base. Mostly likely, for statistical power, it would have to
be a multicenter study, which significantly complicates the matter
(especially with regard to funding). It would be very important too to
properly design the study to have enough power to detect and control for
any differences between various arms."
I greatley appreciate your imput here and appreciate your good will
and spirit in this project. Personaly I feel it would be very interesting
and theraputic for all "sides" perhaps in an joint effort to establish
scientificaly the true theraputic potential of antioxidants to work
together in designing clinical trials of these antioxidant, mineral,
amino acid, micro nutrient agents.
Such a joint effort would benefit patients worldwide in establishing
what is and what is not effective. I feel it would also benefit all
"sides" Doctors/scientists who have taken time and effort in participating
in this debate which I am aware has or can be frustrating for all "sides".
Although all the "sides" may not be able to agree on everything it would
be fantastic if something constructive and positive could come out of this
for all "sides" patients and doctors.
Although at times it looks like all the different "sides" have no
common ground, I feel that by looking at things in another way I can see
that there is some common ground between the "sides" and feel it would be
in the best interests of patients/doctors and science to work together
both in clinical trial designe/investigation and experimentational models
in order to establish greater understanding.
Despite having opposing views or differing views I am sure that
actually we are all on the same side. That is I think all the "sides" all
want to help patients live longer , healthier more productive lives. To
this end I salute Nicholas Bennett for his good spirit and encourage
others from all "sides" to do the same.
In Reply to Nicholas Bennett :
"In fact, the type of immunosuppressive therapy used differs for
renal transplant and liver transplant recipients. In our study, the
majority of liver transplant recipients did not receive corticosteroids,
whereas all renal transplant recipients were treated with cortisone. It
was recently demonstrated in vitro that hydrocortisone acts directly on
the activation of the lytic cycle of HHV-8 in latently infected cells."
[1] "
Your quite right, I have been looking into this as well for quite
some time and it is interesting. I was even reading only a day or two ago
a paper that claimed to link increased KS occurance in people using
corticosteriod creams. With reference to this I found the following
studies interesting.
""Corticosteroid use in transplant recipients increases the incidence
and severity of Kaposi's sarcoma (KS), a disease associated with KS-
associated herpesvirus (KSHV) infection. Recently, the prototypic
corticosteroid, hydrocortisone, was shown to directly induce lytic cycle
reactivation of KSHV in latently-infected BCBL-1 cells." (1)
" Patients undergoing chronic steroid therapy for organ
transplantation are at increased risk for development of human herpes
virus 8(HHV-8)-associated Kaposi's sarcoma (KS). It has also been reported
that following steroid withdrawal, KS lesions often undergo partial or
complete regression. METHODS: We have examined the effect of
corticosteroid treatment on HHV-8 replication, gene expression, and lytic
protein expression in BCBL-1 cells in vitro. BCBL-1 cells were collected
after culture for 24-72 hr with hydrocortisone (HC) 1-5 microM, phorbol
ester 20 ng/ml (positive control), and culture medium only (negative
control). HHV-8 genomic conformation was examined by Gardella gel
analysis. mRNA expression of viral cyclin (v-Cyc), viral Bcl-2 (v-Bcl-2),
viral macrophage inflammatory protein-I (v-MIP-I), viral interferon
regulatory factor-1(v-IRF-1), and viral tegument protein (TP) was examined
by RT-PCR Southern blot. Viral protein expression within the cells was
examined by indirect immunofluorescence using 5 different HHV-8 positive
antisera from 4 renal transplant recipients and 1 patient with classic KS.
RESULTS: Gardella gel analysis revealed that HC induced an accumulation of
the linear replicative genomic form of the virus in a time-dependent
fashion. Southern blot analysis of the RT-PCR products revealed that HC
induced increased expression of v-IRF-1, v-Bcl-2, and TP mRNA, with little
discernible effect on v-Cyc, and v-MIP-I. Immunofluorescence revealed that
HC induced increased numbers of cells expressing lytic antigens.
CONCLUSIONS: These data indicate that hydrocortisone acts directly on BCBL
-1 cells to activate the lytic cycle of HHV-8 and provide further support
for the hypothesis that HHV-8 is activated in corticosteroid-treated
immunocompromised patients. " (2)
"Liver tissue is one of the principal targets of glucocorticoids,
therefore changes in the balance between hepatic oxidative and reductive
capacity may greatly influence adverse effects of glucocorticoid therapy.
In this study, effects of glucocorticoid on the activities of hepatic
antioxidant defence enzymes were examined by using developing chick
embryos.
After the administration of 0.25 micromol hydrocortisone sodium
succinate, a typical glucocorticoid, to 15-day-old chick embryos,
glutathione peroxidase, glutathione reductase, catalase and superoxide
dismutase in the liver generally began to decrease at around 4 h, reaching
60-70% of control levels between 24 and 48 h.
These changes were observed much earlier than the elevation of the
hepatic thiobarbituric acid reacting substance (TBARS) level which began
to increase from 20h, reaching about six times the control level at 48 h
after hydrocortisone administration. Conversely, the elevated TBARS level
decreased back to the normal level with the recoveries of these enzyme
activities. Furthermore, it was found that the aniline hydroxylase
activity, measured as a marker of oxidative activity, began to increase
after around 12 h.
These results suggested that TBARS levels were possibly produced by
the suppression of antioxidant defence abilities and the significant
induction of oxidative activity in the liver by glucocorticoid.
As the elevated TBARS in the liver can be distributed to tissues,
TBARS will be involved in the occurrence of some of the glucocorticoid-
induced adverse effects such as cataract formation." (3)
"In developing chick embryos, hydrocortisone induces cataract
formation following a decrease in lens glutathione content but an increase
in lipid peroxide content in lens, blood and liver.
The preventive effects of ascorbic acid 2-O-alpha-glucoside (AA-2G)
on these parameters were compared on cataract formation with those of
ascorbic acid (AsA) and ascorbic acid 2-O-phosphate (AA-2P). In these
tissues, AA-2G inhibited a decrease in glutathione content and an increase
in lipid peroxide content more effectively than either AsA or AA-2P.
Various tissues including lens and liver have alpha-glucosidase
activity, strongly suggesting that AsA is enzymatically liberated from AA-
2G in these tissues. In summary, these results suggest that AA-2G exerts a
potent anti-cataract activity via a reduction in oxidative damage through
AsA release." (4)
"he aim of this work was to determine the effects of dietary intake
vitamin E and selenium (Se) on lipid peroxidation as thiobarbituric acid
reactive substances (TBARS) and on the antioxidative defense mechanisms in
the liver of rats treated with high doses of prednisolone.
Two hundred fifty adult male Wistar rats were randomly divided into
five groups. The rats were fed a normal diet, but groups 3, 4, and 5
received a daily supplement in their drinking water of 20 mg vitamin E,
0.3 mg Se, and a combination of vitamin E and Se, respectively, for 30 d.
For 3 d subsequently, the control group (group 1) was treated with a
placebo, and the remaining four groups were injected intramuscularly with
100 mg/kg body weight (BW) prednisolone. After the last administration of
prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48
h and the activities of glutathione peroxidase (GSH-Px), superoxide
dismutase (SOD), and catalase (CAT) enzymes and the levels of glutathione
(GSH) and TBARS in their livers were measured.
GSH-Px, SOD, and CAT enzyme activities and GSH levels in prednisolone
-treatment group (group 2) began to decrease gradually at 4 h, falling
respectively to 38%, 55%, and 40% of the control levels by 24 h, and
recovering to the control levels at 48 h.
In contrast, prednisolone administration caused an increase in the
hepatic TBARS, reaching up to four times the levels of the control at 24
h. However, supplementation with vitamin E and Se had a preventive effect
on the elevation of the hepatic TBARS and improved the diminished
activities of the antioxidative enzymes and the levels of GSH.
Therefore, the present study demonstrates the effectiveness of
vitamin E and Se in reducing hepatic damage in glucocorticoid- treated
rats and suggests that reductions in increased TBARS as a result of
prednisolone may be an important factor in the action of vitamin E and
Se." (5)
I have also posted some more studies on cortisol here
Stress -Cortisol-drugs-infections-cancer-immune-suppression
http://groups.msn.com/aidsmythexposed/healthissues.msnw?action=get_messa...
While reading today as a result of what Nicholas Bennett said I found
some very interesting papers on the above subject which I will be adding
to the above post shortley which answered one or two long standing
questions I had for which again I thank him.
Best Wishes
James J Whitehead
Clinical trials volunteer
Member www.altheal.org and www.aidsmythexposed.com
References
1.J Med Virol. 2002 Mar;66(3):378-83.
Minimal reactivation of Kaposi's sarcoma-associated herpesvirus by corticosteroids in latently infected B cell lines.
Zoeteweij JP, Rinderknecht AS, Davis DA, Yarchoan R, Blauvelt A.
Dermatology Branch, National Cancer Institute, Bethesda, Maryland 20892-1908, USA.
2.Transplantation. 1999 Mar 15;67(5):648-52.
Hydrocortisone activation of human herpesvirus 8 viral DNA replication and gene expression in vitro.
Hudnall SD, Rady PL, Tyring SK, Fish JC.
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0741, USA. shudnall@utmb.edu
3.Pharm Pharmacol. 1998 Jun;50(6):655-60.
Alteration of activities of hepatic antioxidant defence enzymes in developing chick embryos after glucocorticoid administration--a factor to produce some adverse effects?
Lee JW, Iwatsuru M, Nishigori H.
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan. 4. Ocul Pharmacol. 1994 Fall;10(3):537-42. Related Articles, Links
Effect of ascorbic acid 2-O-alpha-glucoside on hydrocortisone-induced cataract formation in developing chick embryos: II. Influence on glutathione and lipid peroxide contents in the lens.
Nagata M, Hikida M, Mibu H, Muto N, Yamamoto I.
Central Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan. 5.Biol Trace Elem Res. 2003 Mar;91(3):231-41. Effects of dietary vitamin E and selenium on antioxidative defense mechanisms in the liver of rats treated with high doses of glucocorticoid.
Beytut E, Aksakal M.
Department of Physiology, Veterinary Faculty of Kafkas University, Kars, Turkey.
Competing interests:
Clinical trials volunteer
Competing interests: No competing interests
Gregory P Benvenuti has:
> "found this pearler on PubMed entitled "How HIV causes AIDS: implications for Prevention and treatment" by Foster HD..."
Foster is a Professor in the Department of Geography, University of Victoria Canada. There was no need to go to PubMed, Foster has put a response right here on this page (not that I'm blaming anyone for overlooking 1 of a whopping 700 responses).
The full title of the article on PubMed is:
Foster HD.
How HIV-1 causes AIDS: implications for prevention and treatment.
Med Hypotheses. 2004;62(4):549-53. Review
As you can see it was published in Medical Hypotheses. He chooses to believe that HIV is a necessary cause of AIDS, however deficiencies in certain nutrients are what causes the progression of disease. He also claims to have a patent pending on a nutritional cure for AIDS.
> "this Foster guy can't be an AIDS denialist because he hedges his bets by blaming HIV for decreasing glutathione levels (probably the only way he would get his article published)"
I don't think anyone here can necessarily define who is and who isn't a denialist. There are many sub groups even amongst respondents here. Such as HIV exists but doesn't cause AIDS (Rasnick et al), AIDS exists but HIV doesn't exist at all ('perth group' et al), HIV causes AIDS but it was brought here by aliens (JQ Smith) and other 'mixers' including Foster. At least Foster is consistent from what I've read unlike the absurdity of respondents who try and support 'perth group' arguments whilst quoting from Duesberg's work.
Suggesting that Foster was 'blaming' HIV as a way to get published overlooks the fact that Med Hypotheses publishes just about anything anyway, and Foster's views are repeated on his web site, his BMJ Response and his other (earlier) Med Hypoth article. If the putative mainstream enforcers were forcing him to say anything they have been very busy.
Competing interests:
None declared
Competing interests: No competing interests
In his Rapid Response “HIV diagnostics”, 1 February, Peter Flegg
wrote “The [antibody] tests used are approved for their purpose, namely
detection of HIV-antibodies, and not diagnosis of HIV infection”.
How does a person develop “HIV-antibodies” apart from being infected
with “HIV”?
Is Peter Flegg trying to tell us “HIV-antibodies” are not necessarily
induced by “HIV” infection?
If there are no other “clues from the history and examination”, in
other words, if the patient is no risk, healthy with normal CD4s but
nonetheless has “HIV-antibodies”, what is the diagnosis?
If "HIV antibodies" are not always caused by "HIV" how does Peter
Flegg know the “HIV antibodies" in AIDS patients are caused by “HIV”?
When was the last time Peter Flegg told a patient of any description
with “HIV-antibodies” he is not infected with “HIV”?
Competing interests:
None declared
Competing interests: No competing interests
In the vein of this discussion on antioxidants I found this pearler
on PubMed entitled "How HIV causes AIDS: implications for Prevention and
treatment" by Foster HD. Now isn't that the million dollar question? The
abstract reads as follows.
"HIV-1 encodes for one of the human glutathione peroxidases. As a
consequence, as it is replicated, its genetic needs cause it to deprive
HIV-1 seropositive individuals not only of glutathione peroxidase, but
also of the four basic components of this selenoenzyme, namely selenium,
cysteine, glutamine, and tryptophan. Eventually this depletion process
causes severe deficiencies of all these substances. These, in turn, are
responsible for the major symptoms of AIDS which include immune system
collapse, greater susceptibility to cancer and myocardial infarction,
muscle wasting, depression, diarrhea, psychosis and dementia. As the
immune system fails, associated pathogenic cofactors become responsible
for a variety of their own unique symptoms. Any treatment for HIV/AIDS
must, therefore, include normalization of body levels of glutathione,
glutathione peroxidase, selenium, cysteine, glutamine, and tryptophan.
Although various clinical trials have improved the health of AIDS patients
by correcting one or more of these nutritional deficiencies, they have
not, until the present, been addressed together. Physicians involved in a
selenium and amino-acid field trial in Botswana, however, are reporting
that this nutritional protocol reverses AIDS in 99% of patients receiving
it, usually within three weeks."
Oh really? So it IS antioxidant deficiency that causes AIDS after
all. Um, isn't that what the Perth Group have been saying for over 20
years? But this Foster guy can't be an AIDS denialist because he hedges
his bets by blaming HIV for decreasing glutathione levels (probably the
only way he would get his article published). Of course, another fabulous
trait of the all singing all dancing virus. This is all the more
interesting in the light of SC De Rosa's observation in his clinical trial
"GSH replenishment in HIV infection" (European Journal of Clinical
Investigation. 30, 915-929) where it is stated in the results section: "
Interestingly, the baseline values for GSH were significantly lower among
subjects who were taking AZT or other nucleoside reverse transcriptase
inhibitors (NRTI) than subjects not taking these drugs (respectively, n=27
and 26: median baseline GSH, 0.8 and 0.98 P=0.02, Wilcoxon one way CHI
squared)." Hmmmm... so HIV causes a decrease in GSH which leads to AIDS;
and people who have AIDS and who are taking AIDS drugs have lower GSH than
those who are not. Thus it would seem that once again the AIDS denialists
are vindicated.... AZT and its brothers accellerate the onset of AIDS
becuase they lower GSH, the levels of which determine the progression to
AIDS. What's also quite amusing is that HIV-1 apparently encodes for
glutathione peroxidase as it's being replicated. But hang about, I thought
that's what AIDS drugs stop the virus from doing. This also doesn't tie up
with de Rosa's observations that those on NRTI's have lower GSH. They
should have higher GSH if their drugs are stopping the virus from
replicating. Erm, maybe the AIDS denialists were right again - NRTI's do
not stop viral replication, maybe they just bugger up all the cellular
processes and that is the real reason for the lower GSH in the poor souls
on NRTI's.
What I wonder is what happens then to all those other millions of
theories of how the "virus" induces programmed cell death and why only CD4
cells supposedly are decreased in "infected" people. Now that we've
discovered that HIV-1 genetically codes for glutathione peroxidase why has
NAC treatment not been rolled out? The trials have been done, almost ten
years ago. We now have a so-called "mechanism" for the disease and a well
run trial proving that the increasing GSH improves clinical and health
outcomes.
James Whitehead, don't hold your breath for any more trials, they
won't be forthcoming. BigPharma can't make money out of nutritional
therapies.
Competing interests:
None declared
Competing interests: No competing interests
I appreciate Mr Whitehead's clarification - the quote makes rather
more sense knowing it came from that particular source.
The mice developed the disease after repeated cross-matings, which
apparently activated ERV's from each inbred species (which then became
exogenous!). The disease was present in donors and recipients. As far as
I'm aware no herpes virus was present (or even looked for!) but it did
appear as if the combination of activated endogenous RVs was able to
induce a hemoproliferative disease that looked similar to KS. I can see
no theoretical reason why one particular RV can't induce a proliferative
disease in lymphocytes, and another in reticulocytes or whatever.
KS does occur in people with higher CD4 counts that most AIDS-
defining OI's, but they are still suppressed to a degree. The correlation
is less, I agree, because it seems to require lower levels of immune
suppression (hence perhaps why it is so much more common in HIV+ people
compared to uninfected controls). The Thai data is very interesting,
since the serology to HHV8 seems reasonably high compared to the clinical
picture. Something is clearly different compared to the American
experience.
As regards liver versus kidney transplants, I think this is due to
the particular anti-rejection drugs being used. Amazingly the Andreoni
study's results were not statistically significant regarding KS appearance
between liver and kidney transplant recipients (despite having a rate of
zero in liver transplant recipients)! They do however address the issue
by pointing out that:
"In fact, the type of immunosuppressive therapy used differs
for renal transplant and liver transplant recipients. In
our study, the majority of liver transplant recipients did
not receive corticosteroids, whereas all renal transplant
recipients were treated with cortisone. It was recently
demonstrated in vitro that hydrocortisone acts directly on
the activation of the lytic cycle of HHV-8 in latently
infected cells." [1]
Which as well as pointing out a potential confounding factor, further
implicates HHV8 in causing KS. What should be obvious though, is that if
Yang et al can cause a near-idential lesion to KS in transgenic mice with
a single gene of HHV8, what prevents this from happening in the majority
of those with clinically inapparent HHV8 infection? Maybe the Thai data
will shed some light on this, if further investigations have been/are to
be performed.
Speaking of which: the necessary steps involved in organising a
clinical study of the kind proposed are relatively simple, providing one
has the infrastructure in place. Superficially it looks likely to get
through an Institutional Review Board and then all you would need would be
funding and a patient base. Mostly likely, for statistical power, it
would have to be a multicenter study, which significantly complicates the
matter (especially with regard to funding). It would be very important
too to properly design the study to have enough power to detect and
control for any differences between various arms.
Nick Bennett njb35@cantab.net
1. Andreoni J Infect. 2001 Oct;43(3):195-9. "Prevalence, incidence
and correlates of HHV-8/KSHV infection and Kaposi's sarcoma in renal and
liver transplant recipients."
Competing interests:
None declared
Competing interests: No competing interests
Mr Russell makes several statements as if they are truisms, when they
are not.
"Contrary to Bennett’s claim, Etienne de Harven's methodology is far
more rigorous at isolation/purification of virus than other methods and
all other indirect surrogate markers which are non-specific."
Firstly it is not "my" claim, but a simple fact and a well known
problem with most oncoretroviruses. The transforming virus is usually
defective and requires a replication competant helper virus - structurally
indistinguishable, and therefore requiring molecular methods in other to
differentiate the mixture. The De Harven viruses have been clearly
demonstrated to be mixtures by various experiments, whereas those of HIV
contain only a single type of nucleic acid. The very fact that the genome
CAN be sequenced is proof enough, because the di-deoxy chain-termination
method and subsequent gel electrophoresis very easily detects mixed
samples (as any unlucky graduate student or postdoc will attest).
Secondly the molecular methods are far from non-specific. By their
very nature, DNA and antibody-based detection methods are extraordinarily
accurate.
"If you have to amplify the putative 'HIV' in the first place by
using PCR to show that it is there at all then there was obviously not
enough 'virus' present to have any pathogenic relevance or even an
infectious relevance. "
The conclusions doesn't follow at all - I repeat my request for Mr
Russell to show high peripheral titers of other pathogenic viruses such as
influenza, rabies, HPV etc. Lymph node titers are around 10-100 fold
higher than those in peripheral blood, and there is clear evidence that
sufficient virus is there to cause disease (Pantaleo et al found up to 10%
of all lymph node cells infected with HIV, of which only some will
actually be CD4 T cells). Ho et al found 3,500 tissue-culture infectious
doses of HIV per milliliter of peripheral blood. How much HIV would Mr
Russell like?
PCR is an aid, not a last resort.
HIV has certainly been isolated to extraordinary levels of purity
from lab cultures of peripheral blood and lymph nodes. Since culture is a
well used technique applied throughout virology and bacteriology, why
should it not be applied here to aid in detection? If there is enough
virus to culture, then clearly there is enough to be infectious and
potentially pathogenic!
De Harven for example performed plasma-derived virus detection after
injecting leukemic spleens into a particular mouse strain. Hardly an
appropriate model for a natural virus infection! Most of the structural
work he performed was on cultured virus, although I do admire the clarity
of the EM's he did acquire from some peripheral samples. Perhaps if we
were to inject an inbred human strain with high doses of lymph node
cultures of HIV we might achieve the same kind of electron micrographs.
De Harven's standard plasma protocol used virus obtained within 4-10 days
post innoculation, in exactly the same timeframe as Gelderblom was asking
for with his HIV experiments.
The only problem present here is Mr Russell's personal opinion on
what constitutes good science. Nothing more. What he criticises is only
aimed at HIV, and doesn't take into account any kind of background general
virological techniques. There have been almost identical EM's published
of HIV in semen [1] as have been seen with sexually transmitted murine
retroviruses [2]. Would this be possible in Mr Russell's world view of
HIV?
Nick Bennett njb35@cantab.net
1. Baccetti et al J Cell Biol. 1994 Nov;127(4):903-14. "HIV-particles
in spermatozoa of patients with AIDS and their transfer into the oocyte."
2. Portis et al J Virol. 1987 Apr;61(4):1037-44. "Horizontal
transmission of murine retroviruses."
Competing interests:
None declared
Competing interests: No competing interests
Several times in his recent posts Alex Russell has referred to HIV as
"an epiphenomenon" and the viruses purportedly involved as "endogenous
entities." Can he please explain in greater detail what he means by these
terms?
For example, as I provisionally grasp this idea, does he mean to say
that viruses are simply random products of deranged cells? In which case,
does this apply only to certain viruses, all viruses and what about
bacteria?
Does he then further mean to say that such "endogenous entities"
cannot realistically be regarded as the *causes* of a disease process, but
that they might be better understood as mere 'associative factors' or even
products of a disease? It would be very helpful if Alex Russell could
clarify these points.
Competing interests:
None declared
Competing interests: No competing interests
Dear Nicholas Bennett,
I thank you for your support for large scale clinical trials into
antioxidants.
In reply to Nicholas Bennett
"One wonders what description of a lesion Mr Whitehead would consider
better than this, as evidence supporting HHV8 in causing Kaposi's Sarcoma?
He uses the phrase "at best" as if the findings somehow fall short of
meeting his expectations, whereas for me as a virologist they far exceed
my wildest expectations! For example, we cannot (yet?) induce an AIDS-
like illness by adding a single gene from HIV into an animal model. To do
this for HHV8 and KS is a holy grail of viral pathogenesis. "
I apologise for any confusion I may of caused but the quote you use
"He uses the phrase "at best" "was not from me but The Perth Group.
In Reply Nicholas Bennett
"The report of a possible mouse model of AIDS mentioned by Mr
Whitehead is interesting because it highlights the problem I previously
mentioned to Alex Russell some time ago, regarding the prolific number of
mouse retroviruses: both exogenous and endogenous. The followup papers to
that report clearly demonstrate the fact that this was the result of a
previously unknown retrovirus infection, which is sexually and
horizontally transmissible. Two endogenous retroviruses were activated and
the co-infection results in the disease process mentioned (a
lymphoproliferative condition and an autoimmune CD4 T cell depletion) [2].
"
And
"HHV8 is not only epidemiologically associated with KS, but can be
detected in all forms of KS, from almost all samples, but not from
surrounding tissues. The fact that it contains genes that are demonstrably
and theoretically capable of causing cancer is enough for most people. "
So the donnor mice had not one but two exogenous and endogenous
retroviruses that did not cause "aids" like diseases or KS like legions in
the donnors but only the recipients ?
Was HHV-8 also present in the donnor mice ? Was HHV-8 present in the
recipient mice ?
KS does occur in people who are not immunosuppressed with high CD4's,
It occurs in people with hiv with CD4's above 700.KS occurs in hiv
negative non immunosuppressed people on kidney dialysis with high
CD4's.Yet it is very rare in hiv positive hhv-8 positive people from
Thailand with aids who I presume are immunosuppressed ?The degree of
severity of KS in my view in no way corresponds with CD4. Like the
incidence of KS in immunosuppressed liver transplant recipients who HHV-8
positive being lower than the incidence of KS in immunosuppresses Kidney
transplant recipients despite having a higher HHV-8 incidence. IE.
"Although Andreoni et al. found that 21.4% of liver recipients, but
only 8.6% of kidney recipients, seroconverted for KSHV, the risk of KS was
higher in the kidney transplant recipients." .(1). "
""Iatrogenic Kaposi's sarcoma develops in patients undergoing
immunosuppressive treatment and is considered to be induced by activation
of latent HHV8. In most cases the first manifestation of Kaposi's sarcoma
develops after 1 year from when the drug was first administered. In a
recent study from Italy on HHV8 positivity in patients with Kaposi's
sarcoma, it was found that 52% of the control group were positive (Masini
C., et al. G Ital Dermatol Venereol 1999; 134: 315-320). For this reason
we could expect a larger number of cases of iatrogenic Kaposi's sarcoma
given the number of patients who undergo immunosuppressive treatment for
one reason or another. Thus, we have to look to a contemporaneous presence
of other factors that co-operate with the HHV8. We present a case of a 49-
year-old woman, HHV8 and HCV positive, who develops a Kaposi's sarcoma
after 9 months of steroid therapy (methylprednisolone 16 mg/die). The low
dose of steroids prescribed to our patient and the fact that the first
skin manifestation developed after a shorter period than average from the
start of therapy do not explain the acute onset of an extensive Kaposi's
sarcoma even taking into account the HHV8 positive status." (4)
Courtesy Christopher Tyler.
"Human herpesvirus 8 (HHV-8) is associated with Kaposi sarcoma (KS) in
patients with AIDS and KS, classical KS, or endemic KS. Because HIV
infections and HIV/AIDS are common in Thailand but KS is very rare (only
0.2% of reported patients with AIDS in Thailand had KS), researchers
determined the HHV-8 seroprevalence among populations who were HIV
positive or at risk of HIV infection. " (1)
"The antibody prevalence was 24.2% in the total population. The
prevalence was higher among HIV-negative men (13.0%) but was similar among
HIV-positive women (27.9%) and HIV-negative women (23.8%). The HHV-8
seroprevalence among wives whose husbands were HIV-1 positive did not
differ according to their husband's HHV-8 status. There was no association
between HHV-8 seroprevalence and reported sexual behavior or STD history.
"(1)
"Conclusion Despite the rarity of KS among patients with AIDS in
Thailand, HHV-8 infections are common and do not appear to be frequently
transmitted sexually in these populations. "(1)
"In this issue of Clinical Infectious Diseases (October 1, 2004),
Chen et al. report on HHV-8 seroprevalence in northern Thailand, a region
notable for a very low incidence of KS despite a relatively high incidence
of HIV/AIDS, and lend further support to the related concepts that HHV-8
infection is not uncommon in HIV-negative adults in regions of the world
in which KS is not endemic and that transmission of HHV-8 often occurs by
nonsexual means. " (2)
"Another interesting finding reported by Chen et al. is the lack of
correlation between the relatively high incidence of HIV/AIDS and HHV-8
infection and the very low incidence of KS. "(2)
"As the authors suggest, it is very likely that there are
unrecognized cofactors involved in KS pathogenesis that have yet to be
accounted for. " (2)
Last question while reading up on the seroprevelance of HHV-8 I
noticed that the incidence of HHV-8 seropositivity was higher (average
twice as high) amongst patients with ESRD who where on dialysis compared
with the seroprevelance of control groups from the same geographical area
(references available). Why ?
Best Wishes
James J Whitehead
Clinical trials volunteer
Member www.altheal.org and www.aidsmythexposed.com
References
(1)N Chen and others. Seroprevalence of Human Herpesvirus 8 Infection
in Northern Thailand. Clinical Infectious Diseases 39(7): 1052-1058.
October 1, 2004.
(2)S D Hudnall. Crazy 8: Unraveling Human Herpesvirus 8
Seroprevalence (Editorial Commentary). Clinical Infectious Diseases 39(7):
1059-1061. October 1, 2004.
(3). (1)MMBR Online Microbiology and Molecular Biology Reviews, June
2003, p. 175-212, Vol. 67, No. 2 1092-2172/03/$08.00+0 DOI:
10.1128/MMBR.67.2.175-212.2003 Copyright © 2003, American Society for
Microbiology. All Rights Reserved.
http://mmbr.asm.org/cgi/content/full/67/2/175#Iatrogenic%20KS
(4)J Eur Acad Dermatol Venereol. 2004 Mar;18(2):191-3.
Iatrogenic Kaposi's sarcoma and HCV infection.
Monti M, Mancini LL, Ceriani R, Hendrickx I, Guizzardi M.
Departement of Dermatology, I.C. Humanitas, University of Milan, Via
Manzoni, 56 - Rozzano (Milano), Italy. marcello.monti@humanitas.it
Competing interests:
Clinical trials volunteer
Competing interests: No competing interests
Dear All,
What would be the best ways to actually get these long over due large
clinical trials done ??
The rest is a side issue which could be resolved by experimentation.
I would hope , suggest all "sides" have an imput and designes both in
clinical trial designe and experimentation designes.Either way I think
oxidative stress is criticaly involved and there for antioxidants
particulary pro GSH ones eg: just a few NAC,SAG,ALA, ect might be of
theraputic value (yet to be fully determined).
References (1)and (2) Was courtesy Christopher Tyler via a post on KS
found here
http://groups.msn.com/aidsmythexposed/healthissues.msnw?action=get_messa...
And the original source Can be reached here.
http://www.hivandhepatitis.com/recent/std/hhv8/092704_d.html
Best Wishes
James Whitehead
Member www.altheal.org and www.aidsmythexposed.com
Competing interests:
Clinicaal trials volunteer
Competing interests: No competing interests
Re: Re: Re: Re: Re: Clinical trials of antioxidants
In reply to Mr Benvenuti, and in the spirit of Prime Minister's
Questions "I refer the gentleman to the answer I (and others) gave some
weeks ago".
This particular topic and paper were discussed in Mid-January, and
the findings and logic largely rejected! I appreciate that the entire
thread of responses is very difficult to view (impossible for me with
Internet Explorer) but I have had 100% success using Firefox (an open
source, free web browser). I highly recommend this particular program, at
least for the purposes of viewing the complete list of responses in this
thread.
http://www.mozilla.org/products/firefox/
http://bmj.bmjjournals.com/cgi/eletters/326/7387/495
Nick Bennett njb35@cantab.net
Competing interests:
I am a Firefox convert, but have no commercial interest in the program.
Competing interests: No competing interests