Simply because temperature can be measured, and there is elevated temperature, does not mean that the elevated temperature caused what ever adverse effect is observed. In Reyes Syndrome, one of the symptoms besides fever is fatty liver. How does elevated temperature cause fatty liver?

She was compensated for an encephalopathy – a vaccine act table injury – which the court, on a very low standard of evidence, intentionally set to favor claimants – accepted to have occurred within the time-frame set out in the table.

Most conspicuously, her claim made no reliance on the work of Dr Andrew Wakefield, Big Pharma’s friend, whose involvement in litigation has devastated the interests of thousands of families in the US and UK.

My research relates to basal levels of NO. These cannot be measured in vivo because there are no techniques to do so. The levels that are important are in the nM/L range, less than a ppb. All immune system responses are characterized by both pro-inflammatory and anti-inflammatory responses. When these two responses are balanced, nothing much bad happens. When they are not balanced, then the patient can die.

Nitric oxide is mostly an anti-inflammatory agent. Its production during immune system stimulation is balanced by the production of superoxide which is mostly pro-inflammatory. When these two things get out of whack, then the patient dies. In sepsis, too much NO can cause generalized vasodilatation and low blood pressure. That takes a very high NO level, around 10 nM/L (which for NO is very high). Usually NO that is so high that it causes systemic hypotension can be dealt with temporarily (in an ICU). If the high NO goes on for too long, then the patient becomes depleted in glucose and there is insufficient glucose to produce ATP via glycolysis, so the mitochondria have to turn on to generate ATP via oxidation. It is mitochondria turning on in a high NO environment that causes mitochondria failure. I think this is what causes the multiple organ failure of sepsis (my hypothesis).

Each tissue compartment and each cell, and each mitochondrion regulates the NO/superoxide balance itself. If a few get out of whack, a few mitochondria may be damaged. A few mitochondria are expendable. It probably takes a loss of 50-90% of mitochondria to cause cell death (depending on a lot of other things), but that is really hard to measure.

What determines the NO level during immune system stimulation is how much iNOS is expressed. That is regulated by NFkB, which is inhibited by NO. So the lower the basal NO level, the higher the NO level will be following immune system stimulation. Much of this NO is generated in immune cells, and these cells move around, and are also controlled by multiple cytokines and also by temperature.

A high fever is not necessary for a good immune response. I suspect that a vaccine with an adjuvant like aluminum hydroxide would be safer than a vaccine that produces the same antibody titer without an adjuvant. Much of the antigen in an aluminum hydroxide adjuvanted vaccine is sequestered on the aluminum hydroxide and so it takes a longer time for the immune system to process it. That longer time translates into a lower peak level of cytokines and (probably) a reduced peak fever.

I think that a lot of the malaise effects during fever are a consequence of the interaction between the pro and anti-inflammatory responses. Blocking those responses might (my hypothesis) adversely affect the body’s ability to regulate them and so keep them in balance.

The immune system is far too complex to be able to predict what is going to happen in great detail, particularly at the extreme ends of the distribution. Vaccines are demonstrably safe for virtually all children; there is no way to predict who they might not be safe for at which time under what conditions. It is inconceivable to me that a vaccine could possibly be worse than the disease. An actual infection with an actual disease agent would almost certainly be far worse than the vaccine which has been demonstrated to be safer in 99.99% of cases, which is about at the limit of what clinical trials can measure.

Virtually all cases of ASDs are not characterized by neuropathy and are not characterized by mitochondrial dysfunction. An acute vaccination can’t have long term effects on mitochondria unless the regulation of mitochondria biosynthesis is affected long term. There is nothing special about vaccines that would cause long term disruption of mitochondria regulation. An actual infection would be expected to be much worse. If Hannah Poling had gotten one of the diseases she had been vaccinated for, it might have killed her. A single dose of some antibiotics might affect long term regulation of mitochondria (months even). If Hannah Poling was given antibiotics that affected mitochondrial protein synthesis, that might explain her sensitivity to mitochondrial damage. I am speculating, but it might be the combination of an antibiotic and her mitochondrial polymorphism that gave her that increases sensitivity. If so, then the Polings are being reckless by not releasing information on her antibiotic history.

It isn’t the fever per se that damages neurons. Temperatures have to get very high to do that, it is something associated with the immune response that is associated with the fever that does it. That something is unknown.

Of course duration and severity of a febrile episode can have a profound effect on mitochondrial function or damage but the cause of the fever is irrelevant, be it via vaccination or natural infection.

However, the creation of cytokines, which can affect the severity and duration of fever isn’t necessarily equivalent between natural infection and vaccination, especially if, as did Hannah Poling, you get many vaccines simultaneously. Why? Because the toll like receptors which initiate the innate immune response respond synergistically when several are triggered simultaneously.

Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: Implications for vaccines

Although TLR ligands individually may be ignored at certain low doses, the host may have evolved to recognize some together as a combinatorial assault and mount immune responses against these combinations in a synergistic manner. This strategy would allow the immune system to rapidly respond to infection. Studies have addressed the questions on what combinations of TLR ligands can synergistically increase the magnitude of cytokine production by DCs (15–22). However, in addition to discovering new synergistic combinations, questions still remain about whether there is a logic to the TLR synergistic patterns that can be identified, what the underlying mechanism is for TLR synergy within target cells, and from a translational point of view, what can be learned for vaccine design.

We first found that the MyD88-dependent and MyD88-independent DC functions are divergent in response to nonrandom, synergistic TLR ligands. MALP-2- and CpG-ODN-associated MyD88-dependent DC function in producing IL-12, TNF?, and IL-6 was remarkably augmented when poly(I·C) was included.

If your body believes it is under attack by several agents simultaneously, it responds synergistically; in this observation, by creating aditional pyrogenic cytokines. If our measurement of interest is robustness of the innate immune response, which can in turn affect febrile response, triggering several TLRs at once is qualitatively different than one at a time.

The argument has long been that getting one vaccine, two vaccine, or eight vaccines at once didn’t make a difference; but clinically we are beginning to understand that this isn’t true.

– pD

I could grant that fevers can be of different types in terms of severity and duration, but outside of this, do they actually work differently depending on their cause?

Very interesting question, I think that to some, ahem, degree, the answer is yes. Take a look at the abstract I posted above:

Recombinant human tumor necrosis factor (rTNF alpha) injected intravenously into rabbits produces a rapid-onset, monophasic fever indistinguishable from the fever produced by rIL-1. On a weight basis (1 microgram/kg) rTNF alpha and rIL-1 produce the same amount of fever and induce comparable levels of PGE2 in rabbit hypothalamic cells in vitro; like IL-1, TNF fever is blocked by drugs that inhibit cyclooxygenase. At higher doses (10 micrograms/kg) rTNF alpha produces biphasic fevers. The first fever reaches peak elevation 45-55 min after bolus injection and likely represents a direct action on the thermoregulatory center. During the second fever peak (3 h later), a circulating endogenous pyrogen can be shown present using passive transfer of plasma into fresh rabbits. This likely represents the in vivo induction of IL-1. In vitro, rTNF alpha induces the release of IL- 1 activity from human mononuclear cells with maximal production observed at 50-100 ng/ml of rTNF alpha.

Here, we observe the initiation of a biphasic fever, but only at specific concentrations of the pyrogenic cytokine in question. I guess it could be debated as to if a secondary increase in temperature is really a “different” fever or not, but my view is that if it bothered to be defined, it has distinctive characteristics. But even if we disagreed on this, severity and duration are very important components of a fever.

I imagine that daedulus2u could speak intelligently towards this question, his post concerning fever therapy is rather robust. Daedulus2u?

BTW, based on this study I posted, should children not be put in day-care if they are too young? I’m being pretty serious with that question, but I also wanted to note that perhaps Big Day-Care wants to cover up this information.

Indeed. To my mind this is a similar mass cultural change that has occurred in the past generation that could be having very difficult to understand impacts; very similar to the gradual increase in parental age. By way of example, some studies indicate that attendance at day care is provides protection from asthma, though other studies indicate that this effect is time dependent. But then again, a more recent study found no such protective effect, but did report additional infections in children attending daycare.

– pD

I have also not seen any reliable documentation that states that Hannah Poling was definitively diagnosed with autism, but rather statements such as, “”regressive encephalopathy with features consistent with an autistic spectrum disorder, following normal development.” and, “The clinicians concluded that CHILD was developmentally delayed and demonstrated features of autistic disorder.” From: http://www.huffingtonpost.com/.....88558.html

To my knowledge, the particular de novo mutation Ms. Poling posses has not been shown to be associated with developmental problems in any study. If I am incorrect, a reference would be nice.

First, I don’t know what makes you think that her T2387C point mutation is a de novo one and secondly, this is a point mutation on the 16S ribosomal RNA gene and other point mutations on this gene have been associated with encephalopathy: http://www.theness.com/neurologicablog/?p=203 Furthermore, the girl had a biochemical profile that was consistent for mitochondrial function deficits so it is rather difficult to argue that this mutation didn’t have anything to do with clinical manifestations of a mitochondrial disorder and subsequent encephalopathy.

BTW, based on this study I posted, should children not be put in day-care if they are too young? I’m being pretty serious with that question, but I also wanted to note that perhaps Big Day-Care wants to cover up this information.

pD – Hannah Poling does (did?) indeed have autism. But thats not to say that the vaccine caused the autism. Even the paper co-authored by John Poling doesn’t carry enough diagnostically appropriate symptoms to say that.