The US spends over 17% of income, two trillion dollars a year, on medicine, mostly on new intensive treatments. You might think this was because we long ago carefully studied all the simple cheap treatments, and got as much mileage as we could from them, so now must consider complex expensive treatments. You’d be very very wrong.
robin...why did you write Is that #$@%-ed up ethics or what? as opposed to "Is that fuck-ed up ethics or what?" Why are you so willing to be provocative with your ideas but you are scared to write the word "fuck"? It's actually a serious question.
It may not be scientific (because n=1), but I've found that when I have the 'flu, going to bed and turning the electric blanket up to "broil" works pretty well at shortening the time I'm sick.
Without any previous discussion, I asked my father, a practicing surgeon, what the standard treatment was for fevers in the hospital. Paraphrased, he said "Well, the fever is your body's natural response to infection, so as a rule of thumb we do nothing. However, we will give antipyretics in case of (1) significant patient discomfort when we do not think bringing down the fever would introduce any substantial risks (which is most of the time) or (2) certain injuries or complicating illnesses (usually only indirectly related to the infection) which are exacerbated by high body temperatures.
Nitrite (NO2-), previously viewed as a physiologically inert metabolite and biomarker of the endogenous vasodilator NO, was recently identified as an important biological NO reservoir in vasculature and tissues, where it contributes to hypoxic signaling, vasodilation, and cytoprotection after ischemia-reperfusion injury. Reduction of nitrite to NO may occur enzymatically at low pH and oxygen tension by deoxyhemoglobin, deoxymyoglobin, xanthine oxidase, mitochondrial complexes, or NO synthase (NOS). We show that nitrite treatment, in sharp contrast with the worsening effect of NOS inhibition, significantly attenuates hypothermia, mitochondrial damage, oxidative stress and dysfunction, tissue infarction, and mortality in a mouse shock model induced by a lethal tumor necrosis factor challenge. Mechanistically, nitrite-dependent protection was not associated with inhibition of mitochondrial complex I activity, as previously demonstrated for ischemia-reperfusion, but was largely abolished in mice deficient for the soluble guanylate cyclase (sGC) α1 subunit, one of the principal intracellular NO receptors and signal transducers in the cardiovasculature. Nitrite could also provide protection against toxicity induced by Gram-negative lipopolysaccharide, although higher doses were required. In conclusion, we show that nitrite can protect against toxicity in shock via sGC-dependent signaling, which may include hypoxic vasodilation necessary to maintain microcirculation and organ function, and cardioprotection.
The argument here isn't over whether we should treat fever under certain circumstances; the argument is over whether we should treat fever in most cases. FDA approval of fever-reduction methods has no bearing on how often someone's disease or discomfort warrants such treatment.
In the case of cholera, diarrhea is the disease. The only thing cholera toxin does is cause diarrhea, leading to dehydration. It does not damage your intestines, or any other tissues of your body. If you prevent the diarrhea from occurring, you have, in fact, cured the disease.
I only have limited experience, but I don't think I've seen doctors fever-reduction for the sake of fever reduction in adults for mild or moderate fevers (<~105 F), at least in adults.
Note that the Mayo Clinic guidelines for adults only say to take antipyretics "if you feel uncomfortable". And they discourage their use for minor fevers.
The linked randomized studies don&#039t show much of a benefit for antipyretic, but they don&#039t show a harm, either, so symptomatic treatment for patient comfort doesn&#039t seem like a big problem.
Diarrhea is the response of the host. The host evolved the capacity to exhibit diarrhea. Virtually all organisms with a gut have the capacity to exhibit diarrhea.
Organisms didn't evolve to avoid all bad things, they evolved to maximize survival and reproduction. Diarrhea may be fatal. Bacteria chewing at the gut until it perforates is orders of magude more likely to be fatal. Flushing out a gut that is filled with bacteria that are killing the cells that line the gut may kill the organism due to dehydration, but it may save the organism from a perforated gut.
Evolution configured the gut to try and minimize deaths due to dehydration while also minimizing deaths due to a perforated gut. What is minimized is the sum of deaths from both conditions. Because a perforated gut is virtually certain death, a fairly large number of deaths due to dehydration can be tolerated to prevent a perforated gut.
In other words, if the absence of diarrhea resulted in a perforated gut (and death) 90% of the time, but only 5% of the time in the presence of diarrhea, an organism would be better off inducing diarrhea that killed from dehydration 40% of the time because then diarrhea would be a great survival factor, changing 90% of deaths due to a perforated gut to 5% from a perforated gut and 40% from dehydration, a 50% reduction in deaths. A fabulously advantageous evolved feature.
Actually they are both accurate. I think the "diarrhea reaction" originally evolved to eliminate internal contaminants, then was "appropriated" by some pathogenic organisms as a way to spread.
Re: cholera, notice what the treatment is that keeps people alive -- allow diarrhea (to rid the body of pathogens), but give the host an IV rehydration solution. It is not to keep diarrhea from happening in the first place.
I and Ewald know that diarrhea is the pathogens' way of getting to the next host. Do you agree or disagree -- preventing diarrhea results in a higher concentration of pathogens in the current host than letting the diarrhea happen? Do you agree or disagree -- a higher concentration of pathogens in the host causes greater long-term damage to overall health?
Keep your eye on the ball kids. A thing can serve more than one purpose -- ridding the body of pathogens and thus lowering long-term damage, and by that very ridding, convey the pathogens to their next host.
If it's not in Plague Time, then it's in the more academic one, Evolution of Infectious Disease.
I was just about to say that. I read "Plague Time" fairly recently and that doesn't sound like Ewald. He actually got his idea while sick after he reconsidered his previous theory about the body's natural mechanisms and recognized it's just diarrhea's way of making more diarrhea. Having a better sanitation system which prevents diarrhea from spreading so easily from tainted water causes the disease to become less virulent. I don't know what would result from inhibiting the symptoms of it though.
You might want to examine IV acetaminophen (Ofirmev) and its clinical trials in fever. IV ibuprofen (Caldolor) was approved in 2008 for treating fever, so the FDA thinks that this is a clinically meaningful outcome.
Obviously not — this symptom is our way of getting the pathogens out of the body. Preventing the symptom would only keep their concentration high and allow them to cause greater damage.
How do you know this?
Counterargument: Diarrhea is the result of damage to the lower intestine caused by the infectious bacteria. It's not part of the body's defenses, and the harm caused by loss of fluids and impaired ability to absorb nutrients is much greater than the benefit of physically removing material from the body. It's the opposite: a mechanism evolved by pathogens to spread themselves and remove other, competing bacteria from the gut. It's also how cholera kills people: through diarrhea-induced dehydration.
robin...why did you write Is that #$@%-ed up ethics or what? as opposed to "Is that fuck-ed up ethics or what?" Why are you so willing to be provocative with your ideas but you are scared to write the word "fuck"? It's actually a serious question.
It may not be scientific (because n=1), but I've found that when I have the 'flu, going to bed and turning the electric blanket up to "broil" works pretty well at shortening the time I'm sick.
Without any previous discussion, I asked my father, a practicing surgeon, what the standard treatment was for fevers in the hospital. Paraphrased, he said "Well, the fever is your body's natural response to infection, so as a rule of thumb we do nothing. However, we will give antipyretics in case of (1) significant patient discomfort when we do not think bringing down the fever would introduce any substantial risks (which is most of the time) or (2) certain injuries or complicating illnesses (usually only indirectly related to the infection) which are exacerbated by high body temperatures.
Anon, very nice paper, thank you for the link.
Related: Nitrite protects against morbidity and mortality associated with TNF- or LPS-induced shock in a soluble guanylate cyclase–dependent manner
http://www.ncbi.nlm.nih.gov...
Nitrite (NO2-), previously viewed as a physiologically inert metabolite and biomarker of the endogenous vasodilator NO, was recently identified as an important biological NO reservoir in vasculature and tissues, where it contributes to hypoxic signaling, vasodilation, and cytoprotection after ischemia-reperfusion injury. Reduction of nitrite to NO may occur enzymatically at low pH and oxygen tension by deoxyhemoglobin, deoxymyoglobin, xanthine oxidase, mitochondrial complexes, or NO synthase (NOS). We show that nitrite treatment, in sharp contrast with the worsening effect of NOS inhibition, significantly attenuates hypothermia, mitochondrial damage, oxidative stress and dysfunction, tissue infarction, and mortality in a mouse shock model induced by a lethal tumor necrosis factor challenge. Mechanistically, nitrite-dependent protection was not associated with inhibition of mitochondrial complex I activity, as previously demonstrated for ischemia-reperfusion, but was largely abolished in mice deficient for the soluble guanylate cyclase (sGC) α1 subunit, one of the principal intracellular NO receptors and signal transducers in the cardiovasculature. Nitrite could also provide protection against toxicity induced by Gram-negative lipopolysaccharide, although higher doses were required. In conclusion, we show that nitrite can protect against toxicity in shock via sGC-dependent signaling, which may include hypoxic vasodilation necessary to maintain microcirculation and organ function, and cardioprotection.
The argument here isn't over whether we should treat fever under certain circumstances; the argument is over whether we should treat fever in most cases. FDA approval of fever-reduction methods has no bearing on how often someone's disease or discomfort warrants such treatment.
In the case of cholera, diarrhea is the disease. The only thing cholera toxin does is cause diarrhea, leading to dehydration. It does not damage your intestines, or any other tissues of your body. If you prevent the diarrhea from occurring, you have, in fact, cured the disease.
I only have limited experience, but I don't think I've seen doctors fever-reduction for the sake of fever reduction in adults for mild or moderate fevers (<~105 F), at least in adults.
Note that the Mayo Clinic guidelines for adults only say to take antipyretics "if you feel uncomfortable". And they discourage their use for minor fevers.
The linked randomized studies don&#039t show much of a benefit for antipyretic, but they don&#039t show a harm, either, so symptomatic treatment for patient comfort doesn&#039t seem like a big problem.
Sounds reasonable. Then we need some drug that relieves the discomfort without lowering the fever.
Diarrhea is the response of the host. The host evolved the capacity to exhibit diarrhea. Virtually all organisms with a gut have the capacity to exhibit diarrhea.
Organisms didn't evolve to avoid all bad things, they evolved to maximize survival and reproduction. Diarrhea may be fatal. Bacteria chewing at the gut until it perforates is orders of magude more likely to be fatal. Flushing out a gut that is filled with bacteria that are killing the cells that line the gut may kill the organism due to dehydration, but it may save the organism from a perforated gut.
Evolution configured the gut to try and minimize deaths due to dehydration while also minimizing deaths due to a perforated gut. What is minimized is the sum of deaths from both conditions. Because a perforated gut is virtually certain death, a fairly large number of deaths due to dehydration can be tolerated to prevent a perforated gut.
In other words, if the absence of diarrhea resulted in a perforated gut (and death) 90% of the time, but only 5% of the time in the presence of diarrhea, an organism would be better off inducing diarrhea that killed from dehydration 40% of the time because then diarrhea would be a great survival factor, changing 90% of deaths due to a perforated gut to 5% from a perforated gut and 40% from dehydration, a 50% reduction in deaths. A fabulously advantageous evolved feature.
Actually they are both accurate. I think the "diarrhea reaction" originally evolved to eliminate internal contaminants, then was "appropriated" by some pathogenic organisms as a way to spread.
Re: cholera, notice what the treatment is that keeps people alive -- allow diarrhea (to rid the body of pathogens), but give the host an IV rehydration solution. It is not to keep diarrhea from happening in the first place.
I and Ewald know that diarrhea is the pathogens' way of getting to the next host. Do you agree or disagree -- preventing diarrhea results in a higher concentration of pathogens in the current host than letting the diarrhea happen? Do you agree or disagree -- a higher concentration of pathogens in the host causes greater long-term damage to overall health?
Keep your eye on the ball kids. A thing can serve more than one purpose -- ridding the body of pathogens and thus lowering long-term damage, and by that very ridding, convey the pathogens to their next host.
If it's not in Plague Time, then it's in the more academic one, Evolution of Infectious Disease.
I was just about to say that. I read "Plague Time" fairly recently and that doesn't sound like Ewald. He actually got his idea while sick after he reconsidered his previous theory about the body's natural mechanisms and recognized it's just diarrhea's way of making more diarrhea. Having a better sanitation system which prevents diarrhea from spreading so easily from tainted water causes the disease to become less virulent. I don't know what would result from inhibiting the symptoms of it though.
You might want to examine IV acetaminophen (Ofirmev) and its clinical trials in fever. IV ibuprofen (Caldolor) was approved in 2008 for treating fever, so the FDA thinks that this is a clinically meaningful outcome.
Obviously not — this symptom is our way of getting the pathogens out of the body. Preventing the symptom would only keep their concentration high and allow them to cause greater damage.
How do you know this?
Counterargument: Diarrhea is the result of damage to the lower intestine caused by the infectious bacteria. It's not part of the body's defenses, and the harm caused by loss of fluids and impaired ability to absorb nutrients is much greater than the benefit of physically removing material from the body. It's the opposite: a mechanism evolved by pathogens to spread themselves and remove other, competing bacteria from the gut. It's also how cholera kills people: through diarrhea-induced dehydration.