WIFI, VACCINES, ASPARTAME KILL!
Dedicated to all parents and in particular to all my grandchildren
including my granddaughters Jumaymah, Aïshah and Baby Layana, and my grandson Kenji born 30 January 2016.
Corinne Gouget, interview sur les additifs alimentaires et l'aspartame
BRITONS MICROWAVED IRISH CATHOLICS ! 
 WIFI IS CRIMINAL AND DAMAGES HUMAN DNA (GENES)!
Barrie Trower at the Open Mind Conference 2012, part 1
   VACCINES KILL BABIES!
Désirée Röver at the Open Mind Conference 2012. Part 1
 
        
      
    
  
  
  Edition: International |
Wednesday 18 March, 2015
Tension 
       Increases 
        - Federal Judge 
       Orders CDC to Produce Secret Documents... 
          
          
The CDC Has Known All Along How Dangerous Vaccines Are - And Has Covered It Up... (Part Six)
       
       
        
       
       
        
The CDC Has Known All Along How Dangerous Vaccines Are - And Has Covered It Up... (Part Six)
Opinion by Consumer Advocate 
           Tim 
          Bolen 
Friday, July 6th,  2012
          
       
This article is the sixth in a series 
          about THE MOST IMPORTANT CASE ABOUT 
          AUTISM currently being litigated - the 
          Hooker v. United States Department of 
          health and Humans Services, et al case.
Why is this the most important case?  
Because of what happened in what was 
          called the  "Omnibus 
          Autism Proceedings" (OAP) in 2010. 
The special Vaccine Court created by 
          the 
          
          National Childhood Vaccine Injury Act 
          (NCVIA), in 1987, had become overloaded 
          with claims about 2007, and the Special 
          Masters running the court simply did not 
          want to have to trudge through the 
          backlog of the 5,400 cases facing it 
          over vaccine injuries.  
There in 2010,  a special Vaccine 
          Court sub-set, called the OAP, decided 
          six test cases - three from the MMR 
          Vaccine causes Autism argument, and 
          three from the Thimerosal (mercury) 
          in vaccines causes Autism argument.  
          Those cases were themselves, 
          representing a backlog of the 5,400 
          cases, which, in turn, represented the 
          interests of over 2,000,000 vaccine 
          damaged children in the US.  More, 
          those cases, if won by the Plaintiffs, 
          would have set the stage for relief for 
          the families of the one in six children 
          vaccine damaged showing neurological 
          damage.
The OAP judges relied COMPLETELY, for 
          all six cases, on the truth and validity 
          of the five so-called studies ordered 
          and run by the Center for Disease 
          Control and Prevention (CDC).
Now you see the importance...
After reviewing Hooker's research it is 
          easy to come to a conclusion  - 
          EVERY one of the CDC studies showing the 
          so-called safety of mercury in vaccines 
          has been intentionally faked, so as 
          to lead the American Public, and every 
          entity worldwide that relies on the CDC 
          for information, to believe that mercury 
          in vaccines is safe - it is not.
The case was a 
          setup...
Brian Hooker sued the CDC to get copies 
          of their internal memorandums, emails, 
          letters, etc.
       
       "In late 2004 Biochemist Scientist Brian Hooker PhD 
       had had enough.  He'd been looking, carefully, 
       through the US Center for Disease Control and 
       Prevention (CDC)'s so-called "Evidence" that 
       Thimerosal was "Safe and Effective" as a 
       preservative in vaccines.  Having read all of the 
       then available CDC studies making that claim, he, as 
       a PhD Scientist, couldn't help but shake his head 
       "NO."  To him, none of the purported proof was 
       anywhere near being scientifically adequate.  Far 
       from it.
       So, like any math teacher would do to a student he 
       began to communicate to the CDC his questions.   In 
       essence he was saying "Show me your work.  Show me 
       how you came up with these answers" - a reasonable 
       question series among scientists, teachers and 
       students, and frankly, the population of Planet 
       Earth.
       What was CDC's response?  STONEWALL -  a six year 
       knock-down, drag-out brawl to get that information.  
       Brian Hooker would not let up.  Neither would the 
       CDC
       
But Hooker and his team were playing a 
          trick.  They knew that the same 
          people who would create fake studies 
          would try to cover up their tracks any 
          way they could.  So, they set up a 
          trap - and the CDC walked right into it.
What was the trap?  Hooker had a 
          good many of the documents, already, he 
          was being denied.  More, he knew 
          where more of them were stored, and he 
          had been promised access.  So, they 
          demanded documents, let the CDC reply 
          that (1) there weren't any, (2)  
          the documents didn't say anything 
          pertinent, (3) blah, blah, blah.
And then they spring the trap with the 
          Judge.  As in "Gee Judge, these 
          bastards are lying."
Why do this?  To set them up for 
          CRIMINAL Indictment.  Period.
So, What's 
          Happening?
I love the US court system sometimes.  
          Not all the time, of course, but, 
          frankly, quite often.  
Smile now. 
          Things are heating up in the Hooker v. 
          United States Department of Health AND 
          Human Services, et al federal court 
          case.  The federal judge in the 
          case, has issued the following Order:
        
           
           "Defendants are directed to deliver 
           the documents withheld under 5 U.S.C. 
           § 552(b)(5) to chambers for an in 
           camera inspection to assist the 
           Court in making a responsible de 
           novo determination. In-Camera 
           Submission is due by Friday, 
           7/13/2012. (jth)" 
          
What the 
          Judge's Order actually means...
FOIA Section
          
          
          
          5 U.S.C. § 552(b)(5) 
          authorizes agencies to withhold 
          information related solely to the 
          internal personnel rules and practices 
          of an agency.  The Judge is saying
          "show me where this rule applies in 
          these communications."
          In Camera inspection happens when a 
          judge reviews evidence (depositions, 
          documents, photos and the like) to 
          determine whether it should be provided 
          to other parties. This usually occurs 
          when both sides in a case disagree about 
          whether a certain, usually crucial piece 
          of evidence should come in.
The Court will review non-jury cases
          
          de novo to determine if the agency 
          came to a reasonable conclusion.
So, in short, the Judge isn't buying the 
          CDC's arguments about why it is 
          withholding information.  The trap 
          Hooker set paid off.  It looks to 
          me that the federal judge is beginning 
          to smell the rat in the CDC's position.
Where is this 
          going?
The search for documents, in this court 
          case, is uncovering a pattern of 
          criminal activity.  Whoever is 
          running, making the decisions to 
          withhold documents at CDC, knows where 
          all this is going.  I am certain 
          that within the walls of the CDC, right 
          this minute, certain CDC employees - 
          past and present, contractors, and 
          consultants, etc. are quietly being told 
          to personally "lawyer-up," and 
          familiarize themselves on how to make 
          claim to the Fifth Amendment provisions 
          of the US Constitution (taking the 
          Fifth).
Is there really 
          criminal activity here?
You bet there is.  Major criminal 
          activity.  The people involved in 
          this denial of the effects of Thimerosal 
          in vaccines, and the cover up of the 
          real situation, are some of, perhaps, 
          the worst criminals in the history of 
          mankind.  Just look at the numbers 
          of children damaged, and the cost to 
          society - worldwide.  This is far 
          worse than anything the NAZIs, or 
          Stalin, did.  This overshadows any 
          genocide effort in the history of 
          mankind.
This isn't about simple fraud, the 
          marketing of vaccines, or some 
          comparison of preservatives in vaccines.  
          This is about major damage to children.  
          And it is all coming out.
And that's the bottom line.
          Stay tuned...
Tim Bolen - Consumer 
  Advocate
- See more at: http://www.bolenreport.com/Mark%20Geier/foiasuit6.htm#sthash.yTiNZKX9.dpuf
Tension 
       Increases 
        - Federal Judge 
       Orders CDC to Produce Secret Documents... 
          
          
The CDC Has Known All Along How Dangerous Vaccines Are - And Has Covered It Up... (Part Six)
       
       
The CDC Has Known All Along How Dangerous Vaccines Are - And Has Covered It Up... (Part Six)
Opinion by Consumer Advocate 
           Tim 
          Bolen 
Friday, July 6th,  2012
 - See more at: http://www.bolenreport.com/Mark%20Geier/foiasuit6.htm#sthash.yTiNZKX9.dpuf
This article is the sixth in a series 
          about THE MOST IMPORTANT CASE ABOUT 
          AUTISM currently being litigated - the 
          Hooker v. United States Department of 
          health and Humans Services, et al case.
Why is this the most important case?  
Because of what happened in what was 
          called the  "Omnibus 
          Autism Proceedings" (OAP) in 2010. 
The special Vaccine Court created by 
          the 
          
          National Childhood Vaccine Injury Act 
          (NCVIA), in 1987, had become overloaded 
          with claims about 2007, and the Special 
          Masters running the court simply did not 
          want to have to trudge through the 
          backlog of the 5,400 cases facing it 
          over vaccine injuries.  
There in 2010,  a special Vaccine 
          Court sub-set, called the OAP, decided 
          six test cases - three from the MMR 
          Vaccine causes Autism argument, and 
          three from the Thimerosal (mercury) 
          in vaccines causes Autism argument.  
          Those cases were themselves, 
          representing a backlog of the 5,400 
          cases, which, in turn, represented the 
          interests of over 2,000,000 vaccine 
          damaged children in the US.  More, 
          those cases, if won by the Plaintiffs, 
          would have set the stage for relief for 
          the families of the one in six children 
          vaccine damaged showing neurological 
          damage.
The OAP judges relied COMPLETELY, for 
          all six cases, on the truth and validity 
          of the five so-called studies ordered 
          and run by the Center for Disease 
          Control and Prevention (CDC).
Now you see the importance...
After reviewing Hooker's research it is 
          easy to come to a conclusion  - 
          EVERY one of the CDC studies showing the 
          so-called safety of mercury in vaccines 
          has been intentionally faked, so as 
          to lead the American Public, and every 
          entity worldwide that relies on the CDC 
          for information, to believe that mercury 
          in vaccines is safe - it is not.
The case was a 
          setup...
Brian Hooker sued the CDC to get copies 
          of their internal memorandums, emails, 
          letters, etc.
       
       "In late 2004 Biochemist Scientist Brian Hooker PhD 
       had had enough.  He'd been looking, carefully, 
       through the US Center for Disease Control and 
       Prevention (CDC)'s so-called "Evidence" that 
       Thimerosal was "Safe and Effective" as a 
       preservative in vaccines.  Having read all of the 
       then available CDC studies making that claim, he, as 
       a PhD Scientist, couldn't help but shake his head 
       "NO."  To him, none of the purported proof was 
       anywhere near being scientifically adequate.  Far 
       from it.
       So, like any math teacher would do to a student he 
       began to communicate to the CDC his questions.   In 
       essence he was saying "Show me your work.  Show me 
       how you came up with these answers" - a reasonable 
       question series among scientists, teachers and 
       students, and frankly, the population of Planet 
       Earth.
       What was CDC's response?  STONEWALL -  a six year 
       knock-down, drag-out brawl to get that information.  
       Brian Hooker would not let up.  Neither would the 
       CDC
       
But Hooker and his team were playing a 
          trick.  They knew that the same 
          people who would create fake studies 
          would try to cover up their tracks any 
          way they could.  So, they set up a 
          trap - and the CDC walked right into it.
What was the trap?  Hooker had a 
          good many of the documents, already, he 
          was being denied.  More, he knew 
          where more of them were stored, and he 
          had been promised access.  So, they 
          demanded documents, let the CDC reply 
          that (1) there weren't any, (2)  
          the documents didn't say anything 
          pertinent, (3) blah, blah, blah.
And then they spring the trap with the 
          Judge.  As in "Gee Judge, these 
          bastards are lying."
Why do this?  To set them up for 
          CRIMINAL Indictment.  Period.
So, What's 
          Happening?
I love the US court system sometimes.  
          Not all the time, of course, but, 
          frankly, quite often.  
Smile now. 
          Things are heating up in the Hooker v. 
          United States Department of Health AND 
          Human Services, et al federal court 
          case.  The federal judge in the 
          case, has issued the following Order:
        
           
           "Defendants are directed to deliver 
           the documents withheld under 5 U.S.C. 
           § 552(b)(5) to chambers for an in 
           camera inspection to assist the 
           Court in making a responsible de 
           novo determination. In-Camera 
           Submission is due by Friday, 
           7/13/2012. (jth)" 
          
What the 
          Judge's Order actually means...
FOIA Section
          
          
          
          5 U.S.C. § 552(b)(5) 
          authorizes agencies to withhold 
          information related solely to the 
          internal personnel rules and practices 
          of an agency.  The Judge is saying
          "show me where this rule applies in 
          these communications."
          In Camera inspection happens when a 
          judge reviews evidence (depositions, 
          documents, photos and the like) to 
          determine whether it should be provided 
          to other parties. This usually occurs 
          when both sides in a case disagree about 
          whether a certain, usually crucial piece 
          of evidence should come in.
The Court will review non-jury cases
          
          de novo to determine if the agency 
          came to a reasonable conclusion.
So, in short, the Judge isn't buying the 
          CDC's arguments about why it is 
          withholding information.  The trap 
          Hooker set paid off.  It looks to 
          me that the federal judge is beginning 
          to smell the rat in the CDC's position.
Where is this 
          going?
The search for documents, in this court 
          case, is uncovering a pattern of 
          criminal activity.  Whoever is 
          running, making the decisions to 
          withhold documents at CDC, knows where 
          all this is going.  I am certain 
          that within the walls of the CDC, right 
          this minute, certain CDC employees - 
          past and present, contractors, and 
          consultants, etc. are quietly being told 
          to personally "lawyer-up," and 
          familiarize themselves on how to make 
          claim to the Fifth Amendment provisions 
          of the US Constitution (taking the 
          Fifth).
Is there really 
          criminal activity here?
You bet there is.  Major criminal 
          activity.  The people involved in 
          this denial of the effects of Thimerosal 
          in vaccines, and the cover up of the 
          real situation, are some of, perhaps, 
          the worst criminals in the history of 
          mankind.  Just look at the numbers 
          of children damaged, and the cost to 
          society - worldwide.  This is far 
          worse than anything the NAZIs, or 
          Stalin, did.  This overshadows any 
          genocide effort in the history of 
          mankind.
This isn't about simple fraud, the 
          marketing of vaccines, or some 
          comparison of preservatives in vaccines.  
          This is about major damage to children.  
          And it is all coming out.
And that's the bottom line.
          Stay tuned...
Tim Bolen - Consumer 
  Advocate
- See more at: http://www.bolenreport.com/Mark%20Geier/foiasuit6.htm#sthash.yTiNZKX9.dpufH1N1 vaccine linked to 700 percent increase in miscarriages
Wednesday, December 08, 2010 by: Ethan A. Huff, staff writerTags: vaccines, miscarriages, health news
(NaturalNews) Recent data presented to the U.S. Centers for Disease 
Control and Prevention's (CDC) Advisory Committee on Children's Vaccines
 has revealed some shocking information about the effects of the H1N1 / 
swine flu vaccine on pregnant women. According to the report, the rate 
of miscarriage among pregnant women during the 2009 H1N1 / swine flu 
pandemic soared by over 700 percent compared to previous years, pointing
 directly to the vaccine as the culprit -- but the CDC denies the truth 
and continues to insist nobody has been harmed.
According to the CDC, nearly 50 percent of all pregnant women were vaccinated with the H1N1 vaccine during the 2009 / 2010 influenza season. Those whose physicians instructed them to get a seasonal flu shot were three times more likely to get it, while those instructed specifically to get the H1N1 shot were ten times more likely to get it. And the numbers clearly show that along with the rise in vaccinations due to the H1N1 scare came the sharp increase in miscarriages, including a slew of actual reported adverse events.
But the CDC does not seem to care about the facts, as numerous reports indicate the agency has failed to report any of this vital information to vaccine suppliers. In fact, when presented with the data for the third time, Dr. Marie McCormick, chair of the U.S. Department of Health and Human Services (HHS) Vaccine Risk and Assessment Working Group, actually had the audacity to claim that there were no vaccine-related adverse events in pregnant women caused by the vaccine.
"This baseless and fallacious assessment by the CDC assessment group has given the green light to the CDC's Advisory Committee on Immunization Practices (ACIP) to continue their recommendation to give the 2010/11 flu shot to all people, including pregnant women," explained Eileen Dannemann, director of the National Coalition of Organized Women, presenter of the information.
"This upcoming 2010/11 flu vaccine contains the same elements that are implicated in the killing of these fetuses, the H1N1 viral component and the neurotoxin mercury (Thimerosal). Additionally, it contains two other viral strains -- a three-in-one shot for all people."
Overall, the number of vaccine-related "fetal demise" reports increased by 2,440 percent in 2009 compared to previous years, which is even more shocking than the miscarriage statistic. Meanwhile, the CDC continues to lie to the public about the vaccine, urging everyone, including pregnant women, to get it.
To read the report for yourself, visit: http://www.progressiveconvergence.com/H1N1-R...
Sources for this story include:
http://www.guerillahealthreport.com/post.php...
http://thepopulist.net/?p=6630
According to the CDC, nearly 50 percent of all pregnant women were vaccinated with the H1N1 vaccine during the 2009 / 2010 influenza season. Those whose physicians instructed them to get a seasonal flu shot were three times more likely to get it, while those instructed specifically to get the H1N1 shot were ten times more likely to get it. And the numbers clearly show that along with the rise in vaccinations due to the H1N1 scare came the sharp increase in miscarriages, including a slew of actual reported adverse events.
But the CDC does not seem to care about the facts, as numerous reports indicate the agency has failed to report any of this vital information to vaccine suppliers. In fact, when presented with the data for the third time, Dr. Marie McCormick, chair of the U.S. Department of Health and Human Services (HHS) Vaccine Risk and Assessment Working Group, actually had the audacity to claim that there were no vaccine-related adverse events in pregnant women caused by the vaccine.
"This baseless and fallacious assessment by the CDC assessment group has given the green light to the CDC's Advisory Committee on Immunization Practices (ACIP) to continue their recommendation to give the 2010/11 flu shot to all people, including pregnant women," explained Eileen Dannemann, director of the National Coalition of Organized Women, presenter of the information.
"This upcoming 2010/11 flu vaccine contains the same elements that are implicated in the killing of these fetuses, the H1N1 viral component and the neurotoxin mercury (Thimerosal). Additionally, it contains two other viral strains -- a three-in-one shot for all people."
Overall, the number of vaccine-related "fetal demise" reports increased by 2,440 percent in 2009 compared to previous years, which is even more shocking than the miscarriage statistic. Meanwhile, the CDC continues to lie to the public about the vaccine, urging everyone, including pregnant women, to get it.
To read the report for yourself, visit: http://www.progressiveconvergence.com/H1N1-R...
Sources for this story include:
http://www.guerillahealthreport.com/post.php...
http://thepopulist.net/?p=6630
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Salicylates and Pandemic Influenza Mortality, 1918–1919 Pharmacology, Pathology, and Historic Evidence
- Reprints or correspondence: Dr Karen M. Starko, 1515 Floribunda Ave, Burlingame, CA 94010 (karenstarko{at}gmail.com).
Abstract
The high case-fatality rate—especially 
among young adults—during the 1918–1919 influenza pandemic is 
incompletely understood.
                     Although late deaths showed bacterial pneumonia, 
early deaths exhibited extremely “wet,” sometimes hemorrhagic lungs. The
                     hypothesis presented herein is that aspirin 
contributed to the incidence and severity of viral pathology, bacterial 
infection,
                     and death, because physicians of the day were 
unaware that the regimens (8.0–31.2 g per day) produce levels associated
 with
                     hyperventilation and pulmonary edema in 33% and 3% 
of recipients, respectively. Recently, pulmonary edema was found at 
autopsy
                     in 46% of 26 salicylate-intoxicated adults. 
Experimentally, salicylates increase lung fluid and protein levels and 
impair
                     mucociliary clearance. In 1918, the US Surgeon 
General, the US Navy, and the Journal of the American Medical Association recommended use of aspirin just before
 the October death spike. If these recommendations were followed, and if
 pulmonary edema occurred in 3% of persons, a significant
                     proportion of the deaths may be attributable to 
aspirin.
                  
In February 1919…Edward's fever kept getting higher and higher…aspirin…was given to him by the 1/2-handful over and over…Edward
                  sweated through his mattress…Dr.…could not save his patient.
               
—Clella B. Gregory, Pandemic Influenza Storybook, US Department of Health and Human Services [1]
               
The unprecedented overall mortality and the 
mortality rate among young adults during the 1918–1919 influenza 
pandemic are
                  incompletely understood. Deaths in the United States 
peaked with a sudden spike in October 1918. Later, Wade Hampton Frost
                  [2]
 studied surveys of 8 US cities and found that, for every 1000 persons 
aged 25–29 years, ∼30% were infected with influenza
                  virus, and 1% died of pneumonia or influenza. This 3% 
case-fatality rate has been called, “perhaps the most important unsolved
                  mystery of the pandemic” [3, p 1022].
               
Mortality was driven by 2 overlapping clinical-pathologic syndromes: an early, severe acute respiratory distress (ARDS)-like
                  condition, which was estimated to have caused 10%-15% of deaths (sequential autopsy series are lacking) [3)]; and a subsequent, aggressive bacterial pneumonia “superinfection,” which was pres-ent in the majority of deaths [4, 5].
               
Factors that contributed to the severity of 
illness and death (eg, viral pathogenicity, bacterial colonization, 
immune response,
                  smoking, preexisting conditions, and treatment) remain
 to be elucidated. Of most interest are those amenable to intervention,
                  because fear of another 1918-like influenza pandemic 
drives pandemic planning today.
               
Recent studies suggest enhanced pathogenicity
 of certain influenza viruses as well as abnormal immune host responses.
 The
                  1918 influenza H1N1 virus, in contrast to a 
conventional human H1N1 influenza virus (A/Kawasaki/173/01), infected 
the lower
                  respiratory tract, produced acute respiratory 
distress, and was associated with a dysregulated antiviral response in a
 cynomologous
                  macaque model [6]. Also, the 1918 viral polymerase complex (PA, PB1, and PB2) promoted growth of the 1918 virus in the lower respiratory tract
                  of ferrets [7]. Similarly, 2003 human H5N1 isolates, like 1997 human H5N1 isolates, induced overproduction of proinflammatory cytokines
                  in human macrophages in vitro [8].
               
However, it is unlikely that the virus and immune responses alone were responsible for the 1918 deaths. As recently reviewed
                  by Brundage and Shanks [4],
 most persons had self-limited disease with case-fatality rates of 
<2%, and mortality and case-fatality rates differed widely
                  among populations. During the fall of 1918, death and 
influenza case-fatality rates ranged from 0.58% to 3.3% and 2.1% to
                  10%, respectively, in the 12 US Army camps with 
>10,000 cases of influenza or pneumonia each [9, 10]. Frost [2]
 noted that the wide variation in mortality rates between cities, some 
of which were close together, was not explained by
                  climate, population density, preventive measures, or 
other environmental characteristics. These observations suggest the 
importance
                  of factors related to location rather than the virus 
itself. Likewise, the unusual mortality rate among young adults remains
                  unexplained. Salicylate has been suggested [3, 11, 12], and increased mortality rates have been found in ferrets exposed to influenza, aspirin, and an arginine-deficient diet,
                  compared with each alone or in 2 combinations [13], yet mechanistic and epidemiologic evidence has not been fully explored.
               
The hypothesis presented herein is that 
salicylate therapy for influenza during the 1918–1919 pandemic resulted 
in toxicity
                  and pulmonary edema, which contributed to the 
incidence and severity of early ARDS-like lungs, subsequent bacterial 
infection,
                  and overall mortality. Pharmacokinetic data, which 
were unavailable in 1918, indicate that the aspirin regimens recommended
                  for the “Spanish influenza” predispose to severe 
pulmonary toxicity.
               
A confluence of events created a “perfect 
storm” for widespread salicylate toxicity. The loss of Bayer's patent on
 aspirin
                  in February 1917 allowed many manufacturers into the 
lucrative aspirin market. Official recommendations for aspirin therapy
                  at toxic doses were preceded by ignorance of the 
unusual nonlinear kinetics of salicylate (unknown until the 1960s), 
which
                  predispose to accumulation and toxicity; tins and 
bottles that contained no warnings and few instructions; and fear of 
“Spanish”
                  influenza, an illness that had been spreading like 
wildfire.
               
More recently, influenza deaths have been 
attributed to salicylate. From the 1950s to the 1980s, thousands of 
deaths among
                  children following influenza and other infections (eg,
 Reye syndrome) were unexplained until studies identified aspirin as
                  the major contributor [14-16], and aspirin label warnings were followed by a disappearance of the condition [17]. Reye syndrome toxicity (vomiting, hyperventilation, delirium, and coma, with brain swelling and fat in the liver and proximal
                  renal tubules) develops after ∼4 days of salicylate therapy [14] with reported mean daily doses of 25 mg/kg [18]. (Adults with salicylate toxicity present mainly with abnormal consciousness and respiratory distress [19].) Also, a recent avian influenza A-associated fatality involved Reye syndrome and aspirin use [20], and several autopsies of persons who had avian influenza revealed hemorrhagic lungs, fatty liver changes, and swollen kidneys
                  [21] consistent with salicylate intoxication.
               
Four lines of evidence support the role of 
salicylate intoxication in 1918 influenza mortality: pharmacokinetics, 
mechanism
                  of action, pathology, and the spate of official 
recommendations for toxic regimens of aspirin immediately before the 
October
                  1918 death spike. (Grains of aspirin used in older 
texts are converted to milligrams as follows: 1 grain equals 65 mg).
               
Aspirin Regimens (Dose and Schedule) Recommended in 1918 Are Now Known to Regularly Produce Toxicity
In 1977, a US Food and Drug Administration panel [22]
 recommended that the maximum safe daily dose of aspirin for the general
 population was 4000 mg, with a mean hourly rate
                     of 167 mg/h, and that “dosing regimens exceeding 
either this total daily dosage or mean hourly rate provide a 
significantly
                     greater risk without a compensating therapeutic 
benefit” (p 35360). As an example of the unusual nonlinear kinetics of 
salicylate,
                     the panel noted that simulations show that, after 
increasing the dose from 2 to 4 g daily (given every 6 h), “the total 
amount
                     of drug in the body at steady state will increase 
from 1.3 grams to 5.3 grams, a 400% increase.” In 2007, an 
evidence-based
                     consensus guideline [23]
 recommended that anyone with an acute ingestion of 150 mg/kg or 6.5 g 
of aspirin equivalent, whichever is lower, warrants
                     referral to an emergency department and recognized 
that, after multiple doses, it is difficult to generalize any dose 
associated
                     with toxicity, because lower daily doses (2–3 g for
 several days) may lead to toxicity in some patients.
                  
In the early 1900s, physicians treating 
serious conditions (eg, rheumatic fever) generally “pushed” salicylate 
until the appearance
                     of toxicity and then backed off [24].
 In 1918, dosing recommendations for pandemic influenza were similar to 
these high-dose, hospital-based regimens, except
                     that the recommendations for influenza generally 
offered no instruction for dose adjustment if toxicity occurred.
                  
French's historic 1920 report for the British Ministry of Health [25] on the pandemic states that the aspirin dose was “15 to 20 grains” (975–1300 mg). No frequency was given. One London doctor
                     “drenched” his patient with salicin: 20 grains (1300 mg) hourly for 12 hours nonstop [26]. Others suggested sodium salicylate, 6 grains (390 mg) over 3 hours for several days [27]. Aspirin was recommended for pulmonary edema [28]. On 26 September 1918, the US Navy recommended a cathartic and 5 grains (325 mg) of aspirin, warning against large doses
                     [29]. However, the Navy's Materia Medica stated that the maximum dose was 1300 mg [30]. On 5 October 1918, The Journal of the American Medical Association [31]
 recommended aspirin: “The acetylsalicylic acid may be given in a dosage
 of 1 gm. (15 grains) every three hours…or a smaller
                     dose combined with 0.1 gm. (2 grains) 
acetophenetidin, until symptomatic relief is secured” (p 1137). These 
recommended doses
                     (1000–1300 mg), with frequencies ranging from 
hourly to every 3 hours, resulting in daily doses of 8–31.2 grams, are 
above
                     the maximum safe dose defined above and would lead 
to accumulation, as noted below.
                  
Hints of unusual pharmacokinetics and 
individual variation were noted before the pandemic but largely ignored.
 In 1906, Langmeade
                     [32]
 observed “great variation in the amount required” (p 1824) for toxicity
 and reported a hospitalized child (receiving 325
                     mg every 6 hours) who, on day 4, developed 
vomiting, fever, dyspnea, cyanosis, and coma and died. He recommended 
caution early
                     in treatment so “the personal factor may be 
estimated.” In 1913, Hanzlik [24]
 studied records of 400 hospitalized persons treated with a common 
regimen, 10–20 grains of a salicylate hourly with sodium
                     bicarbonate until toxicity occurred (headache, 
nausea, tinnitus or deafness, delirium, or hallucinations). He found 
that the
                     mean toxic dose of aspirin for male persons was 165
 grains (10,725 mg), a probable overestimation, because sodium 
bicarbonate
                     greatly enhances salicylate excretion. The toxic 
dose of synthetic salicylate in males ranged from 1300 to 31,200 mg.
                  
The development of tests to measure salicylate in the blood in the 1940s allowed Alvin F. Coburn [33] of the US Navy, while studying rheumatic fever, to find that a dose of 10 g daily led to levels that averaged 36 mg/dL on
                     day 3 in 9 adults. In 1948, Graham and Parker [34]
 were among the first to correlate the blood salicylate level with 
symptoms of toxicity. First, after studying 58 individuals,
                     they found considerable variation in the level at 
which symptoms developed, such as vomiting (16.3–38.6 mg/dL), 
hyperventilation
                     (21–44.2 mg/dL), pulmonary edema (49.4 mg/dL), and 
severe dyspnea (46–53.6 mg/dL). They also studied 33 patients who 
attained
                     levels of 35 mg/dL during the first 7 days of 
therapy and found the following severe toxicities: hyperventilation (in 
33%),
                     vomiting (in 30%), marked sweating (in 12%), 
headache (in 12%) severe drowsiness (in 12%), confusion (in 6%), severe 
dyspnea
                     (in 6%), excitement (in 6%), epistaxis (in 6%), 
vertigo (in 3%), pulmonary edema (in 3%), and hemorrhage (in 3%). The 
incidence
                     of these toxicities may be higher, because 
administration was halted when hyperventilation occurred. A 
retrospective study
                     [35]
 of 56 salicylate-intoxicated adults, with intoxication defined as a 
peak salicylate level ⩾30 mg/dL, found 6 patients (11%)
                     with noncardiogenic pulmonary edema. For adults 
aged >30 years, the incidence of noncardiogenic pulmonary edema was 
35%. Interestingly,
                     none of 55 consecutive intoxicated pediatric 
patients had pulmonary edema.
                  
In the 1960s, scientists learned why 
toxicity occurs with intense aspirin therapy: salicylates have unusual 
and complex pharmacokinetic
                     characteristics that predispose to accumulation, 
rendering both dose and schedule critically important. In 1965, Levy [36] showed that, when the amount of drug in the body reaches ∼360 mg, the half-life increases as elimination changes from first
                     order to zero order. Later, Bardare et al [37],
 who studied children, observed half-lives of ∼5 h at a dosage of ∼50 
mg/kg per day (3500 mg in a 70-kg person), of ∼15
                     h at dosages of 75–95 mg/kg per day, and of ∼40 h 
at dosages >100 mg/kg per day. Dosing at intervals of the half-life 
or less
                     will lead to accumulation.
                  
In addition to the saturable metabolism described by Levy and colleagues [36, 38, 39], accumulation of salicylate can occur for other reasons, including individual variation in elimination rate [38], reduced renal excretion [40], and low urine pH [41]. Higher doses, as mentioned above, slow elimination [42] and enhance the volume of distribution [43]. Acidosis [44] and hypoproteinemia [45] increase brain uptake and toxicity. The salicylate level [42] and the level at which toxicity occurs [24, 34] vary among individuals. Therefore, it is likely that severe salicylate intoxication, including pulmonary edema, developed
                     in some persons who followed the recommended 1918 dosing regimens.
                  
Salicylates Cause Immediate Lung Toxicity and May Predispose to Bacterial Infection by Increasing Lung Fluid and Protein Levels and Impairing Mucociliary Clearance
The occurrence of pulmonary edema in humans with salicylate intoxication is well documented [19, 35]. Increased pulmonary vascular bed permeability to fluid and protein, decreases in arterial pO2, and increases in postmortem
                     extravascular lung water followed salicylate administration in sheep [46]. Salicylate also depresses the lung's mucociliary transport system [47].
                  
The Pathology of the Early Deaths Is Consistent with Aspirin Toxicity and Virus-Induced Pathology
Autopsy reports by pathologists of the 
day describe extremely wet, sometimes hemorrhagic lungs in early deaths.
 On 23 September
                     1918 at Camp Devens in Massachusetts, 12,604 
soldiers had influenza, and 727 had pneumonia; after examining the lungs
 of a
                     dead soldier, Colonel Welch concluded, “This must 
be some new kind of infection or plague” [48, p 190]. What struck E. R. Le Count [49],
 consulting pathologist to the US Public Health Service, as most unusual
 was the amount of lung tissue actually “pneumonic”
                     seemed “too little in many cases to explain death 
by pneumonia.” He saw a thin, watery, bloody liquid in the lung tissue,
                     “like the lungs of the drowned,” as well as pleural
 exudates with small hemorrhages unlike those seen in “any other form of
                     acute pneumonia of which I am familiar.” 
Importantly, he also noted the brain was “quite regularly swollen,” the 
kidneys were
                     “regularly the seat of cloudy swelling,” and the 
liver had “superficial fatty change,” (changes noted in children with 
salicylate
                     intoxication; see below). He concluded, “It is 
difficult to believe that a disease with so many distinctive features 
and…novelty…can
                     fail to possess a correspondingly definite 
etiology.” Brain weight was increased by 100–200 g in ∼50% of persons, 
most likely
                     indicating cerebral edema; cerebral bleeding was 
common [9, 10]. Wolbach [50],
 chief pathologist at the Peter Bent Brigham Hospital in Boston, 
Massachusetts, found bacterial infection in late deaths,
                     yet a person dying on day 2 exhibited edema and 
congestion of the lung, a purpuric rash, and no bacterial growth. He 
surmised
                     a natural progression from the early lesion to the 
bacterial lesions: “Two types of lungs stand out.” In early deaths, the
                     lungs were “dark red and wet…dripping wet.” French [25]
 described the lesion as “albuminuous, non-cellular, coagulable.…One 
realized that this albuminous exudate…was the probable
                     cause of the cyanosis.” The exudates were “so 
entirely unlike what is met with in any ordinary forms of pneumonia that
 they
                     seemed to be essential importance, the other 
changes—haemorrhages, broncho-pneumonia and so on—being super 
additions.…”
                  
Although these pathology findings have been induced with the 1918 influenza virus in models [6],
 they are also consistent with aspirin toxicity. A study of 177 adults 
with aspirin toxicity (and a 15% mortality rate)
                     found the most common presentations were depressed 
consciousness (61%) and respiratory failure (47%), even “at therapeutic
                     levels” [19].
 Autopsy findings for patients with the 26 fatal cases were pulmonary 
edema (46%), ulcers (46%), cerebral hemorrhage (23%),
                     and cerebral edema (31%). Coagulation disturbance 
or thrombocytopenia was found in 38%. A detailed autopsy of an adult 
with
                     aspirin poisoning revealed cyanosis, pulmonary 
congestion, alveolar hemorrhage, subpleural and subepicardial 
hemorrhages,
                     petechiae, cloudy swelling of the kidneys, and 
fatty degeneration of the liver [51, 52]. ARDS-like disease has also been reported [53]. Children with aspirin toxicity (or Reye syndrome) are less likely than adults to present with pulmonary edema [35], although in addition to brain swelling, fatty liver, and cloudy swelling of the kidneys [54, 55], some have pulmonary edema [55, 56], “frothy, blood-tinged fluid” [57], and lung hemorrhages [54].
                  
A report from Camp Dix noted, “The 
disease was a veritable plague. The extraordinary toxicity, the marked 
prostration, the
                     extreme cyanosis and the rapidity of development 
stamp this disease as a distinct clinical entity heretofore not fully 
described.…Pneumonia
                     is an important but somewhat secondary factor” [58, p 1817]. Salicylate toxicity is often overlooked [59]
 because another condition is present, the dose is thought to be 
trivial, and the symptoms (hyperventilation, vomiting, sweating,
                     headache, drowsiness, confusion, dyspnea, 
excitement [salicylate jag], epistaxis, vertigo, pulmonary edema, and 
hemorrhage)
                     are nonspecific [34].
 In 1918, differentiating progressive salicylate intoxication from 
infection pathologically or clinically, “the dyspnea
                     lasts from a few hours to a day…followed by 
respiratory failure, circulatory collapse, convulsions, and death” [40], was almost impossible.
                  
Aspirin Advertisements in August 1918 and a Series of Official Recommendations for Aspirin in September and Early October Preceded the Death Spike of October 1918
In May 1918, usual but highly contagious influenza was publicized in Spain (hence, “Spanish influenza”) [48]. In June, after 6 weeks of usual influenza in Europe, serious pulmonary lesions and deaths increased in those “admitted
                     to the special inf luenza centres,” especially those with an “old-standing renal lesion” [60]. In July, increased mortality of young Londoners was documented [61].
                  
Farbenfabriken Bayer's worldwide efforts 
had left few places lacking aspirin. In the United States, Bayer's giant
 factory
                     produced aspirin under “American” management. After
 Bayer executives were charged with violating the Trading with the 
Enemies
                     Act in August 1918, advertisements encouraged 
confidence in aspirin [62].
 The “Spanish lady” came to the United States and struck 2000 Navy men 
in Boston in late August. The majority recovered,
                     but oddly, 5%-10% developed a “very severe and 
massive bronchopneumonia,” which, in many, lacked an accompanying 
leukocytosis
                     [63]. Influenza spread.
                  
Official recommendations for aspirin were issued on 13 September 1918 by the US Surgeon General [64], who stated aspirin had been used in foreign countries “apparently with much success in the relief of symptoms” (p 13),
                     on 26 September 1918 by the US Navy [29], and on 5 October 1918 by The Journal of the American Medical Association [31]. Recommendations often suggested dose regimens that predispose to toxicity as noted above. At the US Army camp with the
                     highest mortality rate, doctors followed Osler's treatment recommendations, which included aspirin [48], ordering 100,000 tablets [65]. Aspirin sales more than doubled between 1918 and 1920 [66].
                  
The number of deaths in the United States increased steeply, peaking first in the Navy in late September, then in the Army
                     in early October, and finally in the general population in late October [67]. Homeopaths, who thought aspirin was a poison, claimed few deaths [11, 48]. Others may have suspected that aspirin was responsible. On 23 November, 1918, Horder [68] wrote in The Lancet that, for “intensely toxic cases…aspirin and all so-called febrifuge drugs must be rigidly excluded from the treatment” (p
                     695)
                  
In summary, just before the 1918 death 
spike, aspirin was recommended in regimens now known to be potentially 
toxic and to
                     cause pulmonary edema and may therefore have 
contributed to overall pandemic mortality and several of its mysteries. 
Young
                     adult mortality may be explained by willingness to 
use the new, recommended therapy and the presence of youth in regimented
                     treatment settings (military). The lower mortality 
of children may be a result of less aspirin use. The major pediatric 
text
                     [69] of 1918 recommended hydrotherapy for fever, not salicylate; its 1920 edition [70]
 condemned the practice of giving “coal tar products” in full doses for 
reduction of fever. The occurrence of Reye syndrome-like
                     illness before the 1950s is debated and consistent 
with the fact that children's aspirin was not marketed until the late 
1940s.
                     Varying aspirin use may also contribute to the 
differences in mortality between cities and between military camps.
                  
To determine the proportion of 
virus-induced pathology, subsequent bacterial infection, and overall 
1918 pandemic mortality
                     attributable to salicylate, experimental models and
 analysis of primary consecutive individual treatment and pathology 
records
                     are needed. Prospectively, aspirin should be 
investigated in countries where aspirin is used for influenza.
                  
- Received March 29, 2009.
- Accepted June 25, 2009.
- © 2009 by the Infectious Diseases Society of America



 
Thanks for your post. I’ve been thinking about writing a very comparable post over the last couple of weeks, I’ll probably keep it short and sweet and link to this instead if thats cool. Thanks.
ReplyDeleteGM Diet Plan Day 6
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