Marshall Protocol Knowledge Base - home:alternate

Autoimmune theory of disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Environmental causation of disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Genetic predisposition to disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Psychosomatic explanations for disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Spontaneous remission is a myth

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

10.21.2018		current
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	One of the important factors in how symptoms of illness relapse and remit, is that infections relapse and remit. For example, //Staphylococcus aureus// is a major human pathogen which plays a role in deep tissue infections, osteomyelitis, and chronic lung infections.		One of the important factors in how symptoms of illness relapse and remit, is that infections relapse and remit. For example, //Staphylococcus aureus// is a major human pathogen which plays a role in deep tissue infections, osteomyelitis, and chronic lung infections.

-	A key characteristic of these infections is that relapse can occur months or years after an apparent cure. These relapses, Dr. Bettina Löffler and her team from the Institut für Medizinische Mikrobiologie in Münster, Germany, [[http://www.sciencedaily.com/releases/2011/01/110126081521.htm\|believe]] are due to phenotype switching, a change in the bacterial behaviour. After infection and invasion of the patient's host cells, the bacteria form small colony variants (SCVs), tiny bacterial subpopulations that can evade the immune system and many antibiotics and grow slowly.(({{pubmed>long:21268281}}))	+	A key characteristic of these infections is that relapse can occur months or years after an apparent cure. These relapses, Dr. Bettina Löffler and her team from the Institut für Medizinische Mikrobiologie in Münster, Germany, [[https://www.sciencedaily.com/releases/2011/01/110126081521.htm\|believe]] are due to phenotype switching, a change in the bacterial behaviour. After infection and invasion of the patient's host cells, the bacteria form small colony variants (SCVs), tiny bacterial subpopulations that can evade the immune system and many antibiotics and grow slowly.(({{pmid>long:21268281}}))

	Microbes ability to easily switch between forms explains both their persistence and the variability in patients' symptom presentation from one time point to another.		Microbes ability to easily switch between forms explains both their persistence and the variability in patients' symptom presentation from one time point to another.
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	===== Sarcoidosis =====		===== Sarcoidosis =====

-	Researchers at Jefferson Medical Center in Philadelphia found a 74% relapse rate in sarcoidosis patients with treatment-induced remission, while only 60% of patients identified as having a favorable prognosis actually sustained remission over 130 months.(({{pubmed>long:9118698}}))	+	Researchers at Jefferson Medical Center in Philadelphia found a 74% relapse rate in sarcoidosis patients with treatment-induced remission, while only 60% of patients identified as having a favorable prognosis actually sustained remission over 130 months.(({{pmid>long:9118698}}))

	Many argue that the most accurate study of sarcoidosis to date is the 2003 NIH ACCESS study, which followed 215 sarcoidosis patients for two years - a period during which it is sometimes mistakenly thought that the disease can go into remission. The study found that measures of sarcoidosis severity remain unchanged over the two-year period, despite the fact that many patients were using corticosteroids and other drugs.		Many argue that the most accurate study of sarcoidosis to date is the 2003 NIH ACCESS study, which followed 215 sarcoidosis patients for two years - a period during which it is sometimes mistakenly thought that the disease can go into remission. The study found that measures of sarcoidosis severity remain unchanged over the two-year period, despite the fact that many patients were using corticosteroids and other drugs.
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	It has also been argued that there is a gap between how patients themselves and members of the medical community perceive success and improvement, as well as their concept of cure. The medical community has a tendency to be satisfied by results that show a patient has stabilized thanks to a particular medication, without taking into account systemic effects of disease, such as fatigue and pain, which are often excluded as endpoints.		It has also been argued that there is a gap between how patients themselves and members of the medical community perceive success and improvement, as well as their concept of cure. The medical community has a tendency to be satisfied by results that show a patient has stabilized thanks to a particular medication, without taking into account systemic effects of disease, such as fatigue and pain, which are often excluded as endpoints.

-	A [[http://www.wired.com/medtech/health/news/2005/03/66806\|2005 article]] on gene therapy described patients who had undergone treatment as “basically cured” – even though three had developed leukemia and one died.	+	A [[https://www.wired.com/medtech/health/news/2005/03/66806\|2005 article]] on gene therapy described patients who had undergone treatment as “basically cured” – even though three had developed leukemia and one died.

	The above example is a misuse of the word “cure.” For one thing, an actual cure results from a treatment that allows all participants to become well, including no long-term side effects or harm. Did the above study check in with its subjects a decade down the road in order to access their health years later? Probably not. But if they did, the subjects were probably symptomatic again, as gene therapy has not yet been adopted as an effective way to treat disease.		The above example is a misuse of the word “cure.” For one thing, an actual cure results from a treatment that allows all participants to become well, including no long-term side effects or harm. Did the above study check in with its subjects a decade down the road in order to access their health years later? Probably not. But if they did, the subjects were probably symptomatic again, as gene therapy has not yet been adopted as an effective way to treat disease.
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	===== Common misperceptions =====		===== Common misperceptions =====
		+
		+	(//the protocol is continued for 3-5 years//) In actuality, the impact of Th1 disease is different for each individual. Patients themselves vary in personality, physiological reactions, environmental conditions, degree of impact that social attitudes make to their morale. Stress is an important factor interfering with recovery, it often contributed to collapse of innate immunity.
		+
		+	A majority of patients have chosen to continue the therapy for as long as they experience improvement; this has been known to continue for ten years. Minimally for as long as it takes to bring 1,25 D into the healthy range and maintain this over one year of testing (if available). Often for at least as long as it takes to experience continuing improvement.
		+
		+	(//patients must wear wrap-around NoIR sunglasses at all times, including inside//) Those people who already wear sunglasses have been known to find the wrap-around NoIR give superior comfort. Actually some patients never wear NoIR because not photosensitive, for others it hits hard and fast. A few have been obliged to postpone the MP journey because they could no longer practice their profession effectively while photosensitive.
		+
		+	(//Protocol relies on massive amounts of pharmaceutical drugs//) Not massive amounts, and only one drug, to cure problems which may have been caused by previous use of pharmaceutical drugs (penicillin type drugs). Any MP compatible Abx used while on MP is optional and used in minimal doses.
		+
		+	(//MP gives you one reason for pain. 'Too much vitamin D'//) The MP explains most pain as caused by microbial die-back producing cytokines as the immune system begins to work normally. Other pain may be caused by irreversible damage. This type of pain can be controlled by judicious use of opiates. Patients and doctors who desire only reduction of pain may be advised to avoid the MP. Patients who desire roll-back leading to cure of immune problems must look to developments in immune protection, restoration and support.
		+
		+	(//MP could be dangerous?//) Young children and pregnant women are warned they must postpone this therapy, as a precaution. Olmesartan is one of the safest medications known. It is far safer than many drugs available without prescription, such as aspirin..
		+
		+	(//MP recommends the opposite of natural practitioners, seems all that MP does is shut down bodily ability to heal//) Olmesartan does the opposite, when dose is taken frequently, enables recovery of innate immunity, including healing where damage is not irreversible. Patients are encouraged to find a natural whole foods diet which is suited to their individual digestive process. Moderate exercise appropriate to the individual is encouraged, going all out is not.
		+
		+	(//MP staff are not open-minded//) I do not understand this reaction. IMO patients must be pretty open minded to stick with MP long enough to be nominated as support staff. They welcome discussion of the experience of all participants, learn from failure and success as does any competent scientific study.

	{{tag>Alternate_models}}		{{tag>Alternate_models}}
		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

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	*		*

-	===== References =====	+	===== References =====</nodisp>

02.15.2019		current
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-	Chronic diseases have been around for at least thousands of years, suggesting that a number of the proposed environmental causes for disease, like smoking, man-made toxins and junk food, are not the exclusive causes. Manifestations of both arteriosclerosis(({{pubmed>long:10495769}})) ((Ackerknecht, E. H. (1955). //A Short History of Medicine//. New York: Ronald Press)) and cardiac disease(({{pubmed>long:10938170}})) can be observed in mummies of ancient Egypt. [[http://en.wikipedia.org/wiki/Ötzi_the_Iceman\|Ötzi the Neolithic Iceman]] who lived around 3300 BC was found to have arthritis.(({{pubmed>long:12701332}})) According to a 2011 retrospective cohort study, people with exceptional longevity are not distinct in terms of lifestyle factors from the general population.(({{pubmed>long:21812767}}))	+	Chronic diseases have been around for at least thousands of years, suggesting that a number of the proposed environmental causes for disease, like smoking, man-made toxins and junk food, are not the exclusive causes. Manifestations of both arteriosclerosis(({{pmid>long:10495769}})) ((Ackerknecht, E. H. (1955). //A Short History of Medicine//. New York: Ronald Press)) and cardiac disease(({{pmid>long:10938170}})) can be observed in mummies of ancient Egypt. [[https://en.wikipedia.org/wiki/Ötzi_the_Iceman\|Ötzi the Neolithic Iceman]] who lived around 3300 BC was found to have arthritis.(({{pmid>long:12701332}})) According to a 2011 retrospective cohort study, people with exceptional longevity are not distinct in terms of lifestyle factors from the general population.(({{pmid>long:21812767}}))

	===== Modern suppression of immune system =====		===== Modern suppression of immune system =====

-	Besides 20th century medical interventions in chronic disease, which overwhelmingly consist of immune suppressive drugs which reduce symptoms in individuals, there in this century the increasing and often unrecognized (or denied) assault of EMF on mass populations. (({{pubmed>long:27412293}}))	+	Besides 20th century medical interventions in chronic disease, which overwhelmingly consist of immune suppressive drugs which reduce symptoms in individuals, there in this century the increasing and often unrecognized (or denied) assault of EMF on mass populations. (({{pmid>long:27412293}}))

	Attempts to measure and deal with these problems are addressed in a whole new group of articles placed within [[home:special:\|Special Issues]].		Attempts to measure and deal with these problems are addressed in a whole new group of articles placed within [[home:special:\|Special Issues]].
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	</blockquote>		</blockquote>

-	But, a 2010 observational study found that increasing fruit and vegetable intake had a marginal impact on risk of cancer.(({{pubmed>long:20371762}})) According to the research if Europeans increased their consumption of fruit and vegetables by 150g a day (about two servings, or 40% of the WHO's recommended daily allowance), it would result in a decrease of just 2.6% in the rate of cancers in men and 2.3% in women. Even those who eat virtually no fruit and vegetables, the paper suggests, are only 9% more likely to develop cancer than those who stick to the WHO recommendations.	+	But, a 2010 observational study found that increasing fruit and vegetable intake had a marginal impact on risk of cancer.(({{pmid>long:20371762}})) According to the research if Europeans increased their consumption of fruit and vegetables by 150g a day (about two servings, or 40% of the WHO's recommended daily allowance), it would result in a decrease of just 2.6% in the rate of cancers in men and 2.3% in women. Even those who eat virtually no fruit and vegetables, the paper suggests, are only 9% more likely to develop cancer than those who stick to the WHO recommendations.

	Further, even some of the most ambitious obesity intervention programs, which have gone to great lengths to increase rates of exercise and improve eating habits of a population, have been failures.		Further, even some of the most ambitious obesity intervention programs, which have gone to great lengths to increase rates of exercise and improve eating habits of a population, have been failures.

-	One 1999 $200,000 NIH-funded intervention, known as the Pathways program, was performed on two groups of children. Pathways involved a substantial increase in physical education programs, classes about nutrition, significant reduction in fat and calorie content of all school meals, and several other health related measures - and all as part of a randomized controlled trial, the gold standard in studies. The primary goal of the study was to reduce the rate of body fat in the intervention group, but after the three-year intervention the percent of body fat in both groups was essentially identical.(({{pubmed>long:14594792}}))	+	One 1999 $200,000 NIH-funded intervention, known as the Pathways program, was performed on two groups of children. Pathways involved a substantial increase in physical education programs, classes about nutrition, significant reduction in fat and calorie content of all school meals, and several other health related measures - and all as part of a randomized controlled trial, the gold standard in studies. The primary goal of the study was to reduce the rate of body fat in the intervention group, but after the three-year intervention the percent of body fat in both groups was essentially identical.(({{pmid>long:14594792}}))

	Studies such as these suggest that the official dietary advice given over the last decades do nothing to curb the increase in obesity. But just as the lack of effect of using a 10 day course of penicillin for the treatment of an L-form bacteria infection is not evidence of antibiotics not being helpful in the treatment of L-form bacteria, neither is one specific life style intervention evidence of lifestyle measures not having effect.		Studies such as these suggest that the official dietary advice given over the last decades do nothing to curb the increase in obesity. But just as the lack of effect of using a 10 day course of penicillin for the treatment of an L-form bacteria infection is not evidence of antibiotics not being helpful in the treatment of L-form bacteria, neither is one specific life style intervention evidence of lifestyle measures not having effect.

-	Other interventions, such as a change in the amount and type of carbohydrate, have shown much greater promise.(({{pubmed>long:17341711}})) (({{pubmed>long:15148063}})) (({{pubmed>long:12640371}})) (({{pubmed>long:16306558}})) (({{pubmed>long:12912783}})) (({{pubmed>long:16674818}})) (({{pubmed>long:24829736}}))	+	Other interventions, such as a change in the amount and type of carbohydrate, have shown much greater promise.(({{pmid>long:17341711}})) (({{pmid>long:15148063}})) (({{pmid>long:12640371}})) (({{pmid>long:16306558}})) (({{pmid>long:12912783}})) (({{pmid>long:16674818}})) (({{pmid>long:24829736}}))

	Attrition was high in most of these studies, as they usually are in any kind of long term diet studies where major diet components are changed. Therefore these studies are just as much a test of the patients’ motivation and the skills of the health professional giving them advice as a pure diet test.		Attrition was high in most of these studies, as they usually are in any kind of long term diet studies where major diet components are changed. Therefore these studies are just as much a test of the patients’ motivation and the skills of the health professional giving them advice as a pure diet test.

-	The mechanisms behind the effects of a low carbohydrate, - or a low glycemic, diet on weight loss are generally believed by the authors of the studies foremost to be a result of a reduced insulin secretion. Indeed, insulin administration leads to weight gain(({{pubmed>long:17924864}})) and insulin suppression leads to weight loss.(({{pubmed>long:12587002}}))	+	The mechanisms behind the effects of a low carbohydrate, - or a low glycemic, diet on weight loss are generally believed by the authors of the studies foremost to be a result of a reduced insulin secretion. Indeed, insulin administration leads to weight gain(({{pmid>long:17924864}})) and insulin suppression leads to weight loss.(({{pmid>long:12587002}}))

-	There could however be other mechanisms at play for the effects of a low-carbohydrate diet, such as changes in the body’s (gut) microbiota. (({{pubmed>long:17183309}}))(Note the sharper increase in //Bacteriodetes// on the low-carbohydrate diet in Figure 1.)	+	There could however be other mechanisms at play for the effects of a low-carbohydrate diet, such as changes in the body’s (gut) microbiota. (({{pmid>long:17183309}}))(Note the sharper increase in //Bacteriodetes// on the low-carbohydrate diet in Figure 1.)

-	In another study, the relative level of the bacterium Selenomonas noxia in the oral cavity was able to predict obesity with a larger than 98 per cent certainty.(({{pubmed>long:19587155}})) As infection is the main cause of inflammation in the oral cavity, it is interesting to note that a diet devoid of refined carbohydrates significantly reduces markers of gingival inflammation.(({{pubmed>long:19405829}}))	+	In another study, the relative level of the bacterium Selenomonas noxia in the oral cavity was able to predict obesity with a larger than 98 per cent certainty.(({{pmid>long:19587155}})) As infection is the main cause of inflammation in the oral cavity, it is interesting to note that a diet devoid of refined carbohydrates significantly reduces markers of gingival inflammation.(({{pmid>long:19405829}}))


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-	In contrast to infectious agents, little evidence implicates typical doses of dietary chemicals as primary causes of human cancer, probably because humans have evolved effective flexible enzymatic systems for degrading potentially carcinogenic chemicals.(({{pubmed>long:9255573}})) Even aflatoxins, which are one of the most carcinogenic of dietary constituents, may exert their negative effects largely in conjunction with viral infection(({{pubmed>long:9270015}})) such as the hepatitis C virus.(({{pubmed>long:19850960}}))	+	In contrast to infectious agents, little evidence implicates typical doses of dietary chemicals as primary causes of human cancer, probably because humans have evolved effective flexible enzymatic systems for degrading potentially carcinogenic chemicals.(({{pmid>long:9255573}})) Even aflatoxins, which are one of the most carcinogenic of dietary constituents, may exert their negative effects largely in conjunction with viral infection(({{pmid>long:9270015}})) such as the hepatitis C virus.(({{pmid>long:19850960}}))



-	{{tag>Alternate_models emf}}	+	{{tag>Alternate_models }}
		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

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	Gut. 2010 Jan;59(1):88-97.		Gut. 2010 Jan;59(1):88-97.
-	Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens.(({{pubmed>long:19850960}}))	+	Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens.(({{pmid>long:19850960}}))

	Fox JG, Feng Y, Theve EJ, Raczynski AR, Fiala JL, Doernte AL, Williams M, McFaline JL, Essigmann JM, Schauer DB, Tannenbaum SR, Dedon PC, Weinman SA, Lemon SM, Fry RC, Rogers AB.		Fox JG, Feng Y, Theve EJ, Raczynski AR, Fiala JL, Doernte AL, Williams M, McFaline JL, Essigmann JM, Schauer DB, Tannenbaum SR, Dedon PC, Weinman SA, Lemon SM, Fry RC, Rogers AB.
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	PMID: 19850960</blockquote>		PMID: 19850960</blockquote>

-	===== References =====	+	===== References =====</nodisp>

08.22.2017		current
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	Conversely, the Marshall Pathogenesis explains that so-called "autoantibodies" are merely antibodies generated in response to pathogenic bacterial cells that have been destroyed as a result of an active immune response – in essence, collateral damage.		Conversely, the Marshall Pathogenesis explains that so-called "autoantibodies" are merely antibodies generated in response to pathogenic bacterial cells that have been destroyed as a result of an active immune response – in essence, collateral damage.

-	At least [[http://en.wikipedia.org/wiki/Autoimmune_disease\|forty different chronic diseases]] are suspected or accepted as being caused by an autoimmune response. According to Yehuda Shoenfeld, when it comes to autoimmune disease, "Everything is infectious until proven otherwise."	+	At least [[https://en.wikipedia.org/wiki/Autoimmune_disease\|forty different chronic diseases]] are suspected or accepted as being caused by an autoimmune response. According to Yehuda Shoenfeld, when it comes to autoimmune disease, "Everything is infectious until proven otherwise."


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	===== Autoimmune patients show signs of being immunocompromised =====		===== Autoimmune patients show signs of being immunocompromised =====

-	* sarcoidosis – Barna, Kanchwala, //et al.// showed that patients with sarcoidosis expressed the antimicrobial peptide cathelicidin less than healthy subjects, and that sicker sarcoidosis patients expressed it least of all.(({{pubmed>long:22759465}})) ((Kanchwala, A., B. Barna, et al. (2009). [[http://meeting.chestpubs.org/cgi/content/abstract/136/4/127S-a\|Deficiencies of cathelicidin and vitamin D accompany disease severity in sarcoidosis]].)) This was true even despite "healthy" levels of 1,25-D. Wiken //et al.// showed that there was a reduced TLR2 mRNA expression in patients with Lofgren's syndrome (a type of acute sarcoidosis).(({{pubmed>long:20813038}})) Note that TLR2 (which the Marshall Pathogenesis theorizes is downregulated in autoimmune disease states) is expressed by the VDR.	+	* sarcoidosis – Barna, Kanchwala, //et al.// showed that patients with sarcoidosis expressed the antimicrobial peptide cathelicidin less than healthy subjects, and that sicker sarcoidosis patients expressed it least of all.(({{pmid>long:22759465}})) ((Kanchwala, A., B. Barna, et al. (2009). [[https://meeting.chestpubs.org/cgi/content/abstract/136/4/127S-a\|Deficiencies of cathelicidin and vitamin D accompany disease severity in sarcoidosis]].)) This was true even despite "healthy" levels of 1,25-D. Wiken //et al.// showed that there was a reduced TLR2 mRNA expression in patients with Lofgren's syndrome (a type of acute sarcoidosis).(({{pmid>long:20813038}})) Note that TLR2 (which the Marshall Pathogenesis theorizes is downregulated in autoimmune disease states) is expressed by the VDR.
-	* Crohn's disease – Chamaillard concluded in 2011 that "clinical studies have linked the defective expression of both α- and β-defensin to the reduced killing of certain microorganisms by the intestinal mucosa of patients suffering from ileal and colonic Crohn's disease (CD), respectively."(({{pubmed>long:21350705}})) Wang //et al.// have demonstrated in Crohn's patients a decline in expression of key antimicrobial peptides including cathelicidin and Beta-defensin-2.(({{pubmed>long:19948723}})) Consistent with the Marshall Pathogenesis, the Wang group points to the Vitamin D Receptor as being important in Crohn's patients.	+	* Crohn's disease – Chamaillard concluded in 2011 that "clinical studies have linked the defective expression of both α- and β-defensin to the reduced killing of certain microorganisms by the intestinal mucosa of patients suffering from ileal and colonic Crohn's disease (CD), respectively."(({{pmid>long:21350705}})) Wang //et al.// have demonstrated in Crohn's patients a decline in expression of key antimicrobial peptides including cathelicidin and Beta-defensin-2.(({{pmid>long:19948723}})) Consistent with the Marshall Pathogenesis, the Wang group points to the Vitamin D Receptor as being important in Crohn's patients.

-	Conversely, skin diseases like psoriasis(({{pubmed>long:19919305}})) and cutaneous lupus(({{pubmed>long:21353331}})) have higher expression of AMPs. This immune response protects the skin of the symptomatic host from further bacterial colonization.	+	Conversely, skin diseases like psoriasis(({{pmid>long:19919305}})) and cutaneous lupus(({{pmid>long:21353331}})) have higher expression of AMPs. This immune response protects the skin of the symptomatic host from further bacterial colonization.
	===== "Autoantibodies" are produced in response to microbial DNA =====		===== "Autoantibodies" are produced in response to microbial DNA =====

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	A litany of research implies a re-evaluation of the "autoantibody." Recently researchers have shown that certain autoantibodies are created in response to several well-studied pathogens and in a variety of states.		A litany of research implies a re-evaluation of the "autoantibody." Recently researchers have shown that certain autoantibodies are created in response to several well-studied pathogens and in a variety of states.

-	* lupus – "Lupus specific autoantibodies" such as RO, La or dsDNA are often generated in response to Epstein-Barr Virus.(({{pubmed>long:17917546}})) Similarly, anti-EBNA-1 antibodies are able to bind lupus-specific autoantigens such as Sm or Ro.Harley.(({{pubmed>long:17917546}}))	+	* lupus – "Lupus specific autoantibodies" such as RO, La or dsDNA are often generated in response to Epstein-Barr Virus.(({{pmid>long:17917546}})) Similarly, anti-EBNA-1 antibodies are able to bind lupus-specific autoantigens such as Sm or Ro.Harley.(({{pmid>long:17917546}}))
-	* rheumatoid arthritis – Casali and Slaughter found that in humans, EBV is a polyclonal B cell activator, and in vitro transformation with EBV results in production of rheumatoid factor (RF).(({{pubmed>long:3105056}})) (({{pubmed>long:214511}})) Possnett et al. argues that high titers of RF are associated with severe rheumatoid arthritis but also appear in a number of other diseases including viral, bacterial, and parasitic infections.(({{pubmed>long:9198668}})) Maturation of RF can be initiated by chronic infections.(({{pubmed>long:8898963}})) For example, patients with subacute bacterial endocarditis, which is frequently tied to the presence of Streptococcus, also often present with high levels of RF.(({{pubmed>long:1299798}})) Williams //et al.// showed that once the offending infectious agent is removed with antibiotic therapy, the RF disappears.(({{pubmed>long:14007218}}))	+	* rheumatoid arthritis – Casali and Slaughter found that in humans, EBV is a polyclonal B cell activator, and in vitro transformation with EBV results in production of rheumatoid factor (RF).(({{pmid>long:3105056}})) (({{pmid>long:214511}})) Possnett et al. argues that high titers of RF are associated with severe rheumatoid arthritis but also appear in a number of other diseases including viral, bacterial, and parasitic infections.(({{pmid>long:9198668}})) Maturation of RF can be initiated by chronic infections.(({{pmid>long:8898963}})) For example, patients with subacute bacterial endocarditis, which is frequently tied to the presence of Streptococcus, also often present with high levels of RF.(({{pmid>long:1299798}})) Williams //et al.// showed that once the offending infectious agent is removed with antibiotic therapy, the RF disappears.(({{pmid>long:14007218}}))
-	* idiopathic thrombocytopenic purpura (ITP) – is mediated by what are considered to be anti-platelet autoantibodies. However, Asahi et al. found that eradication of H. pylori is effective in increasing platelet count in nearly half of ITP patients infected with the bacterium.(({{pubmed>long:16963398}})) Barzilai and team also found that Hepatitis B shares amino acid sequences with different autoantigens, further suggesting that so-called autoantibodies may actually be created in response to pathogens.(({{pubmed>long:17917546}}))	+	* idiopathic thrombocytopenic purpura (ITP) – is mediated by what are considered to be anti-platelet autoantibodies. However, Asahi et al. found that eradication of H. pylori is effective in increasing platelet count in nearly half of ITP patients infected with the bacterium.(({{pmid>long:16963398}})) Barzilai and team also found that Hepatitis B shares amino acid sequences with different autoantigens, further suggesting that so-called autoantibodies may actually be created in response to pathogens.(({{pmid>long:17917546}}))
	* Crohn's disease – Crohn's disease is classified as an autoimmune condition based largely on the presence of perinuclear anti-nuclear cytoplasmic antibodies (pANCA) in patients with the disease. Yet recently two major species of proteins immunoreactive to pANCA were detected in bacteria from anaerobic libraries, implicating colonic bacteria as a possible trigger for the disease-associated immune response.		* Crohn's disease – Crohn's disease is classified as an autoimmune condition based largely on the presence of perinuclear anti-nuclear cytoplasmic antibodies (pANCA) in patients with the disease. Yet recently two major species of proteins immunoreactive to pANCA were detected in bacteria from anaerobic libraries, implicating colonic bacteria as a possible trigger for the disease-associated immune response.

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	==== Patients without autoimmune disease have autoantibodies during infection ====		==== Patients without autoimmune disease have autoantibodies during infection ====

-	Autoantibodies have been detected in patients without autoimmune disease during periods of infection. Berlin et al. collected sera from 88 patients with acute infections (41 bacterial, 23 viral, 17 parasitic, and 7 rikettsial.(({{pubmed>long:17894023}})) Elevated titers of autoantibodies including annexin-V, prothrombin, ASCA, ANA, or antiphospholipid antibodies were detected in approximately half of the subjects, with 34 individuals harboring elevated titers of at least two "autoantibodies."	+	Autoantibodies have been detected in patients without autoimmune disease during periods of infection. Berlin et al. collected sera from 88 patients with acute infections (41 bacterial, 23 viral, 17 parasitic, and 7 rikettsial.(({{pmid>long:17894023}})) Elevated titers of autoantibodies including annexin-V, prothrombin, ASCA, ANA, or antiphospholipid antibodies were detected in approximately half of the subjects, with 34 individuals harboring elevated titers of at least two "autoantibodies."


-	An increasing number of studies also show that what are currently perceived as autoantibodies can often be detected in so called healthy individuals years before the full presentation of an autoimmune disease state. A 2006 study found that 20% of healthy Chinese subjects had one of three autoantibodies.(({{pubmed>long:16878294}})) Many researchers now espouse that early detection of these antibodies can help predict whether or not such a "healthy" person will develop an autoimmune disease. For example, in an eight-year prospective study, Swaak //et al.// examined the diagnostic significance of anti-double-stranded deoxyribonucleic acid (anti-dsDNA) determination in a group of 441 patients without systemic lupus erythematosus whose sera were found to contain antibodies to dsDNA on routine screening.(({{pubmed>long:3872637}})) Within one year, 69% (304) of these patients fulfilled the preliminary American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). Eighty-two of the remaining 137 patients were followed up for several years. At the end of the study, 52% of these patients had also developed systemic lupus erythematosus. The team concluded that about 85% of patients without systemic lupus erythematosus with anti-dsDNA in the circulation would develop SLE within a few years.	+	An increasing number of studies also show that what are currently perceived as autoantibodies can often be detected in so called healthy individuals years before the full presentation of an autoimmune disease state. A 2006 study found that 20% of healthy Chinese subjects had one of three autoantibodies.(({{pmid>long:16878294}})) Many researchers now espouse that early detection of these antibodies can help predict whether or not such a "healthy" person will develop an autoimmune disease. For example, in an eight-year prospective study, Swaak //et al.// examined the diagnostic significance of anti-double-stranded deoxyribonucleic acid (anti-dsDNA) determination in a group of 441 patients without systemic lupus erythematosus whose sera were found to contain antibodies to dsDNA on routine screening.(({{pmid>long:3872637}})) Within one year, 69% (304) of these patients fulfilled the preliminary American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). Eighty-two of the remaining 137 patients were followed up for several years. At the end of the study, 52% of these patients had also developed systemic lupus erythematosus. The team concluded that about 85% of patients without systemic lupus erythematosus with anti-dsDNA in the circulation would develop SLE within a few years.

	Another recent study of blood from 441 healthy Portuguese blood-donors found autoantibodies for rheumatoid factor, anti cyclic citrunillated peptides, anti-mitochondria, anti-Sacharomyces cerevisiae, ANA, anti-TTG, and anti-Beta2- glycoprotein.((Tavares-Ratado, P., A. Geraldes, //et al.// 2009. Prevalence of Circulating Autoantibodies in Portugese Blood Donors. 4th Asian Congress on Autoimmunity, Singapore.)) More than 30% of the blood contained one or more of the antibodies, 4% exhibited two antibodies, and nearly 1% had three or more antibodies present. It is clear that sub-clinical autoimmune disease is much more common than previously thought.		Another recent study of blood from 441 healthy Portuguese blood-donors found autoantibodies for rheumatoid factor, anti cyclic citrunillated peptides, anti-mitochondria, anti-Sacharomyces cerevisiae, ANA, anti-TTG, and anti-Beta2- glycoprotein.((Tavares-Ratado, P., A. Geraldes, //et al.// 2009. Prevalence of Circulating Autoantibodies in Portugese Blood Donors. 4th Asian Congress on Autoimmunity, Singapore.)) More than 30% of the blood contained one or more of the antibodies, 4% exhibited two antibodies, and nearly 1% had three or more antibodies present. It is clear that sub-clinical autoimmune disease is much more common than previously thought.
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	The concept of autoimmune disease has progressed to the point that now even researchers who previously dismissed the possibility of infection are accepting the possibility that “autoimmune” disease could be triggered by infection. This is some progress, but it’s not enough. Especially since the concept of autoimmunity encourages doctors to prescribe immunosuppressive steroids to patients. But if persistent infection is involved these steroids may exacerbate the fire by allowing pathogens to spread.		The concept of autoimmune disease has progressed to the point that now even researchers who previously dismissed the possibility of infection are accepting the possibility that “autoimmune” disease could be triggered by infection. This is some progress, but it’s not enough. Especially since the concept of autoimmunity encourages doctors to prescribe immunosuppressive steroids to patients. But if persistent infection is involved these steroids may exacerbate the fire by allowing pathogens to spread.

-	//Paul Ewald, [[http://bacteriality.com/2008/02/11/ewald/\|Bacteriality.com]]// </blockquote>	+	//Paul Ewald, [[https://bacteriality.com/2008/02/11/ewald/\|Bacteriality.com]]// </blockquote>

	To think that autoimmune disease is caused by an interaction between the environment and human genetics, as a number of commentators have, is only marginally more plausible. Evolutionary theory is clear that any kind of consistent reproductive disadvantage is consistently and ultimately weeded out of the population.		To think that autoimmune disease is caused by an interaction between the environment and human genetics, as a number of commentators have, is only marginally more plausible. Evolutionary theory is clear that any kind of consistent reproductive disadvantage is consistently and ultimately weeded out of the population.
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	===== Conventional therapies for autoimmunity =====		===== Conventional therapies for autoimmunity =====

02.13.2019		current
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-	Many researchers have long argued that most chronic diseases are caused by humans' genetic predisposition for a condition. However, despite ambitious efforts, there is substantial evidence that chronic diseases are not caused by human genes. Studies of monozygotic (fraternal) twins are particularly damning. The high percentage of disease-discordant pairs of monozygotic twins demonstrates the central role of environmental factors (like microbes) in the cause of autoimmune diseases, to say nothing of similar data about other inflammatory diseases such as cancer.(({{pubmed>long:16278064}}))	+	Many researchers have long argued that most chronic diseases are caused by humans' genetic predisposition for a condition. However, despite ambitious efforts, there is substantial evidence that chronic diseases are not caused by human genes. Studies of monozygotic (fraternal) twins are particularly damning. The high percentage of disease-discordant pairs of monozygotic twins demonstrates the central role of environmental factors (like microbes) in the cause of autoimmune diseases, to say nothing of similar data about other inflammatory diseases such as cancer.(({{pmid>long:16278064}}))

	According to the [[home::pathogenesis\|Marshall Pathogenesis]], humans accumulate a plethora of pathogenic bacteria during their lifetimes, and it is the genetic mutations and disruption of key transcriptional pathways which result from active infection that play a major role in what is commonly thought of as “genetic susceptibility.”		According to the [[home::pathogenesis\|Marshall Pathogenesis]], humans accumulate a plethora of pathogenic bacteria during their lifetimes, and it is the genetic mutations and disruption of key transcriptional pathways which result from active infection that play a major role in what is commonly thought of as “genetic susceptibility.”
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	<blockquote>If anything, we don't really know how to read the genome and it can't tell us very much right now. So what's the ethical debate about?... We couldn't even be certain from my genome what my eye color was. Isn't that sad? Everyone was looking for miracle 'yes/no' answers in the genome. "Yes, you'll have cancer." Or "No, you won't have cancer." But that's just not the way it is.... [The Human Genome Project has had] close to zero [medical benefit] to put it precisely.... We have, in truth, learned nothing from the genome other than probabilities. How does a 1 or 3 percent increased risk for something translate into the clinic? It is useless information.		<blockquote>If anything, we don't really know how to read the genome and it can't tell us very much right now. So what's the ethical debate about?... We couldn't even be certain from my genome what my eye color was. Isn't that sad? Everyone was looking for miracle 'yes/no' answers in the genome. "Yes, you'll have cancer." Or "No, you won't have cancer." But that's just not the way it is.... [The Human Genome Project has had] close to zero [medical benefit] to put it precisely.... We have, in truth, learned nothing from the genome other than probabilities. How does a 1 or 3 percent increased risk for something translate into the clinic? It is useless information.

-	//J. Craig Venter, [[http://www.spiegel.de/international/world/0,1518,709174,00.html\|Der Spiegel interview]]//	+	//J. Craig Venter, [[https://www.spiegel.de/international/world/0,1518,709174,00.html\|Der Spiegel interview]]//
	</blockquote>		</blockquote>

	===== Human genetics as a cause for chronic disease =====		===== Human genetics as a cause for chronic disease =====

-	The bulk of the human genome was [[http://www.genome.gov/11006929\|first fully sequenced]] in the year 2003. For some, the "Genomic Era" - as it has been called (({{pubmed>long:12954750}})) - represents the future of medical therapies for chronic disease. Using rapid throughput genomic sequencing technology, researchers have conducted studies comparing the genetic makeup of people suffering from a given chronic disease, sometimes as many as 1,000 or more, to healthy controls. Researchers have long hoped that these studies will produce a list of which human genes cause which chronic diseases and allow for true genomically-based "personalized medicine" including the administration of genomic-based designer drugs as well as gene therapies.(({{pubmed>long:11176855}}))	+	The bulk of the human genome was [[https://www.genome.gov/11006929\|first fully sequenced]] in the year 2003. For some, the "Genomic Era" - as it has been called (({{pmid>long:12954750}})) - represents the future of medical therapies for chronic disease. Using rapid throughput genomic sequencing technology, researchers have conducted studies comparing the genetic makeup of people suffering from a given chronic disease, sometimes as many as 1,000 or more, to healthy controls. Researchers have long hoped that these studies will produce a list of which human genes cause which chronic diseases and allow for true genomically-based "personalized medicine" including the administration of genomic-based designer drugs as well as gene therapies.(({{pmid>long:11176855}}))

	Optimism that this avenue of research will improve clinical outcomes has always been high and is epitomized by this 2001 paper in //JAMA//:		Optimism that this avenue of research will improve clinical outcomes has always been high and is epitomized by this 2001 paper in //JAMA//:
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	It should be possible to identify disease gene associations for many common illnesses in the next 5 to 7 years.		It should be possible to identify disease gene associations for many common illnesses in the next 5 to 7 years.

-	//Francis Collins, et al.// (({{pubmed>long:11176855}})) </blockquote>	+	//Francis Collins, et al.// (({{pmid>long:11176855}})) </blockquote>


	==== Failed promise of human genetic research ====		==== Failed promise of human genetic research ====

-	It may yet be too early to call human genomic research an unqualified failure, but certain researchers have noted a distinct lack of results, and limited progress in the genetic analysis of common diseases has been widely acknowledged:(({{pubmed>long:16243094}})) (({{pubmed>long:16255080}})) (({{pubmed>long:10866211}}))	+	It may yet be too early to call human genomic research an unqualified failure, but certain researchers have noted a distinct lack of results, and limited progress in the genetic analysis of common diseases has been widely acknowledged:(({{pmid>long:16243094}})) (({{pmid>long:16255080}})) (({{pmid>long:10866211}}))
-	* "Expectations regarding the benefits of genetic research" have been "overly enthusiastic."(({{pubmed>long:11976443}}))	+	* "Expectations regarding the benefits of genetic research" have been "overly enthusiastic."(({{pmid>long:11976443}}))
-	* "Much effort has been expended on research into their causes, with the aim of predicting who will be affected or preventing effects before they arise, but progress has been halting at best."(({{pubmed>long:16540539}}))	+	* "Much effort has been expended on research into their causes, with the aim of predicting who will be affected or preventing effects before they arise, but progress has been halting at best."(({{pmid>long:16540539}}))
-	* "Given the continuing difficulty of identifying genes for complex disorders in a robust, replicable manner, and the extensive resources devoted to this effort, it is becoming increasingly important to analyze the relative benefits of genomics research for public health applications and for the understanding of disease pathogenesis."(({{pubmed>long:14576422}}))	+	* "Given the continuing difficulty of identifying genes for complex disorders in a robust, replicable manner, and the extensive resources devoted to this effort, it is becoming increasingly important to analyze the relative benefits of genomics research for public health applications and for the understanding of disease pathogenesis."(({{pmid>long:14576422}}))
-	* "Heritable causes of complex diseases remain largely elusive, despite tremendous efforts to understand them.... Technological excellence in genomics does not automatically lead to benefits in human health."(({{pubmed>long:17139327}}))	+	* "Heritable causes of complex diseases remain largely elusive, despite tremendous efforts to understand them.... Technological excellence in genomics does not automatically lead to benefits in human health."(({{pmid>long:17139327}}))

-	In a striking image from a 1999 lecture, Francis Collins of the US National Human Genome Research Institute described a hypothetical consultation in 2010, in which a 23-year old man has a high concentration of cholesterol identified during screening and undergoes extensive genetic testing.(({{pubmed>long:10387940}})) The scenario listed eight genetic variants which at the time were thought to contribute to disease. What has been the fate of these genetic variants? According to Smith: "With few exceptions, later [more conclusive] evidence suggests that these variants are related to much smaller increased risks of disease, if any," and would not be of value during a medical consultation.(({{pubmed>long:16243094}}))	+	In a striking image from a 1999 lecture, Francis Collins of the US National Human Genome Research Institute described a hypothetical consultation in 2010, in which a 23-year old man has a high concentration of cholesterol identified during screening and undergoes extensive genetic testing.(({{pmid>long:10387940}})) The scenario listed eight genetic variants which at the time were thought to contribute to disease. What has been the fate of these genetic variants? According to Smith: "With few exceptions, later [more conclusive] evidence suggests that these variants are related to much smaller increased risks of disease, if any," and would not be of value during a medical consultation.(({{pmid>long:16243094}}))


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	<blockquote>We know that diseases [[home:pathogenesis:familial_aggregation\|cluster in families]]. In some diseases, the risk might be two or three times higher than normal, or 30 times higher, for a relative of someone with a disease. But when we do these genomic studies, we find maybe a 50 percent increase in risk. That gap is what’s missing.		<blockquote>We know that diseases [[home:pathogenesis:familial_aggregation\|cluster in families]]. In some diseases, the risk might be two or three times higher than normal, or 30 times higher, for a relative of someone with a disease. But when we do these genomic studies, we find maybe a 50 percent increase in risk. That gap is what’s missing.

-	//Teri Manolio, Director of the National Human Genome Research Institute’s Office of Population Genomics, discussing missing heritability in a 2009 [[http://www.wired.com/wiredscience/2009/10/beyond-the-genome/\|Wired interview]]//</blockquote>	+	//Teri Manolio, Director of the National Human Genome Research Institute’s Office of Population Genomics, discussing missing heritability in a 2009 [[https://www.wired.com/wiredscience/2009/10/beyond-the-genome/\|Wired interview]]//</blockquote>

	==== Conventional explanations for why genetic studies have failed ====		==== Conventional explanations for why genetic studies have failed ====

07.07.2019		current
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	====== Psychosomatic explanations for disease ======		====== Psychosomatic explanations for disease ======

-	Sigmund Freud and Jean-Martin Charcot were born 150 years ago, but their ideas about the effect of the subconscious on disease continue to resonate in the scientific community.(({{pubmed>long:335422}})) Freud and colleagues argued that unconscious mental processes such as sublimated rage could manifest as physical symptoms. However, with the advent of superior technology, one by one, many diseases once supposed to be caused by psychological stress have since been attributed to other factors including infections.	+	Sigmund Freud and Jean-Martin Charcot were born 150 years ago, but their ideas about the effect of the subconscious on disease continue to resonate in the scientific community.(({{pmid>long:335422}})) Freud and colleagues argued that unconscious mental processes such as sublimated rage could manifest as physical symptoms. However, with the advent of superior technology, one by one, many diseases once supposed to be caused by psychological stress have since been attributed to other factors including infections.

-	According to the Marshall Pathogenesis, chronic fatigue syndrome, multiple chemical sensitivity and other chronic inflammatory diseases are likely caused by pathogens, yet many physicians consider these diseases to be "medically unexplained." Medically unexplained diseases are widely prevalent(({{pubmed>long:11448704}})) but at the same time have few discernible markers or objectively measurable symptoms. While a lot of Freudian ideas have fallen out of favor, one legacy remains: difficult-to-explain diseases are still routinely attributed to psychological causes. The process by which patients supposedly manifest psychological problems as a disease has been named and renamed, classified and reclassified: hysteria, psychosomatic disorder, somatoform disorder, conversion disorder, functional disorder, etc. In each of these diagnoses, however, the stated origin of disease is unchanged: symptoms that cannot be explained are ultimately "all in a patient's head."	+	According to the Marshall Pathogenesis, chronic fatigue syndrome, multiple chemical sensitivity and other chronic inflammatory diseases are likely caused by pathogens, yet many physicians consider these diseases to be "medically unexplained." Medically unexplained diseases are widely prevalent(({{pmid>long:11448704}})) but at the same time have few discernible markers or objectively measurable symptoms. While a lot of Freudian ideas have fallen out of favor, one legacy remains: difficult-to-explain diseases are still routinely attributed to psychological causes. The process by which patients supposedly manifest psychological problems as a disease has been named and renamed, classified and reclassified: hysteria, psychosomatic disorder, somatoform disorder, conversion disorder, functional disorder, etc. In each of these diagnoses, however, the stated origin of disease is unchanged: symptoms that cannot be explained are ultimately "all in a patient's head."

-	While there is no denying the existence of some sort of "mind-body connection," there is minimal compelling evidence that as the 19th century Swiss physician Georg W. Groddeck claimed: "Illness has a purpose; it has to resolve the conflict, to repress it, or to prevent what is already repressed from entering consciousness."((Webster, R. 1996. //Why Freud was wrong: sin, science and psychoanalysis//. London, HarperCollins.)) Despite the stark absence of evidence supporting these views, it is not unusual to read papers describing how patients with long-term so-called psychological illnesses may be subconsciously manifesting them, because it would allow them to have more "care, attention, disengagement, or even financial benefits."(({{pubmed>long:10375340}})) Nor, is it uncommon for new theories to spring up along these lines. In one example, a 2008 [[http://www.cmej.org.za/index.php/cmej/article/view/459/305\|continuing medical education]] publication taught physicians that when a celebrity becomes ill, healthy people are suggestible enough to develop long-term illnesses consistent with the celebrity's descriptions of their conditions. Such claims are recklessly speculative, harming patients and stalling needed research.	+	While there is no denying the existence of some sort of "mind-body connection," there is minimal compelling evidence that as the 19th century Swiss physician Georg W. Groddeck claimed: "Illness has a purpose; it has to resolve the conflict, to repress it, or to prevent what is already repressed from entering consciousness."((Webster, R. 1996. //Why Freud was wrong: sin, science and psychoanalysis//. London, HarperCollins.)) Despite the stark absence of evidence supporting these views, it is not unusual to read papers describing how patients with long-term so-called psychological illnesses may be subconsciously manifesting them, because it would allow them to have more "care, attention, disengagement, or even financial benefits."(({{pmid>long:10375340}})) Nor, is it uncommon for new theories to spring up along these lines. In one example, a 2008 [[https://www.cmej.org.za/index.php/cmej/article/view/459/305\|continuing medical education]] publication taught physicians that when a celebrity becomes ill, healthy people are suggestible enough to develop long-term illnesses consistent with the celebrity's descriptions of their conditions. Such claims are recklessly speculative, harming patients and stalling needed research.

-	Treating patients who complain of so-called medically unexplained symptoms with cognitive behavioral therapy or, in the case of chronic fatigue syndrome, graded exercise therapy, may do more harm than good.(({{pubmed>long:19855350}})) The emergence of metagenomic technologies offers a more sophisticated set of tools for detecting and characterizing microbes in these disease states. Perhaps it is only the use of this technology that will finally relegate the notion of patient as attention-seeking victim to historical relic.	+	Treating patients who complain of so-called medically unexplained symptoms with cognitive behavioral therapy or, in the case of chronic fatigue syndrome, graded exercise therapy, may do more harm than good.(({{pmid>long:19855350}})) The emergence of metagenomic technologies offers a more sophisticated set of tools for detecting and characterizing microbes in these disease states. Perhaps it is only the use of this technology that will finally relegate the notion of patient as attention-seeking victim to historical relic.


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	===== Many patients' complaints are "medically unexplained" =====		===== Many patients' complaints are "medically unexplained" =====

-	Numerous studies have demonstrated that many of the physical complaints presented to physicians are unexplained from a medical perspective.((Nezu AM, Nezu CM, Lombardo ER. Cognitive-behavior therapy for medically unexplained symptoms: A critical review of the treatment literature. Behavior Therapy. 2001;32(3):537-83.)) ((Lombardo ER, Nezu AM. Medically Unexplained Symptoms. In: Freeman A, Felgoise SH, Nezu CM, Nezu AM, Reinecke MA, editors. //Encyclopedia of Cognitive Behavior Therapy// Springer US; 2005. p. 241-4.)) Depending on the setting, between 30 and 66% of patients who seek medical care have unexplained symptoms.(({{pubmed>long:10644789}})) (({{pubmed>long:11448704}})) (({{pubmed>long:14999491}})) According to a 1996 estimate, the eight most common physical complaints (fatigue, backache, headache, dizziness, chest pain, dyspnea, abdominal pain, anxiety) account for more than 80 million physician visits annually in the United States, and only 25% of these symptoms have a demonstrable organic (of the body) cause.(({{pubmed>long:8675547}})) According to the Marshall Pathogenesis and as described elsewhere in the Knowledge Base, many of these "unexplained" symptoms [[home:pathogenesis:evidence_bacteria\|are likely due to microbes]].	+	Numerous studies have demonstrated that many of the physical complaints presented to physicians are unexplained from a medical perspective.((Nezu AM, Nezu CM, Lombardo ER. Cognitive-behavior therapy for medically unexplained symptoms: A critical review of the treatment literature. Behavior Therapy. 2001;32(3):537-83.)) ((Lombardo ER, Nezu AM. Medically Unexplained Symptoms. In: Freeman A, Felgoise SH, Nezu CM, Nezu AM, Reinecke MA, editors. //Encyclopedia of Cognitive Behavior Therapy// Springer US; 2005. p. 241-4.)) Depending on the setting, between 30 and 66% of patients who seek medical care have unexplained symptoms.(({{pmid>long:10644789}})) (({{pmid>long:11448704}})) (({{pmid>long:14999491}})) According to a 1996 estimate, the eight most common physical complaints (fatigue, backache, headache, dizziness, chest pain, dyspnea, abdominal pain, anxiety) account for more than 80 million physician visits annually in the United States, and only 25% of these symptoms have a demonstrable organic (of the body) cause.(({{pmid>long:8675547}})) According to the Marshall Pathogenesis and as described elsewhere in the Knowledge Base, many of these "unexplained" symptoms [[home:pathogenesis:evidence_bacteria\|are likely due to microbes]].


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	The chronic fatigue syndrome and fibromyalgia (probably the same disorder) are characterized by considerable suffering and disability. We must not add to that suffering by trivializing patients with “functional” labels. Marginal care inevitably ensues.		The chronic fatigue syndrome and fibromyalgia (probably the same disorder) are characterized by considerable suffering and disability. We must not add to that suffering by trivializing patients with “functional” labels. Marginal care inevitably ensues.

-	//Thomas L. English, M.D.//(({{pubmed>long:10681297}}))</blockquote>	+	//Thomas L. English, M.D.//(({{pmid>long:10681297}}))</blockquote>


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	^Disease ^Early and erroneous claims ^More valid explanations ^		^Disease ^Early and erroneous claims ^More valid explanations ^
-	\|cardiac disease \|Type A behavior – in which people are impatient, time-conscious and controlling – was first described as a substantial risk factor in coronary disease by the cardiologists Meyer Friedman and R. H. Rosenman.((Friedman, M., & Rosenman, R. H. (1974). //Type A behavior and your heart//. New York: Knopf.)) \|Research since then has found that Type A behavior is not a good predictor of coronary heart disease.(({{pubmed>long:16934002}})) On the basis of this and other criticisms, Type A theory has been termed obsolete by many researchers in contemporary health psychology and personality psychology. \|	+	\|cardiac disease \|Type A behavior – in which people are impatient, time-conscious and controlling – was first described as a substantial risk factor in coronary disease by the cardiologists Meyer Friedman and R. H. Rosenman.((Friedman, M., & Rosenman, R. H. (1974). //Type A behavior and your heart//. New York: Knopf.)) \|Research since then has found that Type A behavior is not a good predictor of coronary heart disease.(({{pmid>long:16934002}})) On the basis of this and other criticisms, Type A theory has been termed obsolete by many researchers in contemporary health psychology and personality psychology. \|
-	\|camptocormia - forced posture with a forward-bent trunk \|supposedly seen in soldiers during World Wars I and II; claimed it could be cured quickly and durably by a "persuasive" electrotherapy(({{pubmed>long:10423797}})) \|muscle weakness; an organic comorbidity of Parkinson's and ALS \|	+	\|camptocormia - forced posture with a forward-bent trunk \|supposedly seen in soldiers during World Wars I and II; claimed it could be cured quickly and durably by a "persuasive" electrotherapy(({{pmid>long:10423797}})) \|muscle weakness; an organic comorbidity of Parkinson's and ALS \|
-	\|schizophrenia \|claimed to be caused by cold, distant mothers(({{pubmed>long:10681297}})) (({{pubmed>long:13945453}})) \|communities of microbes have been increasingly implicated. A viral infection of pregnant woman during critical brain development of foetus is credible. (({{pubmed>long:22488761}})), (({{pubmed>long:30068405}})), (({{pubmed>long:28463237}})), (({{pubmed>long: 28844435}})), (({{pubmed>long: 25464029}})) \|	+	\|schizophrenia \|claimed to be caused by cold, distant mothers(({{pmid>long:10681297}})) (({{pmid>long:13945453}})) \|communities of microbes have been increasingly implicated. An infection of pregnant woman during critical brain development of foetus is credible. (({{pmid>long:22488761}})), (({{pmid>long:30068405}})), (({{pmid>long:28463237}})), (({{pmid>long: 28844435}})), (({{pmid>long: 25464029}})) \|
	\|stomach ulcers \|claimed to be cause by stress \|//Helicobacter pylori// \|		\|stomach ulcers \|claimed to be cause by stress \|//Helicobacter pylori// \|
-	\|tuberculosis \|in the developed world, claimed to be caused by tubercular personality((Hartz, J. (1944). [[http://www.psychosomaticmedicine.org/cgi/content/abstract/6/1/17\|Tuberculosis and personality conflicts]]. //Psychosomatic Medicine// 6(1): 17.)) – romantic, unfulfilled, cosmopolitan people that need change and excitement \|//Mycobacterium tuberculosis// \|	+	\|tuberculosis \|in the developed world, claimed to be caused by tubercular personality((Hartz, J. (1944). [[https://www.psychosomaticmedicine.org/cgi/content/abstract/6/1/17\|Tuberculosis and personality conflicts]]. //Psychosomatic Medicine// 6(1): 17.)) – romantic, unfulfilled, cosmopolitan people that need change and excitement \|//Mycobacterium tuberculosis// \|
	\|ulcerative colitis \|in children, according to one author's claims, caused by interdependent on relationship between patients, parents, and grandparents((Adams, P. (1968). Childhood Ulcerative Colitis: Outlines of Psychotherapy. //Psychosomatics// 9(2): 75.)) \|no widely accepted cause, however, communities of microbes have been increasingly implicated \|		\|ulcerative colitis \|in children, according to one author's claims, caused by interdependent on relationship between patients, parents, and grandparents((Adams, P. (1968). Childhood Ulcerative Colitis: Outlines of Psychotherapy. //Psychosomatics// 9(2): 75.)) \|no widely accepted cause, however, communities of microbes have been increasingly implicated \|

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	==== Ancient Greece – origin of hysteria ====		==== Ancient Greece – origin of hysteria ====

-	The notion of hysteria can be traced to ancient times. In the gynecological treatises of the Hippocratic corpus (5th and 4th centuries BCE), the father of medicine describes an illness in which the uterus dries up and wanders the body in search of moisture. They called this hysteria. Symptoms would then be caused by the uterus pressing on other organs. If it had wandered as far as the cranium, for example, the symptom would be headaches.(({{pubmed>long:18568070}})) Plato's dialogue //Timaeus// tells of the uterus wandering throughout a woman’s body, strangling the victim as it reaches the chest and causing disease. This theory is the source of the name, which stems from the Greek cognate of uterus, //hystera//. Galen, a prominent physician from the second century, wrote that hysteria was a disease caused by sexual deprivation in particularly passionate women. In the 17th century, Sydenham said, "hysteria could simulate any medical disease."((Kallivayalil RA, Punnoose VP. [[http://www.indianjpsychiatry.org/article.asp?issn=0019-5545;year=2010;volume=52;issue=7;spage=240;epage=245;aulast=Kallivayalil\|Understanding and managing somatoform disorders: Making sense of non-sense]]. //Indian J Psychiatry// 2010;52:240-5.))	+	The notion of hysteria can be traced to ancient times. In the gynecological treatises of the Hippocratic corpus (5th and 4th centuries BCE), the father of medicine describes an illness in which the uterus dries up and wanders the body in search of moisture. They called this hysteria. Symptoms would then be caused by the uterus pressing on other organs. If it had wandered as far as the cranium, for example, the symptom would be headaches.(({{pmid>long:18568070}})) Plato's dialogue //Timaeus// tells of the uterus wandering throughout a woman’s body, strangling the victim as it reaches the chest and causing disease. This theory is the source of the name, which stems from the Greek cognate of uterus, //hystera//. Galen, a prominent physician from the second century, wrote that hysteria was a disease caused by sexual deprivation in particularly passionate women. In the 17th century, Sydenham said, "hysteria could simulate any medical disease."((Kallivayalil RA, Punnoose VP. [[https://www.indianjpsychiatry.org/article.asp?issn=0019-5545;year=2010;volume=52;issue=7;spage=240;epage=245;aulast=Kallivayalil\|Understanding and managing somatoform disorders: Making sense of non-sense]]. //Indian J Psychiatry// 2010;52:240-5.))