MEpedia - User contributions [en]

Ibudilast

2023-03-04T18:55:47Z

Davidshq:

{{stub}}
''Ibudilast'' (brand names Ketas or Pinatos in [[Japan]], drug development names AV411 and MN166 the [[United States]])) is a drug used for over 20 years in Japan, mostly for asthma and post-stroke [[dizziness]].<ref name="Rolan2009" /> Ibudilast is a phosphodiesterase inhibitor, an immunomodulator, reduces microglial activation, and has anti-inflammatory effects.<ref name="Rolan2009" />

==Potential uses==
Ibudilast is under investigation for a number of new purposes, and evidence exists that it can be combined with [[opioid]]s to reduce chronic [[nerve pain]].<ref name="Rolan2009">{{Cite journal | title = Ibudilast: a review of its pharmacology, efficacy and safety in respiratory and neurological disease | date = Dec 2009|url=https://www.researchgate.net/publication/40023191_Ibudilast_A_review_of_its_pharmacology_efficacy_and_safety_in_respiratory_and_neurological_disease|journal=Expert Opinion on Pharmacotherapy|volume=10|issue=17 | pages = 2897–2904 | last = Rolan | first = P | authorlink = | last2 = Hutchinson | first2 = MR | authorlink2 = | last3 = Johnson | first3 = KW | authorlink3 = |language=en|doi=10.1517/14656560903426189|pmc=|pmid=|access-date=|issn=1465-6566|quote=|via=}}</ref> Many studies of ibudilast are on rats or other animals rather than humans.<ref name="Rolan2009" /> Ibudilast crosses the [[blood-brain barrier]] and suppresses glial cell activation.

==Theory==

==Evidence==

==Clinicians==

==Risks and safety==

==Costs and availability==

==See also==

==Learn more==
*

==References==
{{reflist}}

[[Category:Potential treatments]]
[[Category:Immunomodulators]]
[[Category:Analgesics]]
[[Category:Anti-inflammatories]]

Iceland moss

2023-02-28T04:07:20Z

Davidshq:/* Costs and availability */

'''Cetraria islandica''' L. Ach or '''Lichen islandicus''' or '''Iceland moss''' or '''Iceland lichen''' is an edible moss used as a food supplement, and for making soaps and cold creams.<ref>{{Cite web|url=https://www.britannica.com/science/Iceland-moss | title = Iceland moss {{!}} lichen | last = | first = | authorlink = | date = | website = Britannica|language=en|archive-url=|archive-date=|url-status=|access-date=2022-01-16}}</ref><ref name="WebMD">{{Cite web|url=https://www.webmd.com/vitamins/ai/ingredientmono-516/iceland-moss | title = Iceland Moss|website=WebMD |access-date=2022-01-16}}</ref>

Iceland moss has been analysed and found to contain the compounds:
*protolichesterinic acid
*lichesterinic acid
*protocetraric acid and
*fumarprotocetraric acid<ref name="Igoli2014">{{Cite journal | title = Antitrypanosomal Activity & Docking Studies of Isolated Constituents from the Lichen Cetraria islandica: Possibly Multifunctional Scaffolds | date = 2014-04-01|url=https://www.ingentaconnect.com/content/ben/ctmc/2014/00000014/00000008/art00006|journal=Current Topics in Medicinal Chemistry|volume=14|issue=8|pages=1014–1021 | last = Ogbaji Igoli | first = John | last2 = Irvine Gray | first2 = Alexander | last3 = Jean Clements | first3 = Carol | last4 = Kantheti | first4 = Poorna | last5 = Kumar Singla | first5 = Rajeev}}</ref>

Analysis suggests that these compounds may be active on the targets of [[trypanosoma brucei]], the parasite that causes [[African trypanosomiasis|African sleeping sickness]] - these targets are riboflavin kinase, sterol-14α-demethylase ([[CYP51]]), rohedsain and [[glutathione]] synthetase.<ref name="Igoli2014" />

==Theory==

==Evidence==
The [[European Medicines Agency]] has stated there is enough evidence for the use of Iceland moss for agent for treating mouth and throat irritation and associated dry cough, and for temporary [[anorexia (appetite loss)|loss of appetite]] in adults, adolescents and children aged over six years-old.<ref name="ema">https://www.ema.europa.eu/en/medicines/herbal/lichen-islandicus{{Cite web|url=https://www.ema.europa.eu/en/medicines/herbal/lichen-islandicus | title = Lichen islandicus | last = | first = | authorlink = | date = | website = European Medicines Agency|archive-url=|archive-date=|url-status=|access-date=2022-01-16}}</ref>

Freysdottir et al (2008) found that Iceland Moss had anti-inflammatory properties and acted as an immunomodulator in rats and human cells.<ref name="Freysdottir2008">{{Cite journal | title = In vitro and in vivo immunomodulating effects of traditionally prepared extract and purified compounds from Cetraria islandica | date = Mar 2008|url=https://pubmed.ncbi.nlm.nih.gov/18279796/|journal=International Immunopharmacology|volume=8|issue=3 | pages = 423–430 | last = Freysdottir | first = J. | authorlinklink= | last2 = Omarsdottir | first2 = S. | authorlink2 = | last3 = Ingólfsdóttir | first3 = K. | authorlink3 = | last4 = Vikingsson | first4 = A. | authorlink4 = | last5 = Olafsdottir | first5 = E.S. | authorlink5 = |doi=10.1016/j.intimp.2007.11.007|pmc=|pmid=18279796|access-date=|issn=1567-5769|quote=|via=}}</ref> It may also have antioxidant effects.<ref name="Gulcin2002">{{Cite journal | title = Determination of antioxidant activity of lichen Cetraria islandica (L) Ach | date = 2002-03-01|url=https://www.sciencedirect.com/science/article/pii/S0378874101003968|journal=Journal of Ethnopharmacology|volume=79|issue=3 | pages = 325–329 | last = Gülçin | first = İlhami | last2 = Oktay | first2 = Münir | last3 = Küfrevioğlu | first3 = Ö. İrfan | last4 = Aslan | first4 = Ali|language=en|doi=10.1016/S0378-8741(01)00396-8|issn=0378-8741}}</ref>

==Clinicians==

==Risks and safety==

==Costs and availability==
It is available in powdered form as a supplement.

==See also==

==Learn more==
*[https://www.webmd.com/vitamins/ai/ingredientmono-516/iceland-moss Iceland Moss] - WebMD
*[https://www.ema.europa.eu/en/medicines/herbal/lichen-islandicus European Medicines Agency]

==References==
{{reflist}}

[[Category:Potential treatments]]
[[Category:Alternative medicine‎]]
[[Category:Analgesics‎]]
[[Category:Anti-inflammatories‎‎]]
[[Category:Antioxidants‎‎]]
[[Category:Flavonoids‎]]
[[Category:Herbs‎]]
[[Category:Immunomodulators‎]]
[[Category:Medicinal foods‎]]
[[Category:Supplements‎]]

Yakammaoto

2023-02-28T04:03:58Z

Davidshq:

Yakammaoto is a [[traditional Chinese medicine]] (TCM) formulation containing nine ingredients, including [[Ephedra sinica]], [[Pinellia ternate]], [[Zingiber officinale]], [[Tussilago farfara]], [[Aster tataricus]], [[Ziziphus jujube]], [[Belamcanda chinensis]], [[Asarum sieboldii]], and [[Schisandra chinensis]].

One study showed it had antiviral activity against [[Coxsackie B4]].<ref>{{Citation| doi = 10.1016/j.jep.2013.11.049| issn = 1872-7573| volume = 151| issue = 3| pages = 1056–1063| last1 = Yen| first1 = Ming Hong | last2 = Lee | first2 = Jia Jung | last3 = Yeh | first3 = Chia Feng | last4 = Wang | first4 = Kuo Chih | last5 = Chiang | first5 = Ya Wen | last6 = Chiang | first6 = Lien Chai | last7 = Chang | first7 = Jung San| title = Yakammaoto inhibited human coxsackievirus B4 (CVB4)-induced airway and renal tubular injuries by preventing viral attachment, internalization, and replication| journal = Journal of Ethnopharmacology| date = 2014-02-12| pmid = 24361333}}</ref>

==References==
{{Reflist}}

[[Category:Potential treatments]]
[[Category:Traditional Chinese medicine]]

Breakdown of homeostasis hypothesis

2022-12-24T19:10:51Z

Davidshq:

{{stub}}
The breakdown of homeostasis hypothesis proposes that (by [[David Marks|David F. Marks]]) [[ME/CFS]] is caused by a breakdown in homeostasis.<ref name="Marks2021" /> Marks published this hypothesis in 2021, although a failure to maintain homeostasis has also been referred to as a part of the cause of ME/CFS by a number of other researchers.{{citation needed | date = 2021}}

==Theory==

==Evidence==

==Treatment==

==Notable studies ==
* 2021, Myalgic encephalomyelitis/ chronic fatigue syndrome as a breakdown of homeostasis<ref name="Marks2021">{{Cite journal | last = Marks | first = David F. | authorlink = David Marks | date = 2021-05-31 | title = Myalgic encephalomyelitis/ chronic fatigue syndrome as a breakdown of homeostasis |url =https://www.qeios.com/read/FZ1Y68.2|journal=Qeios|language=en|volume=|issue= | pages = |doi=10.32388/FZ1Y68.2|issn=2632-3834|pmc=|pmid=|access-date=|quote=|via=}}</ref> [https://doi.org/10.32388/FZ1Y68.2 (Full text)]

==See also ==
*[[David Marks]]

==Learn more ==

==References ==
{{Reflist}}

[[Category:Medical hypotheses]]

Amino acid

2022-12-24T18:06:59Z

Davidshq:/* ME/CFS */

'''Amino acids''' are organic compounds comprise mainly from the elements carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino acids. Because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements, fertilizers, and food technology. Industrial uses include the production of drugs, biodegradable plastics, and chiral catalysts.

== Types ==
===Branched chain amino acids===
The [[branched chain amino acid]]s (BCAAs): (BCAAs) are [[leucine]], [[isoleucine]] and [[valine]].<ref name="vanderPollch">{{Cite book | title = Guide to Nutritional Supplements | pages = 7-8|isbn=978-0-12-375661-9|edition=|volume=|language=en| title-link = | url = https://books.google.co.uk/books?id=_VjxiHvdlOQC&newbks=0&lpg=PA7&pg=PA7#v=snippet&f=true|access-date= | date = 2009-09-02| publisher = Academic Press | last = van der Poll | first = MCG | authorlink = | last2 = Luiking | first2 = YC | authorlink2 = | last3 = Dejong | first3 = CHC | authorlink3 = | last4 = Soeters | first4 = PB | authorlink4 = |veditors=|others=|doi=|oclc=|quote=|archive-url=|archive-date=|location=Oxford, UK|editor-last = Caballero|editor-first = Benjamin|editor1link = |editor-last2 = |editor-first2 = |chapter=Amino Acids}}</ref>
{{See also|Branched chain amino acid}}

===Long neutral amino acids===
The long neutral amino acids (LNNAs) are [[tyrosine]], [[tryptophan]], [[threonine]], [[methionine]], [[valine]], [[isoleucine]], [[leucine]], [[histidine]] and [[phenylalanine]].

===Essential amino acids===
The essential amino acids in humans are those which cannot be made by the body, and must be taken in from food (diet).<ref name="Lopez2022" />
The nine essential amino acids are [[phenylalanine]], [[valine]], [[tryptophan]], [[threonine]], [[isoleucine]], [[methionine]], [[histidine]], [[leucine]], and [[lysine]].<ref name="Lopez2022">{{Cite book | title = Biochemistry, Essential Amino Acids | date = 2022 | url = http://www.ncbi.nlm.nih.gov/books/NBK557845/ | last = Lopez | first = Michael J. | last2 = Mohiuddin | first2 = Shamim S.|location=Treasure Island (FL)| publisher = StatPearls Publishing|pmid=32496725}}</ref>

==ME/CFS==
Several studies have found altered serum levels of amino acids in ME/CFS patients, including reduced branch chain amino acid intermediates<ref>{{Cite journal | last = Naviaux| first = Robert K. | authorlink1=Robert Naviaux | last2 = Naviaux| first2 = Jane C. | last3 = Li | first3 = Kefeng | last4 = Bright | first4 = A. Taylor | last5 = Alaynick | first5 = William A. | last6 = Wang | first6 = Lin | last7 = Baxter | first7 = Asha | last8 = Nathan | first8 = Neil | last9 = Anderson | first9 = Wayne | date = 2016-08-29 | title = Metabolic features of chronic fatigue syndrome | url =https://www.pnas.org/content/113/37/E5472.short|journal=Proceedings of the National Academy of Sciences|language=en|volume=113|issue=37| pages = E5472–E5480|doi=10.1073/pnas.1607571113|issn=0027-8424}}</ref> (i.e., [[2-Hydoxyisocaproic acid]] (HICA)), reduced levels of BCCAs and LNNAs during exhaustion<ref name=":0">{{Cite journal | last = Georgiades | first = Evelina | last2 = Behan | first2 = Wilhelmina M.H. | last3 = Kilduff| first3 = Liam P. | last4 = Hadjicharalambous | first4 = Marios | last5 = Mackie | first5 = Eileen E. | last6 = Wilson | first6 = John | last7 = Ward | first7 = Susan A. | last8 = Pitsiladis | first8 = Yannis P. | date = Aug 2003 | title = Chronic fatigue syndrome: new evidence for a central fatigue disorder |url =https://www.ncbi.nlm.nih.gov/pubmed/12708966|journal=Clinical Science (London, England: 1979)|volume=105|issue=2 | pages = 213–218|doi=10.1042/CS20020354|issn=0143-5221|pmid=12708966}}</ref> and reduced levels of long chain amino acids (LNAAs) during recovery.<ref name=":0" /> One study found reduced urinary BCCA excretion.<ref name=":1">{{Cite journal | last = Niblett | first = Suzanne H. | last2 = King | first2 = Katrina E. | last3 = Dunstan | first3 = R. Hugh | last4 = Clifton-Bligh | first4 = Phillip | last5 = Hoskin | first5 = Leigh A. | last6 = Roberts | first6 = Timothy K. | last7 = Fulcher | first7 = Greg R. | last8 = McGregor | first8 = Neil R. | last9 = Dunsmore | first9 = Julie C. | date = 2007-09-01 | title = Hematologic and Urinary Excretion Anomalies in Patients with Chronic Fatigue Syndrome | url =https://doi.org/10.3181/0702-RM-44|journal=Experimental Biology and Medicine|language=en|volume=232|issue=8 | pages = 1041–1049|doi=10.3181/0702-RM-44|issn=1535-3702}}</ref>

{| class="wikitable mw-collapsible"
|+Plasma amino acids in ME/CFS patients relative to healthy controls
!Amino acid
!Georgiades et al (2003)<ref name=":0" />
!Jones et al (2005)<ref name=":2">{{Cite journal | last = Jones | first = Mark G. | last2 = Cooper | first2 = Elizabeth | last3 = Amjad | first3 = Saira | last4 = Goodwin | first4 = C. Stewart | last5 = Barron | first5 = Jeffrey L. | last6 = Chalmers | first6 = Ronald A. | date = 2005-11-01 | title = Urinary and plasma organic acids and amino acids in chronic fatigue syndrome | url =http://www.sciencedirect.com/science/article/pii/S0009898105003116|journal=Clinica Chimica Acta|volume=361|issue=1 | pages = 150–158|doi=10.1016/j.cccn.2005.05.023|issn=0009-8981}}</ref>
!Armstrong et al. (2012)<ref>{{Cite journal | last1 = Armstrong | first1 = Christopher W. | authorlink1=Christopher Armstrong | last2 = McGregor | first2 = Neil R. | authorlink2=Neil McGregor | last3 = Sheedy | first3 = John R. | authorlink3= | last4 = Buttfield | first4 = Ianauthorlink4= | last5 = Butt | first5 = Henry L. | authorlink5=Henry Butt | last6 = Gooley | first6 = Paul R. | authorlink6=Paul Gooley | title = NMR metabolic profiling of serum identifies amino acid disturbances in chronic fatigue syndrome|journal= Clinica Chimica Acta|volume=413|issue=19–20| page=1525–1531 | date = 2012|doi=10.1016/j.cca.2012.06.022}}</ref>
!
!
|-
|[[beta-alanine]]
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|Aspartate
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|Glutamate
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|Asparagine
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|Hydroxyproline
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|Serine
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|Glycine
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|Glutamine
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|Reduced
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|[[Taurine]]
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|Reduced
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|[[Histidine]]
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|Reduced
|Reduced
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|Citrulline
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|Threonine
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|Alanine
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|Arginine
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|Proline
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|[[a-aminobutyric acid]]
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|Reduced
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|-
|[[Tyrosine]]
|Reduced (at rest, exercise, exhaustion, recovery)
|Reduced
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|-
|'''Branched chain amino acids'''
|Reduced (exhaustion)
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|'''Long neutral amino acids'''
|Reduced (exhaustion, recovery)
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|Isoleucine
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|Valine
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|Leucine
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|Methionine
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|Cystine
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|b-amino-isobutyric acid
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|Phenylalanine
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|Ornithine
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|Reduced
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|Lysine
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|
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|}

{| class="wikitable mw-collapsible"
|+Urinary amino acids in ME/CFS patients relative to healthy controls
!Amino acid
!Jones et al (2005)<ref name=":2" />
!Niblet et al (2007)<ref name=":1" />
!
|-
|b -alanine
|Reduced
|
|
|-
|Aspartate
|
|
|
|-
|Glutamate
|
|
|
|-
|Asparagine
|
|Reduced
|
|-
|Hydroxyproline
|Reduced
|
|
|-
|Serine
|
|
|
|-
|Glycine
|
|
|
|-
|Glutamine
|
|
|
|-
|Taurine
|
|
|
|-
|Histidine
|Reduced
|Increased
|
|-
|Citrulline
|
|
|
|-
|Threonine
|
|
|
|-
|Alanine
|
|
|
|-
|Arginine
|
|
|
|-
|Proline
|
|
|
|-
|a-aminobutyric acid
|
|
|
|-
|Tyrosine
|
|Increased
|
|-
|Valine
|
|
|
|-
|Methionine
|Reduced
|
|
|-
|Cystine
|Reduced
|
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|-
|Isoleucine
|
|
|
|-
|Leucine
|
|
|
|-
|b-amino-isobutyric acid
|
|
|
|-
|Phenylalanine
|Reduced
|Reduced
|
|-
|Ornithine
|
|
|
|-
|Lysine
|
|
|
|-
|'''Branched chain amino acids'''
|
|Reduced
|
|}

==See also==

==Learn more==

==References==
{{Reflist}}

[[Category:Amino acids]]
[[Category:Supplements]]

Alpha-lipoic acid

2022-12-24T18:03:29Z

Davidshq:/* Side Effects */

'''Alpha-lipoic acid''' (ALA) is a chemical compound naturally found in the human body. It exists in two chemical forms, ''R''-ALA and ''L''-ALA, although only ''R''-ALA is naturally found in the human body, in a protein-bound form.<ref>{{Cite web | url = https://lpi.oregonstate.edu/mic/dietary-factors/lipoic-acid | title = Lipoic Acid | date = 2014-04-28 | website = Linus Pauling Institute|language=en | access-date = 2019-12-20}}</ref> It has sometimes been touted as an "antioxidant",<ref>{{Cite journal | last = Kaiser | first = Jon D. | authorlink = Jon Kaiser | date = 2015 | title = A prospective, proof-of-concept investigation of KPAX002 in chronic fatigue syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/26379906|journal=International Journal of Clinical and Experimental Medicine|volume=8|issue=7 | pages = 11064–11074|doi=|issn=1940-5901|pmc=4565289|pmid=26379906|access-date=|quote=|via=}}</ref> or a "chelator", although the biochemical context in which it naturally operates is much more complex than a simple solvated antioxidant or chelator. In its natural biochemical context, it serves as an important cofactor for many mitochondrial enzyme complexes.<ref>{{Cite journal | last = Ong | first = Sharon L.H. | last2 = Vohra | first2 = Harpreet | last3 = Zhang | first3 = Yi | last4 = Sutton | first4 = Matthew | last5 = Whitworth | first5 = Judith A.| date = 2013 | title = The Effect of Alpha-Lipoic Acid on Mitochondrial Superoxide and Glucocorticoid-Induced Hypertension | url =http://www.hindawi.com/journals/omcl/2013/517045/|journal=Oxidative Medicine and Cellular Longevity|language=en|volume= | pages = 1–9|doi=10.1155/2013/517045|issn=1942-0900|pmc = 3600316|pmid=23533693}}</ref> In particular, it serves as a necessary cofactor for mitochondrial α-ketoacid dehydrogenases, performing a critical role in mitochondrial energy metabolism.<ref>{{Cite journal | last = Shay | first = Kate Petersen | authorlink = | last2 = Moreau| first2 = Régis F. | authorlink2 = | last3 = Smith | first3 = Eric J. | author-link3= | last4 = Smith | first4 = Anthony R. | author-link4= | last5 = Hagen | first5 = Tory M. | author-link5= | date = Oct 2009 | title = Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential | url = https://linkinghub.elsevier.com/retrieve/pii/S0304416509002153|journal=Biochimica et Biophysica Acta (BBA) - General Subjects|language=en|volume=1790|issue=10 | pages = 1149–1160|doi=10.1016/j.bbagen.2009.07.026|pmc = 2756298|pmid=19664690|access-date=|quote=|via=}}</ref> ALA in food sources is protein-bound, just as in the human body, which limits its ability to increase free-form ALA plasma levels upon ingestion.<ref name=":0">{{Cite journal | last = Park | first = Sungmi | last2 = Karunakaran | first2 = Udayakumar | last3 = Jeoung | first3 = Nam Ho | last4 = Jeon | first4 = Jae-Han | last5 = Lee | first5 = In-Kyu| date = 2014 | title = Physiological effect and therapeutic application of alpha lipoic acid | url =https://www.ncbi.nlm.nih.gov/pubmed/25005184|journal=Current Medicinal Chemistry|volume=21|issue=32 | pages = 3636–3645|doi=10.2174/0929867321666140706141806|issn=1875-533X|pmid=25005184}}</ref>

Alpha-lipoic acid is a cofactor for some of the key enzymes (alpha-keto acid dehydrogenase, [[pyruvate dehydrogenase]], etc) involved in generating energy from food and oxygen in mitochondria and thus plays a critical role in energy production within the cell’s mitochondria.<ref name=":0" /> Since one theory of CFS/ME is mitochondria dysfunction, supplementation may aid in energy production and reduce fatigue. Co-administration of ALA with other mitochondrial nutrients, such as [[acetyl-L-carnitine]] and [[coenzyme Q10]], appears more effective in improving cognitive dysfunction and reducing oxidative mitochondrial dysfunction.<ref>{{Cite journal | last = Liu| first = Jiankang | date = Jan 2008 | title = The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview | url =https://www.ncbi.nlm.nih.gov/pubmed/17605107|journal=Neurochemical Research|volume=33|issue=1 | pages = 194–203|doi=10.1007/s11064-007-9403-0|issn=0364-3190|pmid=17605107 | last2 = | first2 = |pmc=|quote=|access-date=|via=}}</ref>

=== Uses ===
In Germany lipoic acid has long been prescribed for diabetic neuropathy, cirrhosis, and mushroom and heavy metal poisonings.<ref name=":1">{{Cite journal | last = Waslo | first = Carin | last2 = Bourdette | first2 = Dennis | last3 = Gray | first3 = Nora | last4 = Wright | first4 = Kirsten | last5 = Spain | first5 = Rebecca | date = 2019-05-06 | title = Lipoic Acid and Other Antioxidants as Therapies for Multiple Sclerosis |url =https://www.ncbi.nlm.nih.gov/pubmed/31056714|journal=Current Treatment Options in Neurology|volume=21|issue=6 | pages = 26|doi=10.1007/s11940-019-0566-1|issn=1092-8480|pmid=31056714}}</ref>

Lipoic acid can be administered intravenously. Supplemental oral ALA is 30-40% absorbed from the gastrointestinal tract. Supplemental forms often comprise a 50-50 mixture of R- and S-lipoic acid enantiomers. The R-form is better absorbed. Liquid formulas are also better absorbed.<ref>{{Cite journal | last = Uchida | first = Ryota | last2 = Okamoto | first2 = Hinako | last3 = Ikuta | first3 = Naoko | last4 = Terao | first4 = Keiji | last5 = Hirota | first5 = Takashi | date = 2015-09-21 | title = Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats |url =https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613335/|journal=International Journal of Molecular Sciences|volume=16|issue=9 | pages = 22781–22794|doi=10.3390/ijms160922781|issn=1422-0067|pmc=4613335|pmid=26402669}}</ref>

=== Side Effects ===
Supplementing ALA can result in nausea, malodorous urine, headache, weakness, pain, spasm, and rash. Side effects are more commonly seen it higher doses.<ref name=":1" /> It may interact with diabetic medications to cause hypoglycemia.

=== Clinical Trials ===

==== Diabetic Neuropathy ====
Meta-analyses of randomized controlled trials suggest that infusion of 300 to 600 mg/day of lipoic acid for 2 to 4 weeks significantly reduced symptoms of diabetic neuropathy.<ref>{{Cite journal | last = Han | first = Tingting | last2 = Bai | first2 = Jiefei | last3 = Liu| first3 = Wei | last4 = Hu| first4 = Yaomin | date = Oct 2012 | title = A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy | url = https://www.ncbi.nlm.nih.gov/pubmed/22837391|journal=European Journal of Endocrinology|volume=167|issue=4 | pages = 465–471|doi=10.1530/EJE-12-0555|issn=1479-683X|pmid=22837391|pmc=|quote=|access-date=|via=}}</ref> A randomized, double-blind, placebo-controlled trial in 181 patients with diabetic neuropathy found that oral supplementation with either 600 mg/day, 1,200 mg/day, or 1,800 mg/day of lipoic acid for 5 weeks significantly improved neuropathic symptoms. There was no difference between the low, moderate or high dose groups.<ref>{{Cite journal | last = Ziegler | first = Dan | last2 = Ametov| first2 = Alexander | last3 = Barinov| first3 = Alexey | last4 = Dyck | first4 = Peter J. | last5 = Gurieva | first5 = Irina | last6 = Low| first6 = Phillip A. | last7 = Munzel | first7 = Ullrich | last8 = Yakhno | first8 = Nikolai | last9 = Raz | first9 = Itamar | date = Nov 2006 | title = Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial | url = https://www.ncbi.nlm.nih.gov/pubmed/17065669|journal=Diabetes Care|volume=29|issue=11 | pages = 2365–2370|doi=10.2337/dc06-1216|issn=0149-5992|pmid=17065669|pmc=|quote=|access-date=|via=}}</ref> Improvements in neuropathy from these trials are not always corroborated with electrodiagnostic testing. It is thought, that the beneficial effects of ALA on neuropathy may be due to effects on the small nerve fibers, making it a candidate treatment for [[Small fiber peripheral neuropathy|small fiber neuropathy]].<ref>{{Cite journal | last = Swiecka | first = Marta | authorlink = | last2 = Maslinska | first2 = Maria | authorlink2 = | last3 = Kwiatkowska | first3 = Brygida | authorlink3 = | date = 2018 | title = Small fiber neuropathy as a part of fibromyalgia or a separate diagnosis? | url = https://www.openaccessjournals.com/articles/small-fiber-neuropathy-as-a-part-of-fibromyalgia-or-a-separate-diagnosis.pdf | journal=International Journal of Clinical Rheumatology|volume=13|issue=6 | pages = 353-359|doi=|pmc=|pmid= | access-date = 2019-10-29|quote=|via=}}</ref>

==== Multiple Sclerosis ====
A small pilot study designed to evaluate the safety of lipoic acid in 30 people with relapsing or progressive multiple sclerosis found that treatment with 1,200 to 2,400 mg/day of oral lipoic acid for 2 weeks was safe. Those with the higher serum concentrations of lipoic acid had the lowest serum concentrations of MMP-9 — a marker of inflammation.<ref>{{Cite journal | last = Yadav| first = V. | last2 = Marracci | first2 = G. | last3 = Lovera | first3 = J. | last4 = Woodward | first4 = W. | last5 = Bogardus | first5 = K. | last6 = Marquardt | first6 = W. | last7 = Shinto | first7 = L. | last8 = Morris | first8 = C. | last9 = Bourdette | first9 = D. | date = Apr 2005 | title = Lipoic acid in multiple sclerosis: a pilot study | url = https://www.ncbi.nlm.nih.gov/pubmed/15794388|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=11|issue=2 | pages = 159–165|doi=10.1191/1352458505ms1143oa|issn=1352-4585|pmid=15794388|pmc=|quote=|access-date=|via=}}</ref> A 2-year trial of 1,200 mg/day LA in secondary progressive MS demonstrated a significant reduction of whole-brain atrophy and trend toward improvement in walking speed.<ref name=":1" />

== References ==
{{reflist}}

[[Category:Potential treatments]]
[[Category:Biochemistry and cell biology]]

Adenosine monophosphate deaminase

2022-12-24T17:49:42Z

Davidshq:

'''Adenosine monophosphate deanimase''' is an [[enzyme]] that converts [[adenosine monophosphate]] (AMP) to [[inosine monophosphate]] (IMP), freeing an [[ammonia]] molecule in the process.

Deficiency in AMP deaminase results in the loss of AMP from the cell, an important source of [[ribose]].

Adenosine monophosphate deaminase deficiency type 1 (AMDP1) is a [[genetic]] disorder fatigue, muscle pain, muscle cramping and delayed recovery from [[exercise]]. Supplementation with [[ribose]] and [[creatine]] monohydrate are thought to be helpful.

==References==

<references />

[[Category:Biochemistry and cell biology]]
[[Category:Enzymes]]
[[Category:Genes]]

Active Hexose Correlated Compound

2022-12-24T17:44:53Z

Davidshq:

'''Active hexose correlated compound''' (AHCC) is a supplement derived from shiitake mushrooms. It is rich in the polysaccharides [[alpha-glucan]] and [[beta-glucan]] and is a popular adjuvant cancer treatment in [[Japan]].

In animal studies, AHCC had antioxidant<ref name="suppressive2003" /> and anti-inflammatory<ref name="activehexose2014" /> effects. It may enhance host resistance to bacterial<ref name="prophylactic2003" /><ref name="klebsiella2003" /> and viral infections.<ref name="supplementation2006" />

== Immune modulation ==

=== Natural killer cell function ===

In animal models, AHCC has been shown to increase [[Natural killer cell|NK]] activity.<ref name="supplementation2006" /> Other studies have found no significant increase in NK function.<ref name="immunological2008" />

== Cancer ==

''In vitro'' and animal studies show AHCC may have anticancer effects.<ref name="H-22002" /><ref name="influence2007" /><ref name="mushroom2000" /><ref name="antitumor2015" />

In humans, there is some evidence that AHCC may prolong survival in liver cancer patients.<ref name="prognostic2006" />

==References==
<references>
<ref name="suppressive2003">{{Citation| issn = 0024-3205| volume = 74| issue = 5| pages = 593–602| last1 = Ye | first1 = She-Fang | last2 = Ichimura | first2 = Kaoru| last3 = Wakame | first3 = Koji | last4 = Ohe | first4 = Masato| title = Suppressive effects of Active Hexose Correlated Compound on the increased activity of hepatic and renal ornithine decarboxylase induced by oxidative stress| journal = Life Sciences| date = 2003-12-19| pmid = 14623030}}</ref>
<ref name="activehexose2014">{{Citation| doi = 10.1002/mnfr.201400364| issn = 1613-4133| volume = 58| issue = 12| pages = 2379–2382| last1 = Mascaraque | first1 = Cristina | last2 = Suárez | first2 = María Dolores | last3 = Zarzuelo | first3 = Antonio | last4 = Sánchez de Medina | first4 = Fermín | last5 = Martínez-Augustin | first5 = Olga| title = Active hexose correlated compound exerts therapeutic effects in lymphocyte driven colitis| journal = Molecular Nutrition & Food Research| date = December 2014| pmid = 25186628}}</ref>
<ref name="prophylactic2003">{{Citation| issn = 0916-4804| volume = 44| issue = 2| pages = 127–131| last1 = Ikeda | first1 = Tatsuo | last2 = Ishibashi | first2 = Hiroko | last3 = Fujisaki | first3 = Ryuichi | last4 = Yamazaki | first4 = Masatoshi | last5 = Wakame | first5 = Kohji | last6 = Kosuna | first6 = Kenichi | last7 = Yamaguchi | first7 = Hideyo | last8 = Ono | first8 = Yasuo | last9 = Abe | first9 = Shigeru| title = [Prophylactic efficacy of a basidiomycetes preparation AHCC against lethal Candida albicans infection in experimental granulocytopenic mice]| journal = Nihon Ishinkin Gakkai Zasshi = Japanese Journal of Medical Mycology| date = 2003 | pmid = 12748595}}</ref>
<ref name="klebsiella2003">{{Citation| doi = 10.1152/japplphysiol.00259.2003| issn = 8750-7587| volume = 95| issue = 2| pages = 491–496| last1 = Aviles | first1 = Hernan | last2 = Belay | first2 = Tesfaye | last3 = Fountain | first3 = Kimberly | last4 = Vance | first4 = Monique | last5 = Sun | first5 = Buxiang | last6 = Sonnenfeld | first6 = Gerald| title = Active hexose correlated compound enhances resistance to Klebsiella pneumoniae infection in mice in the hindlimb-unloading model of spaceflight conditions| journal = Journal of Applied Physiology (Bethesda, Md.: 1985)| date = August 2003| pmid = 12692142}}</ref>
<ref name="supplementation2006">{{Citation| issn = 0022-3166| volume = 136| issue = 11| pages = 2868–2873| last1 = Ritz | first1 = Barry W. | last2 = Nogusa | first2 = Shoko | last3 = Ackerman | first3 = Elizabeth A. | last4 = Gardner | first4 = Elizabeth M.| title = Supplementation with Active Hexose Correlated Compound Increases the Innate Immune Response of Young Mice to Primary Influenza Infection| journal = The Journal of Nutrition| access-date = 2016-11-09| date = 2006-11-01| url = http://jn.nutrition.org/content/136/11/2868| pmid = 17056815}}</ref>
<ref name="immunological2008">{{Citation| doi = 10.1080/01635580801993280| issn = 0163-5581| volume = 60| issue = 5| pages = 643–651| last1 = Terakawa | first1 = Naoyoshi | last2 = Matsui | first2 = Yoichi | last3 = Satoi | first3 = Sohei | last4 = Yanagimoto | first4 = Hiroaki | last5 = Takahashi | first5 = Kanji | last6 = Yamamoto | first6 = Tomohisa | last7 = Yamao | first7 = Jun | last8 = Takai | first8 = Soichiro | last9 = Kwon | first9 = A.-Hon | last10 = Kamiyama | first10 = Yasuo| title = Immunological Effect of Active Hexose Correlated Compound (AHCC) in Healthy Volunteers: A Double-Blind, Placebo-Controlled Trial| journal = Nutrition and Cancer| access-date = 2016-11-09| date = 2008-09-05| url = http://dx.doi.org/10.1080/01635580801993280| pmid = 18791928}}</ref>
<ref name="H-22002">{{Citation| issn = 0258-851X| volume = 16| issue = 1| pages = 49–54| last1 = Yagita | first1 = Akikuni | last2 = Maruyama | first2 = Syoji | last3 = Wakasugi | first3 = Shinji | last4 = Sukegawa | first4 = Yasushi | title = H-2 haplotype-dependent serum IL-12 production in tumor-bearing mice treated with various mycelial extracts| journal = In Vivo (Athens, Greece)| date = February 2002| pmid = 11980361}}</ref>
<ref name="influence2007">{{Citation| doi = 10.1016/j.taap.2007.03.031| issn = 0041-008X| volume = 222| issue = 2| pages = 152–158| last1 = Hirose | first1 = Aya | last2 = Sato | first2 = Eri | last3 = Fujii | first3 = Hajime | last4 = Sun | first4 = Buxiang | last5 = Nishioka | first5 = Hiroshi | last6 = Aruoma | first6 = Okezie I.| title = The influence of active hexose correlated compound (AHCC) on cisplatin-evoked chemotherapeutic and side effects in tumor-bearing mice| journal = Toxicology and Applied Pharmacology| date = 2007-07-15| pmid = 17555784}}</ref>
<ref name="mushroom2000">{{Citation| issn = 1089-5159| volume = 5| issue = 1| pages = 4–27| last = Kidd | first = P.M. | title = The use of mushroom glucans and proteoglycans in cancer treatment| journal = Alternative Medicine Review: A Journal of Clinical Therapeutic| date = February 2000| pmid = 10696116}}</ref>
<ref name="antitumor2015">{{Citation| doi = 10.4162/nrp.2015.9.2.129| issn = 1976-1457| volume = 9| issue = 2| pages = 129–136| last1 = Cao | first1 = Zhiyun | last2 = Chen | first2 = Xuzheng | last3 = Lan | first3 = Lan | last4 = Zhang | first4 = Zhideng | last5 = Du| first5 = Jian | last6 = Liao | first6 = Lianming| title = Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice| journal = Nutrition Research and Practice| access-date = 2016-11-09| date = April 2015| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388943/| pmid = 25861418| pmc = 4388943}}</ref>
<ref name="prognostic2006">{{Citation| issn = 0125-877X| volume = 24| issue = 1| pages = 33–45| last1 = Cowawintaweewat | first1 = Suwanna | last2 = Manoromana | first2 = Suphon | last3 = Sriplung | first3 = Hutcha | last4 = Khuhaprema | first4 = Thiravud | last5 = Tongtawe | first5 = Pongsri | last6 = Tapchaisri | first6 = Pramuan | last7 = Chaicumpa | first7 = Wanpen| title = Prognostic improvement of patients with advanced liver cancer after active hexose correlated compound (AHCC) treatment| journal = Asian Pacific Journal of Allergy and Immunology| date = March 2006| pmid = 16913187}}</ref>
</references>

[[Category:Potential treatments]]
[[Category:Supplements]]

Acid reflux

2022-12-24T17:40:50Z

Davidshq:

{{stub}}
'''Acid reflux''' is when stomach acid travels back up from your stomach to your esophagus, often causing heartburn.<ref name="WebMD">https://www.webmd.com/heartburn-gerd/guide/what-is-acid-reflux-disease</ref> [[Gastroesophageal reflux disease]] (GERD) is a severe form of acid reflux.<ref name="difference">https://health.clevelandclinic.org/whats-the-difference-between-heartburn-acid-reflux-and-gerd/</ref>

==Signs and symptoms==
* heartburn
* an unpleasant sour taste in your mouth (caused by stomach acid)

Some people also have:
* a cough or hiccups that keep coming back
* a hoarse voice
* bad breath
* [[bloating]] and [[nausea]]

Symptoms are often worse after eating, when lying down, and when bending over.<ref name="NHS">https://www.nhs.uk/conditions/heartburn-and-acid-reflux/</ref>

==Treatment==

==ME/CFS==

==Notable articles==

==See also==
*[[Gastroesophageal reflux disease]] (GERD)

==Learn more==
*[https://www.webmd.com/heartburn-gerd/guide/what-is-acid-reflux-disease What Is Acid Reflux Disease?] - WebMD
*[https://health.clevelandclinic.org/whats-the-difference-between-heartburn-acid-reflux-and-gerd/ Difference Between Heartburn, GERD & Reflux] - Cleveland Clinic Health

==References==
{{reflist}}

[[Category:Diagnoses]]
[[Category:Allergy signs and symptoms‎]]
[[Category:Digestive diseases and disorders‎]]

Gordon Parish

2022-12-24T03:10:54Z

Davidshq:

'''J. Gordon Parish''', M.D., F.R.C.P.(C),D. Phys. Med, (1925 - Sept 13, 2017)<ref>{{Cite web | url = https://www.meresearch.org.uk/dr-gordon-parish-an-appreciation/ | title = Dr Gordon Parish – an appreciation | last = | first = | authorlink = | date = 2017 | website = [[ME Research UK]]|language=en|archive-url=|archive-date=|url-status=|access-date=2021-03-07}}</ref> worked at Passmore Edwards Medical Rehabilitation Centre, Clacton-on-Sea,
Essex, UK, and Department of Rheumatology and Rehabilitation, St. Mary's Hospital, Colchester, Essex, UK.

Dr. Parish organized pre-1980s data on the outbreaks and epidemics of illnesses that may have been [[Myalgic Encephalomyelitis]] or a variant of [[Myalgic Encephalomyelitis]].<ref>{{Cite journal | last = Fraser | first = Douglas T. | authorlinklink= | date = 2011-10-30 | title = BCDC| url = https://www.bmj.com/rapid-response/2011/10/30/bcdc|journal=The BMJ|language=en|volume=|issue= | pages = |doi=|pmc=|pmid=|access-date=|quote=|via=}}</ref>

[[:File:ME-Research-UK-Research-Publications-on-ME-epidemics-1934-1980.pdf | Outline by Dr Parrish of outbreaks from 1943-1980]] ''(pdf)'' <ref>ME Research UK</ref>

==Journal articles==
*1970, [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700986/ Epidemic malaise]<ref>{{Cite journal | last = Parish | first = J G | date = 1970-07-04 | title = Epidemic malaise.| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700986/|journal=British Medical Journal|volume=3|issue=5713 | pages = 47–48|doi=10.1136/bmj.3.5713.47-c|issn=0007-1447|pmc=1700986|pmid=4316803}}</ref>
*1973, Benign myalgic encephalomyelitis<ref name="Parish, 1973" />
*1974, [[:File:Parish_letter_1974.pdf |Letter to the editor, British Medical Journal]] ''(PDF)'' Epidemic Neuromyasthenia<ref name="letter1974">{{Cite journal | last = Parish | first = J G | date = 1974-05-04 | title = Letter: Epidemic neuromyasthenia.| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1610570/|journal=British Medical Journal|volume=2|issue=5913 | pages = 276|issn=0007-1447|pmc=1610570|pmid=4827091}}</ref>
*1977, [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1607215/ Letter to the editor - Icelandic disease (benign myalgic encephalomyelitis or Royal Free disease)]<ref name="Ramsay, 1977" />
*1978, [[Royal Free Disease]]: worldwide outbreaks.<ref>{{Cite journal | last = Parish | first = J.G. |date = 1978-04-27 | title = Royal free disease: worldwide outbreaks| url = https://pubmed.ncbi.nlm.nih.gov/652543/|journal=Nursing Times|volume=74|issue=17 | pages = 699–701|issn=0954-7762|pmid=652543}}</ref>
*1978, [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425322/ Early outbreaks of "epidemic neuromyasthenia"] Dr. Parrish explains the illness and several early outbreaks.<ref name="Parish, 1978" />
*1981, [[Myalgic encephalomyelitis]]<ref>{{Cite journal | last = Parish | first = J.G. |date = 1981-04-25 | title = Myalgic encephalomyelitis| url = https://pubmed.ncbi.nlm.nih.gov/6112360/|journal=Lancet (London, England)|volume=1|issue=8226 | pages = 950–951|doi=10.1016/s0140-6736(81)91652-4|issn=0140-6736|pmid=6112360}}</ref>

==References==
<references>
<ref name="Parish, 1973">{{Citation | last1 = Parish | first1 = JG | authorlink1 = Gordon Parish | title = Benign myalgic encephalomyelitis | journal = Britsh Journal of Psychiatry | volume = 122 | issue = 571 | page = 735 | date = Jun 1973 | pmid = 4716076 | url=https://www.ncbi.nlm.nih.gov/pubmed/4716076 | last2 = | first2 = | pages = |chapter=|edition=|isbn=}}
</ref>
<ref name="Parish, 1978">{{Citation | last1 = Parish | first1 = J.G. | authorlink1 = Gordon Parish | title = Early outbreaks of 'epidemic neuromyasthenia' | journal = Postgraduate Medical Journal | volume = 54 | issue = 637 | page = 711-717 | date = Nov 1978 | pmid = 370810 | url = http://www.ncbi.nlm.nih.gov/pubmed/370810 | last2 = | first2 = | pages = |chapter=|edition=|isbn=}}
</ref>
<ref name="Ramsay, 1977">{{Citation | last1 = Ramsay | first1 = AM | authorlink1 = Melvin Ramsay | last2 = Dowsett | first2 = EG | authorlink2 = | last3 = Dadswell | first3 = JV | authorlink3 = | last4 = Lyle | first4 = WH | authorlink4 = | last5 = Parish | first5 = JG | authorlink5 = Gordon Parish | title = Icelandic disease (benign myalgic encephalomyelitis or Royal Free disease) | journal = British Medical Journal | volume = 1 | issue = 6072 | page = 1350 | date = May 21, 1977 | pmid = 861618 | url=https://www.ncbi.nlm.nih.gov/pubmed/861618 | pages = |chapter=|edition=|isbn=}}
</ref>
</references>

[[Category:Researchers]]
[[Category:UK researchers]]

Ginkgo biloba

2022-12-24T03:08:58Z

Davidshq:

[[File:Gingko herbal tea.jpg|alt=image of blue box of tea bags |thumb|Ginkgo herbal tea.
Source: [https://world.openfoodfacts.org/cgi/product_image.pl?code=4012824402744&id=front_fr Open Food Facts]. License: CC BY-4.0.
]]
'''Ginkgo biloba''' or '''ginkgo''' is an extract of the leaves of the herb ginkgo.<ref name="drugscom">{{Cite web | url = https://www.drugs.com/mtm/ginkgo-biloba.html | title = Ginkgo Biloba Uses, Side Effects & Warnings|website=Drugs.com|language=en|access-date=2020-10-01}}</ref><ref name="drugbank">{{Cite web | url = https://go.drugbank.com/drugs/DB01381 | title = Ginkgo biloba|website=go.drugbank.com|access-date=2020-10-01}}</ref>

==Alternative names ==
Ginkgo biloba is also known as ginkgo biloba biloba, abricot argenté japonais/Japanese Silver Apricot, adiantifolia, arbre aux écus, arbre du ciel, arbre fossile (fossil tree), Bai Guo Ye, Baiguo, ginkgo seed, graine de ginkgo biloba, Kew Tree, maidenhair tree, Noyer du Japon, Pei Go Su Ye, salisburia adiantifolia, yen xing, yinhsing, and other names.<ref name="drugbank" /><ref>{{Cite web | url = https://www.webmd.com/vitamins/ai/ingredientmono-333/ginkgo | title = Ginkgo: Uses, Side Effects, Interactions, Dosage, and Warning | website = webmd.com|language=en|access-date=2020-10-01}}</ref> Ginkgo biloba leaf oil is also known as common ginkgo leaf oil/water, ginkgo biloba leaf oil/water, ginkgo macrophylla or salisburia macrophylla leaf oil/leaf water, maidenhair tree leaf oil/water, pterophyllus salisburiensis leaf oil/water, salisburia adiantifolia or salisburia biloba leaf oil/water, and salisburia ginkgo leaf oil/water.<ref name="drugbank-oil">https://go.drugbank.com/drugs/DB14285</ref> Ginkgo is sometimes incorrectly known as gingko bilboa or ginkgo biloba.

==Potential uses==
Ginkgo is commonly used for symptoms of [[brain fog]] including to help improve concentration, or for [[memory problems]]. Ginkgo may also be used for [[vertigo]].<ref name="drugbank" />

==Theory==
Ginkgo extract appears to improve blood flow to many organs and tissues.<ref name="drugbank" />

Ginkgo also appears to reduce blood clotting and platelet aggregation by blocking platelet-activating factor (PAF), which have been linked to a number of central nervous system disorders, and some cardiovascular, kidney and respiratory illnesses.<ref name="drugbank" />

==Evidence==

==Risks and safety==

==Costs and availability==
Ginkgo and ginkgo biloba leaf oil available over the counter without a prescription.<ref name="drugbank" /><ref name="drugbank-oil" />

==See also==
*[[Brain fog]]

==Learn more==
* [https://www.drugs.com/mtm/ginkgo-biloba.html Ginkgo biloba - drugs.com]
* [https://go.drugbank.com/drugs/DB01381 Ginkgo biloba - drugbank.ca]
* [https://www.webmd.com/vitamins/ai/ingredientmono-333/ginkgo Ginkgo Biloba - webmd]
* Memorial Sloan Kettering

==References==
{{reflist}}

[[Category:Supplements]]
[[Category:Herbs]]
[[Category:Potential treatments]]

Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al

2022-12-24T00:04:31Z

Davidshq:

'''Evidence of widespread metabolite abnormalities in Myalgicencephalomyelitis/chronic fatigue syndrome: assessmentwith whole-brain magnetic resonance spectroscopy''' is a 2019 research study of [[neuroinflammation]] in [[ME/CFS]].

== Authors ==
[[Christine Mueller|Christina Mueller]] (MS), [[Joanne Lin]], [[Sulaiman Sheriff]], [[Andrew Maudsley]], under the direction of Dr. [[Jarred Younger]] of the Neuroinflammation, Pain and Fatigue Laboratory at University of Alabama at Birmingham and with University of Miami Miller School of Medicine radiology experts.<ref name="Mueller2019">{{Cite journal| url = https://link.springer.com/epdf/10.1007/s11682-018-0029-4 | title = Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy | last = Mueller | first = Christina | authorlink = Christina Mueller | last2 = Lin| first2 = Joanne C | authorlink2 = Joanne Lin | date = 2019 | doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|url-status=|access-date=2019-01-17 | authorlink3 = Sulaiman Sheriff | authorlink4 = Andrew Maudsley | authorlink5 = Jarred Younger | last3 = Sheriff | last4 = Maudsley | last5 = Younger | first3 = Sulaiman | first4 = Andrew A | first5 = Jarred W|volume=|issue= | pages = | page = |journal=Brain Imaging and Behavior}}</ref><ref name="RamsayAward20190117">{{Cite web | url=http://go.solvecfs.org/webmail/192652/97033877/74d435097e87231f24cffe4d9de93da8e3f71c0e077a67417eba10cbd269ccb1 | title = Brain Imaging and Behavior publication from Dr. Jarred Younger’s SMCI Ramsay pilot study supports involvement of neuroinflammation in ME/CFS|website=go.solvecfs.org|access-date=2019-01-17 | date = | last = | first = | authorlink = |archive-url=|archive-date=|url-status=}}</ref>

== Funding ==
This study was funded through [[Solve ME/CFS Initiative]]s' Ramsay Award Program<ref name="RamsayAward20190117" /><ref name="RamsayAward">{{Cite web | url=https://solvecfs.org/ramsay-award-program/ | title = Ramsay Award Program|website=Solve ME/CFS Initiative|language=en-US|access-date=2019-01-17}}</ref> and the [[National Institutes of Health]] (NIH) [grant number EB016064].<ref name="Mueller2019" />

== Abstract and Conclusion ==
'''Abstract'''<blockquote>Previous neuroimaging studies have detected markers of [[neuroinflammation]] in patients with [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS). Magnetic Resonance Spectroscopy (MRS) is suitable for measuring [[brain]] metabolites linked to [[inflammation]], but has only been applied to discrete regions of interest in ME/CFS. We extended the MRS analysis of ME/CFS by capturing multi-voxel information across the entire brain. Additionally, we tested whether MRS-derived brain temperature is elevated in ME/CFS patients. Fifteen women with ME/CFS and 15 age- and gender-matched healthy controls completed fatigue and mood symptom questionnaires and whole-brain echo-planar spectroscopic imaging (EPSI). [[choline]] (CHO), myoinositol (MI), [[lactate]] (LAC), and N-acetylaspartate (NAA) were quantified in 47 regions, expressed as ratios over [[creatine]] (CR), and compared between ME/CFS patients and controls using independent-samples t-tests. Brain temperature was similarly tested between groups. Significant between-group differences were detected in several regions, most notably elevated CHO/CR in the left anterior cingulate (p < 0.001). Metabolite ratios in seven regions were correlated with fatigue (p < 0.05). ME/CFS patients had increased temperature in the right insula, putamen, frontal cortex, thalamus, and the cerebellum (all p < 0.05), which was not attributable to increased [[body temperature]] or differences in cerebral perfusion. Brain temperature increases converged with elevated LAC/CR in the right insula, right thalamus, and cerebellum (all p < 0.05). We report metabolite and temperature abnormalities in ME/CFS patients in widely distributed regions. Our findings may indicate that ME/CFS involves neuroinflammation.<ref name="Mueller2019" /></blockquote>'''Conclusion'''<blockquote>This study is the first to investigate whole-brain MRS markers of [[neuroinflammation]] in ME/CFS. We report metabolite and temperature abnormalities in ME/CFS patients in widely distributed brain areas, suggesting ME/CFS is driven by diffuse pathophysiological processes affecting the whole [[brain]], rather than regionally limited, which is consistent with the heterogeneity of its clinical symptoms. Our findings add support to the hypothesis that ME/CFS is the result of chronic, low-level neuroinflammation. While the whole-brain results are preliminary, we note that they largely agree with past publications that use MRS in ME/CFS. These results should be replicated in future studies with larger samples to further establish the profile of pathophysiological abnormalities in the brains of ME/CFS patients. Ultimately, the development of sensitive MRI markers of ME/CFS could supplement clinical tests to help guide treatment decisions.<ref name="Mueller2019" /></blockquote>

== Overview ==
The following information is provided by Solve ME/CFS Initiative.<ref name="RamsayAward20190117" />

'''''What you need to know:'''''
* Dr. Jarred Younger and his co-authors completed a [[Neuroimaging|neuroimaging]] study of a female cohort of 15 individuals with ME/CFS (who met a modified [[Fukuda criteria|Fukuda]] case definition) and 15 age-matched healthy controls using magnetic resonance spectroscopy (MRS).
* MRS, a type of [[Magnetic resonance imaging|MRI]] scan, provides a non-invasive method for evaluating the types and quantities of chemicals in the brain using 3D images and can give a readout of [[metabolic]] changes.
* The researchers found that ''“''metabolite and temperature abnormalities were distributed across large portions of the brain''” ''in ME/CFS participants, as compared to controls.
** The most significant finding was elevation of choline in the [[anterior cingulate]] (ACC) area of the brain on the left side. Increases in choline are associated with [[immune cell activation]] and the authors note that previous research indicates a critical role for the ACC region in [[cytokine]]-induced [[fatigue]].
** Lactate (a byproduct of [[glycolysis]] in an oxygen-limited environment) was found to be increased in a number of brain areas, consistent with [[Neuroinflammation|brain inflammation]] and an [[energy deficit]] at the cellular level.
** Higher average temperatures were observed in five brain areas; the researchers included assessments that showed this finding wasn’t attributable to differences in blood flow or whole-body temperature. Inflammation requires more metabolic expenditures and three of the five areas also measured increased lactate, suggesting increased metabolism that could be related to neuroinflammation.
* The authors acknowledge a few limitations of the study, including the small sample size, but these preliminary results support a hypothesis of neuroinflammation in ME/CFS and provide a benchmark for replication using larger study groups.<ref name="RamsayAward20190117" />

== Talks and interviews ==
{{Video|id=https://www.youtube.com/watch?v=rxdzaWD5wfU|service=youtube|dimensions=550|description=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study. December 2018.|alignment=left|urlargs=start=0&rel=0&autoplay=0}}
* 2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study]<ref name="Younger2018video">{{Cite web | url=https://www.youtube.com/watch?v=rxdzaWD5wfU | title = ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study | date = Dec 14, 2018|access-date=|website=YouTube | last = Younger | first = Jarred | authorlink = Jarred Younger|archive-url=|archive-date=|url-status=| publisher = [[Solve ME/CFS Initiative]]}}</ref>

== See also ==
* [[Brain#Inflammation|Brain inflammation]]
* [[Jarred Younger]]
* [[Neuroinflammation]]
* [[Solve ME/CFS Initiative]]
* [[Neurology of ME/CFS]]
* [[List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis]]

== Learn more ==
* 2019, [http://go.solvecfs.org/webmail/192652/97033877/74d435097e87231f24cffe4d9de93da8e3f71c0e077a67417eba10cbd269ccb1 ''Brain Imaging and Behavior'' publication from Dr. Jarred Younger’s SMCI Ramsay pilot study supports involvement of neuroinflammation in ME/CFS]<ref name="RamsayAward20190117" />

== References ==
{{Reflist}}

[[Category:Notable studies]]

Cusack Protocol

2022-12-23T23:55:18Z

Davidshq:

The Cusack Protocol is a protocol of various nutritional supplements that can purportedly improve connective tissue integrity and some digestive symptoms in people with [[Ehlers-Danlos Syndrome]].<ref name="plenary2017">{{Cite web | url = https://www.ehlers-danlos.com/wp-content/uploads/2017-Hypermobility-Plenary-Session-Transcript-S.pdf | title=HYPERMOBILITY PLENARY SESSSION and Q&A (Transcript) | last = The Ehlers Danlos Society|first = | authorlink = | date = Sep 8, 2017 | website = Ehlers-danlos.com|archive-url=|archive-date=|access-date=Oct 4, 2020}}</ref> It was created Deborah Cusack, a patient with EDS.<ref name="plenary2017" />

== Components ==
* [[Polysaccharide]]s:
** Either 100% fractionally distilled [[Aloe vera]] or aloe vera juice capsules
** or [[maitake]] mushroom<ref name="website">{{Cite web | url = http://ouredsjourney.weebly.com/what-works.html | title = What Works? | last = Cusack|first = Deborah| authorlink = | date = | website = EDS & Polysaccharides|archive-url=|archive-date=|access-date=2020-10-04}}</ref>
* [[Lactobacillus rhamnosus|Lactobacillus rhamnosus GG]] (L-GG) - a [[probiotic]] (10-15 billion cfu)
* [[Pyrroloquinoline Quinone]] (PQQ)
* [[L-arginine]]
* [[D-Ribose]]
* [[Lion's mane]] (hericium erinaceus, a type of [[mushroom]])
* [[Diatomaceous earth]] (food grade DE) - a powdered fossilized [[algae]])
* [[Glucosamine chondroitin]]<ref name="slides2016">{{Cite web | url = https://www.facebook.com/media/set/?set=a.1749260648627557.1073741829.1680359948850961&type=3 | title = Cusack Protocol (slides) | last = Ehlers-Danlos Support Wilmington | first = | authorlink = | date = Mar 10, 2016 | website = facebook.com|archive-url=|archive-date=|access-date=2020-10-04}}</ref>
* Hyaluronic Acid
* Astragalus Extract

== Theory ==
The Cusack protocol aims to regenerate connective tissue and resolve mast cell disease symptoms. It is a treatment strategy that is expected to be continued in the long term, possibly indefinitely, rather than a cure for [[Ehlers-Danlos syndrome]]s.<ref name="website" /><ref name="slides2016" />

== Evidence ==
Despite anecdotal reports of improvement, neither the protocol nor its components have ever been studied in EDS.<ref name="plenary2017" />

==Risks, safety, and side effects ==
Risks are largely unknown due to lack of clinical trials and an absence of medical practitioners reporting on the effects of patients using the Cusack protocol.<ref name="plenary2017" /> The Cusack protocol includes eight supplements, so side effects may result from any of these or from combinations of them.

Deborah Cusack has stated that some side effects will be experienced initially, and may last between one day and several weeks in EDS patients, which she refers to as the "healing curve" or a "healing crisis". Cusack states this includes [[joint stiffness|stiff joints]], [[myalgia|aching muscles]], and that [[fatigue]], [[limb w-grade|mild fever]], [[nausea]] and [[headache]] may also occur.<ref name="slides2016" />

A [[Mast cell activation disorder|mast cell disease]] flare may also occur in patients with mast cell disease, according to Cusack. There is lack of information about the impact of the protocol on people with other illnesses in addition to EDS, or effects on people without EDS.<ref name="slides2016" />

These is a lack of information about the safety and risks of taking these supplements with existing medications or other supplements.<ref name="slides2016" />

== Learn more ==
*[https://ouredsjourney.weebly.com/what-works.html Our Family's Journey] - Deborah Cusack's website
*[https://www.facebook.com/media/set/?set=a.1749260648627557.1073741829.1680359948850961&type=3 Cusack Protocol (slides)] - Ehlers-Danlos Support Wilmington

== See also ==
* [[Aloe vera]]
* [[Alternative medicine]]
* [[Ehlers-Danlos Syndrome|Ehlers-Danlos syndrome]]
* [[Polysaccharide]]

== References ==
{{Reflist}}

[[Category:Supplements]]
[[Category:Alternative medicine]]
[[Category:Potential treatments]]
[[Category:Protocols]]

Ashok Gupta

2022-12-23T23:43:29Z

Davidshq:/* Illness */

{{NeedsImage}}
'''Ashok Gupta''' is a former [[ME/CFS]] patient who claims to have healed himself, and now sells his own program to patients with a variety of [[chronic illness]]es.<ref name="website" /> He also conducts coaching webinairs and workshops.<ref name="website" />

==Qualifications and training ==
Ashok Gupta graduated from Cambridge University with a Bachelor of Arts degree in Economics. He was then automatically awarded an honorary MA (Cantab), as all Cambridge University graduates are. After graduating he worked as a management consultant for PricewaterhouseCoopers, and states he had alternative and complementary health certifications (DHyp PNLP MNCH, [[Neurolinguistic programming]] Practitioner and Clinical Hypnotherapist, member of the National Council for Hypnotherapy).<ref name="HSC2003">{{Cite web | url = http://www.harleystressclinic.com/Practitioners.htm|archive-url=http://web.archive.org/web/20030416020149/http://www.harleystressclinic.com/Practitioners.htm|archive-date=2003-04-19 | title = Practioners|website=Harley Street Stress Clinic}}</ref>

Gupta describes himself as a "chronic illness expert" but holds no medical qualifications or certifications, and as an "expert on stress", and has given a number of media interviews about stress, but does not appear to hold any academic or professional qualifications in psychology or mental health either.<ref name="website" />

Gupta states he has designed "Revolutionary Neuroplasticity Techniques" based on his "20 plus years of experience and research". He has not completed a research degree, does not have a medical licence, and is not affiliated to any academic institution.<ref name="website" /><ref name="Hypothesis2002" />

==Illness ==
Gupta states he fell ill with [[Chronic fatigue syndrome|CFS]] during his time studying Economics in Cambridge; he states he was partying hard, studying hard, feeling pretty [[stress|stressed out]], and not taking care of himself when he contracted "some kind of stomach bug" on a trip to [[India]] and developed a host of symptoms that did not improve.<ref name="KF2021">{{Cite web | url = https://www.drkarafitzgerald.com/2021/07/12/the-role-of-neuroplasticity-in-chronic-illness-healing/ | title =The Role of Neuroplasticity in Chronic Illness & Healing|website=Dr Kara Fitzgerald ND | access-date = 2022-06-03}}</ref> Gupta states he found a way to heal his ME/CFS and has been fully well since.<ref name="PMC8325493" /> Gupta reports being ill with CFS, which he regards as the same as ME, for over three years in the late 1990s.<ref name="PositiveH">{{Cite web | publisher = Positive Health | url = http://www.positivehealth.com/article/cfs-me-long-covid/me-chronic-fatigue-syndrome-causes-and-the-amygdala-retraining-recovery-programme | title = ME / Chronic Fatigue Syndrome - Causes and the Amygdala Retraining Recovery Programme |issue=157 | date = April 2009 | last = Gupta | first = Ashok | access-date = 2022-06-04}}</ref>

==Research ==
Ashok Gupta states he has spent over 20 years researching [[neuroplasticity]].<ref name="website">{{Cite web |url = https://www.guptaprogram.com | title = The Secret of Amygdala Retraining | access-date = 2022-06-04 | website = The Gupta Program}}</ref>

==Gupta Program ==
Gupta published his hypothesis of ME/CFS in 2002, and has sold the Gupta Program, which he describes as a [[brain training]] and holistic health course, it has been commercially available since 2007.<ref name="KF2021" /> The Gupta Program was originally called the ''Gupta Programme'' and later a variety of different terms have been used to promote it, with Amygdala and Insula Retraining (AIR) being the most recent.<ref name="website" />
{{See also|Gupta program}}
{{See also|Criticisms of The Gupta Program}}

==Complaints ==
The UK's [[Advertising Standards Authority]] upheld a complaint in 2018.<ref name="ASA2018">{{Cite web | url = https://www.asa.org.uk/rulings/harley-street-solutions-ltd-a17-400324.html | title = Harley Street Solutions Ltd | last = Advertising Standards Authority {{!}} Committee of Advertising Practice | authorlink = Advertising Standards Authority | first = |website=Advertising Standards Authority | date = April 11, 2018 | access-date = 2020-08-29}}</ref>

==Notable studies published by others==
*2020, Mindfulness-Based Program Plus Amygdala and Insula Retraining (MAIR) for the Treatment of Women with Fibro<ref name="MAIR2020">{{Cite journal | title = Mindfulness-Based Program Plus Amygdala and Insula Retraining (MAIR) for the Treatment of Women with Fibromyalgia: A Pilot Randomized Controlled Trial | date = Oct 2020 | url = https://www.mdpi.com/2077-0383/9/10/3246/htm|journal=Journal of Clinical Medicine|volume=9|issue=10 | pages = 3246 | last = Sanabria-Mazo | first = Juan P. | authorlink = | last2 = Montero-Marin | first2 = Jesus | authorlink2 = | last3 = Feliu-Soler | first3 = Albert | authorlink3 = | last4 = Gasión | first4 = Virginia | authorlink4 = | last5 = Navarro-Gil | first5 = Mayte | authorlink5 = | last6 = Morillo-Sarto | first6 = Héctor | authorlink6 = | last7 = Colomer-Carbonell | first7 = Ariadna | last8 = Borràs | first8 = Xavier | last9 = Tops | first9 = Mattie | last10 = Luciano | first10 = Juan V. | last11 = García-Campayo | first11 = Javier|language=en|doi=10.3390/jcm9103246|pmc=PMC7599726|pmid=33050630|access-date=|issn=2077-0383|quote=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/10/3246/htm (Full text)]
::'''Conflict of interest not declared:''' Author and investigator Virginia Gasión (Virginia Gasión Royo) had been a Gupta coach since 2014, which means she earns from people doing the Gupta Program, giving a direct final financial conflict of interest.<ref name="Guptacoaches">{{Cite web | url = https://www.guptaprogram.com/coaches | title = Our Professional Team of Coaches | last = | first = | authorlink = | date = |website=Gupta Program|language=en-US|archive-url=|archive-date=|url-status= | access-date = 2022-06-03}}</ref>
*2012, A mind-body technique for symptoms related to fibromyalgia and chronic fatigue<ref name="Toussaint2012">{{Cite journal | title = A mind-body technique for symptoms related to fibromyalgia and chronic fatigue | date = Mar 2012 | url = https://pubmed.ncbi.nlm.nih.gov/22385563/|journal=Explore (New York, N.Y.)|volume=8|issue=2 | pages = 92–98 | last = Toussaint | first = Loren L. | authorlink = Loren Toussaint | last2 = Whipple | first2 = Mary O. | authorlink2 = | last3 = Abboud | first3 = Lana L. | authorlink3 = | last4 = Vincent | first4 = Ann | authorlink4 = Ann Vincent | last5 = Wahner-Roedler | first5 = Dietlind L.|doi=10.1016/j.explore.2011.12.003|pmc=|pmid=22385563|access-date=|issn=1878-7541|quote=|via=}}</ref> - [https://www.researchgate.net/profile/Loren-Toussaint/publication/229324365_A_Mind-Body_Technique_for_Symptoms_Related_to_Fibromyalgia_and_Chronic_Fatigue/links/59e3bb3f458515393d5b935f/A-Mind-Body-Technique-for-Symptoms-Related-to-Fibromyalgia-and-Chronic-Fatigue.pdf (Full text)]
::The Advertising Standards Authority rejected this as evidence of effectiveness of the Gupta Program.<ref name="ASA2018" />
::This was open to patients with [[chronic fatigue syndrome]] but none completed it. Of the 32 patients randomly assigned to Amygdala and Insula Retraining (AIR) plus standard care, 19% (6 patients) dropped out before starting, 19% (6 patients) did not complete baseline measures but did AIR, 41% (13 patients) did AIR but not the follow-up assessments, 22% (7 patients) did AIR and completed follow-up assessments. Twice as many patients completed standard care, including both assessments - 56% (14 out of 25).<ref name="Toussaint2012" />

===Articles not peer reviewed or from non-academic journals===
*2010, Can amygdala retraining techniques improve the wellbeing of patients with chronic fatigue syndrome? A clinical audit of subjective outcomes in a small sample<ref name="GuptaAudit">{{Cite journal |archive-url = http://web.archive.org/web/20111119095503/http://www.guptaprogramme.com/Amygdala_Retraining_JHH_Sept_2010.pdf |archive-date=2011-11-11 | url = https://www.guptaprogram.com/wp-content/uploads/2019/02/amygdala-retraining-jhh-sept-2010.pdf | last = Gupta | first = A | authorlink = Ashok Gupta | date =September 2010 | title = Can amygdala retraining techniques improve the wellbeing of patients with chronic fatigue syndrome? A clinical audit of subjective outcomes in a small sample. |journal = Journal of Holistic Healthcare |volume= 7 |issue =2 | pages = 12-15 | access-date = 2022-06-02}}</ref> - [http://web.archive.org/web/20111119095503/http://www.guptaprogramme.com/Amygdala_Retraining_JHH_Sept_2010.pdf (Full text)]
::The Advertising Standards Authority rejected this as evidence of effectiveness of the Gupta Program.<ref name="ASA2018" />
::This was not published in an academic journal<ref name="JHH">{{Cite web | url = https://bhma.org/journal-information-for-contributors/ | title = Journal - information for contributors | last = | first = | authorlink = | date = |website=British Holistic Medical Association|archive-url=|archive-date=|url-status= | access-date = 2022-06-03}}</ref>
*2002, Unconscious amygdalar fear conditioning in a subset of chronic fatigue syndrome patients<ref name="Hypothesis2002">{{Cite journal | last = Gupta | first = Ashok | authorlink = Ashok Gupta | date = 2002 | title = Unconscious amygdalar fear conditioning in a subset of chronic fatigue syndrome patients |url = https://www.guptaprogram.com/wp-content/uploads/2019/02/cfs-hypothesis-medical-hypotheses-article.pdf | journal=Medical Hypotheses|volume=59|issue=6 | pages = 727–735|quote=|via=}}</ref> - [https://www.guptaprogram.com/wp-content/uploads/2019/02/cfs-hypothesis-medical-hypotheses-article.pdf (Full text)]
::The ''Medical Hypotheses'' journal that published this is reported to be the world's most controversial journal,<ref name="MHcontroversial">{{Cite journal | title = Editor says no to peer review for controversial journal | date = 2010-03-18 | url = https://www.nature.com/articles/news.2010.132|journal=Nature | last = Cressey | first = Daniel|language=en|doi=10.1038/news.2010.132|issn=1476-4687}}</ref> and describes itself as publishing hypotheses that are "radical, speculative and non-mainstream scientific ideas" and some "where experimental support is yet fragmentary".<ref name="MH">{{Cite web | url = https://www.elsevier.com/journals/medical-hypotheses/0306-9877/guide-for-authors | title = Guide for authors - Medical Hypotheses - ISSN 0306-9877 | last = | first = | authorlink = | date = |website=Elsevier|language=en|archive-url=|archive-date=|url-status= | access-date = 2022-06-03}}</ref><ref name="MH-SS">{{Cite web | url = https://www.sciencedirect.com/journal/medical-hypotheses | title = Medical Hypotheses {{!}} Journal | last = | first = | authorlink = | date = |website=ScienceDirect.com by Elsevier|language=en-us|archive-url=|archive-date=|url-status= | access-date = 2022-06-03}}</ref> It is peer-reviewed.

==Clinic location==
Previously called Harley Street Stress Solutions, Gupta's clinic is now in Harrow, Middlesex, UK.

==Talks and interviews==
*2021, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325493/ Conversation With Ashok Gupta, MA (Cantab), MSc: Treating Long-Haul Covid]<ref name="PMC8325493">{{Cite journal | title = Conversation With Ashok Gupta, MA (Cantab), MSc: Treating Long-Haul Covid | date = Apr 2021 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325493/|journal=Integrative Medicine (Encinitas, Calif.)|volume=20|issue=2 | pages = 42–46 | last = Benson | first = Dick | authorlink = |doi=|pmc=8325493|pmid=34377093|access-date=|issn=1546-993X|quote=|via=}}</ref> - Dick Benson
* 2021, [https://www.drkarafitzgerald.com/2021/07/12/the-role-of-neuroplasticity-in-chronic-illness-healing/ The Role of Neuroplasticity in Chronic Illness & Healing] - Kara Fitzgerald, Naturopath
* 2008, [https://web.archive.org/web/20081224002122/http://www.thisislondon.co.uk/news/article-3116268-details/Can+this+man+cure+ME/article.do Can this man cure ME?] Alice Hart-Davis - This is London

==Online presence==
* PubMed
* [https://www.twitter.com/GuptaProgramme Twitter]
* [https://www.facebook.com/Guptaprogram Facebook]
* [https://uk.linkedin.com/in/ashok-gupta-8495a0 LinkedIn]
* [https://www.guptaprogram.com Website]
* [https://youtube.com/c/GuptaProgramme YouTube (Gupta Program)]
* Email: info@guptaprogram.com
* Clinic address: unknown

==See also==
*[[Brain training]]
*[[Gupta program]]
*[[Criticisms of The Gupta Program]]

==Learn more==


==References==
{{reflist}}

[[Category:Clinicians]]
[[Category:British clinicians]]

1955 Durban outbreak

2022-12-23T23:29:38Z

Davidshq:/* Onset */

In February, 1955, near the end of summer, a disease resembling [[poliomyelitis]] struck the nursing staff of Addington Hospital in Durban, [[South Africa]]. A total of 98 nurses became ill.<ref name=":0">{{Cite journal | last = Hill | first = RC | date = April 4, 1959 | title = Epidemic myalgic encephalomyelopathy: the Durban outbreak | url =https://www.ncbi.nlm.nih.gov/pubmed/13642847|journal=The Lancet|volume=1 | pages = 689-693|via=}}</ref>

Addington Hospital at the time served the European and "Coloured" populations of Durban, but not Asians or Africans.

== Onset ==
Patients typically presented with severe headache 14 days after onset.

== Symptoms ==
* [[Respiratory tract infection|respiratory-tract infection]] or [[flu-like illness]]
* severe [[headache]]
* extreme lassitude
* stiffness of the [[Neck stiffness|neck]], [[backache]]
* [[Myalgia|muscle pain]] and cramps
* [[muscle weakness]]
* [[paresthesia]]
* temporary [[paralysis]] worsened by [[exertion]]
* [[sweating]] of the extremities

"In certain cases symptoms and signs were very slight, and recovery was rapid; in others the illness proved extremely debilitating and protracted, with residual signs or relapses three years after the onset."<ref name=":0" />

== Signs & findings ==
* low-grade [[fever]] or absence of fever
* [[tachycardia]]
* [[stiff neck|neck stiffness]]
* [[sleep reversal|reversal of normal sleeping pattern]]
* slight facial [[Paresis|muscle weakness]], diminution of facial sensation
* difficulty initiating movement
* reflexes variable (some abnormal)
* patchy areas of diminished sensation

"Since [[exercise]] definitely aggravated [[weakness]] and [[pain]], physiotherapy in the initial stages was contraindicated."<ref name=":0" />

== Epidemiology ==
The absence of spread to other hospital personnel or patients initially led physicians to suspect a toxic substance common to the nurses' quarters might be the cause. However, the disease eventually spread to nurses who were not living in the hospital, and sporadic cases were later admitted from the city, all supporting a theory of infection.

After a field investigation, it was suspected that the hospital outbreak was an episode in an infection which has been occurring in the general population for some weeks and months, but went unrecognized until it "broke out with explosive force among the nurses."<ref name=":0" />

Among the 98 cases within the hospital, the ages of those affected ranged from 17 to 49, although the majority of cases were 25 years of age or younger. While several nurses became ill while working in the children's ward, none of the children themselves became ill, suggesting that while children could be carriers, they were themselves immune: "...unlike [[poliomyelitis]], the changes at puberty render the individual susceptible, since cases occurred in adolescents and the incidence among teenagers was high."<ref name=":0" /> In the 30 cases outside the hospital, the age range was 15 to 54.

== Prognosis ==
More than 11% of the patients were still severely disabled after three years<ref name=":0" /><ref>Bannister, B. A. (1988). Post-infectious disease syndrome. Postgraduate Medical Journal, 64(753), 559–567.</ref> (a greater proportion may have had more mild impairments, but this was not reported).

The study authors noted, "In the acute phase complete bed rest is essential, since any form of activity tends to evoke painful cramps in the affected [[muscle]]-groups. Moreover, in our most serious relapse cases, most of the nurses admit to having been active during the acute phase."<ref name=":0" />

== See also ==
*[[Epidemic myalgic encephalomyelitis]]
*[[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks]]

==Learn more==

== References ==
{{Reflist}}

[[Category:Outbreaks]]
[[Category:History]]
[[Category:Outbreaks in the 1950s]]
[[Category:Outbreaks in the Republic of South Africa]]

1949-53 Adelaide outbreak

2022-12-21T07:33:51Z

Davidshq:

From 1949 to 1953 in '''Adelaide, Australia,''' there was an [[Epidemic myalgic encephalomyelitis|outbreak]] of a disease resembling [[poliomyelitis]], during and after a poliomyelitis epidemic. In August of 1949, cases of [[myalgic encephalomyelitis]] began to appear and continued to be seen until 1951, by which time 800 patients had been admitted to Northfield Infectious Diseases Hospital.

Patients had slight, diffuse muscle weakness mainly affecting the legs. In some, weakness appeared for the first time up to three months after the onset of the initial symptoms.<ref name=":0">{{Cite journal | last = Parish | first = JG | date = 1978 | title = Early outbreaks of 'epidemic neuromyasthenia' | url = https://www.ncbi.nlm.nih.gov/pubmed/370810|journal=Postgraduate Medical Journal|volume=54 | pages = 711-7|via=}}</ref> Dr. R.A. Pellew, of Adelaide, believed that most of the 3,130 polio cases during this period suffered from a mild form of polio (i.e., [[abortive poliomyelitis]], [[atypical poliomyelitis]]).<ref>[http://trove.nla.gov.au/newspaper/article/47377426? "Conference on Polio"] "The Advertiser'', Adelaide Australia, 01 February 1952''</ref>

== Onset ==
Onset was either gradual or sudden, often in the form of an upper respiratory tract infection and/or gastrointestinal distress with low-grade fever. Sudden onset was often accompanied by severe headache.<ref name=":12">Dr R.A. Pellew, [http://www.cabdirect.org/abstracts/19522700678.html;jsessionid=AA4534CA199AC800732B3877608F5CE0 "A Clinical Description of a Disease resembling Poliomyelitis, seen in Adelaide, 1949-1951"] ''Medical Journal of Australia'', Medical Journal of Australia 1951, June 30 Vol. 1 No. 26 pp. 944-6</ref> Pellew describes the initial symptoms as indistinguishable from poliomyelitis: "bursting [[headache]], stiff back, stiff neck, aching limbs, pain behind the eyes, [[upper respiratory tract infection]], mild [[muscle weakness]], and a fever followed by [[lysis]] over a period of three days."<ref name=":2">{{Cite journal | last = Pellew| first = R.A.A. | date = September 24, 1955 | title = Further Investigations on a Disease Resembling Poliomyelitis Seen in Adelaide | url =https://www.ncbi.nlm.nih.gov/pubmed/13272481|journal=The Medical Journal of Australia|volume=2 | pages = 480-2|via=}}</ref>

Also noted was a rise in temperature between the seventh and tenth days, with a recurrence of symptoms.<ref name=":2" />

== Symptoms ==
* [[headache]]
* muscle weakness
* cognitive dysfunction (lack of concentration, depression, irritability, emotional instability)<ref name=":2" />
* sound sensitivity
* pain behind the eyes<ref name=":12" />
* hyperaesthesia

"Muscle weakness - generally slight and diffuse in distribution - occurred more commonly in the legs than in the arms. Where paralysis was severe, rapid recovery generally ensued. Two noteworthy features of the muscle involvement in this disease were as follows: the pain frequently persisted in various muscles for periods up to six months after the acute illness; in some cases the onset of muscle weakness was delayed for several months.<ref name=":1">Dr R.A. Pellew, [http://www.cabdirect.org/abstracts/19522700678.html;jsessionid=AA4534CA199AC800732B3877608F5CE0 "A Clinical Description of a Disease resembling Poliomyelitis, seen in Adelaide, 1949-1951"] ''Medical Journal of Australia'', Medical Journal of Australia 1951, June 30 Vol. 1 No. 26 pp. 944-6</ref>

== Findings ==
As with other epidemics, no virus was isolated and there was an absence of abnormal findings in [[cerebrospinal fluid]]<ref name=":12" /> However, there were some interesting finding in animal studies.

Pellew collected throat washings, feces, and cerebrospinal fluid from a subset of patients and inoculated rhesus monkeys, mice, and hen eggs. Several monkeys displayed sluggishness and subnormal body temperature. One died. On autopsy, two monkeys showed red spots along the sciatic nerves and microscopic damage:<blockquote>"There were lesions in the nerve roots and in the sciatic nerves. In the nerve roots close to their point of exit from the spinal canal there was pronounced infiltration with lymphocytes and mononuclear cells, and in a percentage of the nerve fibres were found vacuoles in the myelin sheaths and axon swellings. In the sciatic nerves there were small localized infiltrations with inflammatory cells associated with exudation of a few red blood corpuscles. The only abnormality in the skeletal muscle was the presence of sarcoporidiosis in all sections from one animal; but examination of the heart muscle of the monkey which had died showed severe myocarditis with widespread infiltration mainly with lymphocytes and mononuclear cells."<ref name=":2" /></blockquote>

== Epidemiology ==
The male : female ratio was 1: 1.<ref name=":0" />
{| class="wikitable"
|+'''Age distribution in the Adelaide outbreak'''<ref name=":12" />
!Age set
!Percentage
|-
|< 5
|15%
|-
|5-9
|20%
|-
|10-15
|10%
|-
|15-20
|10%
|-
|20-25
|10%
|-
|25-30
|10%
|-
|30-65
|25%
|-
|> 65
|none
|}
During the Adelaide outbreak of atypical polio, while the number of reported polio cases increased in New South Wales and Queensland, and remained constant in the rest of Australia, there was a 43% reduction in typical polio cases in South Australia (where Adelaide is located).<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542300/ "Poliomyelitis in 1953"] ''Bulletin of the World Health Organization.'' 1955;12(4):595-649.</ref> This may have been indirect evidence of [[Poliovirus#Cross-immunity|cross-immunity]], that is, partial immunity to poliovirus acquired via exposure to a related [[enterovirus]].

A similar phenomenon was observed in Iceland, when children from an area that had recently had an outbreak of [[epidemic myalgic encephalomyelitis]] had a stronger response to [[poliovirus]] vaccination, with higher antibody titers.<ref name=":0" /><ref>{{Cite journal | url = https://www.ncbi.nlm.nih.gov/pubmed/13515219 | title = Response to poliomyelitis vaccination | last = Sigurdsson | first = B | authorlink = Björn Sigurdsson | date = February 15, 1958|journal=The Lancet|volume=1 | pages = 370-1|via=}}</ref> Conversely, in a study of children exposed to live and inactive poliovirus vaccines in Estonia and Finland,<ref>{{Cite journal | last = Juhela | first = S | date = July 1999 | title = Comparison of enterovirus-specific cellular immunity in two populations of young children vaccinated with inactivated or live poliovirus vaccines |url =https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905481/|journal=Clinical & Experimental Immunology|volume=117 | pages = 100–105|via=}}</ref> where those who had been exposed to the live polio vaccine had a stronger antibody response to [[Coxsackievirus B4]].

== Prognosis ==
Pellew followed up with five cases, three years after onset.

== See also ==
*[[Epidemic myalgic encephalomyelitis]]
*[[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks]]

==Learn more==

== References ==
{{Reflist}}
[[Category:History]]
[[Category:Outbreaks]]
[[Category:Outbreaks in the 1940s]]
[[Category:Outbreaks in the 1950s]]
[[Category:Outbreaks in Australia]]

Poliomyelitis

2022-12-21T07:29:48Z

Davidshq:

{{stub}}
'''Poliomyelitis''', also known as '''polio,''' is a disease caused by the [[poliovirus]].

Acute onset with flulike symptoms. Complications may be severe. Because of vaccination, it is not found in industrialized countries like the U.S. However, it's still common in other areas. Children are at greatest risk. Virus is spread primarily through fecal-oral contamination. <ref>{{Cite web|url=https://www.cdc.gov/polio/about/index.htm | title = CDC Global Health - Polio - What Is Polio? | date = 2018-12-12 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-08-28}}</ref><ref>{{Cite web|url=http://www.childrenshospital.org/conditions-and-treatments/conditions/p/poliomyelitis/symptoms-and-causes | title = Poliomyelitis Symptoms & Causes {{!}} Boston Children's Hospital|website=childrenshospital.org|access-date=2019-08-28}}</ref>

==See also==
*[[Abortive poliomyelitis]]
*[[Poliovirus]]
*[[Post-polio syndrome]]

== References ==
{{reflist}}

[[Category:Disease names]]
[[Category:Infectious diseases]]
[[Category:Viral diseases]]

1970 London outbreak

2022-12-21T07:29:05Z

Davidshq:/* Mass hysteria theory */

'''1970 London outbreak''': In 1970-1971, at least 145 cases of [[epidemic neuromyasthenia]] (ENM) were observed in the staff of the Hospital for Sick Children, Great Ormond Street, London, England, although there may have been additional undiagnosed cases. The majority of those affected were nurses. The chief medical investigators, MJ Dillon, WC Marshall, JA Dudgeon, and AJ Steigman, believed this [[Epidemic myalgic encephalomyelitis|outbreak]] was similar to outbreaks of unknown etiology in the US, Denmark, Australia, South Africa, Germany, Greece, and the UK which were described by many names, such as, [[Poliomyelitis|poliomyelitis-like illness]], [[1948-49 Akureyri outbreak|Icelandic Disease]], Akureyi disease, [[Royal Free disease]], benign myalgic encephalomyelitis, and epidemic neuromyasthenia.<ref name="Dillon, 1974" />

==Timeline==
The [[Epidemic myalgic encephalomyelitis|outbreak]] occurred in two waves. The first wave, between mid-August and the end of September 1970, had thirty-three cases. Most were student nurses with one case being a nun who taught the students. The second wave ended towards the end of January 1971 and affected all levels of hospital staff, including administrative and domestic staff. A few sporadic cases developed between February and June 1971.<ref name="Dillon, 1978" />

==Demographics==

The breakdown of who became ill was: 103 student nurses, 21 senior nurses, 6 doctors and 15 hospital staff. The vast majority were female, but four males (two doctors and two administrators), also, became ill. No patients were affected. <ref name="Dillon, 1978" />

==Symptomatology==

Symptomatology in order of prevalence was [[headache]], sore throat, [[nausea]], back pain, [[malaise]], vomiting, neck pains, tiredness, limb pains, [[depression]], dizziness, sore eyes, cough, coryza, chest pain, abdominal pain, photophobia, diarrhea, earache, laryngitis, paresthesia, faintness, jaw pain, bladder symptoms, [[Anorexia and eating disorders|anorexia]], [[Paresis|subjective limb weakness]], blurred vision, diplopia, and painful joints. A striking symptom reported was rapid fatigability with exercise and relapses over a prolonged period sometimes lasting several years. Duration of the illness varied greatly and was hard to determine because of relapses. Even those who recovered from the illness never fully regained their pre-illness level of health.<ref name="Dillon, 1978" />

Invasive testing was kept to a minimum so as to not create an atmosphere of anxiety in a vulnerable population. Serological tests were done for viruses, such as [[cytomegalovirus]], adenovirus, [[herpes simplex]], influenza A and B, parainfluenza 1 and 3, mumps, and [[Epstein-Barr virus]]; electron and immune electon microscopy; cell cultures were inoculated into lab animals; hematological, biochemical, bacteriological tests; cerebrospinal fluid examination; immunoglogulin, interferon, phyohemagglutin stimulation of peripheral lymphphocyctes, and lymphocyte cultures testing was done.<ref name="Dillon, 1974" /> Laboratory and other testing was unable to uncover an infectious agent, although the investigators believed the pattern of the outbreak pointed to an infective etiology.<ref name="Dillon, 1978" />

==Mass hysteria theory==

Mass [[hysteria]] was considered by several physicians not directly involved in the investigation or treatment of the outbreak. In 1974, in a letter to the [[British Medical Journal]], the chief investigators defended their lack to psychiatric intervention: "we did not feel sufficient psychiatric symptomatology to justify psychiatric referral." They went on to explain that morale was good and no "belle indifference," that is, hysteria or [[conversion disorder]], was observed.<ref name="Dillon, L1974" />

In 1994, Nathaniel C. Briggs and [[Paul Levine|Paul H. Levine]], from the Viral Epidemiology Branch, Epidemiology and Biostatistics Program of the [[National Institutes of Health]], wrote a review comparing twelve [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] referred to as [[chronic fatigue syndrome]], epidemic neuromyasthenia, and [[myalgic encephalomyelitis]]. They grouped the outbreaks into four levels of increasing neurological involvement, ranked I-IV. The 1970 London outbreak was rated as level I, which meant that they found minimal neuropsychological changes. Briggs and Levine stated: "With the exception of affective neuropsychological symptoms, neurological symptomatology was virtually absent...Paresthesias were reported as a symptom in only five (3%) of the 145 cases, subjective limb weakness was reported in 2 (1%), and depression was reported in 18 (12%)."<ref name="Briggs, 1994" />

==References==
<references>
<ref name="Dillon, 1978">{{Citation | last1 = Dillon | first1 = M.J. | authorlink1 = | title = “Epidemic neuromyasthenia” at the Hospital for Sick Children, Great Ormond Street, London | journal = Postgraduate Medical Journal | volume = 54 | issue = 637 | page = 725–730 | date = 1978 | pmid = 746019 }}</ref>
<ref name="Briggs, 1994">{{Citation | last1 = Briggs | first1 = Nathaniel C. | authorlink1 = | last2 = Levine | first2 = Paul H. | authorlink2 = Paul Levine | title = A Comparative Review of Systemic and Neurological Symptomatology in 12 Outbreaks Collectively Described as Chronic Fatigue Syndrome, Epidemic Neuromyasthenia, and Myalgic Encephalomyelitis | journal = Clinical Infectious Diseases | volume = 18 | issue = Suppl 1 | page = S32-42 | date = 1994 | pmid = 8148451 | doi = 10.1093/clinids/18.Supplement_1.S32 }}</ref>
<ref name="Dillon, L1974">{{Citation | last1 = Dillon | first1 = M.J. | authorlink1 = | last2 = Marshall | first2 = W.C. | authorlink2 = | last3 = Dudgeon | first3 = J.A. |authorlink3 = | last4 = Steigman | first4 = A.J. | authorlink4 = | title = Letter: Epidemic neuromyasthenia | journal = British Medical Journal | volume = 2 | issue = 5918 | page = 559 | date = 1974 | pmid = 4407290 }}</ref>
<ref name="Dillon, 1974">{{Citation | last1 = Dillon | first1 = M.J. | authorlink1 = | last2 = Marshall | first2 = W.C. | authorlink2 = | last3 = Dudgeon | first3 = J.A. |authorlink3 = | last4 = Steigman | first4 = A.J. | authorlink4 = | title = Epidemic neuromyasthenia: outbreak among nurses at a children's hospital. | journal = British Medical Journal | volume = 1 | issue = 5903 | page = 301–305 | date = 1974 | pmid = 4819151 }}</ref>
</references>

[[Category:History]]
[[Category:Outbreaks]]
[[Category:Outbreaks in the 1970s]]
[[Category:Outbreaks in the United Kingdom]]

1955 North of England outbreak

2022-12-21T07:04:13Z

Davidshq:

In 1955, an extensive [[Epidemic myalgic encephalomyelitis|outbreak]] of [[myalgic encephalomyelitis]] in the North of England in 1955 was recorded. It primarily struck primary school children starting in February and spread to the adults in March and April. By July, 233 cases had been recorded. The male: female ratio was 1:1. Twenty children boarding at the Carlisle Corporation Home, Dalston, mainly boys aged 5 to 15 years, were all affected. Secondary attacks in contacts occurred in several families after a primary host relapsed, suggesting that the patient had again become infectious.

Symptoms included:
* swollen, tender lymph nodes, liver and spleen
* marked fatigability
* impairment of memory and concentration
* changes of mood with behavior disorders in children
* sleep disorders
* irritability or depression
* involvement of the autonomic nervous system resulting in [[Postural orthostatic tachycardia syndrome|orthostatic tachycardia]], coldness of the extremities, episodes of sweating or profound pallor, sluggish pupillary responses, constipation and frequency of micturition, possibly as the result of a [[Hypothalamus|hypothalamic]] disturbance
* diffuse and variable involvement of the nervous system leading to [[ataxia]], weakness or sensory changes in a limb, nerve root or a peripheral nerve distribution, especially involving the [[ulnar nerve]]
* muscle pain, tenderness and myasthenia
* recurrences in about 20% of patients over a period of several years.

Also observed were morphological changes in the [[Lymphocyte|lymphocytes]] with relative lymphocytosis and eosinophilia. In some cases the abnormal blood films persisted for at least 18 months. In most of the Dalston cases the onset was abrupt after an incubation period of 5 to 7 days, but some of the adults showed a delayed onset with the illness reaching the maximum severity after 6 weeks. Neurological symptoms occurred in 60% of the patients, but objective changes were mild and seen only in 20% of cases. There were ulnar nerve lesions in eight patients. Non-specific abnormalities were noted in the [[EEG|EEGs]] in fifteen of the twenty-three patients tested. The [[Cerebrospinal fluid|CSF]] was normal in the few examinations made. Virus studies were also negative. The case incidence and percentage of neurological involvement were similar to that observed in the [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks#Switzerland|Swiss military epidemics]].<ref name=":0">{{Cite journal | last = Parish | first = JG | date = 1978 | title = Early outbreaks of 'epidemic neuromyasthenia' | url = https://www.ncbi.nlm.nih.gov/pubmed/370810|journal=Postgraduate Medical Journal|volume=54 | pages = 711-7|via=}}</ref>
==See also ==

==Learn more==

== References ==
{{Reflist}}

[[Category:History]]
[[Category:Outbreaks]]
[[Category:Outbreaks in the 1950s]]
[[Category:Outbreaks in the United Kingdom]]

1984 Tapanui & West Otago Outbreak

2022-12-21T07:00:40Z

Davidshq:

[[File: Tapanui, New Zealand.png |right|Source:en.wikipedia.org]]
In 1984, an epidemic outbreak of [[chronic fatigue syndrome]] occurred in the small, rural town of '''Tapanui, in West Otago''' in New Zealand's South Island, close to the boundary with Southland region.<ref name="Snow2002" /> Dr. [[Peter Grahame Snow]] was a General Practitioner in Tapanui, [[New Zealand]] when the [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|chronic fatigue syndrome outbreak]], then called [[Tapanui Flu]], occurred.<ref name="Maclean2010">{{Cite web | url = https://www.odt.co.nz/regions/southland/murdoch-be-towns-next-gp | title = Murdoch to be town's next GP | last = McLean | first = Elspeth | date = 2010-07-17 | website = Otago Daily Times Online News|language=en | access-date = 2022-07-30}}</ref> Dr Snow was considered the first doctor in New Zealand to diagnosis and treat [[chronic fatigue syndrome|CFS]] patients. His obituary states: "It was that farmer's wisdom, that ability to see phenomena clearly, and to perceive the connections among them, that led Peter to describe an epidemic of [[chronic fatigue syndrome]] (CFS) in West Otago, a syndrome that was then recognized elsewhere in New Zealand, and that the media soon dubbed [[Tapanui Flu]]."<ref name="obituary">{{Cite web | date = 2006 | title = Annual Report 2006| publisher = Royal New Zealand College of General Practitioners| pages=38-42 | url = http://www.rnzcgp.org.nz/documents/ANNUAL_REPORT_2006.pdf | archive-url=https://web.archive.org/web/20061007204023/http://www.rnzcgp.org.nz/documents/ANNUAL_REPORT_2006.pdf | archive-date=July 17, 2016}}</ref>

The outbreak was characterized by [[Flu-like illness|flu-like]] [[malaise]] and prolonged unexplained [[fatigue]]. Levine, P.H. et al. 1997, stated: "This outbreak resembled other reported outbreaks of [[Epidemic neuromyasthenia|epidemic neuromyasthenia]] in that affected individuals presented with a spectrum of complaints ranging from transient diarrhea and upper respiratory disorders to chronic fatigue syndrome."<ref name="Levine1997">{{Cite journal | title = Epidemic neuromyasthenia and chronic fatigue syndrome in west Otago, New Zealand. A 10-year follow-up | date = 1997-04-14 | url = https://pubmed.ncbi.nlm.nih.gov/9125006/|journal=Archives of Internal Medicine|volume=157|issue=7 | pages = 750–754 | last = Levine | first = P.H. | authorlink = | last2 = Snow| first2 = P.G. |authorlink2 = Peter Grahame Snow | last3 = Ranum| first3 = B.A. |author-link3= | last4 = Paul | first4 = C. | author-link4= | last5 = Holmes | first5 = M.J. | author-link5=|doi=|pmc=|pmid=9125006|access-date=|issn=0003-9926|quote=|via=}}</ref>

Two other physicians studied the illness outbreak with Dr. Snow: Dr. [[Marion Poore]] and Dr. [[Charlotte Paul]]. Together they wrote a piece in 1984 for ''The New Zealand Medical Journal'': "An apparent epidemic of undiagnosed illness in a rural general practice was investigated. The aims were to describe the illness, the characteristics of the people affected, and to look for possible causes. The patients were questioned about their symptoms, and both patients and controls matched for age and sex, were questioned about possible aetiological factors. Twenty-eight cases were identified; all but three were less than 45 years of age; there were equal numbers of females and males. The most commonly experienced symptoms were [[Fatigue|tiredness]], [[Mood swings|mood]] and [[Sleep dysfunction|sleep disturbances]], [[headache]], and [[Arthralgia|joint]] or [[Myalgia|muscle pains]]. Results of the case-control study suggested that pollution of the water supply, [[zoonotic]] infections, contact with agricultural chemicals, and self-dosing with selenium were unlikely to be causes of this illness. An unidentified [[virus]] was regarded as the most likely cause."<ref name="Poore1984">{{Cite journal | title = An unexplained illness in West Otago | date = 1984-06-13 | url = https://pubmed.ncbi.nlm.nih.gov/6589518/|journal=The New Zealand Medical Journal|volume=97|issue=757 | pages = 351–354 | last = Poore | first = M. | authorlink = | last2 = Snow| first2 = P. | authorlink2 = Peter Grahame Snow | last3 = Paul | first3 = C. | author-link3=|doi=|pmc=|pmid=6589518|access-date=|issn=0028-8446|quote=|via=}}</ref>

A ten-year follow-up concluded that: "A return to premorbid activity was seen in most (n=16) patients, although some reported the need to modify their lifestyle to prevent [[Relapse|relapses]]. A [[Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome|female predominance]] was noted in those meeting the [[Centers for Disease Control and Prevention]] (CDC) case definition for [[Chronic fatigue syndrome|CFS]], whereas males predominated in patients diagnosed as having prolonged or [[Idiopathic chronic fatigue|idiopathic fatigue]]."<ref name="Levine1997" /> It is unknown if the difference in diagnoses between males and females was because the presentation of the disease differed in the sexes or whether physician bias lead one sex to be diagnosed differently that the other.

Eighteen years later, in 2002, Dr. Peter Snow wrote a reminiscing piece for ''New Zealand Family Physician'' journal, in which he discussed the dismissive nature in which patients of the outbreak were treated. "I can recall poems, cartoons (''NZ Herald'') and songs – ''I have got those old Tapanui flu blues''... [where] the press made light, dumbing down if you wish, of the subject, which I considered an important cause of distress in our community." Later, after the medical and research fields began to view the illness seriously, the pendulum began to swing the other way. "What I find disturbing now is the exact opposite to the problem we started in 1985. Then it was getting physicians to accept that there was a chronic fatiguing condition, whereas today I fear that the diagnosis is being applied [[misdiagnosis of myalgic encephalomyelitis and chronic fatigue syndrome|before adequate investigation has taken place]] often leaving the patient's real disorder undiagnosed and untreated. Unfortunately chronic fatigue syndrome has become a convenient dumping ground for the difficult to diagnose."<ref name="Snow2002">{{Cite journal | last = Snow| first = P.G. | authorlink = Peter Grahame Snow | title = Reminiscences of the chronic fatigue syndrome|journal=New Zealand Family Physician|volume = 29|issue=6 | pages = 385-386 | url = https://www.rnzcgp.org.nz/assets/documents/Publications/Archive-NZFP/Dec-2002-NZFP-Vol-29-No-6/Snow-December-02.pdf | archive-url=http://web.archive.org/web/20160206073445/https://www.rnzcgp.org.nz/assets/documents/Publications/Archive-NZFP/Dec-2002-NZFP-Vol-29-No-6/Snow-December-02.pdf |archive-date=2016-02-06 | date = 2002}}</ref>

To illustrate this phenomenon, Dr. Snow and Dr. [[Mike Holmes]], of the Microbiology Department of the University of Otago, further studied the present local population with diagnoses of CFS and found that 65% were actually suffering from a bowel disorder caused by [[giardia lamblia]] which responded to the [[antibiotic]], [[nitroimidazole]]. Initially left untreated, the giardia had moved into a chronic phrase, presenting as "[[diarrhea|diarrhoea]], [[constipation]], frequent [[Loose bowels|mushy bowel]] motions, rotten egg [[Gas|flatus]], post prandial [[bloating]], [[abdominal distention]], [[Hypersensitivity|food intolerances]] particularly to milk products, alcohol, fatty foods, spicy foods, along with the multiplicity of signs such as [[headache]], [[lymphadenopathy]] and others." This symptom cluster is atypical for CFS. He cautioned other physicians that only 5% of patients with a fatiguing illness "probably is [of] the group that would fulfill the criteria of the Centre of Disease Control USA [sic] for the chronic fatigue syndrome."<ref name="Snow2002" />

==Learn more==
*[https://www.southerncross.co.nz/group/medical-library/chronic-fatigue-syndrome-tapanui-flu Medical description of Tapanui Flu]
*[https://en.wikipedia.org/wiki/Peter_Snow_(doctor) Dr. Peter Snow] - Wikipedia
*[https://www.rnzcgp.org.nz/assets/documents/Publications/Archive-NZFP/Dec-2002-NZFP-Vol-29-No-6/Snow-December-02.pdf "Reminiscences of the chronic fatigue syndrome" by Dr. Peter Snow]
*[http://anzmes.org.nz/ ANZMES - The Associated New Zealand ME Society]

==See also==
*[[Tapanui Flu]]
*[[Peter Grahame Snow]]
*[[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks]]
*[[New Zealand]]

==References==
{{Reflist}}

[[Category:History]]
[[Category:Outbreaks]]
[[Category:Outbreaks in the 1980s]]
[[Category:Outbreaks in New Zealand]]

1948-49 Akureyri outbreak

2022-12-21T06:26:00Z

Davidshq:

The '''Akureyri outbreak''' was an [[Epidemic myalgic encephalomyelitis|outbreak]] of [[myalgic encephalomyelitis]] in Northern [[Iceland]] during the winter of 1948-1949. It lasted for three months and a total of 488 cases were reported in Akureyri, and a total of 1,090 across Iceland.<ref name=":1" /> The outbreak may have been related to the earlier [[1946-47 Iceland outbreak]].<ref name="PoliomyelitisAkureyri1959">{{Cite journal | last = Sigurjonsson | first = J | authorlink = | date = 1959-01-01 | title = Poliomyelitis & Akureyri disease|trans-title=Poliomyelitis & Akureyri disease; differentiation of poliomyelitis from poliomyelitis-like disease with characteristics of Akuteyri disease.|url=|journal=Nordisk Medicin|language=da|volume=61|issue=5 | pages = 174-177|doi=|pmc=|pmid=13623058|access-date=|quote=|via=}}</ref> It was after this outbreak that the term ''Icelandic disease'', an early name for myalgic encephalomyelitis, was coined.

== Onset ==
Initial symptoms involved pain in the neck and back accompanied by a rise in temperature. The estimated period of incubation was five to eight days.<ref name=":2">{{Cite journal | last = Sigurdsson | first = B | authorlink = Björn Sigurdsson | date = May 1956 | title = The Lancet | url = https://www.ncbi.nlm.nih.gov/pubmed/13320872|journal=Clinical findings six years after outbreak of Akureyri disease|volume=270 | pages = 766-7|via=}}</ref>

== Symptoms ==
The systemic form of the illness was present in 70% of patients with the characteristic [[Low-grade fever|low fever]], [[myalgia|muscle tenderness]] and marked lassitude. 30% had [[Paresis|muscle weakness]]. [[Infectious disease testing]] failed to find evidence of [[poliovirus]], [[Coxsackie]] or other known [[encephalitis]] viruses.

== Findings ==

== Epidemiology ==
In town, the incidence was 6.7%.<ref name=":2" /> In rural areas, it was 0.8%.<ref name=":1" /> While the incidence among adults was significantly higher for females, there was no significant difference in incidence between sexes among those under twenty.<ref name=":1" />

Rates of infection were highest among those 15-19 years of age.<ref name=":1" /><ref name=":2" /> Multiple cases were often found in the same household and schools. Schools (with the exception of the elementary school) were heavily struck.

No toxic, food, or waterborne agent was found. The dairy in Akureyri pasteurised the milk and did not appear to have spread the illness to other communities served by it.<ref name=":1">{{Cite journal | last = Sigurdsson | first = Björn | authorlink = Björn Sigurdsson | last2 = Sigurjonsson | first2 = Júlíus | authorlink2 = | last3 = Sigurdsson | first3 = Jón HG | authorlink3 = | last4 = Thorkelsson | first4 = Jóhann | authorlink4 = | last5 = Gudmundsson | first5 = Kjartan R | authorlink5 = | date = 1950 | title = A Disease Epidemic in Iceland Simulating Poliomyelitis |url =http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.1012.5349|journal=Am. J. Hyg.|volume=52|issue= | pages = 222-238|doi=|pmc=|pmid=14771044|access-date=|quote=|via=}}</ref> When infections spread beyond Akureyri, the first cases appeared along the main land transportation route from Akureyri to Reykjavik, suggesting person-to-person transmission.<ref name=":1" /> Ultimately, 1,090 cases were reported, with the majority (70%) coming from three districts: Akureyri, Saudarkrokur and Isafjordur.

==Course & prognosis ==
In 1955, neurologist Kjartan Gudmundsson reexamined 39 patients affected by the outbreak. He found that 31% were free from objective clinical signs and only 13% considered themselves completely recovered.<ref name=":2" />

Of the most severely affected, only 25% had completely recovered, 52% had residual muscle tenderness, and 65% had objective [[Nervous system|neurological]] signs. Many patients still complained of nervousness, abnormal [[Muscle fatigability|fatiguability of muscles]], [[Myalgia|muscle pain]], [[Insomnia|sleeplessness]] and [[Memory problems|loss of memory]]. Of those mildly affected in 1948 only 44% had fully recovered, 50% had muscular tenderness, and 19% had residual objective neurological signs.<ref name=":0">{{Cite journal | last = Parish | first = JG | authorlink = Gordon Parish | date = 1978 | title = Early outbreaks of 'epidemic neuromyasthenia' | url = https://www.ncbi.nlm.nih.gov/pubmed/370810|journal=Postgraduate Medical Journal|volume=54 | pages = 711-7|via=}}</ref><ref name=":2" /> There were no deaths.<ref name=":2" />

In 1988, [[Byron Hyde]] published a long term follow-up in [[the Lancet]], 40 years after the initial outbreak. He managed to examine 10 patients, of which only 2 reported a full recovery.<ref>{{Cite journal | last = Hyde | first = B. | authorlink = Byron Hyde | last2 = Bergmann | first2 = S. | date = 1988-11-19 | title = Akureyri disease (myalgic encephalomyelitis), forty years later |url =https://www.ncbi.nlm.nih.gov/pubmed/2903396|journal=Lancet (London, England)|volume=2|issue=8621 | pages = 1191–1192|issn=0140-6736|pmid=2903396|quote=|via=}}</ref>

== Polio vaccine ==
In a study of children in Iceland vaccinated against polio in 1956, [[Björn Sigurdsson|Sigurdsson]], et. al found significant differences in antibody response to [[Vaccine|vaccination]] depending on where the children lived. Children in Egilsstadir had only a slight antibody rise to type 2 and type 3 [[poliovirus]], while children in Thorshofn, which had recently had an outbreak of [[epidemic myalgic encephalomyelitis]], had a much stronger antibody response to the polio vaccine. Sigurdsson postulated that this might be explained by "the existence of basic immunity acquired through a related infection."<ref>{{Cite journal | last = Sigurdsson | first = B | authorlink = Björn Sigurdsson | date = February 15, 1958 | title = Response to poliomyelitis vaccination | url =https://www.ncbi.nlm.nih.gov/pubmed/13515219|journal=The Lancet|volume=1 | pages = 370-1|via=}}</ref>

Indirect evidence of [[Poliovirus#Cross-immunity|cross-immunity]] was also seen in the outbreak in [[1949-53 Adelaide outbreak|Adelaide]], [[Australia]],<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542300/ "Poliomyelitis in 1953"] ''Bulletin of the World Health Organization.'' 1955;12(4):595-649.</ref> where there was a 43% reduction in polio cases following an [[Myalgic encephalomyelitis|ME]] outbreak. Conversely, in a study of children exposed to live and inactive poliovirus vaccines in [[Estonia]] and [[Finland]],<ref>{{Cite journal | last = Juhela | first = S | date = July 1999 | title = Comparison of enterovirus-specific cellular immunity in two populations of young children vaccinated with inactivated or live poliovirus vaccines |url =https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905481/|journal=Clinical & Experimental Immunology|volume=117 | pages = 100–105|via=}}</ref> where those who has been exposed to the live polio vaccine had a stronger antibody response to [[Coxsackievirus B4]].

==See also==
* [[Björn Sigurdsson]]
*[[1946-47 Iceland outbreak]]
*[[Epidemic myalgic encephalomyelitis]]
*[[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|List of outbreaks]]

==References==
{{reflist}}
[[Category:History]]
[[Category:Outbreaks]]
[[Category:Outbreaks in the 1940s]]
[[Category:Outbreaks in Iceland]]

1937 Erstfeld outbreak

2022-12-21T06:21:44Z

Davidshq:/* Symptoms */

In July 1937, 130 of 930 soldiers stationed in the small town of Erstfeld, [[Switzerland]] became ill with what the time was thought to be "[[Abortive poliomyelitis]]."<ref name=":0">{{Cite journal | last = Parish | first = JG | date = 1978 | title = Early outbreaks of 'epidemic neuromyasthenia' | url = https://www.ncbi.nlm.nih.gov/pubmed/370810|journal=Postgraduate Medical Journal|volume=54 | pages = 711-7|via=}}</ref>

== Onset ==
Four days after training commenced the troops were all wet through on a field exercise. Two days later, a case of [[poliomyelitis]] occurred among them, this case was at once diagnosed and removed to hospital. This was followed within twelve days by six cases with [[meningeal]] and [[myelitic]] symptoms, 16 purely meningeal cases and 108 with symptoms involving inflammation of the upper respiratory tract. The incubation period was 4-7 days.<ref name=":1">{{Cite journal | last = Stahel | first = H | date = July 1937 | title = An Epidemie of Poliomyelitis among Swiss Troops at Erstfeld from July 18 to 30, 1937, with a Large Number of Abortive Cases |url =https://www.cabdirect.org/cabdirect/abstract/19382701151|journal=Schweizerische Medizinische Wochenschrift|volume=68 | pages = 86-91|via=}}</ref>

== Symptoms ==

Of the 130 cases, 83 percent had systemic symptoms and were regarded as abortive poliomyelitis<ref name=":0" /><ref name=":1" />; 12% had meningeal involvement (involvement of the lining of the brain and spinal cord); and 5% developed encephalomyelitis with [[paresis]] ([[muscle weakness]] caused by nerve damage or disease or partial paralysis).<ref name=":0" />

Symptoms<ref name=":0" /> included:

* Sweating
* Sensitivity to touch, pain, or other sensory stimuli
* Diminished muscle tone was noted in those who complained of sharp pain in their legs.

== Findings ==
The cerebrospinal fluid was normal.<ref name=":0" />

== Epidemiology ==
This outbreak was notable for its high attack rate: 14% of soldiers were affected, as compared to 1.3% for a confirmed poliomyelitis outbreak in 1936.<ref name=":1" /> (This was a common feature of [[epidemic myalgic encephalomyelitis]] that distinguished it from polio outbreaks.)

The troops had been recruited in Zurich, where a case of the disease was reported on July 11th. The epidemic did not spread to any citizens of the town. A similar epidemic was recorded in September, 1937, less than three months later, in the women's section of a [[1937 St. Gallen outbreak | St. Gallen hospital]], Switzerland, less than 200 km or 125 miles away from Erstfeld.<ref name=":0" />

== Prognosis ==
The meningeal and upper respiratory forms cleared up in 2-5 days and all cases recovered within five weeks. There were no deaths and no residual paralysis.<ref name=":1" />

==See also==

* [[1937 St. Gallen outbreak]]
* [[1939 Degersheim outbreak]]

*[[Epidemic myalgic encephalomyelitis]]
*[[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks]]

==Learn more==

==References==
{{Reflist}}

[[Category:Outbreaks]]
[[Category:Outbreaks in the 1930s]]
[[Category:Outbreaks in Switzerland]]
[[Category:History]]

1937 Erstfeld outbreak

2022-12-21T06:20:27Z

Davidshq:/* Onset */

In July 1937, 130 of 930 soldiers stationed in the small town of Erstfeld, [[Switzerland]] became ill with what the time was thought to be "[[Abortive poliomyelitis]]."<ref name=":0">{{Cite journal | last = Parish | first = JG | date = 1978 | title = Early outbreaks of 'epidemic neuromyasthenia' | url = https://www.ncbi.nlm.nih.gov/pubmed/370810|journal=Postgraduate Medical Journal|volume=54 | pages = 711-7|via=}}</ref>

== Onset ==
Four days after training commenced the troops were all wet through on a field exercise. Two days later, a case of [[poliomyelitis]] occurred among them, this case was at once diagnosed and removed to hospital. This was followed within twelve days by six cases with [[meningeal]] and [[myelitic]] symptoms, 16 purely meningeal cases and 108 with symptoms involving inflammation of the upper respiratory tract. The incubation period was 4-7 days.<ref name=":1">{{Cite journal | last = Stahel | first = H | date = July 1937 | title = An Epidemie of Poliomyelitis among Swiss Troops at Erstfeld from July 18 to 30, 1937, with a Large Number of Abortive Cases |url =https://www.cabdirect.org/cabdirect/abstract/19382701151|journal=Schweizerische Medizinische Wochenschrift|volume=68 | pages = 86-91|via=}}</ref>

== Symptoms ==

Of the 130 cases, 83 percent were had systemic symptoms and were regarded as abortive poliomyelitis<ref name=":0" /><ref name=":1" />; 12% had meningeal involvement (involvement of the lining of the brain and spinal cord); and 5% developed encephalomyelitis with [[paresis]] ([[muscle weakness]] caused by nerve damage or disease or partial paralysis).<ref name=":0" />

Symptoms<ref name=":0" /> included:

* Sweating
* Sensitivity to touch, pain, or other sensory stimuli
* Diminished muscle tone was noted in those who complained of sharp pain in their legs.

== Findings ==
The cerebrospinal fluid was normal.<ref name=":0" />

== Epidemiology ==
This outbreak was notable for its high attack rate: 14% of soldiers were affected, as compared to 1.3% for a confirmed poliomyelitis outbreak in 1936.<ref name=":1" /> (This was a common feature of [[epidemic myalgic encephalomyelitis]] that distinguished it from polio outbreaks.)

The troops had been recruited in Zurich, where a case of the disease was reported on July 11th. The epidemic did not spread to any citizens of the town. A similar epidemic was recorded in September, 1937, less than three months later, in the women's section of a [[1937 St. Gallen outbreak | St. Gallen hospital]], Switzerland, less than 200 km or 125 miles away from Erstfeld.<ref name=":0" />

== Prognosis ==
The meningeal and upper respiratory forms cleared up in 2-5 days and all cases recovered within five weeks. There were no deaths and no residual paralysis.<ref name=":1" />

==See also==

* [[1937 St. Gallen outbreak]]
* [[1939 Degersheim outbreak]]

*[[Epidemic myalgic encephalomyelitis]]
*[[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks]]

==Learn more==

==References==
{{Reflist}}

[[Category:Outbreaks]]
[[Category:Outbreaks in the 1930s]]
[[Category:Outbreaks in Switzerland]]
[[Category:History]]

1955 Royal Free Hospital outbreak

2022-12-21T06:07:12Z

Davidshq:/* Long-term follow-up */

[[File:RoyalFreeOld.jpg|right|frame|The building that housed the Royal Free Hospital in 1955 when the outbreak occurred]]
The '''Royal Free Hospital outbreak''' was a [[Epidemic myalgic encephalomyelitis|cluster outbreak]] of [[myalgic encephalomyelitis]] at the [[Royal Free Hospital]] in London.

In 1955, between July and November, 292 members of the medical, nursing, auxiliary medical, ancillary, and administrative staff fell ill, of which 255 were admitted to the hospital.<ref name="RoyalFree1957">{{Cite journal | last = ((The Medical Staff Of The Royal Free Hospital))| first = | date = Oct 19, 1957 | title = An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/|journal=British Medical Journal|volume=2 | pages = 895–904|via=}}</ref> The disease name [[myalgic encephalomyelitis]] was first coined to describe the illness in an editorial in the Lancet, in 1956.<ref name="MyalgicEncephalomyelitis-first-named">{{Cite journal | journal = Lancet|volume=1|issue= | pages = 789–790 | date = 1956 | title = A new clinical entity? | url = https://mecfsj.files.wordpress.com/2019/05/lancet_e383a9e383b3e382bbe38383e383881956_me.pdf}}</ref><ref name="Ramsay1965">{{Cite journal | last = Ramsay | first = A. Melvin | authorlink = Melvin Ramsay | date = 1965-10-30 | title = Hysteria and “Royal Free Disease.” | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847119/|journal=British Medical Journal|volume=2|issue=5469 | pages = 1062|doi=|issn=0007-1447|pmc=1847119|pmid=|access-date=|quote=|via=}}</ref>
==Location==
The outbreak occurred at the [[Royal Free Hospital]], then situated at 256 Grays Inn Road, London, [[England]], which is now the Eastman Dental Hospital.<ref name="Ramsay56">{{Cite journal | last = Ramsay | first = A. Melvin | authorlink = Melvin Ramsay | last2 = O'Sullivan | first2 = E | date = May 26, 1956 | title = Encephalomyelitis simulating poliomyelitis |url =https://www.sciencedirect.com/science/article/pii/S0033350657800225|journal=The Lancet|volume=270 | pages = 761-764|via=}}</ref> (The current Royal Free Hospital site is now in the Hampstead area of London.)

== Onset ==

Onset involved symptoms of an [[upper respiratory infection]], [[sore throat]], [[Gastrointestinal system|gastrointestinal]] disturbances including [[nausea]] and [[vomiting]], or acute [[vertigo]].<ref name="Ramsay1978">{{Cite journal | last = Ramsay | first = A. Melvin | date = November 1978 | title = 'Epidemic neuromyasthenia' 1955-1978 | url = https://www.ncbi.nlm.nih.gov/pubmed/746017|journal=Postgraduate Medical Journal|volume=54 | pages = 718-721|via=}}</ref>

== Symptoms ==
Symptoms included:
<div style="column-count:2">
* Severe [[headache]]
* [[Malaise]]
* Lassitude
* [[Vertigo]]
* Pain in limbs
* [[Nausea]]
* [[Dizziness]]
* [[Neck stiffness]], [[neck pain]]
* [[lower back pain|Pain in back]]
* [[Myalgia]], which in some patients caused them to cry out in [[pain]], [[muscle weakness]], [[muscle cramps|cramps]], [[muscle fasciculations|twitching]]
* [[Depression]]
* [[Abdominal pain]]
* [[Vomiting]]
* [[Double vision|Diplopia]] (double vision)
* [[Tinnitus]]
* [[Diarrhea]]
* [[Swollen lymph nodes]]
* [[Paraesthesia]]<ref name="Ramsay1978" />
</div>

Usually by the second or third week of the disease, there was objective evidence of involvement of the [[central nervous system]] which appeared to be characteristic of the outbreak.

== Signs ==

* [[Low-grade fever]] (tended to transiently occur with relapse of symptoms)
* Swollen lymph nodes
* Objective sensory impairment and muscle tenderness
* Extensor plantar responses
* [[Nystagmus]]
* [[Double vision|Diplopia]]

== Findings ==

* Inconsistent or normal [[cerebrospinal fluid]]<ref name="Ramsay56" /><ref name="Underhill2021" />
* [[Electromyogram]]s showed abnormalities of activity, but no evidence of lower [[motor neuron]] degeneration<ref name="Ramsay56" /> (12 of 25 abnormal).<ref name="Ramsay1978" />
* non-specific [[EEG]] abnormalities<ref name="Ramsay56" />
* [[Neutropenia]] and abnormal [[lymphocyte]]s,<ref name="Compston">{{Cite journal | last = Compston | first = N.D. | date = 1978 | title = An outbreak of encephalomyelitis in the Royal Free Hospital Group, London, in 1955 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425309|journal=Postgraduate Medical Journal|volume=54 | pages = 722-724|via=}}</ref><ref name="Ramsay56" /><ref name="Underhill2021" /> consistent with a viral infection
* normal or slightly elevated [[erythrocyte sedimentation rate]]<ref name="Ramsay1978" />
* negative virology<ref name="Ramsay56" />
* abnormally high [[lactic dehydrogenase]] and [[glutamic oxaloacetic transaminase]]<ref name="Ramsay1978" />

"Evidence of involvement of the sympathetic nervous system or actual [[Hypothalamus|hypothalamic]] damage was to be found in most cases. This often took the form of [[orthostatic tachycardia]] chilliness of the extremities with increased [[Body temperature|sensitivity to cold]], circulatory impairment and hypothermia."<ref name="Ramsay1978" />

==Epidemiology==
Between July 13, 1955 and November 24, 1955, 292 people, of whom the vast majority were hospital personnel, became ill. Personnel from the medical, nursing, auxiliary medical, ancillary, and administrative departments were affected. Of these two hundred fifty-five were admitted to the hospital.<ref name="Compston" /> Despite the hospital census being near capacity, only 12 patients were afflicted.<ref name="Ramsay1984">{{Cite book | last = Ramsay | first = A. Melvin | authorlink = Melvin Ramsay | title = Post-viral fatigue: The saga of the Royal Free Disease | date = 1984| publisher = Gower|location=London|isbn=978-0906923962| title-link = Myalgic Encephalomyelitis and Postviral Fatigue States: The Saga of Royal Free Disease}}</ref>

By October 5, 1955, the hospital had to close to new admissions to contain the outbreak and because of the shortage of unaffected staff.<ref name="Underhill2021" /> The first to report ill were a resident doctor and a ward sister.<ref name="Dawson1988">{{Cite journal | last = Dawson | first = J | date = Feb 7, 1987 | title = Royal Free disease: perplexity continues|journal=British Medical Journal (Clinical Research Ed.)|volume=294|issue =6568 | pages = 327–328 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1245346/pdf/bmjcred00006-0005.pdf | pmc=PMC1245346|doi= 10.1136/bmj.294.6568.327}}</ref> More females became ill than males, but at the time it was believed to be because of the staff's living quarters not gender, as more females than males resided at the facility.<ref name="Compston" />

Similar cases had occurred in the population of North West London before this outbreak and sporadic cases continued to occur after the outbreak.<ref name="Ramsay56" />

== Prognosis ==
For many patients, symptoms waxed and waned in intensity over a long period. A very large majority had complete recovery of neurological function.

==Long-term follow-up==

A follow-up study 65 years later found that there was one group of patients that recovered completely or nearly completely, a second group that recovered but was subject to relapses, and a third that showed little or no recovery, these patients remaining incapacitated.<ref name="Ramsay1978" />

Another follow-up study in 2021 interviewed twenty-seven former hospital staff who were present during the outbreak (including a few who developed ME), and reported on their recollection of patient symptoms and circumstances at the time. The accounts of the former staff were found to be inconsistent with the McEvedy and Beard hypothesis that the illness was [[psychosomatic illness|psychosomatic]] in nature, caused by [[mass hysteria]] or psychoneurosis. Observable signs of physical illness reported by the former staff included enlarged posterior cervical glands, ptosis (drooping of the eyelids), hemiparesis (one-sided paralysis), some patients crying due to extreme [[muscle pain]], nausea, and vomiting. Patients typically delayed seeking medical treatment for the first few days, which is also inconsistent with patients overly anxious about the possibility of contracting an illness. Some patients had blood tests which found leukopenia, or lymphocytes typical of [[virus]]es. While some patients seemed to be neurotic and lacked physical signs, a large number of patients were seriously ill with significant physical signs, leading to most hospital staff at the time believing that the cause of illness was an [[infection|infectious disease]]. Some patients remained hospitalized for over six months.<ref name="Underhill2021" />

Five patients developed long-term [[paralysis]] in a part of their body.<ref name="Underhill2021" />

==Notable studies and publications==
*2021, [https://dx.doi.org/10.3390%2Fmedicina57010012 Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Organic Disease or Psychosomatic Illness? A Re-Examination of the Royal Free Epidemic of 1955]<ref name="Underhill2021">{{Cite journal | last = Underhill | first = Rosemary | authorlink = Rosemary Underhill | last2 = Baillod | first2 = Rosemarie | authorlink2 = Rosemarie Baillod | date = Jan 2021 | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Organic Disease or Psychosomatic Illness? A Re-Examination of the Royal Free Epidemic of 1955 | url = https://www.mdpi.com/1648-9144/57/1/12|journal=Medicina|language=en|volume=57|issue=1 | pages = 12|doi=10.3390/medicina57010012|pmc=PMC7824095|pmid=33375343|access-date=|quote=|via=}}</ref>
*2020, [https://www.tandfonline.com/doi/full/10.1080/21641846.2020.1793058 Myalgic Encephalomyelitis (ME) outbreaks can be modelled as an infectious disease: a mathematical reconsideration of the Royal Free Epidemic of 1955]<ref name="Waters2020">{{Cite journal | last = Waters | first = F.G. |last2 = McDonald | first2 = G.J. | last3 = Banks | first3 = S. | last4 = Waters | first4 = R.A. | date = 2020-04-02 | title = Myalgic Encephalomyelitis (ME) outbreaks can be modelled as an infectious disease: a mathematical reconsideration of the Royal Free Epidemic of 1955 | url = https://www.tandfonline.com/doi/full/10.1080/21641846.2020.1793058|journal = Fatigue: Biomedicine, Health & Behavior |language=en|volume=8|issue=2 | pages = 70–83|doi=10.1080/21641846.2020.1793058|issn=2164-1846}}</ref>
*2016, [http://www.theguardian.com/lifeandstyle/2016/apr/04/chronic-fatigue-syndrome-cfs-taken-seriously#comment-71789644 Is chronic fatigue syndrome finally being taken seriously?]
*1987, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1245346/?page=1 Royal Free disease: perplexity continues]
*1984, [[Myalgic Encephalomyelitis and Postviral Fatigue States: The Saga of Royal Free Disease]], A. Melvin Ramsay, Gower Medical Publishing, London (book)
*1978, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1604957/pdf/brmedj00128-0006b.pdf Epidemic myalgic encephalomyelitis] ([[The BMJ]])
*1978, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425324/ Epidemic neuromyasthenia 1955-1978] ([[Melvin Ramsay|A. Melvin Ramsay]], [[The BMJ]])
*1977, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1607215/?page=1 Icelandic disease (benign myalgic encephalomyelitis or Royal Free disease)] ([[Melvin Ramsay|A. Melvin Ramsay]], [[Elizabeth Dowsett]], J V Dadswell, W H Lyle, and J G Parish, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699088/?page=1 Epidemic malaise] (Dr Betty Scott, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699022/?page=1 Epidemic malaise] (Dr Nigel Dean Compston, H. E. Dimsdale, [[Melvin Ramsay|A. Melvin Ramsay]], and A. T. Richardson, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1698971/?page=1 Epidemic malaise] (Dr E D Acheson, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699452/ Epidemic malaise] (Dr Paula Gosling, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699458/?page=1 Epidemic malaise] (Dr G J Burke, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699426/ Epidemic malaise] (Dr E J Hopkins, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699416/?page=1 Epidemic malaise] (Dr J F Galpine, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700311/ Epidemic malaise] (Dr D C Poskanzer, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700986/ Epidemic malaise] (Dr J G Parish, [[The BMJ]])
*1978, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425309/pdf/postmedj00263-0019.pdf An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955], Dr Nigel Dean Compston
*1965, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1846496/?page=1 Eclipse of hysteria] (Dr Betty Scott, [[Melvin Ramsay|A. Melvin Ramsay]], [[The BMJ]])
*1965, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847119/?page=1 Hysteria and 'Royal Free Disease'] ([[Melvin Ramsay|A. Melvin Ramsay]], [[The BMJ]])
*1957, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/ An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955], The Medical Staff Of The Royal Free Hospital

==See also==
*[[Epidemic myalgic encephalomyelitis]]
*[[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|List of outbreaks]]
*[[Royal Free Hospital]]
*[[Melvin Ramsay|A. Melvin Ramsay]]
*[[Myalgic Encephalomyelitis]]
*[[Royal Free Disease]]
*[[1948-49 Akureyri outbreak]] (Iceland)

==Learn more==
*[https://dx.doi.org/10.3390%2Fmedicina57010012 Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Organic Disease or Psychosomatic Illness? A Re-Examination of the Royal Free Epidemic of 1955]

==References==
{{Reflist}}

[[Category:History]]
[[Category:Outbreaks]]
[[Category:Outbreaks in the 1950s]]
[[Category:Outbreaks in the United Kingdom]]

1955 Royal Free Hospital outbreak

2022-12-21T06:03:46Z

Davidshq:/* Epidemiology */

[[File:RoyalFreeOld.jpg|right|frame|The building that housed the Royal Free Hospital in 1955 when the outbreak occurred]]
The '''Royal Free Hospital outbreak''' was a [[Epidemic myalgic encephalomyelitis|cluster outbreak]] of [[myalgic encephalomyelitis]] at the [[Royal Free Hospital]] in London.

In 1955, between July and November, 292 members of the medical, nursing, auxiliary medical, ancillary, and administrative staff fell ill, of which 255 were admitted to the hospital.<ref name="RoyalFree1957">{{Cite journal | last = ((The Medical Staff Of The Royal Free Hospital))| first = | date = Oct 19, 1957 | title = An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/|journal=British Medical Journal|volume=2 | pages = 895–904|via=}}</ref> The disease name [[myalgic encephalomyelitis]] was first coined to describe the illness in an editorial in the Lancet, in 1956.<ref name="MyalgicEncephalomyelitis-first-named">{{Cite journal | journal = Lancet|volume=1|issue= | pages = 789–790 | date = 1956 | title = A new clinical entity? | url = https://mecfsj.files.wordpress.com/2019/05/lancet_e383a9e383b3e382bbe38383e383881956_me.pdf}}</ref><ref name="Ramsay1965">{{Cite journal | last = Ramsay | first = A. Melvin | authorlink = Melvin Ramsay | date = 1965-10-30 | title = Hysteria and “Royal Free Disease.” | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847119/|journal=British Medical Journal|volume=2|issue=5469 | pages = 1062|doi=|issn=0007-1447|pmc=1847119|pmid=|access-date=|quote=|via=}}</ref>
==Location==
The outbreak occurred at the [[Royal Free Hospital]], then situated at 256 Grays Inn Road, London, [[England]], which is now the Eastman Dental Hospital.<ref name="Ramsay56">{{Cite journal | last = Ramsay | first = A. Melvin | authorlink = Melvin Ramsay | last2 = O'Sullivan | first2 = E | date = May 26, 1956 | title = Encephalomyelitis simulating poliomyelitis |url =https://www.sciencedirect.com/science/article/pii/S0033350657800225|journal=The Lancet|volume=270 | pages = 761-764|via=}}</ref> (The current Royal Free Hospital site is now in the Hampstead area of London.)

== Onset ==

Onset involved symptoms of an [[upper respiratory infection]], [[sore throat]], [[Gastrointestinal system|gastrointestinal]] disturbances including [[nausea]] and [[vomiting]], or acute [[vertigo]].<ref name="Ramsay1978">{{Cite journal | last = Ramsay | first = A. Melvin | date = November 1978 | title = 'Epidemic neuromyasthenia' 1955-1978 | url = https://www.ncbi.nlm.nih.gov/pubmed/746017|journal=Postgraduate Medical Journal|volume=54 | pages = 718-721|via=}}</ref>

== Symptoms ==
Symptoms included:
<div style="column-count:2">
* Severe [[headache]]
* [[Malaise]]
* Lassitude
* [[Vertigo]]
* Pain in limbs
* [[Nausea]]
* [[Dizziness]]
* [[Neck stiffness]], [[neck pain]]
* [[lower back pain|Pain in back]]
* [[Myalgia]], which in some patients caused them to cry out in [[pain]], [[muscle weakness]], [[muscle cramps|cramps]], [[muscle fasciculations|twitching]]
* [[Depression]]
* [[Abdominal pain]]
* [[Vomiting]]
* [[Double vision|Diplopia]] (double vision)
* [[Tinnitus]]
* [[Diarrhea]]
* [[Swollen lymph nodes]]
* [[Paraesthesia]]<ref name="Ramsay1978" />
</div>

Usually by the second or third week of the disease, there was objective evidence of involvement of the [[central nervous system]] which appeared to be characteristic of the outbreak.

== Signs ==

* [[Low-grade fever]] (tended to transiently occur with relapse of symptoms)
* Swollen lymph nodes
* Objective sensory impairment and muscle tenderness
* Extensor plantar responses
* [[Nystagmus]]
* [[Double vision|Diplopia]]

== Findings ==

* Inconsistent or normal [[cerebrospinal fluid]]<ref name="Ramsay56" /><ref name="Underhill2021" />
* [[Electromyogram]]s showed abnormalities of activity, but no evidence of lower [[motor neuron]] degeneration<ref name="Ramsay56" /> (12 of 25 abnormal).<ref name="Ramsay1978" />
* non-specific [[EEG]] abnormalities<ref name="Ramsay56" />
* [[Neutropenia]] and abnormal [[lymphocyte]]s,<ref name="Compston">{{Cite journal | last = Compston | first = N.D. | date = 1978 | title = An outbreak of encephalomyelitis in the Royal Free Hospital Group, London, in 1955 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425309|journal=Postgraduate Medical Journal|volume=54 | pages = 722-724|via=}}</ref><ref name="Ramsay56" /><ref name="Underhill2021" /> consistent with a viral infection
* normal or slightly elevated [[erythrocyte sedimentation rate]]<ref name="Ramsay1978" />
* negative virology<ref name="Ramsay56" />
* abnormally high [[lactic dehydrogenase]] and [[glutamic oxaloacetic transaminase]]<ref name="Ramsay1978" />

"Evidence of involvement of the sympathetic nervous system or actual [[Hypothalamus|hypothalamic]] damage was to be found in most cases. This often took the form of [[orthostatic tachycardia]] chilliness of the extremities with increased [[Body temperature|sensitivity to cold]], circulatory impairment and hypothermia."<ref name="Ramsay1978" />

==Epidemiology==
Between July 13, 1955 and November 24, 1955, 292 people, of whom the vast majority were hospital personnel, became ill. Personnel from the medical, nursing, auxiliary medical, ancillary, and administrative departments were affected. Of these two hundred fifty-five were admitted to the hospital.<ref name="Compston" /> Despite the hospital census being near capacity, only 12 patients were afflicted.<ref name="Ramsay1984">{{Cite book | last = Ramsay | first = A. Melvin | authorlink = Melvin Ramsay | title = Post-viral fatigue: The saga of the Royal Free Disease | date = 1984| publisher = Gower|location=London|isbn=978-0906923962| title-link = Myalgic Encephalomyelitis and Postviral Fatigue States: The Saga of Royal Free Disease}}</ref>

By October 5, 1955, the hospital had to close to new admissions to contain the outbreak and because of the shortage of unaffected staff.<ref name="Underhill2021" /> The first to report ill were a resident doctor and a ward sister.<ref name="Dawson1988">{{Cite journal | last = Dawson | first = J | date = Feb 7, 1987 | title = Royal Free disease: perplexity continues|journal=British Medical Journal (Clinical Research Ed.)|volume=294|issue =6568 | pages = 327–328 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1245346/pdf/bmjcred00006-0005.pdf | pmc=PMC1245346|doi= 10.1136/bmj.294.6568.327}}</ref> More females became ill than males, but at the time it was believed to be because of the staff's living quarters not gender, as more females than males resided at the facility.<ref name="Compston" />

Similar cases had occurred in the population of North West London before this outbreak and sporadic cases continued to occur after the outbreak.<ref name="Ramsay56" />

== Prognosis ==
For many patients, symptoms waxed and waned in intensity over a long period. A very large majority had complete recovery of neurological function.

==Long-term follow-up==

A follow-up study 65 years later found that there was one group of patients that recovered completely or nearly completely, a second group that recovered but was subject to relapses, and a third that showed little or no recovery, these patients remaining incapacitated.<ref name="Ramsay1978" />

Another follow-up study in 2021 interviewed former hospital staff who were present during the outbreak, and reported on their recollection of patient symptoms and circumstances at the time. Twenty-seven former hospital staff were, including a few who developed ME. The accounts of the former staff were found to be inconsistent with the McEvedy and Beard hypothesis that the illness was [[psychosomatic illness|psychosomatic]] in nature, caused by [[mass hysteria]] or psychoneurosis. Observable signs of physical illness reported by the former staff included enlarged posterior cervical glands, ptosis (drooping of the eyelids), hemiparesis (one-sided paralysis), some patients crying due to extreme [[muscle pain]], nausea, and vomiting. Patients typically delayed seeking medical treatment for the first few days, which is also inconsistent with patients overly anxious about the possibility of contracting an illness. Some patients had blood tests which found leukopenia, or lymphocytes typical of [[virus]]es. While some patients seemed to be neurotic and lacked physical signs, a large number of patients were seriously ill with significant physical signs, leading to most hospital staff at the time believing that the cause of illness was an [[infection|infectious disease]]. Some patients remained hospitalized for over six months.<ref name="Underhill2021" />

Five patients developed long-term [[paralysis]] in a part of their body.<ref name="Underhill2021" />

==Notable studies and publications==
*2021, [https://dx.doi.org/10.3390%2Fmedicina57010012 Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Organic Disease or Psychosomatic Illness? A Re-Examination of the Royal Free Epidemic of 1955]<ref name="Underhill2021">{{Cite journal | last = Underhill | first = Rosemary | authorlink = Rosemary Underhill | last2 = Baillod | first2 = Rosemarie | authorlink2 = Rosemarie Baillod | date = Jan 2021 | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Organic Disease or Psychosomatic Illness? A Re-Examination of the Royal Free Epidemic of 1955 | url = https://www.mdpi.com/1648-9144/57/1/12|journal=Medicina|language=en|volume=57|issue=1 | pages = 12|doi=10.3390/medicina57010012|pmc=PMC7824095|pmid=33375343|access-date=|quote=|via=}}</ref>
*2020, [https://www.tandfonline.com/doi/full/10.1080/21641846.2020.1793058 Myalgic Encephalomyelitis (ME) outbreaks can be modelled as an infectious disease: a mathematical reconsideration of the Royal Free Epidemic of 1955]<ref name="Waters2020">{{Cite journal | last = Waters | first = F.G. |last2 = McDonald | first2 = G.J. | last3 = Banks | first3 = S. | last4 = Waters | first4 = R.A. | date = 2020-04-02 | title = Myalgic Encephalomyelitis (ME) outbreaks can be modelled as an infectious disease: a mathematical reconsideration of the Royal Free Epidemic of 1955 | url = https://www.tandfonline.com/doi/full/10.1080/21641846.2020.1793058|journal = Fatigue: Biomedicine, Health & Behavior |language=en|volume=8|issue=2 | pages = 70–83|doi=10.1080/21641846.2020.1793058|issn=2164-1846}}</ref>
*2016, [http://www.theguardian.com/lifeandstyle/2016/apr/04/chronic-fatigue-syndrome-cfs-taken-seriously#comment-71789644 Is chronic fatigue syndrome finally being taken seriously?]
*1987, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1245346/?page=1 Royal Free disease: perplexity continues]
*1984, [[Myalgic Encephalomyelitis and Postviral Fatigue States: The Saga of Royal Free Disease]], A. Melvin Ramsay, Gower Medical Publishing, London (book)
*1978, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1604957/pdf/brmedj00128-0006b.pdf Epidemic myalgic encephalomyelitis] ([[The BMJ]])
*1978, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425324/ Epidemic neuromyasthenia 1955-1978] ([[Melvin Ramsay|A. Melvin Ramsay]], [[The BMJ]])
*1977, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1607215/?page=1 Icelandic disease (benign myalgic encephalomyelitis or Royal Free disease)] ([[Melvin Ramsay|A. Melvin Ramsay]], [[Elizabeth Dowsett]], J V Dadswell, W H Lyle, and J G Parish, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699088/?page=1 Epidemic malaise] (Dr Betty Scott, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699022/?page=1 Epidemic malaise] (Dr Nigel Dean Compston, H. E. Dimsdale, [[Melvin Ramsay|A. Melvin Ramsay]], and A. T. Richardson, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1698971/?page=1 Epidemic malaise] (Dr E D Acheson, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699452/ Epidemic malaise] (Dr Paula Gosling, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699458/?page=1 Epidemic malaise] (Dr G J Burke, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699426/ Epidemic malaise] (Dr E J Hopkins, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1699416/?page=1 Epidemic malaise] (Dr J F Galpine, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700311/ Epidemic malaise] (Dr D C Poskanzer, [[The BMJ]])
*1970, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700986/ Epidemic malaise] (Dr J G Parish, [[The BMJ]])
*1978, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425309/pdf/postmedj00263-0019.pdf An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955], Dr Nigel Dean Compston
*1965, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1846496/?page=1 Eclipse of hysteria] (Dr Betty Scott, [[Melvin Ramsay|A. Melvin Ramsay]], [[The BMJ]])
*1965, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847119/?page=1 Hysteria and 'Royal Free Disease'] ([[Melvin Ramsay|A. Melvin Ramsay]], [[The BMJ]])
*1957, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/ An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955], The Medical Staff Of The Royal Free Hospital

==See also==
*[[Epidemic myalgic encephalomyelitis]]
*[[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|List of outbreaks]]
*[[Royal Free Hospital]]
*[[Melvin Ramsay|A. Melvin Ramsay]]
*[[Myalgic Encephalomyelitis]]
*[[Royal Free Disease]]
*[[1948-49 Akureyri outbreak]] (Iceland)

==Learn more==
*[https://dx.doi.org/10.3390%2Fmedicina57010012 Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Organic Disease or Psychosomatic Illness? A Re-Examination of the Royal Free Epidemic of 1955]

==References==
{{Reflist}}

[[Category:History]]
[[Category:Outbreaks]]
[[Category:Outbreaks in the 1950s]]
[[Category:Outbreaks in the United Kingdom]]

Mitochondrion

2022-12-21T00:37:34Z

Davidshq:/* Infection and immunity */

[[File:Mitochondrion.png|frame|A single mitochondrion|alt=A single mitochondrion, with exterior and interior membranes.]]A '''mitochondrion''' (plural: mitochondria) is an organelle found in all cells that have a nucleus. In the human body, that would be all cells except red blood cells. Mitochondria generate most of a cell's energy by manufacturing [[adenosine triphosphate]], ATP. Mitochondria have their own independent genome called [[mitochondrial DNA]].

==Biogenesis==

[[Mitochondrial biogenesis]] (the creation of new mitochondria) can be increased via [[hormesis]], the exposure of the body to short-term stressors. Healthy stressors include [[exercise]], [[fasting]], [[cryotherapy|cold]], [[thermotherapy|heat]] and light. [[Resveratrol]] may also increase mitochondrial biogenesis.

==Infection and immunity==

Mitochondria play a crucial role in [[innate immune system|innate immunity]], namely through their induction of [[interferon]] production and apoptosis through [[mitochondrial antiviral signaling protein]] (MAVS).<ref>{{Cite journal|url=http://jvi.asm.org/content/84/5/2421.short | title = The Interferon Stimulator Mitochondrial Antiviral Signaling Protein Facilitates Cell Death by Disrupting the Mitochondrial Membrane Potential and by Activating Caspases | last = Yu | first = Chia-Yi | date = December 2009|journal=Journal of Virology|volume=|pages=|via=}}</ref> Many viruses, including [[Coxsackievirus B3]], [[echovirus]] 7, and [[enterovirus]] 71 inhibit interferon induction and evade host immunity by cleaving or downregulating MAVS.<ref>{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pubmed/21436888?dopt=Abstract | title = The coxsackievirus B 3C protease cleaves MAVS and TRIF to attenuate host type I interferon and apoptotic signaling | last = Mukherjee | first = A | date = March 2011|journal=PLoS Pathology|volume=7|pages=|via=}}</ref>

[[Herpes simplex virus]] (HSV-1),<ref name=":0">{{Cite journal | last = Derakhshan | first = Mohammed | date = August 1, 2006 | title = Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport|url=http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.81949-0|journal=Journal of General Virology|volume=87|pages=2155-2159|via=}}</ref> influenza virus,<ref name=":0" /> and poliovirus<ref>{{Cite journal | last = Koundouris | first = A | date = May 2000 | title = Poliovirus Induces an Early Impairment of Mitochondrial Function by Inhibiting Succinate Dehydrogenase Activity|url=https://www.ncbi.nlm.nih.gov/pubmed/10814509|journal=Biochemical and Biophysical Research Communications|volume=271 | pages = 610-4|via=}}</ref> have all been found to reduce [[cellular respiration]]. Hepatitis C reduces [[aerobic metabolism]] and upregulates [[glycolysis]].<ref>{{Cite journal | last = Ripoli | first = Maria | date = October 2009 | title = Hepatitis C Virus-Linked Mitochondrial Dysfunction Promotes Hypoxia-Inducible Factor 1α-Mediated Glycolytic Adaptation | url =http://jvi.asm.org/content/84/1/647.short|journal=Journal of Virology|volume=|pages=|via=}}</ref>

== In human disease ==

Infection with pathogens, including viruses, bacteria, and parasites, can all induce changes in mitochondrial function and energy metabolism.

Viruses can induce or inhibit mitochondrial processes in order to replicate. "Viruses like [[Herpes simplex virus]] 1 deplete the host mitochondrial DNA and some, like human immunodeficiency virus and Hepatitis C Virus, hijack the host mitochondrial proteins to function fully inside the host cell."<ref>{{Cite journal | last = Anand | first = Sanjeev K. | last2 = Tikoo | first2 = Suresh K.| date = 2013 | title = Viruses as Modulators of Mitochondrial Functions|url=http://www.hindawi.com/journals/av/2013/738794/|journal=Advances in Virology|language=en|volume=|pages=1–17|doi=10.1155/2013/738794|issn=1687-8639}}</ref><ref>{{Cite journal | last = Siu | first = Gavin Ka Yu|author-link= | last2 = Zhou | first2 = Fan | authorlink2 = |last3 = Yu | first3 = Mei Kuen | authorlink3 = | last4 = Zhang | first4 = Leiliang | authorlink4 = | last5 = Wang | first5 = Tuanlao | authorlink5 = | last6 = Liang | first6 = Yongheng | authorlink6 = | last7 = Chen | first7 = Yangchao | last8 = Chan | first8 = Hsiao Chang | last9 = Yu | first9 = Sidney | date = Mar 2016 | title = Hepatitis C virus NS5A protein cooperates with phosphatidylinositol 4-kinase IIIα to induce mitochondrial fragmentation | url =http://www.nature.com/articles/srep23464|journal=Scientific Reports|language=en|volume=6|issue=1|pages=23464|doi=10.1038/srep23464|issn=2045-2322|pmc=4806301|pmid=27010100|access-date=|quote=|via=}}</ref> [[Hepatitis C]] has also been shown to "fragment host mitochondria".<ref>{{Cite journal | last = Siu | first = Gavin Ka Yu|author-link= | last2 = Zhou | first2 = Fan | authorlink2 = |last3 = Yu | first3 = Mei Kuen | authorlink3 = | last4 = Zhang | first4 = Leiliang | authorlink4 = | last5 = Wang | first5 = Tuanlao | authorlink5 = | last6 = Liang | first6 = Yongheng | authorlink6 = | last7 = Chen | first7 = Yangchao | last8 = Chan | first8 = Hsiao Chang | last9 = Yu | first9 = Sidney | date = Mar 2016 | title = Hepatitis C virus NS5A protein cooperates with phosphatidylinositol 4-kinase IIIα to induce mitochondrial fragmentation | url =http://www.nature.com/articles/srep23464|journal=Scientific Reports|language=en|volume=6|issue=1|pages=23464|doi=10.1038/srep23464|issn=2045-2322|pmc=4806301|pmid=27010100|access-date=|quote=|via=}}</ref>

Parasites such as [[toxoplasma gondii]] have also been shown to modulate host energy metabolism and dysregulate mitochondrial function,<ref name="Saric2009" /> as have bacteria<ref name="Rudel2010" /> such as [[E. coli]] (''Escherichia coli''), which has been shown to modulate mitochondrial receptor function.<ref name="Nagai2005" />

Mitochondrial diseases have a high prevalence of [[fatigue]] and debilitation, with the severity of disease predicting the level of fatigue; Gorman et al (2015) found the degree of [[Paresis|muscle weakness]] was not related to fatigue severity.<ref name="Gorman2015">{{Cite journal | last = Gorman | first = Grainne S. | authorlinklink=Grainne Gorman | last2 = Elson | first2=Joanna L.|authorlink2 = Joanna Elson|last3 = Newman | first3 = Jane | authorlink3 = Jane Newman | last4 = Payne | first4=Brendan | authorlink4 = Brendan Payne | last5 = McFarland | first5 = Bobby | authorlink5 = Bobby McFarland | last6 = Newton | first6 = Julia L. | authorlink6 = Julia Newton | last7 = Turnbull | first7 = Doug M. | authorlink7 = Doug Turnbull | date = 2015 | title=Perceived fatigue is highly prevalent and debilitating in patients with mitochondrial disease|url=https://eprint.ncl.ac.uk/pub_details2.aspx?pub_id=214073|journal=Neuromuscular Disorders|language=en|volume=25|issue=7 | pages = 563-566|doi=10.1016/j.nmd.2015.03.001|quote=|via=}}</ref>

===<span id="dysfunction">ME/CFS</span>===

There is increasing evidence of '''mitochondrial dysfunction''' in [[myalgic encephalomyelitis]]/[[chronic fatigue syndrome]] patients.<ref name="Sweetman2020" /> [[Muscle biopsy|Muscle biopsies]] have shown evidence of mitochondrial degeneration,<ref name="Behan1991" /> deletions of mitochondrial DNA,<ref name="Vecchiet1996" /><ref name="ZhangC1995" /> the reduction of mitochondrial activity,<ref name="Vecchiet1996" /> and [[Sarah Myhill]] found measurable mitochondrial dysfunction correlating with severity of illness.<ref name="Booth2012" /><ref name="Myhill2009" /> Myhill also produced improvement by targeting those dysfunctions.<ref name="Myhill2013" /> Mitochondrial DNA variants correlate with symptoms, symptom clusters & symptom severity.<ref name="BillingRoss2016" />
[[File:ME-CFS mitochondrion differences.jpg|alt=Complex diagram of labeling proteins found to be different in ME/CFS |thumb|'''Differences in protein expression in ME/CFS including proteins related to mitochondria'''<br />Green arrows show increases and red arrows show decreases.<ref name="Sweetman2020" /><br />Source: [https://doi.org/10.1186/s12967-020-02533-3 Journal of Translational Medicine 18(1):365] Sweetman et al. 2020.
doi: 10.1186/s12967-020-02533-3. PMC7512220.]]
A small study by Sweetman et al. (2020) found a large number of proteins were over or under expressed in ME/CFS patients compared to controls, with many of those proteins known to be involved in mitochondrial function, [[oxidative phosphorylation]], [[ion transportation|electron transport]] chain complexes, and redox regulation. The study supported the model of deficient ATP production in ME/CFS, and also suggesting increased oxidative stress.<ref name="Sweetman2020" />

[[Mitochondrial disorder]]s can be mistaken for chronic fatigue syndrome.<ref name="Galán2015" />

There is evidence of genetic risk factors for mitochondrial dysfunction in related diseases such as complex regional pain syndrome, [[postural orthostatic tachycardia syndrome]] (POTS), and [[dysautonomia]].<ref name="Boles2015" />

A small study of 20 ME/CFS patients meeting the [[Canadian Consensus Criteria]] found that re-activation of [[Human herpesvirus 6|Human Herpesvirus-6]] caused mitochondria dysfunction and reduced the ATP content of cells.<ref name="Schreiner2020" />

==Notable studies==
* 1991, Mitochondrial abnormalities in the postviral fatigue syndrome<ref name="Behan1991">{{citation | last1 = Behan | first1 = WMH| authorlink1 = Wilhelmina Behan | last2 = More | first2 = IAR| authorlink2 = IAR More | last3 = Behan| first3 = PO | authorlink3 = Peter Behan | title = Mitochondrial abnormalities in the postviral fatigue syndrome | journal = Acta Neuropathologica | volume = 83| issue = 1| pages = 61–65 | date = 1991 | pmid = 1792865 | url = http://www.ncbi.nlm.nih.gov/pubmed/1792865/ }}</ref>
*1995, Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome <ref name="ZhangC1995">{{citation | last1 = Zhang | first1 = C | last2 = Baumer | first2 = A | last3 = Mackay | first3 = IR | last4 = Linnane | first4 = AW | last5 = Nagley | first5 = P
| title = Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome | journal = Human Molecular Genetics | volume = 4| issue = 4| pages = 751–754 | date = Apr 1995 | pmid = 7633428 | url = http://www.ncbi.nlm.nih.gov/pubmed/7633428 }}</ref>
*1996, Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome<ref name="Vecchiet1996">{{citation | last1 = Vecchiet | first1 = L | last2 = Montanari | first2 = G | last3 = Pizzigallo | first3 = E | last4 = Iezzi | first4 = S | last5 = de Bigontina | first5 = P | last6 = Dragani | first6 = L | last7 = Vecchiet | first7 = J | last8 = Giamberardino | first8 = MA
| title = Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome | journal = Neuroscience Letters | volume = 208| issue = 2| pages = 117–120 | date = 19 Apr 1996 | pmid = 8859904 | url = http://www.ncbi.nlm.nih.gov/pubmed/8859904 }}</ref>
* 1997, [https://www.ncbi.nlm.nih.gov/pubmed/9149090 Chronic fatigue syndrome and skeletal muscle mitochondrial function]<ref name="Lodi1997">{{Cite journal | last = Lodi | first = R. | last2 = Taylor | first2= D.J. | last3 = Radda | first3=G.K. | date = 1997 | title=Chronic fatigue syndrome and skeletal muscle mitochondrial function | url =https://www.ncbi.nlm.nih.gov/pubmed/9149090|journal=Muscle & Nerve|volume=20|issue=6 | pages = 765–766|issn=0148-639X|pmid=9149090|via=}}</ref>
* 2005, Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for bacterial pathogenesis: critical role of the 16th leucine residue in EspF<ref name="Nagai2005">{{Citation | last1 = Nagai | first1 = T | authorlink1 = T Nagai | last2 = Abe | first2 = A | authorlink2 = A Abe | last3 = Sasakawa | first3 = C | authorlink3 = C Sasakawa
| display-authors = | title = Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for bacterial pathogenesis: critical role of the 16th leucine residue in EspF | journal = J Bio. Chem. | volume = | issue = | page = | date = January 2005 | pmid = 15533930
| doi = 10.1074/jbc.M411550200 }}</ref>
*2009, Chronic fatigue syndrome and mitochondrial dysfunction<ref name="Myhill2009">{{citation | last1 = Myhill | first1 = S | authorlink1 = Sarah Myhill | last2 = Booth | first2 = NE | authorlink2 = Norman Booth | last3 = McLaren-Howard | first3 = J | authorlink3 = John McLaren-Howard | title = Chronic fatigue syndrome and mitochondrial dysfunction | journal = Int J Clin Exp Med | volume = 2| issue = 1| pages = 1–16 | date = 15 Jan 2009 | pmid = 19436827 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680051/ }}</ref>
*2009, Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents<ref name="Saric2009">{{citation | last1 = Saric | first1 = J | last2 = Li | first2 = JV | last3 = Swann| first3 = JR | last4 = Utzinger | first4 = J | last5 = Calvert | first5 = G
| title = Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents | journal = Journal of proteome research | volume = 9| pages = 2255-2264 | date = 8 Nov 2010 |pmid = | url = https://doi.org/10.1021/pr901019z }}</ref>
*2009, Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder<ref name="Maes2009">{{Citation | last1 = Maes | first1 = M| authorlink1 = Michael Maes | last2 = Mihaylova | first2 = I| authorlink2 = Ivanka Mihaylova | last3 = Kubera | first3 = M| authorlink3 = Marta Kubera | last4 = Uytterhoeven | first4 = M| authorlink4 = Marc Uytterhoeven | last5 = Vrydags | first5 = N| authorlink5 = Nicholas Vrydags | last6 = Bosmans | first6 = E| authorlink6 = Eugene Bosmans
| display-authors = | title = Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder | journal = Neuro Endocrinol Lett. | volume = | issue = | page = | date = 2009 | pmid = 20010505
| doi = }}</ref>
*2010, Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity<ref name="Vermeulen2010">{{Citation | last1 = Vermeulen | first1 = RC| authorlink1 = RC Vermeulen | last2 = Kirk | first2 = RM| authorlink2 = RM Kirk | last3 = Visser | first3 = FC| authorlink3 = FC Visser | last4 = Sluiter | first4 = W | authorlink4 = W Sluiter | last5 = Scholte | first5 = HR| authorlink5 = HR Scholte
| display-authors = | title = Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity | journal = Journal of Translational Medicine | volume = | issue = | page = | date = October 2010 | pmid = 20937116
| doi = 10.1186/1479-5876-8-93 }}</ref>
* 2010, Interactions between bacterial pathogens and mitochondrial cell death pathways<ref name="Rudel2010">{{Citation | last1 = Rudel T | first1 = T | authorlink1 = T Rudel | last2 = Kepp O | first2 = O | authorlink2 = O Kepp | last3 = Kozjak-Pavlovic V | first3 = V | authorlink3 = V Kozjak-Pavlovic
| display-authors = | title = Interactions between bacterial pathogens and mitochondrial cell death pathways | journal = Nat Rev Microbiol. | volume = | issue = | page = | date = October 2010 | pmid = 20818415
| doi = 10.1038/nrmicro2421 }}</ref>
*2012, Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref name="Booth2012">{{citation | last1 = Booth | first1 = NE | authorlink1 = Norman Booth | last2 = Myhill | first2 = S | authorlink2 = Sarah Myhill | last3 = McLaren-Howard | first3 = J | authorlink3 = John McLaren-Howard | title = Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | journal = Int J Clin Exp Med | volume = 5| issue = 3| pages = 208–220 | date = 2012 | pmid = 22837795 | url = http://www.ncbi.nlm.nih.gov/pubmed/22837795 }}</ref>
*2013, Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit<ref name="Myhill2013">{{Citation | last1 = Myhill | first1 = Sarah | authorlink1 = Sarah Myhill | last2 = Booth | first2 = Norman E| authorlink2 = Norman Booth | last3 = McLaren-Howard | first3 = John | authorlink3 = John McLaren-Howard
| display-authors = | title = Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit. | journal = International Journal of Clinical and Experimental Medicine | volume = | issue = | page = | date = 2013 | pmid = 23236553
| doi = | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515971/ }}</ref>
*2013, Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics.<ref name="Morris2013">{{Citation | last1 = Morris | first1 = G | authorlink1 = Gerwyn Morris | last2 = Maes | first2 = M | authorlink2 = Michael Maes
| display-authors = | title = Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. | journal = BMC Med | volume = | issue = | page = | date = September 2013 | pmid = 24229326
| doi = 10.1186/1741-7015-11-205 }}</ref>
*2013, [http://www.hindawi.com/journals/av/2013/738794/abs/ Viruses as Modulators of Mitochondrial Functions]<ref name="Anand2013">{{citation | last1 = Anand | first1 = Sanjeev K | authorlink1 = Sanjeev Anand | last2 = Tikoo | first2 = Suresh K | authorlink2 = Suresh Tikoo | title = Viruses as Modulators of Mitochondrial Functions | journal = Advances in Virology, Advances in Virology | volume = 2013| pages = 738794 | date = 2013-10-24
| doi = 10.1155/2013/738794 | url = http://www.hindawi.com/journals/av/2013/738794/abs/ }}</ref>
* 2013, The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets?<ref name="Meeus2013">{{Citation | last1 = Meeus | first1 = M | authorlink1 = Mira Meeus | last2 = Nijs | first2 = J | authorlink2 = Jo Nijs | last3 = Hermans | first3 = L | authorlink3 = | last4 = Goubert | first4 = D | authorlink4 = | last5 = Calders | first5 = P | authorlink5 = | display-authors = | title = The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets? | journal = Expert Opin Ther Targets | volume = | issue = | page = | date = September 2013 | pmid = 23834645 | doi = 10.1517/14728222.2013.818657 }}</ref>
* 2014, Metabolism in chronic fatigue syndrome<ref name="Armstrong2014">{{Citation | last1 = Armstrong | first1 = CW | authorlink1 = Christopher Armstrong | last2 = McGregor | first2 = NR | authorlink2 = Neil McGregor | last3 = Butt | first3 = HL | authorlink3 = Henry Butt | last4 = Gooley | first4 = PR | authorlink4 = Paul Gooley
| display-authors = | title = Metabolism in chronic fatigue syndrome | journal = Adv Clin Chem | volume = 66 | issue = | page = 121-72 | date = Oct 2014 | pmid = 25344988
| doi = 10.1016/B978-0-12-801401-1.00005-0 | url = http://www.academia.edu/11578244/CHAPTER_FIVE_Metabolism_in_Chronic_Fatigue_Syndrome }}</ref>
*2014, Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways<ref name="Morris2014">{{Citation | last1 = Morris | first1 = Gerwyn | authorlink1 = Gerwyn Morris | last2 = Maes | first2 = Michael| authorlink2 = Michael Maes
| display-authors = | title = Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways | journal = Metab Brain Dis. | volume = | issue = | page = | date = March 2014 | pmid = 24557875
| doi = 10.1007/s11011-013-9435-x }}</ref>
*2015, Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Caloric restriction, fasting, and ketogenic diets<ref name="Craig2015">{{citation | last1 = Craig | first1 = Courtney | authorlink1 = Courtney Craig | title = Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Caloric restriction, fasting, and ketogenic diets | journal = Medical Hypotheses | volume = 85 | issue = 5 | page = 690-693 | date = Nov 2015 | pmid = 26315446
| doi = 10.1016/j.mehy.2015.08.013 | url = http://www.medical-hypotheses.com/article/S0306-9877(15)00318-7/abstract }}</ref>
*2015, Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome<ref name="Galán2015">{{citation | last1 = Galán | first1 = Fernando | authorlink1 = Galán Fernando | last2 = de Lavera | first2 = Isabel | authorlink2 = Isabel de Lavera | last3 = Cotán| first3 = David | authorlink3 = David Cotán | last4 = Sánchez-Alcázar | first4 = José A | authorlink4 = Sánchez-Alcázae | title = Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome | journal = J Investig Med High Impact Case Rep | volume = 3| issue = 3 | date = 24 Sep 2015 | pmid = 26904705
| doi = 10.1177/2324709615607908 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748504/ }}</ref>
*2015, Increased prevalence of two mitochondrial DNA polymorphisms in functional disease: Are we describing different parts of an energy-depleted elephant?<ref name="Boles2015">{{citation | last1 = Boles | first1 = RG | authorlink1 = Richard Boles | last2 = Zaki | first2 = EA | authorlink2 = Essam Zaki | last3 = Kerr | first3 = JR | authorlink3 = Jonathan Kerr | last4 = Das | first4 = K | authorlink4 = Kingshuk Das | last5 = Biswas | first5 = S | authorlink5 = Sawona Biswas | last6 = Gardner | first6 = A | authorlink6 = Ann Gardner
| title = Increased prevalence of two mitochondrial DNA polymorphisms in functional disease: Are we describing different parts of an energy-depleted elephant? | journal = Mitochondrion | volume = 23 | page = 1-6 | date = Jul 2015 | pmid = 25934187 | doi = 10.1016/j.mito.2015.04.005 | url = http://www.sciencedirect.com/science/article/pii/S1567724915000483 }}</ref>
* 2015, [https://www.researchgate.net/profile/Neil_Mcgregor/publication/277979239_Metabolic_profiling_reveals_anomalous_energy_metabolism_and_oxidative_stress_pathways_in_chronic_fatigue_syndrome_patients/links/55aecf4408ae98e661a6f1eb/Metabolic-profiling-reveals-anomalous-energy-metabolism-and-oxidative-stress-pathways-in-chronic-fatigue-syndrome-patients.pdf Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients]<ref name="Armstrong2015">{{Cite journal|url= https://www.researchgate.net/profile/Neil_Mcgregor/publication/277979239_Metabolic_profiling_reveals_anomalous_energy_metabolism_and_oxidative_stress_pathways_in_chronic_fatigue_syndrome_patients/links/55aecf4408ae98e661a6f1eb/Metabolic-profiling-reveals-anomalous-energy-metabolism-and-oxidative-stress-pathways-in-chronic-fatigue-syndrome-patients.pdf | title = Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients | last = Armstrong | first = Christopher W. | authorlinklink=Christopher Armstrong | last2 = McGregor | first2 = Neil R.|authorlink2 = Neil McGregor | date = May 22, 2015|journal= Metabolomics|volume=11|pages =1626–1639|access-date=|last3 = Lewis | first3=Donald P. | authorlinklink3 =Donald P Lewis | last4 = Butt | first4=Henry L. | last5 = Gooley | first5 = Paul R.}}</ref>
* 2016, Hepatitis C virus NS5A protein cooperates with phosphatidylinositol 4-kinase IIIα to induce mitochondrial fragmentation<ref name="Siu2016">{{Citation | last1 = Siu | first1 = GK| authorlink1 = GK Siu | last2 = Zhou | first2 = F | authorlink2 = F Zhou | last3 = Yu | first3 = MK| authorlink3 = MK Yu | last4 = Zhang | first4 = L | authorlink4 = L Zhang | last5 = Wang | first5 = T | authorlink5 = T Wang | last6 = Liang | first6 = Y | authorlink6 = Y Liang | last7 = Chen | first7 = Y | authorlink7 = Y Chen | last8 =Chan | first8 = HC| authorlink8 = HC Chan | last9 = Yu | first9 = S | authorlink9 = S Yu
| display-authors = | title = Hepatitis C virus NS5A protein cooperates with phosphatidylinositol 4-kinase IIIα to induce mitochondrial fragmentation | journal = Sci. Rep. | volume = | issue = | page = | date = March 2016 | pmid = 27010100
| doi = 10.1038/srep23464 }}</ref>
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27389587 Exercise-induced mitochondrial dysfunction: a myth or reality?]<ref name="Ostojic2016">{{Cite journal | last = Ostojic | first = Sergej M. | date = Aug 1, 2016 | title = Exercise-induced mitochondrial dysfunction: a myth or reality?|url=https://www.ncbi.nlm.nih.gov/pubmed/27389587|journal=Clinical Science (Lond.)|volume=130|issue=16|pages=1407–1416|doi=10.1042/CS20160200|issn=1470-8736|pmid=27389587|via=}}</ref>
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/25788480 Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I-Mutant Fibroblasts]<ref name="Felici2016">{{Cite journal | last = Felici | first = Roberta | last2 = Lapucci | first2 = Andrea|last3 = Cavone | first3 = Leonardo | last4 = Pratesi | first4 = Sara | last5 = Berlinguer-Palmini | first5 = Rolando | last6 = Chiarugi | first6 = Alberto | date = 2015 | title=Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I-Mutant Fibroblasts|url=https://www.ncbi.nlm.nih.gov/pubmed/25788480|journal=Molecular Pharmacology|volume=87|issue=6 | pages = 965–971|doi=10.1124/mol.114.097204|issn=1521-0111|pmid=25788480|via=}}</ref>
*2016, Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome<ref name="BillingRoss2016">{{citation | last1 = Billing-Ross | first1 = Paul | authorlink1 = Paul Billing-Ross | last2 = Germain | first2 = Arnaud | authorlink2 = Arnaud Germain | last3 = Ye | first3 = Kaixiong | authorlink3 = Kaixiong Ye | last4 = Keinan | first4 = Alon | authorlink4 = Alon Keinan | last5 = Gu | first5 = Zhenglong | authorlink5 = Zhenglong Gu | last6 = Hanson | first6 = Maureen R | authorlink6 = Maureen Hanson
| title = Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome | journal = Journal of Translational Medicine| issn = 1479-5876| volume = 14| pages = 19 | date = 2016 | pmid = 26791940 | doi = 10.1186/s12967-016-0771-6 | url = http://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-0771-6
| lay-url = http://hansonlab.org/research/cfs_me/mitochondria/ }}</ref>
*2018, [https://www.nature.com/articles/s41586-018-0448-9 Parkin and PINK1 mitigate STING-induced inflammation]<ref name="Sliter2018">{{Cite journal | last = Sliter | first = Danielle A. | last2 = Martinez | first2 = Jennifer | last3 = Hao | first3 = Ling | last4 = Chen | first4=Xi | last5 = Sun | first5 = Nuo | last6 = Fischer | first6 = Tara D. | last7 = Burman | first7 = Jonathon L. | last8 = Li | first8 = Yan | last9 = Zhang | first9 = Zhe | date = 2018-08-22 | title = Parkin and PINK1 mitigate STING-induced inflammation | url =https://www.nature.com/articles/s41586-018-0448-9|journal=Nature|language=en|doi=10.1038/s41586-018-0448-9|issn=0028-0836}}</ref>
*2020, Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Schreiner2020">{{Cite journal | last = Schreiner | first = Philipp|author-link= | last2 = Harrer | first2=Thomas | authorlink2 = Thomas Harrer | last3 = Scheibenbogen | first3=Carmen | authorlink3 = Carmen Scheibenbogen | last4 = Lamer | first4=Stephanie | authorlink4 = | last5 = Schlosser | first5 = Andreas | authorlink5 = | last6 = Naviaux | first6 = Robert K. | authorlink6 = Robert Naviaux | last7 = Prusty | first7 = Bhupesh K. | authorlink7 = Bhupesh Prusty | date = 2020-04-01 | title = Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.immunohorizons.org/content/4/4/201|journal=ImmunoHorizons|language=en|volume=4|issue=4|pages=201–215|doi=10.4049/immunohorizons.2000006|issn=2573-7732|pmc=|pmid=32327453|access-date=|quote=|via=}}</ref> [https://www.immunohorizons.org/content/4/4/201 (Full text)]
*2020, An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients<ref name="Missailidis2020">{{Cite journal | last = Missailidis | first = Daniel | author-link= | last2 = Annesley | first2 = Sarah |authorlink2 = |last3 = Allan | first3=Claire | authorlink3 = | last4 = Sanislav | first4 = Oana | authorlink4 = | last5 = Lidbury | first5 = Brett | authorlink5 = Brett Lidbury | last6 = Lewis | first6 = Don | authorlink6 = Donald Lewis | last7 = Fisher | first7 = Paul | authorlink7 = Paul Fisher | date = 2020-02-06 | title = An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients|url= https://www.mdpi.com/1422-0067/21/3/1074/htm|journal=Int. J. Mol. Sci.|volume=21|issue=3|pages=1074|doi= 10.3390/ijms21031074|pmc=7036826|pmid=32041178|access-date=|quote=|via=}}</ref> - [https://www.mdpi.com/1422-0067/21/3/1074/htm (Full text)]
* 2020, A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction<ref name="Sweetman2020">{{Cite journal | last = Sweetman | first = Eiren | author-link= | last2 = Kleffmann | first2=Torsten | authorlink2 = |last3 = Edgar | first3=Christina | authorlink3 = | last4 = de Lange | first4=Michel | authorlink4 = | last5 = Vallings | first5 = Rosamund | authorlink5 = Rosamund Vallings | last6 = Tate | first6 = Warren | authorlink6 = Warren Tate | date = 2020-09-24 | title = A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction | url =https://doi.org/10.1186/s12967-020-02533-3|journal=Journal of Translational Medicine|volume=18|issue=1|pages=365|doi=10.1186/s12967-020-02533-3|issn=1479-5876|pmc=7512220|pmid=|access-date=|quote=|via=}}</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02533-3 (Full text)]

==Videos==

*[https://www.youtube.com/watch?v=uSlEmBeHlgg "Mitochondria: The Powerhouse of the Cell" by Bozeman Science]<ref>{{Cite web|url=https://www.youtube.com/watch?v=uSlEmBeHlgg | title = Mitochondria: The Powerhouse of the Cell | last = Andersen | first = Paul | date = May 5, 2016 | website = YouTube|publisher=Bozeman Science|access-date=}}</ref>

==See also==
*[[Cellular respiration]]
*[[Exercise]]
*[[Genetics of chronic fatigue syndrome|Genetics]]
*[[Ketogenic diet]]
*[[Mitochondrial antiviral signaling protein]] (MAVS)
*[[NADH]]
*[[NT Factor]]
*[[Robert Naviaux]]
*[[Sarah Myhill]]

==Learn more==
* [http://www.drmyhill.co.uk/wiki/CFS_-_The_Central_Cause:_Mitochondrial_Failure CFS - The Central Cause - Mitochondrial Failure]<ref>{{Cite web|url=http://www.drmyhill.co.uk/wiki/CFS_-_The_Central_Cause:_Mitochondrial_Failure | title = CFS - The Central Cause: Mitochondrial Failure - DoctorMyhill | website = drmyhill.co.uk|language=en|access-date=2018-09-06}}</ref>

*2016, [http://www.labroots.com/trending/immunology/3536/immune-system-conserves-energy-altering-metabolism Immune System Conserves Energy By Altering Metabolism]<ref>{{Cite news | url=http://www.labroots.com/trending/immunology/3536/immune-system-conserves-energy-altering-metabolism | title = Immune System Conserves Energy By Altering Metabolism | last = Marker | first = Kara | date = Jul 10, 2016|work=LabRoots|access-date=2018-09-06}}</ref>
*2016, [http://www.meassociation.org.uk/2016/03/me-association-to-fund-fourth-study-into-the-role-of-the-mitochondria-in-mecfs-10-march-2016/ ME Association to fund fourth study into the role of the mitochondria in ME/CFS]<ref>{{Cite web|url=http://www.meassociation.org.uk/2016/03/me-association-to-fund-fourth-study-into-the-role-of-the-mitochondria-in-mecfs-10-march-2016/ | title = ME Association to fund fourth study into the role of the mitochondria in ME/CFS {{!}} 10 March 2016 | website = [[The ME Association]]|language=en-US|access-date=2018-09-06}}</ref>
*2016, [http://www.healthrising.org/forums/threads/me-association-goes-all-in-on-the-mitochondria-in-chronic-fatigue-syndrome-me-cfs.4645/ ME Association Goes All in on the Mitochondria in Chronic Fatigue Syndrome (ME/CFS)]<ref>{{Cite news | url=http://www.healthrising.org/forums/threads/me-association-goes-all-in-on-the-mitochondria-in-chronic-fatigue-syndrome-me-cfs.4645/ | title = ME Association Goes All in on the Mitochondria in Chronic Fatigue Syndrome (ME/CFS) | last = Morten | first = Karl | date = Mar 2016|work=Health Rising's Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Forums|access-date=2018-09-06|language=en-US|quote=|author-link=Karl Morten}}</ref>
*2016, [https://meaustralia.net/2016/07/06/australian-metabolomics-study-of-young-women/ Australian metabolomics study of young women with ME/CFS (CCC)]<ref>{{Cite news | url=https://meaustralia.net/2016/07/06/australian-metabolomics-study-of-young-women/ | title = Australian metabolomics study of young women with ME/CFS (CCC) | last = Nimmo | first = Sasha | date = 2016-07-06|work=ME Australia|access-date=2018-09-06|language=en-US}}</ref>
*2016, [http://www.healthrising.org/blog/2016/05/19/mitochondria-man-gets-money-uk-goes-mega-chronic-fatigue-syndrome-research-moves-forward/ "Mitochondria Man Gets Money UK Goes Mega Chronic Fatigue Syndrome Research Moves Forward"]<ref>{{Cite news | url=http://www.healthrising.org/blog/2016/05/19/mitochondria-man-gets-money-uk-goes-mega-chronic-fatigue-syndrome-research-moves-forward/ | title = The Mitochondria Man Gets His Money and The UK Goes MEGA: ME/CFS Research Moving Forward - Health Rising | last = Johnson | first = Cort | date = 2016-05-19|work=Health Rising|access-date=2018-09-06|language=en-US}}</ref>

== Citations to add to text ==

Lodi1997 <ref name="Lodi1997" />
Armstrong2015 <ref name="Armstrong2015" />
Craig2015<ref name="Craig2015" />
Felici2016<ref name="Felici2016" />
Ostojic2016 <ref name="Ostojic2016" />
Sliter2018 <ref name="Sliter2018" />
Missailidis2020 <ref name="Missailidis2020" />.

Vermeulen2010 <ref name="Vermeulen2010" />
Maes2009 <ref name="Maes2009" />
Morris2013 <ref name="Morris2013" />
Morris2014 <ref name="Morris2014" />
Armstrong2014 <ref name="Armstrong2014" />
Meeus2013 <ref name="Meeus2013" />

==References==
{{Reflist}}

[[Category:Biochemistry and cell biology]]
[[Category:Organelles]]
[[Category:Mitochondria]]
[[Category:Energy system]]

Herpes simplex virus

2022-12-19T22:28:56Z

Davidshq:/* Hypothesized role in ME/CFS */ fixed anound to and found

'''Herpes simplex virus''' 1 and 2 ('''HSV-1''' and '''HSV-2'''), also known as human [[herpesvirus]] 1 and 2 (HHV-1 and HHV-2), are two members of the eight known members of the '''herpesviridae''' family. Both are lifelong infections and mostly asymptomatic.<ref name="WHO">{{Cite web | url=https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus | title = Herpes simplex virus|website=[[World Health Organization]]|language=en|access-date=2019-04-22}}</ref>

== Overview ==
HSV-1 is mainly transmitted by oral contact and causes cold sores, but can also cause genital herpes (persons with oral HSV-1 are unlikely to subsequently contract genital HSV-1.)<ref name="WHO" /> HSV-1 is a highly common virus, found in an estimated 67% of the worldwide population under the age of 50.<ref name="WHO" /> HSV-1 is most contagious while symptomatic, but can also be transmitted while asymptomatic.<ref name="WHO" />

HSV-2 is sexually transmitted and causes most cases of genital herpes.<ref name="WHO" /> HSV-2 infection increases the risk of contracting and transmitting [[HIV]].<ref name="WHO" /> In the age group of 15 to 49, an estimated 11% of the global population has HSV-2.<ref name="WHO" />

== Treatment ==
Standard treatment for herpes simplex virus include [[Aciclovir|acyclovir]], [[famciclovir]], and [[valacyclovir]].<ref name="WHO" /> These medications can reduce frequency and severity of symptoms (but do not cure the infection).<ref name="WHO" />

== Basic research ==
An [[In vitro studies|in vitro study]] found HSV-1 (as well as the [[Influenza|influenza virus]]) inhibited the [[mitochondrion|mitochondrial]] respiratory chain. In the case of HSV-1, it reduced [[cellular respiration]] by targeting a site between complexes II and III, mediated by protein US3, and reduced the [[oxygen]] consumption rate by 31%.<ref name="Derakhshan2006">{{Cite journal | last = Derakhshan | first = Mohammad | last2 = Willcocks | first2 = Margaret M. | last3 = Salako | first3 = Michael A. | last4 = Kass | first4 = George E.N. | last5 = Carter | first5 = Michael J. | date = 2006 | title=Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport|url=https://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.81949-0|journal=Journal of General Virology|volume=87|issue=8 | pages = 2155–2159|doi=10.1099/vir.0.81949-0|quote=|via=}}</ref>

== Implication in other diseases ==
Dr. [[William Pridgen]] hypothesizes that [[fibromyalgia]] may be caused by HSV-1 infection in the [[dorsal root ganglia]] of the spine (and/or in other nerve ganglia), and treats fibromyalgia with an antiviral combination drug, called [[IMC-1]],<ref name="IMC-2019">{{Cite web | url=http://innovativemedconcepts.com/pipeline.html | title = Pipeline|website=Innovative Med Concepts|access-date=2019-04-22}}</ref> comprised of [[famciclovir]] (Famvir) and the [[COX-2 inhibitors|COX-2 inhibitor]] drug [[celecoxib]].<ref>{{Cite web | url=https://patents.google.com/patent/US20130203710 | title = Patent: Antiviral compound and cox-2 inhibitor combination therapy for functional somatic syndromes, including combination of famciclovir and celecoxib | last = Pridgen | first = William L. | authorlink = | date = | website = Google patents|archive-url=|archive-date=|url-status=|access-date=}}</ref> A randomized, double-blinded, placebo-controlled study clinical trial of 143 fibromyalgia patients by Pridgen et al. (2017) found IMC-1 safe and effective<ref name="Pridgen2017a">{{Cite journal | last = Pridgen | first = William L | last2 = Duffy | first2 = Carol | last3 = Gendreau | first3 = Judy F | last4 = Gendreau | first4 = R Michael | date = 2017-02-22 | title = A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328426/|journal=Journal of Pain Research|volume=10 | pages = 451–460|doi=10.2147/JPR.S127288|issn=1178-7090|pmc=5328426|pmid=28260944|issue=|quote=|via=}}</ref><ref name="Pridgen2017b">{{Cite journal | title = Pos0017 Imc-1, a Fixed Dose Combination of Famciclovir and Celecoxib, Improves Common Symptoms Associated with Fibromyalgia in Addition to Pain: Post Hoc Analysis of a Phase 2a Trial | date = 2021-06-01|url=https://ard.bmj.com/content/80/Suppl_1/210.1|journal=Annals of the Rheumatic Diseases|volume=80|issue=Suppl 1 | pages = 210–210 | last = Pridgen | first = W. | last2 = Duffy | first2 = C. | last3 = Gendreau | first3 = J.F. | last4 = = Gendreau | first4 = R.M.|language=en|doi=10.1136/annrheumdis-2021-eular.1424|issn=0003-4967}}</ref> and the US Food & Drug Administration (FDA) granted it fast-track designation for development as a fibromyalgia treatment.<ref name="Press2021">{{Cite web | url=https://ir.virios.com/news/press-releases/detail/70/virios-therapeutics-achieves-over-50-enrollment-milestone | title = Virios Therapeutics Achieves Over 50% Enrollment Milestone in its Phase 2b Clinical Trial for Fibromyalgia|website=Virios Therapeutics, Inc.|language=en|access-date=2022-08-04}}</ref> A newer IMC-1 trial known as FORTRESS began recruiting fibromyalgia patients in 2021.<ref name="FORTRESS-trial">{{Cite web | title = A Double-Blinded, Randomized, Placebo-Controlled, Phase 2B Trial of IMC-1 for the Treatment of Fibromyalgia | date = 2022-05-13|url=https://clinicaltrials.gov/ct2/show/NCT04748705|journal=ClinicalTrials.gov|volume=|issue=|pages = | last = Virios Therapeutics, Inc. | first = | authorlink = |access-date=Aug 4, 2022|quote=|via=}}</ref>

Itzhaki et al. (2017) has hypothesized that [[Alzheimer's disease]] may be caused by viral or bacterial infection, noting "many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1, [[Chlamydophila pneumoniae|chlamydia pneumoniae]] and several types of spirochatete",<ref name="Itzhaki 2017">{{Cite journal | title = Microbes and Alzheimer’s Disease | date = 2016-01-01|url=https://content.iospress.com/articles/journal-of-alzheimers-disease/jad160152|journal=Journal of Alzheimer's Disease|volume=51|issue=4 | pages = 979–984 | last = Itzhaki | first = Ruth F. | last2 = Lathe | first2 = Richard | last3 = Balin | first3 = Brian J. | last4 = Ball | first4 = Melvyn J. | last5 = Bearer | first5 = Elaine L. | last6 = Braak | first6 = Heiko | last7 = Bullido | first7 = Maria J. | last8 = Carter | first8 = Chris | last9 = Clerici | first9 = Mario | last10 = Cosby | first10 = S. Louise | last11 = Del Tredici | first11 = Kelly|language=en|doi=10.3233/JAD-160152|pmc=PMC5457904|pmid=26967229|issn=1387-2877}}</ref> although there is clear evidence supporting this hypothesis, it is currently not one of the two top hypotheses about the cause of Alzheimer's disease.<ref name="Breijyeh2020">{{Cite journal | title = Comprehensive Review on Alzheimer’s Disease: Causes and Treatment | date = Jan 2020|url=https://www.mdpi.com/1420-3049/25/24/5789|journal=Molecules|volume=25|issue=24 | pages = 5789 | last = Breijyeh | first = Zeinab|author-link= | last2 = Karaman | first2 = Rafik | authorlink2 = |language=en|doi=10.3390/molecules25245789|pmc=|pmid=|access-date=|issn=1420-3049|quote=|via=}}</ref>

Several herpesviruses including HSV-2 may cause false positives on [[Lyme disease]] tests.<ref name="Strasfeld2005">{{Cite journal | last = Berardi | first = Victor P. | last2 = Seder | first2 = Richard H. | last3 = Romanzi | first3 = Lauri | last4 = Strasfeld | first4 = Lynne | date = 2005-12-15 | title = False-Positive Serological Test Results for Lyme Disease in a Patient with Acute Herpes Simplex Virus Type 2 Infection | url =https://academic.oup.com/cid/article/41/12/1826/346681|journal=Clinical Infectious Diseases|language=en|volume=41|issue=12|pages=1826–1827|doi=10.1086/498319|issn=1058-4838|quote=|via=}}</ref>

==Hypothesized role in ME/CFS==
In a 1993 paper in ''Medical Hypotheses (journal)'', P. A. Bond hypothesized that HSV-1 could cause the symptoms of [[chronic fatigue syndrome]] (CFS) in a two-stage process Bond analogized to the relationship of [[HIV/AIDS|HIV to AIDS]]: as (untreated) HIV weakens the immune system and makes the body vulnerable to opportunistic infections and cancers, which then are recognized as the symptoms of AIDS, Bond suggests a variety of conditions could produce immune dysfunction and consequent vulnerability to HSV-1 (either primary infection or reactivation), which in turn could be the cause of a range of CFS symptoms.<ref name="Bond1993">{{Cite journal | last = Bond | first = P.A. |authorlinklink= | date = May 1993 | title = A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/8394501|journal=Medical Hypotheses|volume=40|issue=5 | pages = 301–308|issn=0306-9877|pmid=8394501|quote=|via=}}</ref> In 2006, Bond did a study of 27 CFS patients meeting the [[Fukuda criteria]], and found that antibodies to both HSV-1 and HSV-2 were more common in CFS patients that controls,<ref name="Bond2006">{{Cite journal | title = Antibodies to Herpes Simplex Types 1 and 2 in Chronic Fatigue Syndrome | date = 2006-01-01|url=https://doi.org/10.1300/J092v13n01_04|journal=Journal of Chronic Fatigue Syndrome|volume=13|issue=1 | pages = 35–40 | last = Bond | first = P.A. |last2 = Dinan | first2 = T. G. |doi=10.1300/J092v13n01_04|issn=1057-3321}}</ref> however a larger study by Blomberg et al. (2019) found levels of HSV-1 and HSV-2 in ME/CFS and fibromyalgia patients were similar to or slightly lower than those of healthy blood donors.<ref name="Blomgberg2019">{{Cite journal | title = Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients | date = 2019 | url=https://www.frontiersin.org/articles/10.3389/fimmu.2019.01946|journal=Frontiers in Immunology|volume=10|issue=|pages=1946 | last = Blomberg | first = Jonas | authorlink = Jonas Blomberg | last2 = Rizwan | first2 = Muhammad | authorlink2 = Muhammad Rizwan | last3 = Böhlin-Wiener | first3 = Agnes | authorlink3 = | last4 = Elfaitouri | first4 = Amal | authorlink4 = | last5 = Julin | first5 = Per | authorlink5 = | last6 = Zachrisson | first6 = Olof | authorlink6 = Olof Zachrisson | last7 = Rosén | first7 = Anders | last8 = Gottfries | first8 = Carl-Gerhard | authorlink8 = Carl-Gerhard Gottfries|doi=10.3389/fimmu.2019.01946|pmc=PMC6702656|pmid=31475007|access-date=|issn=1664-3224|quote=|via= | last9 = | first9 = }}</ref> The ME/CFS patients were those that met the [[Canadian Consensus Criteria]].<ref name="Blomgberg2019" />

In 2018, [[Hector Bonilla]], MD and Clinical Assistant Professor of Medicine in Infectious Diseases at [[Stanford University]], received a [[Ramsay Award Program|Ramsay Award Grant]] from the [[Solve ME/CFS Initiative]] for a "Cross-sectional study to assess the prevalence of [[Apolipoprotein E|APOE]] e4 alleles in patients with ME/CFS and the association with herpes virus infection".<ref name="Solve2019">{{Cite web | url=https://solvecfs.org/hector-bonilla/ | title = Hector Bonilla|website=Solve ME/CFS Initiative|language=en-US|access-date=2019-03-29}}</ref> The project follows on preliminary findings that HSV-1 infection in the sera of individuals with ME/CFS is related to severity of the disease.<ref name="Solve2019" />

Pridgen suggests that an approach related to IMC-1 also merits investigation as an ME/CFS treatment.<ref name="IMC-2019" />

==News, interviews and articles ==
*2016, [https://www.telegraph.co.uk/news/science/science-news/12188092/Alzheimers-disease-could-be-caused-by-herpes-virus-warn-experts.html Alzheimer's disease could be caused by herpes virus, warn experts] - The Telegraph

==Notable studies==
* 1993, A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders.<ref name="Bond1993" /> ([https://vdocuments.site/a-role-for-herpes-simplex-virus-in-the-aetiology-of-chronic-fatigue-syndrome.html Full text])
* 1994, Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?<ref name="Manian1994">{{Cite journal | last = Manian | first = F.A. | date = Sep 1994 | title = Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?|url=https://www.ncbi.nlm.nih.gov/pubmed/7811864|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=19|issue=3 | pages = 448–453|issn=1058-4838|pmid=7811864|quote=|via=}}</ref>
* 1996, Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.<ref name="Buchwald1996">{{Cite journal | last = Buchwald | first =D. | last2 = Ashley | first2 = R.L. | last3 = Pearlman | first3 = T. | last4 = Kith | first4 = P. | last5 = Komaroff | first5 = A.L. | date = Sep 1996 | title = Viral serologies in patients with chronic fatigue and chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8890037|journal=Journal of Medical Virology|volume=50|issue=1 | pages = 25–30|doi=10.1002/(SICI)1096-9071(199609)50:13.0.CO;2-V|issn=0146-6615|pmid=8890037|quote=|author-link=Dedra Buchwald | authorlink2 = | authorlink3 = | authorlink4 = | authorlink5 = Anthony Komaroff|via=}}</ref>
* 2002, Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome.<ref name="Koelle2002">{{Cite journal | last = Koelle | first = David M. | last2 = Barcy | first2 = Serge | last3 = Huang | first3 = Meei-Li | last4 = Ashley | first4 = Rhoda L. | last5 = Corey | first5 = Lawrence | last6 = Zeh | first6 = Judy | last7 = Ashton | first7 = Suzanne | last8 = Buchwald | first8 = Dedra | date = 2002-09-01 | title = Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12173124|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=35|issue=5 | pages = 518–525|doi=10.1086/341774|issn=1537-6591|pmid=12173124|quote=|via= | authorlink6 = | last9 = | authorlink7 = | authorlink8 = Dedra Buchwald}}</ref>
* 2006, Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport<ref name="Derakhshan2006" />
* 2013, Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders.<ref name="Carter2013">{{Cite journal | last = Carter | first = Chris J. | date = Dec 2013 | title = Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/23913659|journal=Pathogens and Disease|volume=69|issue=3 | pages = 240–261|doi=10.1111/2049-632X.12077|issn=2049-632X|pmid=23913659|quote=|via=}}</ref>

==See also==
*[[Infection]]
*[[:Category:Triggers and risk factors|Triggers and risk factors]]
*[[:Category:Virology|Virology]]
*[[Vagus nerve infection hypothesis]]
*[[List of herpesvirus infection studies]]

==Learn more ==

==References==
{{Reflist}}

[[Category:Viruses]]
[[Category:Infectious agents]]
[[Category:Triggers and risk factors]]
[[Category:Virology]]
[[Category:Herpesviruses]]

Herpes simplex virus

2022-12-19T22:26:39Z

Davidshq:/* Implication in other diseases */ Remove extra not

'''Herpes simplex virus''' 1 and 2 ('''HSV-1''' and '''HSV-2'''), also known as human [[herpesvirus]] 1 and 2 (HHV-1 and HHV-2), are two members of the eight known members of the '''herpesviridae''' family. Both are lifelong infections and mostly asymptomatic.<ref name="WHO">{{Cite web | url=https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus | title = Herpes simplex virus|website=[[World Health Organization]]|language=en|access-date=2019-04-22}}</ref>

== Overview ==
HSV-1 is mainly transmitted by oral contact and causes cold sores, but can also cause genital herpes (persons with oral HSV-1 are unlikely to subsequently contract genital HSV-1.)<ref name="WHO" /> HSV-1 is a highly common virus, found in an estimated 67% of the worldwide population under the age of 50.<ref name="WHO" /> HSV-1 is most contagious while symptomatic, but can also be transmitted while asymptomatic.<ref name="WHO" />

HSV-2 is sexually transmitted and causes most cases of genital herpes.<ref name="WHO" /> HSV-2 infection increases the risk of contracting and transmitting [[HIV]].<ref name="WHO" /> In the age group of 15 to 49, an estimated 11% of the global population has HSV-2.<ref name="WHO" />

== Treatment ==
Standard treatment for herpes simplex virus include [[Aciclovir|acyclovir]], [[famciclovir]], and [[valacyclovir]].<ref name="WHO" /> These medications can reduce frequency and severity of symptoms (but do not cure the infection).<ref name="WHO" />

== Basic research ==
An [[In vitro studies|in vitro study]] found HSV-1 (as well as the [[Influenza|influenza virus]]) inhibited the [[mitochondrion|mitochondrial]] respiratory chain. In the case of HSV-1, it reduced [[cellular respiration]] by targeting a site between complexes II and III, mediated by protein US3, and reduced the [[oxygen]] consumption rate by 31%.<ref name="Derakhshan2006">{{Cite journal | last = Derakhshan | first = Mohammad | last2 = Willcocks | first2 = Margaret M. | last3 = Salako | first3 = Michael A. | last4 = Kass | first4 = George E.N. | last5 = Carter | first5 = Michael J. | date = 2006 | title=Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport|url=https://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.81949-0|journal=Journal of General Virology|volume=87|issue=8 | pages = 2155–2159|doi=10.1099/vir.0.81949-0|quote=|via=}}</ref>

== Implication in other diseases ==
Dr. [[William Pridgen]] hypothesizes that [[fibromyalgia]] may be caused by HSV-1 infection in the [[dorsal root ganglia]] of the spine (and/or in other nerve ganglia), and treats fibromyalgia with an antiviral combination drug, called [[IMC-1]],<ref name="IMC-2019">{{Cite web | url=http://innovativemedconcepts.com/pipeline.html | title = Pipeline|website=Innovative Med Concepts|access-date=2019-04-22}}</ref> comprised of [[famciclovir]] (Famvir) and the [[COX-2 inhibitors|COX-2 inhibitor]] drug [[celecoxib]].<ref>{{Cite web | url=https://patents.google.com/patent/US20130203710 | title = Patent: Antiviral compound and cox-2 inhibitor combination therapy for functional somatic syndromes, including combination of famciclovir and celecoxib | last = Pridgen | first = William L. | authorlink = | date = | website = Google patents|archive-url=|archive-date=|url-status=|access-date=}}</ref> A randomized, double-blinded, placebo-controlled study clinical trial of 143 fibromyalgia patients by Pridgen et al. (2017) found IMC-1 safe and effective<ref name="Pridgen2017a">{{Cite journal | last = Pridgen | first = William L | last2 = Duffy | first2 = Carol | last3 = Gendreau | first3 = Judy F | last4 = Gendreau | first4 = R Michael | date = 2017-02-22 | title = A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328426/|journal=Journal of Pain Research|volume=10 | pages = 451–460|doi=10.2147/JPR.S127288|issn=1178-7090|pmc=5328426|pmid=28260944|issue=|quote=|via=}}</ref><ref name="Pridgen2017b">{{Cite journal | title = Pos0017 Imc-1, a Fixed Dose Combination of Famciclovir and Celecoxib, Improves Common Symptoms Associated with Fibromyalgia in Addition to Pain: Post Hoc Analysis of a Phase 2a Trial | date = 2021-06-01|url=https://ard.bmj.com/content/80/Suppl_1/210.1|journal=Annals of the Rheumatic Diseases|volume=80|issue=Suppl 1 | pages = 210–210 | last = Pridgen | first = W. | last2 = Duffy | first2 = C. | last3 = Gendreau | first3 = J.F. | last4 = = Gendreau | first4 = R.M.|language=en|doi=10.1136/annrheumdis-2021-eular.1424|issn=0003-4967}}</ref> and the US Food & Drug Administration (FDA) granted it fast-track designation for development as a fibromyalgia treatment.<ref name="Press2021">{{Cite web | url=https://ir.virios.com/news/press-releases/detail/70/virios-therapeutics-achieves-over-50-enrollment-milestone | title = Virios Therapeutics Achieves Over 50% Enrollment Milestone in its Phase 2b Clinical Trial for Fibromyalgia|website=Virios Therapeutics, Inc.|language=en|access-date=2022-08-04}}</ref> A newer IMC-1 trial known as FORTRESS began recruiting fibromyalgia patients in 2021.<ref name="FORTRESS-trial">{{Cite web | title = A Double-Blinded, Randomized, Placebo-Controlled, Phase 2B Trial of IMC-1 for the Treatment of Fibromyalgia | date = 2022-05-13|url=https://clinicaltrials.gov/ct2/show/NCT04748705|journal=ClinicalTrials.gov|volume=|issue=|pages = | last = Virios Therapeutics, Inc. | first = | authorlink = |access-date=Aug 4, 2022|quote=|via=}}</ref>

Itzhaki et al. (2017) has hypothesized that [[Alzheimer's disease]] may be caused by viral or bacterial infection, noting "many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1, [[Chlamydophila pneumoniae|chlamydia pneumoniae]] and several types of spirochatete",<ref name="Itzhaki 2017">{{Cite journal | title = Microbes and Alzheimer’s Disease | date = 2016-01-01|url=https://content.iospress.com/articles/journal-of-alzheimers-disease/jad160152|journal=Journal of Alzheimer's Disease|volume=51|issue=4 | pages = 979–984 | last = Itzhaki | first = Ruth F. | last2 = Lathe | first2 = Richard | last3 = Balin | first3 = Brian J. | last4 = Ball | first4 = Melvyn J. | last5 = Bearer | first5 = Elaine L. | last6 = Braak | first6 = Heiko | last7 = Bullido | first7 = Maria J. | last8 = Carter | first8 = Chris | last9 = Clerici | first9 = Mario | last10 = Cosby | first10 = S. Louise | last11 = Del Tredici | first11 = Kelly|language=en|doi=10.3233/JAD-160152|pmc=PMC5457904|pmid=26967229|issn=1387-2877}}</ref> although there is clear evidence supporting this hypothesis, it is currently not one of the two top hypotheses about the cause of Alzheimer's disease.<ref name="Breijyeh2020">{{Cite journal | title = Comprehensive Review on Alzheimer’s Disease: Causes and Treatment | date = Jan 2020|url=https://www.mdpi.com/1420-3049/25/24/5789|journal=Molecules|volume=25|issue=24 | pages = 5789 | last = Breijyeh | first = Zeinab|author-link= | last2 = Karaman | first2 = Rafik | authorlink2 = |language=en|doi=10.3390/molecules25245789|pmc=|pmid=|access-date=|issn=1420-3049|quote=|via=}}</ref>

Several herpesviruses including HSV-2 may cause false positives on [[Lyme disease]] tests.<ref name="Strasfeld2005">{{Cite journal | last = Berardi | first = Victor P. | last2 = Seder | first2 = Richard H. | last3 = Romanzi | first3 = Lauri | last4 = Strasfeld | first4 = Lynne | date = 2005-12-15 | title = False-Positive Serological Test Results for Lyme Disease in a Patient with Acute Herpes Simplex Virus Type 2 Infection | url =https://academic.oup.com/cid/article/41/12/1826/346681|journal=Clinical Infectious Diseases|language=en|volume=41|issue=12|pages=1826–1827|doi=10.1086/498319|issn=1058-4838|quote=|via=}}</ref>

==Hypothesized role in ME/CFS==
In a 1993 paper in ''Medical Hypotheses (journal)'', P. A. Bond hypothesized that HSV-1 could cause the symptoms of [[chronic fatigue syndrome]] (CFS) in a two-stage process Bond analogized to the relationship of [[HIV/AIDS|HIV to AIDS]]: as (untreated) HIV weakens the immune system and makes the body vulnerable to opportunistic infections and cancers, which then are recognized as the symptoms of AIDS, Bond suggests a variety of conditions could produce immune dysfunction and consequent vulnerability to HSV-1 (either primary infection or reactivation), which in turn could be the cause of a range of CFS symptoms.<ref name="Bond1993">{{Cite journal | last = Bond | first = P.A. |authorlinklink= | date = May 1993 | title = A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/8394501|journal=Medical Hypotheses|volume=40|issue=5 | pages = 301–308|issn=0306-9877|pmid=8394501|quote=|via=}}</ref> In 2006, Bond did a study of 27 CFS patients meeting the [[Fukuda criteria]], anound that antibodies to both HSV-1 and HSV-2 were more common in CFS patients that controls,<ref name="Bond2006">{{Cite journal | title = Antibodies to Herpes Simplex Types 1 and 2 in Chronic Fatigue Syndrome | date = 2006-01-01|url=https://doi.org/10.1300/J092v13n01_04|journal=Journal of Chronic Fatigue Syndrome|volume=13|issue=1 | pages = 35–40 | last = Bond | first = P.A. |last2 = Dinan | first2 = T. G. |doi=10.1300/J092v13n01_04|issn=1057-3321}}</ref> however a larger study by Blomberg et al. (2019) found levels of HSV-1 and HSV-2 in ME/CFS and fibromyalgia patients were similar to or slightly lower than those of healthy blood donors.<ref name="Blomgberg2019">{{Cite journal | title = Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients | date = 2019 | url=https://www.frontiersin.org/articles/10.3389/fimmu.2019.01946|journal=Frontiers in Immunology|volume=10|issue=|pages=1946 | last = Blomberg | first = Jonas | authorlink = Jonas Blomberg | last2 = Rizwan | first2 = Muhammad | authorlink2 = Muhammad Rizwan | last3 = Böhlin-Wiener | first3 = Agnes | authorlink3 = | last4 = Elfaitouri | first4 = Amal | authorlink4 = | last5 = Julin | first5 = Per | authorlink5 = | last6 = Zachrisson | first6 = Olof | authorlink6 = Olof Zachrisson | last7 = Rosén | first7 = Anders | last8 = Gottfries | first8 = Carl-Gerhard | authorlink8 = Carl-Gerhard Gottfries|doi=10.3389/fimmu.2019.01946|pmc=PMC6702656|pmid=31475007|access-date=|issn=1664-3224|quote=|via= | last9 = | first9 = }}</ref> The ME/CFS patients were those that met the [[Canadian Consensus Criteria]].<ref name="Blomgberg2019" />

In 2018, [[Hector Bonilla]], MD and Clinical Assistant Professor of Medicine in Infectious Diseases at [[Stanford University]], received a [[Ramsay Award Program|Ramsay Award Grant]] from the [[Solve ME/CFS Initiative]] for a "Cross-sectional study to assess the prevalence of [[Apolipoprotein E|APOE]] e4 alleles in patients with ME/CFS and the association with herpes virus infection".<ref name="Solve2019">{{Cite web | url=https://solvecfs.org/hector-bonilla/ | title = Hector Bonilla|website=Solve ME/CFS Initiative|language=en-US|access-date=2019-03-29}}</ref> The project follows on preliminary findings that HSV-1 infection in the sera of individuals with ME/CFS is related to severity of the disease.<ref name="Solve2019" />

Pridgen suggests that an approach related to IMC-1 also merits investigation as an ME/CFS treatment.<ref name="IMC-2019" />

==News, interviews and articles ==
*2016, [https://www.telegraph.co.uk/news/science/science-news/12188092/Alzheimers-disease-could-be-caused-by-herpes-virus-warn-experts.html Alzheimer's disease could be caused by herpes virus, warn experts] - The Telegraph

==Notable studies==
* 1993, A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders.<ref name="Bond1993" /> ([https://vdocuments.site/a-role-for-herpes-simplex-virus-in-the-aetiology-of-chronic-fatigue-syndrome.html Full text])
* 1994, Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?<ref name="Manian1994">{{Cite journal | last = Manian | first = F.A. | date = Sep 1994 | title = Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?|url=https://www.ncbi.nlm.nih.gov/pubmed/7811864|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=19|issue=3 | pages = 448–453|issn=1058-4838|pmid=7811864|quote=|via=}}</ref>
* 1996, Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.<ref name="Buchwald1996">{{Cite journal | last = Buchwald | first =D. | last2 = Ashley | first2 = R.L. | last3 = Pearlman | first3 = T. | last4 = Kith | first4 = P. | last5 = Komaroff | first5 = A.L. | date = Sep 1996 | title = Viral serologies in patients with chronic fatigue and chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8890037|journal=Journal of Medical Virology|volume=50|issue=1 | pages = 25–30|doi=10.1002/(SICI)1096-9071(199609)50:13.0.CO;2-V|issn=0146-6615|pmid=8890037|quote=|author-link=Dedra Buchwald | authorlink2 = | authorlink3 = | authorlink4 = | authorlink5 = Anthony Komaroff|via=}}</ref>
* 2002, Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome.<ref name="Koelle2002">{{Cite journal | last = Koelle | first = David M. | last2 = Barcy | first2 = Serge | last3 = Huang | first3 = Meei-Li | last4 = Ashley | first4 = Rhoda L. | last5 = Corey | first5 = Lawrence | last6 = Zeh | first6 = Judy | last7 = Ashton | first7 = Suzanne | last8 = Buchwald | first8 = Dedra | date = 2002-09-01 | title = Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12173124|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=35|issue=5 | pages = 518–525|doi=10.1086/341774|issn=1537-6591|pmid=12173124|quote=|via= | authorlink6 = | last9 = | authorlink7 = | authorlink8 = Dedra Buchwald}}</ref>
* 2006, Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport<ref name="Derakhshan2006" />
* 2013, Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders.<ref name="Carter2013">{{Cite journal | last = Carter | first = Chris J. | date = Dec 2013 | title = Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/23913659|journal=Pathogens and Disease|volume=69|issue=3 | pages = 240–261|doi=10.1111/2049-632X.12077|issn=2049-632X|pmid=23913659|quote=|via=}}</ref>

==See also==
*[[Infection]]
*[[:Category:Triggers and risk factors|Triggers and risk factors]]
*[[:Category:Virology|Virology]]
*[[Vagus nerve infection hypothesis]]
*[[List of herpesvirus infection studies]]

==Learn more ==

==References==
{{Reflist}}

[[Category:Viruses]]
[[Category:Infectious agents]]
[[Category:Triggers and risk factors]]
[[Category:Virology]]
[[Category:Herpesviruses]]

Important events timeline

2022-12-18T23:03:54Z

Davidshq:/* 1980s */ Corrected location of Lake Tahoe from California to Nevada

==Victorian Period==
{| class="wikitable" width="100%"
! style="width:6%" | Year || style="width:12%" | Date || Event
|-
|1869 || || [[George Miller Beard]] coined the term "[[neurasthenia]]." He thought it was an especially American affliction of nervous exhaustion, affected men who were "brain workers" and women who advanced too far in their education.
|-
|?? || || [[Jean-Martin Charcot]] - [[hysteria]]. Many of his patients were suffering from [[epilepsy]]. Influence on [[Sigmund Freud]] and the concept of [[functional disorder]]s.
|}

== Early 20th century ==
{| class="wikitable" width="100%"
! style="width:6%" | Year || style="width:12%" | Date || Event
|-
|1934 || || [[Atypical poliomyelitis]] - an [[Epidemic myalgic encephalomyelitis|outbreak]] at [[1934 Los Angeles atypical polio outbreak|Los Angeles County Hospital]] of a disease "resembling poliomyelitis" was recorded.
|}

==1950s==
{| class="wikitable" width="100%"
! style="width:6%" | Year || style="width:12%" | Date || Event
|-
|1955 || || [[Royal Free Hospital outbreak]] in London, England, which led to the use of the name [[Myalgic encephalomyelitis]].
|}

==1960s==
{| class="wikitable" width="100%"
! style="width:6%" | Year || style="width:12%" | Date || Event
|-
|1969 || || [[Myalgic encephalomyelitis]] classified by the [[World Health Organization]] (WHO) as a neurological disease.<ref name=":3">{{Cite book | url =https://apps.who.int/iris/bitstream/handle/10665/70934/ICD_10_1969_eng_v2a.pdf?sequence=3&isAllowed=y | title = International Classification of Diseases | last = World Health Organization | first = |publisher=WHO| year = 1969|isbn=|editor-link=|edition=Eighth revision|volume=2|location=Geneva|pages=173|chapter=|quote=Encephalomyelitis (chronic),<br>(myalgic, benign) 323|editor-last2 = |editorlink2 = }}</ref>
|}

==1970s==
{| class="wikitable" width="100%"
! style="width:6%" | Year || style="width:12%" | Date || Event
|-
|1975 || || [[1975 Sacramento outbreak|Outbreak in Mercy San Juan Hospital]], in a suburb of Sacramento, California, Unites States
|-
|1976 || || [[ME Association]] charity founded in [[UK]]
|}

==1980s==
{| class="wikitable" width="100%"
! style="width:6%" | Year || style="width:12%" | Date || Event
|-
|1980 || || Outbreak in Ayrshire, Scotland ([[1980-81 Ayrshire outbreak]]).
|-
|1984 || || Disease outbreak in [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] near Lake Tahoe in Nevada, United States.
|-
|1984 || || Disease outbreak in Chapel Hill, North Carolina, United States([[1984 Chapel Hill outbreak]]).
|-
|1985 || || Disease outbreak in Lyndonville, New York, United States ([[1985 Lyndonville outbreak]]).
|-
|1988 || || First definition of [[Chronic fatigue syndrome]] produced, later updated in 1994.
|}

==1990s==
{| class="wikitable" width="100%"
! style="width:6%" | Year || style="width:12%" | Date || Event
|-
|1994 || || [[Chronic fatigue syndrome]] criteria update to the 1994 [[Fukuda criteria]].
|-
|1994 || September || Publication of the [[1994 National Task Force Report on CFS/PVFS/ME]] by [[Westcare UK]], notably the [[London criteria]]
|-
|1996 || || ''[[Osler's Web]]: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic'' by [[Hillary Johnson]] is published chronicling the governmental inaction and fraud in investigating [[ME/CFS]]
|-
|}

==2000s==
{| class="wikitable" width="100%"
! style="width:6%" | Year || style="width:12%" | Date || Event
|-
|2003 || || [[Canadian Consensus Criteria]] is developed by [[Bruce Carruthers]], et al.
|-
|2009 || || Publication of the [[Judy Mikovits]] study in ''[[Science]]'' claiming a link between [[Chronic fatigue syndrome]] and the [[XMRV]] retrovirus.
|-
|2009 || || Preliminary research published by Norwegian researchers proposes assessment of the use of cancer drug [[Rituximab]] to treat the disease.
|}

==2010s==
{| class="wikitable" width="100%"
! style="width:6%" | Year || style="width:12%" | Date || Event
|-
|2011 || || [[International Consensus Criteria]] is developed by [[Bruce Carruthers]], et al.
|-
|2011 || || The controversial British [[PACE trial]] is published in ''[[The Lancet]]'', recommending [[cognitive behavioral therapy]] and [[graded exercise therapy]] as treatments.
|-
|2011 || || The ''[[Science]]'' journal retracts the [[XMRV]] paper.
|-
|2015 || || The [[Institute of Medicine report]] is released: "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an illness", which reviewed thousands of articles, and concluded that "ME/CFS is a serious, chronic, complex and multisystem disease that frequently and dramatically limits the activities of affected patients" (p. 209). The report recommended new diagnostic criteria, and a new name for the condition: [[Systemic Exertion Intolerance Disease]] (SEID).
|-
|2015 || || [[Francis Collins]] announces the intent of the [[National Institutes of Health]] to take the disease more seriously.
|-
|2015 || || The [[Open Medicine Foundation]] announces its [[End ME/CFS Project]], led by [[Ronald Davis]], has support of three Nobel prize laureates.
|-
|2016 || || [[National Institutes of Health]], United States begins study of ME/CFS patient in their in-house Clinical Center in Bethesda
|}

==See also==
*[[Osler's Web]] by [[Hillary Johnson]]
*[[Thirty Years of Disdain]] by [[Mary Dimmock]]
*[[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|List of outbreaks]]
*[[ME and CFS in popular culture]]
*[[Notable studies]]

==References==
{{Reflist}}

[[Category:History]]