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| {{CMG}}; {{AE}} | | {{CMG}}; {{AE}} |
| ==Overview== | | ==Overview== |
| The exact pathogenesis of [disease name] is not fully understood.
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| It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
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| [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
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| Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
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| [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
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| The progression to [disease name] usually involves the [molecular pathway].
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| The pathophysiology of [disease/malignancy] depends on the histological subtype.
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| ==Pathophysiology== | | ==Pathophysiology== |
| Initially, IBS was considered a psychosomatic illness, and the involvement of biological and pathogenic factors was not verified until the 1990s, a process common in the [[history of emerging infectious diseases]]. The risk of developing IBS increases six-fold after acute gastrointestinal infection. Post-infection, further risk factors are young age, prolonged [[fever]], [[anxiety]] and [[depression]].<ref>{{cite journal | author = Thabane M, Kottachchi DT, Marshall JK | title = The incidence and prognosis of post-infectious irritable bowel syndrome. | journal = Aliment Pharmacol Ther | volume = 26 | issue = 4 | pages = 535-44 | year = 2007 | pmid = 17661757}}</ref>
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| ===Psychosomatic illness===
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| One of the first references to the concept of an "Irritable Bowel" appeared in the Rocky Mountain Medical Journal in 1950.<ref name="BROWN_1950">{{cite journal |author=BROWN PW |title=The irritable bowel syndrome |journal=Rocky Mountain medical journal|volume=47 |issue=5 |pages=343-6 |year=1950 |pmid=15418074 |doi=}}</ref> The term was used to categorize patients who developed symptoms of diarrhea, abdominal pain, [[constipation]], but where no well-recognized infective cause could be found. Early theories suggested that the Irritable Bowel was caused by a [[Somatoform disorder|somatic]], or mental disorder. One paper from the 1980s investigated "learned illness behavior" in patients with IBS and [[peptic ulcers]].<ref name="WHITEHEAD_1982">{{cite journal |author=Whitehead WE, Winget C, Fedoravicius AS, Wooley S, Blackwell B|title=Learned illness behavior in patients with irritable bowel syndrome and peptic ulcer |journal=Dig. Dis. Sci. |volume=27|issue=3 |pages=202-8 |year=1982 |pmid=7075418 |doi=}}</ref> Another study suggested that both IBS and stomach ulcer patients would benefit from 15 months of [[psychotherapy]].<ref name="pmid3895386">{{cite journal |author=Svedlund J, Sjödin I |title=A psychosomatic approach to treatment in the irritable bowel syndrome and peptic ulcer disease with aspects of the design of clinical trials |journal=Scand. J. Gastroenterol. Suppl. |volume=109 |issue= |pages=147-51 |year=1985 |pmid=3895386 |doi=}}</ref> Later, it was found that most stomach ulcers were caused by a bacterial infection with ''[[Helicobacter pylori]].''<ref name="pmid9191460">{{cite journal |author=Damianos AJ, McGarrity TJ |title=Treatment strategies for Helicobacter pylori infection|journal=American family physician |volume=55 |issue=8 |pages=2765–74, 2784–6 |year=1997 |pmid=9191460 |doi=}}</ref>
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| Additional publications suggesting the role of brain-gut "axis" appeared in the 1990s, such as a study entitled ''Brain-gut response to stress and cholinergic stimulation in IBS'' published in the ''Journal of Clinical Gastrotnerology'' in 1993.<ref>{{cite journal|author=Fukudo S, Nomura T, Muranaka M, Taguchi F |title=Brain-gut response to stress and cholinergic stimulation in irritable bowel syndrome. A preliminary study |journal=J. Clin. Gastroenterol. |volume=17 |issue=2 |pages=133-41 |year=1993 |pmid=8031340|doi=}}</ref> A 1997 study published in ''Gut'' magazine suggested that IBS was associated with a "derailing of the brain-gut axis."<ref>{{cite journal |author=Orr WC, Crowell MD, Lin B, Harnish MJ, Chen JD |title=Sleep and gastric function in irritable bowel syndrome: derailing the brain-gut axis |journal=Gut |volume=41 |issue=3 |pages=390-3 |year=1997 |pmid=9378397 |doi=}}</ref>
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| <div class="noprint" style="clear: center; border: solid #aaa 1px; margin: 0 0 1em 1em; background: #efeff9; width: 50%; padding: 4px; text-align: justify; float: center;">
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| {{"
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| |There was a greater improvement in the psychotherapy groups for patients with IBS after three months and for both IBS and PUD (peptic ulcer disease) patients after 15 months. The difference had become more pronounced after 15 months, with the patients given psychotherapy showing further improvement, and the patients who had received medical treatment only showing some deterioration.
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| |by J Svedlund, ''A psychosomatic approach to treatment in the irritable bowel syndrome and peptic ulcer disease with aspects of the design of clinical trials'', 1985.
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| ''Most peptic ulcers are now treated with 1-2 weeks of antibiotic therapy, since it has been discovered that they are caused by a combination of a genetic trait in the patient and infection with the bacteria [[H. Pylori]].''<ref name="EL-OMAR_2000">{{cite journal |author=El-Omar EM, Carrington M, Chow WH, ''et al'' |title=Interleukin-1 polymorphisms associated with increased risk of gastric cancer |journal=Nature |volume=404 |issue=6776 |pages=398-402 |year=2000 |pmid=10746728 |doi=10.1038/35006081}} </ref>
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| </div>
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| ===Immune reaction===
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| From the late 1990s, research publications began identifying specific biochemical changes present in tissue biopsies and serum samples from IBS patients that suggested symptoms had an organic rather than [[psychosomatic]] cause. These studies identified [[cytokine]]s and secretory products in tissues taken from IBS patients. The cytokines identified in IBS patients produce [[inflammation]] and are associated with the body's [[Immunity (medical)|immune]] response.
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| * A study showed that intestinal [[biopsies]] from patients with constipation predominant IBS secreted higher levels of [[serotonin]] in-vitro.<ref>{{cite journal |author=Miwa J, Echizen H, Matsueda K, Umeda N |title=Patients with constipation-predominant irritable bowel syndrome (IBS) may have elevated serotonin concentrations in colonic mucosa as compared with diarrhea-predominant patients and subjects with normal bowel habits |journal=Digestion |volume=63 |issue=3 |pages=188-94|year=2001 |pmid=11351146 |doi=}}</ref> [[Serotonin]] plays a role in regulating gastrointestinal motility and water content and can be altered by some diseases and infections.<ref name="MCGOWAN_1983">{{cite journal |author=McGowan K, Kane A, Asarkof N, ''et al'' |title=Entamoeba histolytica causes intestinal secretion: role of serotonin |journal=Science |volume=221 |issue=4612|pages=762-4 |year=1983 |pmid=6308760 |doi=}} </ref><ref name="MCGOWAN_1985">{{cite journal |author=McGowan K, Guerina V, Wicks J, Donowitz M |title=Secretory hormones of Entamoeba histolytica |journal=Ciba Found. Symp. |volume=112 |issue= |pages=139-54|year=1985 |pmid=2861068 |doi=}} </ref><ref>{{cite journal |author=Banu, Naheed, et al. |title=Neurohumoral alterations and their role in amoebiasis. |journal=Indian J. Clin Biochem |volume=20 |issue=2 |pages=142-5 |year=2005|url=http://medind.nic.in/iaf/t05/i2/iaft05i2p142.pdf}}</ref>
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| * A study of rectal biopsy tissue from IBS patients showed increased levels of cellular structures involved in the production of the cytokine [[Interleukin 1]] Beta.<ref>{{cite journal |author=Gwee KA, Collins SM, Read NW, ''et al'' |title=Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome |journal=Gut |volume=52 |issue=4|pages=523-6 |year=2003 |pmid=12631663 |doi=}}</ref>
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| * A study of blood samples from IBS patients identified elevated levels of cytokines [[Tumor necrosis factor-alpha]], [[Interleukin 1]], and [[Interleukin 6]] in patients with IBS.<ref name="pmid17383420">{{cite journal |author=Liebregts T, Adam B, Bredack C, ''et al'' |title=Immune activation in patients with irritable bowel syndrome |journal=Gastroenterology |volume=132 |issue=3 |pages=913-20|year=2007 |pmid=17383420 |doi=10.1053/j.gastro.2007.01.046}}</ref>
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| * A study of intestinal biopsies from IBS patients showed increased levels of [[protease]] enzymes used by the body to digest proteins, and by infectious agents to combat the host's [[immune system]].<ref>{{cite journal |author=Cenac N, Andrews CN, Holzhausen M, ''et al'' |title=Role for protease activity in visceral pain in irritable bowel syndrome |journal=J. Clin. Invest.|volume=117 |issue=3 |pages=636-47 |year=2007 |pmid=17304351 |doi=10.1172/JCI29255}}</ref>
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| * A study of blood samples from IBS patients found elevated levels of [[antibodies]] to the [[protozoan]] ''[[Blastocystis]]''.<ref name="HUSSAIN_1997">{{cite journal |author=Hussain R, Jaferi W, Zuberi S, ''et al'' |title=Significantly increased IgG2 subclass antibody levels to Blastocystis hominis in patients with irritable bowel syndrome |journal=Am. J. Trop. Med. Hyg. |volume=56|issue=3 |pages=301-6 |year=1997 |pmid=9129532 |doi=}}</ref>
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| Specific forms of immune response that have been implicated in IBS symptoms include [[coeliac disease]] and other [[food allergy]] conditions.<ref name="Wangen_2006">Wangen, Dr. Stephen. ''The Irritable Bowel Syndrome Solution''. 2006. ISBN 0976853787. Excerpted with author's permission at [http://www.IBSTreatmentCenter.com/]</ref> [[Coeliac disease]] (also spelled "celiac") is an immunoglobulin type A-(IgA) mediated allergic response to the [[gliadin]] protein in gluten grains,which exhibits wide variety of symptoms and can present as IBS. "Some patients with diarrhea-predominant irritable bowel syndrome (IBS-D) may have undiagnosed celiac sprue (CS). Because the symptoms of CS respond to a gluten-free diet, testing for CS in IBS may prevent years of morbidity and attendant expense."<ref>{{cite journal |author=Spiegel BM, ''et al'' |title=Testing for celiac sprue in irritable bowel syndrome with predominant diarrhea: a cost-effectiveness analysis. |journal=Gastroenterology |volume=126 |issue=7 |pages=1721-32 |year=2004|pmid=15188167 |doi=}}</ref> "Coeliac disease is a common finding among patients labelled as having irritable bowel syndrome. In this sub-group, a gluten free diet may lead to a significant improvement in symptoms. Routine testing for coeliac disease may be indicated in all patients being evaluated for irritable bowel syndrome."<ref>{{cite journal |author=Shahbazkhani B, ''et al''|title=Coeliac disease presenting with symptoms of irritable bowel syndrome. |journal=Aliment Pharmacol Therapy |volume=18 |issue=2|pages=231-5 |year=2003 |pmid=12869084 |doi=}}</ref> Food allergies, particularly those mediated by IgE and IgG-type antibodies have been implicated in IBS.<ref>{{cite journal |author=Li H, ''et al'' |title=Allergen-IgE complexes trigger CD23-dependent CCL20 release from human intestinal epithelial cells. |journal=Gastroenterology |volume=133 |issue=6 |pages=1905-15 |year=2007|pmid=18054562 |doi=}}</ref><ref>{{cite journal |Yang CM, Li YQ |title=The therapeutic effects of eliminating allergic foods according to food-specific IgG antibodies in irritable bowel syndrome - Article in Chinese |journal=Zhonghua Nei Ke Za Zhi.|volume=46 |issue=8 |pages=641-3 |year=2007 |pmid=17967233 |doi=}}</ref><ref>{{cite journal |author=Drisko ''et al'' |title=Treating Irritable Bowel Syndrome with a Food Elimination Diet Followed by Food Challenge and Probiotics |journal=Journal of the American College of Nutrition |volume=25 |issue=6 |pages=514-22 |year=2006 |pmid=17229899 |doi=}}</ref>
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| ===Active infections===
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| <div class="noprint" style="clear: center; border: solid #aaa 1px; margin: 0 0 1em 1em; background: #efeff9; width: 50%; padding: 4px; text-align: left; float: right;">
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| {{"
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| |Clearly this study highlights a new concept in the potential pathogenesis of IBS. An infectious cause may offer a tremendous opportunity to manage an otherwise frustrating disease -- both for patients and their treating physician.
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| |by Dr. David A. Johnson, President of the [[American College of Gastroenterology]] , commenting on results from study of Rifaximin in treatment of IBS<ref>{{cite journal |author=Johnson, David. |title=Viewpoints: Efficacy of Rifaximin vs Placebo in Reducing Symptoms in Adults With IBS. |journal=Medscape Gastroenterology |volume=8 |issue=2 |year=2006|url=http://www.medscape.com/viewarticle/547055}}</ref>
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| </div>
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| There is research to support IBS being caused by an as-yet undiscovered active infection. Most recently, a study has found that the antibiotic [[Rifaximin]] provides sustained relief for IBS patients.<ref name="pmid17043337">{{cite journal |author=Pimentel M, Park S, Mirocha J, Kane SV, Kong Y |title=The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial |journal=Ann. Intern. Med. |volume=145 |issue=8 |pages=557-63 |year=2006 |pmid=17043337 |doi=}}</ref> While some researchers see this as evidence that IBS is related to an undiscovered agent, others believe IBS patients suffer from overgrowth of [[Gut flora|intestinal flora]] and the antibiotics are effective in reducing the overgrowth (known as ''[[Small bowel bacterial overgrowth syndrome|small intestinal bacterial overgrowth]]'').<ref name="pmid17148502">{{cite journal |author=Posserud I, Stotzer PO, Björnsson ES, Abrahamsson H, Simrén M |title=Small intestinal bacterial overgrowth in patients with irritable bowel syndrome |journal=Gut |volume=56 |issue=6 |pages=802-8 |year=2007 |pmid=17148502 |doi=10.1136/gut.2006.108712}}</ref> Other researchers have focused on an unrecognized [[protozoa]]l infection as a cause of IBS<ref name="STARK_2007">{{cite journal|author=Stark D, van Hal S, Marriott D, Ellis J, Harkness J |title=Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis |journal=Int. J. Parasitol. |volume=37 |issue=1 |pages=11-20 |year=2007|pmid=17070814 |doi=10.1016/j.ijpara.2006.09.009}}</ref> as certain protozoal infections occur more frequently in IBS patients.<ref name="YAKOOB_2004">{{cite journal |author=Yakoob J, Jafri W, Jafri N, ''et al'' |title=Irritable bowel syndrome: in search of an etiology: role of Blastocystis hominis |journal=Am. J. Trop. Med. Hyg. |volume=70 |issue=4 |pages=383-5 |year=2004 |pmid=15100450|doi=}}</ref><ref name="GIACOM_1999">{{cite journal |author=Giacometti A, Cirioni O, Fiorentini A, Fortuna M, Scalise G|title=Irritable bowel syndrome in patients with Blastocystis hominis infection |journal=Eur. J. Clin. Microbiol. Infect. Dis.|volume=18 |issue=6 |pages=436-9 |year=1999 |pmid=10442423 |doi=}}</ref> Two of the protozoa investigated have a high prevalence in industrialized countries and infect the bowel, but little is known about them as they are recently emerged pathogens.
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| ''[[Blastocystis]]'' is a single-celled organism which has been reported to produce symptoms of abdominal pain, constipation and diarrhea in patients, along with headaches and depression,<ref name="QADRI_1989">{{cite journal |author=Qadri SM, al-Okaili GA, al-Dayel F |title=Clinical significance of Blastocystis hominis |journal=J. Clin. Microbiol. |volume=27 |issue=11 |pages=2407-9|year=1989 |pmid=2808664 |doi=}}</ref> though these reports are contested by some physicians.<ref name="MARKELL_1986">{{cite journal|author=Markell EK, Udkow MP |title=Blastocystis hominis: pathogen or fellow traveler? |journal=Am. J. Trop. Med. Hyg. |volume=35|issue=5 |pages=1023-6 |year=1986 |pmid=3766850 |doi=}}</ref> Studies from research hospitals in various countries have identified high [[Blastocystis]] infection rates in IBS patients, with 38% being reported from [[London School of Hygiene & Tropical Medicine]],<ref name="WINDSOR_2007">{{cite journal |author=Windsor J |title=B. hominis and D. fragilis: Neglected human protozoa|journal=British Biomedical Scientist |pages=524-7 |year=2007 |pmid= |doi= |url=http://www.ibms.org/index.cfm?method=publications.biomedical_scientist&subpage=contents_2007_July}}</ref> 47% reported from the Department of Gastroenterology at [[Aga Khan University]] in Pakistan<ref name="YAKOOB_2004" /> and 18.1% reported from the Institute of Diseases and Public Health at [[University of Ancona]] in Italy.<ref name="GIACOM_1999" /> Reports from all three groups indicate a [[Blastocystis]] prevalence of approximately 7% in non-IBS patients. Researchers have noted that clinical diagnostics fail to identify infection,<ref name="STENSVOLD_2006">{{cite journal |author=Stensvold R, Brillowska-Dabrowska A, Nielsen HV, Arendrup MC |title=Detection of Blastocystis hominis in unpreserved stool specimens by using polymerase chain reaction |journal=J. Parasitol. |volume=92 |issue=5|pages=1081-7 |year=2006 |pmid=17152954 |doi=}}</ref> and ''Blastocystis'' may not respond to treatment with common antiprotozoals.<ref name="pmid15250669">{{cite journal |author=Yakoob J, Jafri W, Jafri N, Islam M, Asim Beg M |title=In vitro susceptibility of Blastocystis hominis isolated from patients with irritable bowel syndrome |journal=Br. J. Biomed. Sci. |volume=61|issue=2 |pages=75-7 |year=2004 |pmid=15250669 |doi=}}</ref><ref name="pmid10357863">{{cite journal |author=Haresh K, Suresh K, Khairul Anus A, Saminathan S |title=Isolate resistance of Blastocystis hominis to metronidazole |journal=Trop. Med. Int. Health|volume=4 |issue=4 |pages=274-7 |year=1999 |pmid=10357863 |doi=}}</ref><ref name="pmid3766850">{{cite journal |author=Markell EK, Udkow MP |title=Blastocystis hominis: pathogen or fellow traveler? |journal=Am. J. Trop. Med. Hyg. |volume=35 |issue=5 |pages=1023-6|year=1986 |pmid=3766850 |doi=}}</ref><ref name="pmid10566723">{{cite journal |author=Ok UZ, Girginkardeşler N, Balcioğlu C, Ertan P, Pirildar T, Kilimcioğlu AA |title=Effect of trimethoprim-sulfamethaxazole in Blastocystis hominis infection |journal=Am. J. Gastroenterol. |volume=94 |issue=11 |pages=3245-7 |year=1999 |pmid=10566723 |doi=}}</ref>
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| [[Image:Wiki ibs cause figures.jpg|thumb|800px|center|Prevalence of protozoal infections in industrialized countries (United States and Canada) in 21st century.<ref name="CMAJ_2006" /><ref name="pmid12224595">{{cite journal |author=Amin OM |title=Seasonal prevalence of intestinal parasites in the United States during 2000 |journal=Am. J. Trop. Med. Hyg. |volume=66 |issue=6|pages=799-803 |year=2002 |pmid=12224595 |doi=}}</ref>]]
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| ''[[Dientamoeba fragilis]]'' is a single-celled organism which produces abdominal pain and diarrhea. Studies have reported a high incidence of infection in developed countries, and symptoms of patients resolve following antibiotic treatment.<ref name="CMAJ_2006">{{cite journal |author=Lagacé-Wiens PR, VanCaeseele PG, Koschik C |title=Dientamoeba fragilis: an emerging role in intestinal disease |journal=CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne|volume=175 |issue=5 |pages=468-9 |year=2006 |pmid=16940260 |doi=10.1503/cmaj.060265}}</ref><ref name="STENSVOLD_2007f">{{cite journal |author=Stensvold CR, Arendrup MC, Mølbak K, Nielsen HV |title=The prevalence of Dientamoeba fragilis in patients with suspected enteroparasitic disease in a metropolitan area in Denmark |journal=Clin. Microbiol. Infect. |volume=13 |issue=8|pages=839-42 |year=2007 |pmid=17610603 |doi=10.1111/j.1469-0691.2007.01760.x}}</ref> One study reported on a large group of patients with IBS-like symptoms who were found to be infected with ''Dientamoeba fragilis'' and experienced resolution of symptoms following treatment.<ref name="BORODY_2002">{{cite journal |author=Borody T, Warren E, Wettstein A, et al. | title = Eradication of Dientamoeba fragilis can resolve IBS-like symptoms. | journal=J Gastroenterol Hepatol | year= 2002 | volume=17 | issue=Suppl; pages=A103}}</ref> Researchers have noted that methods used clinically may fail to detect some ''[[Dientamoeba fragilis]]'' infections.<ref name="STENSVOLD_2007f" />
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| ==Pathophysiology==
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| ===Pathogenesis===
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| *The exact pathogenesis of [disease name] is not fully understood.
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| OR
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| *It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
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| *[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
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| *Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
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| *[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
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| *The progression to [disease name] usually involves the [molecular pathway].
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| *The pathophysiology of [disease/malignancy] depends on the histological subtype.
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|
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| ==Genetics== | | ==Genetics== |