01 October 2007
What is Inflammatory Bowel Disease?
That is was my first question when divulging into this week. The lay article from the Saturday Evening Post was a nice introduction. Not to be confused with irritable bowel syndrome, IBD is a fairly severe but typically non-fatal disease(such exceptions include a ruptured colon). Symptoms include upset stomach, diharrea, vomiting and nasuea. There are two types of IDB, ulcerative colitis and Crohn’s Disease. The differences are that UC affects the only the mucosa in the colon whereas Crohn’s has the potential to affect any and/or all of GI tract including the entire wall of the GI. The actual cause of the disease is unknown but it has a genetic trace in 10-15% of subjects with familial clustering of CD and UC families occurring such that 75% of families are concordant for disease type, and 25% have both CD and UC within the same family. (Abreu et al. Translational Research in Inflammatory Bowel Disease) Treatments are somewhat limited, typical anti-inflammatory protocol such as the use of prednisone is used often. However there has been some break through with the use of cyclosporine, a drug used in organ transplants as mentioned by the Saturday Evening Post. Overall, this disease is somewhat of a quandry. Hopefully a cure is in sight!
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In a current publication (1) researchers identify a signaling pathway that may be involved in Crohn’s disease and Ulcerative Colitis. Researchers have identified NF-kB to be a key transcription factor involved in Inflammatory Bowel Disease. NF-kB is the final transcription factor most commonly activated in inflammation and a signaling molecule that helps cope with stress (1). It is also known to be an anti-apoptosis molecule. According to A. Nenci et al. (2007) NF-kB acts as a survival signal for cells. Nf-KB is activated by the protein NEMO (2). Without NEMO present, Nf-KB activation is not present causing damage to the gut epithelium. Epithelial cells apoptose, causing the gut lining to be disrupted. With this disruption in the gut lining, bacteria are able to make there way into the intestine, causing an immune response and an increase in inflammation. This may be one understanding of the mechanism behind Crohn’s Disease and/or Ulcerative Colitis.
(1) A. Nenci, C. Becker, M. Neurath, M. Pasparakis et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation, Nature, 14 March 2007
(2) Agou et al. (2004) J. Biol. Chem., 279, 27861-27869
I found from an external web site that found that the nicotine from cigarettes affect the gut motility (the rate at which waste is processed through the colon), and this is what links cigarette smoking to IBD. The nicotine probably allows the bacteria more time to make its way into the intestine, thus increasing the tendency to develop Crohn's disease and Ulcerative colitis.
In the "Future" of IBD, it states that researchers are very confident that in the future this disease will be treated quickly and precisely. Mass spectroscopy and other techniques are being used that make a cure seem almost definite! The claims seem so confident, you start to wonder what diseases in the future they aren't going to be able to cure...
Dr. William J. Sandborn is one of a group of investigators doing a study on UC. He told Reuters that they found a drug, Adalimumab, that has "cured" UC. Patients given this treatment had no symptoms after 2-4 weeks. This disease did not reappear if the patient keeps on taking this drug every other week after the initial dose is given.
http://www.ccfa.org/reuters/adalimumabmaint
One treatment that has been found to work for patients suffering from ulcerative colitis is something known as fecal floa infusion. Yes, it may sound hideous, but a couple of studies have shown that if bacterial flora from the fecal matter of a healthy person is transplated into a person suffering from ulcerative colitis, the patients go into remission. Apparently the bacterial flora are able to "home in" on the pathogen that is thought to cause UC. Although this is not a widely accepted form of therapy due to cultural fecalphobia, it might be a good idea to research this further.
Borody T (2000). ""Flora Power"-- fecal bacteria cure chronic C. difficile diarrhea.". Am J Gastroenterol 95 (11): 3028-9)
http://www.cdd.com.au/pdf/paper32.pdf
That was supposed to be "fecal flora infusion" which is also known as human fecal bacteriotherapy. After I commented, I found another study by the same doctor that give more information on the treament. (Borody T, Warren E, Leis S, Surace R, Ashman O (2003). "Treatment of ulcerative colitis using fecal bacteriotherapy.". J Clin Gastroenterol 37 (1): 42-7.)
Can diet of worms help cure IBD? I followed up on an article posted by the NewScientist stating the remission rate for patients with UC was 50 percent and 70 percent for patients with CD after being treated with a drinkable concoction of 2000 pig whipworms eggs. This study is being done by gastroenterologist Joel Weinstock of the University of Iowa. Which may be one of the most interesting treatments for IBD!
http://www.newscientist.com/article.ns?id=dn4852
Related articles:
http://www.sciencemag.org/cgi/reprint/305/5681/170.pdf
http://www.usatoday.com/news/health/2004-07-07-leeches-maggots_x.htm
http://www.sciencemag.org/cgi/reprint/305/5681/170.pdf
When people throw out the term, cured, the disease is not cured but actually with that drug it is termed a treatment, not a cure. Just as insulin is not a cure for type I diabetes, it is merely a treatment.
After our discussion today about the bowel resection as a treatment for IBD, I decided to look into it a little more.Before getting into the "heavy" stuff of bowel resection, I want to share something my dad sent me a while back. I hope you enjoy it...
"Working Where the Sun Don't Shine (Ode to the Colorectal Surgeon)" by Bowser and Blue
http://youtube.com/watch?v=wlCLHf76q_w
During a resection, the diseased portion of the bowel is removed and the healthy parts are connected (resected). There are a couple types of resection:
1)The less invasive laparoscopic bowel resection for more "minor" cases;
2) A "medium" case where the patient must be opened and a larger part of the bowel removed;
3) Proctocolectomy - where the entire colon and rectum is removed for the more serious/advanced cases of the disease.
Post-operatively, most patients will wear a temporary colostomy bag until they are fully healed. Patients requiring more bowel removal will most likely have a permanent colostomy bag in place.
("Large Bowel Resection", MedlinePlus, http://www.nlm.nih.gov/medlineplus/
ency/article/002941.htm)
A study was just published this June from the Centre for Colorectal Disease in Dublin, Ireland which doctors followed 139 patients with CD who had an ilocecal resection performed between 1980 and 2000. The study followed the long term outcomes of patients post-operatively. They found that 52% of patients reported disease recurrence and 35% required a repeat resection surgery after 10 years. The researchers reported that long-term outcomes for CD patients post-bowel resection were encouraging since only 35% required another resection operation and 48% remained "symptom free" after their operation.
(Cullen, G. et al, "Long-term clinical results of ileocecal resection for Crohn's disease", Inflammatory Bowel Disease, 28 Jun. 2007)
Although this study provides "promising" outlooks for this operation, I believe that less invasive therapies with a minimal to no chance of recurrence will prove to be more beneficial to patients suffering from IBD.
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