Cirrhosis is defined as a condition of irreversible scarring liver as a
result of liver tissue by fibrosis due to final phase of chronic liver diseases
of that can lead to poor function of the liver and liver failure. According to
the statistics, Number of discharges with chronic liver disease or cirrhosis as
the first-listed diagnosis: 101,000 in 2009 and Deaths per 100,000 population:
10.3 in 2010(a). Hepatitis B infection cause of the disease is very prevalent in
South-East Asia.
Risk factors
1. Gender
Female who are chronic alcohol drinkers are at increase to develop
Cirrhosis. According to the study in a population-based prospective
cohort of 13,285 men and women aged 30-79 years, and diagnoses
indicating alcoholic liver disease (n = 261) or cirrhosis
(n = 124) were obtained from the Danish National Health Registers,
indicated that women had a significantly higher relative risk of
developing alcohol related liver disease than men for any given level of alcohol intake(8).
2. Diabetes mellitus (DM)
If you are diabetic, you are associated with increased risk of
cirrhosis. According to the study by the University Hospital, Monterrey,
about 30% of patients with cirrhosis
have diabetes mellitus (DM). There exists in relation to: type 2 DM
alone or as part of the metabolic syndrome in the development of liver disease; factors involved in the genesis of hepatogenous diabetes; the impact of DM on the clinical outcome of liver disease; the management of DM in cirrhotic patients and the role of DM as a risk factor for the occurrence and exacerbation of hepatocellular carcinoma(9). Other study indicated that Insulin resistance in liver cirrhosis
was higher than the other type 2 DM, and impaired hepatic insulin
degradation might be an important mechanism of hyperinsulinemia in liver cirrhosis(10).
3. Excessive alcohol drinking
People who drinks abusively, in most case died
as a result of the progression of liver diseases. According to the
review of Seventeen studies alcohol consumption had a significantly larger impact on mortality of liver cirrhosis compared with morbidity. Also, the same amount of average consumption was related to a higher risk of liver cirrhosis in women than in men(11).
4. Medication induced cirrhosis
Certain medication may cause increased risk of
cirrhosis to the takers. According to the study by the Seoul National
University College of Medicine, anti-tuberculosis (TB) drug-induced liver injury (DILI) in patients with chronic liver disease including cirrhosis, but the drugs may be safely used in the patients with chronic liver disease including compensated cirrhosis
if number of hepatotoxic drugs used is adjusted appropriately(12). In
other study by University "Magna Græcia" of Catanzaro, there is a case
of a male patient who developed severe drug-induced
hepatotoxicity during the treatment with Cyproterone acetate (CPA). The
case, presenting sub-acute hepatitis, was characterized by a rapid
evolution of cirrhosis and a protracted
activity during the period of a few months despite the treatment
withdrawal and an apparent benefits of corticosteroids, suggesting their
indication in life threatening cases(13).
5. Age
Risk of cirrhosis is
increased with progression of age. According to the study by the
University of Sydney, there is evidence that the sinusoidal changes in cirrhosis and aging
contribute to hepatocyte hypoxia, thus providing a mechanism for the
apparent differential reduction of oxygen-dependent phase I metabolic
pathways in these conditions. Structural change and subsequent
dysfunction of the liver sieve warrant
consideration as a significant factor in the impairment of overall
substrate handling and hepatic drug metabolism in cirrhosis and aging(14).
6. Obesity
Risk of cirrhosis is increased for obese people. In the study to evaluate the role of obesity, in relationship to other recognized predictors, in the development of CD in patients with compensated cirrhosis, found that obesity has a deleterious effect on the natural history of compensated cirrhosis
of all etiologies, independent of portal pressure and liver function.
Weight reduction may be a valuable therapeutic measure in this patient
population(15).
7. Heredity
Alpha-1-anti-trypsin deficiency is the most common genetic cause of liver disease in children and liver transplantation is currently the only available treatment, according to the study by Telethon Institute of Genetics and Medicine(16).
8. Toxins
Toxins can damage the liver. according
to the study by University Hospital Regensburg, Xanthohumol, the major
prenylated chalcone found in hops, is known for its anti-inflammatory
properties exerts a protective effects of xanthohumol in this toxic liver
injury model involves direct mechanisms related to its ability to block
both hepatic inflammation and the activation of hepatic stellate cells,
presumable at least in part via decreasing NFκB activity(17).
9. Etc.
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Sources
(a) http://www.cdc.gov/nchs/fastats/liverdis.htm
(8) http://www.ncbi.nlm.nih.gov/pubmed/9214055
(9) http://www.ncbi.nlm.nih.gov/pubmed/19140227
(10) http://www.ncbi.nlm.nih.gov/pubmed/17237630
(11) http://www.ncbi.nlm.nih.gov/pubmed/20636661
(12) http://www.ncbi.nlm.nih.gov/pubmed/20670648
(13) http://www.ncbi.nlm.nih.gov/pubmed/23293208
(14) http://www.ncbi.nlm.nih.gov/pubmed/15656697
(15) http://www.ncbi.nlm.nih.gov/pubmed/21567436
(16) http://www.ncbi.nlm.nih.gov/pubmed/23381957
(17) http://www.ncbi.nlm.nih.gov/pubmed/22295144
Tuesday, 3 December 2013
Cirrhosis - The Causes
Cirrhosis is defined as a condition of irreversible scarring liver as a
result of liver tissue by fibrosis due to final phase of chronic liver diseases
of that can lead to poor function of the liver and liver failure. According to
the statistics, Number of discharges with chronic liver disease or cirrhosis as
the first-listed diagnosis: 101,000 in 2009 and Deaths per 100,000 population:
10.3 in 2010(a). Hepatitis B infection cause of the disease is very prevalent in
South-East Asia.
A. Causes
Most cases of Cirrhosis are caused by excessive and chronic alcohol drink and hepatitis.
1. Excessive and chronic alcohol drink
Prolonged period of excessive alcohol drink can lead to onset of the disease. In the study to provide a quantitative assessment of the association between alcohol intake and risk of liver cirrhosis, by the Centre for Addiction and Mental Health, showed that alcohol consumption had a significantly larger impact on mortality of liver cirrhosis compared with morbidity. Also, the same amount of average consumption was related to a higher risk of liver cirrhosis in women than in men.(1).
2. Hepatitis
a. Heptitis C
Hepatitis C virus (HCV) infects more than 170 million people worldwide, and thereby becomes a series global health challenge. Chronic infection with HCV is considered one of the major causes of end-stage liver disease including cirrhosis and hepatocellular carcinoma(2).
b. Hepatitis B
Following development of liver cirrhosis in patients with chronic hepatitis B, liver disease may continue to progress and decompensation or hepatocellular carcinoma (HCC) may occur(3).
3. Biliary cirrhosis
a. Primary Biliary cirrhosis
Primary Biliary cirrhosis is defined as a chronic liver diseases as a result of the slow destruction of the bile duct of the liver. According to the study by, Nagasaki University Graduate School of Biomedical Sciences, patients with primary biliary cirrhosis (PBC) exhibit a variety of clinical manifestations and patterns of disease progression. The genetic variants of CYP7A1 and its transcriptional activators (HNF4A and PPARGC1A) may activate bile acid synthesis, resulting in the accumulation of bile acids in hepatocytes and eventually leading to the predisposition to PBC progression(4). Other study in the examined single nucleotide polymorphisms (SNPs) in cytotoxic T-lymphocyte antigen 4 (CTLA4) and solute carrier family 4 anion exchanger, member 2 (SLC4A2), which have been associated with the pathogenesis of PBC in Caucasian patients, found that CTLA4 and SLC4A2 genetic polymorphisms are differentially associated with PBC development and progression, as well as anti-gp210 or anti-centromere antibody production, in Japanese PBC patients(5).
b. Secondary Biliary cirrhosis
Secondary Biliary cirrhosis is defined as a condition of the blocking of the bile duct of the liver as a result infection or iatrogenic bile duct injury (BDI), bile duct strictures, gallstones, sclerosing, etc.
Secondary biliary cirrhosis was the indication for liver transplantation (LT) in 5 (1.7%) out of 300 LTs performed in our center between Feb 2002 and April 2011, according to the Surgery and Liver Transplantation, M. Curie Hospital, Szczecin(6).
4. Other causes (non-B, non-C liver cirrhosis (NBNC LC))
In a nationwide survey of NBNC LC in Japan at the 15th General Meeting of the Japan Society of Hepatology, 6999 NBNC LC with patients were registered at 48 medical institutions. Epidemiological and clinical factors, indicated that The percentage of NBNC LC among LC patients was 26%. NBNC LC patients were categorized into 11 types according to etiological agents: non-alcoholic steatohepatitis (NASH), 14.5%; alcoholic liver disease (ALD), 55.1%; fatty liver disease (FLD), except NASH, ALD, and other known etiology, 2.5%; primary biliary cirrhosis, 8.0%; other biliary cirrhosis, 0.8%; autoimmune hepatitis, 6.8%; metabolic disease, 0.6%; congestive disease, 0.8%; parasitic disease, 0.2%; other known etiology, 0.2%; and unknown etiology, 10.5%(7).
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Sources
Sources
(a) http://www.cdc.gov/nchs/fastats/liverdis.htm
(1) http://www.ncbi.nlm.nih.gov/pubmed/20636661
(2) http://www.ncbi.nlm.nih.gov/pubmed/23355912
(3) http://www.ncbi.nlm.nih.gov/pubmed/22504333
(4) http://www.ncbi.nlm.nih.gov/pubmed/23354620
(5) http://www.ncbi.nlm.nih.gov/pubmed/21594562
(6) http://www.ncbi.nlm.nih.gov/pubmed/22743721
(7) http://www.ncbi.nlm.nih.gov/pubmed/23347437
A. Causes
Most cases of Cirrhosis are caused by excessive and chronic alcohol drink and hepatitis.
1. Excessive and chronic alcohol drink
Prolonged period of excessive alcohol drink can lead to onset of the disease. In the study to provide a quantitative assessment of the association between alcohol intake and risk of liver cirrhosis, by the Centre for Addiction and Mental Health, showed that alcohol consumption had a significantly larger impact on mortality of liver cirrhosis compared with morbidity. Also, the same amount of average consumption was related to a higher risk of liver cirrhosis in women than in men.(1).
2. Hepatitis
a. Heptitis C
Hepatitis C virus (HCV) infects more than 170 million people worldwide, and thereby becomes a series global health challenge. Chronic infection with HCV is considered one of the major causes of end-stage liver disease including cirrhosis and hepatocellular carcinoma(2).
b. Hepatitis B
Following development of liver cirrhosis in patients with chronic hepatitis B, liver disease may continue to progress and decompensation or hepatocellular carcinoma (HCC) may occur(3).
3. Biliary cirrhosis
a. Primary Biliary cirrhosis
Primary Biliary cirrhosis is defined as a chronic liver diseases as a result of the slow destruction of the bile duct of the liver. According to the study by, Nagasaki University Graduate School of Biomedical Sciences, patients with primary biliary cirrhosis (PBC) exhibit a variety of clinical manifestations and patterns of disease progression. The genetic variants of CYP7A1 and its transcriptional activators (HNF4A and PPARGC1A) may activate bile acid synthesis, resulting in the accumulation of bile acids in hepatocytes and eventually leading to the predisposition to PBC progression(4). Other study in the examined single nucleotide polymorphisms (SNPs) in cytotoxic T-lymphocyte antigen 4 (CTLA4) and solute carrier family 4 anion exchanger, member 2 (SLC4A2), which have been associated with the pathogenesis of PBC in Caucasian patients, found that CTLA4 and SLC4A2 genetic polymorphisms are differentially associated with PBC development and progression, as well as anti-gp210 or anti-centromere antibody production, in Japanese PBC patients(5).
b. Secondary Biliary cirrhosis
Secondary Biliary cirrhosis is defined as a condition of the blocking of the bile duct of the liver as a result infection or iatrogenic bile duct injury (BDI), bile duct strictures, gallstones, sclerosing, etc.
Secondary biliary cirrhosis was the indication for liver transplantation (LT) in 5 (1.7%) out of 300 LTs performed in our center between Feb 2002 and April 2011, according to the Surgery and Liver Transplantation, M. Curie Hospital, Szczecin(6).
4. Other causes (non-B, non-C liver cirrhosis (NBNC LC))
In a nationwide survey of NBNC LC in Japan at the 15th General Meeting of the Japan Society of Hepatology, 6999 NBNC LC with patients were registered at 48 medical institutions. Epidemiological and clinical factors, indicated that The percentage of NBNC LC among LC patients was 26%. NBNC LC patients were categorized into 11 types according to etiological agents: non-alcoholic steatohepatitis (NASH), 14.5%; alcoholic liver disease (ALD), 55.1%; fatty liver disease (FLD), except NASH, ALD, and other known etiology, 2.5%; primary biliary cirrhosis, 8.0%; other biliary cirrhosis, 0.8%; autoimmune hepatitis, 6.8%; metabolic disease, 0.6%; congestive disease, 0.8%; parasitic disease, 0.2%; other known etiology, 0.2%; and unknown etiology, 10.5%(7).
Chinese Secrets To Fatty Liver And Obesity Reversal
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Sources
Sources
(a) http://www.cdc.gov/nchs/fastats/liverdis.htm
(1) http://www.ncbi.nlm.nih.gov/pubmed/20636661
(2) http://www.ncbi.nlm.nih.gov/pubmed/23355912
(3) http://www.ncbi.nlm.nih.gov/pubmed/22504333
(4) http://www.ncbi.nlm.nih.gov/pubmed/23354620
(5) http://www.ncbi.nlm.nih.gov/pubmed/21594562
(6) http://www.ncbi.nlm.nih.gov/pubmed/22743721
(7) http://www.ncbi.nlm.nih.gov/pubmed/23347437
Colitis - Treatments in Traditional Chinese medicine
Colitis is defined as a condition of inflammation of the large intestine, including the colon, caecum and rectum.
Treatments
In traditional Chinese medicine perspective
According to traditonal Chinese medicine, colitis is a result of irregular functioning of the stomach and spleen systems of that enhances bleeding, mucus, and diarrhea(123).
Also according to the article of Dr. John Zhang (MD, China), an experienced Acupuncturist and Herbal Medicine Specialist with a private practice in Toronto.
1. In case study of involved a 50-year-old male
Colitis can be result of the accumulation of damp-heat in the patient’s body of that prevented the stomach and spleen systems from working to their full potential with symptoms of frequented bowel movements (over 20 time a day), along with plenty of mucus and bleeding.
2. In case study of involved a a 34-year-old female
Or as the result of a spleen and stomach deficiency due to a prolong period of illness with symptoms of mucus in the stool, and constant rectal bleeding resulting in significant blood loss every day.
During the courses of treatment with above differentiation, Dr. Chang also indicated that Dietary therapy is an important part of treatment. Patients should avoid or limit mucous-forming foods such as dairy (milk, cheese, ice cream), as well as cold (raw) foods and spicy/greasy deep fried foods. Easily digested, bland, and cooked foods are recommended. If you want do know more of above article, please visit(123).
Other study in using TCM herbal extract ((Forsythia koreana, Corydalis saxicola, Semiaquilegia adoxoides, Taraxacum officinale, Chrysanthemum coronarium, Glycyrrhiza inflate, and Lonicera japonica) ) in treating Inflammatory bowel disease (IBD) in Female Swiss-Webster mice, showed that treatment with the combination of medicinal herbs decreases leukocyte infiltration and mucosal ulceration, ameliorating the course of acute colonic inflammation. This herbal remedy may prove to be a novel and safe therapeutic alternative in the treatment of IBD(124).
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight
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Sources
(123) http://vitalitymagazine.com/article/healing-colitis-with-acupuncture-chinese-herbs/.
(124) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596578/
Treatments
In traditional Chinese medicine perspective
According to traditonal Chinese medicine, colitis is a result of irregular functioning of the stomach and spleen systems of that enhances bleeding, mucus, and diarrhea(123).
Also according to the article of Dr. John Zhang (MD, China), an experienced Acupuncturist and Herbal Medicine Specialist with a private practice in Toronto.
1. In case study of involved a 50-year-old male
Colitis can be result of the accumulation of damp-heat in the patient’s body of that prevented the stomach and spleen systems from working to their full potential with symptoms of frequented bowel movements (over 20 time a day), along with plenty of mucus and bleeding.
2. In case study of involved a a 34-year-old female
Or as the result of a spleen and stomach deficiency due to a prolong period of illness with symptoms of mucus in the stool, and constant rectal bleeding resulting in significant blood loss every day.
During the courses of treatment with above differentiation, Dr. Chang also indicated that Dietary therapy is an important part of treatment. Patients should avoid or limit mucous-forming foods such as dairy (milk, cheese, ice cream), as well as cold (raw) foods and spicy/greasy deep fried foods. Easily digested, bland, and cooked foods are recommended. If you want do know more of above article, please visit(123).
Other study in using TCM herbal extract ((Forsythia koreana, Corydalis saxicola, Semiaquilegia adoxoides, Taraxacum officinale, Chrysanthemum coronarium, Glycyrrhiza inflate, and Lonicera japonica) ) in treating Inflammatory bowel disease (IBD) in Female Swiss-Webster mice, showed that treatment with the combination of medicinal herbs decreases leukocyte infiltration and mucosal ulceration, ameliorating the course of acute colonic inflammation. This herbal remedy may prove to be a novel and safe therapeutic alternative in the treatment of IBD(124).
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
Back to General health http://kylejnorton.blogspot.ca/p/general-health.html
Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca
Sources
(123) http://vitalitymagazine.com/article/healing-colitis-with-acupuncture-chinese-herbs/.
(124) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596578/
Colitis - Treatments in Herbal medicine
Colitis is defined as a condition of inflammation of the large intestine, including the colon, caecum and rectum.
Treatments
C. In herbal medicine perspective
1. Ambrotose complex and Advanced Ambrotose (aloe vera gel, arabinogalactan, fucoidan, and rice starch)
In the study to test the efficacy of Plant-derived polysaccharide supplements in inhibiting dextran sulfate sodium-induced colitis in the rat, conducted by the Eurofins Product Safety Laboratories, indicated that Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown anti- inflammatory activity(118).
2. Flax seed
People use flaxseed for many conditions related to the gastrointestinal (GI) tract, including ongoing constipation, colon damage due to overuse of laxatives, diarrhea, inflammation of the lining of the large intestine (diverticulitis), irritable bowel syndrome (IBS) or irritable colon, sores in the lining of the large intestine (ulcerative colitis), inflammation of the lining of the stomach (gastritis), and inflammation of the small intestine (enteritis)(119).
3. Boswellia
In the study to evaluate the antioxidant effect of an extract of the plant Boswellia serrata in an experimental model of acute ulcerative colitis induced by administration of acetic acid (AA) in rats, found that the extract of B. serrata has active antioxidant substances that exert protective effects in acute experimental colitis(120).
4. Peppermint Oil
Peppermint oil is the major constituent of several over-the-counter remedies for symptoms of irritable bowel syndrome (IBS). According to the study by Postgraduate Medical School, University of Exeter, found that 8 randomized, controlled trials were located. Collectively they indicate that peppermint oil could be efficacious for symptom relief in IBS. A metaanalysis of five placebo-controlled, double blind trials seems to support this notion(121).
5. Ginger
Ginger is a commonly used spice with anti-inflammatory potential. In the study to investigate the therapeutic effects of ginger and its component zingerone in mice with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis, showed that nuclear factor-κB (NF-κB) and interleukin-1β (IL-1β) were key molecules involved in the expression of ginger- and zingerone-affected genes. Ex vivo imaging and immunohistochemical staining further verified that ginger and zingerone suppressed TNBS-induced NF-κB activation and IL-1β protein level in the colon. In conclusion, ginger improved TNBS-induced colitis via modulation of NF-κB activity and IL-1β signalling pathway. Moreover, zingerone might be the active component of ginger responsible for the amelioration of colitis induced by TNBS(122).
6. Etc.
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight
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Back to General health http://kylejnorton.blogspot.ca/p/general-health.html
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Sources
(118) http://www.ncbi.nlm.nih.gov/pubmed/19513840
(119) http://www.nlm.nih.gov/medlineplus/druginfo/natural/991.html
(120) http://www.ncbi.nlm.nih.gov/pubmed/22451119
(121) http://www.ncbi.nlm.nih.gov/pubmed/9672344
(122) http://www.ncbi.nlm.nih.gov/pubmed/23017409
Treatments
C. In herbal medicine perspective
1. Ambrotose complex and Advanced Ambrotose (aloe vera gel, arabinogalactan, fucoidan, and rice starch)
In the study to test the efficacy of Plant-derived polysaccharide supplements in inhibiting dextran sulfate sodium-induced colitis in the rat, conducted by the Eurofins Product Safety Laboratories, indicated that Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown anti- inflammatory activity(118).
2. Flax seed
People use flaxseed for many conditions related to the gastrointestinal (GI) tract, including ongoing constipation, colon damage due to overuse of laxatives, diarrhea, inflammation of the lining of the large intestine (diverticulitis), irritable bowel syndrome (IBS) or irritable colon, sores in the lining of the large intestine (ulcerative colitis), inflammation of the lining of the stomach (gastritis), and inflammation of the small intestine (enteritis)(119).
3. Boswellia
In the study to evaluate the antioxidant effect of an extract of the plant Boswellia serrata in an experimental model of acute ulcerative colitis induced by administration of acetic acid (AA) in rats, found that the extract of B. serrata has active antioxidant substances that exert protective effects in acute experimental colitis(120).
4. Peppermint Oil
Peppermint oil is the major constituent of several over-the-counter remedies for symptoms of irritable bowel syndrome (IBS). According to the study by Postgraduate Medical School, University of Exeter, found that 8 randomized, controlled trials were located. Collectively they indicate that peppermint oil could be efficacious for symptom relief in IBS. A metaanalysis of five placebo-controlled, double blind trials seems to support this notion(121).
5. Ginger
Ginger is a commonly used spice with anti-inflammatory potential. In the study to investigate the therapeutic effects of ginger and its component zingerone in mice with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis, showed that nuclear factor-κB (NF-κB) and interleukin-1β (IL-1β) were key molecules involved in the expression of ginger- and zingerone-affected genes. Ex vivo imaging and immunohistochemical staining further verified that ginger and zingerone suppressed TNBS-induced NF-κB activation and IL-1β protein level in the colon. In conclusion, ginger improved TNBS-induced colitis via modulation of NF-κB activity and IL-1β signalling pathway. Moreover, zingerone might be the active component of ginger responsible for the amelioration of colitis induced by TNBS(122).
6. Etc.
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
Back to General health http://kylejnorton.blogspot.ca/p/general-health.html
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Sources
(118) http://www.ncbi.nlm.nih.gov/pubmed/19513840
(119) http://www.nlm.nih.gov/medlineplus/druginfo/natural/991.html
(120) http://www.ncbi.nlm.nih.gov/pubmed/22451119
(121) http://www.ncbi.nlm.nih.gov/pubmed/9672344
(122) http://www.ncbi.nlm.nih.gov/pubmed/23017409
Fulminant colitis - Treatments in Conventional medicine
Colitis is defined as a condition of inflammation of the large intestine, including the colon, caecum and rectum.
Treatments
A. In conventional medicine perspective
Fulminant colitis
A.7.1. Non surgical therapy
1. Immunosuppressive drug
a. Tacrolimus (FK-506)
Immunosuppressive drugs are increasingly being used as a therapeutic alternative to colectomy in patients with ulcerative or Crohn's colitis. According to the study of Tacrolimus (FK-506) Treatment of Fulminant Colitis in a Child in Journal of Pediatric Gastroenterology & Nutrition:October 1996 - Volume 23 - Issue 3 - pp 329-333, oral tacrolimus offers a potential alternative to cyclosporine in patients with steroid-resistant fulminant colitis and offers the potential advantages of more reliable oral absorption and greater ease of administration. The side effects of tacrolimus are similar to those of cyclosporine, but some adverse effects (including hypertension, gingival hyperplasia, and coarsening of facial features)(112).
b. Cyclosporine
The use of immunosuppressive medications such as 6-mercaptopurine in individuals with fulminant disease is often limited by its very slow onset of action, unfortunately. According to the study by Hartford Hospital, there is cases of two adolescents with fulminant colitis who were being considered for colectomy and who were treated with oral cyclosporine. Each appeared to have a prompt response to this medication, and both entered into a complete clinical remission. A mild increase in serum creatinine and hirsutism were the only side effects noted(113).
2. Other medicines
According to the study by Hahnemann University School of Medicine, patients with fulminant disease may require intravenous steroids and antibiotic therapy. If frequent relapses prevent discontinuation or significant reduction of prednisone therapy, azathioprine or 6-mercaptopurine may offer benefit as steroid-sparing agents. Also, intravenous cyclosporine has proved useful in patients with fulminant inflammatory bowel disease that is unresponsive to other therapy(114).
A.7.2. Surgical treatment
1. Total colectomy
Although total abdominal colectomy has long been considered definitive treatment for fulminant ulcerative colitis refractory to medical management, the optimal timing of surgery remains controversial. According to the study by The Mount Sinai Medical Center, showed that prolonged duration of preoperative medical treatment correlates with poor postoperative outcomes after total abdominal colectomy for fulminant ulcerative colitis. In addition, sustaining postoperative complications did not prevent patients from eventually undergoing IPAA(115).
Also in the study to to define clinical and radiographic variables associated with postoperative mortality after urgent colectomy for fulminant Clostridium difficile colitis with data obtained regarding patients undergoing colectomy for fulminant C. difficile colitis at two institutions (1997-2005), showed that
hirty-five patients (mean age 70 years, 46% male) underwent urgent colectomy for C. difficile colitis. The 30-day mortality rate was 45.7 per cent (16/35). The only clinical variable associated with mortality was preoperative multisystem organ failure (nonsurvivors 9/16 vs survivors: 4/19; P = 0.037). None of the three patients undergoing partial colectomy survived, although the difference in survival versus those undergoing subtotal colectomy was not significant. Patients with fulminant C. difficile colitis undergoing colectomy have a high mortality rate. Preoperative presence of multisystem organ failure was independently predictive of mortality(116).
2. Laparoscopic creation of an ileostomy
Due to several recent studies have elucidated factors that contribute to the unacceptably high postoperative mortality rate of colectomy, an alternative surgical strategy for fulminant C. difficile colitis is laparoscopic creation of an ileostomy with total colonic washout(117).
Chinese Secrets To Fatty Liver And Obesity Reversal
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Sources
(112) http://journals.lww.com/jpgn/fulltext/1996/10000/tacrolimus__fk_506__treatment_of_fulminant_colitis.23.aspx
(113) http://www.ncbi.nlm.nih.gov/pubmed/2614627
(114) http://www.ncbi.nlm.nih.gov/pubmed/7762487
(115) http://www.ncbi.nlm.nih.gov/pubmed/23062652
(116) http://www.ncbi.nlm.nih.gov/pubmed/20420254
(117) http://www.ncbi.nlm.nih.gov/pubmed/20583866
Treatments
A. In conventional medicine perspective
Fulminant colitis
A.7.1. Non surgical therapy
1. Immunosuppressive drug
a. Tacrolimus (FK-506)
Immunosuppressive drugs are increasingly being used as a therapeutic alternative to colectomy in patients with ulcerative or Crohn's colitis. According to the study of Tacrolimus (FK-506) Treatment of Fulminant Colitis in a Child in Journal of Pediatric Gastroenterology & Nutrition:October 1996 - Volume 23 - Issue 3 - pp 329-333, oral tacrolimus offers a potential alternative to cyclosporine in patients with steroid-resistant fulminant colitis and offers the potential advantages of more reliable oral absorption and greater ease of administration. The side effects of tacrolimus are similar to those of cyclosporine, but some adverse effects (including hypertension, gingival hyperplasia, and coarsening of facial features)(112).
b. Cyclosporine
The use of immunosuppressive medications such as 6-mercaptopurine in individuals with fulminant disease is often limited by its very slow onset of action, unfortunately. According to the study by Hartford Hospital, there is cases of two adolescents with fulminant colitis who were being considered for colectomy and who were treated with oral cyclosporine. Each appeared to have a prompt response to this medication, and both entered into a complete clinical remission. A mild increase in serum creatinine and hirsutism were the only side effects noted(113).
2. Other medicines
According to the study by Hahnemann University School of Medicine, patients with fulminant disease may require intravenous steroids and antibiotic therapy. If frequent relapses prevent discontinuation or significant reduction of prednisone therapy, azathioprine or 6-mercaptopurine may offer benefit as steroid-sparing agents. Also, intravenous cyclosporine has proved useful in patients with fulminant inflammatory bowel disease that is unresponsive to other therapy(114).
A.7.2. Surgical treatment
1. Total colectomy
Although total abdominal colectomy has long been considered definitive treatment for fulminant ulcerative colitis refractory to medical management, the optimal timing of surgery remains controversial. According to the study by The Mount Sinai Medical Center, showed that prolonged duration of preoperative medical treatment correlates with poor postoperative outcomes after total abdominal colectomy for fulminant ulcerative colitis. In addition, sustaining postoperative complications did not prevent patients from eventually undergoing IPAA(115).
Also in the study to to define clinical and radiographic variables associated with postoperative mortality after urgent colectomy for fulminant Clostridium difficile colitis with data obtained regarding patients undergoing colectomy for fulminant C. difficile colitis at two institutions (1997-2005), showed that
hirty-five patients (mean age 70 years, 46% male) underwent urgent colectomy for C. difficile colitis. The 30-day mortality rate was 45.7 per cent (16/35). The only clinical variable associated with mortality was preoperative multisystem organ failure (nonsurvivors 9/16 vs survivors: 4/19; P = 0.037). None of the three patients undergoing partial colectomy survived, although the difference in survival versus those undergoing subtotal colectomy was not significant. Patients with fulminant C. difficile colitis undergoing colectomy have a high mortality rate. Preoperative presence of multisystem organ failure was independently predictive of mortality(116).
2. Laparoscopic creation of an ileostomy
Due to several recent studies have elucidated factors that contribute to the unacceptably high postoperative mortality rate of colectomy, an alternative surgical strategy for fulminant C. difficile colitis is laparoscopic creation of an ileostomy with total colonic washout(117).
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Sources
(112) http://journals.lww.com/jpgn/fulltext/1996/10000/tacrolimus__fk_506__treatment_of_fulminant_colitis.23.aspx
(113) http://www.ncbi.nlm.nih.gov/pubmed/2614627
(114) http://www.ncbi.nlm.nih.gov/pubmed/7762487
(115) http://www.ncbi.nlm.nih.gov/pubmed/23062652
(116) http://www.ncbi.nlm.nih.gov/pubmed/20420254
(117) http://www.ncbi.nlm.nih.gov/pubmed/20583866
Indeterminate colitis and Atypical colitis - Treatments in Conventional medicine
Colitis is defined as a condition of inflammation of the large intestine, including the colon, caecum and rectum.
Treatments
A. In conventional medicine perspective
A.6. Indeterminate colitis and Atypical colitis
A.6.1. Indeterminate colitis
Indeterminate colitis (IC) originally referred to those 10–15% of cases of inflammatory bowel disease (IBD) in which there was difficulty distinguishing between ulcerative colitis (UC) and Crohn’s disease (CD) in the colectomy specimen(104). Other researchers defined that a diagnosis of indeterminate colitis (IC) is based on endoscopic, histologic, and radiologic findings when the criteria for either Crohn's colitis or ulcerative colitis (UC) cannot be definitively established(105). Others indicated that most cases of IC represent UC upon long-term clinical follow-up. Although, in some instances, serologic testing for ANCA or ASCA may be helpful in separating UC from CD in patients with IC, there is much overlap in the results of these assays for cases in which CD involves the colon in a UC-like pattern. Approximately 20% of IC patients develop severe pouch complications, which is intermediate in frequency between that seen in ulcerative colitis (UC) or CD. The risk of pouch complications, such as perianal fistulas or abscesses, and the risk of pouch breakdown is, overall, quite similar between IC and UC patients, supporting the notion that most patients with IC probably have UC and can safely undergo an ileal pouch-anal anastomosis (a procedure involves the creation of a pouch of small intestine to recreate the removed rectum) procedure and have a reasonably good chance of having a good outcome(106).
According to the study by Center for Crohn's and Colitis, Brigham and Women's Hospital, no studies have been undertaken to determine the optimum treatment regimen for IC. Recent studies have shown that patients with IC are still appropriate candidates for ileal pouch anal anastomosis. In conclusion, the current data support the premise that IC may be a separate entity, but future studies will have to focus on the genotypic and phenotypic characterization of these patients(107).
1. Medical therapy
Medication used to treatment commonly in treating IBD, is also being used in IC.
2. Surgical therapy
Total proctocolectomy and ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for a large number of patients with UC(108).
A.6.2. Atypical colitis
Treatment of atypical colitis is dependence to the differentiation
1. C. difficile colitis
According to the study by St. Thomas' Hospital, Guy's & St Thomas' NHS Foundation Trust, in patients with cystic fibrosis, imaging findings of a pancolitis should raise the possibility of C. difficile colitis despite the lack of watery diarrhea. Anticlostridial treatment can be initiated before bacteriologic confirmation is obtained(109).
2. Atypical forms of microscopic colitis
Microscopic colitis is defined as a syndrome of chronic watery diarrhea with a chronic inflammatory cell infiltrate in the colonic mucosa but without significant abnormalities at colonoscopy. According to the study by St. Thomas' Hospital, Guy's & St Thomas' NHS Foundation Trust, London, by considering the clinical history and symptoms, the pathologist should be able to reach the correct diagnosis in most cases. However, the spectrum of morphologic changes associated with watery diarrhea syndrome appears to be broader than originally thought. Morphologic changes more often associated with chronic inflammatory bowel disease or even chronic ischemic or infectious colitis have been noted in patients with clinically established microscopic colitis. The data presented in this article suggest that microscopic colitis is a heterogeneous entity, which includes both classic and "atypical" forms(110).
3. Atypical allergic colitis
There is a report of 2 atypical cases of colitis due to cow's milk protein intolerance (CMPI) are reported, affecting preterm infants. One developed a toxic dilatation of the colon and responded well to a casein hydrolysate based feed. The second presented insidiously and failed to tolerate a casein hydrolysate, but responded well to a chicken-based modular feed(111)
4. Etc.
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
Back to General health http://kylejnorton.blogspot.ca/p/general-health.html
Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca
Sources
(107) http://www.ncbi.nlm.nih.gov/pubmed/15115931
(108) www.annalsgastro.gr/index.php/annalsgastro/article/download/681/497
(109) http://www.ncbi.nlm.nih.gov/pubmed/9930816
(110) http://www.ncbi.nlm.nih.gov/pubmed/16096382
(111) http://www.ncbi.nlm.nih.gov/pubmed/1750352
Treatments
A. In conventional medicine perspective
A.6. Indeterminate colitis and Atypical colitis
A.6.1. Indeterminate colitis
Indeterminate colitis (IC) originally referred to those 10–15% of cases of inflammatory bowel disease (IBD) in which there was difficulty distinguishing between ulcerative colitis (UC) and Crohn’s disease (CD) in the colectomy specimen(104). Other researchers defined that a diagnosis of indeterminate colitis (IC) is based on endoscopic, histologic, and radiologic findings when the criteria for either Crohn's colitis or ulcerative colitis (UC) cannot be definitively established(105). Others indicated that most cases of IC represent UC upon long-term clinical follow-up. Although, in some instances, serologic testing for ANCA or ASCA may be helpful in separating UC from CD in patients with IC, there is much overlap in the results of these assays for cases in which CD involves the colon in a UC-like pattern. Approximately 20% of IC patients develop severe pouch complications, which is intermediate in frequency between that seen in ulcerative colitis (UC) or CD. The risk of pouch complications, such as perianal fistulas or abscesses, and the risk of pouch breakdown is, overall, quite similar between IC and UC patients, supporting the notion that most patients with IC probably have UC and can safely undergo an ileal pouch-anal anastomosis (a procedure involves the creation of a pouch of small intestine to recreate the removed rectum) procedure and have a reasonably good chance of having a good outcome(106).
According to the study by Center for Crohn's and Colitis, Brigham and Women's Hospital, no studies have been undertaken to determine the optimum treatment regimen for IC. Recent studies have shown that patients with IC are still appropriate candidates for ileal pouch anal anastomosis. In conclusion, the current data support the premise that IC may be a separate entity, but future studies will have to focus on the genotypic and phenotypic characterization of these patients(107).
1. Medical therapy
Medication used to treatment commonly in treating IBD, is also being used in IC.
2. Surgical therapy
Total proctocolectomy and ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for a large number of patients with UC(108).
A.6.2. Atypical colitis
Treatment of atypical colitis is dependence to the differentiation
1. C. difficile colitis
According to the study by St. Thomas' Hospital, Guy's & St Thomas' NHS Foundation Trust, in patients with cystic fibrosis, imaging findings of a pancolitis should raise the possibility of C. difficile colitis despite the lack of watery diarrhea. Anticlostridial treatment can be initiated before bacteriologic confirmation is obtained(109).
2. Atypical forms of microscopic colitis
Microscopic colitis is defined as a syndrome of chronic watery diarrhea with a chronic inflammatory cell infiltrate in the colonic mucosa but without significant abnormalities at colonoscopy. According to the study by St. Thomas' Hospital, Guy's & St Thomas' NHS Foundation Trust, London, by considering the clinical history and symptoms, the pathologist should be able to reach the correct diagnosis in most cases. However, the spectrum of morphologic changes associated with watery diarrhea syndrome appears to be broader than originally thought. Morphologic changes more often associated with chronic inflammatory bowel disease or even chronic ischemic or infectious colitis have been noted in patients with clinically established microscopic colitis. The data presented in this article suggest that microscopic colitis is a heterogeneous entity, which includes both classic and "atypical" forms(110).
3. Atypical allergic colitis
There is a report of 2 atypical cases of colitis due to cow's milk protein intolerance (CMPI) are reported, affecting preterm infants. One developed a toxic dilatation of the colon and responded well to a casein hydrolysate based feed. The second presented insidiously and failed to tolerate a casein hydrolysate, but responded well to a chicken-based modular feed(111)
4. Etc.
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
Back to General health http://kylejnorton.blogspot.ca/p/general-health.html
Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca
Sources
(107) http://www.ncbi.nlm.nih.gov/pubmed/15115931
(108) www.annalsgastro.gr/index.php/annalsgastro/article/download/681/497
(109) http://www.ncbi.nlm.nih.gov/pubmed/9930816
(110) http://www.ncbi.nlm.nih.gov/pubmed/16096382
(111) http://www.ncbi.nlm.nih.gov/pubmed/1750352
Infectious colitis - Treatments in Conventional medicine
Colitis is defined as a condition of inflammation of the large intestine, including the colon, caecum and rectum.
Treatments
A. In conventional medicine perspective
Infectious colitis
Clostridium difficile, atypes of infectous colitis, has become an increasingly important nosocomial pathogen and is one of the most common causes of hospital-acquired diarrhea. The incidence of C difficile infection (CDI) is increasing worldwide(97a).
A.5.1. Non surgical therapy
1. Antimotility therapy
If patients are expereince with diarrhea of small bowel origin, then Antimotility therapy can be helpful. According to the study by the Service de Médecine B Centre hospitalier universitaire de l'hôpital d'adultes, although effective therapy is not available for patients with enteric viruses, Cryptosporidium, and Microsporidium, therapy is useful for children with amebiasis, antimicrobial-associated colitis, cholera, giardiasis, various forms of Escherichia coli diarrhea and Salmonella disease, isosporiasis, shigellosis, and strongyloidiasis(98).
2. Probotic
Perturbation of bacterial microflora of the gastrointestinal (GI) tract may play an important role in the pathophysiology of some GI disorders. Probiotics have been used as a treatment modality for over a century. They may restore normal bacterial microflora and effect the functioning of the GI tract by a variety of mechanisms. According to the study by Columbia University College of Physicians and Surgeons, the efficacy of probiotics, either as a single strain or a combination of probiotics, has been tested in antibiotic-associated diarrhea, Clostridium difficile colitis, infectious diarrhea, ulcerative colitis, Crohn's disease, pouchitis, and irritable bowel syndrome, among other disorders. Results of the studies are reviewed in this article and recommendations for probiotic use in these disorders are made. Although probiotics appear to be generally safe in an outpatient setting, the situation may be different in immunocompromised, hospitalized patients who may be at a greater risk of developing probiotic sepsis(99).
3. Other treatments
In the study to review and to investigate the efficacy of antibiotic therapy for C. difficile-associated diarrhea (CDAD), conducted by Northern General Hospital, indicated that the studies provide little evidence for antibiotic treatment of severe CDAD as many studies excluded these patients. A recommendation to achieve these goals cannot be made because of the small numbers of patients in the included studies and the high risk of bias in these studies, especially related to dropouts. Most of the active comparator studies found no statistically significant difference in efficacy between vancomycin and other antibiotics including metronidazole, fusidic acid, nitazoxanide or rifaximin. Teicoplanin may be an attractive choice but for its limited availability (Teicoplanin is not available in the USA) and great cost relative to the other options. More research of antibiotic treatment and other treatment modalities of CDAD is required(100).
Other researcher indicated that treatment of Clostridium difficile CDI is challenging due to the limited number of drugs that have proven to be effective, concerns about antibiotic resistance, and recurring disease. The recent approval of fidaxomicin provides a new alternative. Immune therapy will likely play a greater role in the future(101).
A.5.2. Surgical treatment
Sugical treatment may be necessary for patients with microscopic colitis if patients are not respond to medication treatment, depending to the patients conditions.
In the study of sixty-seven patients (mean age, 69 (range, 40-86) years; 99 percent males) were identified. All 67 patients had C. difficile verified in the colectomy specimens, found that twenty-six of 67 patients (39 percent) underwent colonoscopy; all 26 were found to have severe inflammation or pseudomembranes. Fifty-three of 67 patients (80 percent) underwent total colectomy; 14 of 67 underwent segmental colonic resection. Perforation and infarction were found in 59 of 67 patients (58 percent) at surgery. Overall mortality was 48 percent (32/67). Mean hospitalization was 36 (range, 2-297) days(102). Several recent studies have elucidated factors that contribute to the unacceptably high postoperative mortality rate: Surgical intervention too late in the course of the disease, lack of clearly defined guidelines for patient selection, and difficulty in predicting the clinical course of the disease. Perforation, need for vasopressor support, and end-organ damage all affect the postoperative mortality rate negatively(103).
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
Back to General health http://kylejnorton.blogspot.ca/p/general-health.html
Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca
Sources
(97) http://www.ncbi.nlm.nih.gov/pubmed/7297823
(98) http://www.ncbi.nlm.nih.gov/pubmed/2007952
(99) http://www.ncbi.nlm.nih.gov/pubmed/21180611
(100) http://www.ncbi.nlm.nih.gov/pubmed/21901692
(101) http://www.ncbi.nlm.nih.gov/pubmed/22260856
(102) http://www.ncbi.nlm.nih.gov/pubmed/15540290
(103) http://www.ncbi.nlm.nih.gov/pubmed/20583866
(104) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770507/
Treatments
A. In conventional medicine perspective
Infectious colitis
Clostridium difficile, atypes of infectous colitis, has become an increasingly important nosocomial pathogen and is one of the most common causes of hospital-acquired diarrhea. The incidence of C difficile infection (CDI) is increasing worldwide(97a).
A.5.1. Non surgical therapy
1. Antimotility therapy
If patients are expereince with diarrhea of small bowel origin, then Antimotility therapy can be helpful. According to the study by the Service de Médecine B Centre hospitalier universitaire de l'hôpital d'adultes, although effective therapy is not available for patients with enteric viruses, Cryptosporidium, and Microsporidium, therapy is useful for children with amebiasis, antimicrobial-associated colitis, cholera, giardiasis, various forms of Escherichia coli diarrhea and Salmonella disease, isosporiasis, shigellosis, and strongyloidiasis(98).
2. Probotic
Perturbation of bacterial microflora of the gastrointestinal (GI) tract may play an important role in the pathophysiology of some GI disorders. Probiotics have been used as a treatment modality for over a century. They may restore normal bacterial microflora and effect the functioning of the GI tract by a variety of mechanisms. According to the study by Columbia University College of Physicians and Surgeons, the efficacy of probiotics, either as a single strain or a combination of probiotics, has been tested in antibiotic-associated diarrhea, Clostridium difficile colitis, infectious diarrhea, ulcerative colitis, Crohn's disease, pouchitis, and irritable bowel syndrome, among other disorders. Results of the studies are reviewed in this article and recommendations for probiotic use in these disorders are made. Although probiotics appear to be generally safe in an outpatient setting, the situation may be different in immunocompromised, hospitalized patients who may be at a greater risk of developing probiotic sepsis(99).
3. Other treatments
In the study to review and to investigate the efficacy of antibiotic therapy for C. difficile-associated diarrhea (CDAD), conducted by Northern General Hospital, indicated that the studies provide little evidence for antibiotic treatment of severe CDAD as many studies excluded these patients. A recommendation to achieve these goals cannot be made because of the small numbers of patients in the included studies and the high risk of bias in these studies, especially related to dropouts. Most of the active comparator studies found no statistically significant difference in efficacy between vancomycin and other antibiotics including metronidazole, fusidic acid, nitazoxanide or rifaximin. Teicoplanin may be an attractive choice but for its limited availability (Teicoplanin is not available in the USA) and great cost relative to the other options. More research of antibiotic treatment and other treatment modalities of CDAD is required(100).
Other researcher indicated that treatment of Clostridium difficile CDI is challenging due to the limited number of drugs that have proven to be effective, concerns about antibiotic resistance, and recurring disease. The recent approval of fidaxomicin provides a new alternative. Immune therapy will likely play a greater role in the future(101).
A.5.2. Surgical treatment
Sugical treatment may be necessary for patients with microscopic colitis if patients are not respond to medication treatment, depending to the patients conditions.
In the study of sixty-seven patients (mean age, 69 (range, 40-86) years; 99 percent males) were identified. All 67 patients had C. difficile verified in the colectomy specimens, found that twenty-six of 67 patients (39 percent) underwent colonoscopy; all 26 were found to have severe inflammation or pseudomembranes. Fifty-three of 67 patients (80 percent) underwent total colectomy; 14 of 67 underwent segmental colonic resection. Perforation and infarction were found in 59 of 67 patients (58 percent) at surgery. Overall mortality was 48 percent (32/67). Mean hospitalization was 36 (range, 2-297) days(102). Several recent studies have elucidated factors that contribute to the unacceptably high postoperative mortality rate: Surgical intervention too late in the course of the disease, lack of clearly defined guidelines for patient selection, and difficulty in predicting the clinical course of the disease. Perforation, need for vasopressor support, and end-organ damage all affect the postoperative mortality rate negatively(103).
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
Back to General health http://kylejnorton.blogspot.ca/p/general-health.html
Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca
Sources
(97) http://www.ncbi.nlm.nih.gov/pubmed/7297823
(98) http://www.ncbi.nlm.nih.gov/pubmed/2007952
(99) http://www.ncbi.nlm.nih.gov/pubmed/21180611
(100) http://www.ncbi.nlm.nih.gov/pubmed/21901692
(101) http://www.ncbi.nlm.nih.gov/pubmed/22260856
(102) http://www.ncbi.nlm.nih.gov/pubmed/15540290
(103) http://www.ncbi.nlm.nih.gov/pubmed/20583866
(104) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770507/
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