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Fish oil fatty acid supplementation in active
ulcerative colitis: A double-blind, placebo-controlled,
crossover study
Aslan A.; Triadafilopoulos G.
Gastroenterology Section, Martinez VA Medical Center, 150
Muir Road, Martinez, CA 94553 USA
Am. J. Gastroenterol. (USA), 1992, 87/4
(432-437)
Arachidonic acid metabolites formed by both the
cyclooxygenase and lipoxygenase pathways may contribute to the
clinical diarrhea and colitis of inflammatory bowel disease.
Patients with active ulcerative colitis have increased levels
of leukotriene B4 in their rectal mucosa, and these levels
tend to correlate with severity of the disease. In this study,
we evaluated the efficacy of ingestion of fish oil
n-3-omega-fatty acids, inhibitors of leukotriene synthesis, in
the treatment of ulcerative colitis. Eleven patients with
ulcerative colitis of mild to moderate severity were studied
in a 8-month, double-blind, placebo-controlled, crossover
trial of dietary supplementation with fish oil, which provided
about 4.2 g of omega-3- fatty acids per day. A disease
activity index based on patient symptoms and sigmoidoscopic
appearance was used to assess efficacy. Mucosal leukotriene B4
production was measured by radioimmunoassay. Mean disease
activity index declined 56% for patients receiving fish oil
and 4% for patients on placebo (p < 0.05). There were no
statistically significant differences in histopathologic
scores or colonic mucosal leukotriene B4 levels. All patients
tolerated fish oil ingestion and showed no alteration in
routine blood studies. No patient worsened; anti-inflammatory
drugs could be reduced or eliminated in eight patients (72%)
while receiving fish oil. We conclude that fish oil dietary
supplementation results in clinical improvement of active mild
to moderate ulcerative colitis but is not associated with
significant reduction in mucosal leukotriene B4 production,
compared with placebo therapy. Further studies are needed to
elucidate the mechanism of action and optimal dose and
duration of fish oil supplementation in ulcerative
colitis.
Omega-3 fatty acids in health and disease and in
growth and development
Simopoulos A.P.
The Center for Genetics, Nutrition and Health, 2001 S Street,
NW, Washington, DC 20009 USA
Am. J. Clin. Nutr. (USA), 1991, 54/3 (438-463)
Several sources of information suggest that man evolved on
a diet with a ratio of omega6 to omega3 fatty acids of similar
1 whereas today this ratio is similar 10:1 to 20-25:1,
indicating that Western diets are deficient in omega3 fatty
acids compared with the diet on which humans evolved and their
genetic patterns were established. Omega-3 fatty acids
increase bleeding time; decrease platelet aggregation, blood
viscosity, and fibrinogen; and increase erythrocyte
deformability, thus decreasing the tendency to thrombus
formation. In no clinical trial, including coronary artery
graft surgery, has there been any evidence of increased blood
loss due to ingestion of omega3 fatty acids. Many studies show
that the effects of omega3 fatty acids on serum lipids depend
on the type of patient and whether the amount of saturated
fatty acids in the diet is held constant. In patients with
hyperlipidemia, omega3 fatty acids decrease
low-density-lipoprotein (LDL) cholesterol if the saturated
fatty acid content is decreased, otherwise there is a slight
increase, but at high doses (32 g) they lower LDL cholesterol;
furthermore, they consistently lower serum triglycerides in
normal subjects and in patients with hypertriglyceridemia
whereas the effect on high-density lipoprotein (HDL) varies
from no effect to slight increases. The discrepancies between
animal and human studies most likely are due to differences
between animal and human metabolism. In clinical trials
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in
the form of fish oils along with antirheumatic drugs improve
joint pain in patients with rheumatoid arthritis; have a
beneficial effect in patients with ulcerative colitis; and in
combination with drugs, improve the skin lesions, lower the
hyperlipidemia from etretinates, and decrease the toxicity of
cyclosporin in patients with psoriasis. In various animal
models omega3 fatty acids decrease the number and size of
tumors and increase the time elapsed before appearance of
tumors. Studies with nonhuman primates and human newborns
indicate that DHA is essential for the normal functional
development of the retina and brain, particularly in premature
infants. Because omega3 fatty acids are essential in growth
and development throughout the life cycle, they should be
included in the diets of all humans. Omega-3 and omega6 fatty
acids are not interconvertible in the human body and are
important components of practically all cell membranes.
Whereas cellular proteins are genetically determined, the
polyunsaturated fatty acid (PUFA) composition of cell
membranes is to a great extent dependent on the dietary
intake. Therefore appropriate amounts of dietary omega6 and
omega3 fatty acids need to be considered in making dietary
recommendations, and these two classes of PUFAs should be
distinguished because they are metabolically and functionally
distinct and have opposing physiological functions. Their
balance is important for homeostasis and normal development.
Canada is the first country to provide separate dietary
recommendations for omega6 and omega3 fatty acids.
Does nutritional therapy in inflammatory bowel
disease have a primary or an adjunctive role?
O'Morain C.A.
Department of Gastroenterology, Meath/Adelaide Hospitals,
Peter Street, Dublin 8 Ireland
Scand. J. Gastroenterol. Suppl. (Norway), 1990, 25/172
(29-34)
The aetiology of inflammatory bowel disease (IBD) remains
unknown, and many methods of treatment have been advocated.
Patients with IBD are often nutritionally deficient and in
negative nitrogen balance. The cause is multifactorial and
includes decreased intake and absorption due to previous
resection or mucosal involvement or increased exudation.
General recommendations of vitamin and mineral supplements are
usually made for these patients. Diet may have a more
fundamental role in the aetiology and treatment of Crohn's
disease, although this is not certain. Several controlled
studies have confirmed that an elemental diet is as effective
as steroids in inducing a remission in patients with acute
Crohn's disease. Bacteria have also been implicated in the
aetiology of Crohn's disease. Dietary measures may alter the
intestinal flora and could result in a decrease of toxin
production, which has been shown to correlate with clinical
improvement. Although elemental diets are not effective in the
treatment of ulcerative colitis, dietary measures may still be
important. Preliminary studies suggest that eicosapentaenoic
acid, which inhibits the production of mediators of
inflammation by competing with enzymes in the arachidonic acid
pathway, may be effective. Recent findings of increased faecal
bile acids in patients with long-standing ulcerative colitis
who developed dysplasia or carcinoma suggest that dietary
measures may counteract these developments. It does appear
that nutritional therapy in patients with IBD has both a
primary and adjunctive role.
Food allergy: The major cause of infantile
colitis
Jenkins H.R.; Pincott J.R.; Soothill J.F.; et al.
Department of Gastroenterology, The Hospital for Sick
Children, London United Kingdom
Arch. Dis. Child. (England), 1984, 59/4
(326-329)
Forty six children presented with colitis between 1977 and
1981, and all 8 of those below the age of 2 years had food
allergic colitis which resolved completely after exclusion of
certain foods. In most of the 8 the onset was soon after
starting foods other than breast milk. The most common
offending food was cows' milk protein, but soya (3 cases) and
beef (1 case) were also implicated. A history of allergy in
the child or family was common as were blood eosinophilia,
high concentrations of serum IgE, and positive IgE antibodies.
Colonoscopic appearances were distinctive and biopsies showed
a noticeable increase in eosinophils and IgE-containing cells
in the lamina propria. We suggest that food allergy is the
major cause of colitis in infancy and that an exclusion diet
is the treatment of choice.
Is continuous enteral alimentation effective in
gastrointestinal patients? Results in a series of 92
consecutive patients treated for 3 to 7 weeks
Cosnes J.; Tello H.; Le Quintrec M.; et al.
Service d'Hepato Gastroenterologie, Hopital Rothschild,
F-75571 Paris Cedex 12 France
Gastroenterol. Clin. Biol. (France), 1983, 7/12
(1003-1009)
In order to assess the effectiveness and potential
limitations of continuous enteral nutrition (CEN) to correct
denutrition related to underlying digestive diseases, 10
nutritional criteria were measured weekly in 92 undernourished
patients fed with CEN for a 3-7 week period. All the patients
received a standard non-elemental diet providing a mean daily
energy intake of 52.8 kcal/kg BW (36.5 kcal/kg BW by tube
feeding and 16.3 kcal/kg BW orally). The influence of
preexisting intestinal malabsorption, hypercatabolic status,
and post-radiation or inflammatory bowel disease was studied
by an a posteriori classification of patients in one of the
six following groups: I (no limiting factor), II
(malabsorption), III (catabolic disease), IV (catabolic
disease and malabsorption), V (colitis), VI (enteritis).
During CEN, 8 patients had transient and one had persistent
vomiting while 3 developed bronchopneumonia. Gains in body
weight, triceps skinfold, midarm muscle circumference,
creatinine-height index, urinary sodium and serum transferrin
were significant as early as the 2nd week of CEN. Serum
albumin and cholesterol, hemoglobin, and total count of
lymphocytes were not significantly affected. Sixty-five
patients (71 per cent) had an objective nutritional
improvement and mean spontaneous oral intake increased from
17.8 to 28.7 kcal/kg BW per day. Significant increase of oral
intake and objective nutritional improvement were observed in
each group, but a longer period of CEN was necessary to
achieve this result in groups II, IV and VI. These results a)
confirm that CEN is an effective and well tolerated
nutritional treatment in gastrointestinal patients, b)
describe the kinetics of nutritional improvement during CEN,
and c) show that, in the alimentary conditions of this study,
malabsorption, hypercatabolic disease or inflammatory
enteropathy are not a contra-indication to the use of CEN. In
chronic denutrition CEN must be administered during at least 3
weeks and prolonged until nutritional autonomy is
obtained.
The faecal flora of patients with Crohn's
disease
Wensinck F.; Custers-Van Lieshout L.M.C.;
Poppelaars-Kustermans P.A.J.; Schroder A.M.
Dept. Med. Microbiol., Erasmus Univ., Rotterdam
Netherlands
J. Hyg. (England), 1981, 87/1 (1-12)
The faecal flora of patients with Crohn's disease was
compared with that of healthy subjects. In patients with
terminal ileitis, numbers of anaerobic gram-negative and
coccoid rods (species of Eubacterium and Peptostreptococcus)
were higher than in the controls whereas anaerobic
gram-positive rods and cocci and aerobes occurred in normal
numbers. The composition of the flora was neither influenced
by duration of the disease nor by ileocaecal resection. In
healthy subjects and patients, a chemically defined diet
induced only slight changes in the flora. Thus, the flora in
terminal ileitis although stable was permanently abnormal. In
patients with Crohn's colitis, abnormally low numbers of
anaerobes were found in patients with severe, bloody diarrhoea
while aerobic counts were normal. The flora in patients with
mild colitis was similar to that in terminal ileitis. It is
suggested that the abnormal flora composition might be an
expression of the genetic predisposition to Crohn's
disease.
Elemental diet in gastrointestinal diseases:
experience from a case material of 59 patients
Axelsson C.; Jarnum S.
Div. Gastroenterol., Med. Dept. P, Rigshosp., Univ.
Copenhagen Denmark
Infusionsther. Klin. Ernahr. (Switzerland), 1977, 4/6
(313-318)
During a 4-year period 59 patients were treated with an
elemental diet (Vivasorb(Reg.trademark)) for 1-6 weeks. The
great majority (41 patients) were suffering from chronic
inflammatory bowel disease. The indication for treatment was
insufficient remission on prednisone 10-60 mg daily for 1-4
weeks or no remission after a high dose of prednisone (6O-120
mg) for 1-4 weeks. Remission was obtained in 14 patients on
elemental diet and a constant or decreasing dose of prednisone
and in another 6 on elemental diet and a high dose of
prednisone. Thus, a total of 2O patients (50%) remitted. This
includes 12 out of 24 with ulcerative colitis, and 8 out of 17
with Crohn's disease. It was not possible to demonstrate
significant differences between the groups having moderate and
severe disease activity, or between those with topographically
restricted and with extensive lesions. The remission was long.
During this treatment of patients with chronic inflammatory
bowel disease there occurred a significant reduction in faecal
bulk, frequency of bowel movements, and the ESR (erythrocyte
sedimentation rate). A number of parameters, including serum
protein and albumin, remained greatly reduced. Moreover, there
was a significant decrease in serum urea and in the renal
excretion of urea, due to the low nitrogen content of
Vivasorb(Reg.trademark). Treatment of patients with intestinal
fistulae (13 patients), the short bowel syndrome (6 patients),
intractable diarrhoea (4 patients), recurrent pancreatitis (2
patients) and hyperlipaemia (2 patients) gave good results in
several, but far from all cases. In particular, no effect was
obtained in patients having the short bowel syndrome.
Elemental diet as an alternative to intravenous
nutrition in severe gastrointestinal disease
Goschke H.; Buess H.; Gyr K.; et al.
Dept. Inn. Med., Univ., Basel Switzerland
Schweiz.Med.Wschr. (Switzerland), 1977, 107/2
(43-49)
21 patients with gastroenterological disease and indication
for the use of intravenous nutrition received an elemental
diet (ED) for 5-44 days. In 6 out of 8 patients with
exacerbation of Crohn's disease remissions were achieved,
apart from 3 persistent fistulas. In 5 out of 9 cases with
various primary diseases and postoperative intestinal
fistulas, spontaneous healing was observed. Furthermore, 2
patients with ulcerative colitis, 1 with radiation enteritis
and 1 with pancreatitis were treated with ED. On ED,
hemoglobin increased from 11.3 + or - 0.4 (m + or - SEM) to
12.0 + or - 0.5 g% (p <0.01) and serum albumin from 2.7 +
or - 0.1 to 3.4 + or - 0.1 g% (p <0.001). Nitrogen
requirements were studied in 11 patients receiving various
quantities of ED. Nitrogen balance was found to be in
equilibrium or positive in 7 patients, and negative in 4. In
one patient with severe ulcerative colitis, fecal nitrogen
losses were higher than urinary nitrogen losses. The
unpleasant taste of ED resulting from free amino acids limited
the ED supply in 3 patients and led to premature ending of ED
administration in 3 other patients. In such cases ED may be
given by nasogastric tube feeding. From the results presented
it appears that ED is indicated in Crohn's disease and
intestinal fistulas. However, the results obtained require
confirmation by further observations and comparison with an
intravenously fed control group.
Selective immunoglobulin A deficiency, ulcerative
colitis, and gluten sensitive enteropathy. A unique
association
Falchuk K.R.; Falchuk Z.M.
Dept. Med., Massachusetts Gen. Hosp., Peter Bent Brigham
Hosp., Boston, Mass. USA
Gastroenterology (USA), 1975, 69/2 (503-506)
A patient with selective immunoglobulin A deficiency,
severe ulcerative colitis, and malabsorption had a flat
jejunal mucosa demonstrated by peroral biopsy. Treatment at
different times with a gluten free diet for the jejunal lesion
and corticosteroids for the ulcerative colitis, led to
improvement of the malabsorption. A great jejunal biopsy
demonstrated histological improvement of the jejunal mucosa,
even though the colitis remained active. The occurrence of
immunoglobulin A deficiency in a patient with ulcerative
colitis and gluten sensitive enteropathy is uncommon.
Absorption of medium chain triglyceride and its
clinical appraisal
Ito T.
I Dept. Int. Med., Hirosaki Univ. Sch. Med., Hirosaki
Japan
Hirosaki Med.J. (Japan), 1974, 26/2 (167-186)
A comparative study of the absorption of various kinds of
fatty acids and corresponding triglycerides and a study of MCT
metabolism in experimental animals is presented. Time lapse
absorption of MCT and LCT was studied in fasted albino rats by
giving orally sup 1sup 4C labeled fatty acid preparations.
Octanoic acids were mostly absorbed within an hr but only 32%
of palmitate. The absorption of sup 1sup 4C labeled glycerol
trioctanoate was studied. Small intestines of the dog were
ligated and segmented into 3 parts (upper, middle and lower).
Of the 3 segments, the middle showed the fastest absorption of
glycerol trioctanoate 1 sup 1sup 4C. Experiments in dogs with
indwelling cannulas in the thoracic ducts showed that only
5.21 x 10sup -sup 2 muCi of administered glycerol trioctanoate
1 sup 1sup 4C was transported to the lymphatics in 120 min.
The radioactivity in the lipids of albino rat liver was
studied 60 and 120 min after an oral administration of
glycerol trioctanoate 1 sup 1sup 4C. The radioactivity of the
lipid fraction was 1.3% of all activity that was absorbed.
Nearly 54.1% of the radioactivity of lipids from liver slices
was detected in phospholipids and 36.8% in triglycerides but
in free fatty acids and cholesterol esters the activity was
extremely low. The radioactivity of administered glycerol was
detected in the form of sup 1sup 4COsub 2 as early as 15 min
after ingestion and this activity increased abruptly after 30
min and in 75 min it reached 21.3% of the administered dose
and 28% of the total absorbed glycerol. Clinical study was
performed to evaluate MCT therapy in 10 patients, 7 of them
with postoperative malabsorption syndrome, one with liver
cirrhosis, one with pancreatic cyst and one with postoperative
ulcerative colitis. After a control period, 150 g of MCT was
added daily to the diet of the patients. Because of the
untoward effects, the MCT regimen was discontinued in 3 cases.
The other 7 patients treated for more than a mth showed an
increase in body weight of over one kilogram on average.
Abnormally low serum cholesterol and albumin in a patient
attained a normal range after one month of MCT administration.
sup 1sup 3sup 1I triolein test improved and the frequency of
bowel movements decreased in all patients. To achieve clinical
effectiveness, MCT was continuously administered for at least
a mth. In patients with malabsorption syndrome, there was an
increase in body weight, serum cholesterol and serum albumin,
a decrease in frequency of bowel movements and an improvement
in the nature of the stool.
Crohn's disease
Jarnum S.
Med. Afd. P, Gastroenterol. Afsnit, Rigshosp., Kobenhavn
Denmark
Ugeskr.Laeg. (Denmark), 1974, 136/17 (912-920)
Crohn's disease attracts increasing interest on account of
its many clinical and pathophysiological aspects and because
it seems to be becoming more frequent. Based on case material
of 179 patients with Crohn's disease treated in hospital over
a 10 yr period, certain epidemiological, clinical and
pathophysiological features are discussed. Diagnostic accuracy
is considered high. Thus the small intestine was involved in
approximately 90%. However, the case material is selected and,
therefore, less suited for an epidemiological study. One third
was transferred from other hospitals, one fourth lived in
Copenhagen, one third in Jutland. Copenhagen citizens in the
case material represented a 'minimal' prevalence of 7.8 per
100,000 inhabitants in Copenhagen City, and the total case
material a prevalence of 3.6 per 100,000 in the whole country.
Owing to selection the true prevalence must be considerably
higher. There were 50% more women than men. The
pathophysiological characteristics of Crohn's disease are
largely due to its liability to involve the ileum.
Enterogenous vitamin Bsub 1sub 2 malabsorption occurred in 67%
of 118 patients studied. It was also present in 11% of 70
patients with ulcerative colitis. Extensive intestinal
resection is another, less frequent consequence of Crohn's
disease. Studies in 24 patients subjected to extenseive but
intestinal resection (75-270 cm) showed Bsub 1sub 2
malabsorption to occur only after ileal resection, whereas
decreased serum folic acid developed mainly following jejunal
resection. The serum protein pattern shows a characteristic
bun nonspecific change. Albumin and often transferrin are
decreased, orosomucoid increased. Immunoglobulin levels are
within normal range, but higher in patients who respond
favourably to medical treatment than in patients who do not.
Intestinal plasma protein loss is almost consistently present.
Treatment of Crohn's disease should be a combined and
harmonized surgical medical undertaking. Resection is now
preferred to 'by pass' interventions. Medical treatment
comprises specific and individualized treatment. Specific
treatment aiming at suppression of the inflammatory process is
possible with salicylazosulfapyridine which is effective in
mild and moderate cases, glucocorticoids which may have a
dramatic effect in severe cases without obstruction, and,
possibly, immunosuppressive agents, the value of which is
still disputable. Individualized medical treatment covers a
wide range of therapeutic measures: vitamin substitution
(especially vitamin Bsub 1sub 2), electrolytes, bile acid
binding resin to counteract cholegenic diarrhoea, dietary fat
restriction (40 g fat per day) in the short bowel syndrome,
symptomatic therapy with analgetic, spasm relieving and
constipating drugs. Complete parenteral nutrition or treatment
with 'elementary diet' may be beneficial in selected, severe
cases, in particular when intestinal fistulas are present.
Disaccharidase deficiency in adults with
gastrointestinal disease
Tasev T.; Nedkova Bratanova N.; Nikolov N.; et al.
Kat. Gastroenterol. Dietet., ISUL, Sofia Bulgaria
Vatr.Bolesti (Sofia) (Bulgaria), 1973, 12/2
(24-31)
The results are reported from simultaneous clinical,
morphological and enzymological examinations of 105 patients
with different gastrointestinal diseases. The quantitative
determination of lactase, maltase and invertase in homogenate
of jejunal mucous membrane was carried out by the Dahlquist
method. A decrease of lactase was found in 65.45% of the
patients with non specific chronic enteritis, of maltase on
56% and invertase in 43.9%. In patients with gastric resection
the figures for these 3 examinations were 45.4%, 25% and
33.3%; and in patients with ulcerative colitis in 55.5%,
57.14% and 25% resp. Comparison of the data after disaccharide
loading and the quantitative enzyme determination showed a
certain parallelism in 2/3 of the cases. No correlation was
established between the morphological investigations and
enzyme values. The excluding of non tolerated disaccharides
from the diet for a relatively longer time led to clinical
improvement and restoration of jejunal mucous membrane with
the exception of lactase, the disaccharide content was
elevated.
Short chain fatty acid rectal irrigation for
left-sided ulcerative colitis: A randomised, placebo
controlled trial
Breuer R.I.; Soergel K.H.; Lashner B.A.; Christ M.L.; Hanauer
S.B.; Vanagunas A.; Harig J.M.; Keshavarzian A.; Robinson M.;
Sellin J.H.; Weinberg D.; Vidican D.E.; Flemal K.L.; Rademaker
A.W.
Dr. R.I. Breuer, Evanston Hospital, Special GH Laboratory,
2650 Ridge Avenue, Evanston, IL 60201 USA
Gut (United Kingdom), 1997, 40/4 (485-491)
Background - Short chain fatty acid (SCFA) deficiency is
associated with colitis in animals and humans, and the mucosal
metabolism of these compounds is decreased in ulcerative
colitis. Aims - To assess the efficacy of topical SCFA
treatment in ulcerative colitis.
Patients and Methods - 103 patients with distal ulcerative
colitis were entered into a six week, double-blind, placebo
controlled trial of rectal SCFA twice daily; patients who were
unchanged on placebo were offered SCFA in an open-label
extension trial.
Results - Of the 91 patients completing the trial, more
patients in the SCFA treated than in the placebo treated group
improved (33% v 20%, p = 0.14, NS). Those on SCFA also had
larger, but statistically non-significant, reductions in every
component of their clinical and histological activity scores.
In patients with a relatively short current episode of colitis
(<6 months, n = 42), more responded to SCFA than to placebo
(48% v 18%, p = 0.03). These patients also had larger, but
statistically non-significant, decreases in their clinical
activity index (p = 0.08 v placebo). Every patient who
improved used at least five of six of the prescribed rectal
SCFA irrigations, whereas only 37% who did not improve were as
compliant. In the open-label extension trial, 65% improved on
SCFA; these patients also had significant reductions (p <
0.02) in their clinical and histological activity scores.
Conclusions - Although SCFA enemas were not of therapeutic
value in this controlled trial, the results suggest efficacy
in subsets of patients with distal ulcerative colitis
including those with short active episodes. Prolonged contact
with rectal mucosa seems to be necessary for therapeutic
benefit.
Special issues in nutritional therapy of
inflammatory bowel disease
Williams C.N.
CRC, Dalhousie University, 5849 University Avenue, Halifax,
NS B3H 4H7 Canada
Can. J. Gastroenterol. (Canada), 1993, 7/2
(196-199)
There are many issues and controversies concerning
nutrition in inflammatory bowel disease (IBD). Most
authorities now accept that total parenteral nutrition (TPN)
is useful, both as primary and adjunct therapy in the
management of patients with Crohn's disease, but only useful
as adjunct therapy in patients with acute flare-ups of
ulcerative colitis. In both, there is a role for TPN in
preparing patients for imminent surgery. In comparison with
TPN, defined formula (elemental diet) therapy has less
complications, is easier to monitor, is less costly, and gives
equivalent results. Several controlled trials have shown that
elemental diet therapy is as useful as prednisone in inducing
remission in patients with active Crohn's disease. Elemental
diets have been compared with polymeric diets in patients with
Crohn's disease, and have been shown to be effective; recently
a semi-elemental diet has also been shown to be as effective
as elemental diet, but with a conferred benefit of maintaining
essential fatty acid levels. Elemental diets do not appear to
be effective in closing fistulas. If the problems of
palatability and, in some patients, nausea, vomiting,
abdominal cramps and diarrhea persist, these can be overcome
to some extent by flavour changes, chilling, gradual
introduction and counselling or nasogastric tube feeding.
Recently, fish oils have been used in patients with IBD. There
is suggestive evidence that they are of benefit in patients
with ulcerative colitis but not in Crohn's disease. There is a
suggestion that fish oils have a steroid-sparing effect which,
if confirmed, will be of great potential benefit to patients
with ulcerative colitis.
A randomized controlled study of evening primrose
oil and fish oil in ulcerative colitis
Greenfield S.M.; Green A.T.; Teare J.P.; Jenkins A.P.;
Punchard N.A.; Ainley C.C.; Thompson R.P.H.
Gastrointestinal Laboratory, The Rayne Institute, St Thomas'
Hospital, London SE1 7EH United Kingdom
Aliment. Pharmacol. Ther. (United Kingdom), 1993, 7/2
(159-166)
In a placebo-controlled study, 43 patients with stable
ulcerative colitis were randomized to receive either MaxEPA (n
= 16), super evening primrose oil (n = 19), or olive oil as
placebo (n = 8) for 6 months, in addition to their usual
treatment. Treatment with MaxEPA increased red-cell membrane
concentrations of eicospentaenoic acid (EPA) at 3 months by
three-fold and at 6 months by four-fold (both P < 0.01),
and doubled docosahexaenoic acid (DHA) levels at 6 months (P
< 0.05). Treatment with super evening primrose oil
increased red-cell membrane concentrations of
dihomogamma-linolenic acid (DGLA) by 40% at 6 months (P <
0.05), whilst treatment with placebo reduced levels of DGLA
and DHA at 6 months (both P < 0.05). Clinical outcome was
assessed by patient diary cards, sigmoidoscopy and histology
of rectal biopsy specimens. Super evening primrose oil
significantly improved stool consistency compared to MaxEPA
and placebo at 6 months, and this difference was maintained 3
months after treatment was discontinued (P < 0.05). There
was however, no difference in stool frequency, rectal
bleeding, disease relapse, sigmoidoscopic appearance or rectal
histology in the three treatment groups. Despite manipulation
of cell-membrane fatty acids, fish oils do not exert a
therapeutic effect in ulcerative colitis, while evening
primrose oil may be of some benefit.
Treatment of ulcerative colitis with fish oil
supplementation: A prospective 12 month randomised controlled
trial
Hawthorne A.B.; Daneshmend T.K.; Hawkey C.J.a; Belluzzi A.;
Everitt S.J.; Holmes G.K.T.; Malkinson C.; Shaheen M.Z.;
Willars J.E.
Department of Therapeutics, University Hospital, Nottingham
NG7 2UH United Kingdom
Gut (United Kingdom), 1992, 33/7 (922-928)
The effect of fish oil on the course of ulcerative colitis
was investigated in a randomised blinded controlled study.
Eighty seven patients received supplements of 20 ml HiEPA fish
oil as triglyceride (4.5 g of eicosapentaenoic acid) or olive
oil placebo daily for one year. The oils were given in
addition to standard drug therapy and trial entry was
stratified for disease activity. Fish oil significantly
increased the eicosapentanoic acid content of rectal mucosa to
3.2% of total fatty acids at six months, compared with 0.63%
for patients on olive oil. This was associated with increased
synthesis of leukotriene B5, and 53% suppression of
leukotriene B4 synthesis by ionophore-stimulated neutrophils.
Leukotriene B4 suppression persisted for at least two months
after treatment was stopped. Treatment with fish oil resulted
in measurable, but only limited clinical benefit. For patients
entering the trial in relapse (n = 53), there was a
significant reduction in corticosteroid requirement after one
and two months treatment. There was a trend towards achieving
remission (off corticosteroids) faster in the patients on fish
oil, although differences were not significant. For patients
in remission at trial entry or during the trial (n = 69),
there was no significant difference in the rate of relapse by
log rank analysis. We conclude that fish oil supplementation
produces a modest corticosteroid sparing effect in active
disease, but there is no benefit in maintenance therapy.
Incorporation of fatty acids from fish oil and
olive oil into colonic mucosal lipids and effects upon
eicosanoid synthesis in inflammatory bowel disease
Hillier K.; Jewell R.; Dorrell L.; Smith C.L.
Clinical Pharmacology Group, Faculty of Medicine, University
of Southampton, Southampton SO9 3TU United Kingdom
Gut (United Kingdom), 1991, 32/10 (1151-1155)
The incorporation of the fatty acids in fish and olive oil
into the colonic mucosa of patients with inflammatory bowel
disease was examined during 12 weeks' dietary supplementation
with the oils, and the influence on colonic mucosal
prostaglandin and thromboxane generation was measured. With a
dietary supplement of 18 g fish oil daily, concentrations of
the major polyunsaturated fatty acids in fish oil,
eicosapentaenoic acid and docosahexaenoic acid, were
significantly raised in mucosal lipids. The first time these
were measured, after three weeks' supplementation, the mean
increases in eicosapentaenoic and docosahexaenoic acid were
seven fold and 1.5 fold respectively, and these increases were
maintained during the 12 week study. Arachidonic acid values
fell throughout the study and this reduction was significant
at 12 weeks. Mucosal prostaglandin E2 (PGE2), thromboxane B2,
and 6-keto prostaglandin F(1alpha) synthesis were suppressed,
and this reached significance (p < 0.05) at three and 12
weeks for PGE2 and at 12 weeks for thromboxane B2. The
predominant fatty acid in olive oil is oleic acid.
Supplementation with 18 g/day resulted in a significant
increase in oleic acid in colonic mucosa at 12 weeks (p <
0.05) and a fall in stearic acid and docosahexaenoic acid;
there was no significant change in eicosanoid synthesis. It is
concluded that colonic lipids and prostaglandin and
thromboxane synthesis can be readily altered by dietary
supplementation with fish oil. The extent of incorporation of
the fatty acids present in oils is dependent upon the
individual fatty acid.
Carlsbad mineral water drinking cure
Krizek V.; Sadilek L.
Vyzkumny Ustav Balneologicky, Marianske Lazne Czech
Republic
Fysiatr. Revmatol. Vestn. (Czech Republic), 1993, 71/4
(195-212)
1. Carlsbad mineral water is a hydrogencarbonate-sulphur
containing thermal water with a mineralization of cca 6.4
g.l-1. It is drunk at the springs in the spa and is bottled
under the name 'Mlynsky pramen' (Mill spring).
2. 28-day controlled clinical trial comprising two weeks of
drinking Carlsbad water was to provide new information on the
suitability of this water in nephrourological indication.
3. The trial comprised 16 experimental subjects, mostly
suffering from urolithiasis, four suffered from gout. During
the first and fourth week the subjects drank 1.5 litres of
ordinary drinking water, during the second and third week the
same amount of Carlsbad water. The standard diet which was the
same every week made it possible to compare the excretion of
minerals and other substances during individual periods in the
course of the investigation.
4. Drinking of Carlsbad water induced desirable diuresis.
The demand of a diuresis of more than 2 l.d-1 was met only by
52 to 55% of the daily amounts.
5. Drinking of Carlsbad water led to slight alkalization of
the urine from pH 5.8 to 6.8 with a corresponding decline of
titratable acid and ammonia in urine. Acid-base indicators in
blood were not affected.
6. Calciuria rose by 4 to 7%, magnesiuria, on the other
hand, declined slightly. The Ca/Mg quotient in urine rose
insignificantly. The blood levels of calcium and magnesium
declined slightly. It was not possible to confirm analogous
effects to those described formerly by Stransky.
7. A 20% rise of natriuria was recorded and elevated
inorganic sulphaturia by 45 to 57%. The urinary potassium
excretion increased slightly. The chloride excretion, on the
other hand, declined by 8.5%. Serum electrolytes did not
display major changes.
8. The tolerance of the Carlsbad water drinking cure - 3
times 0.5 l - was good. The water had a minor purgative
effect. The daily frequency of bowel movements increased by 36
to 60% and there was a higher proportion of loose but not
diarrhoeal stools.
9. Uricaemia declined by 17% and uricuria by 13 to 16%. The
uric acid clearance declined by 7 to 11%. In the four patients
suffering from gout analogous effects were recorded as in
subjects without gout. No uricosuric effect was found.
10. During the drinking cure in the investigated
non-diabetic subjects the morning blood sugar and insulin
level were not affected.
11. The Carlsbad water drinking cure is indicated in
particular in urate and cystine urolithiasis. It will be
useful to use the drinking cure more frequently to ensure
primary and secondary prevention of oxalate lithiasis in
gastroenterological patients with malabsorption syndromes, in
conditions following intestinal bypasses, jejunostomies,
similarly as in the prevention of urate lithiasis in
ulcerative colitis, in particular after operations such as
ileostomies, colectomies etc.
12. The Carlsbad water drinking cure, in particular larger
amounts, must be indicated carefully in conditions where the
ingestion of sodium or alkalization of urine are not
desirable.
Intestinal epithelial cells contribute to the
enhanced generation of platelet activating factor in
ulcerative colitis
Ferraris L.; Karmeli F.; Eliakim R.; Klein J.; Fiocchi C.;
Rachmilewitz D.
Department of Medicine, Hadassah University Hospital, Mount
Scopus, PO Box 24035, Jerusalem 91240 Israel
Gut (United Kingdom), 1993, 34/5 (665-668)
Generation of platelet activating factor by intestinal
mucosal epithelial cells and lamina propria mononuclear cells
was evaluated to elucidate the possible role of this mediator
in the pathogenesis of inflammatory bowel disease. Epithelial
and lamina propria mononuclear cells were isolated from
surgical specimens from control, Crohn's disease, and
ulcerative colitis patients. Platelet activating factor was
extracted from highly purified cell preparations with 80%
ethanol after stimulation with and without 0.2 uM calcium
ionophore A23187 and was measured by platelet aggregation
assay. Both cell types generated platelet activating factor
activity and this was generally comparable for epithelial and
lamina propria cells. Basal and stimulated platelet activating
factor activity of epithelial and lamina propria cells from
ulcerative colitis but not Crohn's disease patients was
appreciably higher than that of control. Stimulation with
calcium ionophore increased appreciably platelet activating
factor activity in lamina propria cells from all groups. In
contrast, only epithelial cells from ulcerative colitis showed
an appreciable increase after calcium ionophore induction.
These results suggest that epithelial cells are important
contributors to intestinal platelet activating factor
generation under normal and inflammatory conditions and that
epithelial cells actively play a part in the pathogenesis of
ulcerative colitis.
Inflammatory bowel disease, Part II; Clinical and
therapeutic aspects
Kirsner J.B.
Department of Medicine, University of Chicago, Chicago, IL
USA
Dis. Mon. (USA), 1991, 37/11 (673-675)
Once regarded as medical curiosities, ulcerative colitis
and Crohn's disease have achieved a remarkable change in
status recently and today are among the more compelling of all
human illnesses. The cause(s) of inflammatory bowel disease
(IBD) are not known. Genetic, environmental, microbial, and
immunologic factors are involved, but the precise mechanisms
are obscure. The incidence of ulcerative colitis is relatively
stable, while Crohn's disease continues to increase in
frequency. In 10% to 15% of patients, it is hard to
differentiate between ulcerative colitis and Crohn's colitis,
however, problems with diagnosis usually resolve with time and
repeated examinations. In part I of his two-part monograph on
IBD, Dr. Kirsner addressed the nature and pathogenesis of the
disease. Increased study of ulcerative colitis and Crohn's
disease in recent years has generated new knowledge regarding
their etiology. Part I focused on microbial, immunologic, and
genetic mechanisms of, and the inflammatory process involved
in the disease. In this part, Dr. Kirsner deals with the
clinical features, course, and management of IBD, based on the
author's 55 years of experience with these problems and
supplemented by critical examination of the recent (1988-1990)
literature. Particular attention is directed to the symptoms
and physical findings of ulcerative colitis and Crohn's
disease. The laboratory, radiologic, endoscopic, and
pathologic features, and the many systemic complications. IBDs
are mimicked by several enterocolonic infections and other
conditions making differential diagnosis necessary.
Inflammatory bowel disease in children and the elderly
conforms to conventional clinical patterns modified by the
health circumstances of the respective age groups. Because the
cause of IBD has not been established, current medical therapy
is facilitative and supportive rather than curative. The
principles of medical treatment are approximately the same for
ulcerative colitis and Crohn's disease. Treatment emphasizes a
program rather than a drug and also considers the
individuality of the therapeutic response. A clearer
understanding of dietary and nutritional needs, including
hyperalimentation and electrolyte and fluid balance, aids
treatment. Antidiarrheal and antispasmodal preparation and
sedatives are prescribed for symptom relief. The bowel
inflammation is controlled with sulfasalazine or the newer
5-amino-salicylic acid (5-ASA) compounds, antibacterial drugs
for complications of Crohn's disease and IBD, adrenocortical
steroids, and the immunosuppressive compounds 6-mercaptopurine
(6MP), azathioprine, and cyclosporine, as determined in each
patient. The surgical procedures available for treatment of
ulcerative colitis include total protocolectomy and ileostomy
or ileoanal anastomosis. In Crohn's disease of the small
bowel, the usual approach is intestinal resection and
reanastomosis. Strictureplasty is possible in some instances
of stenotic intestinal disease. For treatment of Crohn's
colitis, procedures include total proctocolectomy, total
colectomy with ileal anastomosis, and occasionally, segmental
resection of the large intestine. Chronic IBD requires
prolonged observation, periodic adjustments in therapy, and
colonic and radiologic surveillance. The prognosis of
ulcerative colitis and Crohn's disease is much improved over
the years, but a cure has not yet been found reemphasizing the
need for further investigation of these challenging
diseases.
Vitamin D status in Crohn's disease: Association
with nutrition and disease activity
Harries A.D.; Brown R.; Heatley R.V.; et al.
Department of Gastroenterology, University Hospital of Wales,
Cardiff United Kingdom
Gut (England), 1985, 26/11 (1197-1203)
Forty patients with Crohn's disease were divided into
undernourished (18) and well nourished (22) groups depending
on whether their midarm circumference was below or above 90%
of the ideal standard. Plasma 25-(OH)D3 and the dihydroxylated
metabolites, 24,25-(OH)sub 2D3 and 1,25-(OH)sub 2D3 were
measured in the summer. Results were related to clinical and
biochemical parameters and also compared with results from
patients with ulcerative colitis and healthy subjects who
served as controls. Plasma 25-(OH)D3 was reduced in the
undernourished Crohn's group compared with the well nourished
Crohn's group, who did not differ from the controls. Over 50%
of the undernourished Crohn's group had evidence of secondary
hyperparathyroidism and raised alkaline phosphatase
concentrations, although concentrations of 1,25-(OH)sub 2D3
were normal. The low 25-(OH)D3 concentrations related to
disease activity. It is suggested that undernourished Crohn's
patients who have high levels of disease activity are at risk
of vitamin D deficiency, and attempts should be made to
improve their vitamin D nutrition.
Contribution of sigmoidoscopy with bioptic
microbiology to the etiologic diagnosis of acute diarrhea in
adults. A prospective study in sixty-five patients
Bellaiche G.; Le Pennec M.P.; Slama J.L.; Ley G.; Choudat L.;
Giacomini T.; Godefroy Y.; Paugam B.
Service de Gastroenterologie, Ctr. Hosp. General Robert
Ballanger, Boulevard Robert-Ballanger, 93602 Aulnay-Sous-Bois
Cedex France
Annales de Gastroenterologie et d'Hepatologie (France), 1996,
32/1 (11-17)
The goal of this study was to evaluate the contribution of
sigmoidoscopy with bioptic microbiology to the etiologic
diagnosis of acute diarrhea in adults. Patients and methods.
Sixty-five patients with acute diarrhea were included
prospectively from February 1993 to November 1994. Ages ranged
from 17 to 83 years. In each patient, two stool samples were
cultured and three examined for parasites. Clostridium
difficile toxin was looked for in the 18 patients who had
taken antimicrobials before onset of the diarrhea.
Sigmoidoscopy with collection of biopsy specimens for
bacteriologic cultures was performed routinely. Results. A
pathogenic organism was identified in 35 patients (54%).
Eighteen patients (28%) had positive stool cultures.
Clostridium difficile toxin was detected in six patients.
Colonic biopsy cultures were positive in 26 patients (40%).
Endoscopic findings established the diagnosis of
pseudomembranous colitis with negative tests for C. difficile
toxin in two patients, diverticulitis in one, ischemic colitis
in two, and cryptogenic colitis in seven. Conclusions.
Sigmoidoscopy ensured the diagnosis in over 72% of cases of
acute diarrhea. This investigation complements stool cultures
and should be done routinely in adults with severe acute
diarrhea.
Serologic testing for amoebiasis
Patterson M.; Healy G.R.; Shabot J.M.
Gastroenterol. Div., Dept. Med., Univ. Texas Med. Branch,
Galveston, Tex. 77550 USA
Gastroenterology (USA), 1980, 78/1 (136-141)
The diagnosis of amoebiasis presents problems, particularly
if one relies on finding the organism. Thus, serologic tests
are expedient. A gel diffusion precipitin test (GDP),
commercially available, simple to perform, and inexpensive,
was compared with the indirect hemagglutination test (IHA).
257 Patients' sera were tested; 14 had amoebic colitis, 21 had
amoebic liver abscess, 63 had suspected amoebic liver abscess,
and 46 had inflammatory bowel disease. GDP tests were positive
in 85% of amoebic colitis and 95% of amoebic liver abscess
patients; IHA was positive in 91% of amoebic colitis and 94%
of abscess patients. Within 6 mo, GDP tests became negative in
66% of patients. IHA tests were observed positive up to 20 yr.
The performance characteristics of diagnostic methods for
amoebiasis, fecal examination, IHA and GDP, show serologic
tests have superior sensitivity and predictive value in
recognizing invasive disease.
Autoimmune factors in inflammatory bowel
disease
Solomon G.E.
Mount Sinai Sch. Med., City Univ. New York, N.Y. 10029
USA
Mt.Sinai J.Med. (USA), 1976, 43/5 (602-624)
The currently available clinical and laboratory data (119
references) make it still premature to conclude that IBD
represents an autoimmune process. None of the 6 definitive
criteria for autoimmune disease have been well established for
either chronic ulcerative colitis (CUC) or Crohn's disease
(CD). Nevertheless, there is a good deal of available data
which supports an autoimmune etiology. Virtually all of the
ancillary findings which Sell labels as presumptive evidence
for autoimmune disease have been demonstrated in IBD. These
include: a morphologic picture consistent with known allergic
reactions; the demonstration of antibody or a positive delayed
skin reaction; a depression of complement during any stage of
the disease; a beneficial effect from agents known to inhibit
some portions of an allergic reaction (steroids, radiation,
anti-metabolites, etc.); an association with other possible
autoimmune diseases; identification of a reasonable
experimental model in animals that mimics the human disease:
an increased familial susceptibility to the same or other
autoimmune disease; and an association between the disease
state and specific HLA (human histocompatibility antigen)
types (Sell, S; Immunol., Immunopathol., and Immunity, New
York, 1972). A framework, consistent with the available data,
in which these criteria are satisfied consists of a breakdown
of colonic mucosal barriers, which might represent a distinct
immunizing event in which the underlying enteric lymphatic
tissue becomes exposed to coliform antigens. Following
immunization, a latent period might ensue during which
sensitized cells or antigen or both communicate with the
systemic immune system, possibly via Peyer's patches. Clones
of cells programmed to respond to the coliform antigen are
produced, possibly in the thymus, and migrate to the lamina
propria of the enteric tract. Subsequent exposure to coliform
antigen or cross-reacting colonic antigens causes release of
lymphotoxin from these sensitized lymphocytes resulting in
local cytolysis. Damage to mucosal cells leads to the release
of mucosal cell antigens and further compromises the mucosal
barrier, allowing a self perpetuating reaction in which the
inflammatory process leads to the release of those antigens
which initiated the inflammation. These antigens, both
bacterial and colonic, have been fairly well identified. The
evidence for a transmissable agent may well represent a
transfer of the sensitive state by cells from an affected
individual to a normal individual, and the periods of
remission which punctuate IBD may represent the temporary
induction of tolerance by optimal concentration of antigen.
Although these proposed mechanisms are purely speculative,
they are useful in that they clearly point out those areas to
which future research must be directed.
The effect of exogenous administration of
Lactobacillus reuteri R2LC and oat fiber on acetic
acid-induced colitis in the rat
Fabia R.; Ar'Rajab A.; Johansson M.-L.; Willen R.; Andersson
R.; Molin G. Bengmark S.
Dept. of Surgery, Lund University, S-221 85 Lund Sweden
Scand. J. Gastroenterol. (Norway), 1993, 28/2
(155-162)
The potential beneficial effect of exogenous administration
of Lactobacillus on acetic acid-induced colitis was evaluated
in the rat. Colitis was induced by instillation of 4% acetic
acid for 15 sec in an exteriorized colonic segment. This
produced uniform colitis with a threefold increase in
myeloperoxidase (MPO) activity of the colonic tissue (an index
of neutrophil infiltration) and a sixfold increase in plasma
exudation into the lumen of the colon (mucosal permeability)
as evaluated 4 days after acetic acid administration.
Intracolonic administration of L. reuteri R2LC immediately
after acetic acid administration, at a dose of 5 ml of 7 x 107
colony-forming units (CFU)/ml in two forms: either as pure
bacterial suspension or as fermented oatmeal soup, prevented
the development of colitis. Thus, the morphologic score, MPO
activity, and mucosal permeability were almost normalized by
Lactobacillus treatment. Initiating the treatment 24 h after
acetic acid administration or using lower doses of 1 ml for 3
consecutive days resulted in a smaller protective effect. We
conclude that exogenous administration of L. reuteri R2LC
prevents the development of acetic acid-induced colitis in the
rat.
Gut hormones in inflammatory bowel disease
Besterman H.S.; Mallinson C.N.; Modigliani R.; et al.
Dep. Med., R. Postgrad. Med. Sch., London W12 0HS United
Kingdom
Scand. J. Gastroenterol. (Norway), 1983, 18/7
(845-852)
We have studied fasting levels and the response to a
standard test breakfast of blood glucose and several gut
hormones in 24 patients with ulcerative colitis, in 14
patients with Crohn's disease, and in 14 healthy control
subjects. Patients with ulcerative colitis had significantly
elevated fasting human pancreatic polypeptide (HPP)
concentrations, and both basal and postprandial levels of
gastrin, gastric inhibitory polypeptide (GIP), and motilin
were greater than normal. In contrast, patients with Crohn's
disease had normal gastrin levels but had increased fasting
and postprandial levels of GIP and motilin and, in addition,
of enteroglucagon, compared with controls. These patients also
had greater than normal HPP concentrations 30 min after the
breakfast. Normal levels of insulin, pancreatic glucagon,
neurotensin, and vasoactive intestinal polypeptide were found
in both groups of patients. Much remains to be known about the
pathophysiology of these two debilitating diseases, and the
abnormal release of gut hormones may be of importance.
Kinetics of primary bile acids in patients with
non-operated Crohn's disease
Rutgeerts P.; Ghoos Y.; Vantrappen G.
Dept. Med., Univ. Hosp. St Rafael, 3000 Leuven Belgium
Eur. J. Clin. Invest. (England), 1982, 12/2
(135-143
The metabolism of cholic acid and chenodeoxycholic acid was
studied in seventeen patients with non-operated Crohn's
disease, eleven ileitis and six ileocolitis patients. The
turnover of cholic acid was significantly increased in
patients with ileitis (k = 2.0 + or - 1.13 dayssup -sup 1; P
< 0.001) and ileocolitis (k = 0.91 + or - 0.47 dayssup -sup
1; P < 0.005) as compared to normals (k = 0.35 + or - 0.19
dayssup -sup 1). Although chenodeoxycholic acid was better
preserved in the enterohepatic circulation than cholic acid
its turnover was also significantly faster in ileitis (k =
0.81 + or - 0.56 dayssup -sup 1; P < 0.005) and ileocolitis
patients (k = 0.62 + or - 0.18 dayssup -sup 1; P < 0.01)
than in normals (k = 0.20 + or - 0.09 dayssup -sup 1). The
fractional turnover of cholic acid was related to the length
of ileal involvement (r = 0.761; P < 0.001; n = 17).
Patients with Crohn's ileitis tended to preserve normal
fasting total bile acid pools by increased synthesis of
primary bile acids and efficient absorption of deoxycholic
acid and ursodeoxycholic acid by the normal colon. Patients
with active ileocolitis had decreased total fasting pool sizes
(2.62 + or - 1.83 mmol; P < 0.001) as compared to normals
(7.69 + or - 1.61 mmol). In these patients there was no
increase in bile acid synthesis as compared to normals and
secondary bile acids were absent frome bile. It is concluded
that the colon has an important role in maintaining the
fasting pool size to a normal level in the presence of an
interrupted enterohepatic circulation of bile acids due to
ileal disease.
Bile acid studies in uncomplicated Crohn's
disease
Vantrappen G.; Ghoos Y.; Rutgeerts P.; Janssens J.
Lab. Gastrointest. Pathophysiol., Dept. Med. Res., Univ.
Leuven Belgium
Gut (England), 1977, 18/9 (730-735)
The pool size and composition of bile acids were studied in
13 unoperated patients with uncomplicated Crohn's disease, 10
patients with ulcerative colitis, and 10 normal subjects. Many
patients with Crohn's disease had in their bile a
significantly increased amount of ursodeoxycholic acid. The
bile acid pool size was significantly decreased and the ratio
of glycine to taurine conjugates was significantly increased
in the Crohn's disease patients. The reduction in bile acid
pool size was related to the activity of the disease. The
disorders of bile acid metabolism suggest that the intestinal
involvement in Crohn's disease is much more extensive than can
be demonstrated by careful radiological examinations.
Bile acid metabolism and vitamin Bsub 1sub 2
absorption in ulcerative colitis
Lenz K.
Med. Dept. P, Div. Gastroenterol., Rigshosp., Copenhagen
Denmark
Scand.J.Gastroent. (Norway), 1976, 11/8
(769-775)
Bile acid and vitamin Bsub 1sub 2 malabsorption were
evaluated in 34 cases of ulcerative colitis. Twenty four
patients were non operated and 10 patients were colectomized.
The postprandial duodenal bile acid concentration was
abnormally low in 13 of 24 non operated cases and found to be
correlated to the activity of the disease. Two of six patients
subjected to colectomy had a reduced bile acid concentraion.
Bile acid absorption was assessed by the cholyl glycine 1 sup
1sup 4C breath test combined with faecal analysis. The sup
1sup 4C excretion in breath was abnormally elevated in only
one of the patients in the total material. The faecal sup 1sup
4C output was related to the disease activity in the non
operated group. Patients colectomized for ulcerative colitis
had an extremely high excretion of isotope in the ileal
effluent, from 15 to 81 per cent of the dose given. The faecal
sup 1sup 4C output was correlated with the duration of the
ileostomy and the mass of ileal discharge. Vitamin Bsub 1sub 2
malabsorption was only present in five patients. It is
concluded that patients with ulcerative colitis during the
active phase of the disease have bile acid malabsorption, and
patients colectomized for ulcerative colitis have an abnormal
high bile acid deconjugation in the ileal effluent.
Refined carbohydrate, smooth muscle spasm and
disease of the colon
Grimes D.S.
Dept. Med., Withington Hosp., Manchester United Kingdom
Lancet (England), 1976, 1/7956 (395-397)
A diet high in refined carbohydrate is implicated in the
aetiology ofsome diseases of the colon i.e., diverticular
disease, irritable bowel syndrome, ulcerative colitis, non
occlusive ischaemic colitis, and pseudomembranous colitis. It
is suggested that spasm of the smooth muscle is the common
pathogenetic mechanism in these colonic diseases. The strength
of the spasm producing increased pressure in the colonic lumen
or wall and the length of time for which the colon has been
affected are believed to determine the type of disease
resulting. A diet high in refined carbohydrate allows the
intense muscle spasm to occur because the physical buffering
effect of faecal bulk is considerably reduced.
Pantothenic acid, coenzyme A, and human chronic
ulcerative and granulomatous colitis
Ellestad Sayed J.J.; Nelson R.A.; Adson M.A.; et al.
Dept. Ped., Univ. Manitoba, Winnipeg USA
Amer.J.Clin.Nutr. (USA), 1976, 29/12 (1333-1338)
To investigate further an apparent relationship between
chroniculcerative and granulomatous colitis and pantothenic
acid deficiency,colonic tissues obtained at the time of
colectomy in 29 patients with these disorders were assayed for
pantothenic acid and for coenzyme A (CoA) activity. For
comparison, normal colonic tissues free of pathological
lesions were obtained from 31 patients having colectomy for
carcinoma or diverticulitis. Plasma, red blood cells, and
colonic mucosa were assayed microbiologically for free and
total pantothenic acid. The activity of CoA in colonic mucosa
was determined by assaying the acetylation of sulfanilamide.
Concentrations of free, bound and total pantothenic acid in
blood and in colonic mucosa did not differ between the two
groups of patients. Bound pantothenic acid increased linearly
with total pantothenic acid. Colonic mucosa concentrated free
pantothenic acid to about 50 times the level of blood, and
pantothenic acid in red cells was similar to the concentration
in plasma. Compared to normal gut mucosa, CoA activity was
markedly low in mucosa from patients with chronic ulcerative
or granulomatous disease despite the presence of normal
amounts of free and bound pantothenic acid. A block in the
conversion of bound pantothenic acid to CoA in diseased mucosa
is suggested.
Disruption of sulphated glycosaminoglycans in
intestinal inflammation
Murch S.H.; MacDonald T.T.; Walker-Smith J.A.; Levin M.;
Lionetti P.; Klein N.J.
Dept. Paediatric Gastroenterology, St Bartholomew's Hospital,
London EC1A 8BE United Kingdom
Lancet (United Kingdom), 1993, 341/8847
(711-714)
We have studied the distribution and nature of sulphated
glycosaminoglycans (GAGs) within normal and inflamed
intestine. There is increasing evidence that these negatively
charged polysaccharides, which both regulate the ability of
albumin to leave the vasculature and inhibit thrombosis, may
be affected by inflammatory cells and their products. We
obtained samples of freshly resected intestinal tissue from
eight controls, eleven patients with Crohn's disease, and six
with ulcerative colitis. Sulphated GAGs were detected by means
of a gold-conjugated poly-L-lysine probe, and the tissue
density of anionic sites was assessed semiquantitatively by
means of a Lennox graticule. In normal intestine there was
staining in the vascular endothelium and the subepithelial
basal lamina and throughout the extracellular matrix of the
lamina propria and submucosa. Tissue from the patients with
inflammatory bowel disease showed inflammation macroscopically
and on histology. There were profound abnormalities of
extracellular matrix GAGs, limited to the mucosa in ulcerative
colitis and greatest in the submucosa in Crohn's disease.
There was also substantial loss of GAGs from the subepithelial
basal lamina in both disorders and from the vascular
endothelium in submucosa in Crohn's disease. The extent of
local GAG disruption was associated with the distribution of
macrophages immunoreactive for tumour necrosis factor alpha
and the activation marker RM 3/1. We suggest that inflammatory
disruption of vascular and connective tissue GAGs may be an
important pathogenetic mechanism, contributing to the leakage
of protein and fluid, thrombosis, and tissue remodelling seen
in inflammatory bowel disease.
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