Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010346 (Crohn's disease)
 21,615 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sulphasalazine consists of 5-aminosalicylic acid and sulphapyridine both linked together by an azo bond. Sulphasalazine is clearly useful in long-term management of ulcerative colitis and may be useful in Crohn's disease. The absorption, metabolism and excretion of sulphasalazine is similar in volunteers and patients with ulcerative colitis or Crohn's disease. Sulphasalazine serves as a vehicle to deliver its possible active components, 5-aminosalicylic acid and sulphapyridine, to the colon in higher concentrations than could be achieved by oral administration of either one alone. Sulphasalazine reaches the colon mostly unchanged and is split by gut bacteria at the azo linkage, releasing 5-aminosalicylic acid and sulphapyridine. 5-Aminosalicylic acid may act locally and is not absorbed to any great extent. On the contrary, sulphapyridine is mostly absorpbed from the colon and may act both locally, during mucosal absorption, and systemically. A positive correlation exists between serum total sulphapyridine concentration and both therapeutic efficacy and toxicity. Sulphapyridine metabolism is largely determined by inherited acetylator phenotype, either slow or fast. Slow acetylators have higher levels of free sulphapyridine and lower levels of acetylated sulphapyridine than fast acetylators, and are likely to have more toxic symptoms on equivalent doses of sulphasalazine. Therapeutic effects of sulphasalazine in ulcerative colitis and Crohn's disease correlate with serum concentrations of total sulphapyridine (20 to 50 microng/ml), and toxicity with total sulphapyridine concentration greater than 50 microng/ml. Side-effects are mostly observed among slow acetylators. In long-term therapy of ulcerative colitis doses of 2 to 3g/day of sulphasalazine are most likely to sustain remissions and avoid toxicity. During therapy with sulphasalazine, determination of acetylator phenotype and total sulphapyridine concentration can guide effective dosage and avoid side-effects. A single serum sample for free and acetylated sulphapyridine concentrations is sufficient for this purpose.
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PMID:Clinical pharmacokinetics of sulphasalazine. 1 52

The authors offer a critical review of eight cases of hemorrhagic colorectitis and Crohn's disease (regional ileitis) managed with medical treatments, and eleven like cases treated surgically, during the last ten years. After a discussion of the resources and limitations of medical therapy, the authors describe the various surgical strategies adopted in their cases; they define the possibility of obtaining final cures in Crohn's disease with extended ileocolectomy; and concerning ulcerative forms, they point out the greater efficacy of surgical procedures involving sacrifice of the rectum compared to those in which the terminal segment of the gut is used immediately or later for restoring continuity of the intestinal canal.
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PMID:[Reflections on ten years' experience in the treatment of hemorrhagic colorectitis and Crohn's disease (author's transl)]. 3 14

There has been a definite increase in the incidence of Crohn's disease in recent years. A particular feature of this disease is the high incidence of recurrence after surgical removal of affected portions of the gut. This may be due to a resection carried out through a diseased segment and this stresses the importance of recognising early changes. This is not possible by conventional radiology (small bowel examination, barium enema) and is therefore an indication for pre-operative visceral angiography. The results obtained in ten patients, who subsequently came to surgery, were compared with the findings on conventional radiology and endoscopy. Angiography proved the best method for the early demonstration of inflammatory changes. This was confirmed by histological examination of the resected specimen.
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PMID:[Angiography in Crohn's regional enteritis. Its relation to conventional radiological, endoscopic and micro-angiographic findings]. 13 19

We have developed an enzymatic technique for isolating human intestinal mucosal lymphoid cells. This method was found to be superior to mechanical methods in regard to cell yield and survival. It is based on treating mucosa with serum-free solutions containing collagenase and deoxyribonuclease, followed by isolating the lymphoid cells through centrifugation steps involving fetal calf serum and ficoll-hypaque. Exposure of peripheral blood lymphocytes to the components of the enzymatic solution did not appreciably alter their uptake of tritiated thymidine in the presence or absence of mitogens. Application of the method to derive lymphoid cells from Crohn's disease, ulcerative colitis, and normal intestinal mucosa has shown that gut mucosal lymphocytes from inflammatory bowel disease (1) exceed the number of those from normal mucosa by a factor of 3 to 5; (2) show different degrees of tritiated thymidine uptake, spontaneously and in response to mitogens, depending upon the time they are harvested during the dissociation process; (3) are better stimulators than responders in the allogeneic mixed lymphocyte reaction; (4) generate suppressor cell activity comparable to that of peripheral blood lymphocytes; (5) cannot, in contrast to peripheral blood lymphocytes, generate antibody-dependent cell mediated cytotoxicity; and (6) produce an average of 5 times more IgM than equal numbers of peripheral blood lymphocytes.
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PMID:Gut mucosal lymphocytes in inflammatory bowel disease: isolation and preliminary functional characterization. 15 97

In order to investigate the prevalence of iodine depletion in chronic inflammatory bowel disease two separate studies have been performed. One was devoted to the 24-hour urinary iodine excretion and 50 patients with ulcerative colitis or Crohn's disease were examined and compared with 102 controls. In the other study the thyroid 131I uptake was compared in 38 patients and 36 controls. Ten of the 50 patients with chronic inflammatory bowel disease had a 24-hour urinary iodine excretion less than 40 mug, compared with 5 of the 102 controls (p greater than 0.01). Sixteen of the 38 patients had a 24-hour thyroid 131I uptake of 50% or more of the administered test does, compared with 4 of the 36 controls (p smaller than 0.01). These results are compatible with an increased occurrence of iodine deficiency in patients with chronic inflammatory bowel disease. Treatment with corticosteroids or Salazopyrin or a milk-free diet did not influence these findings. No evidence was found of an impaired absorption of inorganic iodide from the gut.?31
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PMID:The thyroid in ulcerative colitis and Crohn's disease. I. Thyroid radioiodide uptake and urinary iodine excretion. 23 26

Metastatic tumors from livers of 5 patients with gastrointestinal carcinomas and from the liver of 1 patient with malignant breast carcinoma were extracted with 3 M KCl; similar extracts were prepared from normal human colon and liver and from human fetal gut. The extracts were depleted of serum globulins by passage through reverse immunoadsorbent columns consisting of rabbit antibodies to the F(ab)2 fragment of human IgG and were then coupled to CNBr-activated paper disks. These "antigen" disks were used in a radioimmunoassay, with the aid of 125I-labeled rabbit antihuman F(ab')2 antibodies for the assay of circulating tumor antibodies produced by cancer patients. Statistical evaluation of the results with plasma samples from 47 patients with colorectal carcinomas and from 7 patients with other gastrointestinal disorders (polyps, villous papilloma, diverticulitis, and Crohn's disease) indicated that a significant number of patients had antibodies to cross-reactive tumor antigen(s). The cross-reactive tumor antigen(s) involved in the reaction was not detected in extracts of the gastrointestinal tract from 12-week human fetuses and did not cross-react with carcinoembryonic antigen.
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PMID:Detection of tumor antibodies in patients with gastrointestinal carcinomas by a solid-phase radioimmunoassay. 28 24

It has become widely recognised that oral lesions may occur in patients with Crohn's disease of the lower gastro-intestinal tract. Patients have also been described with oral lesions of this kind unassociated with gut lesions. The purpose of this paper is to describe the clinical presentation of seven such patients. The resemblance of their lesions to those of the condition known as chronic granulomatous cheilitis is pointed out. The association between the oral lesions and those of the lower gut is discussed and it is reported that in one patient acute toxic dilation of the colon due to Crohn's disease followed a period in which oral lesions only were recognised.
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PMID:Oral Crohn's disease and related conditions. 28 11

There is a considerable range in the dose of many drugs that is required to produce a given pharmacological effect in an individual patient. This individual variation in dose requirement is sometimes reflected in the wide scatter in the steady state plasma concentration that follows the same oral dose of a drug given to any group of subjects. Such individual differences are largely due to variation in the rate of elimination of drugs. Gastrointestinal disease may also alter oral dose requirements by producing variation in both the amount and rate of drug absorption. These changes may be reflected in the plasma concentration/time curve that follows an oral dose. The amount of drug abosorbed is simultaneously affected by many factors. These include the physicochemical properties of the drug and the physiological factors that operate within the gut, as well as the presence of other substances such as food, or interaction with other drugs in the gut. The availability of the drug within the intestinal lumen is largely governed by its dissolution characteristics, particularly factors which can interfere with dissolution of the drug product in the gut. Physiological factors within the gut that affect oral drug absorption include gastric emptying rate and intestinal motility, the pH of the gastrointestinal fluids, the activity of gastrointestinal drug metabolising enzymes (e.g. monoamine oxidase and dopa decarboxylase) or drug metabolising bacteria and the surface area of the gut. Many factors affect gastric emptying. These include disease, surgery and other drugs. A change in the rate of gastric emptying alters the rate of drug delivery from the stomach to the duodenum and upper small intestine. This may profoundly alter the plasma concentration/time curve that follows oral administration of many drugs. For some drugs, proximal jejunal disease may reduce, delay or increase the apparent amount of drug absorbed. Reduced absorption of an antibiotic leads to a fall in the peak plasma concentration. If the peak falls below the minimum inhibitory concentration for a particular organism then therapeutic failure may occur, if it is assumed that the peak plasma concentration is all important for antimicrobial activity. Excessive drug absorption may lead to drug toxicity. Abnormal drug absorption is a feature of lower small intestinal conditions such as Crohn's disease. This suggests that drug absorption is not confined to the jejunum but continues throughout the small intestine. It is not always possible to predict the pattern of drug malabsorption from a knowledge of the physicochemical and pharmacokinetic properties of the drug and the pathophysiology of the disease. The rate and amount of drug absorbed be one patient may differ from that in another patient with the same condtion. Although these differences reflect normal individual variation, they are also related to the extent and activity of disease at the time of study...
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PMID:Drug absorption in gastrointestinal disease with particular reference to malabsorption syndromes. 32 10

In most cases the ano-cutaneous clinical symptoms correlated to diseases of the gastro-intestinal tract are not specific (erythema, itching, wounds or scarring). However in the following diseases occasional dermatological lesions may directly contribute to their diagnosis: in Crohn's disease, tuberculosis of bowel, chronic entamoebiasis and bilharziosis, the skin lesions of the anal area have the same histological structure as the gut lesions. Perianal fistulas and ulcers are frequent in Crohn's disease especially if there is a colonic and rectal spreading; they respond badly to steroid therapy and are often correlated with a worse prognosis. Perianal specific lesions occur often in oxyuriasis in children, in candidiasis of the digestive tract, in systemic aphthosis and in some malignancies. In other gastro-intestinal disturbances, the dermatological and features are less specific and can only be suggestive: iatrogenic and microbial diarrheas, side-effects of laxatives, proctological diseases. It has to be emphasized that pruritus ani is only induced by deeper lesions when they spread to the perianal skin. In proctological practice, contact dermatitis by sensitivity to anaesthetics or suppository balsams (Peruvian balsam), itching or burning atrophy by topical steroid abuse, non-diagnosed fungal (candidiasis), bacterial (erythrasma) or psoriatic intertrigos (flexural psoriasis) may sometimes explain the failure of therapy.
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PMID:[Anal symptoms of gastro-intestinal diseases]. 48 13

Finger clubbing, measured objectively by using the hyponychial angle, was present in 75 out of 200 (38%) patients with Crohn's disease, 15 out of 103 (15%) with ulcerative colitis, and two out of 24 (8%) with proctitis. In Crohn's disease and ulcerative colitis the hyponychial angle was significantly correlated with both disease activity and the extent of fibrosis in the resected specimens from 47 surgically treated patients. The prevalence of finger clubbing in patients with macroscopic disease within the area of the gut innervated by the vagus nerve was significantly higher than that in patients in whom the disease was confined to the distal colon and rectum. Finger clubbing in patients with Crohn's disease tended to regress after resection of macroscopic disease. It is concluded that finger clubbing is significantly commoner in Crohn's disease than ulcerative colitis. The focal stimuli for finger clubbing include mucosal inflammatory change and fibrosis mediated by the vagus and possibly other autonomic pathways acting as the afferent arc of a finger-clubbing reflex.
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PMID:Finger clubbing in inflammatory bowel disease: its prevalence and pathogenesis. 50 14


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