Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews the published data on novel drug treatments for inflammatory bowel disease. Steroids that are topically active or rapidly metabolized have a definite therapeutic role and have fewer long-term side-effects than other steroids. Methotrexate can promote remission in approximately 50% of patients, but is less effective in maintaining remission. Cyclosporin is valuable for treating patients with severe ulcerative colitis but is less valuable for patients with Crohn's disease. None of the drugs that modify specific inflammatory mediators have proven efficacy but tumour necrosing factor and CD4 antibodies may be promising. In patients with distal colitis, lignocaine appears to be effective.
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PMID:Novel drug therapies in inflammatory bowel disease. 771 10

Initial standard medical treatment for inflammatory bowel disease (IBD) includes a 5-aminosalicylic acid (5-ASA) compound (oral, local or combined) and corticosteroids (oral, local or combined). In both ulcerative colitis and Crohn's disease 5-ASA has proved effective in the acute phase of the disease. As maintenance treatment, it is effective in ulcerative colitis and in some instances also in Crohn's disease. Steroids can be used in active IBD, but their effectiveness as maintenance treatment has never been proven, although in practice low-dose steroids are used for chronic treatment. When the above-mentioned preparations are unsuccessful, other medications could be tried. Flagyl could be used when the colon is involved in Crohn's disease or when anal fistulation develops, but it often fails to maintain its effect after only a few weeks. For refractory IBD more potent immunomodulators are needed. 6-Mercaptopurine and azathioprine have been shown to be effective in ulcerative colitis and Crohn's disease with a response rate between 60 and 70%. Their optimal effect is only reached after 3-4 months. These drugs are therefore not of value for treatment in the acute phase of the disease. 6-Mercaptopurine or azathioprine can be used best in combination with steroids in situations where dose reduction of the latter drug repeatedly leads to relapse. They have therefore a steroid-sparing effect and initiate cessation of the long-term severe side-effects of steroids. Another possibility is the use of methotrexate in patients with refractory ulcerative colitis or Crohn's disease.
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PMID:Medical management of patients with difficult-to-treat inflammatory bowel disease. 793 6

Respiratory involvement in patients with inflammatory bowel disease (IBD) has been reported mainly since 1976. This form of involvement should clearly be separated from interstitial lung disease due to sulfasalazine or mesalamine, although the distinction may be difficult in some cases. We report the data of an ongoing Registry containing 33 cases (23 cases receiving no drug therapy) with ulcerative colitis or, less often, Crohn's disease, who developed varied bronchopulmonary problems. In several cases, the exact diagnosis and the relation of the bronchopulmonary disease to IBD had not been established for many years, thus delaying effective treatment with steroids. In most cases (28/33), respiratory involvement followed the onset of IBD (8 of these 28 cases were postcolectomy), and in the remainder, respiratory manifestations predated the IBD. Patterns of involvement included: 1) Airway inflammation, in the form of subglottic stenosis, chronic bronchitis, severe chronic bronchial suppuration, bronchiectasis, and chronic bronchiolitis. In cases with large airway involvement, endoscopy showed exuberant inflammatory tissue in the airways and narrowing of tracheal and/or bronchial lumen. Histologically, airways were heavily infiltrated by a dense aggregate of inflammatory cells, and there were mucosal ulcerations. 2) Varied patterns of interstitial lung disease, mainly bronchiolitis obliterans with organizing pneumonia, and pulmonary infiltrates and eosinophilia. (3) Miscellaneous other forms of involvement including striking neutrophilic necrotic parenchymal nodules (corresponding histologically to sterile aggregates of neutrophils), and serositis. Steroids were very effective in the majority of cases. Inhaled steroids were of durable benefit in patients with chronic bronchitis, but less often so in those with chronic bronchial suppuration, bronchiectasis, or chronic bronchiolitis. Steroids administered orally led to marked improvement in patients with interstitial lung disease and necrotic nodules, but lacked effectiveness in several patients with severe airway inflammation or chronic bronchiolitis. Intravenous steroids were required in the initial management of life-threatening complications such as asphyxiating subglottic stenosis or extensive interstitial lung disease. Bronchial lavages with methylprednisolone were effective in some patients with severe airway inflammation. Patients with IBD can develop varied inflammatory complications in the lung, and a sizable fraction of these complications is steroid-sensitive.
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PMID:The lung in inflammatory bowel disease. 850 68

The medical treatment of inflammatory bowel disease is dependent on disease activity and bowel involvement. Severe Crohn's disease and ulcerative colitis are primarily treated with corticosteroids. Alternatively, if inflammation is localised in the right colon and ileum, budesonide may be used in view of its low systemic side effects. In distal colitis and perianal disease, topical therapy with steroids is very effective. In moderate disease preparations containing 5-aminosalicylate (5-ASA) may be used. The latter are highly effective applied locally in distal disease. Steroids should be tapered down and whenever possible not used to maintain remission. In patients with ulcerative colitis, 5-ASA is effective in maintaining remission, whereas this medication plays only a limited role in Crohn's disease. Refractory disease or patients with multiple flare-ups should be treated with azathioprine. Infliximab, an anti-TNF-alpha antibody, is a potent therapy for fistulising Crohn's disease or steroid-refractory disease. Other approved and experimental treatments are discussed.
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PMID:[Drug treatment of chronic inflammatory bowel diseases: current status and prospects]. 1071 13

Pharmacological doses of glucocorticosteroids given chronically are associated with a variety of negative side effects which impact the prolonged use of these potent anti-inflammatory agents. They have catabolic effects on protein, resulting in poor tissue healing, an increased incidence of infections and accelerated bone loss. Insulin resistance to both hepatic and peripheral tissues is a common consequence of chronic steroid use, leading at times to impaired carbohydrate metabolism. Steroids affect both the release and the effects of growth hormone (GH) at the target sites, hence becoming functional GH antagonists. When administered to growing children the side effects of glucocorticosteroid treatment are further compounded by a potent and significant suppression of linear growth. Ample experimental and clinical data support a role for GH therapy in counteracting some of the effects of glucocorticosteroids. Using isotope dilution methods we have previously shown that both GH and insulin-like growth factor (IGF)-I can decrease the protein wasting effects of prednisone administration in man. IGF-I has also been shown to enhance type I collagen formation in hydrocortisone-treated human osteoblasts. GH (through IGF-I) significantly enhances linear growth; thus, in states of "functional" GH deficiency, such as that observed in chronic steroid use, GH may also have a potentially beneficial effect. Studies in children on chronic prednisone doses with cystic fibrosis, chronic renal failure or juvenile rheumatoid arthritis have all shown beneficial effects on linear growth after prolonged GH therapy. Data from a recent study of ours using GH in children with steroid-dependent inflammatory bowel disease showed that GH treatment was associated with increased lean body mass, decreased adiposity and increased linear growth. Marked increases in IGF-I concentrations and in kinetic measures of bone calcium accretion (using calcium tracers) were also observed, without any deterioration of disease activity scores or carbohydrate tolerance. In conclusion, GH therapy may play a role in the treatment of children on chronic steroids both as a growth promoting agent and as an anabolic agent on whole body protein and bone. Longer term studies will be needed to better define the safety and efficacy of this approach.
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PMID:Growth hormone therapy in the glucocorticosteroid-dependent child: metabolic and linear growth effects. 1178 79

Steroids are the best known anti-inflammatory drugs and have been in use for more than 50 years. Their chronic use however was limited by safety concerns. Non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors although devoid of steroid side effects often possess gastrointestinal side effects. In addition recent data suggest that chronic use of some Cox inhibitors is associated with cardiovascular risk. Currently biologics represent the best option for many inflammatory diseases where TNFalpha is the main culprit. These include rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease and psoriasis. A wealth of information is now available on the role of different cytokines and adhesion molecules in the origin and progression of inflammatory diseases. With the success of protein therapeutics such as Etanercept (Enbrel), which binds TNFalpha and inhibits its activity, research has been focused on developing small peptides that can interfere with cytokines or specific cell surface molecules and inhibit the inflammatory reactions. Here we review these peptides that are in discovery and development phases and their potential in the treatment of inflammatory diseases.
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PMID:Emerging peptide therapeutics for inflammatory diseases. 1691 1

We have analysed data from 150 patients initially classified as having CVID. About 10% had laboratory abnormalities suggesting known single gene disorders (eg: hyper-IgM syndrome), and in a few a genetic defect has been confirmed. We have attempted to sub-classify the remaining patients by analysis of their circulating lymphocytes. B lymphocyte markers have been used to estimate the numbers of circulating immature and class switched B cells; there is an association between the presence of high relative numbers of immature circulating B cells, splenomegaly and autoimmune disease. About 25% of CVID patients have a moderate CD4+ T lymphopenia, sometimes with a relative expansion of CD8+ T cells. About 30% of CVID patients have persistent relatively high levels of circulating CD8+ T cells binding immunogenic peptides from EBV or CMV. Many of these patients also have high relative numbers of circulating CD8+ perforin positive T cells, and there is evidence that these cells may be responsible for neutropenia or inflammatory bowel disease in some patients. The clinical spectrum of CVID is diverse, with some patients suffering from few infections, and over 50% have evidence of structural lung damage. About 25% of UK patients have chronic inflammation in various organs, particularly the lungs, liver and spleen, often with granulomatous changes. Steroids are used to treat many of the patients with chronic inflammatory complications, although trials are in progress with anti-TNF agents. The incidence of these inflammatory complications is different between countries, being rare in Sweden. Attempts to correlate clinical phenotypes with the laboratory abnormalities described above have been disappointing, suggesting that unknown genetic factors unrelated to the cause of the immunodeficiency determine the complications; attempts to identify some of these factors will be discussed. Finally a provisional scheme to sub classify CVID patients according to lymphocyte abnormalities will be presented, the purpose being to focus the screening of candidate genes causing CVID to specific subsets of patients.
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PMID:Clinical and Immunological Spectrum of Common Variable Immunodeficiency (CVID). 1730

The German clinical practice guideline on diagnosis and therapy of Crohn's disease is the result of an evidence-based consensus conference under the auspices of the German Gastroenterologic Society and the Competence Network IBD. This article will summarize the recommendations most important for the general practitioner.Crohn's disease is diagnosed in cooperation with a gastroenterologist who is performing endoscopy and possibly ultrasound. Uncomplicated relapses can nevertheless be successfully treated at the office of a family physician - mostly with steroids. Steroids are not appropriate for long-term treatment though. In those cases an early treatment with immunosuppressants in collaboration with a gastroenterologist is required. Cooperation with several different sub specialists is necessary when surgery is required as well as for the treatment of fistula, psychosomatic aspects and extraintestinal manifestations.
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PMID:[Clinical practice guideline on diagnosis and treatment of Crohn's disease - summary for the general practitioner]. 1933 14

The major goal of therapy in inflammatory bowel disease is to induce remission. Remission has multiple definitions - clinical remission, where the patient's symptoms have remitted, and endoscopic remission, in which there has been complete mucosal healing. Mucosal healing is a harder endpoint of remission but may be more difficult to achieve. In clinical trials we are forced to use activity indices such as the Crohn's disease activity index that may not completely reflect the endoscopic and histologic state of the bowel. Ideally we would like to see remission as quickly as possible to improve patient quality of life. The time to remission varies between different therapeutic approaches. Steroids tend to have a rapid clinical effect with remission seen in some patients as early as two weeks. In early anti-TNF trials, a single dose of infliximab lead to 27% remission at two weeks compared to 4% of placebo patients. Adalimumab and certolizumab have similar reports of early induction of remission. Mesalamine in Crohn's disease has inconsistent and delayed remission rates, whereas in ulcerative colitis, response and remission rates are more consistent in the three-week time frame. Azathioprine and 6-mercaptopurine have delayed onset of action but may induce remission as early as six weeks if dosing is optimized. In this presentation induction of clinical remission and mucosal healing in Crohn's disease and ulcerative colitis will be discussed. The impact of early remission on disease course will also be reviewed.
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PMID:How rapidly should remission be achieved? 2092 85

Thiopurine therapy effectively maintains remission in inflammatory bowel disease. However, many patients are unable to achieve optimum benefits from azathioprine or 6-mercaptopurine because of undesirable metabolism related to high thiopurine methyltransferase (TPMT) activity characterized by hepatic transaminitis secondary to increased 6-methylmercaptopurine (6-MMP) production and reduced levels of therapeutic 6-thioguanine nucleotide (6-TGN). Allopurinol can optimize this skewed metabolism. We discuss two brothers who were both diagnosed with ulcerative colitis (UC). Their disease remained active despite oral and topical mesalamines. Steroids followed by 6-mercaptopurine (MP) were unsuccessfully introduced for both patients and both were found to have high 6-MMP and low 6-TGN levels, despite normal TMPT enzyme activity, accompanied by transaminitis. Allopurinol was introduced in combination with MP dose reduction. For both brothers addition of allopurinol was associated with successful remission and optimized MP metabolites. These siblings with active UC illustrate that skewed thiopurine metabolism may occur despite normal TPMT enzyme activity and can lead to adverse events in the absence of disease control. We confirm previous data showing that addition of allopurinol can reverse this skewed metabolism, and reduce both hepatotoxicity and disease activity, but we now also introduce the concept of a family history of preferential MP metabolism as a clue to effective management for other family members.
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PMID:Two brothers with skewed thiopurine metabolism in ulcerative colitis treated successfully with allopurinol and mercaptopurine dose reduction. 2214 54


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