Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.
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PMID:[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. 892 65

Hepatocellular carcinoma (HCC) is a common tumor in the developing countries. Most patients present with relatively advanced disease and have a poor survival. Due to lack of any effective therapy, there is an urgent need to investigate new drugs. We conducted a prospective trial to evaluate the efficacy and tolerability of ifosfamide (IFEX) in patients with histologically proved, inoperable, localized HCC. Eligibility criteria included World Health Organization (WHO) performance status (PS) of 0-2, bilirubin < or = 3.0 mg/dl, albumin > or = 2.5 g/dl, creatinine < or = 2.0 mg/dl, correctable coagulation profile, adequate bone marrow function, and no prior therapy. Hepatic arterial infusion of IFEX (6 g/m2) was given continuously over 96 hours. Mesna was given intravenously, in same doses, throughout IFEX infusion and for 12 hours afterwards. Nineteen patients were enrolled in the trial. Mean age was 51.1 years and all were men. Most of the patients had PS 1. The majority had viral hepatitis and cirrhosis. Eleven had raised serum alpha fetoprotein (AFP) levels. Thirteen patients had multiple lesions involving both lobes of the liver. Mean size of ultrasonographically evident largest lesion was 11.0 cm. Three patients are inevaluable; one died early, one refused further therapy, and another was lost to follow-up. Among the 16 evaluable patients, 6 (37.5%) had partial remission and 4 (25%) had a minor response. An additional four (25%) patients had stable disease. Only two (12.5%) patients had progression of disease while on therapy. Overall response rate (partial plus minor) was 62.5%. Mean duration of partial response was 5.0 months and mean survival was 7.1 months. Subjective improvement in pain was observed in all but two patients and correlated well with the objective response. Chemotherapy-related side effects were predominantly grade III-IV anemia and alopecia. Three patients had catheter-related complications (one local infection, one bleeding, and one thrombosis). Two patients developed mild encephalopathy and two had hepatic decompensation as evidenced by worsening liver function tests. The results of this pilot study suggest that IFEX, given as a continuous hepatic arterial infusion, is an active drug in inoperable localized HCC. Toxicity is manageable. This drug deserves further trials to properly evaluate its therapeutic potential.
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PMID:A prospective phase II trial to evaluate the efficacy and toxicity of hepatic arterial infusion of ifosfamide in patients with inoperable localized hepatocellular carcinoma. 916 56