Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.
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PMID:The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT) 832 44

Acute pancreatitis in HIV-infected patients with or without AIDS has been reported with increasing frequency over the past several years. Drugs used to treat HIV-infected patients are often the cause. We report a case of a 46-year-old HIV-infected man who presented to the emergency department with abdominal pain and was diagnosed with acute pancreatitis. The patient had recently begun taking 2',3'-dideoxyinosine (ddI). He died shortly after admission to the hospital; CT scan and autopsy confirmed the cause of death as hemorrhagic pancreatitis. We briefly review the literature on the incidence and severity of pancreatitis in association with ddI and pentamidine therapy.
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PMID:Fatal pancreatitis as a complication of therapy for HIV infection. 853 Jul 81

A nonrandomized trial was undertaken to evaluate the combination of didanosine and interferon-alpha (INF-alpha) in human immunodeficiency virus (HIV)-infected patients. Thirty-six volunteers with >200 x 10(6) CD4 cells/L received didanosine (one 100-, 250-, or 375-mg sachet twice daily) for at least 6 weeks, following which IFN-alpha (1, 5, 10, or 15 MU/day) was begun. Didanosine (one 375-mg sachet twice daily) was substituted for zidovudine in 14 additional patients who had received IFN-alpha and zidovudine for 7-45 months. Thirty-five patients completed the 34-week study. Clinical or chemical pancreatitis was the most common (6 patients) dose-limiting toxicity. CD4 cell counts increased with didanosine but declined following the addition of IFN-alpha; CD4 cell percents tended to increase and remain elevated. Thus, combination therapy with didanosine and IFN-alpha can be safely administered to patients with HIV infection. The clinical benefit of this combination therapy will require further evaluation.
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PMID:Combination therapy with didanosine and interferon-alpha in human immunodeficiency virus-infected patients: results of a phase I/II trial. 860 61

Pancreatic involvement has been studied in 70 HIV infected patients, in diverse stages, that were treated with didanosine (ddI), both as monotherapy or associated to zidovudine; 38% of patients presented adverse reaction that obliged to withdraw the medication: pancreatitis (4%), hyperamylasemia (21%) and abdominal pain and/or diarrhea (12%). The possible causes in presentation of adverse effects were evaluated: route of infection, stage of HIV infection, use of pentamidine or trimethoprim-sulfamethoxazole for preventing Pneumocystis carinii pneumonia, administration of ddI in monotherapy or in combined form with zidovudine, time of treatment and level of CD4 lymphocytes. The outcome of adverse effects is related significantly only with the most advanced stage of HIV infection.
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PMID:[Pancreatic disease in patients with HIV treated with didanosine (DDI)]. 866 67

This study evaluated the efficacy of switching to didanosine in patients who were clinically or immunologically progressing despite zidovudine therapy. This multicenter, open-label study involved 400 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), who had tolerated zidovudine for at least 12 weeks and had signs of clinical or immunological disease progression. They were randomly assigned to receive 600 mg/d of zidovudine (n=133), 500 mg/d of didanosine (n=131), or 200 mg/d of didanosine (n=136). The primary end point was a new AIDS-defining event or death. The study was prematurely terminated, after the first interim analysis, mainly owing to results of two controlled studies demonstrating that a change to didanosine was associated with an improved outcome in patients with advanced HIV-1 disease. The median duration of follow-up was 53 weeks. The primary end point rates were 41, 58, and 59 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups (zidovudine vs. didanosine 500 mg, relative risk 1.28, 95% confidence interval, 0.88-1.86, p = 0.19; didanosine 200 vs. 500 mg, relative risk 1.24, 95% confidence interval, 0.85-1.79, p = 0.26). In subjects with a baseline CD4 count of 100/mm3 or more, the primary end point rates were 8, 29, and 25 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups, respectively (zidovudine vs. didanosine 500 mg, relative risk 2.96, 95% confidence interval 0.91-9.62, p = 0.07). No difference was seen in survival. In the didanosine 500 mg group, more patients had a 50% increase in CD4 cells (10% vs. 1% in zidovudine group, p = 0.01) and an increase of > or = 2.5 kg in body weight (2% versus 3%). Fatal pancreatitis developed in one patient assigned to didanosine 500 mg and in one to zidovudine. Our data suggest that switching from zidovudine to currently recommended doses of didanosine in subjects with ARC or AIDS who show evidence of clinical and laboratory disease progression can be associated with improvements in clinical outcome as well as in surrogate markers of HIV disease progression. This effect tended to be greater among individuals with higher CD4 counts (>100/mm3).
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PMID:Switching from zidovudine to didanosine in patients with symptomatic HIV infection and disease progression. ddI Iberian Study Group. 867 28

To determine the frequency of pancreatitis and to define risk factors for pancreatitis in patients with AIDS, we compared patients with pancreatitis to patients without pancreatitis in an urban infectious disease practice. Pancreatitis was defined as at least one clinical sign or symptom (nausea, vomiting, abdominal pain, or tenderness) accompanied by elevation of serum amylase or lipase. Twenty-four (22%) of 105 patients with AIDS, 2 (4%) of 46 patients with AIDS-related complex, 1 (3%) of 39 asymptomatic patients infected with HIV-1, and none of 9 uninfected patients at risk for HIV-1 developed pancreatitis as defined above. Fourteen patients experienced multiple episodes and three were symptomatic for more than 2 months. Pancreatitis was more likely to have occurred in patients with AIDS (P < .001), biliary tract disease (P = .013), and hypertriglyceridemia (P = .032). After matching for these factors and duration of current HIV disease, cryptosporidiosis, intravenous pentamidine, and isoniazid were each associated independently with pancreatitis (P < .05). Before didanosine (ddl) became available, 22% of the patients with AIDS in this practice had pancreatitis. Cryptosporidiosis, isoniazid, and intravenous pentamidine should be considered among the potential etiologies.
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PMID:Pancreatitis associated with human immunodeficiency virus infection: a matched case-control study. 882 75

Few data exist about the incidence of drug-induced pancreatitis in the general population. 20 cases of drug-related pancreatitis were reported in Switzerland over a period of 12 years. The proportion of cases of pancreatitis caused by drugs is estimated to be around 2% in the general population, with much higher proportions in specific subpopulations, such as children and patients who are HIV positive. The literature about drug-induced pancreatitis consists mainly of anecdotal case reports. Clear evidence of a definite association with pancreatitis, by means of rechallenge tests, or consistent case reports, supported by animal experiments or data on the incidence of acute pancreatitis in drug trials exists for didanosine, valproic acid (sodium valproate), aminosalicylates, estrogen, calcium, anticholinesterases and sodium stibogluconate. An association with drug-induced pancreatitis is likely but not definitely proven for thiazide diuretics, pentamidine, ACE inhibitors, asparaginase, vinca alkaloids, some nonsteroidal anti-inflammatory drugs and clozapine. Pancreatitis is possibly caused by azathioprine, furosemide (frusemide), tetracycline, metronidazole, isoniazid, rifampicin (rifampin), sulphonamides, cyclosporin and some antineoplastic drugs. Many drugs have been reported to be associated with acute pancreatitis. However, lack of rechallenge evidence, consistent statistical data, or evidence from experimental studies on a possible mechanism prohibit definitive conclusions about most of them. The high incidence of concurrent illnesses known to induce acute pancreatitis, makes a trigger role or co-factor role for the drug seem most likely.
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PMID:Drug-induced pancreatitis. 882 18

Didanosine is a dideoxynucleoside analogue, which is phosphorylated to the active metabolite dideoxyadenosine triphosphate (ddATP) intracellularly. At therapeutic concentrations, ddATP inhibits HIV replication by inhibiting HIV reverse transcriptase. Didanosine is established as a first-line treatment for patients with HIV disease and has recently been shown to be superior to zidovudine monotherapy in the treatment of patients with intermediate-stage HIV infection. In clinical practice, however, combination regimens of antiretroviral drugs are generally considered preferable to monotherapy as first-line treatment for most patients with HIV disease. Importantly, 2 large multicentre studies have demonstrated that combination therapy with didanosine and zidovudine was more effective than zidovudine monotherapy in delaying disease progression and death in patients with intermediate or advanced HIV disease. In other comparative studies, improvements in surrogate markers of HIV disease were generally greater in patients who received combination therapy than in recipients of antiretroviral drug monotherapy. Improvements in surrogate markers were also observed in children who received didanosine monotherapy in several clinical trials. Although the efficacy of combination antiretroviral drug therapy has not yet been investigated extensively in children, a combination regimen of didanosine and zidovudine was well tolerated and achieved beneficial effects on surrogate markers if HIV disease. In addition, preliminary findings of a larger study have shown that disease progression was delayed in children and adolescents who received didanosine plus zidovudine combination therapy compared with those receiving zidovudine monotherapy. Didanosine has a tolerability profile that is distinctly different from that of zidovudine. In particular, didanosine exhibits only minimal haematological toxicity when administered either as a single agent or in combination with zidovudine. The most serious dose-limiting adverse effects associated with didanosine treatment are peripheral neuropathy and pancreatitis. In conclusion, didanosine monotherapy is an effective treatment of HIV infection. However, combination antiretroviral therapy is the optimal treatment strategy for most patients, and didanosine is now firmly established as a component of combination antiretroviral drug regimens for the first-line treatment of patients with HIV disease.
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PMID:Didanosine. An update on its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV disease. 895 61

Dideoxyinosine (ddI) is a widely used antiretroviral agent in treatment of HIV infection. Pancreatitis is a serious side effect. Two cases are reported, one with rapid development of a pseudocyst.
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PMID:Dideoxyinosine-induced pancreatitis in human immunodeficiency virus-infected children. 902 60

Therapeutic observations suggest that azidothymidine (AZT)-resistant HIV+/AIDS patients are frequently offered AZT/dideoxycytidine (DDC) or dideoxyinosine (DDI) therapy. The latter therapies have been associated with the development of acute pancreatitis. During the initial portion of this study, when patients reported limiting ethanol consumption, an increase in CD4+, a decrease in amylase, and a decrease in lipase was observed in patients on DDI monotherapy. Marinol/marijuana usage was associated with depressed CD4+ counts and elevated amylase levels within the DDI subgroup. The purpose of this study was to follow these patients over 1 year and compare clinical indicators of pancreatitis and HIV progression. After 1 year, the remaining 56 patients were reexamined in the follow-up portion for clinical indicators of HIV disease progression and pancreatoxic/hepatotoxic effects. Those in the AZT group, who remained on this therapy throughout the year, had significantly increased amylase values from 55.3 to 69.3 IU/liter (p < 0.05). In the AZT/DDC group, those who remained on combination therapy throughout the year, 4 of the 5 clinical indicators of disease progression changed. Amylase, ALT, and AST all increased significantly from 55.2 to 77.8 IU/liter (p < 0.01), from 38.0 to 92.3 IU/liter (p < 0.05), and from 55.2 to 97.0 IU/liter (p < 0.05), respectively. Lipase levels decreased significantly (106.0 to 74.6 IU/liter, p < 0.05). The most remarkable changes occurred in the AZT/DDC group (who reduced ethanol consumption), wherein clinical indicators of pancreatitis and liver dysfunction declined, including amylase (65.0 to 20.0 IU/liter, p < 0.05), ALT (350.0 to 100.0 IU/liter, p < 0.01), and AST (240.0 to 95.0 IU/liter, p < 0.01). No significant changes were noted in the DDI or AZT groups. Marinol/marijuana use was associated with declining health status in both the AZT and AZT/DDC groups. In contrast, all clinical indicators of pancreatitis improved in the DDI patients who utilized Marinol/marijuana, including amylase (-34%), lipase (-30.8%), ALT (-21.4%), and AST (-20.1%). This paired follow-up study suggests that HIV+/AIDS patients on antiretroviral therapies should restrict their ethanol consumption. In HIV+/AIDS patients with the lowest CD4+ counts (those on DDI monotherapy), utilization of Marinol/marijuana does not seem to have a deleterious impact.
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PMID:The impact of ethanol and Marinol/marijuana usage on HIV+/AIDS patients undergoing azidothymidine, azidothymidine/dideoxycytidine, or dideoxyinosine therapy. 904 84


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