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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phase I clinical trials of the purine analog 2',3'-dideoxyinosine (ddl) revealed that 10% of the patients developed pancreatitis, yet there was no clear relationship between increasing doses of ddl and the development of pancreatitis. To test the effects of chronic ddl administration on the structure and function of the rat pancreas, male Wistar rats were given ddl at 100 mg/kg/day i.p. for 35 days or 1400 mg/kg/day for 30 days, in two divided doses. Serum amylase levels, pancreatic tissue water content (edema) and pancreatic morphology by light and electron microscopic examination of pancreata from ddl-treated rats were similar to those of rats receiving saline injections only (controls). 2',3'-Dideoxyinosine administration did not alter the subcellular distribution of the lysosomal enzyme cathepsin B, whose redistribution to a more dense zymogen granule-enriched subcellular fraction is an early indicator of acute pancreatitis. Dispersed pancreatic acini from rats receiving ddl (100 mg/kg/day for 30 days) were incubated in vitro for 15 min with either caerulein or carbamylcholine as secretory stimuli. There was no detectable difference in the stimulatable amylase secretion from ddl-treated animals compared to the control group. Based on these findings, we conclude that ddl has no direct toxic effect on the rat pancreas. 2',3'-Dideoxyinosine may be contributing to pancreatitis in acquired immunodeficiency syndrome patients by potentiating other pancreatotoxic agents or by its action on a pancreas that is already altered by the human immunodeficiency virus infection.
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PMID:In vivo and in vitro effects of the azidothymidine analog dideoxyinosine on the exocrine pancreas of the rat. 137 99

Acute pancreatitis is observed in patients with the acquired immunodeficiency syndrome (AIDS) (4-22%), and is reported with increasing frequency as a complication of therapy in human immunodeficiency virus-spectrum disease. The cause is multifactorial (virus, neoplasm, drugs), and the natural history generally mild and uncomplicated. 2',3'-Dideoxyinosine (ddI) is an experimental antiretroviral agent implicated as a cause of acute pancreatitis in a small number (0.9-2%) of patients. To better define this relationship, we conducted a retrospective analysis of a prospective clinical trial involving 51 homosexual males with AIDS treated with ddI (10-12 mg/kg/day) and reported on the incidence and natural history of pancreatitis. Clinical pancreatitis (symptoms, elevated serum amylase, and lipase and, in most cases, abnormal radiographic studies of the pancreas) was observed in 12 patients (23.5%). Asymptomatic elevations of amylase and lipase were identified in 10 additional patients (39.2%). The onset of pancreatitis was consistently delayed in both groups (overall mean 14.1 +/- 1.2 wk, 98% confidence interval). Ten of 12 symptomatic patients required hospitalization (mean length of stay, 9.4 days); two of 12 progressed to fulminant pancreatitis and died. Two patients with asymptomatic pancreatitis which occurred after starting ddI were rechallenged; severe symptomatic pancreatitis developed shortly after drug reinstitution. In each case, complete recovery followed discontinuation of the drug. We conclude that 1) The incidence (62.7%) and severity of pancreatitis in patients with AIDS receiving ddI therapy are significantly greater than expected, 2) the onset is predictably delayed about 14 wk, 3) ddI should be added to the list of drugs that cause acute pancreatitis, and 4) careful sequential monitoring of pancreatic function and early identification of potential "risk factors" for pancreatitis in AIDS patients treated with ddI may be essential in avoiding this serious complication.
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PMID:Acute pancreatitis as a common complication of 2',3'-dideoxyinosine therapy in the acquired immunodeficiency syndrome. 843 64

Zidovudine (azidothymidine, Retrovir) and ddI (di-deoxy-inosine, Videx) interfere with the multiplication of HIV by incorporation into nascent DNA chains and interruption of the further linking of nucleotides. Zidovudine lowers early mortality in patients with Aids and pneumocystis carinii pneumonia. However, much of the effectiveness of zidovudine is lost later on; the average prolongation of life in treated patients is estimated to be about 1 year. About two thirds of patients with Aids can be treated with zidovudine; in the others, the drug is ineffective or contraindicated. Frequent blood counts are necessary to monitor myelotoxicity, even at relatively low doses of 500 mg/day. In contrast, zidovudine is well tolerated by asymptomatic patients with 200 to 500 CD4 lymphocytes/mm3, in whom it diminishes the incidence of Aids from about 7 to 3% during the first year of treatment, with less than 2% severe anemia or leukopenia. For patients who do not tolerate zidovudine, ddI is an alternative. It is not myelotoxic but can cause neuritis and pancreatitis, especially at doses in excess of 10 mg/kg/day. Although its antiviral effect is excellent both in vitro and in vivo, there is still a lack of firm data on its clinical value, such as the decrease in opportunistic infections and increase in survival.
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PMID:[Antiretroviral therapy in Switzerland 1991]. 192 47

2',3'-Dideoxyinosine (didanosine; ddI) was administered to 37 adults with AIDS or AIDS-related complex in an escalating-dose phase I study. Groups of three or four patients received intravenous dosages of 0.4 mg/(kg.d) to 25.6 mg/(kg.d) divided into two or three daily doses for 2 weeks, followed by oral ddI at twice the intravenous dosages. When given with antacids, ddI was well absorbed by the oral route and penetrated into the cerebrospinal fluid. The patients had an increase in mean number of CD4+ cells from 114/mm3 at entry to 161/mm3 at week 6 (P = .00004). They also had an increase in the CD4+/CD8+ ratio and in total number of lymphocytes. Sixteen of 18 evaluable patients had a decrease in levels of human immunodeficiency virus p24 antigen by week 6 (P = .0034). Many patients reported increased energy and appetite and gained weight. Dose-limiting toxicities at high dosages were painful peripheral neuropathy and sporadic pancreatitis. However, dosages up to 9.6 mg/(kg.d) have been tolerated in patients for 11-14 months. Thus, ddI has activity against human immunodeficiency virus at dosages that can be tolerated for approximately 1 year. However, life-threatening pancreatitis is a possible complication even at low dosages, and the best ways to manage and avoid adverse effects are still under study.
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PMID:The National Cancer Institute phase I study of 2',3'-dideoxyinosine administration in adults with AIDS or AIDS-related complex: analysis of activity and toxicity profiles. 197 24

We performed a phase I study of escalating dosages of 2',3'-dideoxyinosine (didanosine; ddI) in 19 patients with AIDS or AIDS-related complex in order (1) to establish the maximal tolerated dosage, (2) to determine the nature of toxic adverse effects, (3) to measure changes in levels of circulating human immunodeficiency virus p24 antigen and in CD4+ cell counts, and (4) to evaluate the pharmacokinetics of ddI. Almost all patients had received zidovudine therapy previously. The maximal tolerated dosage of ddI was found to be approximately 12 mg/(kg.d) when it was administered orally for 28 weeks. The major dosage-limiting adverse effects encountered were neuropathy, pancreatitis, and hepatitis. These occurred at dosages higher than those associated with decreases in levels of p24 antigen. The major toxic effects of ddI are different from those associated with zidovudine. At the proper dosage, ddI may prove to be an effective agent for the chronic treatment of infection with human immunodeficiency virus and should be especially useful in the treatment of patients who cannot tolerate zidovudine.
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PMID:Phase I study of 2',3'-dideoxyinosine: experience with 19 patients at New York University Medical Center. 197 25

Twenty-one patients with AIDS or AIDS-related complex (ARC) received 2',3'-dideoxyinosine (didanosine; ddI) intravenously and then orally (initial dosages of 0.4 mg/kg and 0.8 mg/kg every 12 hours, respectively) for 6-44 weeks in an escalating-dose study. The major dose-limiting effects were peripheral neuropathy (three patients) and pancreatitis (two patients), which were observed at dosages greater than or equal to 20 mg/(kg.d). Hyperuricemia occurred at greater than or equal to 30 mg/(kg.d). No hematologic toxicity developed except for possible sporadic thrombocytopenia (two patients). Significant decreases in serum levels of p24 antigen and increases in CD4+ and CD8+ lymphocytes were noted at 2, 6, and 10-20 weeks and over a wide range of dosages, including the lowest given. Most patients had an increased feeling of well-being and/or a weight gain of greater than or equal to 2 kg at 6 weeks. For this population, ddI has promise as a therapeutic agent, thus warranting further study of this agent in controlled clinical trials.
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PMID:2',3'-Dideoxyinosine in patients with AIDS or AIDS-related complex. 197 26

In a phase I dosage-finding trial, 2',3'-dideoxyinosine (didanosine; ddI) was administered once daily to 36 patients with AIDS or AIDS-related complex for up to 65 weeks (mean, 32.1 weeks) at six dosage levels. Thirteen of 18 patients previously treated with zidovudine had developed hematologic intolerance. The maximal tolerated dosage of ddI was 12 mg/(kg.d); dose-limiting toxicities were pancreatitis and peripheral neuropathy. Other toxicities included elevation in hepatic transaminase levels, rash, cardiac conduction abnormality, and asymptomatic hyperuricemia. Eighty-six percent of patients who completed 6 weeks of treatment showed improvement in constitutional symptoms and significant weight gain. In patients treated with ddI, the mean number of CD4+ lymphocytes increased from 124/mm3 at baseline to 199/mm3 at 24 weeks (P = .0027) and the mean leukocyte count, total lymphocyte count, and hemoglobin level showed increases (all P less than .01) after 12 weeks. Serum levels of viral p24 antigen decreased greater than or equal to 50% in 14 of 19 assessable patients. No differences between the responses of patients previously treated with zidovudine and those of zidovudine-naive patients were observed. These results indicate that ddI has significant antiretroviral activity in vivo and a toxicity profile different from that of zidovudine.
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PMID:Treatment of AIDS and AIDS-related complex with 2',3'-dideoxyinosine given once daily. 197 27

2',3'-Dideoxyinosine (ddI) is a purine analogue that after intracellular metabolic conversion suppresses the replication of the human immunodeficiency virus (HIV). We conducted a Phase I dose-escalation study of ddI in 17 patients with the acquired immunodeficiency syndrome (AIDS) and 20 patients with AIDS-related complex. The drug was administered twice daily over a dose range of 0.4 to 66 mg per kilogram of body weight per day for 2 to 44 weeks. The maximal tolerated oral dose of ddI was estimated to be 12 mg per kilogram per day. The major dose-limiting toxic effects were a painful peripheral neuropathy (in eight patients) and pancreatitis (in five). Asymptomatic elevations of the serum aminotransferase levels (in 13 patients) and the serum urate level (in 10) were also noted, but there was no dose-related hematologic toxicity. At the maximal tolerated dose, the peak plasma levels of ddI were 6.3 to 9.6 mumol per liter 0.6 to 1 hour after oral administration; the mean plasma half-life was 1.5 hours. The administration of ddI was associated with statistically significant decreases in serum level of p24 antigen and increases in the numbers of CD4 cells at 2, 6, 10, and 20 weeks. These changes were seen at all dose levels studied. Either a clinical improvement or a weight gain of greater than or equal to 2 kg was observed in 25 of 34 patients at six weeks. We conclude that ddI is a promising therapeutic agent in patients with AIDS or AIDS-related complex. Its efficacy is currently being evaluated in large-scale, controlled clinical trials.
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PMID:2',3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. A phase I trial. 210 98

Ninety-two adult patients with AIDS or severe AIDS-related complex were treated with 2',3'-dideoxyinosine (didanosine; ddI) at dosages ranging from 0.8 to 66.0 mg/(kg.d) for at least 6 weeks in phase I trials. Potentially beneficial changes in weight (40% of patients), clinical signs or symptoms (40% of patients), CD4+ cell counts (25% of patients), and serum levels of HIV p24 antigen (50% of antigen-positive patients) were reported. Response rates tended to be higher among patients with AIDS-related complex and among those who had not received prior zidovudine therapy. A major response (improvement in at least one clinical parameter and in at least one laboratory marker) occurred in 29% of patients, and rates of major response tended to be higher in patients receiving higher dosages. The primary dose-limiting toxicity observed was peripheral neuropathy, which was observed with increasing frequency in patients receiving greater than 20 mg/(kg.d). Of the other adverse effects, pancreatitis was possibly dose-dependent and hyperuricemia (without clinical gout) occurred only at high doses. Dosages of 250 mg and 375 mg of ddI twice daily will be used in extended phase II/III studies.
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PMID:Overview of phase I trials of 2',3'-dideoxyinosine (ddI) conducted on adult patients. 216 65

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


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