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

Extensive acute necrotizing pancreatitis occurred in three patients with the acquired immunodeficiency syndrome who had received both aerosolized pentamidine as prophylaxis and intravenous pentamidine for Pneumocystis carinii pneumonia. The clinical manifestations along with gross and microscopic pathologic findings at autopsy are presented.
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PMID:Pathology of pentamidine-induced pancreatitis. 173 11

The pathologic changes associated with human cryptosporidiosis have not been well characterized. In this report, 15 cases of cryptosporidiosis in acquired immunodeficiency syndrome patients are described. Organisms were found in autopsy tissue specimens in 13 cases, and only in antemortem stool samples in two. Gastrointestinal/hepatobiliary distribution of organisms was as follows: small intestine (13 cases), extrahepatic bile ducts (eight), intrahepatic bile ducts (seven), large intestine (six), pancreas (five), stomach (three), and esophagus (one). At all sites, infection was usually associated with nonspecific reactive epithelial changes, architectural abnormalities such as villous flattening in the small intestine, and interstitial edema with mixed inflammatory cell infiltrates. Presence of organisms and associated mucosal injury were patchy and of variable severity in the intestine. In the biliary tract, injury was commonly diffuse and severe. Pancreatic duct injury was generally mild and often limited to hyperplastic squamous metaplasia. In late-stage acquired immunodeficiency syndrome patients with cryptosporidiosis, widespread infection in the gastrointestinal and biliary systems by this coccidian was more common and severe than previously suggested. Although the mechanisms have yet to be determined, infection usually is accompanied by pathologic changes that may be causally related to pathophysiologic abnormalities, such as diarrhea and malabsorption, and may account for other clinical manifestations of pancreatitis, cholangitis, and obstructive cholestasis.
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PMID:Cryptosporidiosis in the acquired immunodeficiency syndrome: a study of 15 autopsy cases. 174 28

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

To evaluate the long-term toxicity and activity profile of 2',3'-dideoxyinosine (ddI), a potent inhibitor of human immunodeficiency virus (HIV) replication, in vitro. 58 patients with AIDS or AIDS-related complex were studied with additional reference to the effect of previous treatment with zidovudine, and the effect of ddI on HIV-induced cognitive dysfunction. Doses above 9.6 mg/kg per day of ddI were frequently associated with toxicity (peripheral neuropathy, pancreatitis, or hepatitis). Doses of 9.6 mg/kg per day or below were well tolerated for up to 21 months. A subset of patients receiving 3.2-9.6 mg/kg per day of ddI had long-term immunological improvement and reduction of serum HIV p24 antigen. Immunological changes were especially seen in patients who had little previous zidovudine therapy. 5 patients with HIV-induced cognitive impairment improved with ddI. Thus, ddI may have anti-HIV activity at doses which are tolerated for long-term therapy, although pancreatitis could be a life-threatening complication.
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PMID:Long-term toxicity/activity profile of 2',3'-dideoxyinosine in AIDS or AIDS-related complex. 197 29

Several dideoxynucleosides, including 3'-azido-2',3'-dideoxythymidine (zidovudine, azidothymidine, AZT), 2',3'-dideoxycytidine (ddC), and 2',3'-dideoxyinosine (ddI), have been shown to be potent inhibitors of human immunodeficiency virus (HIV) replication in human T cells and macrophages. These compounds undergo anabolic phosphorylation within target cells to a 3'-triphosphate moiety; as triphosphates, they act at the level of HIV DNA polymerase (reverse transcriptase). AZT has been shown to reduce the morbidity and mortality of patients with severe HIV infection and to at least temporarily ameliorate certain cases of HIV-induced dementia. In phase 1 studies, ddC and ddI have been shown to induce immunologic and virologic improvements in patients with AIDS or related disorders; phase 2 studies of ddC and ddI are underway. The use of these drugs can be associated with toxicity. AZT can cause bone marrow toxicity or myositis with prolonged use, ddC can cause peripheral neuropathy at high doses, and ddI can cause sporadic pancreatitis and peripheral neuropathy at high doses. For each compound, however, a therapeutic window exists in which an anti-HIV effect can be attained without short-term toxicity in most patients. Dose-intensity appears to be an important determinant of the toxicity of dideoxynucleosides. Studies are underway to explore how the therapeutic profiles of these compounds may be enhanced by attention to scheduling or through the use of combination therapy.
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PMID:Initial clinical experience with dideoxynucleosides as single agents and in combination therapy. 207 27

A 40-year-old man with prolonged constitutional symptoms and clinical evidence of pancreatitis and biliary tract obstruction underwent exploratory laparotomy. Intraoperative liver and pancreatic biopsies revealed acid-fast bacilli. Mycobacterium tuberculosis subsequently grew from both sputum and urine cultures. The patient responded well to antituberculosis therapy, although 8 months later, he returned with acquired immunodeficiency syndrome (AIDS) and died of large cell lymphoma 1.5 years later. A review of the literature showed that most similar cases of pancreatic tuberculosis were diagnosed only at postmortem examination. A high index of suspicion and attention to special stains are warranted for diagnosis of this frequently fatal, but potentially curable, disease.
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PMID:Pancreatic tuberculosis: a frequently fatal but potentially curable disease. 210 92

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


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