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

Because pancreatitis has been reported frequently in adults with human immunodeficiency virus infection, we sought to determine the incidence of pancreatitis in children with acquired immunodeficiency syndrome by reviewing all records of children with AIDS, their serum amylase and lipase levels, and the factors associated with pancreatitis through a case-control analysis. During a 6-year period pancreatitis developed in 9 (17%) of 53 pediatric patients with AIDS. Six children had vertical transmission of infection and three patients had acquired HIV infection through contaminated blood products. Pancreatitis developed at a median age of 5.2 years (range 1.2 to 20 years). All patients had vomiting and abdominal pain. When the patients were first seen, lipase values were elevated more than amylase values (p = 0.028). Amylase and lipase levels declined at comparable rates. In the case-control analysis, pentamidine isethionate was significantly associated with pancreatitis (p = 0.02); the risk was greater in patients who received pentamidine isethionate and had absolute CD4 T-lymphocyte counts less than 100 cells/mm3 (p = 0.001). Infections associated with the onset of pancreatitis included cytomegalovirus (4), Cryptosporidium (1), Pneumocystis carinii pneumonia (3), and Mycobacterium avium intracellulare (1). Coinfection with cytomegalovirus was associated with a protracted course in four children. Ultrasonographic examination demonstrated biliary ductal dilatation 6 months after the onset of pancreatitis in one child. Seven children have died at a mean of 8 months after the initial onset of pancreatitis; the one living child has survived 5 months from the onset of pancreatitis. We conclude that pancreatitis is common in pediatric patients with AIDS and may be related to pentamidine isethionate exposure, especially when absolute CD4 T-lymphocyte counts are less than 100 cells/mm3. Serum amylase levels do not always accurately predict the onset of pancreatitis; serum lipase levels should be measured in children with symptoms. The onset of pancreatitis in an HIV-infected child is a poor prognostic indicator.
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PMID:Pancreatitis in pediatric human immunodeficiency virus infection. 137 Sep 62

To investigate the effect of splenectomy on lymphocyte subpopulations we monitored changes in serum concentrations of soluble suppressor/cytotoxic (sCD8) and soluble helper/inducer (sCD4) antigen in 11 splenectomized patients. Indications for splenectomy were hereditary spherocytosis in 2, idiopathic thrombocytopenic purpura in 2, gastric carcinoma in 4, Hodgkin's disease in 2 and pancreatitis in 1 patient. Lymphocyte subpopulations were also analyzed by means of conventional immunophenotyping with monoclonal antibodies to CD4 and CD8. We consistently found an early postoperative drop of sCD8 and sCD4 levels within the first week after splenectomy, paralleling changes in the percentages of CD4+ and CD8+ lymphocytes. While alterations of lymphocyte subsets in the peripheral blood were completely reversible and sCD4 levels returned to preoperative values, sCD8 concentrations remained suppressed even 3 months after splenectomy. SCD8 levels at the nadir and those 3 months after splenectomy were significantly lower than preoperative values (P = 0.003, P = 0.149 respectively). Since sCD8 levels reflect suppressor/cytotoxic cell activity, we suggest that suppressor cell activity is reduced in splenectomized patients.
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PMID:Decrease in soluble CD8 antigen levels in splenectomized patients as an index for reduced suppressor/cytotoxic cell activity. 168 49

The E variant of encephalomyocarditis (EMC) virus causes an encephalomyelitis and coagulative necrosis of the pancreas and parotid glands in some but not all strains of inbred and outbred mice. In other models of disease caused by picornaviruses, depletion of specific lymphocyte subsets abrogates the development of tissue lesions. In this study, severe encephalomyelitis and acinar pancreatitis and parotitis developed in adult male A/J mice infected with 100 PFU of EMC virus. Depletion of the CD4+ subset of T lymphocytes in vivo with a monoclonal antibody (MAb) prior to EMC virus inoculation protects mice from developing encephalomyelitis, pancreatitis, and parotitis. This effect is also seen when animals are treated with anti-CD4 and anti-CD8 in combination, but the anti-CD8 MAb alone does not ameliorate the disease. Overall, concentrations of virus in tissues from anti-CD4-treated animals are lower than in immunologically intact control mice. Small-plaque variants of virus were also recovered from the tissues in some animals in this group. CD4+ lymphocytes are involved in the expression of EMC virus-induced pancreatitis and parotitis in A/J mice. This specific subset of T cells would appear to influence EMC viral tropism or replication in various organs.
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PMID:Immunomodulation of encephalomyocarditis virus-induced disease in A/J mice. 170 84

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 (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

We conducted a Phase I open-label trial of 2',3'-dideoxyinosine (ddI) for the treatment of the acquired immunodeficiency syndrome (AIDS) and severe AIDS-related complex. A single daily dose of ddI was administered orally to 34 patients (17 with AIDS and 17 with AIDS-related complex) for a median of 12 weeks (range, 2 to 56). We studied six dose levels from 1.6 to 30.4 mg per kilogram of body weight per day. Of the 17 patients previously treated with zidovudine, 13 had had hematologic side effects. The maximal tolerated dose of oral ddI was estimated to be 20.4 mg per kilogram per day. Pancreatitis and peripheral neuropathy were the major dose-limiting toxic effects. Other toxic effects included elevations in hepatic transaminase levels, abnormalities in cardiac conduction, rash, and asymptomatic elevations in serum urate levels and the creatine kinase fraction from skeletal muscle. Treatment with ddI was associated with an increase in the mean number of CD4 lymphocytes from 125 per cubic millimeter at base line to 182 per cubic millimeter after 10 weeks (P = 0.005). There were also increases after 12 weeks in the mean total lymphocyte count (from 0.8 to 1.2 x 10(9) per liter) and the mean hemoglobin level (from 12.9 to 14.1 g per deciliter) (both P less than 0.01). The amount of human immunodeficiency virus p24 antigen decreased by more than 50 percent in 14 of 19 patients with detectable antigen. No differences in response were observed between patients previously treated with zidovudine and those never treated with the drug. We conclude that ddI has antiretroviral activity in patients with AIDS or AIDS-related complex and that the toxicity of ddI differs from that of zidovudine. However, controlled trials are necessary to evaluate the efficacy of ddI.
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PMID:Once-daily administration of 2',3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. Results of a Phase I trial. 210 98

DBA/2 male mice inoculated intraperitoneally with 1.8 X 10(5) plaque-forming units (PFU) coxsackievirus B-3 (CVB3) showed extensive inflammatory cell infiltration of the myocardium and acinar tissue of the pancreas in 7 days. Selective depletion of T lymphocyte subpopulations indicated that CD4 cells were either completely or partially responsible for cell damage in both organs. Other organs such as the liver were infected and contained virus titers equivalent to those seen in the heart and pancreas but showed no apparent tissue injury. The role of the CD4 cell was confirmed by positive selection of either T cell subpopulation from CVB3-immune lymphocytes in vitro and adoptive transfer of these cells into T cell-deficient (thymectomized, irradiated, bone marrow reconstituted, TXBM) DBA/2 recipients. Lymphocytes from CVB3-infected donor mice were adsorbed to myocyte, skin fibroblast, or liver vascular endothelial cell (VEC) monolayers. The adherent population was retrieved and adoptively transferred into uninfected syngeneic recipients. When killed 7 days later, the animals receiving unfractionated immune lymphocytes or cells eluted from heart monolayers developed both myocarditis and pancreatitis. Anti-Thy 1.2 and C' treatment of the unfractionated cells completely abrogated transfer of disease. Cells eluted from either fibroblast or liver VEC monolayers showed no pathogenicity. Adsorption of immune cells to heart monolayers in the presence of anti-IAd (class II major histocompatibility complex antigen, MHC) inhibited attachment of the pathogenic T cell, whereas anti KdDd (a class I MHC antigen) had no effect.
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PMID:Coxsackievirus-induced disease. CD4+ cells initiate both myocarditis and pancreatitis in DBA/2 mice. 257 84

To define predictive or contributory risk factors for pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine (ddI), the authors evaluated 95 children, 3 months to 18 years of age, who had received ddI at 60 to 540 mg/m2 per day for a mean of 56 weeks. Pancreatitis developed in 7 patients (7%) but resolved in all upon withdrawal of ddI. Neither age, sex, nor CD4 count at study entry was predictive of pancreatitis, but pancreatitis appeared more likely to develop in hemophiliacs than in other patients (4 of 23 vs 3 of 72). Pancreatitis developed only in patients who received ddI at the highest dose levels (7 of 60 patients who received ddI at a dose > or = 360 mg/m2 per day vs 0 of 35 patients who received < or = 270 mg/m2 per day). Patients in whom pancreatitis developed had received a higher mean daily dose of ddI than patients with normal amylase and lipase levels throughout the study (348 mg/m2 vs 282 mg/m2), but no relationship with the cumulative dose or the duration of ddI therapy was observed. Although a statistically significant relationship between ddI plasma concentration (area under the curve) and pancreatitis was not conclusively demonstrated, as the number of patients in whom pancreatitis actually developed was small, such a relationship may have been obscured.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine. 768 40

Starting in 1988, 72 patients with advanced human immunodeficiency virus (HIV) infection were enrolled in a phase I study of didanosine at the National Cancer Institute. Beginning in 1992, patients with decreases in CD4 cell counts could switch to a combination of zidovudine and didanosine. The estimated median survival for all patients was 28 months (95% confidence interval, 23-46). However, for patients whose entry CD4 cell counts were 100-300/mm3, the estimated 4-year survival was 80%. Baseline CD4 and CD8 cell counts, hemoglobin, lymphocytes, sedimentation rates, diagnosis of AIDS, and fever were significant predictors of overall survival. Principal toxicities were pancreatitis and peripheral neuropathy; no new toxicities were seen with extended didanosine treatment that had not been observed in shorter-term studies. This 5-year follow-up shows that didanosine can be tolerated for > 4 years in some patients with advanced HIV infection and may have particular long-term utility in patients with moderately advanced immunosuppression.
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PMID:Five-year follow-up of a phase I study of didanosine in patients with advanced human immunodeficiency virus infection. 775 92

The didanosine Expanded Access Program was the largest AIDS treatment program to prospectively evaluate the safety of an antiretroviral agent among patients with advanced human immunodeficiency virus (HIV) disease in whom therapy with zidovudine was failing. A total of 21,198 patients who had infections refractory to zidovudine or who were intolerant of the drug received didanosine as a buffered powder for oral solution (sachet), with total daily doses of 6.6-10 mg/kg; the median CD4 lymphocyte count was 0.04 x 10(9)/L for this population. At the currently recommended dose (6.6-8.29 mg/[kg.d]), 6-month estimated rates of pancreatitis ranged from 1.2% for patients with AIDS-related complex (ARC) and CD4 lymphocyte counts of > or = 0.1 x 10(9)/L to 6.7% for patients with AIDS and CD4 lymphocyte counts of < 0.05 x 10(9)/L. Laboratory toxicities of World Health Organization grades 3 and 4 developed in fewer than 4% of patients entering the study with normal baseline values; the sole exception was leukopenia, which was documented in 8% of these patients. The results of this program demonstrated that patients with CD4 lymphocyte counts of < 0.10 x 10(9)/L or with a diagnosis of AIDS (defined by the 1987 classification system of the Centers for Disease Control and Prevention) were less tolerant of didanosine and significantly more likely to develop adverse clinical reactions and myelosuppression than other patients.
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PMID:Rates and risk factors for adverse events associated with didanosine in the expanded access program. 788 37


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