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)

A randomized pilot study comparing alternating and simultaneous regimens of zidovudine and didanosine (ddl) was conducted in 41 patients with AIDS or symptomatic human immunodeficiency virus (HIV) infection. Patients on each regimen received the same overall amounts of zidovudine and didanosine over time. CD4 cell counts in patients on the simultaneous regimen reached a maximum (mean +/- SE) of 108 +/- 16/mm3 above baseline (two-tailed P < or = .0001) and were significantly higher than in patients on the alternating regimen at all time points during weeks 6-45. At 54 weeks, the CD4 cell counts in the patients on the simultaneous regimen were still 40 +/- 19/mm3 above baseline. Patients on the simultaneous regimen also had significantly greater weight gain. While toxicities were generally mild and comparable between the regimens, 1 patient on the simultaneous regimen died of pancreatitis and lactic acidosis. Thus, simultaneous therapy provided more sustained elevations in CD4 cells than alternating therapy over 1 year and may be worth exploring in larger controlled trials.
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PMID:A randomized pilot study of alternating or simultaneous zidovudine and didanosine therapy in patients with symptomatic human immunodeficiency virus infection. 790 76

When activated, lymphocytes secrete glycoproteins related to particular surface proteins, including soluble forms of the interleukin-2 receptor (sIL-2R) and of the surface proteins CD4 (sCD4) and CD8 (sCD8). We evaluated the release of these glycoproteins in order to assess the activation of the cellular immune system during the course of acute pancreatitis. Thirty-five patients with acute pancreatitis (22 M, 13 F, mean age 64 years, range 16-97) were studied. The diagnosis was based on typical abdominal pain associated with a twofold increase of serum lipase as well as morphological abnormalities compatible with acute pancreatitis seen at computed tomography and/or ultrasonography. The pancreatitis was of biliary origin in 22 patients, due to alcohol abuse in 8, due to pancreas divisum in 1, due to type IV hyperlipoproteinemia in 1 and of unknown origin in 3. Based on clinical outcome, 22 patients had mild pancreatitis, whereas 13 had severe disease. In all patients serum sIL-2R, sCD4 and sCD8 were determined on admission and daily for the following 5 days using enzyme immunoassay (EIA) techniques. Serum concentrations of sIL-2R and sCD8 were significantly higher in acute pancreatitis patients relative to healthy controls during the entire observation period, whereas sCD4 levels were significantly lower in acute pancreatitis patients than in the control group from the 2nd to the 6th day of observation. Serum sIL-2R concentrations were significantly higher in patients with severe pancreatitis than in those with the mild form of the disease, whereas no differences in serum concentrations of sCD8 and sCD4 were found between patients with mild pancreatitis and those with severe disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavior of serum soluble interleukin-2 receptor, soluble CD8 and soluble CD4 in the early phases of acute pancreatitis. 806 32

Long-term follow-up of 44 patients with AIDS or AIDS-related complex (ARC) in a phase 1 trial of didanosine is reported. These patients were monitored for as long as 72 weeks (mean, 34 weeks) for toxicity and activity of didanosine. Pancreatitis and neuropathy, the major clinical toxicities, developed infrequently at the doses of didanosine (250-750 mg/d) employed during the latter part of the study. Consistent hematologic toxicity was not encountered; moreover, mean values for hematologic parameters such as hemoglobin concentration, white blood cell count, neutrophil count, lymphocyte count, and platelet count improved for up to 20-60 weeks. CD4 counts increased significantly through 10 weeks of therapy and in some patients remained at or above counts at enrollment for as long as 60 weeks. Serum concentrations of p24 antigen decreased significantly and remained at the decreased level for up to 48 weeks. An initial diagnosis of ARC (as opposed to AIDS), an initial CD4 count of > 100/mm3, and an increase in CD4 counts during the first 10 weeks of therapy were associated with a higher rate of survival and with lower rates of development of opportunistic infections and of other clinical manifestations of disease progression.
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PMID:Didanosine: long-term follow-up of patients in a phase 1 study. 809 46

One hundred fifty-one patients who were positive for antibody to human immunodeficiency virus (HIV) and intolerant of zidovudine received oral didanosine at a dose adjusted by weight to a maximum of 12.5 mg/(kg.d). After 1 year of follow-up, 49 patients were still receiving didanosine; 19 had died during therapy and 23 thereafter. Therapy had been discontinued in 10 cases because of continued deterioration in health and in the remainder because of adverse reactions. Only 11 of 38 patients with positive results in an ELISA for p24 antigen before therapy had a significant reduction in titer. CD4 lymphocyte subset counts were more likely to rise for patients who had only constitutional disease due to HIV than for those with AIDS. Eleven percent of treated patients gained > 2.5 kg. Diarrhea was the commonest side effect, occurring in 60% of cases. Pancreatitis developed in six cases (with two deaths) and asymptomatic hyperamylasemia in 13. Seven patients developed glucose tolerance in the diabetic range. Peripheral neuropathy was documented in 12 instances but was reversible on cessation of therapy in six.
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PMID:Use of didanosine in zidovudine-intolerant patients infected with human immunodeficiency virus. 809 48

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

Circulating lymphocyte numbers and activation together with granulocyte function were measured in 20 patients in the early stages of an attack of acute pancreatitis and in 20 healthy controls. Circulating lymphocytes, T lymphocytes, and CD4 and CD8 T lymphocyte subsets were decreased in both mild pancreatitis (67-80 per cent of controls) and severe pancreatitis (22-40 per cent of controls). CD4:CD8 ratios were unchanged and median (interquartile range) interleukin 2 receptor expression was increased from less than 1 per cent in controls to 14(6) per cent in severe pancreatitis, suggesting lymphocyte activation. Median granulocyte chemiluminescence was increased to 293 per cent of controls in severe pancreatitis and random motility was reduced to 77 per cent of controls, indicating increased metabolic activity. Complement-mediated antibody-independent opsonization and chemotaxis toward endotoxin were normal. Immune function is not reduced early in acute pancreatitis. Granulocyte hyperactivity may be important in the development of multiple organ failure.
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PMID:Immune function early in acute pancreatitis. 894 82

Gene transfer into the pancreas would be useful for the treatment of a variety of disorders, including cystic fibrosis, diabetes, cancer, and immunomodulation of pancreatic allografts. A hypothesis that various cell populations in the pancreas could be targeted by recombinant adenoviruses was developed and tested. Gene transfer into the rat ductal epithelium, acinar cells, and islets of Langerhans was accomplished with a recombinant adenovirus containing bacterial beta-galactosidase by retrograde delivery of adenovirus into the pancreaticobiliary duct. Maximal gene expression was observed at 3 days and correlated with DNA blot analysis. Histologic analysis of sections from pancreatic tissue in the adenovirus-treated rats demonstrated severe pancreatitis. Immunophenotyping of the inflammatory infiltrate with rat lymphocyte-specific markers showed CD45-, CD8-, and CD4-positive cells. Tissue injury resolved as gene expression was lost, with both features absent by 21 days. Pancreatic regeneration was documented by the presence of 5-bromo-2'-deoxyuridine-positive staining cells. Pancreatic gene transfer with first-generation recombinant adenoviruses can be accomplished by techniques applicable to clinical situations. The use of first-generation recombinant adenoviruses for pancreas-directed gene transfer is limited by the development of inflammation and transient expression.
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PMID:Adenovirus-mediated in vivo gene transfer and expression in normal rat pancreas. 874 Apr 9

In this multicenter study (ISS 902), 554 previously untreated patients with <500 CD4 cells/mm3 and mildly symptomatic human immunodeficiency virus disease were randomized to receive zidovudine or didanosine (ddI). After a mean follow-up of 20 months, 80 patients (40 zidovudine, 40 ddI) had died and 146 had at least one AIDS-defining event (73 zidovudine, 73 ddI). Overall, no difference was found between treatments with respect to progression to AIDS or death. The analysis of relative risk (RR) of progression over time, however, showed an initially minor risk for zidovudine patients and an inversion in the zidovudine-ddI RR in the second and third years of follow-up. Didanosine showed a greater effect on CD4 cell count response. The two drugs confirmed the toxicity patterns already reported in other trials, with a low occurrence of pancreatitis (ddI 1.3%, zidovudine 0.4%). The overall results suggest that, in this population, zidovudine and ddI monotherapies have comparable long-term clinical efficacy and that more powerful regimens should be preferred.
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PMID:A randomized trial (ISS 902) of didanosine versus zidovudine in previously untreated patients with mildly symptomatic human immunodeficiency virus infection. 920 45


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