Glucagon cell adenomatosis: a newly recognized disease of the endocrine pancreas.

BACKGROUND: Glucagon-producing tumors are either solitary neoplasms of the pancreas, occasionally associated with a glucagonoma syndrome, or multiple neoplasms associated with multiple endocrine neoplasia type 1 (MEN1). We observed a previously undescribed multicentric glucagon-producing tumor disease that is not related to MEN1. METHODS: Pancreatic tissue from four patients showing multiple neuroendocrine microadenomas and in two cases also macrotumors were screened for hormones using immunohistochemical and morphometric methods. MEN1, von Hippel-Lindau, and p27 germ line and somatic mutation analysis was performed. Deletion of MEN1 (11q13), von Hippel-Lindau (3p25), and the centromere 11 and 3 gene locus was determined by fluorescence in situ hybridization. DNA copy number changes were studied using array comparative genomic hybridization. RESULTS: The pancreatic tissue from the four patients contained more than 870 microadenomas and 10 macrotumors, all of which expressed exclusively glucagon and none of which showed evidence of malignancy. In addition, many islets were unusually large and showed glucagon cell hyperplasia. There was no clinical or molecular evidence of any hereditary tumor disease, and changes in the MEN1 gene were only seen in individual tumors. Array comparative genomic hybridization of one macrotumor and 20 pooled microadenomas revealed a homogeneous diploid chromosome set. CONCLUSIONS: The findings are sufficiently distinctive to suggest a new neoplastic disease of the endocrine pancreas that we recommend calling glucagon cell adenomatosis. Clinically, this disease may be an incidental finding, or it may lead to a glucagonoma syndrome.

Interleukin-3 is elevated in patients with coronary artery disease and predicts restenosis after percutaneous coronary intervention.

BACKGROUND: Interleukin-3 (IL-3) synthesized by activated T-lymphocytes is a mediator in chronic inflammation and is suspected to promote atherosclerosis. Since there is no data on IL-3 in patients with coronary artery disease (CAD) available, we compared IL-3 concentrations in different subsets of patients with CAD to healthy control patients. METHODS: 205 consecutive patients with CAD, 136 with stable angina and 69 with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention, 61 patients with asymptomatic CAD and 41 patients with normal coronary arteries were investigated. Serum concentrations of IL-3 and hs-CRP were assessed at baseline and after 6 weeks, 6, and 12 months. RESULTS: In patients undergoing coronary angioplasty, IL-3 was detectable more frequently than in those with asymptomatic CAD or without CAD, 21 vs. 8%, p=0.02, and 21 vs. 1%, p<0.001, respectively. Patients undergoing coronary angioplasty who developed symptomatic restenosis more frequently had detectable IL-3 levels than patients without restenosis, 45 vs. 17%, p=0.02. IL-3 was the only independent predictor for restenosis in a multivariate analysis. Hs-CRP was significantly elevated in patients with ACS, 230+/-170 mg/l vs. 100+/-140 mg/l, p=0.02, but did not correlate with IL-3 concentrations at any time. CONCLUSION: IL-3, an important regulator of chronic inflammation, is elevated in patients with CAD, particularly in symptomatic patients undergoing percutaneous coronary intervention. Furthermore, high IL-3 concentrations were found to be predictive of symptomatic restenosis.

A randomized trial in patients undergoing percutaneous coronary angioplasty: roxithromycin does not reduce clinical restenosis but angioplasty increases antibody concentrations against Chlamydia pneumoniae.

BACKGROUND: Elevated antibodies against Chlamydia pneumoniae have been associated with coronary artery disease. In patients undergoing percutaneous coronary angioplasty, we therefore investigated the effect of roxithromycin on symptomatic restenosis and determined antichlamydial antibodies as well as inflammatory and immunological parameters. METHODS: A total of 327 patients undergoing coronary angioplasty were randomized to roxithromycin or placebo and followed-up for 1 year. Antibodies were determined by microimmunofluorescence and enzyme-linked immunosorbent assay; C-reactive protein, interleukin-10, tumor necrosis factor-alpha (TNF-alpha), and eotaxin were determined by enzyme-linked immunosorbent assay. RESULTS: Although the frequency of restenosis was not affected by roxithromycin (25 restenoses vs 32 in the control group), antichlamydial antibodies increased during follow-up (anti-CP IgG +12 +/- 2%, P < .001). Concentrations of TNF-alpha and eotaxin increased as well (TNF-alpha +9 +/- 1% and eotaxin +10 +/- 2%) and correlated with antichlamydial antibody concentrations (TNF-alpha, r = 0.23, P = .02; eotaxin, r = 0.32, P = .002). CONCLUSIONS: Treatment with roxithromycin was not associated with a reduction of symptomatic restenoses. During follow-up, a marked increase in antichlamydial antibodies, TNF-alpha, and eotaxin was observed, suggesting that angioplasty-induced plaque rupture induces a specific immunological response without activation of inflammatory mechanisms as represented by C-reactive protein. Whether this mechanism occurs in all plaque ruptures remains to be determined.