amphotericin-b and Arteriosclerosis

Leukaemic patients with advanced disease and severe fungal infections as well as older patients with substantial co-morbidity are usually excluded from conventional allotransplantation because of increased morbidity and mortality. We approached allogeneic transplantation in four patients with a median age of 62 years (one chronic myeloid leukaemia in blast crisis, one high-risk acute myeloid leukaemia (AML) in first complete remission (CR1), one AML in 2nd relapse, one AML in CR2 with pre-existing fungal lung infections (two aspergillus, two mucor) and additional co-morbidity (diabetes n = 2, aortic aneurysm n = 1, arterial sclerosis n = 2) by combining non-myeloablative conditioning with an intensified supportive care regimen, including amphotericin B and 4-12 (median 9) prophylactic granulocyte transfusions from granulocyte colony-stimulating factor (G-CSF)-stimulated volunteer donors. G-CSF was also given to patients until neutrophil recovery. All four patients recovered to a neutrophil count of 0.5 x 109/l after a median of 11.5 d (range 11-13 d). Prophylactic granulocyte transfusions also reduced the need for platelet transfusions and minimized mucositis. All patients were discharged at a median of 25 d (range 18-59 d) and are alive and well after a median follow-up of > 390 d (range 336-417 d) without evidence of leukaemia. Regression of the fungal lesions was documented in three patients, with a slight progression detected by computerized tomography scan of the chest in one patient. We conclude that pulmonary fungal infections are not a contraindication for allogeneic stem cell transplantation, if non-myeloablative conditioning regimens are used in combination with granulocyte transfusions, intravenous amphotericin B and G-CSF.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Aortic Aneurysm; Arteriosclerosis; Aspergillosis, Allergic Bronchopulmonary; Bone Marrow Transplantation; Cell Count; Diabetes Complications; Diabetes Mellitus; Granulocyte Colony-Stimulating Factor; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Chronic-Phase; Lung Diseases, Fungal; Male; Middle Aged; Neutrophils; Platelet Count; Recurrence; Remission Induction; Tomography, X-Ray Computed; Transplantation, Homologous; Treatment Outcome

A simple and highly reproducible culture method of aortic endothelial cells from cadaver is herein reported. Major bacterial contamination could be prevented by administration of an antibiotic cocktail consisting of gentamicin, ampicillin, and amphotericin B. Endothelial cells from the thoracic aorta were viable up to 17 hours postmortem and successfully culturable from the aorta by dispase desquamation from the subendothelial substrate. The cultured cells varied in size and shape depending on the degree of individual atherosclerotic severity and could be divided into two major subtypes. The first type is a small and polygonal uniform cell (typical endothelial cell) and the second type is a mixture of spindle and giant bizarre cells often associated with multinuclei (variant endothelial cell). Both types of endothelial cells have characteristics specific for endothelium, such as factor VIII related surface antigen, Weibel-Palade body, and high productivity of prostacyclin.

Topics: Adult; Aged; Amphotericin B; Ampicillin; Aorta, Thoracic; Arteriosclerosis; Bacteria; Cells, Cultured; Endothelium; Epoprostenol; Female; Gentamicins; Humans; Male; Microscopy, Electron; Middle Aged

Fungal endarteritis resulting from progressive disseminated histoplasmosis may cause arterial aneurysms, or lead to infection of pre-existing aneurysms. Three patients with Histoplasma capsulatum infections of abdominal aortic aneurysms are reported. All had previous disseminated histoplasmosis and atherosclerotic peripheral vascular disease. All were considered cured of systemic infection when their aneurysms were discovered. Atherosclerotic vascular lesions may become infected during the course of systemic fungal disease and may serve as a haven for viable organisms in patients whose dissemination recurs despite seemingly adequate antifungal therapy. In treating these patients, resection of all infected arterial tissue, revascularization through uninfected tissues, and long-term antimicrobial therapy are recommended.

Topics: Adult; Aged; Amphotericin B; Aorta, Abdominal; Aortic Aneurysm; Arteriosclerosis; Female; Histoplasmosis; Humans; Imidazoles; Ketoconazole; Male; Middle Aged; Piperazines