Biomedical subjects
Publications and source records attributed to M Ilton.
Acute myocardial infarction in pregnancy is a rare condition with substantial risk of maternal and fetal mortality. We present a case of myocardial infarction during pregnancy which was treated by percutaneous coronary artery balloon angioplasty and stenting with excellent pregnancy outcome.
Systemic cytokine therapy in cancer has major side effects, and we reasoned that the local infusion of cytokines into tumors could induce local immunologic responses with minimal toxicity and potentially strong systemic anticancer effects. This study investigated the toxicity and effectiveness of intralesional granulocyte/macrophage-colony-stimulating factor (GM-CSF) infusion in solid-tumor masses. We studied 14 patients (12 men, two women) with malignant mesothelioma (MM), aged 60 years (range, 46-70 years), with stage 2 disease, in whom the tumor was of sufficient size and accessibility for an intralesional catheter to be inserted. Recombinant human GM-CSF (Molgramostim; Schering Plough) was infused intralesionally for 8 weeks, by using a portable pump, at a dose of 2.5-10 micrograms/kg/day. One patient using GM-CSF developed histologically confirmed necrosis of tumor surrounding the distal catheter, one developed a marked lymphocytic infiltrate in the tumor and had a partial response measured by chest computed tomography (CT) scan, 10 progressed, and three had no response. Neutrophilia with morphologic evidence of neutrophil activation and clinical features suggestive of neutrophil plugging of blood vessels occurred at doses > 5 micrograms/kg/day. In vitro, GM-CSF doubled human neutrophil/CD11b/CD18 expression, suggesting that neutrophil clumping as seen in vivo might be due to integrin upregulation. Intralesional infusion of cytokines is feasible but can be associated with systemic toxicity and has considerable technical problems. It produces a localized immune reaction with tumor regression in a minority of patients.
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The multienzyme complex from Mycobacterium phlei which catalyzes the synthesis of long chain fatty acids from acetyl-CoA and malonyl-CoA requires a heat-stable fraction (stimulating factor, SF) for activity. Fractionation of heat-treated M. phlei extracts affords two stimulatory subfractions, one of which (SF(2)) can be replaced by FMN. The other (SF(1)) is further separable into 3 polysaccharides (PS(I), PS(II), and PS(III)). PS(I) contains about 95% 3-O-methylmannose and 5% mannose; the sugar composition of PS(II) and PS(III) is about 55% 6-O-methylglucose and 45% glucose for both. Each of the three purified polysaccharides, in combination with FMN, substitutes for the crude stimulating factor. The polysaccharides exert their effect on the fatty acid synthetase by lowering the K(m) for acetyl-CoA about 50-fold.