The eosinophil, a cell with multiple facets.
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Biomedical subjects
Publications and source records attributed to M Goldman.
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Inflammation is commonly observed in liver diseases and is frequently complicated by fibrosis and cirrhosis in end-stage disease. The only curative treatment for cirrhotic patients is liver transplantation. However, organ shortage as well as an increasing organ demand call for early treatment of liver disease and prevention of fibrosis. Experimental data have shown the critical role of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the development of liver injury. Here, we review our work on the role of endogenously produced interleukin-10 (IL-10), a potent anti-inflammatory cytokine, in several experimental models of acute and chronic liver injury. First, in acute macrophage-mediated hepatitis induced by galactosamine/lipopolysaccharide administration, IL-10 neutralisation led to a more severe liver damage, whereas IL-10 injection, even delayed, was able to limit liver necrosis. A similar protective effect of IL-10 was observed in acute T cell-mediated hepatitis induced by concanavalin A (Con A) injection. The immunoregulatory role of IL-10 was then established after repeated exposition to Con A. In carbon tetrachloride liver injury, two other properties of IL-10 have been suggested: modulation of hepatocyte proliferation and modulation of liver fibrosis. Finally, the potential therapeutic applications in human liver disease as well as the potential side effects are discussed.
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An experimental method for rapid replacement of the transverse aortic arch is presented. Branched intraluminal prostheses were fashioned of varying sizes containing ascending and descending aortic limbs and branches for the brachiocephalic and subclavian vessels. Rigid rings were sewn into the ends to allow rapid fixation of the grafts using extraluminal ligatures. In 31 dogs, arch prostheses were inserted using inflow occlusion at normothermia. Twenty-seven animals successfully underwent aortic arch replacement during periods of circulatory arrest from 2.5 to 6.5 minutes. One animal was electively sacrificed 3 years after arch replacement. Various sized aortic arch prostheses manufactured for clinical use would have the potential advantages of technical simplicity of insertion and reduced cardiopulmonary bypass. Alternatively, varying sized tubular grafts for the brachiocephalic branches could be attached to the currently available tubular intraluminal grafts.
We analysed the impact of the area of the dialysis membrane and of its content in hydroxyl moieties on the magnitude of haemodialysis-induced complement activation and leucopenia. First, in five patients successively treated with cellulose acetate membranes of different areas, we found that increase of the area results in an increase in complement activation determined by C3a levels before and at 15 min of dialysis. The levels of leucopenia were similarly affected, and a significant correlation was found between complement activation and leucopenia (r = 0.89, P less than 0.05). When we compared the biocompatibility characteristics of a dialyser made of saponified cellulose ester with those of two dialysers made of cellulose acetate, we found that index of complement activation (18.1 +/- 2 vs 9.9 +/- 1.1 and 11.5 +/- 1.1, P less than 0.01) as well as index of leucopenia (69 +/- 4 vs 40 +/- 2 and 37 +/- 3, P less than 0.001) were significantly higher on the saponified cellulose ester dialysers suggesting that hydroxyl groups of cellulosic membranes play an important role in the pathophysiology of dialysis-induced changes.
Transcutaneous oxygen tension (TsPO2) was measured in the foot and chest of 39 patients with severe peripheral vascular disease and the Regional Perfusion Index (RPI) calculated (RPI = Foot TcPO2 divided by Chest TcPO2). TcPO2 was equivalent to RPI as a measure of ischaemia and furthermore RPI did not alter significantly when re-assessed under anaesthesia. Successful vascular reconstruction brought about an ontable rise in RPI which rose further but not significantly post-operatively. Continuous monitoring of RPI allowed intra-operative identification of 20 of 22 successful reconstructions and there were no false positive results.
Interest for cytokines involvement in experimental and human liver injury has considerably increased over recent years. The present paper reviews the current knowledge in the field of alcoholic cirrhosis. The role of interleukin-1, tumor necrosis factor, interleukin-6, interleukin-8 and interleukin-10 are discussed together with their possible diagnostic and prognostic significance. Prospects for future investigations such as immunotherapy are underlined.
Interleukin-10 (IL-10) is a new anti-inflammatory and immunosuppressive cytokine produced in the course of several experimental and clinical infections. In this paper, we review the major properties of IL-10 in vitro and we discuss the role of endogenous IL-10 in the pathogenesis of infectious diseases.
Lumbar sympathectomy has a controversial place in the management of severe limb ischemia for limb preservation. In a consecutive clinical series laser Doppler (LD) blood flow was measured at the distal limit of an anterior below knee skin flap in 21 patients. Amputation level was selected by clinical judgement. Mean LD value in 15 patients who had primary BK healing was 42V (range 20-85) compared to 11V (9-20) in six patients who proceeded to AK amputation (p < 0.001) establishing 20V as a critical value for BK healing. To examine the effect of chemical sympathectomy 21 further patients with severe ischemia had LD measurements at the same BK site before and one week after chemical sympathectomy. LD values rose significantly from 26V (10-75) to 50V (10-100), (p < 0.001). In particular seven patients had initial LD levels below 20V and in five chemical sympathectomy produced elevation to levels commensurate with BK healing. We conclude that chemical sympathectomy can improve below knee skin blood flow and may enhance primary wound healing.