Experimental evaluation and clinical application of intraoperative counterpulsation without balloon pumping.

Cardiac assistance in the form of counterpulsation (CP), created by intraaortic balloon pumping (IABP), has recently been utilized to wean patients from cardiopulmonary bypass (CPB) after conventional modalities have failed. The use of IABP, however, is often delayed because it is not part of the standard CPB setup and requires an additional cutdown, an arterial graft, and the retrograde insertion of a foreign body into the arterial tree. To eliminate the disadvantages of IABP, an alternate technique for CP has been developed. A pneumatially actuated external blood reservoir connected via a "Y" connector to the standard arterial line of the CPB circuit can provide pulsatile flow, and when synchronized with the EKG, CP with or without CPB. Experimental evaluation with dogs comparing this technique with IABP has shown that the former can create comparable CP pressure curves to the latter. The technique was applied to 11 patients undergoing either aorto-coronary bypass surgery and/or valvular surgery. Two of the 11 patients could come off CPB only with the assistance of CP. Coronary bypass graft flow, when measured, increased by 25% due to CP in two out of seven patients. The arterial CP technique has proven to be easily adapted to clinical settings and provides immediate and effective CP when required.     

Evaluation of Ultrasmall Superparamagnetic Iron Oxide-Enhanced MRI of Carotid Atherosclerosis to Assess Risk of Cerebrovascular and Cardiovascular Events: Follow-Up of the ATHEROMA Trial

No abstract available.     

A possible autocrine role for interleukin-6 in two lymphoma cell lines

Interleukin-6 (IL-6) is a growth factor with diverse biologic activity. Originally described as a T-cell product that enhances immunoglobulin (Ig) secretion in antigen-stimulated B cells, it also affects the growth of T cells, plasmacytomas, hybridomas, and hematopoietic stem cells. We report the expression and secretion of IL-6 by two lymphoma cell lines, OCI-LY3 and OCI-LY12. Addition of recombinant IL-6 stimulated their growth, whereas addition of polyclonal anti- recombinant IL-6 (anti-rIL-6) had a marked inhibitory effect on proliferation. These results suggest an autocrine role for IL-6 in the growth of these lymphoma cells in culture.     

Demonstration of burst-promoting activity of recombinant human GM-CSF on circulating erythroid progenitors using an assay involving the delayed addition of erythropoietin

We demonstrate through the use of an in vitro assay involving the delayed addition of erythropoietin that human recombinant GM-CSF, cloned from a mature T cell line, Mo, clearly has burst-promoting activity (BPA) on peripheral blood erythroid progenitors at picomolar concentrations. Delay for up to 72 hours of the addition of erythropoietin to semi-solid methylcellulose cultures of concentrated peripheral blood progenitors minimizes or eliminates BPA-independent erythroid colony formation with little loss of BPA-dependent erythroid colony formation. This assay will prove useful in accurately detecting sources of BPA.     

Ultrastructural cytochemical analysis of blastic transformation of chronic myelocytic leukemia.

Ultrastructural cytochemical changes occurring during the blast phase of chronic myelocytic leukemia (CML) are described. Normal developing promyelocytes contain myeloperoxidase (MPO) -positive rough endoplasmic reticulum, nuclear envelope, and Golgi apparatus. All secretory granules of normal promyelocytes are also MPO-positive. In this study we have found abnormal promyelocytes with MPO-positive as well as MPO-negative secretory granules in blast phase CML patients which contrast with the normal pattern of MPO distribution in most CML patients not in the blast phase or in nonleukemic controls. Alkaline phosphatase activity was found in the nuclear envelope of blasts and promyelocytes of one of the blast transformation patients who had a markedly increased leukocyte alkaline phosphatase score. The cytochemical changes in the distribution of MPO suggest that immature leukemic cells may alter their patterns of secretory granule production. Such processes may reflect the emergence of an abnormal clone of cells during the blastic transformation of CML.     

Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown

OBJECTIVE: To determine whether other glycoprotein 130 (gp130) binding cytokines can mimic the effects of oncostatin M (OSM) in acting synergistically with interleukin-1alpha (IL-1alpha) to induce cartilage collagen breakdown and collagenase expression, and to determine which receptors mediate these effects. METHODS: The release of collagen and proteoglycan was assessed in bovine and human cartilage explant cultures. Messenger RNA (mRNA) and protein production from immortalized human chondrocytes (T/C28a4) was analyzed by Northern blotting and specific enzyme-linked immunosorbent assays. Collagenase activity was measured by bioassay. Cell surface receptors were detected by flow cytometry. RESULTS: OSM in combination with IL-1alpha caused a rapid synergistic induction of matrix metalloproteinase 1 mRNA, which was sustained over a 72-hour period. Flow cytometric analyses detected both the OSM-specific receptor and the gp130 receptor at the chondrocyte cell surface, but failed to detect the leukemia inhibitory factor receptor (LIFR). Cartilage degradation assays revealed that, of the gp130 binding cytokines, only OSM and IL-6, in the presence of its soluble receptor (sIL-6R), were able to act synergistically with IL-1alpha to promote collagen release. CONCLUSION: This study demonstrates that IL-6 can mimic OSM in synergizing with IL-1alpha to induce chondrocyte-mediated cartilage collagen breakdown and collagenase production. In order to have this effect, IL-6 requires the presence of its soluble receptor. The apparent absence of LIFR explains why other gp130 binding cytokines do not act in synergy with IL-1alpha. Since OSM, IL-6, and sIL-6R levels have all been shown to be elevated in the rheumatoid joint, our findings suggest that these cytokines may be key mediators of cartilage collagen catabolism in the inflammatory arthritides.     

Validation of a physically based catchment model for application in post-closure radiological safety assessments of deep geological repositories for solid radioactive wastes.

The physically based river catchment modelling system SHETRAN incorporates components representing water flow, sediment transport and radionuclide transport both in solution and bound to sediments. The system has been applied to simulate hypothetical future catchments in the context of post-closure radiological safety assessments of a potential site for a deep geological disposal facility for intermediate and certain low-level radioactive wastes at Sellafield, west Cumbria. In order to have confidence in the application of SHETRAN for this purpose, various blind validation studies have been undertaken. In earlier studies, the validation was undertaken against uncertainty bounds in model output predictions set by the modelling team on the basis of how well they expected the model to perform. However, validation can also be carried out with bounds set on the basis of how well the model is required to perform in order to constitute a useful assessment tool. Herein, such an assessment-based validation exercise is reported. This exercise related to a field plot experiment conducted at Calder Hollow, west Cumbria, in which the migration of strontium and lanthanum in subsurface Quaternary deposits was studied on a length scale of a few metres. Blind predictions of tracer migration were compared with experimental results using bounds set by a small group of assessment experts independent of the modelling team. Overall, the SHETRAN system performed well, failing only two out of seven of the imposed tests. Furthermore, of the five tests that were not failed, three were positively passed even when a pessimistic view was taken as to how measurement errors should be taken into account. It is concluded that the SHETRAN system, which is still being developed further, is a powerful tool for application in post-closure radiological safety assessments.