Fever six weeks after trauma.
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Fever of Unknown Origin↗
Biomedical subjects
R More
Publications and source records attributed to R More.
GPIIbIIIa inhibitors as adjunctive therapy in acute myocardial infarction.
Thrombolytic therapy has proved useful in the treatment of acute myocardial infarction but is frequently associated with limited vessel reperfusion and early reocclusion. Local platelet aggregation and activation play a role in these pathological processes, explaining the benefit of aspirin, a weak antiplatelet agent. Recent interest has turned to GPIIbIIIa antagonists, a class of potent inhibitors of platelet aggregation. Their concomitant use with fibrinolytics, in rescue and primary angioplasty for acute myocardial infarction treatment is explored. Efficacy and safety issues are addressed and the potential pivotal role of these agents in the treatment of acute myocardial infarction is discussed.
Angioplasty, Balloon, Coronary↗
Blood compatibility of TiO films.
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Biocompatible Materials↗
Soluble adhesion molecules in reperfusion during coronary bypass grafting.
OBJECTIVE: Adhesion of activated leukocytes to the endothelial cells as a result of myocardial ischaemia/reperfusion during open chest coronary artery surgery has been shown to be involved in the development of tissue damage. Activated leukocytes adhere to endothelium via adhesion molecules expressed by both cell types, resulting in the impairment of coronary capillary flow. Upon cell activation, adhesion proteins may be released in the soluble form to circulating blood. The purpose of our study was to verify whether myocardial ischaemia/reperfusion occurring during coronary artery bypass grafting results in release of the soluble adhesion molecules VCAM-1, ICAM-1, E-selectin and L-selectin into the circulation. METHODS: Plasma levels of the soluble adhesion molecules were measured in vein, arterial and coronary sinus blood samples taken from 15 patients undergoing coronary artery bypass grafting (CABG). Blood samples for estimations were collected during the procedure: before aorta cross-clamping, at the beginning of reperfusion and 30 min after reperfusion. Soluble adhesion molecules levels were measured by standard ELISA assays. RESULTS: Mean plasma levels of soluble VCAM-1 in arterial samples increased significantly at the beginning of reperfusion and 30 min after reperfusion. In contrast, soluble L-selectin plasma levels in arterial samples remained unchanged. In coronary sinus samples, levels of soluble ICAM-1 significantly increased 30 min after reperfusion. Moreover, in coronary sinus samples collected 30 min after reperfusion, soluble ICAM-1 levels were significantly higher than in arterial samples obtained at the same time. The mean concentration of soluble E-selectin in samples obtained from coronary sinus decreased significantly 30 min after reperfusion. Moreover, plasma levels of soluble E-selectin in coronary sinus samples obtained 30 min after reperfusion were significantly decreased compared with these observed in arterial samples collected at the same time. CONCLUSIONS: The reperfusion of ischaemic myocardium during CABG results in a significant increase in plasma levels of the soluble endothelial adhesion molecules VCAM-1 and ICAM-1 and significant decrease in soluble E-selectin plasma levels. L-selectin plasma levels during CABG procedure remain unchanged. We propose that the increased plasma concentrations of soluble VCAM-1 and ICAM-1 are a result of endothelial cell activation during ischaemia/reperfusion following bypass surgery.
Aged↗
The release of soluble adhesion molecules ICAM-1 and E-selectin after acute myocardial infarction and following coronary angioplasty.
Endothelial cells express surface adhesion molecules for leukocytes in response to myocardial ischaemia. These molecules may be released into plasma by activated cells and be detectable in soluble form. Samples were collected from the peripheral vein of 14 consecutive patients with acute myocardial infarction (AMI) at the time of admission, 6 h, and 1 and 5 days post-admission. Additionally, samples were drawn from the coronary sinus ostium and peripheral artery of seven patients undergoing coronary angioplasty (PTCA) before and after the first balloon inflation. We measured the plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sELAM-1). In patients with AMI plasma levels of sICAM-1 exceeded those observed in age and sex-matched healthy subjects, (mean+/-SEM; 220.6+/-18 ng/ml) at all the time intervals assessed (358.9+/-24.5; 330.9+/-24.4; 379.4+/-39.7 and 366.8+/-47.5 ng/ml, respectively, p<0.01). sELAM-1 levels, however, were normal on admission, increased at 6 h to 52.7+/-3.8 ng/ml, p<0.05, and at day 1 (56.0+/-4.6 ng/ml) before decreasing to normal levels on the fifth day. After brief myocardial ischaemia occurring during PTCA, an increased level of sICAM-1 was observed following balloon deflation in the coronary sinus (329.2+/-20 ng/ml; p<0.05) as compared to the subjects undergoing coronary angiography, but not in the peripheral artery. sELAM-1 levels remained unchanged during angioplasty. Thus, soluble adhesion molecules expressed by activated endothelial cells are released into peripheral blood during both AMI and brief myocardial ischaemia and measurement of such molecules may prove useful for monitoring vascular endothelium activation following myocardial ischaemia/necrosis.
Aged↗
Delay times in the administration of thrombolytic therapy: the Brighton experience.
We reviewed the effectiveness of a strategy involving paramedic ambulances and community education to reduce the delay to thrombolytic therapy in patients admitted with acute myocardial infarction, by analysing delay times recorded during routine treatment. Rapid identification and treatment of patients with acute myocardial infarction who were eligible for thrombolysis was carried out in the Accident and Emergency and Cardiac Care Units. Two hundred seventy-four patients were admitted with acute myocardial infarction over an 18-month period and treated with anistreplase (168) or streptokinase (106). The following median times were recorded: symptom onset to administration of thrombolytic therapy, 142 min (range 43-980 min); symptom onset to ambulance arrival, 60 min; ambulance with patient to arrival in hospital, 35 min; time to treatment in hospital ('door to needle time'), 25 min; in-hospital delays were notably shorter for patients given anistreplase as opposed to streptokinase. Shortened delays for the delivery of thrombolytic therapy can be achieved by a strategy involving public education, the availability of resuscitation ambulances, and close liaison with the Accident and Emergency Department.
Ambulances↗
Effect of intraluminal application of tissue-type plasminogen activator on the fibrinolytic activity of experimental vein grafts.
OBJECTIVE: The aim was to quantify the effect of intraluminally applied tissue-type plasminogen activator (tPA) on the fibrinolytic activity of experimental vein grafts and assess the effect of pretreatment of the vein on early platelet and thrombus formation using histological techniques. METHODS: A pig model of bilateral saphenous venin-carotid artery grafts was used. In each animal one side of the neck was grafted using vein distended to 230 mm Hg and pretreated with tPA (1 mg.ml-1) for a period of 15 min before grafting (treated graft). The perfused in situ for 2 h after implantation and before analysis. Changes in local fibrinolytic activity were quantified using fibrin plate techniques and specific chromogenic assays for tPA and urokinase (uPA) in tissue extract (n = 6 animals). Histological assessment was made using light and scanning microscopy (n = 4 animals). RESULTS: Surgical preparation and distention significantly reduced the fibrinolytic activity of pig saphenous vein in terms of areas of lysis produced on fibrin plates (P < 0.05), tPA activity (P < 0.05), and uPA activity (P < 0.05). Pretreatment of distended vein with tPA before grafting significantly enhanced its fibrinolytic activity after 2 h perfusion compared to control (untreated) grafts, as assessed by areas of lysis on fibrin plates (P < 0.05) and specific tPA activity (P < 0.05). Treated grafts also showed qualitatively less platelet and thrombus formation on histological examination. CONCLUSIONS: Pretreatment of surgically harvested vein by intraluminal application of tPA before grafting enhances its fibrinolytic activity after exposure to 2 h perfusion in vivo. This technique requires further investigation to validate its potential as a means of providing local anticoagulation to veins implanted as arterial grafts thereby reducing the incidence of early graft thrombosis.
Animals↗
A preliminary investigation of shape memory alloys in the surgical correction of scoliosis.
Nitinol, a shape memory alloy, is flexible at low temperatures but retains its original shape when heated. This offers interesting possibilities for scoliosis correction. Of the shape memory alloys, nitinol is the most promising medically because of biocompatibility and the ability to control transition temperature. In vivo: Six goats with experimental scoliosis were instrumented with 6-mm nitinol rods. The rods were transformed, and the scoliosis corrected, in the awakened goats by 450-kHz radio frequency induction heating. The curves averaged 41 degrees before instrumentation, 33 degrees after instrumentation, and 11 degrees after rod transformation. The animals tolerated the heating without discomfort, neurologic injury, or evidence of thermal injury to the tissues or the spinal cord. In vitro: Nitinol rods were tested under both constant deflection and constant loading conditions and plotted temperature versus either force or displacement. The 6-mm rod generated forces of 200 N. The 9-mm rod generated up to 500 N. We safely coupled shape memory alloy transformation to the spine and corrected an experimental spinal deformity in awake animals. The forces generated can be estimated by the rod's curvature and temperature. The use of shape memory alloys allows continuous neurologic monitoring during awake correction, true rotational correction by rod torsion, and the potential option of periodic correction to take advantage of spinal viscoelasticity and the potential of true rotational correction by rod torsion.
Alloys↗
The effect of surgical preparation and in-vitro distension on the intrinsic fibrinolytic activity of human saphenous vein.
The objective of this study was to assess the effect of distension on the intrinsic fibrinolytic activity of human saphenous vein during its preparation for use as a bypass conduit prior to coronary artery surgery. Fibrinolytic activity was studied using fibrin plate techniques and Chromogenic assays for extractable tPA and uPA. Samples were obtained from patients undergoing routine coronary surgery. Fibrinolytic activity was compared in control vein (untouched) vein that had been prepared for use as a bypass conduit (surgical dissection, ligation of side branches and careful but uncontrolled manual distension) and segments of dissected vein distended in vitro to pressures of 230 or 120 mmHg. Uncontrolled distension and distension to 230 mmHg impaired fibrinolytic activity as determined by areas of lysis on fibrin plates (p < 0.05), (p < 0.005), tPA activity (p < 0.005) (p < 0.005) and uPA activity (p < 0.05), (p < 0.005). Distension to 120 mmHg had no effect on the fibrinolytic activity of human saphenous vein. Impaired fibrinolytic activity caused by uncontrolled distension of saphenous vein prior to its use as a vascular conduit may contribute to early vein graft thrombosis and can be avoided using controlled distension to < 120 mmHg.
Female↗
Platelet pathology in minimal curve idiopathic scoliosis: an attempt to predict curve progression.
Platelets from adolescents with minimal curve scoliosis (mcs) (7-18 degrees) and healthy control subjects were examined for morphometry under the electron microscope and tested for calcium content and surface negative charge. These parameters have previously been found to be abnormal in severe idiopathic scoliosis (is) patients. Significantly more patients than control subjects showed deviations from normal in all tests. Two tests in particular, the average number of dense bodies per cell and an increased surface negative charge, were the most frequent abnormalities. In an attempt to assess the possibility of using platelet tests for prediction of curve progression, statistical comparisons were made and discriminant scores were generated for each patient. The results were compared with the clinical findings after a 2- to 3.5-year follow-up. The predictions proved to be incorrect although each of the five patients who had curve progression had some platelet abnormality. It is concluded that although platelet pathology does occur in early idiopathic scoliosis, it cannot be used as a prognostic indicator of curve progression.
Adolescent↗
Cardiovascular pathology induced by passive transfer of splenic cells from syngeneic rats treated with T-2 toxin.
Mononuclear cells were separated from spleens and lymph nodes of Lewis rats treated 5 weeks previously with repeated small doses of T-2 toxin or solvent only. The cells from each site were then injected intraperitoneally into 4 groups of syngeneic Lewis rats. The animals injected with spleen cells from T-2 toxin-treated donors developed marked cardiovascular changes which were similar to those due to T-2 toxin itself. Rats injected with lymph node cells as well as those given each kind of cell from solvent-treated donors showed only occasional mild vascular changes. The changes seen after splenic cell transfer may be due to superinduction of interleukin 2 by T-2 toxin.
Animals↗
T-2 toxin effect on bacterial infection and leukocyte functions.
The effects of T-2 toxin on bacterial infection and leukocyte function and structure were examined in vivo and in vitro. Rats were innoculated with staphylococci after pretreatment with or without T-2 toxin. The T-2 pretreated rats failed to mount a cellular response to the bacteria. Blood and bone marrow cells were markedly suppressed by the T-2 toxin, the myeloid series being the most affected. In vitro studies with human leukocytes showed that small, nonkilling doses of T-2 toxin inhibited chemotaxis, chemiluminescence stimulated by bacteria, and phagocytosis of bacteria. It was concluded that this inhibition may contribute towards sepsis and rapid onset of death in T-2 toxin poisoning.
Animals↗
The effect of T-2 toxin on human platelets.
Human platelets were incubated with T-2 toxin, the most toxic component of Fusarium fungi, at doses of 5 to 500 micrograms/10(9) platelets. A dose-related inhibition of platelet aggregation and release of dense bodies (these consist mainly of serotonin-containing granules) were observed. A change in membrane permeability in the absence of shape changes was also demonstrated by a heavy metal impregnation technique. There was no correlated inhibition of thromboxane synthesis or significant alterations in platelet calcium content. The microtubular system was also unaffected. Suppressed platelet aggregation may contribute to the lethal hemorrhagic phenomenon associated with intoxication by fusarial toxins in man and animals.
Blood Platelets↗
Antibodies to cultured rat heart cells in sera of patients with rheumatoid arthritis.
Since heart lesions occur in many patients with rheumatoid arthritis (RA), sera from these patients were tested with an indirect fluorescent technique for antibodies reactive with rat heart cell cultures. Of 27 sera 22 had reactivity with non-muscle (nM) cells and 3 reacted with cultured beating muscle cells (M). Positive sera reactive with nM cells exerted complement-dependent cell cytotoxicity towards M cells. The nM antibodies were found to belong predominantly to the IgG class. They displayed no cross-reactivity with bovine collagen, human and bovine serum proteins, or human and sheep red blood cells. The relationship of these antibodies to the pathogenesis of RA heart lesions remains to be determined.
Adult↗
Platelet abnormalities in muscular dystrophy.
Platelets which have complex membranes and calcium shifts similar to those in muscles were investigated in 14 patients with muscular dystrophy and 20 suitable controls. In 4 Duchenne and one limb-girdle dystrophy aggregations were done and found to be depressed with adrenaline and ADP. Electron microscopic and chemical examinations revealed an increased number of dense bodies, changed permeability and/or binding of cations and elevated intracellular calcium in all the 9 cases of Duchenne dystrophy while the 2 limb-girdle and 3 myotonic dystrophies varied. A two phase polymer separation system applied to fixed platelets of all patients and controls showed no abnormality of surface negative charge.
Adolescent↗
T-2 toxin-induced pathology in the hearts of rats.
T-2 toxin is the major lethal component of several Fusarium fungi implicated in diseases of man and animals. We report here on the histological and ultrastructural changes in hearts of rats given i.p. single large or repeated small doses of T-2 toxin. One, 2 and 3 days after a single large dose, there were lesions in most hearts. They consisted of interstitial oedema, focal cellularity and damage to single or groups of myocytes. The small intramural coronaries were constricted, swollen and sometimes disrupted. After 7 days, most of the changes subsided. In rats killed 1 or 2 months after the last of 10 daily injections of T-2 toxin, cardiomyopathy-like changes were seen with hypertrophy, focal fibrosis and abundant cellularity especially in the subendocardial regions of the left ventricle. The findings, although non-specific, indicate that T-2 toxin is cardiotoxic.
Animals↗
Studies of platelets with heavy metal impregnation techniques.
Various methods of heavy metal impregnations were performed on human platelets. The optimal technique consisted of glutaraldehyde fixation, incubation in warm uranyl acetate at a pH of 3.5, followed by a double solution of lead and copper, and finally overnight immersion in cold osmium tetroxide. Semi-thin sections, viewed at 90 kV, revealed three types of platelets: (1) 'reticular' cells, with a prominent tubular network and very dark granules in a pale cytoplasm; (2) 'dark' cells, with an electron-dense cytoplasm; and (3) 'pale' cells, with microvesicles and non-staining granules. Pre-treatments with EGTA, aspirin and various platelet activators altered the appearances and proportions of the three cell types. A cell-partitioning two-phase polymer system showed that the sub-grouping is related to surface membrane properties, the cells retained in the top phase being exclusively type 2 'dark' cells. The changes in cell type distribution produced by activation show that metal impregnation may be a useful method for studying structure-function correlations in platelets.
Aspirin↗
Enhancement of human muscle growth in diffusion chambers by bone marrow cells.
Samples of minced human muscle were cultured in millipore diffusion chambers incubated in the peritoneal cavities of mice. In about half the chambers the minced muscle samples were mixed with autogenous bone marrow cells which lead to improved myogenic growth. A similar but less marked effect was produced by mononuclear cells from the patients' blood. No growth enhancement occurred when the muscle and marrow cells were separated by a filter in double chambers. In addition to accelerated myogenesis, the chambers with added bone marrow cells had a much lower incidence of infection. This work may have practical clinical implications for the treatment of muscle injuries. Local implantation of autogenous marrow cells (+/- minced muscle) may prove useful in improving myogenic regeneration.
Adolescent↗