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Biomedical subjects

S Ellis

Publications and source records attributed to S Ellis.

At least 19 recordsLinked to original sources
PubMed1992

Monocyte diapedesis through an in vitro vessel wall construct: inhibition with monoclonal antibodies to thrombospondin.

Human peripheral blood monocytes were examined for migration across an endothelial cell monolayer in an in vitro vessel wall construct. Few monocytes invaded in the absence of a chemotactic gradient, despite significant adhesion to the endothelial monolayer. However, the addition of zymosan-activated human plasma to the lower compartment, to create a chemotactic gradient across the vessel wall, resulted in significantly enhanced monocyte migration. Pretreatment of the monocytes with monoclonal antibodies to thrombospondin (TSP) dramatically inhibited monocyte diapedesis into the vessel wall. The same treatment inhibited monocyte adhesion to endothelial cells in two-dimensional monolayer cultures as well as in vessel wall constructs (no chemotactic gradient). Of interest, however, the monoclonal antibodies had no inhibitory effect on monocyte migration into collagen gels devoid of endothelial cells in response to the same chemotactic gradient, suggesting the importance of TSP in monocyte-endothelial cell interactions. Monoclonal antibodies to fibronectin and normal mouse immunoglobulin G did not inhibit migration in this model of a vessel wall. Furthermore, monoclonal antibodies to TSP showed no inhibition of human peripheral blood neutrophil migration. Previous studies have shown that monocytes synthesize TSP and express this moiety on their surface. The present data suggest that monocytes may utilize TSP to interact with endothelial cells lining the vessel wall during diapedesis.

Antibodies, Monoclonal↗
PubMed1992

The recording and analysis of EMG and jaw tracking. I. The recording procedure.

A computer-based system is described which records and analyses electromyographic (EMG) signals and tracking data for mandibular movements during function. EMG signals were obtained bilaterally from six muscles and a Sirognathograph monitored the position of the lower incisor teeth in three dimensions. Directed jaw movement tasks by subjects were monitored. These data were continuously sampled at a rate of 1 KHz per channel over an operator controlled period. Analysis of the data was performed off-line following the experiment. Individual chewing cycles associated with masticatory function were identified and the timing and dimensions of each chewing envelope established. Corresponding EMG values were also determined and displays of EMG and jaw movement were plotted on a common time base. An average chewing cycle and correlated EMG activity could also be displayed on a high resolution monitor and plotted for a hard copy to enable a comparison to be made between subjects with and without jaw dysfunction.

Analysis of Variance↗
PubMed1992

Muscle sarcomere lesions and thrombosis after spaceflight and suspension unloading.

Spaceflight (flight) and tail suspension-hindlimb unloading (unloaded) produced significant decreases in fiber cross-sectional areas of the adductor longus (AL), a slow-twitch antigravity muscle. However, the mean wet weight of the flight AL muscles was near normal, whereas that of the suspension unloaded AL muscles was significantly reduced. Interstitial edema within the flight AL, but not in the unloaded AL, appeared to account for this apparent disagreement. In both experimental conditions, the slow-twitch oxidative fibers atrophied more than the fast-twitch oxidative-glycolytic and fast-twitch glycolytic fibers. Immunostaining showed that slow-twitch oxidative fibers expressed fast myosin, producing hybrid fibers containing slow and fast myosin isoforms. Two-dimensional gel electrophoresis of flight AL muscles revealed increased content of fast myosin light chains and decreased amounts of slow myosin light chains and fatty acid-binding protein. In the flight AL, absolute mitochondrial content decreased, but the relatively greater breakdown of myofibrillar proteins maintained mitochondrial concentration near normal in the central intermyofibrillar regions of fibers. Subsarcolemmal mitochondria were preferentially lost and reduced below normal concentration. Elevated fiber immunostaining for ubiquitin conjugates was suggestive of ubiquitin-mediated breakdown of myofibrillar proteins. On return to weight bearing for 8-11 h, the weakened atrophic muscles exhibited eccentric contraction-like lesions (hyperextension of sarcomeres with A-band filaments pulled apart and fragmented), tearing of the supporting connective tissue, and thrombosis of the microcirculation. Segmental necrosis of muscle fibers, denervation of neuromuscular junctions, and extravasation of red blood cells were minimal. Lymphocyte antibody markers did not indicate a significant immune reaction. The flight AL exhibited threefold more eccentric-like lesions than the unloaded AL; the high reentry G forces experienced by the flight animals, but not the unloaded group, possibly accounted for this difference. Muscle atrophy appears to increase the susceptibility to form eccentric contraction-like lesions after reloading; this may reflect weakening of the myofibrils and extracellular matrix. Microcirculation was also compromised by spaceflight, such that there was increased formation of thrombi in the post-capillary venules and capillaries. This blockage led to edema by 8-11 h after resumption of weight bearing by the COSMOS 2044 rats. The present findings indicate that defective microcirculation most likely accounted for the extensive tissue necrosis and microhemorrhages observed for COSMOS 1887 rats killed 2 days after landing.

Animals↗
PubMed1991

Coronary bypass surgery improves global and regional left ventricular function following thrombolytic therapy for acute myocardial infarction. TAMI Study Group.

Coronary bypass surgery was performed prior to hospital discharge in 303 (22%) of 1387 consecutive patients enrolled in the TAMI 1 to 3 and 5 trials of intravenous thrombolytic therapy for acute myocardial infarction. Bypass surgery was of emergency nature (less than 24 hours from treatment with intravenous thrombolytic therapy) in 36 (2.6%) and was deferred (greater than 24 hours) in 267 (19.3%) patients. The indications for bypass surgery included failed angioplasty (12%); left main or equivalent coronary disease (9%); complex or multivessel coronary disease (62%); recurrent postinfarction angina (13%); and refractory pump dysfunction, mitral regurgitation, ventricular septal rupture or abnormal predischarge functional test (1% each). Although patients having bypass surgery were older (59.5 +/- 9.8 versus 56.0 +/- 10.2 years, (p less than 0.0001), had more extensive coronary artery disease (46% with three-vessel disease versus 11%, (p less than 0.0001), had more frequent diabetes mellitus (19% versus 15%, (p = 0.048), had more prior infarctions (p less than 0.0001), had more severe initial depression in global left ventricular ejection fraction (48.0 +/- 11.9% versus 51.8 +/- 11.9%, p = 0.0002), and regional infarct zone (-2.7 +/- 0.94 versus -2.5 +/- 1.1 SD/chord, p = 0.02) and noninfarct zone function (-0.36 +/- 1.8 versus 0.43 +/- 1.6 SD/chord, p less than 0.0001) than patients not having coronary bypass surgery, no difference in the incidence of death in hospital (7% surgical versus 6% nonsurgical) or death at long-term follow-up of hospital survivors (7% surgical versus 6% nonsurgical) was noted between groups. Surgical patients demonstrated a greater degree of recovery in left ventricular ejection fraction (3.4 +/- 9.8% versus 0.16 +/- 8.5%, p = 0.036) and infarct zone regional function (0.71 +/- 1.1 versus 0.34 +/- 0.99 SD/chord, p = 0.001) when immediate (90 minutes following initiation of thrombolytic therapy) and predischarge (7 to 14 days after treatment) contrast left ventriculograms were compared than did patients who received only intravenous thrombolytic therapy with or without coronary angioplasty. These data suggest a beneficial influence of coronary bypass surgery on left ventricular function and possibly on the clinical outcome of patients initially treated with intravenous thrombolytic therapy for acute myocardial infarction.

Angioplasty, Balloon, Coronary↗
PubMed1991

Clinical experience with the Palmaz-Schatz coronary stent.

Complications that occurred in 247 patients who underwent successful elective stenting to native coronary arteries with the Palmaz-Schatz balloon expandable stent included subacute thrombosis in 7 patients (2.8%), myocardial infarction in 3 (1.2%), death 3 (1.2%), urgent bypass surgery in 4 (1.6%) and major bleeding events in 24 (9.7%). Angiographic restenosis occurred in 21 (20%) of 103 patients who received a single stent. Subgroup analysis, however, revealed that restenosis of a single stent occurred in 3 (7%) of 45 patients without prior angioplasty compared with 25 (27%) of 91 patients with prior angioplasty. Patients with "suboptimal" angioplasty results (dis-section) who received a single stent seemed to have a higher thrombosis rate perioperatively (4 [4%] of 98), but no higher incidence of restenosis (7 [15%] of 46) than that of the total group of patients who received a single stent. Coronary stenting may be a valuable adjunct to coronary angioplasty in carefully selected patients. Complication rates are similar to those of routine angioplasty; however, angiographic restenosis may be reduced in certain subsets of patients.

Adult↗
PubMed1991

Myocardial infarction with minimal coronary atherosclerosis in the era of thrombolytic reperfusion. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group.

The incidence of minimal residual atherosclerotic coronary obstruction after successful intravenous thrombolytic therapy was evaluated in 799 patients with acute myocardial infarction. Minimal residual coronary obstruction (less than or equal to 50%) was observed on selective coronary angiography performed 90 min after initiation of thrombolytic therapy in 43 patients (5.5%). In 42 other patients (5.4%), a greater than 50% but less than 100% residual stenosis noted at 90 min demonstrated further resolution of obstruction to less than 50% at an angiographic follow-up study 7 to 10 days later. Patients with minimal residual coronary obstruction were significantly younger (52 +/- 10.7 versus 56.7 +/- 10 years; p = 0.002) and had less multivessel coronary disease (p less than 0.001), better initial left ventricular ejection fraction (54 +/- 12% versus 50.2 +/- 11.4%; p = 0.006) and a lower in-hospital mortality rate (1% versus 7%; p = 0.04) than did patients who had a significant (greater than 50%) residual coronary obstruction after intravenous thrombolysis. Long-term follow-up study of patients with a minimal coronary lesion (average 1.5 +/- 0.6 years) and those with significant residual stenosis (average 1.6 +/- 0.7 years) demonstrated that the incidence of death (2.4% in patients with minimal stenosis versus 3.5% in those with significant stenosis) and recurrent myocardial infarction (5% each) were similar in both groups. New strategies are needed to prevent coronary rethrombosis in patients with minimal atherosclerosis after thrombolytic therapy for acute myocardial infarction.

Coronary Angiography↗
PubMed1991

Compensatory mechanisms in platelet production: the response of Sl/Sld mice to 5-fluorouracil.

Sl/Sld mice are a unique animal model for studying platelet production in that they sustain normal platelet mass despite reduced marrow activity. The aim of this study was to determine if the compensatory mechanisms operating in these mice could be augmented by further reducing bone marrow activity with the drug 5-fluorouracil (5-FU), known to induce a strong stimulatory effect on platelet production. The platelet recovery in Sl/Sld mice after 5-FU administration contrasted that found in their normal littermates. Sl/Sld mice did not display the sustained thrombocytosis that was observed in +/+ mice between days 10 and 14. Platelet number was elevated in Sl/Sld mice at day 20, when the marrow megakaryocyte compartment had normalized. A significant increase in marrow megakaryocyte number and size was observed at days 8 and 11 in both +/+ and Sl/Sld mice after 5-FU administration. The data suggest that the increase in megakaryocyte size and number following 5-FU treatment was not able to significantly contribute to a sustained rebound thrombocytosis at the time of increased marrow megakaryocytopoiesis. It is concluded that the already compromised marrow of Sl/Sld mice is able to respond to the damage invoked by 5-FU to produce larger than normal megakaryocytes. In contrast to normal mice (+/+ littermates), the increase in marrow megakaryocytopoiesis observed does not lead to a thrombocytosis, indicating that platelet production and release in Sl/Sld mice cannot be further amplified by a strong marrow stimulation.

Anemia↗
PubMed1990

Maxillofacial surgery and the troubles of Northern Ireland.

In Northern Ireland, for the last 20 years, an evil and unnecessary conflict has presented the maxillofacial surgeons with a spectrum of violent injuries to the face and neck. The result has been a valuable surgical school and it was the object of my elective to study the progression of the methods used in the management of these injuries and the lessons learnt from them.

Blast Injuries↗
PubMed1990

Skeletal muscle fiber, nerve, and blood vessel breakdown in space-flown rats.

Histochemical and ultrastructural analyses were performed postflight on hind limb skeletal muscles of rats orbited for 12.5 days aboard the unmanned Cosmos 1887 biosatellite and returned to Earth 2 days before sacrifice. The antigravity adductor longus (AL), soleus, and plantaris muscles atrophied more than the non-weight-bearing extensor digitorum longus, and slow muscle fibers were more atrophic than fast fibers. Muscle fiber segmental necrosis occurred selectively in the AL and soleus muscles; primarily, macrophages and neutrophils infiltrated and phagocytosed cellular debris. Granule-rich mast cells were diminished in flight AL muscles compared with controls, indicating the mast cell secretion contributed to interstitial tissue edema. Increased ubiquitination of disrupted myofibrils implicated ubiquitin in myofilament degradation. Mitochondrial content and succinic dehydrogenase activity were normal, except for subsarcolemmal decreases. Myofibrillar ATPase activity of flight AL muscle fibers shifted toward the fast type. Absence of capillaries and extravasation of red blood cells indicated failed microcirculation. Muscle fiber regeneration from activated satellite cells was detected. About 17% of the flight AL end plates exhibited total or partial denervation. Thus, skeletal muscle weakness associated with spaceflight can result from muscle fiber atrophy and segmental necrosis, partial motor denervation, and disruption of the microcirculation.

Animals↗
PubMed1990

Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. TAMI Study Group.

To determine the clinical consequences of reocclusion of an infarct-related artery after reperfusion therapy, we evaluated 810 patients with acute myocardial infarction. Patients were admitted into four sequential studies with similar entry criteria in which patency of the infarct-related artery was assessed by coronary arteriography 90 minutes after onset of thrombolytic therapy. Successful reperfusion was established acutely in 733 patients. Thrombolytic therapy included tissue-type plasminogen activator (t-PA) in 517, urokinase in 87, and a combination of t-PA and urokinase in 129 patients. All patients received aspirin, intravenous heparin and nitroglycerin, and diltiazem during the recovery phase. A repeat coronary arteriogram was performed in 88% of patients at a median of 7 days after the onset of symptoms. Reocclusion of the infarct-related artery occurred in 91 patients (12.4%), and 58% of these were symptomatic. Angiographic characteristics at 90 minutes after thrombolytic therapy that were associated with reocclusion compared with sustained coronary artery patency were right coronary infarct-related artery (65% versus 44%, respectively) and Thrombolysis in Myocardial Infarction (TIMI) flow 0 or 1 (21% versus 10%, respectively) before further intervention. Median (interquartile value) degree of stenosis in the infarct-related artery at 90 minutes was similar between groups: 99% for reoccluded (value, 90/100%) compared with 95% for patent (value, 80/99%). Patients with reocclusion had similar left ventricular ejection fractions compared with patients with sustained patency at follow-up. However, patients with reocclusion at follow-up had worse infarct-zone function at -2.7 (value, -3.2/-1.8) versus -2.4 (SD/chord) (value, -3.1/-1.3) (p = 0.016). The recovery of both global and infarct-zone function was impaired by reocclusion of the infarct-related artery compared with maintained patency; median delta ejection fraction was -2 compared with 1 (p = 0.006) and median delta infarct-zone wall motion was -0.10 compared with 0.34 SD/chord (p = 0.011), respectively. In addition, patients with reocclusion had more complicated hospital courses and higher in-hospital mortality rates (11.0% versus 4.5%, respectively; p = 0.01). We conclude that reocclusion of the infarct-related artery after successful reperfusion is associated with substantial morbidity and mortality rates. Reocclusion is also detrimental to the functional recovery of both global and infarct-zone regional left ventricular function. Thus, new strategies in the postinfarction period need to be developed to prevent reocclusion of the infarct-related artery.

Angiography↗
PubMed1989

Morphology of left anterior descending coronary territory lesions as a predictor of anterior myocardial infarction: a CASS Registry Study.

Despite a growing awareness of the correlation of coronary artery stenoses morphology with clinical syndromes, no comprehensive, prospective analysis of the implications of stenosis morphology on risk of myocardial infarction has been reported. Angiograms from 118 patients, representative of the 4.9% of medically treated Coronary Artery Surgery Study (CASS) patients who during subsequent 3 year follow-up study had an anterior myocardial infarction, were matched on the basis of arteriographic anatomy and disease with 141 patients who did not have an anterior infarction. Angiograms from these 259 patients with 557 left anterior descending artery stenoses were reviewed without knowledge of clinical outcome. Conditional regression analyses were performed to determine the importance of stenosis morphology, relative to computer-determined stenosis severity and other clinical variables, in the prediction of risk of infarction. Univariate analysis revealed luminal roughness (odds ratio 4.5; p = 0.001) and lesion length (odds ratio 1.7 per unit length; p = 0.007) to be highly correlated with future risk of infarction. Multivariate analysis revealed left anterior descending artery percent stenosis greater than or equal to 50%, lesion roughness, left circumflex artery stenosis and smoking, in that order, to be predictive of anterior myocardial infarction, whereas 22 other morphologic variables were not independently predictive of outcome. The importance of stenosis roughness may relate to its propensity for thrombogenesis and should be considered in clinical decision making.

Angiography↗
PubMed1989

An investigation of factors affecting progress of patients on a stroke unit.

The aim of the study was to identify factors affecting the progress in physical abilities and activities of daily living of patients admitted to a stroke unit. A series of 70 patients admitted consecutively were assessed on a series of tests of motor, functional and cognitive abilities at admission. They were assessed for level of motor abilities and activities of daily living at discharge and 9 months after stroke. Predictive equations were developed which account for between 61% and 33% of the variance in motor abilities and activities of daily living at discharge and at 9 months after stroke. The most important factor influencing outcome was the degree of motor loss.

Activities of Daily Living↗
PubMed1989

Prenatal development and innervation of the circumvallate papilla in the mouse.

The embryonic development of the circumvallate papilla in the mouse is described. Serial sections of Day 11 to Day 18 mouse embryos were stained by Linder's silver method and examined to determine the temporal events in relation to circumvallate papilla formation. This was complemented by scanning electron micrographs. On Day 13, the earliest sign of a single median circumvallate papilla formation was visible as an epithelial invagination which had bilateral nerve innervation. Scanning electron micrographs of this stage showed a median flattened area demarcated at its periphery by cells invaginating from the surface. On Day 14, the epithelial invagination appeared like an inverted cup with a dense nerve plexus within its core. By the afternoon of Day 14 a furrow had formed by a split in the epithelium. During that period the surface morphology changed from a flattened area to a central dome-shaped structure. As development progressed the furrow became accentuated by the elevation of its lateral walls. Nerve fibres penetrated the epithelium, but taste bud differentiation was not easily observable. The dense innervation of the circumvallate papilla was established from the start of its formation. The role of these nerves as an inductive factor or as providing a trophic effect on the formation of the circumvallate papilla remains to be investigated.

Animals↗
PubMed1988

Metabolism of benz[j]aceanthrylene (cholanthrylene) and benz[l]aceanthrylene by induced rat liver S9.

The metabolites of benz[j]aceanthrylene (B[j]A) produced by incubation with liver S9 proteins from rats induced with Aroclor-1254 and phenobarbital have been identified as: trans-B[j]A-1,2-dihydrodiol, B[j]A-9,10-dihydrodiol, B[j]A-11,12-dihydrodiol, and 10-hydroxy-B[j]A. The major metabolite formed (58-60%) by both induced S9 preparations was trans-B[j]A-1,2-dihydrodiol, the cyclopenta-ring dihydrodiol while oxidation at the k-region or the proximal-bay region was minor. There were no statistical differences in individual or total B[j]A metabolite rates between the 2 induced S9 preparations. B[l]A was metabolized by Aroclor-1254 and phenobarbital induced rat liver S9 preparations to trans-B[l]A-1,2-dihydrodiol, B[l]A-7,8-dihydrodiol, and B[l]A-4,5-dihydrodiol. The major B[l]A metabolite formed (28-40%) by both induced S9 preparations was B[l]A-7,8-dihydrodiol, the k-region dihydrodiol. Cyclopenta-ring oxidation to trans-B[l]A-1,2-dihydrodiol was approximately 50% of that observed for k-region oxidation. Both induced S9s produced similar rates of B[l]A metabolites except for B[l]A-7,8-dihydrodiol formation which was higher for Aroclor-1254-induced S9.

Animals↗
PubMed1988

Prediction of risk of anterior myocardial infarction by lesion severity and measurement method of stenoses in the left anterior descending coronary distribution: a CASS Registry Study.

To assess the 3 year risk of anterior myocardial infarction in patients with left anterior descending coronary artery territory disease (30 to 100% stenosis), National Heart, Lung, and Blood Institute (NHLBI) Coronary Artery Surgery Study (CASS) registry patients were identified who were 1) medically treated, and 2) had evidence of viable anterior myocardium at the time of baseline angiography. Prospectively, 118 patients having an anterior infarction within 3 years of baseline angiography were identified from annual follow-up of 4,535 medically treated patients who had left anterior descending coronary artery disease and viable anterior myocardium. From the large residual pool of patients without infarction, 141 were randomly selected from a stratified matrix to represent the entire group. The maximal percent stenosis was estimated by the CASS multiple angiographers, by a current single observer rereading and by contemporary computer measurement techniques. Absolute lumen dimension was assessed by computer measurement. The 3 year risk of anterior infarction was 2% for patients with their most severe left anterior descending stenosis less than 50%, 6% for patients with one such stenosis greater than or equal to 50% and 11% for patients with two or more such stenoses greater than or equal to 50% (p less than 0.02). Stenoses of 90 to 98% had the highest (15%) 3 year risk of anterior myocardial infarction. The three methods used to measure maximal percent stenosis differed little with regard to their predictiveness. Absolute lumen dimension was less predictive of risk. These results may provide a more rational basis on which to base coronary revascularization decisions.

Clinical Trials as Topic↗