Biomedical subjects

J D Edwards

Publications and source records attributed to J D Edwards.

At least 37 records · Page 2Linked to original sources

PubMed1996

Effects of ischaemia and reperfusion on vasoactive neuropeptide levels in the canine infrarenal aortic revascularization model.

Infrarenal aortic cross-clamping is associated with remote vascular events, including myocardial infarction and renal insufficiency. The purpose of this study was to determine whether hindlimb ischaemia and reperfusion associated with infrarenal aortic cross-clamping results in the production of vasoactive regulatory neuropeptides. A canine model of infrarenal aortic cross-clamping was used for the study. Serial blood samples were drawn, prior to, at the time of, and serially following placement of the clamp and subsequent release of the clamp and reperfusion. Ischaemia resulted in increased mean(s.e.m.) plasma levels of neuropeptide Y (NPY) (initial 10.0(1.8) pmol/l versus ischaemia 24.7(2.3) pmol/l, P < 0.001) and vasoactive intestinal polypeptide (VIP) (initial 2.53(0.5) pmol/l versus ischaemia, 7.3(1.3) pmol/l, P < 0.05). Reperfusion produced three-fold elevation of VIP (initial 2.5(0.5) pmol/l versus reperfusion 9.6(1.5) pmol/l, P < 0.001), two-fold elevation in the plasma levels of endothelin-1 (initial 1.3(0.1) pmol/l versus reperfusion maximum 2.5(0.3) pmol/l, P < 0.01) and NPY (initial 10.0(0.8) pmol/l versus reperfusion maximum 23.9(2.3) pmol/l, P < 0.001). Ischaemia and reperfusion did not alter calcitonin gene-related peptide (CGRP) (a potent vasodilator) levels. Endothelin-1 (ET-1) plasma levels were also increased following haemorrhagic shock (initial 1.3(0.1) pmol/l versus exsanguination 3.4(0.4) pmol/l, P < 0.001), but not during ischaemia (initial 1.3(0.1) pmol/l versus ischaemia maximum 1.7(0.2) pmol/l, P = 0.7). It was concluded that vasoactive regulatory peptides are released following ischaemia, reperfusion and shock in the canine infrarenal aortic revascularization model and, therefore could contribute to remote vascular events observed with infrarenal aortic cross-clamping.

Animals↗

PubMed1996

Modulation of monocyte adherence to endothelial cells by endothelin-1 involvement of Src (p60src) and JAK1-like kinases.

PURPOSE: The purpose of this study was to determine the transmembrane signaling pathway by which endothelin-1 (ET-1) enhances monocyte adherence to human umbilical vein endothelial cells (HUVECs) and to investigate the role of tyrosine kinases in this mechanism. METHODS: Adherence of purified human blood monocytes to HUVEC monolayers was assessed with radiolabeled monocytes. Tyrosine kinase activation was examined by immunoprecipitation and Western blotting. RESULTS: ET-1 potentiated monocyte adherence to HUVECs in a biphasic manner with peaks at 10(-10) mol/L and 10(-7) mol/L. A potent antagonist to ET B receptors, when used alone, had no effect. However, the antagonist, when combined with ET-1, significantly enhanced monocyte adherence to HUVECs. Incubation of ET-1 (10(-12) mol/L to 10(-7) mol/L) with HUVECs activated tyrosine kinases in a biphasic manner as identified by immunoblotting with PY20 antibody to tyrosine phosphorylated proteins. Phosphorylated proteins with Mr 60, 110, and 130 kDa were observed after ET-1 stimulation of HUVECs. Of interest, ET A or ET B receptor antagonists failed to antagonize the effect of ET-1. Rather, these receptor antagonists significantly augmented ET-1 induced tyrosine phosphorylation in HUVECs. Immunoprecipitation with antibodies to p60SRC and JAK1 kinases followed by immunoblotting with PY20 antibody suggested that ET-1 receptor response coupling in HUVECs involves the activation of p60SRC and JAK1-like kinases. CONCLUSIONS: These data suggest an association between activation of p60SRC and JAK1-like kinases and monocyte adherence in response to ET-1. ET-1-induced monocyte adherence is upregulated by ET B receptor antagonist, suggesting a negative feedback on cell adhesion through this receptor.

Blotting, Western↗

PubMed1996

An audit of the cochlear implant service in Manchester.

The adult cochlear implant programme in Manchester was established in 1988 and the evaluation of the cochlear implant service involved the first 58 implants users (mean age = 51.65 years, range 19-75 years). Questionnaires were sent to implant users and their partners to evaluate the service with regard to provision of information, clinical care during in-patient assessments, waiting times, operation for cochlear implant and post-operative rehabilitation. The results show that the majority of patients (78 per cent) felt that the implant gave them as much or more benefit than expected. Areas identified for improvements include provision of more written information about cochlear implants; reduction in waiting times for first appointments; more information about the surgical risks and more instruction about home auditory training exercises for family and friends. As a consequence of the audit results the clinical practice and service provision for cochlear implantation in Manchester has been modified.

Adult↗

PubMed1995

Arterial embolism from anatomical variation at the thoracic outlet.

Thoracic outlet syndrome (TOS) represents a constellation of symptoms arising from the compression of the neurovascular bundle as it exits the thorax. We report a unique case of multiple rare anatomical anomalies resulting in TOS manifested by distal arterial embolism. These anomalies include the combination of: (1) a unilateral right cervical rib, Gruber's type II (Gruber 1869), (2) nonunion of the first thoracic rib, (3) abnormal fibrous insertions of the anterior scalene muscle onto the epineurium of the brachial plexus and adventitia of the subclavian artery, (4) anterior position of the brachial plexus in relation to the third portion of the subclavian artery, and (5) the bifurcation of a single root of the phrenic nerve at the level of the anterior scalene muscle. This series of findings suggest an underlying developmental abnormality with a delayed onset of symptomatology consisting of the thoracic outlet syndrome.

Abnormalities, Multiple↗

PubMed1995

University of Wisconsin solution effects on intimal proliferation in canine autogenous vein grafts.

This study was carried out to investigate if the University of Wisconsin solution (UWs) is suitable for long-term preservation of autogenous vein grafts (AVG) prior to transplantation, compared to autologous whole blood (AWB) and normal saline (NS). Autogenous jugular and femoral veins were harvested from adult mongrel dogs, using a "no-touch" technique. One segment of vein was immediately implanted to serve as a control, while other segments were stored for 24 hr at 4 degrees C in AWB, NS, or UWs. The control and the preserved veins were implanted as reversed interposition grafts in the common carotid or femoral artery positions. After 6 weeks, scanning electron microscopy revealed an intact endothelial cell monolayer in all vein grafts that was stained positively for factor VIII. The degree of intimal thickening, as assessed by light microscopy in the middle position of the grafts, was similar in controls (52.0 +/- 15.8 microns) and in veins stored in UWs (58.5 +/- 16.1 microns), but it was significantly increased (P < 0.05) in veins preserved in NS (198.9 +/- 19.5 microns) and in AWB (312.0 +/- 171.6 microns). Isometric tension studies revealed that maximum contraction and sensitivities (assessed by EC50) to norepinephrine were significantly reduced (P < 0.05) in AVG stored in AWB (0.05 +/- 0.02 g/mm2 and 5.5 +/- 2.8 microM), but not in UWs (0.16 +/- 0.03 g/mm2 0.92 +/- 0.34 microM) and NS (0.09 +/- 0.03 g/mm2 and 3.0 +/- 1.1 microM), compared with controls (0.17 +/- 0.03 g/mm2 and 0.99 +/- 0.38 microM). Acetylcholine (Ach)-induced maximum relaxations were similar in all of the veins.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1995

Effect of endothelin-1 on arterial response to Bay K 8644. A comparison of ischemic and nonischemic arteries.

Endothelin-1 (ET-1) has been proposed as one of the possible mediators of the vasoconstriction seen following ischemia and reperfusion. We investigated the effect of ischemia and reperfusion on the contractile response of canine renal and iliac arteries to the dihydropyridine-type calcium channel agonist (+/-)Bay K 8644, following subthreshold doses of ET-1. No significant difference in the maximum tension was observed between the ischemic and nonischemic arteries in response to Bay K 8644 in the absence of ET-1. The addition of subthreshold dose of ET-1 (10(-10) M) resulted in a significant increase in sensitivity to Bay K 8644 in both the ischemic-reperfused and non-ischemic-reperfused arteries, with a 38 fold increase in iliac arteries and about 8 fold increase in the renal arteries. However, the ET-1 potentiated response was enhanced in the ischemic-reperfused in comparison to the non-ischemic-reperfused vessels in the iliac artery. These data suggest that the potentiating mechanism of ET-1 is not only intact, but enhanced in ischemic-reperfused vessels. Since the enhanced release of ET-1 in vivo is preceded by ischemia and reperfusion, the vasospastic phenomenon observed following these events could well be mediated by ET-1.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1995

G-proteins in rat blood vessels--I. Identification.

1. The purpose of this investigation was to identify various types of conventional, low and high molecular weight G-proteins in purified membranes of rat aorta and mesenteric artery. 2. In both blood vessels, immunoblotting of G-proteins using AS/7 antibody specific for Gi-1/2, EC/2 antibody specific for Gi-3 and RM/1 antibody specific for Gs-type conventional G-proteins demonstrated the presence of M(r) 28-43 kDa, M(r) 41 and 48 kDa, and M(r) 36-46 kDa polypeptides, respectively. Immunoblotting using a common antibody (GA/1) for the Gs and Gi alpha-subunits also revealed the existence of multiple polypeptides (M(r) 24-52 kDa) in both aorta and mesenteric artery, some of which were identified by the specific antibodies. The intensity and number of bands detected by most of the antibodies were greater in mesenteric artery than in aorta. 3. Cholera toxin (CT) catalyzed ADP-ribosylation of two Gs alpha (M(r) 43, 46 kDa) in both types of blood vessels with similar intensities of bands. Pertussis toxin (PT), on the other hand, catalyzed ADP-ribosylation of one Gi alpha (M(r) 41 kDa) polypeptide, and the intensity of this band was greater in aorta than in mesenteric artery. The polypeptides ADP-ribosylated by the toxins corresponded with their identification by antibodies. 4. Nitrocellulose blot overlay with [35S]GTP gamma S identified at least seven low molecular weight G-proteins (M(r) 21-30 kDa) in both aorta and mesenteric artery, with greater intensity of bands in mesenteric artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose↗

PubMed1995

G-proteins in rat blood vessels--II. Assessment of functional involvement.

1. In this study, we compared G-protein-mediated contractile responses of rat aorta and mesenteric artery rings induced by the alpha-adrenoceptor agonist, norepinephrine (NE) and by the direct G-protein activator, sodium fluoride, using various probes. 2. Activator of the stimulatory G-protein (Gs), cholera toxin (CT), attenuated the sensitivity and maximum contractile response of both aorta and mesenteric artery to NE and sodium fluoride. The effect of the toxin on the NE-sensitivity was greater in mesenteric artery. 3. Pretreatment of tissues with the inhibitor of Gi-protein, pertussis toxin (PT), reduced the sensitivity as well as maximum contraction of both the aorta and mesenteric artery to sodium fluoride, and of the mesenteric artery to NE. PT attenuated only the sensitivity but not the maximum contraction of the aorta to NE. The inhibitory effect of PT on sensitivity to NE or sodium fluoride was greater in the aorta. 4. NE and sodium fluoride-induced contractions were reduced by the sulfhydryl G-protein inhibitor, N-ethylmaleimide (NEM) in both blood vessels. NEM produced greater inhibitory effect on the sensitivity of the aorta to both contractile agents. 5. These data demonstrate that CT, PT and NEM-sensitive G-proteins are involved in NE- and sodium fluoride-induced contractile responses of the rat aorta and mesenteric artery. The differential effects of the G-protein probes indicate that certain variations in G-protein-mediated contractile responses exist among the two blood vessels, suggesting that G-protein involvement in functional responses may vary with the type of blood vessel investigated.

Animals↗

PubMed1995

Interobserver variation in the chest radiograph component of the lung injury score.

The lung injury score is a semi-quantitative system used in the definition and grading of the acute respiratory distress syndrome. It is composed of two, three or four equally weighted components. One component is derived from the chest radiograph, which may contribute up to 50% of the total score. A score of 1 is awarded for each quadrant on the chest radiograph which contains alveolar consolidation. We examined the interobserver variation between two anaesthetists, two radiologists and two critical care physicians who scored blindly 100 chest radiographs from patients with adult respiratory distress syndrome. There was very good agreement between the two radiologists in the total scores (kappa 0.97) and in individual scores in each of the 4 quadrants (kappa 0.97-1.0). The agreement between anaesthetists and radiologists was only fair for the total score (kappa 0.37-0.42), but moderate to good for individual quadrant scores (kappa 0.43-0.73). The agreement between the two anaesthetists was moderate for individual quadrant scores (kappa 0.44-0.60), but only fair for total score (kappa 0.34). There was poor agreement between the two critical care physicians for total score (kappa 0.05) and for individual quadrant scores (kappa 0.04-0.20). Agreement between the physicians and other observers was poor to fair for the total score (kappa 0.12-0.32) and poor to moderate for the individual quadrant scores (kappa 0.15-0.63). Both anaesthetists and physician 2 underestimated the overall chest scores (median scores 2, 3 and 1 respectively) in comparison to the radiologists (median scores 3.5). Physician 1 significantly overscored (median score 4). The chest radiograph component of the lung injury score can be consistently assessed by radiologists, but significant variations may be introduced when assessed by other clinicians. This has significant implications for the use of the lung injury score in studies of adult respiratory distress syndrome and other studies which incorporate radiographic appearances in the definition.

Acute Disease↗

PubMed1994

Cigarette smoking increases monocyte adherence to cultured endothelial cell monolayer.

Leukocyte adherence to endothelium represents one of the early responses to injury. Although the underlying mechanisms of atherosclerosis and intimal hyperplasia remain unclear, monocytes/macrophages are associated with this phenomenon. Since cigarette smoking has been identified as a major risk factor for cardiovascular disease, we examined the effects of chronic cigarette smoking on human leukocyte adherence (monocytes, lymphocytes, and neutrophils) to cultured human umbilical vein endothelial cells (HUVEC's) in vitro. Among the cells, the basal adherence of monocytes only was significantly elevated in the smoking group (p < 0.05) compared to the non-smokers. Furthermore, the increase is related to increasing pack per day consumption (p < 0.01). These novel data suggest an alteration of the circulating monocytes by cigarette smoking, resulting in increased adherence to endothelial cells.

Cell Adhesion↗

PubMed1994

Attenuation of human leukocyte adherence to endothelial cell monolayers by tyrosine kinase inhibitors.

Expression of cell adhesion molecules is controlled by various cytokines including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha), but the underlying mechanisms are not clear. In this study, we investigated the role of tyrosine phosphorylated proteins in the regulation of leukocyte adhesion to endothelial cells. We examined the effect of genistein and herbimycin-A, selective inhibitors of tyrosine kinase, on the adherence of human blood neutrophils, lymphocytes, and monocytes to monolayers of human umbilical vein endothelial cells. Both genistein and herbimycin A significantly inhibited IL-1 and TNF alpha-induced upregulation of neutrophils (p < 0.05) and monocyte (p < 0.01) adherence. IL-1 and TNF alpha-stimulated lymphocyte adherence was diminished in the presence of herbimycin A (p < 0.05), but genistein only inhibited TNF alpha-stimulated adherence. There was no significant effect of genistein on IL-1-induced lymphocyte adherence. These novel findings reveal for the first time that tyrosine phosphorylated proteins may regulate leukocyte adherence and cell adhesion molecule expression on the endothelium.

Analysis of Variance↗

PubMed1994

Neuropeptide Y levels during ischemia and reperfusion in the canine infrarenal aortic revascularization model.

Neuropeptide Y (NPY) is a potent vasoconstrictive polypeptide colocalized with norepinephrine in sympathetic neurons. The effects of ischemia and reperfusion on plasma NPY levels were studied and compared in the mongrel dog after infrarenal aortic cross-clamping. We found a two- to threefold increase in NPY levels during ischemia (initial 10.0 +/- 1.8 pmol/L vs. maximum 24.7 +/- 2.31 pmole/L, p < 0.001). The increase in NPY remained following reperfusion (initial 10.0 +/- 0.8 pmole/L vs. maximum 23.9 +/- 2.31 pmole/L, p < 0.001). These data reveal that NPY is released during ischemia and reperfusion and may be involved in mediating remote vascular events associated with infrarenal aortic cross-clamping.

Animals↗

PubMed1994

Early cardiorespiratory patterns in patients with major burns and pulmonary insufficiency.

We examined the case records of 50 consecutive patients with major cutaneous burns who required early mechanical ventilation. In 22 patients full haemodynamic and respiratory data were available within 24 h of their injury. Unexpectedly the haemodynamic and oxygen transport patterns of survivors and non-survivors were essentially similar although pulmonary artery occlusion pressure measurements and estimations of net fluid input suggest that non-survivors were relatively underresuscitated compared with survivors. Both groups showed inadequate oxygen utilization in the early stages of their injury despite normal (or above normal) levels of oxygen delivery. Invasive monitoring could possibly help this subgroup of burns patients.

Adult↗

PubMed1994

Technique for assessment of leukocyte adherence to human umbilical vein endothelial cell monolayers.

The interaction between endothelial cells and immune/inflammatory cells plays an important role in the pathogenesis of vascular diseases. Inflammatory cells also activate endothelial cells and release both proliferative and cytotoxic mediators. In order to examine the interaction between leukocytes and endothelial cells and the effect of various drugs, we established the methodology for isolating and culturing the endothelial cells from human umbilical vein. Endothelial cells were harvested by using 0.1% collagenase within 48 hr of collecting the cord. Cells were grown to confluency in 96-well plates in Medium 199 containing 20% fetal calf serum, endothelial cell growth supplement, heparin, and antibiotics. Using this method, we obtained a confluent layer of the cells in all the 96 wells within 48 hr. We then examined the effect of peptides, endothelin-1, substance P, and neurokinin-A on the adherence of human blood neutrophils (purity and viability > 98%) to endothelial monolayers. All the peptides enhanced (p < 0.05) the adherence of neutrophils to endothelial cells in a time-dependent manner. This method of endothelial cell culturing is reliable, reproducible, and effective in evaluating the role of various mediators and drugs on the adherence of various white blood cells to endothelium.

Cell Adhesion↗

PubMed1994

Endothelin-1 levels in ischaemia, reperfusion, and haemorrhagic shock in the canine infrarenal aortic revascularisation model.

Endothelin-1 (ET-1) is a potent vasoconstrictive polypeptide produced from vascular endothelial cells. The effects of ischaemia, reperfusion, and exsanguination on plasma ET-1 levels were studied and compared in the mongrel dog after infrarenal aortic cross clamping. Ischaemia produced a trend toward increased ET-1 serum levels (p < 0.07 with Bonferroni correction) that did not reach significance. Plasma ET-1 levels were significantly increased during reperfusion and even further elevations were found following exsanguination. We found a 2-3 fold increase in ET-1 levels following reperfusion (Initial 3.19 +/- 0.27 pg/ml vs. Reperfusion maximum 6.32 +/- 0.72 pg/ml, Bonferroni p < 0.01). Haemorrhagic shock was associated with a 3-4 fold increase in ET-1 levels (Initial 3.19 +/- 0.27 pg/ml vs. Exsanguination maximum 8.37 +/- 0.97 pg/ml Bonferroni p < 0.001). These data reveal that ET-1 is released during reperfusion and exsanguination and may mediate remote vascular events associated with infrarenal aortic cross clamping and acute blood loss.

Animals↗

PubMed1994

Comparison of the hemodynamic and oxygen transport responses to modified fluid gelatin and hetastarch in critically ill patients: a prospective, randomized trial.

OBJECTIVE: To compare the hemodynamic and oxygen transport responses to a rapid (< 10-min) infusion of 500 mL of modified fluid gelatin (group A) or hydroxyethyl starch (group B) in patients suffering from acute hypovolemia. DESIGN: Prospective, randomized, noncrossover study. SETTING: University hospital, general intensive care unit. PATIENTS: Twenty-eight patients with hypovolemia mechanically ventilated for concurrent acute respiratory failure. INTERVENTIONS: Patients were mechanically ventilated. Pulmonary and femoral artery catheters were used for hemodynamic monitoring. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport variables were determined at baseline, 15 mins, and 30 mins after the infusion of each fluid. In both groups pulmonary artery occlusion pressure, stroke volume, and cardiac index significantly increased. In neither group did heart rate decrease. Oxygen delivery increased significantly in group A patients but not in group B patients. This result was due to greater hemodilution in group B patients. CONCLUSIONS: There are no significant differences in the hemodynamic responses to hydroxyethyl starch or modified fluid gelatin. The hemodynamic and oxygen transport effects of artificial colloid solutions may not be entirely predictable and should be monitored in critically ill patients.

Adult↗

PubMed1994

The need for quality control in measurement of mixed venous oxygen saturation.

We investigated the variability of arterial, mixed venous and peripheral venous oxygen saturation readings in three co-oximeters in regular use on two Intensive Care Units. Over a 2-week period, 96 readings were obtained from each of the following machines; two AVL 912 co-oxylite co-oximeters (Machines A and B, Biomedical Instruments, Graz, Austria) and one IL-282 (Machine C, Instrumentation Laboratories, Lexington, MA, USA). The coefficient of variation in the arterial oxygen saturations was extremely small on all three machines (< 0.43%). The coefficient of variation in the mixed venous samples, however, ranged from 1.96 to 4.61% on machine A, and from 2.73 to 4.71% on machine B, but only from 0.17 to 1.47% on machine C. The variation in mixed venous saturations obtained from a single blood sample repeatedly analysed on machines A and B was large enough to influence clinical management.

Humans↗

PubMed1994

A re-evaluation of the ventilator score as an indicator of prognosis in the adult respiratory distress syndrome.

OBJECTIVE: To determine whether the ventilator score of Smith and Gordon (1986) can accurately predict outcome in patients with severe Adult Respiratory Distress Syndrome (ARDS). DESIGN: Retrospective study of data from case records and flow sheets. SETTING: University Hospital Intensive Care Unit. SUBJECTS: Fifty-five patients with severe Adult Respiratory Distress Syndrome. MEASUREMENTS AND MAIN RESULTS: The ventilator score of Smith and Gordon (1986), based on a compound score of the patient's age, alveolar to arterial oxygen tension difference and mean peak airway pressure, was calculated daily for for each patient. In contrast to the original report, a high ventilator score ( greater than 80) had a predictive value for death of only 59%, and a specificity of only 29%. The use of a higher ventilator score ( greater than 100) resulted in a predictive value of only 70% with a specificity of 75%. The use of inverse ratio ventilation was associated with a significant improvement in survival in those patients with ventilator scores greater than 100. This finding has not been reported previously. CONCLUSIONS: The ventilator score does not provide a satisfactory predictor of outcome in ARDS and cannot be used as a prognostic tool. It may have some use as an indicator of the severity of respiratory failure. A ventilator score greater than 100 may be an indication for the institution of inverse ratio ventilation.

Adolescent↗