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Biomedical subjects

J Ashton

Publications and source records attributed to J Ashton.

At least 73 records · Page 4Linked to original sources
PubMed1987

Ancrod decreases the frequency of cyclic flow variations and causes thrombolysis following acute coronary thrombosis.

The potential use of ancrod, a purified isolate from the venom of the Malaysian pit viper, Agkistrodon rhodostoma, in decreasing the frequency of cyclic flow variations in severely stenosed canine coronary arteries and causing thrombolysis of an acute coronary thrombus induced by a copper coil was evaluated. Open-chest, anesthetized dogs were used. Ancrod was given intravenously (8 U/kg) over 1 hour and caused a significant reduction in the frequency of cyclic flow variations (5.8 +/- 0.7 to 3.6 +/- 0.8 cyclic flow variations per 30 minutes, p less than 0.05), whereas control animals failed to decrease the frequency of their cyclic flow variations over the same time period (5.3 +/- 0.3 to 5.0 +/- 0.4 cyclic flow variations per 30-minute period). Twenty-seven dogs had a coronary thrombus induced by a copper coil positioned directly in a major coronary artery; of these, four died of ventricular fibrillation prior to treatment, eight received an infusion of saline and showed no thrombolysis over 5 hours, and three died of ventricular fibrillation during the initial part of an intravenous infusion of ancrod. The remaining 12 dogs received ancrod intravenously (16 U/kg); six demonstrated lysis of the coronary thrombus (mean time to lysis, 65 +/- 20 minutes). The concentrations of ancrod used in these studies produced a severe decrease in systemic fibrinogen concentration and a significant decrease in the inhibitor of plasminogen activator levels. Thus, ancrod decreases the frequency of cyclic flow variations in stenosed canine coronary arteries and may cause coronary thrombolysis in approximately 50% of animals within 65 +/- 20 minutes of its intravenous administration.

Acute Disease↗
PubMed1986

Health museums or theme parks: a new approach to intersectoral collaboration.

This paper is an outline of a proposed initiative on intersectoral collaboration in health promotion--collaboration between health, tourist, cultural and entertainment sectors to provide a powerful mass educational experience about the human mind and body. There has been a recent rise in interest in using the technology of museums, science centres, exploratories and theme parks for the promotion of health. This revival is shown to have a historical tradition in the health education museum started in this century in Europe 75 years ago at the Deutsches Hygiene Museum and then spreading to the USA. The proposed Body, Mind, City Museum planned for Liverpool acts as a future model for a new type of health Museum; a mixture of science exploratorium and a Walt Disney-style them park. It is intended that "hand-on" exhibits using interactive video, computers, games and experiences will be used to test people's own capacities or to describe biological functions or processes. This will be combined with park rides and simulations with their inherent appeal of fun, movement and surprise, for example the ride through the blood vessels and the "walk-through brain". This type of venture has a number of special features and advantages; it is truly intersectoral, it may be self-financing, and it can provide a mass audience with a powerful individual experience.

England↗
PubMed1985

Reporting methodology protocols in three acute care journals.

Our study compared the reporting of methodology protocol details in three acute care journals, Annals of Emergency Medicine, Critical Care Medicine, and Journal of Trauma. Eleven criteria previously reported for evaluation of clinical trials in the medical literature were used. These were eligibility criteria, admission before allocation, random allocation, method of randomization, patients' blindness to treatment, blind assessment of outcome, treatment complications, loss to follow-up, statistical methods, statistical analysis, and power. All prospective, interventional, controlled trials appearing in the journals from January 1980 to June 1983 were identified. A total of 45 trials was found. Each study was read independently by two reviewers to determine whether each of the 11 criteria was reported clearly, reported unclearly, or not applicable. Disagreements were resolved by a third reader (adjudicator). The results are reported as the mean proportion of items clearly reported plus or minus the standard deviation: Annals of Emergency Medicine (n = 16), 0.40 +/- 0.18; Journal of Trauma (n = 18), 0.41 +/- 0.24; Critical Care Medicine (n = 11), 0.35 +/- 0.18. A one-way analysis of variance found no statistically significant difference between journals with respect to these proportions (P = .75). The study reveals that these journals, as judged by these criteria, do not report enough methodologic information to allow assessment of bias-reducing techniques and statistical methodology.

Analysis of Variance↗
PubMed1985

Failure of a slow channel calcium antagonist, verapamil, to retard atherosclerosis in the Watanabe heritable hyperlipidemic rabbit: an animal model of familial hypercholesterolemia.

Verapamil and other slow channel calcium antagonists have been reported to retard atherosclerosis in rabbits fed a high cholesterol diet. Because atherosclerosis in such a model may differ significantly from human atherosclerosis, experiments were conducted to prevent atherosclerosis with verapamil in the Watanabe heritable hyperlipidemic (WHHL) rabbit, which is a genetic, metabolic and pathologic model of homozygous familial hypercholesterolemia. At 2 months of age, 23 WHHL rabbits were divided into two groups since earlier studies showed no macroscopic atherosclerosis at 2 months. Group A (n = 11) was fed standard rabbit chow for 6 months. Group B (n = 12) received oral verapamil (46 mg/kg per day) absorbed in the identical chow as fed to Group A and subcutaneous verapamil (0.25 mg/kg twice daily 6 days a week). In Group B, mean serum verapamil concentrations (+/- SEM) averaged 16.9 +/- 1.9 ng/ml at 3 hours after subcutaneous injection. Sex ratios and serum cholesterol concentrations were the same in both groups. The percent of aortic surface area with visible plaque in Group A versus B was 49 +/- 7 versus 43 +/- 7%, respectively, of the entire aorta, and 61 +/- 5 versus 65 +/- 5%, respectively, of the proximal 3 cm of aorta (p = NS). Thus, verapamil did not suppress atherosclerosis in WHHL rabbits at serum drug levels greater than those reported to be effective in other models.

Animals↗
PubMed1985

Cyclic blood flow variations induced by platelet-activating factor in stenosed canine coronary arteries despite inhibition of thromboxane synthetase, serotonin receptors, and alpha-adrenergic receptors.

The phospholipid platelet-activating factor (PAF) stimulates platelet aggregation and coronary vasoconstriction. In this study we determined whether PAF alters coronary flow patterns in vivo in a canine preparation with concentric coronary artery stenosis. This preparation is characterized by cyclic flow variations in coronary blood flow associated with transient platelet aggregation at the site of the coronary constriction. Thirty-nine male mongrel dogs were used in three protocols. In protocol 1, PAF (10(-9) or 10(-8) mol/min) was infused into the coronary artery proximal to the stenosis to determine (1) whether PAF induces cyclic flow variations and (2) whether PAF has an effect on systemic hemodynamics. Cyclic flow variations were induced in three of six dogs; in these animals, mean arterial pressure decreased by 5.5% and 42.1% 10 min after infusion of the lower and higher dose of PAF. In protocol 2, cyclic flow variations were abolished with either the thromboxane synthetase inhibitor UK38485 (mean dose 2.2 mg/kg iv), the serotonin antagonist ketanserin (0.5 mg/kg iv), or the alpha 2-adrenergic antagonist yohimbine (2 mg/kg iv). Subsequent administration of PAF restored the frequency of cyclic flow variations to the preantagonist levels. Thromboxane (Tx) B2 and 6-keto-PGF1 alpha, the stable metabolites of TxA2 and prostacyclin, respectively, were measured in blood obtained distal to the coronary stenosis. TxB2 levels increased substantially during cyclic flow variations and were returned to control values with the thromboxane synthetase inhibitor UK38485. Infusion of PAF subsequently restored cyclic flow variations without altering coronary arterial coronary arterial TxB2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Effects of propranolol and diltiazem alone and in combination on the recovery of left ventricular segmental function after temporary coronary occlusion and long-term reperfusion in conscious dogs.

We evaluated the ability of propranolol and diltiazem alone and in combination to enhance the recovery of left ventricular (LV) segmental function during 1 month of reperfusion after two temporary occlusions of the left anterior descending coronary artery (LAD) in conscious dogs instrumented with ultrasonic crystals for the measurement of regional net systolic wall thickening (NET). LV segments were classified according to their contractile function after 1 hr of LAD occlusion: class 1, greater than 67% of preocclusion (control) NET; class 2, 0% to 66.9%; class 3, less than 0% (paradoxical systolic wall thinning). Propranolol (1 mg/kg iv) or diltiazem (20 micrograms/kg/min) was given 65 min after LAD occlusion in dogs that had 2 (group I) or 4 hr (group II) of LAD occlusion. Diltiazem plus propranolol (same doses) were given to another group of dogs that underwent 4 hr (but not 2) of LAD occlusion. Untreated control dogs received 25 ml of saline and underwent 2 or 4 hr of LAD occlusion. The NET of class 2 and 3 segments in group I control dogs increased significantly during 1 month of reperfusion, from 32 +/- 5% and -43 +/- 6% to 66 +/- 9% and 26 +/- 9%, respectively (p less than .05). Neither diltiazem nor propranolol enhanced the long-term recovery of these segments in group I dogs. However, diltiazem prevented further deterioration of contractile dysfunction observed in control dogs immediately after reperfusion in both segment classes. The NET of class 2 segments in group II control dogs after 4 weeks of reperfusion remained at levels observed during LAD occlusion: 30 +/- 4% to 37 +/- 12%. Class 3 NET increased from -33 +/- 5% to 12 +/- 12% with 1 month of reperfusion, but these segments were essentially akinetic. Propranolol or diltiazem alone did not produce significant overall increases in NET, but diltiazem again prevented further declines in NET of class 2 and 3 segments during early reperfusion. However, the combination of diltiazem and propranolol significantly enhanced overall recovery of class 2 NET in group II dogs (44 +/- 3% to 88 +/- 7%) and prevented the worsening of NET associated with early reperfusion. Compared with untreated dogs, propranolol plus diltiazem also significantly decreased the extent of histologic necrosis in class 2 and 3 segments as well as the macrohistochemically determined infarct size in group II dogs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Neutral metalloendopeptidase in human lung tissue and cultured cells.

The distribution of a neutral metalloendopeptidase (NEP), or "enkephalinase," in human lung tissue and cultured cells was compared with that of angiotensin I converting enzyme (ACE). The specific activities of NEP and ACE were measured in homogenates of fetal lung tissue and in isolated airways and pulmonary vessels. NEP activity was highest in airway tissue, and ACE activity was highest in isolated vessels. Human endothelial cells from either umbilical veins or pulmonary arteries had high ACE activity (80 to 90 nmol/h/10(6) cells) but only a trace of NEP activity (0.5 to 0.6 nmol/h/10(6) cells). Fibroblasts cultured from human lungs were low in ACE but richer in NEP than cultured endothelial cells. Fibroblasts from human foreskins or caesarean section skin were the richest source of NEP activity (60 to 80 nmol/h/10(6) cells). Immunohistochemical studies confirmed the biochemical assays. As expected, ACE was localized on the luminal surface of blood vessels, with a distribution similar to that of factor VIII antigen, an endothelial marker. In contrast, NEP was localized within the alveolar septa. Cultured endothelial cells stained only weakly for NEP in contrast to cultured fibroblasts. The location of these 2 enzymes in different cells and the differences in peptide substrate specificity suggests that they act sequentially on circulating peptides or those released within microvascular beds.

Cells, Cultured↗
PubMed1985

Neutral endopeptidase in serum samples from patients with adult respiratory distress syndrome. Comparison with angiotensin-converting enzyme.

The activities of 2 peptidases, angiotensin-I converting enzyme (ACE) and neutral metalloendopeptidase (NEP), were measured in serum from patients with adult respiratory distress syndrome (ARDS). As noted by others, we found that the specific activity of serum ACE was reduced in patients with severe alveolocapillary damage caused by ARDS. In addition, patients who were severely ill with chronic obstructive lung disease had lower serum ACE than did normal ambulatory control subjects. Patients with cardiogenic pulmonary edema, however, had no consistent loss of the enzyme. The most striking changes occurred in the serum levels of NEP. Whereas the specific activity of this enzyme was very low in the normal subjects, it was elevated as much as 50- to 60-fold in serum samples from patients with ARDS. Serum from patients with cardiogenic pulmonary edema had high levels of NEP, and it was elevated also in a subset of patients with chronic obstructive lung disease. On the assumption that patients with ARDS sustain significant damage at the alveolar-capillary level, these changes in ACE and NEP could signal endothelial damage; ACE loss could result from direct injury to the vascular lumen, and NEP from subendothelial tissues could enter the bloodstream through damaged endothelium. Alternatively, NEP might be released from leukocytes sequestered in the lung and leak into the bloodstream.

Adult↗
PubMed1985

Health in Mersey--an exercise in community diagnosis.

The process of producing a community diagnosis for the Mersey Region is described. Such an exercise is recommended for its potency in agenda-setting, and establishing a frame of reference for health promotion within the context of the strategy of Health For All By The Year 2000.

Community Health Services↗
PubMed1984

The effects of alpha 2-adrenergic and serotonergic receptor antagonists on cyclic blood flow alterations in stenosed canine coronary arteries.

Platelets possess alpha 2-adrenergic and serotonergic (5-hydroxytryptamine) receptors which are thought to mediate the in vitro proaggregatory effects of epinephrine and serotonin, respectively. However, their importance in platelet aggregation in vivo is uncertain. In the present study, we evaluate the ability of yohimbine and ketanserin, relatively selective alpha 2-adrenergic and serotonin antagonists, respectively, to alter cyclic flow reductions in stenosed coronary arteries in open-chest, anesthetized dogs. These cyclic flow reductions, characterized by progressive declines in coronary blood flow interrupted by abrupt and, often spontaneous, restorations of flow, were produced by cylindrical constrictors placed on the left anterior descending coronary artery. A pulsed Doppler flow probe, placed proximal to the constrictor, was used to measure coronary blood flow. Regional myocardial blood flow was measured with 15-micron radiolabeled microspheres before coronary constriction and when coronary blood flow appeared to be at its nadir and zenith during cyclic flow reductions. After the cyclic flow reductions had been observed for 1 hour, yohimbine (1-2 mg/kg), ketanserin (0.25 or 0.5 mg/kg), or saline was given, and coronary blood flow and hemodynamics were monitored for another hour. The frequency of cyclic flow reductions and the mean of the three lowest nadirs of coronary blood flow (mean +/- SE) were compared between the first and second hours. Ketanserin, at doses of 0.25 and 0.50 mg/kg, virtually abolished cyclic flow reductions in all dogs tested. Yohimbine [1 mg/kg ( n = 14)] was partially effective in reducing the frequency (9.6 vs. 5.5 cyclic flow reductions/hr) and severity of cyclic flow reductions (nadirs of coronary blood flow = 6.2 +/- 2.4 vs. 20.9 +/- 6.1% of control). A higher dose of yohimbine [2 mg/kg (n = 7)] was no more effective. The frequency (9.3 +/- 0.9 vs. 9.3 +/- 1.0 CFR/hr) and severity (17.4 +/- 5.4 vs. 12.4 +/- 3.9% of control coronary blood flow) of cyclic flow reductions were not changed by saline. The relatively selective alpha 1-adrenergic antagonist, prazosin (0.01 mg/kg, iv), and the beta-adrenergic antagonist, propranolol (1-2 mg/kg, iv), did not affect the frequency or severity of cyclic flow reductions. Thus, the abilities of yohimbine to inhibit and ketanserin to abolish cyclic flow reductions in stenosed canine coronary arteries suggest that serotonin and, possibly, alpha 2-adrenergic agonists may influence cyclic flow alterations importantly in this model.

Adenosine Diphosphate↗
PubMed1981

The effect of carrier and modulation frequency on lateralization based on interaural phase and interaural group delay.

The sensitivity of Observers to interaural delay in either the envelope or the carrier of an amplitude-modulated sinusoid was measured in a two-interval forced-choice task as a function of the frequency of the modulation and the frequency of the carrier. The two types of delay were set in opposition with the carrier leading in one ear but the modulation leading in the other. Lateralization appeared to be based on carrier (phase) delay when carrier frequency was below 1500 Hz, whatever the modulation frequency. For carrier frequency greater than 1500 Hz, lateralization performance was dependent both on carrier and on modulation frequency and was based on modulation (group) delay.

Acoustic Stimulation↗