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Biomedical subjects

B Hughes

Publications and source records attributed to B Hughes.

At least 73 records · Page 4Linked to original sources
PubMed1990

Is metoprolol CR/ZOK more selective than conventional metoprolol and atenolol?

An alternative, simple method to assess beta 1-selectivity is to establish the impact of the beta blocker on beta 2-stimulated increases in plasma glucose and decreases in plasma potassium during an intravenous infusion of terbutaline. In the present study the effects of metoprolol CR/ZOK 100 mg, conventional metoprolol 100 mg, atenolol 100 mg, and placebo on these biochemical changes have been compared. In 12 healthy volunteers, terbutaline infusion of 6 micrograms/kg was administered intravenously over 1 hour. Three and a half hours before the infusion they were given a single dose of each of the four treatments in random order, single-blind. The maximum increase in plasma above baseline occurred at the end of a 60-minute terbutaline infusion. All three-beta blockers decreased the peak plasma glucose level achieved compared with placebo (P less than .01) but this reduction was significantly less with metoprolol CR/ZOK pretreatment than with atenolol (P less than .05). Similar results were seen for the AUC values for the curves obtained from the increments over the 60 minutes of the infusion and the subsequent 120 minutes after the infusion. In addition, both the AUC values and the maximum fall in potassium were significantly reduced by all treatments (P less than .05). The metoprolol CR/ZOK preparation produced significantly less effect than atenolol with respect to both AUC (P less than .05) and maximum fall (P less than .01) and significantly less effect than conventional metoprolol tablets in maximum fall (P less than .01). In conclusion, the metoprolol CR/ZOK formulation produces lower plasma concentrations and results in less effect on potassium and glucose compared to conventional metoprolol and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Enhanced myocardial salvage by maintenance of microvascular patency following initial thrombolysis with recombinant tissue plasminogen activator.

STUDY OBJECTIVE: The aim was to examine the value of a subthrombolytic maintenance infusion of recombinant double chain tissue plasminogen activator (BW t-PA, Duteplase) in preserving microvascular coronary flow following initial thrombolysis. DESIGN: Coronary arterial thrombi were induced by a copper coil (placed under fluoroscopic control) in the canine left anterior descending coronary artery. Complete vessel occlusion occurred within 10-15 min of coil placement. Following 90 min of thrombotic occlusion, animals received one of three treatments: group 1, vehicle 0.9% saline; group 2, t-PA 1.0 X 10(6) IU.kg-1.h-1 for 1 h; group 3, t-PA 1.0 X 10(6) IU.kg-1.h-1 for 1 h followed by 0.12 X 10(6) IU.kg-1.h-1 throughout the 2 h reperfusion period. Radiolabelled microspheres were administered to assess microvascular coronary flow at various time points throughout the experimental period. SUBJECTS: Experimental subjects were beagle dogs of either sex (n = 30), weight 8.9-14.3 kg. MEASUREMENTS AND MAIN RESULTS: Main vessel patency (assessed fluoroscopically) was achieved within 40.0(SEM 4.0) min and 37.0(3.1) min for group 2 and group 3 animals respectively. Group 1 animals did not reperfuse. Full microvascular coronary flow was achieved following the lytic infusion of t-PA. However, microvascular flow to the ischaemic zone was significantly reduced at the end of the 2 h reperfusion phase in group 2 animals despite "aggressive" anticoagulation with heparin throughout the reperfusion period: subendocardial flow decreased from 0.74(0.14) to 0.24(0.08) ml.min-1.g-1; subepicardial flow decreased from 0.82(0.13) to 0.36(0.09) ml.min-1.g-1, p less than 0.05. Microvascular coronary flow to the ischaemic zone was better preserved following the maintenance infusion of t-PA given throughout the reperfusion phase: subendocardial flow decreased from 0.95(0.07) to 0.50(0.10) ml.min-1.g-1; subepicardial flow decreased from 0.73(0.04) to 0.52(0.08) ml.min-1.g-1. Thrombolytic reperfusion led to salvage of the ischaemic myocardium, with infarct/risk ratio decreasing from 75.0(10.0)% in group 1 to 46.3(11.0)% in group 2, p less than 0.05. Further salvage of the ischaemic myocardium followed a lytic plus maintenance infusion of t-PA, with infarct/risk ratio decreasing to 35.5(6.7)% but this did not reach statistical significance. CONCLUSIONS: t-PA consistently achieved main vessel reperfusion within 40 min (mean) of instituting therapy in our model, leading to marked salvage of ischaemic myocardium. The data also suggest that maintenance infusion of t-PA helps preserve microvascular coronary flow throughout reperfusion and tends to reduce infarct size further.

Animals↗
PubMed1990

An asymmetry in transmodal perceptual learning.

Transmodal perceptual learning was examined in a canonical same/different paradigm. Subjects naive to vibrotactile stimulation and unfamiliar with the task were asked to discriminate sequentially presented shapes moving laterally across an aperture. On all trials, the shapes were presented either visually and then vibrotactually or in the opposite modality order, and on all trials the shapes moved in opposite directions. Analyses of the data revealed that although perceptual learning was evident in both groups, the rate of the learning was more rapid in the visual-vibrotactile group. This interaction of modality order and practice was significant and was considered in terms of E.J. Gibson's theory of perceptual learning and in terms of the constructs, suggested by J.J. Gibson, of available and accessible information-in-stimulation and the education of attention.

Adult↗
PubMed1989

Perceptual learning of spatiotemporal events: evidence from an unfamiliar modality.

Perceptual learning was examined in two experiments in which subjects, originally unfamiliar with vibrotactile stimulation, were required to identify dynamic vibrotactile patterns with static visual patterns of the same two-dimensional shapes. In Experiment 1 we examined changes in performance with practice under a variety of vibrotactile spatial and temporal conditions. In Experiment 2 we investigated transfer of learning from one set of vibrotactile patterns to another different set. In neither experiment were subjects supplied with knowledge of results. Substantial perceptual learning (improvement in identification with practice) was observed in Experiment 1, although a minority of subjects did not exhibit improvement. Experiment 2 confirmed the general findings of Experiment 1 and also provided evidence of substantial positive transfer. In both experiments, multidimensional scaling of pattern confusion data revealed that practice (and improvement in identification) did not qualitatively change the relative confusability of patterns, suggesting that the (informative) structure of the patterns, irrespective of familiarity with a specific set of patterns, determined confusability. The findings are interpreted in terms of learning constructs offered by E. J. and J. J. Gibson. We conclude by considering the prospects that a connectionist mechanism can account for the observed perceptual learning.

Attention↗
PubMed1988

Distribution and binding parameters of GABA and benzodiazepine receptors in the cat motor thalamus and adjacent nuclear groups.

Quantitative receptor binding autoradiography technique was utilized to study GABA and benzodiazepine receptors in the cat motor thalamus (ventral anterior, ventral medial and ventral lateral nuclei) and adjacent thalamic subdivisions. Binding parameters (Bmax and Kd) and distribution pattern of the binding sites for 3 tritiated ligands [3H]muscimol ([3H]MUS), [3H]flunitrazepam ([3H]FLU) and [3H]baclofen ([3H]BAC) were analyzed and compared using measurements from discrete and anatomically well-defined thalamic regions. There was little correlation in the regional distribution of the 3 binding sites. The concentration of [3H]BAC binding sites in thalamic nuclei of interest was very low, practically at the limit of resolution of the quantitative autoradiographic technique; whereas appreciable quantities of [3H]MUS and [3H]FLU binding sites were present in the motor and adjacent limbic nuclei of the thalamus. There was more difference between the nuclei in regard to the number of high affinity GABA receptors than benzodiazepine receptors. Moreover, the ratio of Bmax[3H]MUS/Bmax[3H]FLU varied from 2.2 to 4.4 in different thalamic regions suggesting the presence of a diverse population of GABAA and benzodiazepine receptors. The distribution pattern of the 3 binding sites was compared to the topography of GABAergic afferents of the basal ganglia origin and the frequency of GABAergic synapses formed by thalamic local circuit neurons (LCN) in the motor thalamus that were established earlier. It was concluded that in the cat motor thalamus: (1) none of the ligands studied appear to reveal the receptors associated with nigro- or pallidothalamic synapses; (2) [3H]MUS binding sites may be associated with the dendrodendritic contacts formed by LCN; and (3) the [3H]FLU binding sites are physically unrelated to [3H]MUS binding sites. The concentration of [3H]FLU and [3H]MUS binding sites in the midline nuclei and of [3H]MUS binding sites in the limbic nuclei was remarkably high. It was concluded that in addition to previously suggested limbic structures, the midline nuclei with their very high content of benzodiazepine receptors may be considered as a neuroanatomical substrate of certain forms of anxiety.

Animals↗
PubMed1988

Reversed-phase liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis characteristics of a recombinant DNA derived malaria antigen.

This paper presents results from analysis of a sample of SK&F 105154 (R32NS1(81], a malaria vaccine candidate produced in Escherichia coli, and discusses some analytical issues of general relevance to the characterization of such products derived from recombinant DNA technology. Anomalous migration and staining behavior were observed in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Reversed-phase liquid chromatography (RPLC) appeared to resolve four minor components from the principal band, but the minor peaks were found to consist of numerous components resolvable by SDS-PAGE. Western blotting visualized certain components that were not adequately stained by either Coomassie or silver stain. None of the techniques that were employed were individually adequate to characterize the sample, but, taken together, were adequate to characterize the sample and to identify one principal degradation pathway. Degradation within the NS1(81) region decreases the RPLC retention time, while degradation within the R32 segment increases the retention time.

Amino Acid Sequence↗
PubMed1988

Quantitation of a murine lung endothelial cell protein, P112, with a double monoclonal antibody assay.

Two monoclonal antibodies (MoAb) have been isolated from two different F344 rats immunized with normal BALB/c mouse lung homogenates. The MoAbs 273-34A and 411-201B demonstrate similar staining properties when used in immunohistochemistry and have been shown to bind to endothelial cells in the lung using immunogold electron microscopy. Radiolabeled MoAb 273-34A injected intravenously localizes rapidly to lung. Ratios of MoAb to control and values for percentage of recovered dose/gram are 50-fold higher in lung than in other organs. Both MoAbs recognize the same 112 kilodalton protein (P112) on the surface of lung cells in culture but do not compete for binding with each other. Both antibodies can be used to purify P112 from normal mouse lung homogenate using immunoaffinity chromatography. These MoAb have been used in a two-site, quantitative assay for P112. Data show that normal lung contains high amounts of P112 (500 to 700 ng/mg P), whereas other organs have low (spleen, uterus) or undetectable (liver) levels of P112. We conclude that endothelial cells in different organs are not identical and that P112 is preferentially expressed in lung endothelial cells. Quantitation of P112 may be useful to assess the role of endothelial cells in toxic injury, lung diseases, and growth and vascularization of lung tumors.

Animals↗
PubMed1987

Rapid identification of pathogenic Neisseria species and Branhamella catarrhalis.

Two systems, the Identicult-Neisseria (IDN; Scott Laboratories, Inc., Fiskeville, R.I.) strip and the Neisseria/Haemophilus Identification Test Kit (NHI; Vitek Systems, Inc., Hazelwood, Mo.) card, were compared with the 4-h Minitek system (BBL Microbiology Systems, Cockeysville, Md.) for their ability to rapidly identify 157 pathogenic Neisseria and Branhamella catarrhalis isolates. IDN, limited in its identification to four species, when incubated at 35 degrees C for 10 min identified 99% of the isolates. However, when IDN was incubated at 22 degrees C for 20 min, it identified only 92% of the isolates. The NHI card, a rapid semiautomated system with the ability to identify 25 organisms to the species level, correctly identified all of the isolates. A test for beta-lactamase production included in the NHI card identified the 12 Neisseria gonorrhoeae and 10 B. catarrhalis beta-lactamase-positive isolates included in the study. The IDN strip (35 degrees C) and the NHI card compared favorably with the Minitek system.

Moraxella catarrhalis↗
PubMed1986

Education in cancer prevention for primary care clinicians.

In response to increased public interest in cancer prevention and rapidly escalating health care costs, the National Cancer Institute supported the development of cancer prevention courses for health professionals. A multidisciplinary group of physicians, behavioral scientists, and educators developed, field-tested, revised, and evaluated a 12-module, 24-classroom-hour clinical preventive oncology course for primary care physicians. A rationale for education in cancer prevention is presented, the new clinical discipline of preventive oncology is defined, and contributory disciplines are identified. A curriculum based upon detailed learning objectives is described, short-term evaluation data are presented, and a methodology for incorporating a didactic course into a residency program is suggested. The positive reception given to this course by residents warrants optimism concerning application of a biopsychosocial or self-regulative model rather than the traditional biomedical one to clinical medicine and its teaching.

Attitude of Health Personnel↗
PubMed1986

External detection of beta-adrenoreceptors with 125I-hydroxybenzylpindolol in isolated perfused hearts.

To assess the feasibility of characterizing beta-adrenoreceptors externally with ligands labeled with gamma-emitting radionuclides, we infused 125I-hydroxybenzylpindolol (125I-HYP) a potent, high affinity, beta-adrenoreceptor ligand into isolated perfused hearts and monitored uptake and release of the label externally with a gamma probe. Perfusion with specific beta-adrenergic displacing significantly increased the turnover rate constant of 125I-HYP in comparison to that obtained with non-specific displacing agents. After modifying beta-adrenoreceptor density by pretreatment of animals with thyroid hormone, an increase in 125I-HYP uptake was observed. Thus, beta-adrenoreceptor occupancy and increases in beta-adrenoreceptor density can be detected externally with an approach which may offer promise for their characterization in vivo with radiolabeled adrenergic ligands.

Animals↗
PubMed1986

Is there anything out there? A study of distal attribution in response to vibrotactile stimulation.

Patterns of vibrotactile stimulation were delivered to the index fingertips of naive blindfolded subjects. The attributions made by these subjects when they were allowed to experience transformations of vibrotactile stimulation correlated with self-movement were assessed. Although the subjects became aware of the relationship between self-movement and stimulation transformation, they never developed the hypothesis of distal attribution, ie the hypothesis that the ultimate cause of their vibrotactile experience was an encounter with an object in the environment. It is proposed that further investigations of the course of acquisition of distal attribution in the situation described may be instructive in the study of externalization in other modalities.

Fingers↗
PubMed1986

Effects of an increase in haemoglobin O2 affinity produced by BW12C on myocardial function in the erythrocyte-perfused rabbit heart in vitro and myocardial infarct size in the dog.

The effects of BW12C on myocardial function in the erythrocyte-perfused rabbit heart and on myocardial infarct size in the anaesthetized dog have been evaluated. Perfusion of rabbit hearts with erythrocytes pretreated with BW12C (10(-3) M-4 X 10(-3) M) produced concentration-dependent decreases in left ventricular pressure (LVP), LVP dP/dt and coronary perfusion pressure. A concomitant decrease in PO2 and an increase in lactate production by the myocardium was also observed. Perfusion of rabbit hearts with Krebs Henseleit buffer containing BW12C (10(-5)-10(-4) M) caused no change in measured variables. Although BW12C (10(-3) M) caused a small decrease in LVP, coronary perfusion pressure and heart rate, these changes were not significant. In anaesthetized dogs, an infusion of BW12C (total dose 50 mg kg-1, i.v.) caused small, but significant, changes in haemodynamic status. The oxygen saturation curve was shifted to the left and relative % oxygenation (P20) was shifted to the left throughout the course of the experiment. (P20, control 16.3 +/- 0.4 mmHg; after BW12C 7.9 +/- 1.4 mmHg). Pretreatment with BW12C (total dose 50 mg kg-1) caused no change in area at risk but significantly increased the myocardial infarct size by 410%. These studies with BW12C demonstrate that alteration in haemoglobin-oxygen affinity can induce adaptive physiological changes in tissue function and metabolism and can assume a critical role when oxygen supply may be impaired due to a flow-limiting stenosis.

Aldehydes↗
PubMed1986

Comparative effects of seven antidepressant regimes on appetite, weight and carbohydrate preference.

Appetite, weight, and preference for carbohydrate-containing food were followed in patients treated in double-blind trials of seven antidepressant regimes. Trimipramine and isocarboxazid combined had a significant effect in increasing appetite, carbohydrate preference, and weight; in patients who had lost appetite at presentation and were on this treatment, improvement in Hamilton score was linked to increase in weight--a finding not true of the other treatments.

Antidepressive Agents↗