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Biomedical subjects

K Doyle

Publications and source records attributed to K Doyle.

At least 19 recordsLinked to original sources
PubMed2004

Does a single bolus thrombolytic reduce door to needle time in a district general hospital?

OBJECTIVES: To answer the question "In patients presenting with ST elevation acute myocardial infarction (STEMI) and no contraindication to thrombolysis, does the introduction of Tenecteplase reduce door to needle times?" METHODS: Firstly, an observational study was performed to compare the time taken to prepare standard thrombolytic therapy with Tenecteplase. Secondly, door to needle times were compared before and after the introduction of Tenecteplase. The study was powered to be 80% sure of finding a change of 10% in the number of patients meeting the national service framework standard of a 30 minute door to needle time. RESULTS: Tenecteplase takes 10.5 minutes less time to prepare than standard treatment (p value <0.001). After the introduction of Tenecteplase the percentage of patients receiving thrombolysis in 30 minutes increased from 58% to 76% (p value <0.01) CONCLUSION: Tenecteplase is quicker to prepare than standard therapy, resulting in a significant improvement in performance against the national service framework target.

Emergencies↗
PubMed2001

Developmental themes in women's emotional experiences of motherhood.

In this study, women's levels of ego development and their psychological difficulties were examined in relation to feelings in the maternal role. The sample consisted of 91 mothers from diverse socioeconomic backgrounds. Ego development was assessed by the Washington University Sentence Completion Test, and psychological difficulties were operationalized by self-reported global symptomatology, maternal substance abuse, and expressed anger. Outcome variables included feelings of satisfaction, distress, and support in the maternal role, as well as the degree to which negative and positive emotions were integrated in response to hypothetical vignettes of challenging everyday child-rearing experiences. Hypotheses were that women at high levels of ego development would show greater deterioration in the presence versus absence of self-reported adjustment problems than would those at lower levels. A series of interaction effects each indicated trends consistent with the hypotheses. These results add to accumulating evidence that tendencies toward self-examination, characteristic of high developmental levels, do not inevitably serve protective functions but may be linked with heightened reactivity to negative intrapsychic forces.

Adolescent↗
PubMed1998

Effect of alpha-difluoromethylornithine on rectal mucosal levels of polyamines in a randomized, double-blinded trial for colon cancer prevention.

BACKGROUND: Polyamines (e.g., putrescine, spermidine, and spermine) are required for optimal cell growth. Inhibition of polyamine synthesis suppresses carcinogen-induced epithelial cancers, including colon cancer, in animal models. In a short-term phase IIa trial, we determined that low doses of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (an enzyme involved in polyamine synthesis), reduced the polyamine content of normal-appearing rectal mucosa of subjects with a prior history of resected colon polyps. In a follow-up study, we have attempted to determine the lowest dose of DFMO that can suppress the polyamine content of rectal mucosa over a course of 1 year with no or minimal side effects. METHODS: Participants were randomly assigned to daily oral treatment with a placebo or one of three doses (0.075, 0.20, or 0.40 g/m2) of DFMO. Baseline and serial determinations of polyamine levels in rectal mucosa and extensive symptom monitoring (including audiometric measurements, since DFMO causes some reversible hearing loss at higher doses) were performed over a 15-month period. RESULTS: DFMO treatment reduced putrescine levels in a dose-dependent manner. Following 6 months of treatment, doses of 0.20 and 0.40 g/m2 per day reduced putrescine levels to approximately 34% and 10%, respectively, of those observed in the placebo group. Smaller decreases were seen in spermidine levels and spermidine:spermine ratios. Polyamine levels increased toward baseline values after discontinuation of DFMO. Although there were no statistically significant differences among the dose groups with respect to clinically important shifts in audiometric thresholds and nonaudiologic side effects, statistically significant higher dropout and discontinuation rates were observed in the highest dose group. CONCLUSIONS: Polyamine levels in rectal mucosa can be continuously suppressed by daily oral doses of DFMO that produce few or no side effects. A dose of 0.20 g/m2 can be used safely in combination phase IIb or single-agent phase III chemoprevention trials.

Adult↗
PubMed1995

Preferential association of membrane phospholipids with the human erythrocyte hexose transporter.

This study reports the results of an investigation to determine to what extent the influence of membrane lipids on the human erythrocyte sugar transporter protein activity (Caruthers, A. and Melchior, D.L. (1988) Annu. Rev. Physiol. 50, 257-271) is related to lipid/protein associations in the membrane bilayer. Differential scanning calorimetry was carried out on the human erythrocyte transport protein reconstituted into artificial bilayers formed from preselected lipids. it was found that the transport protein displays a preferential and in some cases strongly preferential affinity for specific lipid types. This association is a function of lipid head group, backbone and hydrocarbon chain length. It appears that the affinity of the transport protein for various lipids can correlate with the lipid's ability to influence transporter activity. This study further suggests that certain lipids (in this case sphingomyelin) can induce an oligomeric association of HEST monomers in the bilayer.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Enhancement of cardiac function by cyclocreatine in models of cardiopulmonary bypass.

This study tests the hypothesis that the administration of cyclocreatine prior to global ischemia enhances recovery of cardiac function during reperfusion. Two models were used. First, in a Langendorff-working heart model of normothermic cardioplegic arrest, rats (n = 6 per group) were injected intravenously with saline or cyclocreatine (600, 300, or 150 mg/kg). After 30 min or 2 h, hearts were excised and perfused in the Langendorff mode for 5 min and then in the working heart mode for 20 min. Normothermic arrest was induced by infusing warm St. Thomas solution once; then hearts were kept at 37 degrees C for 40 min. Following arrest, hearts were reperfused in the Langendorff mode for 15 min and then in the working mode for 30 min. Cyclocreatine consistently produced significantly better recovery of aortic flow and cardiac output compared to that of saline hearts. Second, in an intact canine model of cold cardioplegic arrest, adult mongrel dogs (n = 3 to 6 per group) underwent aortic cross-clamping for 1 h, followed by reperfusion on bypass for 45 min and off bypass for 4 h. Dogs were injected intravenously with saline or cyclocreatine (500 mg/kg) for 1 h before experiment. Post-bypass segmental contractility and cardiac output were significantly better in cyclocreatine hearts compared to that of controls. In a limited study, after a 3 h aortic cross-clamp time, cyclocreatine hearts achieved 91% baseline function while control hearts failed after 2 h. Results of this study suggest that cyclocreatine, without inotropic or chronotropic effect, protects the heart from global ischemic injury.

Animals↗
PubMed1994

Distinguishable patterns of protein-DNA interactions involving complexes of basic helix-loop-helix proteins.

Myogenic factors and TAL1 possess distinguishable DNA binding characteristics when they form a complex with basic helix-loop-helix (bHLH) proteins of class A. These characteristics were evident in electrophoretic mobility shift assays showing that complexes of myogenic factors and HTF4 displayed a relatively high affinity for the enhancer in the muscle creatine kinase gene, whereas TAL1 appeared to greatly attenuate the interaction of HTF4 with this enhancer. In addition, by forming a complex with HTF4 in solution, TAL1 could exert a negative effect on the interactions of HTF4 with elements that include E box motifs of microE2 (CAGCTG) and kappa E2/microE5 (CACCTG) type. Similarly, heterodimers containing TAL1 and the DNA binding domain of E47 exhibited a relatively weak affinity for microE2 and kappa E2/microE5 core motifs. The results of both studies invoked the hypothesis that in vivo TAL1 might act as a negative regulator of microE2 and kappa E2/microE5 sequence motifs by forming a complex with the products of the E2A and HTF4 genes. Support for this hypothesis was obtained by transient expression analyses where TAL1 was found to inhibit the activation effects produced by E2-5 and HTF4a on a reporter gene construct containing repeated microE2 and microE5 motifs, derived from the immunoglobulin gene enhancer.

Amino Acid Sequence↗
PubMed1994

Evidence of cardiac inflammation after open heart operations.

In this study, 6 anesthetized dogs underwent global cardiac arrest for 1 hour, followed by reperfusion on bypass for 45 minutes. The hearts were then weaned off cardiopulmonary bypass and monitored for an additional 2 hours. Using modified Boyden chambers, high levels of neutrophil chemotactic activity were detected (using a checkerboard analysis) in the coronary sinus effluents obtained during cardiac arrest. The activity tended to decline during reperfusion. Assay of myeloperoxidase (a marker for neutrophils) revealed an accumulation of large numbers of neutrophils in the right (14 +/- 1.1 x 10(4) cells/g wet weight) and left (16 +/- 1 x 10(4) cells/g wet weight) ventricles after 2 hours of reperfusion. Light microscopy evaluation confirmed the presence of neutrophils, not only in the ventricles, but also in a greater number in the right and left atria. Electron microscopy study of these hearts revealed the presence of mild reversible changes, indicating good preservation of the hearts during arrest. Results of this study provide evidence for an acute inflammatory reaction that takes place after cardiac operations and suggest a role for myocardial tissues in the initiation of such a response through their release of neutrophil chemotactic factors.

Animals↗
PubMed1994

Preventing AIDS: knowledge, attitudes, and practices.

1. Because health care providers are the key professionals in advising patients about prevention and treatment of HIV/AIDS, the degree to which spread can be prevented is at least partially a function of preventive and education measures taken by health care professionals. 2. Nurses surveyed believe that they do not have the right to refuse treatment to patients infected with HIV. 3. Twenty percent of health care professionals indicated they did not have adequate information concerning HIV, with the largest group being nurse executives in long-term care facilities. 4. The survey indicated that more efficient and effective educational methods should be used to increase health care practitioners' knowledge about AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Halogen-substituted trimetoquinol analogs as thromboxane A2 receptor antagonists in platelets and aorta.

Trimetoquinol (TMQ) is a non-prostanoid compound that blocks prostaglandin H2/thromboxane A2 (TXA2) receptor-mediated responses initiated by a prostaglandin (PG) H2 analog, U46619, in human platelets and rat aorta. Ring fluorine-substituted TMQ analogs selectively antagonized PG-dependent human platelet activation induced by U46619, arachidonic acid, collagen, ADP or epinephrine; and were about 300-fold less potent as inhibitors of PG-independent responses mediated by thrombin or bacterial phospholipase C. For each inducer of the PG-dependent pathway, the rank order of inhibitory potency was identical (TMQ > 8-fluoro-TMQ > 5-fluoro- TMQ). Iodine substitution yielded a similar rank order of antagonism against U46619-induced platelet activation (TMQ > 8-iodo-TMQ > 5-iodo-TMQ), and all TMQ analogs inhibited platelet aggregation in whole blood as well as in platelet-rich plasma. Inhibition of specific [3H]SQ 29,548 binding by TMQ analogs was highly correlated with inhibition of functional responses to U46619. Radioligand binding experiments using TMQ analogs with rat platelets showed no interspecies difference in comparison with human platelets. The rank order of inhibitory potencies for the fluorinated (but not iodinated) TMQ analogs changed in rat thoracic aorta with 8-fluoro-TMQ > TMQ > or = 5-fluoro-TMQ as antagonists of U46619-induced vascular contraction. These findings demonstrate that the primary mechanism of antiplatelet action of TMQ analogs is related to a blockade of TXA2 receptor sites, and ring-halogenated TMQ analogs distinguish between TXA2-mediated functional responses in vascular smooth muscle and platelets.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

A comprehensive assessment plan for professional preparation programs in health education at Eastern Illinois University.

Federal- and state-mandated criteria for accountability have promoted an "assessment movement" in higher education. The federal focus caused higher education's regional accrediting bodies to place greater emphasis on assessment for institutional accountability. Numerous approaches have been identified for the assessment process including comprehensive examinations, evaluation by alumni and internship preceptors, and self-report data by students. The Role Delineation Project Curriculum Framework also has been useful in assessing curricula. Strategies used in a comprehensive assessment plan for the Health Studies Dept. at Eastern Illinois University include focus group interviews, Departmental Advisory Council review, and assessment by internship preceptors. Data indicate the professional preparation program adequately prepares students in Responsibilities I, II, III, IV, and VII. Further consideration will be given to revising the curriculum to include material to prepare students in competencies required for Responsibilities V and VI.

Accreditation↗
PubMed1992

Synthesis of halogenated trimetoquinol derivatives and evaluation of their beta-agonist and thromboxane A2 (TXA2) antagonist activities.

The 5,8-difluoro (4), 5-iodo (5), 8-iodo (6), and 5-trifluoromethyl (7) derivatives of trimetoquinol (TMQ, 1) have been synthesized and evaluated for their ability to stimulate beta 1 (guinea pig atria) and beta 2 (guinea pig trachea) adrenoceptors as well as for their inhibitory activity against U46619 [a thromboxane A2 (TXA2) mimetic]-mediated contraction of rat thoracic aorta and human platelet aggregation. Both 5 and 6 were considerably less active than TMQ on both beta-adrenergic systems and gave a rank order of stimulatory potency of 1 much greater than 6 greater than or equal to 5. Similarly, iodine substitution at either position also caused a reduction in TXA2 antagonist activity with a rank order potency of 1 greater than 6 much greater than 5. Compared to 1, however, 5-iodo-TMQ (5) showed a marked selectivity for blockade of U46619 responses in rat aorta over human platelets. On beta-systems, 4 had reduced potency compared to TMQ and was similarly nonselective. Introduction of a trifluoromethyl group at the 5-position of TMQ completely abolished both beta 1- and beta 2-adrenergic agonist activities while imparting weak antagonist activity on beta 1 receptors. On TXA2 systems, both 4 and 7 possessed significantly decreased inhibitory activity compared to TMQ. The synthetic approaches to the synthesis of 8-(trifluoromethyl)-TMQ (8) are also described. The enantiomers of the 8-fluoro derivative (3) of TMQ were separated on a preparative Chiralcel OD column and evaluated on beta-adrenergic systems and TXA2 systems. On beta-adrenergic systems, (S)-(+)-8-fluoro-TMQ was at least 10-fold more potent than (R)-(-)-8-fluoro-TMQ. Conversely, (R)-(-)-8-fluoro-TMQ was approximately 14-fold more potent as an antagonist of TXA2-mediated aggregation in human platelets than (S)-(+)-8-fluoro-TMQ. In contrast to platelets, (S)-(+)-8-fluoro-TMQ was an agonist in rat aorta whereas (R)-(-)-8-fluoro-TMQ was an antagonist.

Adrenergic beta-Agonists↗
PubMed1992

Handedness in childhood autism shows a dissociation of skill and preference.

Hand preference and hand skill were assessed in 20 children with autism, 20 normal controls and 12 children with mental retardation. 90% of the normal controls and 92% of the children with mental retardation showed concordance for hand preference and hand skill (i.e. the preferred hand was also the more skillful), whereas only 50% of the children with autism showed concordance of preference and skill, the remaining 50% preferring to use the hand which was less skillful. Children with autism also showed a lesser degree of handedness and a lesser degree of consistency than the other groups, although this was unrelated to the discordance of skill and asymmetry. A developmental model of handedness is proposed in which the development of handedness as preference is ontogenetically prior to the development of handedness as skill asymmetry, such that in normal children the development of skill asymmetry occurs as a secondary consequence of the establishment of preference. The causal sequence is disrupted in autism, so that although preference is established, it does not subsequently result in concordant skill asymmetry.

Autistic Disorder↗