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Biomedical subjects

M Ryan

Publications and source records attributed to M Ryan.

At least 73 records · Page 4Linked to original sources

Applications of computer-aided learning in biomedical sciences: considerations in design and evaluation.

Multimedia computer-aided learning (CAL) is an area that has become increasingly prevalent in biomedical science. Here we describe the advances that have taken place in the computing industry that have led to this trend. We also outline areas within the subject of biomedical science that can most benefit from using multimedia CAL as a teaching aid. Furthermore, issues concerning the design of CAL (i.e. iterative design, structure, development tools) are discussed. As the evaluation of CAL is an essential part of the iterative design process, we look at new approaches to evaluation that have emerged in response to the superficial focus on usability that many evaluations take.

Computer-Assisted Instruction↗

The Naval Health Research Center Respiratory Disease Laboratory.

Concern about emerging and reemerging respiratory pathogens prompted the development of a respiratory disease reference laboratory at the Naval Health Research Center. Professionals working in this laboratory have instituted population-based surveillance for pathogens that affect military trainees and responded to threats of increased respiratory disease among high-risk military groups. Capabilities of this laboratory that are unique within the Department of Defense include adenovirus testing by viral shell culture and microneutralization serotyping, influenza culture and hemagglutination inhibition serotyping, and other special testing for Streptococcus pneumoniae, Streptococcus pyogenes, Mycoplasma pneumonia, and Chlamydia pneumoniae. Projected capabilities of this laboratory include more advanced testing for these pathogens and testing for other emerging pathogens, including Bordetella pertussis, Legionella pneumoniae, and Haemophilus influenzae type B. Such capabilities make the laboratory a valuable resource for military public health.

Clinical Laboratory Techniques↗

Bacterial phosphatidylinositol-specific phospholipase C: structure, function, and interaction with lipids.

The bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) is a small, water-soluble enzyme that cleaves the natural membrane lipids PI, lyso-PI, and glycosyl-PI. The crystal structure, NMR and enzymatic mechanism of bacterial PI-PLCs are reviewed. These enzymes consist of a single domain folded as a (betaalpha)(8)-barrel (TIM barrel), are calcium-independent, and interact weakly with membranes. Sequence similarity among PI-PLCs from different bacterial species is extensive, and includes the residues involved in catalysis. Bacterial PI-PLCs are structurally similar to the catalytic domain of mammalian PI-PLCs. Comparative studies of both prokaryotic and eukaryotic isozymes have proved useful for the identification of distinct regions of the proteins that are structurally and functionally important.

Bacteria↗

Preventing stroke in patients with transient ischemic attacks.

Stroke is the third most common overall cause of death and the leading cause of adult disability in the United States. New therapeutic interventions instituted in the period immediately after a stroke have revolutionized the approach to ischemic cerebrovascular disease. Recognition of a transient ischemic attack provides an opportunity to prevent a subsequent stroke. Specific stroke prevention treatment depends on the cause of the transient ischemic attack, its cerebrovascular localization and the presence of associated coexisting medical problems. Modification of stroke risk factors is the principal therapeutic approach. Antiplatelet agents and anticoagulants have been shown to be effective in reducing the occurrence of stroke in certain populations. Several well-designed studies have recently demonstrated the effectiveness of carotid endarterectomy in preventing strokes related to extracranial carotid artery disease.

Adult↗

Interaction of sildenafil and indinavir when co-administered to HIV-positive patients.

OBJECTIVES: The prevalence of erectile dysfunction in HIV-infected men is estimated to be 33%. Sildenafil citrate (Viagra; Pfizer Ltd, Sandwich, Kent, UK) is the first oral drug for this condition. Since sildenafil and the protease inhibitors are both metabolized by, and act as inhibitors of cytochrome P450 3A4, we evaluated the pharmacokinetics of the combination sildenafil plus indinavir in HIV-infected patients. DESIGN AND METHODS: Six patients at steady state in treatment with indinavir participated in the study. On the first day blood samples for indinavir assay were drawn at times 0, 1, 2, 3, 4, 6 and 8 h after dosing. On the second study day patients received a single dose of 25 mg of sildenafil in addition to their routine morning medication. Blood samples were taken as described. Separated plasma was stored at -80 degrees C until analysis by high performance liquid chromatography. In a parallel study, the effect of indinavir, ritonavir, saquinavir and nelfinavir on the in vitro hepatic metabolism of sildenafil was assessed. RESULTS: The geometric mean area under the concentration curve for 0-8 h (AUC0-8h) and maximum plasma concentration (Cmax) for indinavir were 19.69 microg/ml h (range, 9.19-31.99 microg/ml h) and 7.02 microg/ml (range, 2.33-16.17 microg/ml), respectively, on the first study day. In the presence of sildenafil, the mean AUC0-8h and Cmax of indinavir were 22.37 microg/ml h [range, 10.08-37.25 microg/ml h; 95% confidence interval (CI) for difference between means, -15 to 13.25) and 9.11 microg/ml (range, 3.41-22.78 microg/ml; 95% CI, -13 to 6.37), respectively. The geometric mean AUC0-8h and Cmax for sildenafil were 1631 ng/ml h (range, 643-2970 ng/ml h) and 384 ng/ml (range, 209-766 ng/ml) respectively. The AUC for sildenafil was 4.4 times higher than data from historical controls given either 50 mg or 100 mg of sildenafil and dose normalized to 25 mg. Indinavir was a potent inhibitor of sildenafil hepatic metabolism in vitro [concentration producing 50% inhibition of control enzyme activity (IC50) = 0.39 +/- 0.17 microM, mean +/- SD]. CONCLUSIONS: Co-administration of sildenafil 25 mg did not significantly alter the plasma indinavir levels. However, plasma sildenafil AUC was markedly increased in the presence of indinavir compared with historical controls. From the in vitro data, the mechanism of increase is indinavir inhibition of the hepatic metabolism of sildenafil. The magnitude of this interaction suggests a lower starting dose of sildenafil may be more appropriate in this clinical setting.

Adult↗

Cryptocyanin, a crustacean molting protein: evolutionary link with arthropod hemocyanins and insect hexamerins.

Cryptocyanin, a copper-free hexameric protein in crab (Cancer magister) hemolymph, has been characterized and the amino acid sequence has been deduced from its cDNA. It is markedly similar in sequence, size, and structure to hemocyanin, the copper-containing oxygen-transport protein found in many arthropods. Cryptocyanin does not bind oxygen, however, and lacks three of the six highly conserved copper-binding histidine residues of hemocyanin. Cryptocyanin has no phenoloxidase activity, although a phenoloxidase is present in the hemolymph. The concentration of cryptocyanin in the hemolymph is closely coordinated with the molt cycle and reaches levels higher than hemocyanin during premolt. Cryptocyanin resembles insect hexamerins in the lack of copper, molt cycle patterns of biosynthesis, and potential contributions to the new exoskeleton. Phylogenetic analysis of sequence similarities between cryptocyanin and other members of the hemocyanin gene family shows that cryptocyanin is closely associated with crustacean hemocyanins and suggests that cryptocyanin arose as a result of a hemocyanin gene duplication. The presence of both hemocyanin and cryptocyanin in one animal provides an example of how insect hexamerins might have evolved from hemocyanin. Our results suggest that multiple members of the hemocyanin gene family-hemocyanin, cryptocyanin, phenoloxidase, and hexamerins-may participate in two vital functions of molting animals, oxygen binding and molting. Cryptocyanin may provide important molecular data to further investigate evolutionary relationships among all molting animals.

Amino Acid Sequence↗

Response-ordering effects: a methodological issue in conjoint analysis.

Conjoint analysis is a technique relatively new to the evaluation of health care services in the UK. The technique uses data generated from questionnaires. This paper addresses the issue of response-ordering effects that may result from the ordering of dimensions of benefit within a question. Two questionnaires were given to 216 hospital consultants as part of a priority setting exercise. These were identical other than the ordering of the dimensions within each question. The regression analysis was segmented according to questionnaire type and the coefficients of the segmentation were tested for statistically significant differences. The results show no evidence of ordering effects.

Health Services Research↗

The European Donor Hospital Education Programme (EDHEP): addressing the training needs of doctors and nurses who break bad news, care for the bereaved, and request donation.

The competence of critical care staff when it comes to death and organ donation can make the difference between a family's agreeing to or refusing the latter. Doctors and nurses often feel uncomfortable approaching relatives about donation and attribute this to a lack of training. Bereaved relatives express dissatisfaction with inappropriate communication and support when brain death is announced and thereafter when a request for donation is made. The European Donor Hospital Education Programme (EDHEP) was designed to meet the training needs of critical care staff in breaking bad news, caring for the bereaved, and requesting donation. EDHEP is a two-part educational package consisting of a presentation about the donor shortage followed by a one-day workshop. The implementation of EDHEP throughout the world has been facilitated through effective national working groups and standardised "train the trainer" courses. Several countries anecdotally report increases in donation following implementation. Controlled evaluation of the effect(s) of EDHEP, which started at the end of 1995, focuses on the satisfaction of the participants with EDHEP, on the competence of the participants in breaking bad news and requesting donation, on the teamwork regarding death and donation, on the satisfaction of bereaved relatives, and on organ donation rates.

Attitude of Health Personnel↗

Transmural myocardial blood flow distribution in hypertrophic cardiomyopathy and effect of treatment.

Verapamil alleviates symptoms in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism of improvement remains speculative. Baseline and dipyridamole myocardial blood flow (MBF) were measured in 15 HCM patients (14 men, 42 +/- 10 years), before and after 4 weeks of verapamil SR 480 mg daily, using 15O labelled water the positron emission tomography (PET). Subendocardial (endo) and subepicardial (epi) MBF was measured in the septum (thickness 25.4 +/- 5.8 mm). Pre-treatment baseline whole heart MBF was 1.02 +/- 0.28 ml/min/g and 1.01 +/- 0.30 ml/min/g on treatment (p = ns). Dipyridamole MBF was 1.39 +/- 0.31 ml/min/g off treatment and 1.23 +/- 0.34 ml/min/g on treatment (p = ns). Coronary flow reserve (dipyridamole/resting MBF) was 1.45 +/- 0.52 and 1.30 +/- 0.51, respectively (p = ns). At baseline, the septal endo/epi MBF ratio was uniform off and on treatment (1.13 +/- 0.18 vs 1.18 +/- 0.21, p = ns). Before treatment, the endo/epi ratio following dipyridamole decreased to 0.93 +/- 0.24 (p < 0.01 vs baseline) and 5/15 (33%) patients had a ratio < 0.8 which would suggest subendocardial underperfusion. During treatment, the endo/epi ratio following dipyridamole was no more different from baseline (1.06 +/- 0.24, p = ns vs baseline) and 2/14 (14%) patients had an endo/epi < 0.8. PET can be successfully used to determine transmural MBF in vivo in patients with hypertrophied ventricles. Despite symptomatic improvement, high dose verapamil therapy does not increase total MBF in patients with HCM but may improve septal transmural MBF distribution during dipyridamole in some patients.

Adult↗

Using conjoint analysis to take account of patient preferences and go beyond health outcomes: an application to in vitro fertilisation.

There has been an assumption in the health economics literature that health outcomes are all that need to be considered when attempting to measure the benefits from health care interventions. This is most evident in the development of the quality adjusted life year (QALY) approach to benefit assessment. This paper challenges this view and considers the technique of conjoint analysis (CA) as a methodology for both taking account of patient preferences and considering attributes beyond health outcomes. The technique is applied to in vitro fertilisation. CA is shown to be sensitive to considering health outcomes, nonhealth outcomes and process attributes. It is also shown to be internally consistent and internally valid. The paper demonstrates the application of CA to estimating willingness to pay indirectly. It is argued that benefit assessment within health economics should extend beyond health outcomes and future research should investigate more thoroughly the potential application of CA in this area. However, methodological issues need addressing before the instrument becomes an established evaluative instrument.

Choice Behavior↗

Use and monitoring of bromides in epilepsy treatment.

Bromides are no longer a mainstay of epilepsy therapy because of the significant toxicity associated with their use and the availability of safer agents. However, bromides occasionally find a niche in the treatment of patients with refractory seizures, particularly in pediatrics. When the decision to utilize this therapy is made, the clinician may be frustrated by the lack of concise, current information regarding bromides. This review provides an update on the mechanism of action, efficacy, pharmacokinetics, dose, and adverse effects of bromides.

Animals↗

Use of the 2A sequence from foot-and-mouth disease virus in the generation of retroviral vectors for gene therapy.

We describe the construction of retroviral plasmid vectors in which two genes are linked by a minimum of 96 nucleotides encoding the 2A sequence from the picornavirus foot-and-mouth disease virus (FMDV). Transcription and translation gives rise to a bicistronic mRNA and two independent protein products. The system offers advantages to other alternative ways to create polycistronic mRNAs and can be used in gene therapy delivery vectors.

3T3 Cells↗

The confirmation and control of metabolic caffeine in standardbred horses after administration of theophylline.

The origin of caffeine detections in equine serum and urine after theophylline administrations was examined. Three different preparations containing theophylline were administered to standardbred mares. Both blood and urine samples were collected. Caffeine was detected and quantified in theophylline administration samples by high performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS-MS). Further in vitro analysis showed that caffeine metabolites were not detected when caffeine, or caffeine-containing products, were added to urine. Data derived from HPLC-UV and LC-MS-MS analysis of dosages of theophylline and caffeine are used to propose the establishment of a threshold limit to control and discern between metabolic and administered caffeine concentrations. A serum caffeine concentration of 250 ng/mL and a urine caffeine concentration of 1000 ng/mL are suggested. Based on the data supplied, these threshold concentrations could effectively control orally administered caffeine in racehorses, up to the dosage used in this work, up to 72 h before sampling time.

Animals↗