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Biomedical subjects

C A Reilly

Publications and source records attributed to C A Reilly.

At least 19 recordsLinked to original sources

Determination of capsaicin, dihydrocapsaicin, and nonivamide in self-defense weapons by liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry.

Sensitive and selective liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods for the analysis of capsaicin, dihydrocapsaicin, and nonivamide in pepper spray products have been developed. Chromatographic separation of the capsaicinoid analogues was achieved using a reversed-phase HPLC column and a stepwise gradient of methanol and distilled water containing 0.1% (v/v) formic acid. Identification and quantification of the capsaicinoids was achieved by electrospray ionization single-stage mass spectrometry monitoring the protonated molecules of the internal standard (m/z 280), capsaicin (m/z 306), dihydrocapsaicin (m/z 308), and nonivamide (m/z 294) or by tandem mass spectrometry monitoring the appropriate precursor-to-product-ion transitions. The plot of concentration versus peak area ratio was linear over the range of 10-750 ng/ml using LC-MS and 10-500 ng/ml using LC-MS-MS. However, to accurately quantify the capsaicinoids in the pepper spray products calibration curves between 10 and 1000 ng were constructed and fit using a weighted quadratic equation. Using the quadratic curve, the accuracy of the assay ranged from 91 to 102% for all analytes. The intra-assay precision (RSD) for capsaicin was 2% at 25 ng/ml, 10% at 500 ng/ml, and 3% at 800 ng/ml. The inter-assay precision (RSD) for capsaicin was 6% at 25 ng/ml, 6% at 500 ng/ml, and 9% at 800 ng/ml. Similar values for inter- and intra-assay precision were experimentally obtained for both dihydrocapsaicin and nonivamide. The analysis of selected pepper spray products demonstrated that the capsaicinoid concentration in the products ranged from 0.7 to 40.5 microg/microl.

Capsaicin↗

Quantitative analysis of capsaicinoids in fresh peppers, oleoresin capsicum and pepper spray products.

Liquid chromatography-mass spectrometry was used to identify and quantify the predominant capsaicinoid analogues in extracts of fresh peppers, in oleoresin capsicum, and pepper sprays. The concentration of capsaicinoids in fresh peppers was variable. Variability was dependent upon the relative pungency of the pepper type and geographical origin of the pepper. Nonivamide was conclusively identified in the extracts of fresh peppers, despite numerous reports that nonivamide was not a natural product. In the oleoresin capsicum samples, the pungency was proportional to the total concentration of capsaicinoids and was related by a factor of approximately 15,000 Scoville Heat Units (SHU)/microg of total capsaicinoids. The principle analogues detected in oleoresin capsicum were capsaicin and dihydrocapsaicin and appeared to be the analogues primarily responsible for the pungency of the sample. The analysis of selected samples of commercially available pepper spray products also demonstrated variability in the capsaicinoid concentrations. Variability was observed among products obtained from different manufacturers as well as from different product lots from the same manufacturer. These data indicate that commercial pepper products are not standardized for capsaicinoid content even though they are classified by SHU. Variability in the capsaicinoid concentrations in oleoresin capsicum-based self-defense weapons could alter potency and ultimately jeopardize the safety and health of users and assailants.

Capsaicin↗

Requirements development for a patient computing system.

Critical parts of the software development life cycle are concerned with eliciting, understanding, and managing requirements. Though the literature on this subject dates back for several decades, practicing effective requirements development remains a current and challenging area. Some projects flourish with a requirements development process (RDP) that is implicit and informal, but this approach may be overly risky, particularly for large projects that involve multiple individuals, groups, and systems over time. At Partners HealthCare System in Boston, Massachusetts, we have applied a more formal approach for requirements development to the Patient Computing Project. The goal of the project is to create web-based software that connects patients electronically with their physician's offices and has the potential to improve care efficiency and quality. It is a large project, with over 500 function points. Like most technological innovation, the successful introduction of this system requires as much attention to understanding the business needs and workflow details as it does to technical design and implementation. This paper describes our RDP approach, and key business requirements discovered through this process. We believe that a formal RDP is essential, and that informatics as a field must include proficiencies in this area.

Boston↗

A knowledge-based patient assessment system: conceptual and technical design.

This paper describes the design of an inpatient patient assessment application that captures nursing assessment data using a wireless laptop computer. The primary aim of this system is to capture structured information for facilitating decision support and quality monitoring. The system also aims to improve efficiency of recording patient assessments, reduce costs, and improve discharge planning and early identification of patient learning needs. Object-oriented methods were used to elicit functional requirements and to model the proposed system. A tools-based development approach is being used to facilitate rapid development and easy modification of assessment items and rules for decision support. Criteria for evaluation include perceived utility by clinician users, validity of decision support rules, time spent recording assessments, and perceived utility of aggregate reports for quality monitoring.

Artificial Intelligence↗

Examining the symptom experience of hospitalized patients using a pen-based computer.

The purposes of this study were to test the feasibility of using a pen-based computer to capture self-reported symptom data, to evaluate the system, and to evaluate the importance of obtaining symptom data. The sample included 72 patients who were hospitalized for a variety of medical conditions. Self-reported symptom data was obtained with the automated Sign and Symptom Checklist. The feasibility of using an automated symptom checklist to capture self-reported symptom data was demonstrated. Patients' evaluations of the ease of use and the format of the system were primarily positive; mean ratings ranged from 4.58 to 4.70 on a 5-point scale. Patients indicated the importance of documenting symptoms, with a few suggesting that the use of an automated symptom checklist may increase communication between providers and patients. Study findings support the inclusion of self-reported symptom data in electronic health records and national health care databases.

Attitude to Computers↗

Iron loading into ferritin by an intracellular ferroxidase.

An intracellular, membrane-bound enzyme exhibiting both p-phenylenediamine oxidase activity and ferrous iron oxidase activity was isolated with the plasma membrane fraction of horse heart and studied for its ability to load iron into ferritin. The ferroxidase activity of the tissue oxidase was stimulated approximately twofold by horse spleen apoferritin, and the iron was loaded into ferritin. The loading of iron into ferritin by the tissue oxidase was inhibited by anti-horse serum ceruloplasmin antibody. The stoichiometry of iron oxidation and oxygen consumption during iron loading into ferritin by the tissue-derived oxidase and serum ceruloplasmin were 3.6 +/- 0.2 and 3.9 +/- 0.2, respectively. These data provide evidence that an enzyme analogous to ceruloplasmin is present on the plasma membrane of horse heart and that this ferroxidase is capable of catalyzing the loading of iron into ferritin. The implications of these data on the present models for the uptake and storage of iron by cells are discussed.

Animals↗

Evidence for a protein-protein complex during iron loading into ferritin by ceruloplasmin.

The formation of a protein-protein complex for the loading of iron into ferritin by ceruloplasmin was investigated. Ferritin stimulated the ferroxidase activity of ceruloplasmin unless the ferritin was fully loaded, in which case it inhibited the ferroxidase activity of ceruloplasmin. The apparent association constant for the interaction of ferritin and ceruloplasmin was 24 nM. Isothermal titration calorimetry indicated that the interaction of ceruloplasmin and ferritin was endothermic, driven by positive changes in entropy. The association constants for complex formation between ferritin and ceruloplasmin were 4.5 +/- 0.7 x 10(5) and 9.5 +/- 0.3 x 10(4) M-1 for the reduced and oxidized forms of ceruloplasmin, respectively. The oxidized form of ceruloplasmin was retained on an affinity column with ferritin immobilized as the ligand and remained bound to the column with mobile phases of increased hydrophobicity, but was eluted with increased ionic strength. The ability of ceruloplasmin to remain bound to the affinity resin was affected by the species from which ceruloplasmin was isolated. Gradient ultracentrifugation also provided evidence that the two proteins were associated, since ferritin promoted migration of ceruloplasmin through the gradient. Including ferrous iron in the gradient resulted in reduction of ceruloplasmin and increased the mobility of ceruloplasmin with ferritin. These data provide evidence that ferritin and ceruloplasmin form a protein-protein complex during iron loading into ferritin, which may limit redox cycling of iron in vivo.

Animals↗

Stimulation of the ferroxidase activity of ceruloplasmin during iron loading into ferritin.

Ceruloplasmin purified from horse serum was rapidly reduced upon addition of increasing equivalents of ferrous iron, generating an electronically and conformationally distinct form. This form of ceruloplasmin was characterized by significant (80%) loss of EPR detectable type I and type II copper(II), complete loss of visible absorbance at 610 nm, as well as decreased hydrophobic surface area. The reduced form of ceruloplasmin slowly reduced molecular oxygen to complete its catalytic cycle. The presence of varied concentrations of apoferritin, but not apotransferrin, significantly enhanced the rate of ceruloplasmin oxidation. The magnitude of this stimulatory effect increased as the molar ratio of ceruloplasmin to apoferritin approached 1.0, shown previously to be the optimum ratio for loading iron into ferritin. The rate of ferrous iron oxidation by ceruloplasmin was significantly stimulated by the presence of apoferritin; however, apotransferrin had no effect. The length of time required for ceruloplasmin to oxidize all the iron and return to the native form of the enzyme was also affected by the concentration of iron. In addition, the rate of iron loading into ferritin was dependent upon ferrous iron concentration. These results provide evidence for the formation of a specific complex between the reduced form of ceruloplasmin and apoferritin and that reduction of ceruloplasmin by ferrous iron may be the signal for complex formation.

Animals↗

Peroxidase substrates stimulate the oxidation of hydralazine to metabolites which cause single-strand breaks in DNA.

Hydrazines are believed to be oxidized by peroxidases to reactive intermediates responsible for a variety of adverse side effects including cancer and drug-induced lupus. However, hydrazines are regarded as a poor peroxidase substrates because inactivation of the peroxidase occurs during oxidation of these compounds. We have investigated the hypothesis that efficient peroxidase substrates, termed mediators, may stimulate peroxidase-catalyzed oxidation of hydrazines to intermediates capable of causing DNA damage. Oxidation of hydralazine by horseradish peroxidase was stimulated, enzyme inactivation was significantly decreased, and DNA strand breakage was enhanced by the addition of chlorpromazine. Similar results were obtained using other peroxidases, mediators, and hydrazine derivatives. DNA damage required the addition of a minimum of 3 equiv of hydrogen peroxide, suggesting the involvement of a three-electron oxidation product of hydralazine in DNA damage. Efficient substrates may therefore play a critical role in peroxidase-dependent oxidative metabolism and subsequent damage to biological macromolecules by certain chemicals.

DNA Damage↗

Critical care information systems: essential infrastructure for critical care nursing practice.

In the three decades since the installation of the first bedside computer in the "shock ward" at the University of California and Los Angeles County Hospital, both computer technology and critical care practice have evolved rapidly. The premise of this article is that critical care information systems are an essential infrastructure for critical care nursing practice. This premise is described in terms of the critical care environment, clinical decision making in critical care, increasing demands for information about quality and costs, and national initiatives for the sharing of health care information.

Critical Care↗

A comparison of nursing intervention classification and current procedural terminology codes for representing nursing interventions in HIV disease.

The purpose of this study was twofold: 1) to compare the ability of terms from the nursing intervention classification and from the current procedural terminology to represent the clinical terms used by nurses and patients to describe nursing interventions during hospitalization; and 2) to identify the strengths and weaknesses of the two classification systems for representing nursing systems. More NIC than CPT codes matched the concepts in the clinical terms used by nurses and patients to describe nursing interventions demonstrating, not unexpectedly, that NIC represents a broader scope of nursing practice. The major difficulty encountered using NIC was the lack of mutual exclusiveness of the nursing activities within the interventions. CPT codes were easy to apply to the clinical terms, but were limited in scope for nursing practice. The findings of this study demonstrate the necessity of using a nursing-specific classification system for the representation of nursing interventions. This is of particular importance for databases that will be used to examine the effectiveness of healthcare interventions and for databases related to reimbursement for healthcare interventions.

Databases, Factual↗

Capturing patients' perceptions in the computer-based patient record: essential prerequisites to the measurement of health-related outcomes.

The cost, quality, and outcomes of healthcare services have become the focus of national attention as providers, consumers, and payers of healthcare services grapple with healthcare reform in the United States. Given the importance of patient care data to the activities of all segments of the healthcare spectrum, the development and implementation of computer-based patient records (CPRs) has been recommended as CPRs have the potential to improve healthcare delivery, enhance outcomes research programs, and increase hospital efficiency [12]. The current paradigm shift in healthcare requires the active involvement of the patient in the delivery and evaluation of care. The patient must be considered as an essential user of CPRs in order to exploit the benefits of information technology for the purposes of outcome assessment. Research and development of the future CPRs must incorporate the needs of the patient. Systems should be designed to meet these needs in order to capture the patient's perceptions in CPRs.

Medical Records Systems, Computerized↗

The relationship between type of care planning system and patient outcomes in hospitalized AIDS patients.

The purpose of this study was to describe the problems of HIV-infected patients, hospitalized for Pneumocystis carinii pneumonia (PCP), as documented in the nursing care plan and to examine differences in the number and type of activated patient problems and patient outcomes between manually generated, computer-supported, and standardized care planning systems. Of the sample, 22% had no care plan. In the computer-supported care planning system the fewest number of care plans were completed. The total number of problems generated for the 89 patients having care plans was 199. The problems were categorized as PCP-related (37%), AIDS-related (16%), psychosocial (23%), knowledge deficit (14%), and other (10%). There were significant differences among the three groups in the total number of problems, PCP-related problems, and knowledge deficit problems. There were no statistically significant differences in patient outcomes, as measured by HIV-QAM scale scores and patient self-rating of physical condition approximately 1 week after admission, and length of stay among the three care planning systems. Future research is needed to examine the effect of type of care planning system on the quality of patient care.

AIDS-Related Opportunistic Infections↗

Nurses' perspectives on problems of hospitalized PCP patients: implications for the development of a nursing taxonomy.

The phenomena of interest in nursing informatics research are the data, information and knowledge related to nursing. This study presents nurses' perspectives on the problems of patients hospitalized for Pneumocystis carinii pneumonia from four data sources: nurse interview, intershift report, care plan, and nurses' notes. Even within this narrowly specified sample, patient problems showed variation across sources of data. The results of this study demonstrate the difficulties inherent in developing a nursing taxonomy when there is not consensus about the relevant data for nursing within a specific patient sample. Although existing information technology is capable of processing large volumes of nursing data, the lack of a common taxonomy limits the usefulness of the technology for documentation of care and decision support applications.

Acquired Immunodeficiency Syndrome↗

Doppler ultrasound, laser Doppler, and perfusion fluorometry in bowel ischemia.

Improved accuracy and objectivity in the evaluation of intestinal viability has been reported by some investigators using Doppler ultrasound, and more recently laser Doppler velocimetry and perfusion fluorometry. To compare the sensitivity and clinical applicability of these techniques, intestinal viability was evaluated by each method in nine 15- to 50-cm loops of small bowel prepared by division of the mesenteric vasculature in five anesthetized dogs. The sensitivity of Doppler ultrasound was 86%, of laser Doppler flow velocity 85%, of laser Doppler index 94%, and of perfusion fluorometry 95%. Though the sensitivity of Doppler ultrasound is significantly less than that of laser Doppler and perfusion fluorometry, this is not unexpected since the latter two techniques are more quantitative than Doppler ultrasound. Clinically, Doppler ultrasound compares favorably with laser Doppler and perfusion fluorometry, and its low cost and simplicity suggest its adjunctive use in the operative setting.

Animals↗

The use of quantitative perfusion fluorometry to measure relative tumor and liver blood flow after transient microembolization.

Optimal chemotherapy delivery to the tumor depends on regional drug concentration, tumor perfusion, tissue drug uptake, and metabolism. Modulation of tumor blood flow has been used to improve tumor response to treatment. Transient microembolization is one method to alter regional blood flow, but its effects on relative changes in tumor and liver blood flow have not been previously measured. This study used quantitative perfusion fluorometry (QPF) to evaluate blood flow distribution in liver and tumor before and after hepatic arterial infusion of degradable starch microspheres (DSMs) in 10 New Zealand white rabbits. QPF was compared with radioactive xenon-133 washout, an established method for measuring blood flow. Xenon-133 was injected intraparenchymally and the clearance rate was measured allowing calculation of relative blood flow. QPF was then used to measure liver and tumor blood flow in a hepatic VX-2 tumor model after hepatic artery injection of DSMs. Initial tumor blood flow was 55% of liver flow. DSMs produced a significant and transient decrease in hepatic blood flow that was decreased to 40% of baseline after 25 min. Changes in relative hepatic blood flow after DSMs as measured by QPF correlated strongly with results obtained by xenon-133 washout (R = 0.97, P less than 0.01). Fluorometry's simplicity and reliability may be clinically useful to evaluate tumor blood flow characteristics.

Animals↗

Fluorescence assessment of skin perfusion after oral fluorescein.

This study evaluated oral ingestion as the route of fluorescein administration for fluorescence assessment of skin perfusion. In 10 anesthetized rats, dorsal pedicle flaps were raised to produce graded perfusion; then fluorescein (7.5 mg/kg) was administered via an oropharyngeal tube. Quantification of skin fluorescence, performed with the fiberoptic fluorometer 45 minutes after dye ingestion, delineated a significant difference between the perfusion of flap regions that remained viable and those that subsequently became dystrophic (p less than 0.05). The precision was equivalent to that previously reported after intravenous dye. In addition, the gradual delivery of dye after oral administration permitted monitoring of slope of uptake and time to peak. Each of these pharmacokinetic parameters delineated a significant difference between viable and nonviable sections. As measures of relative change in fluorescence, they are independent of skin color and thickness. This feature suggests that the oral route actually may improve the accuracy and reliability of the fluorescein test.

Administration, Oral↗

Phenotypically selective promotion of diethylnitrosamine-initiated altered hepatocyte foci by dietary phenobarbital or a topically applied coal-derived organic mixture in male and female rats.

Relative frequencies of diethylnitrosamine (DEN)-initiated foci of altered hepatocytes appearing in response to promotion by either dietary phenobarbital or a topically applied coal-derived organic mixture (CDM) were investigated in male and female rats. The focus population was examined for two histochemical markers, elevated gamma-glutamyl transpeptidase [GG(+)] and iron exclusion [FE(-)], giving rise to 3 detectable focus phenotypes, i.e., GG(+) foci, FE(-) foci, and GG(+)/(FE(-) foci. Frequencies of the 3 phenotypes were quantitated through the use of serial frozen sectioning and computer-assisted image analysis. In agreement with our prior observations, cutaneous exposure to CDM or dietary phenobarbital promoted the expression of DEN-initiated foci. However, the current data showed that this promoting effect of CDM occurred only in females and was restricted to foci with the GG(+)/FE(-) phenotype. Dietary phenobarbital, on the other hand, promoted both the GG(+) and GG(+)/FE(-) phenotypes and was effective in both males and females, although a sex-related differential in the promoting efficiency of phenobarbital was also observed. The pronounced heterogeneity in the responses of the 3 focus phenotypes suggests that each phenotype is the consequence of a specific type of genomic alteration with a specific capacity to undergo phenotypic expression in response to a given promoting stimulus.

Administration, Topical↗