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Biomedical subjects

Elizabeth White

Publications and source records attributed to Elizabeth White.

10 recordsLinked to original sources
PubMed2006

Highly attenuated smallpox vaccine protects rabbits and mice against pathogenic orthopoxvirus challenge.

The possible reemergence of smallpox through bioterrorism requires the preparation of adequate stockpiles of vaccine. Dryvax, the only US-licensed vaccinia virus smallpox vaccine, has an unacceptable safety profile in the pre-event setting. LC16m8 is a Japanese-licensed attenuated vaccinia virus strain that has been safely used in over 50,000 persons. Until now, efficacy of this vaccine was unproven. Using two animal models, we show that LC16m8 and Dryvax elicit comparable humoral immune responses after a single vaccination and equivalently protect against lethal poxvirus disease. Thus, LC16m8 shows promise as a safe and effective smallpox vaccine with the potential for replacing Dryvax.

Animals↗
PubMed2006

Morphologic, immunologic, and molecular methods to detect bacillus anthracis in formalin-fixed tissues.

Due to the importance of Bacillus anthracis as a cause of naturally occurring infection among humans and as an agent of bioterrorism, there is a vital need for rapid and specific assays, including immunohistochemistry (IHC) and polymerase chain reaction (PCR) assays, to detect the bacterium in formalin-fixed tissues. Colorimetric IHC assays were developed using a multistep indirect immunoalkaline phosphatase method with anti-B. anthracis cell wall (EAII-6G6-2-3) and anti-B. anthracis capsule (FDF-1B9) mAbs to detect B. anthracis antigens in formalin-fixed, paraffin-embedded bacterial cultures and tissues. B. anthracis antigens were localized, using both antibodies, in samples from B. anthracis-infected animals and humans. The colorimetric IHC assay with both antibodies was expedient in diagnosing the presence of B. anthracis in formalin-fixed, paraffin-embedded tissue from bioterrorism-associated cases of inhalational and cutaneous anthrax and from a case of naturally occurring cutaneous anthrax. Using the same antibodies, confocal microscopy demonstrated the structure of replicating B. anthracis in tissues. B. anthracis-specific primers were successfully used with PCR to amplify and detect B. anthracis sequences derived from formalin-fixed tissues of anthrax cases. In this study, morphologic, immunologic, and molecular assays were used to study and diagnose 22 veterinary and human anthrax cases.

Animals↗
PubMed2006

Efficient on-line setup correction strategies using plan-intent functions.

With the introduction of image-guided radiation therapy (IGRT) delivery systems on-line set-up correction strategies have gained in popularity. Usually, the correction workload of these strategies is high compared to off-line strategies as daily setup corrections have to be performed based on a predefined action level. In this work, it is proposed that on-line strategies must not only be judged in terms of workload but also in terms of efficacy. While workload can be easily predicted for such strategies, the efficacy must ultimately reflect the efficiency with which the original treatment plan intent is met. The purpose of this work is to investigate the tradeoff between workload and efficacy of three different on-line set-up correction strategies: The common fixed action level strategy and two novel on-line setup correction strategies, i.e., a dose-volume histogram (DVH) constraint and an equivalent uniform dose (EUD) score strategy that aim directly for better compliance with original treatment plan intent. All strategies were reformulated in terms of a score function that reflected treatment plan intent. A retrospective study was conducted on 5 prostate patients (7-field conformal, 79.8 Gy, 42 fractions). PTV margins were 10 mm except in the posterior direction (7 mm). The original treatment plan intent for these patients was defined using a set of DVH constraints. The results show that the on-line setup correction strategy based on a fixed action level of 3 mm resulted in a considerable correction workload. For larger action levels, a dose benefit (in terms of EUD) in the rectum and bladder was observed for all patients which is clinically "fortuitous" but difficult to take advantage of. In contrast, the application of the two novel strategies generally resulted in a controlled decrease of the dose to the rectum and the bladder with a smaller workload. It is concluded that using information about target anatomy and the planned dose distribution allows the design of specific correction strategies that are better tailored to the individual patient and that comply effectively with initial treatment plan intent.

Artifacts↗
PubMed2005

Telomestatin and diseleno sapphyrin bind selectively to two different forms of the human telomeric G-quadruplex structure.

The human telomeric sequence d[T(2)AG(3)](4) has been demonstrated to form different types of G-quadruplex structures, depending upon the incubation conditions. For example, in sodium (Na(+)), a basket-type G-quadruplex structure is formed. In this investigation, using circular dichroism (CD), biosensor-surface plasmon resonance (SPR), and a polymerase stop assay, we have examined how the addition of different G-quadruplex-binding ligands affects the conformation of the telomeric G-quadruplex found in solution. The results show that while telomestatin binds preferentially to the basket-type G-quadruplex structure with a 2:1 stoichiometry, 5,10,15,20-[tetra-(N-methyl-3-pyridyl)]-26-28-diselena sapphyrin chloride (Se2SAP) binds to a different form with a 1:1 stoichiometry in potassium (K(+)). CD studies suggest that Se2SAP binds to a hybrid G-quadruplex that has strong parallel and antiparallel characteristics, suggestive of a structure containing both propeller and lateral, or edgewise, loops. Telomestatin is unique in that it can induce the formation of the basket-type G-quadruplex from a random coil human telomeric oligonucleotide, even in the absence of added monovalent cations such as K(+) or Na(+). In contrast, in the presence of K(+), Se2SAP was found to convert the preformed basket G-quadruplex to the hybrid structure. The significance of these results is that the presence of different ligands can determine the type of telomeric G-quadruplex structures formed in solution. Thus, the biochemical and biological consequences of binding of ligands to G-quadruplex structures found in telomeres and promoter regions of certain important oncogenes go beyond mere stabilization of these structures.

Binding Sites↗
PubMed2005

Design and synthesis of an expanded porphyrin that has selectivity for the c-MYC G-quadruplex structure.

Cationic porphyrins are known to bind to and stabilize different types of G-quadruplexes. Recent studies have shown the biological relevance of the intramolecular parallel G-quadruplex as a transcriptional silencer in the c-MYC promoter. TMPyP4 also binds to this G-quadruplex and most likely converts it to a mixed parallel/antiparallel G-quadruplex with two external lateral loops and one internal propeller loop, suppressing c-MYC transcriptional activation. To achieve therapeutic selectivity by targeting G-quadruplexes, it is necessary to synthesize drugs that can differentiate among the different types of G-quadruplexes. We have designed and synthesized a core-modified expanded porphyrin analogue, 5,10,15,20-[tetra(N-methyl-3-pyridyl)]-26,28-diselenasapphyrin chloride (Se2SAP). Se2SAP converts the parallel c-MYC G-quadruplex into a mixed parallel/antiparallel G-quadruplex with one external lateral loop and two internal propeller loops, resulting in strong and selective binding to this G-quadruplex. A Taq polymerase stop assay was used to evaluate the binding of TMPyP4 and Se2SAP to G-quadruplex DNA. Compared to TMPyP4, Se2SAP shows a greater selectivity for and a 40-fold increase in stabilization of the single lateral-loop hybrid. Surface plasmon resonance and competition experiments with duplex DNA and other G-quadruplexes further confirmed the selectivity of Se2SAP for the c-MYC G-quadruplex. Significantly, Se2SAP was found to be less photoactive and noncytotoxic in comparison to TMPyP4. From this study, we have identified an expanded porphyrin that selectively binds with the c-MYC G-quadruplex in the presence of duplex DNA and other G-quadruplexes.

Binding, Competitive↗
PubMed2003

Short peritoneal equilibration test: impact of preceding dwell time.

In the original peritoneal equilibration test (PET), which established standard values for membrane categorization in 1987, the dwell time of the preceding exchange was approximately 8 hours. Basing the test on an 8-hour prior exchange was convenient when almost all patients were on continuous ambulatory peritoneal dialysis (CAPD); however, many patients are now on some form of automated peritoneal dialysis (PD), and an 8-hour exchange before the PET requires a change in the dialysis schedule. Our goal in the present study was to determine whether the dialysate-to-plasma ratio (D/P) of solutes and the final dialysate to initial dialysate ratio (D/D0) of glucose in the short PET (2-hour equilibration time) are similar whether a 3-hour exchange or an 8-hour exchange precedes the test. The PETs were performed in 9 stable PD patients using 2 L of 2.5% dextrose dialysis solution (Baxter Healthcare, Deerfield, IL, U.S.A.). Before the equilibration exchange, the patients were on a randomly selected long (approximately 8-hour) or short (3-hour) dwell. During the equilibration exchange, dialysate samples were collected at 0.30, and 60 minutes of dwell time and from the drain bag (120-minute sample). Within a week, the PET was repeated in each patient after the alternate-length exchange. The values for D/P creatinine and urea and for D/D0 glucose were almost identical throughout the 2-hour PET after either the long or the short exchange. The D/P protein values tended to be higher in the PET after the long exchange. The short PET can be used for clinical purposes, and the creatinine and glucose results can be used for membrane categorization. Any dwell time between 3 and 12 hours is acceptable for the preceding exchange, and the equilibration test may be performed with either a 2-hour or a 4-hour dwell. The protein values obtained after a 3-hour prior dwell differ from those obtained after a long prior dwell. Protein values must therefore be standardized in a larger number of patients.

Creatinine↗
PubMed2002

Developing a quality measurement tool and reporting format for long- term care.

BACKGROUND: Quality measurement in long term care (LTC) presents many challenges: the lack of a uniform definition of quality, the existence of multiple domains for measurement, a multitude of potential perspectives, and regulatory influences that emphasize measurement only of poor quality. Research efforts have yet to solve the issues of measurement; however, operators of long term care facilities must use the current state of the art in quality measurement as the basis for their quality improvement efforts. A project was commissioned by management of a large integrated delivery system with a robust network of LTC facilities who wished to implement a continuous quality improvement process on the basis of a measurement tool that provides a comprehensive resident-centered assessment of quality. The objectives of this project, therefore, were to identify domains of quality, to select and adapt validated instruments for measurement within each domain, to pilot test a data collection process, and to develop an operational quality profiling report format for LTC facilities. DESIGN AND METHODS: Using an expert panel and the LTC research literature, an operational measurement tool was developed, consisting of four domains of quality: organizational, clinical, environmental, and social. DISCUSSION: A pilot study conducted in two nursing facilities demonstrated that the data collection process could be operationalized within tight resource and budgetary constraints. The development of an operational quality assessment tool enables management to take a consistent view of diverse institutions, focusing in detail on quality of care as it is perceived by residents. The tool allows evaluation of trends over time and comparison to external norms.

Advisory Committees↗
PubMed2002

Evaluating consumer satisfaction in residential continuing care settings.

The outcome of the project reported on here is a client-centered consumer satisfaction questionnaire designed to evaluate new models of residential continuing care in Alberta, Canada. Satisfaction is defined as a multi-dimensional construct that is grounded in the consumer's experience. Consultation with the clients of the services during development of the instrument ensured that characteristics important to the clients were assessed. The result is an instrument with which to measure satisfaction that is fully client-centered and that, with appropriate modifications, can be used to monitor any client-centered program for cognitively-able continuing care clients.

Aged↗
PubMedDate not supplied

A randomized control trial of nursing-based case management for patients with chronic obstructive pulmonary disease.

This study assessed the impact of a randomized trial of nursing-based case management for patients with chronic obstructive pulmonary disease, their caregivers, and nursing and medical staff. Sixty-six patients were matched by FEV on admission to hospital, and randomized into an intervention or control group. Intervention group patients reported significantly less anxiety at 1 month postdischarge; however, this effect was not sustained. There was little difference between groups in terms of unplanned readmissions, depression, symptoms, support, and subjective well being. Interviews with patients and caregivers found that the case management improved access to resources and staff-patient communication. Interviews with nursing and medical staff found that case management improved communication between staff and enhanced patient care.(1)

Adult↗