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Biomedical subjects

D B Gordon

Publications and source records attributed to D B Gordon.

At least 19 recordsLinked to original sources
PubMed2002

Intact cell mass spectrometry (ICMS) used to type methicillin-resistant Staphylococcus aureus: media effects and inter-laboratory reproducibility.

Intact cell mass spectrometry (ICMS) rapidly analyses the surface composition of microorganisms providing rapid, discriminatory fingerprints for identification and subtyping of important nosocomial pathogens such as methicillin resistant Staphylocccus aureus (MRSA). In this study, ICMS using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI TOF/MS) was assessed for the identification and subtyping of MRSA. An intra- and inter-laboratory reproducibility study was carried out and the effects of culture media (an important source of variation for ICMS) were also studied. Several media used for the cultural identification of MRSA were examined using a panel of well-characterised staphylococcal isolates (n=26). Six MRSA isolates were analysed over a 1-month period for intra-laboratory reproducibility on the same instrument and three different culture media. Spectra were consistent for each isolate between the four experiments on the same culture medium. Individual isolates produced different spectral profiles on different culture media. Spectra from organisms grown on Columbia blood agar contained more peaks (approximately 120) compared to Columbia agar (approximately 50) and methicillin mannitol salt agar (approximately 25). All 26 staphylococcal isolates were subjected to an inter-laboratory study on two MALDI instruments. For each isolate, the overall spectral profile was the same for each of the two instruments but the baseline threshold values was adjusted due to instrument differences in detector sensitivities. Differences between certain regions of the spectra reproducibly identified isolates belonging to the two major MRSA strains (EMRSA phage group 15 and 16). These results demonstrate ICMS with appropriate media selection is a rapid and reproducible technique for identification and discrimination of MRSA.

Culture Media↗
PubMed2001

Exploring the limits of bacterial identification by intact cell-mass spectrometry.

The limits of intact cell-mass spectrometry (ICM-MS) were tested with regard to the minimum number of bacterial cells detectable and its power to discriminate mixed-bacterial cultures. The technique is a surface analysis tool, as is supported by evidence showing that mass fingerprints correspond to material desorbed directly from the cell wall. The brief exposure to solvents, which occurs during sample preparation, does not extract internal cellular material. Spectra were collected over the m/z range of 500 to 10,000. The UV absorbing matrices used were found to be highly specific to bacterial gram type: alpha-cyano-4-hydroxycinnamic acid for gram-negative bacteria and 5-chloro-2-mercaptobenzothiazole for gram-positive bacteria. This specificity allows mixed cultures of different gram types to be differentiated by ICM-MS. The minimum number of cells that could reliably give spectra of sufficient data was 10(4) cells (10(7) cells/mL).

Bacteria↗
PubMed2000

Trading accuracy for speed: A quantitative comparison of search algorithms in protein sequence design.

Finding the minimum energy amino acid side-chain conformation is a fundamental problem in both homology modeling and protein design. To address this issue, numerous computational algorithms have been proposed. However, there have been few quantitative comparisons between methods and there is very little general understanding of the types of problems that are appropriate for each algorithm. Here, we study four common search techniques: Monte Carlo (MC) and Monte Carlo plus quench (MCQ); genetic algorithms (GA); self-consistent mean field (SCMF); and dead-end elimination (DEE). Both SCMF and DEE are deterministic, and if DEE converges, it is guaranteed that its solution is the global minimum energy conformation (GMEC). This provides a means to compare the accuracy of SCMF and the stochastic methods. For the side-chain placement calculations, we find that DEE rapidly converges to the GMEC in all the test cases. The other algorithms converge on significantly incorrect solutions; the average fraction of incorrect rotamers for SCMF is 0.12, GA 0.09, and MCQ 0.05. For the protein design calculations, design positions are progressively added to the side-chain placement calculation until the time required for DEE diverges sharply. As the complexity of the problem increases, the accuracy of each method is determined so that the results can be extrapolated into the region where DEE is no longer tractable. We find that both SCMF and MCQ perform reasonably well on core calculations (fraction amino acids incorrect is SCMF 0.07, MCQ 0.04), but fail considerably on the boundary (SCMF 0.28, MCQ 0.32) and surface calculations (SCMF 0.37, MCQ 0.44).

Algorithms↗
PubMed2000

Designing protein beta-sheet surfaces by Z-score optimization.

Studies of lattice models of proteins have suggested that the appropriate energy expression for protein design may include nonthermodynamic terms to accommodate negative design concerns. One method, developed in lattice model studies, maximizes a quantity known as the " Z-score," which compares the lowest energy sequence whose ground state structure is the target structure to an ensemble of random sequences. Here we show that, in certain circumstances, the technique can be applied to real proteins. The resulting energy expression is used to design the beta-sheet surfaces of two real proteins. We find experimentally that the designed proteins are stable and well folded, and in one case is even more thermostable than the wild type.

Models, Chemical↗
PubMed2000

Effects of ion mode and matrix additives in the identification of bacteria by intact cell mass spectrometry.

Protocols for the identification of bacterial cells by intact cell matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (ICM-TOFMS) are presented. A mass range of 500 to 10,000 m/z is used. The use of formic acid and the crown ether 1, 4, 7, 10, 13, 16-hexaoxacyclooctadecane (18-crown-6) is described. Crown ether is useful for removing metal ion adducts, which degrade spectral purity, and formic acid promotes positive ions, improves spectral signal, and, hence, increases identification certainty.

Bacteria↗
PubMed2000

A quality improvement approach to reducing use of meperidine.

BACKGROUND: In 1991 the University of Wisconsin Hospital and Clinics formed a pain management QI team whose goal was to improve pain management through education, outcome monitoring, and the development of programs intended to improve clinical practice. Longitudinal monitoring mechanisms were established to audit medical records and survey patients to examine both staff practice patterns and patient outcomes. The QI team targeted use of meperidine, one of the most widely used opioid analgesics for the treatment of moderate to severe pain, which is now discouraged as a first-line agent for most painful conditions. IMPLEMENTING THE QI PROCESS: A QI process was implemented using a traditional plan-do-check-act (PDCA) model, resulting in a successful and sustained reduction of inappropriate meperidine use. A cause-and-effect diagram helped highlight the multiple factors contributing to the drug's overuse and was used to prioritize targets for action. A flow chart helped to uncover some of the interrelationships between the myths about meperidine and the resultant customary prescribing and administration practices. While most of the strategies were implemented in 1996 (formulary guideline release, change in stock supply and physician orders, staff education and feedback), a significant impact in practice was not seen until late 1997. Ongoing tracking and feedback loops were established to ensure continued low use of meperidine. CONCLUSION: Use of a QI approach in pain management has been shown to affect the visibility of pain as a clinical priority, enhance interdisciplinary collaboration, facilitate the implementation of clinical guidelines at the bedside, and improve the quality of care for patients.

Analgesics, Opioid↗
PubMed2000

A nurse-run inpatient pain consultation service.

As hospitals across the country work to improve pain management in the face of ever-shrinking resources, one challenge that must be addressed is the delineation of specialized pain management services. Although pain management is an interdisciplinary process, nurses are in a unique position to provide leadership in both the organization and delivery of clinical services. This article describes the development and 2-year experience of a nurse-run inpatient pain management consultation service in an academic tertiary care hospital. The structure of the service, and nature and volume of consults is discussed along with recommendations for institutions considering this strategy.

Adolescent↗
PubMed2000

Rapid discrimination between methicillin-sensitive and methicillin-resistant Staphylococcus aureus by intact cell mass spectrometry.

Rapid, accurate discrimination between methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains is essential for appropriate therapeutic management and timely intervention for infection control. A rapid method involving intact cell mass spectrometry (ICMS) is presented that shows promise for identification, discrimination of MSSA from MRSA and typing. In ICMS, cells from a bacterial colony are emulsified in a chemical matrix, added to a sample slide, dried and analysed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). This technique examines the chemistry of the intact bacterial cell surface, yielding spectra consisting of a series of peaks from 500 to 10000, which represent the mass:charge (m:z) ratios. Each peak corresponds to a molecular fragment released from the cell surface during laser desorption. Specimens can be prepared in a few seconds from plate cultures and a spectrum can be obtained within 2 min. ICMS spectra for 20 staphylococcal isolates showed characteristic peaks, some of which were conserved at species level, some at strain level and some were characteristic of the methicillin susceptibility status of the strain. ICMS may have potential for MRSA identification and typing, and may improve infection control measures.

Cluster Analysis↗
PubMed1999

Branch-and-terminate: a combinatorial optimization algorithm for protein design.

BACKGROUND: Several deterministic and stochastic combinatorial optimization algorithms have been applied to computational protein design and homology modeling. As structural targets increase in size, however, it has become necessary to find more powerful methods to address the increased combinatorial complexity. RESULTS: We present a new deterministic combinatorial search algorithm called 'Branch-and-Terminate' (B&T), which is derived from the Branch-and-Bound search method. The B&T approach is based on the construction of an efficient but very restrictive bounding expression, which is used for the search of a combinatorial tree representing the protein system. The bounding expression is used both to determine the optimal organization of the tree and to perform a highly effective pruning procedure named 'termination'. For some calculations, the B&T method rivals the current deterministic standard, dead-end elimination (DEE), sometimes finding the solution up to 21 times faster. A more significant feature of the B&T algorithm is that it can provide an efficient way to complete the optimization of problems that have been partially reduced by a DEE algorithm. CONCLUSIONS: The B&T algorithm is an effective optimization algorithm when used alone. Moreover, it can increase the problem size limit of amino acid sidechain placement calculations, such as protein design, by completing DEE optimizations that reach a point at which the DEE criteria become inefficient. Together the two algorithms make it possible to find solutions to problems that are intractable by either algorithm alone.

Algorithms↗
PubMed1999

Energy functions for protein design.

Recent successes in protein design have illustrated the promise of computational approaches. These methods rely on energy expressions to evaluate the quality of different amino acid sequences for target protein structures. The force fields optimized for design differ from those typically used in molecular mechanics and molecular dynamics calculations.

Chemical Phenomena↗
PubMed1999

Pain management in the elderly.

Assessment and management of pain are among the skills that perianesthesia nurses need to deliver safe and effective care. The principles of pain management remain fairly consistent across all age groups. However, managing the pain of elderly surgical patients presents unique challenges. Many elderly people have painful chronic conditions. Consequently, during the perioperative period, the nurse must manage both the patient's chronic and acute pain. As a group, the elderly are more vulnerable to inadequate pain assessment and treatment and are more likely to have serious side effects of analgesic therapy. Therefore, this report highlights the unique aspects of pain management in elderly patients.

Age Factors↗
PubMed1999

Build institutional commitment to improving pain management.

In 1997, the University of Wisconsin began working collaboratively with the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) to integrate pain assessment and treatment into the JCAHO standards and accreditation processes. Pain care committees are an effective mechanism for implementing these changes. The authors discuss the critical role nurse managers can play in the development and success of these committees' activities.

Humans↗
PubMed1998

Palliative care: past, present, and future perspectives.

OBJECTIVES: To provide a review of the development and impact of palliative care; to discuss quality of lie as a framework for guiding clinical practice and research in palliative care; and to identify future trends that are likely to affect palliative care services. DATA SOURCES: Research studies, review articles, and book chapters. CONCLUSIONS: Palliative care is in the process of dynamic change. Advocates of palliative care are suggesting that cost-effective holistic care strategies should be available to patients and families throughout the illness trajectory, not just reserved for end of life care. IMPLICATIONS FOR NURSING PRACTICE: Incorporation of palliative care principles across the cancer illness trajectory requires an attitude shift by all members of the multidisciplinary team.

Hospice Care↗
PubMed1997

Automated design of the surface positions of protein helices.

Using a protein design algorithm that quantitatively considers side-chain interactions, the design of surface residues of alpha helices was examined. Three scoring functions were tested: a hydrogen-bond potential, a hydrogen-bond potential in conjunction with a penalty for uncompensated burial of polar hydrogens, and a hydrogen-bond potential in combination with helix propensity. The solvent exposed residues of a homodimeric coiled coil based on GCN4-p1 were designed by using the Dead-End Elimination Theorem to find the optimal amino acid sequence for each scoring function. The corresponding peptides were synthesized and characterized by circular dichroism spectroscopy and size exclusion chromatography. The designed peptides were dimeric and nearly 100% helical at 1 degree C, with melting temperatures from 69-72 degrees C, over 12 degrees C higher than GCN4-p1, whereas a random hydrophilic sequence at the surface positions produced a peptide that melted at 15 degrees C. Analysis of the designed sequences suggests that helix propensity is the key factor in sequence design for surface helical positions.

Algorithms↗
PubMed1997

A role model program to promote institutional changes for management of acute and cancer pain.

This report describes an 18-month project to make acute and cancer pain management an institutional priority in Southeastern Wisconsin health-care facilities. Facility-based teams, each of which included a nurse in a leadership position, were recruited to participate in a project based on the Cancer Pain Role Model Program. The project was conducted in three stages: (a) a 1-day conference focusing on basic pain management issues and clinical standards, (b) a preceptorship at the Medical College of Wisconsin, and (c) a follow-up conference focusing on institutional change. Participants completed an Action Plan, outlining activities aimed at changing practice in their facility. Participants from 17 of the 32 participating facilities partially or completely met their Action Plan goals. Lack of ongoing facility commitment, staff turnover and facility closures were cited as reasons for failure to meet goals. Nurses in key positions, provided with strong institutional commitment and given suitable educational training and nurturing, are ideally suited to help facilitate changes in institutional pain practices.

Acute Disease↗