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Biomedical subjects

D B Gordon

Publications and source records attributed to D B Gordon.

At least 37 records · Page 2Linked to original sources

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↗

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↗

An inhibitor of the sodium pump obtained from human placenta.

BACKGROUND: Much effort has been expended in the search for an endogenous inhibitor of the cellular sodium/potassium pump, a compound of major physiological importance, which has been implicated in the mechanism of essential hypertension. Others have suggested that ouabain or an isomer of ouabain may be the endogenous pump inhibitor. Neonatal cord serum contains an inhibitor of the sodium pump; we attempted to isolate and characterise this substance from human placentas. METHODS: Homogenised placentas were dialysed and the resulting solutes were trapped on octadecylsilyl silica and then separated by high-performance liquid chromatography. Measurement of the activity of the sodium pump of human leucocytes was used to test each fraction for the presence of the inhibitor. FINDINGS: An inhibitor of the sodium pump was obtained by this technique in a mass spectrometrically pure form with a mass of 370 Da, an empirical formula of C24H34O3 and only one hydroxyl group. The characteristic fragmentation pattern observed in negative-ion mass spectrometry was compared with those of various model compounds; this comparison suggested that the active material was a dihydropyrone-substituted steroid. INTERPRETATION: These results suggest that a dihydropyrone-substituted steroid is an endogenous regulator of the sodium pump in humans and, presumably, other mammals. Proof of the endogenous origin will require the demonstration of a previously unrecognised biosynthetic pathway.

Bufanolides↗

Critical pathways: a road to institutionalizing pain management.

Effective strategies to increase the visibility of pain and the accountability of health-care professionals for the treatment of pain are needed to improve the quality of pain management. Critical pathways are tools used to plan and document care for patients within a system of case management. Case management models of care focus on decreased cost, better coordination of services, and improved patient outcomes. This article describes how critical pathways are being used in one setting within a system of case management to help increase awareness of pain as a problem and to institutionalize pain management. As institutions seek to implement outcome-based practice systems, many are turning to the critical pathway to influence practice patterns. Critical pathways provide the vehicle to articulate and implement a standard for quality pain management and a mechanism to analyze persistent failures in achieving desired outcomes of care. Using pathways to track and monitor care promises to uncover clinical barriers to pain management and provide an impetus to increase clinician accountability for pain relief.

Critical Pathways↗

Patient satisfaction and pain severity as outcomes in pain management: a longitudinal view of one setting's experience.

Longitudinal data from quality assurance studies of pain outcomes (pain severity and patient satisfaction) were critically examined to explore the reasons that patients are satisfied with their care even when they are in pain. Data were acquired from three sources: self-report surveys of patients during inpatient admission or ambulatory clinic visit (N = 306), telephone interviews of patients after discharge (N = 869), and chart reviews (N = 112). These data were compared to baseline data obtained 2 years ago, before the implementation of a number of programs designed to improve pain management. Findings reveal little change from baseline with respect to patient satisfaction with pain management--an overwhelming percentage are satisfied or highly satisfied. Similarly, there has been little change in pain intensity ratings--on average, patients' worst pain is approximately 7 on a 0-10 scale. In addition, almost all analgesic orders continue to be written for "as needed" administration. Based on these findings, we postulate that patients are satisfied even though they are in pain because they experience a commonly expected peak and trough pattern of pain relief, a pattern that occurs with "as needed" administration. That is, we conclude that pattern of pain relief, not pain severity, may be the critical determinant of satisfaction.

Humans↗

The rapid identification of intact microorganisms using mass spectrometry.

Antibiotic-resistant strains of bacteria continue to emerge, increasing the need for their fast and accurate identification. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), has become a prominent technique in biological mass spectrometry. We report the application of MALDI-TOF-MS for the identification of intact Gram-negative and Gram-positive microorganisms taken directly from culture. Analysis of bacteria from a single colony is possible, allowing the screening of mixed cultures. Sample preparation is simple and the analysis automated, providing spectra within minutes. The spectra obtained allow identification of microorganisms from different genera, different species, and from different strains of the same species. The procedure provides a unique mass spectral fingerprint of the microorganism, produced from desorbed components of the cell wall. Consistent data were obtained from subcultures grown for 3-day and 6-day periods, from the same cultures 1 day later and from fresh subcultures 2 months later.

Coumaric Acids↗

The electronic patient record: a strategic planning framework.

Sunnybrook Health Science Center (Sunnybrook) is a multifacility academic teaching center. In May 1994, Sunnybrook struck an electronic patient record taskforce to develop a strategic plan for the implementation of a comprehensive, facility wide electronic patient record (EPR). The taskforce sought to create a conceptual framework which provides context and integrates decision-making related to the comprehensive electronic patient record. The EPR is very much broader in scope than the traditional paper-based record. It is not restricted to simply reporting individual patient data. By the Institute of Medicine's definition, the electronic patient record resides in a system specifically designed to support users through availability of complete and accurate data, practitioner reminders and alerts, clinical decision support systems, links to bodies of medical knowledge, and other aids [1]. It is a comprehensive resource for patient care. The taskforce proposed a three domain model for determining how the EPR affects Sunnybrook. The EPR enables Sunnybrook to have a high performance team structure (domain 1), to function as an integrated organization (domain 2), and to reach out and develop new relationships with external organizations to become an extended enterprise (domain 3) [2]. Domain 1: Sunnybrook's high performance teams or patient service units' (PSUs) are decentralized, autonomous operating units that provide care to patients grouped by 'like' diagnosis and resource needs. The EPR must provide functions and applications which promote patient focused care, such as cross functional charting and care maps, group scheduling, clinical email, and a range of enabling technologies for multiskilled workers. Domain 2: In the integrated organization domain, the EPR should facilitate closer linkages between the arrangement of PSUs into clinical teams and with other facilities within the center in order to provide a longitudinal record that covers a continuum of care. Domain 3: In the inter-enterprise domain, the EPR must allow for patient information to be exchanged with external providers including referring doctors, laboratories, and other hospitals via community health information networks (CHINs). Sunnybrook will prioritize the development of first domain functionality within the corporate constraints imposed by the integrated organization domain. Inter-enterprise computing will be less of a priority until Sunnybrook has developed a critical mass of the electronic patient record internally. The three domain description is a useful model for describing the relationship between the electronic patient record enabling technologies and the Sunnybrook organizational structures. The taskforce has used this model to determine EPR development guidelines and implementation priorities.

Medical Records Systems, Computerized↗

Electrospray mass spectrometry of Malayan pit viper (Calloselasma rhodostoma) venom.

A high-performance liquid chromatography protocol has been developed for the analysis of snake venoms. This system has been used to isolate eight fractions from Malayan pit viper (Calloselasma rhodostoma) venom. The fractions have been analysed using electrospray mass spectrometry. A number of major components were found with masses ranging from 13,670 to 22,750 Da.

Chromatography, High Pressure Liquid↗

Studies of intestinal lymphoid tissue. X-observations on granular epithelial lymphocytes (gEL) in normal and diseased human jejunum.

A proportion of epithelial lymphocytes in various mammalian species is characterised by cells containing cytoplasmic granules. We have studied the total number of granular lymphocytes within surface and crypt epithelium of jejunal mucosae (per 10(4) micron2 muscularis mucosae) from six groups of subjects, comprising (i) young healthy volunteers (ii) family relatives of known coeliac patients, patients with gastrointestinal disorders associated with either (iii) normal or (iv) "flat" mucosae, and groups of (v) untreated and (vi) treated patients with coeliac disease. There was no difference in the absolute number of gEL between the three control groups with normal mucosal architecture, the proportion of granular to total EL per unit of tissue varying between 30-40%. In untreated coeliac mucosae, there was a significantly increased population of gEL, compared with the same control groups (p less than 0.001): the ratio of granular to total EL approximated 65%, and did not differ from flat-control mucosae in which the proportion of gEL was 55%. On withdrawal of gluten, the absolute number of gEL fell significantly in comparison with the untreated coeliac group (p less than 0.05). To further evaluate the effect of gluten challenge, granular lymphocytes were monitored during a five-day period in groups of treated coeliac patients orally challenged with increasing doses (500-3000 mg) of a peptic-tryptic digest of gluten. A significant rise in the absolute number of granular lymphocytes occurred at 12 h, but without any deterioration in mucosal architecture.

Adolescent↗

A comparison of the identification of group A streptococci and enterococci by two rapid pyrrolidonyl aminopeptidase methods.

Group A streptococci and enterococci can be differentiated from other streptococci by their ability to cleave L-pyrrolidonyl-beta-napthylamide (PYR). The authors evaluated two pyrrolidonyl aminopeptidase (PYRase) systems--Minitek (BBL Microbiology Systems, Cockeysville, MD) and Identicult-AE (Scott Laboratories, Inc., Fiskeville, RI)--for the presumptive identification of Group A streptococci and enterococci. Eighty-three Group A streptococci, 77 beta-hemolytic non-Group A streptococci, 74 enterococci, 56 nonenterococcal non-beta-hemolytic streptococci, 1 Streptococcus pneumoniae, and 1 Aerococcus were tested. Compared with results obtained with reference methods (bile esculin agar and 6.5% [w/v] sodium chloride for identification of enterococci, and latex agglutination tests by Streptex [Burroughs Wellcome, NC] for grouping of beta-hemolytic streptococci) both the Identicult-AE and MInitek systems were 100% sensitive and specific for identification of both enterococci and Group A beta-hemolytic streptococci. Advantages of the Identicult-AE system compared with Minitek were the use of a smaller inoculum for which subculture was not necessary, incubation at room temperature rather than at 37 degrees C, and lower cost. Both PYRase kits tested, and in particular the Identicult-AE system, were very easy to use and should be considered as rapid, reliable, and cost-effective alternative methods for the presumptive identification of Group A streptococci and enterococci in the clinical laboratory.

Aminopeptidases↗

Measurement of angiotensinogen in human serum by fluorescence polarization immunoassay.

Fluorescence polarization immunoassay (F.P.I.A.) has rarely been used to measure components of the renin system. Using an Abbott TDX polarimeter and fluorescein - labelled angiotensin I as a tracer we measured angiotensin I by F.P.I.A. Combining this procedure with a renin incubation step enabled measurement of angiotensinogen in human serum. Using sera from male patients and from pregnant females, a good correlation between radioimmunoassay (R.I.A.) and F.P.I.A. was found. Two procedures were developed; one involving taking samples from the renin incubation mixture, the other involving measurement of generated angiotensin I at intervals without interrupting the renin incubation procedure. F.P.I.A. is less expensive and somewhat simpler than R.I.A. but, with the instrument used, it was less sensitive. An unexpected observation was that human renin increases polarization in solutions containing fluorescein labelled angiotensin I, indicating possible binding of renin to angiotensin I.

Angiotensin I↗

Reduced dipsogenic responsiveness to intracerebroventricularly administered angiotensin II in estrogen-treated rats.

Chronic administration of two doses of estradiol benzoate (30 and 46 micrograms/kg/day) reduced the drinking response to acute administration of either isoproterenol (25 micrograms/kg, s.c.), the beta-adrenergic agonist, or angiotensin II (Ang II) (200 micrograms/kg, s.c.). The drinking response to intracerebroventricular administration of Ang II (40 ng/kg), but not carbachol (800 ng/kg), was also attenuated in estrogen-treated rats. An assessment of the Ang II binding in a diencephalic block of tissue from estrogen-treated rats revealed a significant reduction compared to untreated controls. The results suggest, but do not prove, that the reduced drinking response observed in estrogen-treated rats may be related to a reduction in the number of Ang II receptors in the brain.

Angiotensin II↗