On to graduate school: step by step.
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Biomedical subjects
Publications and source records attributed to J H Davis.
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Patient-centered hospital units have grown out of the national trend to greater consumerism, but few of these units have been evaluated rigorously. We used a randomized controlled trial to compare patient outcomes on the Planetree Model Hospital Unit with other medical-surgical units in the hospital. Planetree patients were significantly more satisfied than controls with their hospital stay, the unit's environment and nursing care, but did not differ in ratings of physician care. Planetree patients reported more involvement in their care while hospitalized and higher satisfaction with the education they received. There were few differences between Planetree and controls in health behaviors. While Planetree patients reported better mental health status and role functioning after discharge, their health status was similar to controls after 3 to 6 months. There were no differences in length of stay and charges for the index hospitalization, readmissions or outpatient care during the following year.
Thrombotic thrombocytopenic purpura (TTP) is, in most cases, treatable with plasma exchange therapy (PLEX). Rarely, patients do not respond to PLEX or develop refractory disease despite an initial remission. In these cases, treatment options are limited and the response to established alternative therapies is often disappointing. We report the case of a paediatric patient with TTP who developed refractory disease after an initial response to PLEX. She was subsequently treated with cyclosporine A and showed an immediate and sustained response. CSA may be a safe and effective therapy for patients with refractory TTP and should be studied in randomized, prospective clinical trials.
This paper presents 15 deaths of suicidal persons in Oregon and Florida who, by their behavior, sufficiently provoked law enforcement officers into killing them. Four deaths were certified as suicide, one as undetermined and ten as homicide. All of the deaths are individually described in detail and their case characteristics are presented in a table. The method of study is a descriptive analysis of the case characteristics, including 21 variables which are determined to be relevant to the classification of death. The variables were grouped into six categories: (a) personal information; (b) criminal behavior during the fatal incident; (c) dangerous behavior during the fatal incident; (d) toxicological data; (e) mental illness information; and (f) certification data. From the analysis, reasons for the opinions on manner of death classification are presented. All incidents were perceived as life-threatening to law officers, family members, or hostages. All victims were male except one, and all were Caucasian except two. All victims resisted arrest and verbally threatened homicide during the fatal incident. Two-thirds of the victims took hostages. All victims possessed an apparent handgun or other weapon (knife, iron bar). All victims posed their weapon and threatened others during the incident, 60% of victims actually used the weapon with apparent intent to inflict damage to others. 40% of victims were intoxicated with alcohol but other drug-involvement was uncommon. Seven of 15 had previous suicide attempts, 40% had medically documented psychiatric diagnoses and 60% had reasonable historical evidence of psychiatric diagnoses, most commonly depression or substance abuse. One of the co-authors presents the case for some of the deaths to be certified as suicides, whereas two present the case for all to be certified as homicide. A brief discussion of psychiatric issues is also presented concerning individuals who use others to commit suicide and who may engage in dangerous and/or criminal behavior to do so. A major conclusion is that there is lack of a unified opinion on death certification procedures for individuals who have provoked law enforcement officers to kill them. For such cases, it is recommended that professional organizations of medical examiners/coroners develop guidelines to promote consistency in death certification practices including manner of death classification and selection of death certificate wording so that "police-assisted suicide" may be appropriately reported and studied.
A 64-year-old diabetic man underwent total maxillectomy with orbital exenteration because of recurrent carcinoma. In order to decrease pressure at the surgical site, 50 mL of cerebrospinal fluid were withdrawn. After the procedure was completed, 5% glutaraldehyde was inadvertently injected into the subarachnoid space instead of reinjection of the original cerebrospinal fluid. The patient suffered hypotension and coma culminating in death five days after the procedure. Postmortem examination revealed exquisite fixation of the outer cortical shell of the spinal cord and brain stem. The mishap occurred because an unlabeled vial was mistaken for the withdrawn cerebrospinal fluid. Graicunas' theory and formula on relationship complexities in organizations is exemplified by this occurrence. One may calculate the theoretical potential for 24,708 miscommunications during such a complex and lengthy surgical procedure. Proper operating room procedures must be developed and followed in order to prevent such tragedies.
A molecular dynamics simulation of a simple model membrane system composed of a single amphiphilic helical peptide (ace-K2GL16K2A-amide) in a fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer was performed for a total of 1060 ps. The secondary structure of the peptide and its stability were described in terms of average dihedral angles, phi and psi, and the C alpha torsion angles formed by backbone atoms; by the average translation per residue along the helix axis; and by the intramolecular peptide hydrogen bonds. The results indicated that residues 6 through 15 remain in a stable right-handed alpha-helical conformation, whereas both termini exhibit substantial fluctuations. A change in the backbone dihedral angles for residues 16 and 17 is accompanied by the loss of two intramolecular hydrogen bonds, leading to a local but long-lived disruption of the helix. The dynamics of the peptide was characterized in terms of local and global helix motions. The local motions of the N-H bond angles were described in terms of the autocorrelation functions of P2[cos thetaNH(t, t + tau)] and reflected the different degrees of local peptide order as well as a variation in time scale for local motions. The chi1 and chi2 dihedral angles of the leucine side chains underwent frequent transitions between potential minima. No connection between the side-chain positions and their mobility was observed, however. In contrast, the lysine side chains displayed little mobility during the simulation. The global peptide motions were characterized by the tilting and bending motions of the helix. Although the peptide was initially aligned parallel to the bilayer normal, during the simulation it was observed to tilt away from the normal, reaching an angle of approximately 25 degrees by the end of the simulation. In addition, a slight bend of the helix was detected. Finally, the solvation of the peptide backbone and side-chain atoms was also investigated.
alpha-Lytic protease, a bacterial serine protease of 198 amino acids (19 800 Da), has been used as a model system for studies of catalytic mechanism, structure-function relationships, and more recently for studies of pro region-assisted protein folding. We have assigned the backbones of the enzyme alone, and of its complex with the tetrahedral transition state mimic N-tert-butyloxycarbonyl-Ala-Pro-boro Val, using double- and triple-resonance 3D NMR spectroscopy on uniformly 15N- and 13C/15N-labeled protein. Changes in backbone chemical shifts between the uncomplexed and inhibited form of the protein are correlated with distance from the inhibitor, the displacement of backbone nitrogens, and change in hydrogen bond strength upon inhibitor binding (derived from previously solved crystal structures). A comparison of the solution secondary structure of the uninhibited enzyme with that of the X-ray structure reveals no significant differences. Significant line broadening, indicating intermediate chemical exchange, was observed in many of the active site amides (including three broadened to invisibility), and in a majority of cases the broadening was reversed upon addition of the inhibitor. Implications and possible mechanisms of this line broadening are discussed.
A female-produced sex pheromone for the pecan nut casebearer, Acrobasis nuxvorella Neunzig, has been identified from pheromone gland extracts of calling female moths. The compound (9E,11Z)-hexadecadienal [(9E,11Z)-16:Ald] was identified by coupled GC-EAD and retention time matches with a synthetic standard on four capillary GC columns of different polarities. Corroboration of the identification of (9E,11Z)-16:Ald by other analytical chemistry methods was not possible due to the minute quantities of pheromone extracted (< 1 picogram/female). In field studies, gray rubber septa impregnated with 100 micrograms of synthetic (9E,11Z)-16:Ald were attractive to male moths, whereas higher and lower doses were less attractive. The homologous (9E,11Z)-15:Ald was also slightly attractive while the more highly conjugated analogues, (9E,11Z,13Z)- and (9E,11Z,13E)-16:Ald, were not.
BACKGROUND: Information about circumstances leading to disaster-related deaths helps emergency response coordinators and other public health officials respond to the needs of disaster victims and develop policies for reducing the mortality and morbidity of future disasters. In this paper, we describe the decedent population, circumstances of death, and population-based mortality rates related to Hurricane Andrew, and propose recommendations for evaluating and reducing the public health impact of natural disasters. METHODS: To ascertain the number and circumstances of deaths attributed to Hurricane Andrew in Florida and Louisiana, we contacted medical examiners in 11 Florida counties and coroners in 36 Louisiana parishes. RESULTS: In Florida medical examiners attributed 44 deaths to the hurricane. The mortality rate for directly-related deaths was 4.4 per 1 000 000 population and that for indirectly-related deaths was 8.5 per 1 000 000 population. In Louisiana, coroners attributed 11 resident deaths to the hurricane. Mortality rates were 0.6 per 1000 000 population for deaths directly related to the storm and 2.8 for deaths indirectly related to the storm. Six additional deaths occurred among non-residents who drowned in international waters in the Gulf of Mexico. In both Florida and Louisiana, mortality rates generally increased with age and were higher among whites and males. CONCLUSIONS: In addition to encouraging people to follow existing recommendations, we recommend emphasizing safe driving practices during evacuation and clean-up, equipping shelters with basic medical needs for the population served, and modifying zoning and housing legislation. We also recommend developing and using a standard definition for disaster-related deaths, and using population-based statistics to describe the public health effectiveness of policies intended to reduce disaster-related mortality.
Primary health care (PHC) offers nurses a framework for community-based practice in a restructured health care system. This study examined a Nursing in Primary Health Care course model. Self-directed learning readiness among baccalaureate nursing students enrolled in the course was examined in relation to evaluation of course content and instructional methods. The majority of students responded positively to the course methods and significant differences in course evaluations were found to be relative to self-directed learning readiness. The results suggest the Nursing in Primary health care course model effectively introduces students to PHC.
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Wideline 2H NMR of model membranes was used to consider the molecular consequences of factors often suggested as modulators of complex glycosphingolipid oligosaccharide arrangement and motional characteristics at cell surfaces. GM1, asialo-GM1, and globoside were studied as examples of plasma membrane recognition sites. The experimental approach involved substitution of deuterons (D) for protons at specific locations within the carbohydrate chains. Deuterated glycolipids were then dispersed at 7-10 mol% in unsonicated bilayers of 1-palmitoyl-2-oleoylphosphatidylcholine. Factors tested for their significance to carbohydrate chain conformation and dynamics included glycolipid natural alkyl and acyl chain variability, membrane fluidity, and the presence of cholesterol and a charged sugar residue (neuraminic acid). Effects of Ca2+ and membrane-associated protein were briefly considered. Two distinct strategies were employed in substituting deuterons for selected protons of carbohydrate residues. Neither approach necessitated alteration of the glycolipid natural fatty acid composition. (i) Protons of the exocyclic hydroxymethyl group on the terminal Gal residue of GM1 and asialo-GM1, and on the terminal N-acetylgalactosamine (GalNAc) residue of globoside, were replaced with deuterium (producing -CDHOH) by an enzymatic oxidation/reduction cycle. This represents the first application of such an approach to deuteration of complex neutral glycolipids. Spectral results were compared to those obtained for the similarly-deuterated monoglycosyl lipid, galactosylceramide (GalCer), with natural fatty acid composition. Efficacy of this labeling method may in principle be influenced by structural variations within a given glycolipid family. Also, asymmetric rotation of the deuterated group made it less attractive than the second method for relating spectral features to receptor geometry. (ii) A general synthetic, nonenzymatic method was investigated for replacing amino sugar N-acetyl groups with deuterated acetate (-COCD3). The acetate group of the GalNAc residue of globoside, GM1, and asialo-GM1, as well as that on neuraminic acid in GM1, was replaced with -COCD3. This second method afforded better signal-to-noise--an important consideration for 2H NMR. The NMR technique employed had the potential for detecting changes of as little as 10% in oligosaccharide orientation or motional order. Each glycolipid demonstrated clear evidence of preferred average oligosaccharide conformations in all (fluid) membrane environments examined. The most striking observation was that, in fluid matrices, conformation and motional order of the complex oligosaccharide chains were only modestly influenced by factors tested, including natural variation in the glycolipid hydrocarbon chains, membrane fluidity, temperature, and the presence of cholesterol or the N-acetylneuraminic acid (NeuAc) residue on GM1.(ABSTRACT TRUNCATED AT 400 WORDS)
2D 15N-1H correlation spectra are ideal for measuring backbone amide populations to determine amide exchange protection factors in studies of protein folding or other structural features. Most protein NMR spectroscopists use HSQC, which has been shown to be generally superior to HMQC in both resolution and sensitivity. The refocused HSQC experiment is intrinsically less sensitive than the regular HSQC, due to T2 relaxation during the refocusing delays. However, we show here that, when high 15N resolution is needed, an optimized refocused HSQC sequence that utilizes a semi-constant time evolution period and pulsed field gradients has better signal-to-noise ratio and resolution, and integrates more accurately, than a similar HSQC. The differences are demonstrated on a 20 kDa protein. The technique can also be applied to 3D NOESY experiments to eliminate strong NH2 geminal peaks and their truncation artefacts at a modest cost in sensitivity.
OBJECTIVES: To study characteristics of injury events and injuries requiring treatment in a Vermont population. METHOD: A one year 30% prospective sample was studied of persons from 22 communities who received first physician care for injury at the Medical Center Hospital of Vermont. RESULTS: Modal injuries were-superficial involving skin only among children below age 10, overexertion injuries among 10-59 year olds, and fractures among older persons. Among interviewed males ages 20-59, 31% of injuries were work related. Among females 26% were work related. Examining hospitalized cases only would have overemphasized falls, chemical injuries, leg fractures, transportation and nursing home injuries, and undercounted overexertion injuries, especially to the back, arm fractures, and injuries during recreation, work and home activities. Most common products/materials in use when injured were recreational equipment (24%) and motor vehicles (9%). Those most often causing injury were ground (20%) and home structures/construction materials (17%). No product was involved in 39% of injury event initiation and 15% of injury causation. CONCLUSION: In order to adequately reflect the distribution of treated injuries in the community by anatomical area, age, and event type studies must examine both emergency department and hospitalized cases and use a data collection system capable of recording several parameters to describe injury events and products/materials involved.
Although the strong 1H-1H dipolar interaction is known to result in severe homogeneous broadening of the 1H nuclear magnetic resonance (NMR) spectra of ordered systems, in the fluid phase of biological and model membranes the rapid, axially symmetric reorientation of the molecules about the local bilayer normal projects the dipolar interaction onto the motional symmetry axis. Because the linewidth then scales as (3 cos2 theta-1)/2, where theta is the angle between the local bilayer normal and the magnetic field, the dipolar broadening has been reduced to an "inhomogeneous" broadening by the rapid axial reorientation. It is then possible to obtain high resolution 1H-NMR spectra of membrane components by using magic angle spinning (MAS). Although the rapid axial reorientation effectively eliminates the homogeneous dipolar broadening, including that due to n = 0 rotational resonances, the linewidths observed in both lipids and peptides are dominated by low frequency motions. For small peptides the most likely slow motions are either a "wobble" or reorientation of the molecular diffusion axis relative to the local bilayer normal, or the reorientation of the local bilayer normal itself through surface undulations or lateral diffusion over the curved surface. These motions render the peptide 1H-NMR lines too broad to be observed at low spinning speeds. However, the linewidths due to these slow motions are very sensitive to spinning rate, so that at higher speeds the lines become readily visible. The synthetic amphiphilic peptide K2GL20K2A-amide (peptide-20) has been incorporated into bilayers of 1,2-di-d 27-myristoyl-sn-glycero-3-phosphocholine (DMPC-d54) and studied by high speed 1H-MAS-NMR. The linewidths observed for this transbilayer peptide, although too broad to be observable at spinning rates below -5 kHz, are reduced to 68 Hz at a spinning speed of 14 kHz (at 500C). Further improvements in spinning speed and modifications in sample composition designed to reduce the effectiveness of the slow motions responsible for the linewidth should result in significant further reduction in peptide linewidths. With this technique, there is now the potential for the use of 1H-MAS-NMR for the study of conformation, folding, and dynamics of small membrane peptides and protein fragments.
One- and two-dimensional solid-state 1H nuclear magnetic resonance spectra of gramicidin A incorporated in a dimyristoylphosphatidylcholine membrane have been obtained with use of high-speed magic angle spinning. By rotating the sample at 13 kHz, it is possible to observe signals in the 1H spectra between 6.0 and 9.0 ppm attributable to the aromatic protons of the tryptophan residues and the formyl group proton of gramicidin A. Two-dimensional solid-state COSY spectra provided information for the peak assignments. Moreover, changes in the 1H spectra have been observed as a function of the co-solubilization solvent initially used to prepare the samples and therefore as a function of the conformation adopted by gramicidin A. Three organic solvents have been used: trifluoroethanol, a mixture of methanol/chloroform (1:1 v/v), and ethanol. The conformational interconversion of gramicidin A from the double helix conformation to the channel structure for the sample prepared from ethanol was confirmed by following the time evolution of the proton spectra.
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