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Biomedical subjects

J H Davis

Publications and source records attributed to J H Davis.

At least 55 records · Page 3Linked to original sources

Trauma center-related biases in injury research.

OBJECTIVES: Most studies from trauma centers analyze and present combined data on patients from their surrounding communities and patients referred for specialized services from service areas of other hospitals. Information is needed about the effect of combining data from the two groups on conclusions about injury in the community. METHOD: All injured patients seen in a trauma center emergency department of 30% of days over one year were studied concerning referral status, age, sex, type of activity when injured, injury type and severity, hospitalization, and prior medical history. RESULTS: Combining data for both groups suggested an older, more medically impaired population, with more severe injuries, more frequent hospitalization, more serious head and spine injuries, fewer extremity fractures, and fewer household-related and more transportation-related injuries than were actually occurring in the community. CONCLUSIONS: Data from local and out-of-area referred patients at trauma centers should be analyzed and presented separately in studies from this source if an accurate representation is to be provided of the role of injury in the population at large of the community.

Abbreviated Injury Scale↗

Emergency department care and hospitalization as predictors of disability.

Duration of complete and partial disability for work, school, and home activities and activities of daily living during the first 18 months after injury were compared for 2,043 emergency department (ED) patients and 151 hospitalized patients from 22 northwestern Vermont communities who received their initial medical care for injury at the Medical Center Hospital of Vermont and were subsequently interviewed. Larger proportions of hospitalized patients than ED patients had any disability or prolonged disability. During almost all time frames, and even among patients who still had ongoing disability at 18 months, the majority of persons with disability had required ED treatment only. These data suggest that, based on disability, ED patients should not necessarily be considered to have merely minor injuries.

Abbreviated Injury Scale↗

The Injury Impairment Scale as a measure of disability.

Scores on the Injury Impairment Scale (IIS) were compared with reported disability for work or school, household activities, and activities of daily living during the first 18 months after injury for 2,194 persons treated in an emergency department or hospitalized for their injuries. Persons whose most severe injury was more life-threatening or who had larger numbers of injuries more often had higher IIS scores for their most life-threatening injury than did persons with fewer or less life-threatening injuries. Hospitalized patients had higher IIS injuries more often than did emergency department patients. As IIS increased, duration of disability also increased. However, many high IIS patients either reported no disability or disability of only short duration, suggesting only limited association between disability and IIS as it is currently designed.

Academic Medical Centers↗

Treatment charges, payment sources, and disability from alcohol-related trauma.

We examined treatment charges and who paid them and disability for work, school, household activities, and activities of daily living according to identified use of alcohol before injury among 2,416 patients age 15 years or older from 22 northwestern Vermont communities. Over 90% received emergency department treatment only. Among patients reported to have consumed this drug mean hospital and physician charges, respectively, were $2,482 and $565; 31.7% did not pay any portion of their hospital bills, and 27.8% of their total bills were unpaid. Among patients not known to have consumed alcohol, mean hospital and physician charges were $601 and $158, respectively; 10.7% made no payments and 11.3% of their bills were unpaid. Bills of alcohol users more often were paid by Medicaid and less often by Workmen's Compensation or commercial insurance than were those of patients without alcohol. Users also were less likely than the nonalcohol group to pay physicians' bills for hospital care. Alcohol users experienced longer postinjury disability than did persons not known to have been drinking.

Academic Medical Centers↗

Obstructive lung disease in children after allogeneic bone marrow transplantation.

Obstructive lung disease (OLD) has been described as a significant complication after allogeneic bone marrow transplantation (BMT). The incidence of OLD in adults appears to be low (approximately 3%), but there is little data for children. We analyzed 89 consecutive pediatric allogeneic BMTs, > or = 1.5 years post-BMT, performed at British Columbia's Children's Hospital from 1980 to 1992 for evidence of OLD. Diagnosis of OLD was based on clinical findings (nonproductive cough, wheezing, and dyspnea with no evidence of infection), pulmonary function tests (FEV1 < 80% and FEF25-75% < 60% predicted), lung biopsy, and computed tomography scan. Sixty-seven of the 89 children evaluated survived > or = 90 days and were classified as at risk for OLD. Thirteen of 67 (19.4%), developed OLD, 3 of which were transient. The development of OLD was strongly associated with the following high-risk groups: chronic graft-versus-host disease (GVHD) (37.1% OLD), increased donor age, acute GVHD, and either mismatched related or matched unrelated donor transplants. No correlation was found with methotrexate prophylaxis for GVHD, total body irradiation, or cytomegalovirus reactivity in either donor or recipient and the development of OLD. Further analysis of only children with chronic GVHD showed that liver involvement by GVHD before the onset of OLD (57.9%) was the only other significant predictive factor. We observed an overall increased prevalence of OLD in children compared with that previously reported in adults. Further studies are required to confirm whether age is a risk factor for development of OLD after allogeneic BMT.

Acute Disease↗

2H-NMR investigation of DMPC/glycophorin bilayers.

Deuterium nuclear magnetic resonance spectroscopy was used to investigate the phase equilibria, and the temperature and concentration dependences of the phospholipid hydrocarbon chain order, of mixtures of glycophorin in dimyristoylphosphatidyl-choline. In the fluid phase it is found that the protein has only a slight effect on the first moment of the 2H spectrum, which for perdeuterated chains is a direct measure of the average chain orientational order. However, analysis of the rate of change of the first moment with respect to protein concentration, at different temperatures within the fluid phase, shows that at a molar protein concentration of about 0.0295 +/- 0.01, the lipid chain order (or M1) is essentially independent of temperature. At this concentration the chain order is determined by the lipid's interaction with the protein and one can conclude that about 34 (+/- 12) lipids are required to solvate the protein. At higher lipid concentrations these lipids are freely exchanging, on the NMR time scale, with the other lipids in the bilayer. At glycophorin concentrations below about 1 mol% there is a two-phase coexistence region at temperatures below the pure lipid's chain melting transition. The boundary between the fluid phase and this two-phase region curves downwards (is concave downwards), whereas the boundary between the two-phase region and the gel phase, while naturally occurring at lower temperatures than the upper boundary, is concave upwards. As a consequence the protein partitions preferentially into the fluid phase. This behaviour is similar to that observed in a number of other protein/lipid and peptide/lipid mixtures where it was suggested that those systems may have been close to a critical mixing point and some characteristics of a continuous phase change were noted. Indeed, at glycophorin concentrations near and above 1 mol% there are indications that the phase behaviour becomes more complex, suggesting the presence of significant protein/protein interactions and that this system may be close to a critical point.

Deuterium↗

X-ray diffraction studies of oriented dilauroyl phosphatidylcholine bilayers in the L delta and L alpha phases.

X-ray diffraction studies on oriented multilayers of dilauroyl phosphatidylcholine in the lyotropic liquid-crystalline L alpha phase and a not previously reported mono-domain three-dimensional L delta phase at two temperatures (293 and 343 K) and various relative humidities (0-100%) are described. Absolute one-dimensional electron-density profiles of the different structural phase bilayers were constructed to a resolution of 4 A using direct methods (e.g. swelling and triplet structure-invariant relationships) to solve for the phase problem. The absolute electron-density distributions clearly demonstrate differences between the two structural phases of dilauroyl phosphatidylcholine bilayers. In addition, the various structural properties of the two different phases have been quantified. In the case of the L delta phase, the structural quantities (e.g. volumes of the terminal methyl group and headgroup, and the number of waters) are examined for the first time.

Crystallography, X-Ray↗

Characteristics, hospital charges, and effects of road transportation injuries in Vermont.

We studied 470 crash- and noncrash-related road transportation injuries to vehicle occupants, bicyclists, and pedestrians seen at a trauma center in Vermont. Among primary care patients, crash and noncrash groups had similar AIS and average disability at one year. Hospitalized patients had longer disability, but a majority of overall disability days and ongoing disability was found among nonhospitalized patients. Seventy-four percent of hospital bills were paid by insurance, 16% by government, 3% by self, with 7% unpaid. Limiting the sample only to hospitalized patients, or including referred patients, markedly affected--but in different ways--distributions of event type, body area injured, charges, and other characteristics.

Abbreviated Injury Scale↗

Nitroglycerin inhibits experimental thrombosis and reocclusion after thrombolysis.

Nitroglycerin inhibits platelet aggregation in vitro, but its effect on thrombosis and platelet function in vivo is controversial. This study assessed the effect of nitroglycerin on primary thrombus formation in response to vessel wall injury and secondary thrombus formation, or rethrombosis, after lysis of an existing thrombus. In the first protocol the right carotid artery was instrumented with a flow probe, stenosis, an anodal electrode, and a proximal infusion line. A 300 microA anodal current was used to induce endothelial injury and subsequent thrombotic occlusion of the vessel. Anisoylated plasminogen streptokinase activator complex (APSAC; 0.05 U/kg intraarterially) was injected proximal to the thrombus 30 minutes after occlusion. After APSAC, nitroglycerin (1 microgram/kg/min intraarterially, n = 7) or vehicle (n = 6) was infused proximal to the thrombus for 3 hours. Reocclusion occurred in two of seven nitroglycerin-treated dogs and six of six vehicle-treated dogs (p < 0.05). In the second protocol both carotid arteries were instrumented as described previously. Anodal current (300 microA, 180 minutes) was applied to the right carotid (n = 12) artery to determine control times to occlusion. The left carotid artery served as the test vessel, receiving either nitroglycerin (1 microgram/kg/min intraarterially, n = 6) or trimethaphan (0.05 mg/kg/hr intraarterially, n = 6). Trimethaphan was used to produce controlled hypotension to match the approximately 10% decrease in mean arterial blood pressure that was observed during nitroglycerin infusion. Control arteries and those treated with trimethaphan formed occlusive thrombi in all instances. Nitroglycerin infusion resulted in a lower incidence of occlusion (1 of 6; p < 0.05 vs control value) and inhibited ex vivo platelet aggregation to adenosine diphosphate and arachidonic acid (p < 0.05). Local infusion of nitroglycerin reduced the formation of primary thrombi, independent of the hypotensive effect of the drug, and exerted systemic effects on platelet aggregation. Furthermore, platelet inhibition with nitroglycerin reduced the incidence of secondary thrombus formation (rethrombosis) after thrombolysis. The results suggest that a potential benefit of nitroglycerin therapy may be derived from its ability to inhibit thrombotic events in patients with unstable angina or myocardial infarction.

Animals↗

The structure of an integral membrane peptide: a deuterium NMR study of gramicidin.

Solid state deuterium NMR was employed on oriented multilamellar dispersions consisting of 1,2-dilauryl-sn-glycero-3-phosphatidylcholine and deuterium (2H) exchange-labeled gramicidin D, at a lipid to protein molar ratio (L/P) of 15:1, in order to study the dynamic structure of the channel conformation of gramicidin in a liquid crystalline phase. The corresponding spectra were used to discriminate between several structural models for the channel structure of gramicidin (based on the left- and right-handed beta 6.3 LD helix) and other models based on a structure obtained from high resolution NMR. The oriented spectrum is complicated by the fact that many of the doublets, corresponding to the 20 exchangeable sites, partially overlap. Furthermore, the asymmetry parameter, eta, of the electric field gradient tensor of the amide deuterons is large (approximately 0.2) and many of the amide groups are involved in hydrogen bonding, which is known to affect the quadrupole coupling constant. In order to account for these complications in simulating the spectra in the fast motional regime, an ab initio program called Gaussian 90 was employed, which permitted us to calculate, by quantum mechanical means, the complete electric field gradient tensor for each residue in gramicidin (using two structural models). Our results indicated that the left-handed helical models were inconsistent with our observed spectra, whereas a model based on the high-resolution structure derived by Arseniev and coworkers, but relaxed by a simple energy minimization procedure, was consistent with our observed spectra. The molecular order parameter was then estimated from the motional narrowing assuming the relaxed (right-handed) Arseniev structure. Our resultant order parameter of SZZ = 0.91 translates into an rms angle of 14 degrees, formed by the helix axis and the local bilayer normal. The strong resemblance between our spectra (and also those reported for gramicidin in 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) multilayers) and the spectra of the same peptide incorporated in a lyotropic nematic phase, suggests that the lyotropic nematic phase simulates the local environment of the lipid bilayer.

Amino Acid Sequence↗

Dynamics of an integral membrane peptide: a deuterium NMR relaxation study of gramicidin.

Solid state deuterium (2H) NMR inversion-recovery and Jeener-Broekaert relaxation experiments were performed on oriented multilamellar dispersions consisting of 1,2-dilauroyl-sn-glycero-3-phosphatidylcholine and 2H exchange-labeled gramicidin D, at a lipid to protein molar ratio (L/P) of 15:1, in order to study the dynamics of the channel conformation of the peptide in a liquid crystalline phase. Our dynamic model for the whole body motions of the peptide includes diffusion of the peptide around its helix axis and a wobbling diffusion around a second axis perpendicular to the local bilayer normal in a simple Maier-Saupe mean field potential. This anisotropic diffusion is characterized by the correlation times, tau R parallel and tau R perpendicular. Aligning the bilayer normal perpendicular to the magnetic field and graphing the relaxation rate, 1/T1Z, as a function of (1-S2N-2H), where S2N-2H represents the orientational order parameter, wer were able to estimate the correlation time, tau R parallel, for rotational diffusion. Although in the quadrupolar splitting, which varies as (3 cos2 theta D-1), has in general two possible solutions to theta D in the range 0 < or = theta D < or = 90 degrees, the 1/T1Z vs. (1-S2N-2H) curve can be used to determine a single value of theta D in this range. Thus, the 1/T1Z vs. (1-S2N-2H) profile can be used both to define the axial diffusion rate and to remove potential structural ambiguities in the splittings. The T1Z anisotropy permits us to solve for the two correlation times (tau R parallel = 6.8 x 10(-9) s and tau R perpendicular = 6 x 10(-6) s). The simulated parameters were corroborated by a Jeener-Broekaert experiment where the bilayer normal was parallel to the principal magnetic field. At this orientation the ratio, J2(2 omega 0)/J1(omega 0) was obtained in order to estimate the strength of the restoring potential in a model-independent fashion. This measurement yields the rms angle, 1/2 (= 16 +/- 2 degrees at 34 degrees C), formed by the peptide helix axis and the average bilayer normal.

Biophysical Phenomena↗

Antithrombotic effects of DMP 728, a platelet GPIIb/IIIa receptor antagonist, in a canine model of arterial thrombosis.

The platelet glycoprotein IIb/IIIa receptor (GPIIb/IIIa, fibrinogen receptor) represents the final common pathway for platelet aggregation. Inhibition of GPIIb/IIIa with antibodies or peptides containing the RGD sequence has been reported to prevent arterial thrombosis. We examined DMP 728 [(cyclic[D-2-amino-butyryl-N2-methyl-L-arginyl-glycyl-L-aspartyl-3-(a min o- methyl-benzoic acid], methanesulfonic acid salt], a cyclic peptidomimetic, GPIIb/IIIa receptor antagonist, for prevention of thrombosis and rethrombosis in a canine model of carotid artery thrombosis. Dogs were anesthetized, and both carotid arteries were instrumented with an electrode, a flow probe, and a stenosis. A 300-microA current was applied to the intimal surface in the right carotid artery (RCA, control) through the electrode; time to occlusive thrombus formation and thrombus mass was noted. The RCA served as the control vessel; the left carotid artery (LCA) served as the test vessel after DMP 728 administration (0.1 or 1. mg/kg, intravenously, i.v.). As compared with controls, occlusive thrombus formation was reduced by both doses of DMP 728 (control 100% n = 12; 0.1 mg/kg i.v. 17%, p < 0.05, n = 6; 1.0 mg/kg i.v. 0%, p < 0.05, n = 6), time to occlusion was increased (p < 0.05), and thrombus weight was reduced (p < 0.05). Ex vivo platelet aggregation was inhibited in all groups. In a second group of animals, a carotid artery thrombus was formed and lysed with anisoylated plasminogen activator complex (APSAC; 0.05 U/kg intraarterially, i.a.) with or without DMP 728.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dose dependency of granulocyte-macrophage colony stimulating factor for improving survival following burn wound infection.

Infections remain a serious problem following injury. Immune modulation offers an additional strategy for the treatment of infections. We evaluated the ability of a multilineage hematopoietic growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), to improve survival following burn injury with a superimposed burn wound infection. Groups of 12 BDF1 mice received a 15% total body surface area (TBSA) thermal injury by immersion in 100 degrees C water; 6 x 10(3) Pseudomonas was then applied to the burn wound. The GM-CSF was injected subcutaneously B.I.D. for 7 days. Mice receiving the 10-ng dose of GM-CSF had significantly improved survival compared with the controls; other doses had no significant effect on survival. Clinical trials to assess the ability of GM-CSF to reduce infectious complications following burn injury are underway and these data suggest selecting a specific dose may be critical in achieving maximal benefit.

Animals↗

Characteristics, costs, and effects of violence in Vermont.

Study of the distribution, characteristics, costs and effects involving 125 assaults, 22 attempted suicides (plus 5 completed out-of-hospital suicides), and 49 injuries of questionable intent was carried out among local area patients treated in a hospital serving 22 communities (150,000 population) in northern Vermont. Patients referred from the service areas of other hospitals were specifically excluded in order to provide a picture of injuries from violence in the community, rather than of injuries treated at the hospital. The percentages hospitalized were assault, 5%; attempted suicide, 50%; and unknown intent, 6%. Most assault injuries were to the head or upper extremity administered by fist; suicide attempts most often were by medication or a sharp instrument to arms, while injuries of unknown intent usually resulted from smashing a hand against a building structure. Alcohol use was noted for 26%, 38%, and 23% of patients aged 15 years or older in the three respective categories. Average hospital charges (excluding physicians' bills) for the three respective injury events were $420, $2639, and $388. Only 2% of hospital bills were paid by patients or their families, 25% were paid by commercial insurance, 19% by government sources, and 54% remained unpaid. One eighth of physicians' bills for hospital and followup care were paid by patients or their families, and about 60% were still unpaid a year after billing. Among assault patients who could be contacted for followup and who had been employed or in school previously, 27% had no disability for work or school and the remainder averaged 18 days of complete plus partial disability.

Adolescent↗

Prolonged warm ischemia and limb survival: case report.

A 21-year-old woman sustained a supracondylar crush injury of her arm. The extremity underwent severe ischemia for more than 16 hours after an unsuccessful brachial artery repair. The forearm muscles became rigid and the fingers could not be extended passively. Clinically these findings were felt to be similar to rigor mortis. Despite this dismal picture, secondary revascularization resulted in a highly functional hand with no loss of digits. Desperate attempts at revascularization in isolated extremity injury may be successful, despite prolonged warm ischemia time.

Adult↗