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Biomedical subjects

J W Wilson

Publications and source records attributed to J W Wilson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality.

OBJECTIVE: To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. DESIGN: Prospective cohort study. SETTING: University hospital intensive care unit. PATIENTS: A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. CONCLUSIONS: Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.

APACHE↗
PubMed2000

Overview of radiation environments and human exposures.

Human exposures to ionizing radiation have been vastly altered by developing technology in the last century. This has been most obvious in the development of radiation generating devices and the utilization of nuclear energy. But even air travel has had its impact on human exposure. Human exposure increases with advancing aircraft technology as a result of the higher operating altitudes reducing the protective cover provided by Earth's atmosphere from extraterrestrial radiations. This increase in operating altitudes is taken to a limit by human operations in space. Less obvious is the changing character of the radiations at higher altitudes. The associated health risks are less understood with increasing altitude due to the increasing complexity and new field components found in high-altitude and space operations.

Aircraft↗
PubMed2000

Radiation exposure for human Mars exploration.

One major obstacle to human space exploration is the possible limitations imposed by the adverse effects of long-term exposure to the space environment. Even before human space flight began, the potentially brief exposure of astronauts to the very intense random solar energetic particle events was of great concern. A new challenge appears in deep-space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays since the missions are of long duration, and accumulated exposures can be high. Because cancer induction rates increase behind low to moderate thicknesses of aluminum shielding, according to available biological data on mammalian exposures to galactic cosmic ray-like ions, aluminum shield requirements for a Mars mission may be prohibitively expensive in terms of mission launch costs. Alternative materials for vehicle construction are under investigation to provide lightweight habitat structures with enhanced shielding properties. In the present paper, updated estimates for astronaut exposures on a Mars mission are presented and shielding properties of alternative materials are compared with aluminum.

Cosmic Radiation↗
PubMed2000

Comparative evaluation of three human immunodeficiency virus genotyping systems: the HIV-GenotypR method, the HIV PRT GeneChip assay, and the HIV-1 RT line probe assay.

Evaluation of drug resistance by human immunodeficiency virus (HIV) genotyping has proven to be useful for the selection of drug combinations with maximum antiretroviral activity. We compared three genotyping methods for identification of mutations known to confer drug resistance in the reverse transcriptase (RT) and protease genes of HIV type 1 (HIV-1). The HIV-GenotypR method (GenotypR; Specialty Laboratories, Inc., Santa Monica, Calif.) with the ABI 377 DNA sequencer (Applied Biosystems Inc.), the HIV PRT GeneChip assay (GeneChip; Affymetrix, Santa Clara, Calif.), and the HIV-1 RT Line Probe Assay (LiPA; Innogenetics, Alpharetta, Ga.) were used to genotype plasma samples from HIV-infected patients attending the University of Wisconsin Hospitals and Clinics and the Mayo Clinic. At the time of analysis, patients were failing combination therapy (n = 18) or were treatment naive (n = 6). Forty codons of the RT and protease genes were analyzed by GenotypR and GeneChip for resistance-associated mutations. LiPA analyzed seven RT codons for mutations. Each sample was genotyped by all three assays, and each assay was subjected to pairwise comparisons. At least 92% of the codons tested (by the three assays) in paired comparisons were concordant. GenotypR and GeneChip demonstrated 96.6% concordance over the 40 codons tested. GenotypR identified slightly more mutations than GeneChip and LiPA; GeneChip identified all primary mutations that corresponded to failing treatment regimens. Each assay identified at least 84% of the mutations identified by the other assays. Mutations that were discordant between the assays mainly comprised secondary mutations and natural polymorphisms. The assays had better concordance for mutations that corresponded to current failing regimens, present in the more predominant viral quasispecies. In the treatment-naive patients, GenotypR, GeneChip, and LiPA mainly identified wild-type virus. Only the LiPA identified K70R, a possible transmitted zidovudine resistance mutation, in the RT gene of a treatment-naive patient. We conclude that although discrepancies in results exist between assays, each assay showed a similar capacity to identify potentially clinically relevant mutations related to patient treatment regimens.

Anti-HIV Agents↗
PubMed2000

A physician's primer to antiretroviral drug resistance testing.

Evaluating the genetic composition of HIV has evolved from a traditional epidemiologic research tool into a widely used clinical asset in the management of HIV infection. Genotypic and phenotypic testing is designed to identify drugs less likely to be therapeutically effective. Genotypic assays identify specific "gene mutations" or nucleotide substitutions known to confer drug resistance, whereas phenotypic assays measure the amount of drug necessary to inhibit viral replication in vitro. Prospective studies of antiretroviral drug resistance testing have shown its value as an independent predictor of optimal virologic response to drug therapy. Current guidelines recommend use of these tests following treatment failure and during pregnancy; considerations for testing include primary infection and treatment-naive patients. The identification of drug resistance can help the clinician individualize treatment regimens to attain maximal viral suppression and patient longevity.

Anti-HIV Agents↗
PubMed2000

A comparison of the multigroup and collocation methods for solving the low-energy neutron Boltzmann equation.

A low-energy neutron transport algorithm for use in space-radiation protection is developed. The algorithm is based upon a multiple energy group analysis of the straight ahead Boltzmann equation utilizing a mean value theorem for integrals. The algorithm developed is then verified by using a collocation method solution on the same straight ahead Boltzmann equation. This algorithm was then coupled to the existing NASA Langley HZETRN (high charge and energy transport) code through the evaporation source term. Evaluation of the neutron fluence generated by the February 23, 1956 solar particle event for an aluminum-water shield-target configuration is then compared with the LAHET Monte Carlo calculation for the same shield-target configuration. The algorithm developed showed a great improvement in results over the unmodified HZETRN solution. A bidirectional modification of the evaporation source produced further improvement of the fluence.

Algorithms↗
PubMed1999

Medium modified nucleon-nucleon cross sections in a nucleus.

A simple reliable formalism is presented for obtaining nucleon-nucleon cross sections within a nucleus in nuclear collisions for a given projectile and target nucleus combination at a given energy for use in transport, Monte Carlo and other calculations. The method relies on extraction of these values from experiments and has been tested for absorption experiments to give excellent results.

Elementary Particle Interactions↗
PubMed1999

Accurate universal parameterization of absorption cross sections III--light systems.

Our prior nuclear absorption cross sections model [R.K. Tripathi, F.A. Cucinotta, J.W. Wilson, Nucl. Instr. and Meth. B 117 (1996) 347; R.K. Tripathi, J.W. Wilson, F.A. Cucinotta, Nucl. Instr. and Meth. B 129 (1997) 11] is extended for light systems (A < or = 4) where either both projectile and target are light particles or one is light particle and the other is medium or heavy nucleus. The agreement with experiment is excellent for these cases as well. Present work in combination with our original model provides a comprehensive picture of absorption cross sections for light, medium and heavy systems. As a result the extended model can reliably be used in all studies where there is a need for absorption cross sections.

Elementary Particle Interactions↗
PubMed1999

Fragmentation of 200 and 244 MeV/u carbon beams in thick tissue-like absorbers.

Stacks consisting of thin CR-39 sheets sandwiched between thick lucite and water absorbers were perpendicularly bombarded by 12C ions at 200 and 244 MeV/u. Track radius distributions representing the charge composition of the fragmented beams were automatically measured by a particle track analysis system. After analysis of the nuclear charge distributions, the total charge removal cross-sections and elemental production cross-sections of fragments with atomic numbers from 5 to 3, were obtained down to the lower energies (approximately 50 and 100 MeV/u, respectively). It has been found that the measured total charge removal cross-section agrees with theoretical predictions within approximately 10% and very well with previous experiments in corresponding energy regions. Two model calculations for production of B fragment are in good agreement with our measured data while a third model overestimates it by approximately 12%. Theoretical cross-sections for Be and Li fragments differ strongly among the different models and from measured values.

Beryllium↗
PubMed1999

Reversible catecholamine-induced cardiomyopathy in a heart transplant candidate without persistent or paroxysmal hypertension.

BACKGROUND: Both dilated and hypertrophic cardiomyopathy have been reported in patients with pheochromocytoma, who were almost always hypertensive. The outcome frequently has been fatal, yet cardiac dysfunction can be reversible after medical or surgical therapy for the pheochromocytoma. METHODS: We report the case of a patient with dilated cardiomyopathy without persistent or paroxysmal hypertension, who was found to have a pheochromocytoma during initial medical evaluation. RESULTS: The identification and treatment of the pheochromocytoma led to significant improvement in cardiac function and cardiac transplantation was avoided. CONCLUSIONS: This case illustrates some unusual features in pheochromocytoma-induced cardiomyopathy: (1) absence of persistent or paroxysmal hypertension, (2) initial presentation with acute myocardial infarction and normal coronary arteries, and (3) recurrent episodes of nonsustained ventricular tachycardia.

Adrenal Gland Neoplasms↗
PubMed1999

Airway vascular changes in lung allograft recipients.

BACKGROUND: In asthma there has been increasing interest in the contribution of airway microvasculature to airway wall thickness and lumenal narrowing. Post-lung transplant, the survival of the donor airway is generally dependent on mixed-venous blood flow from pulmonary artery collaterals associated with the discontinuation of the bronchial circulation. This may lead to an altered vasculature of the airways post transplant, which may contribute to airflow limitation. METHODS: Endobronchial biopsies were taken from the lower lobe sub-carinae in 22 lung transplant recipients (LTR), 8 with Bronchiolitis Obliterans Syndrome (BOS), 14 without, and 14 controls. Seven microm frozen sections were stained for type IV collagen with a monoclonal antibody, using an indirect immunoperoxidase method. Bronchial vessels were identified by typical staining of type IV collagen in the true basement membrane supporting the endothelium. The number of vessels per mm2 of submucosa to a depth of 150 microm below the basement membrane, the percent vascularity and average vessel size were quantified using a computerised image analyser. RESULTS: Compared to the controls, a higher percent vascularity was found in LTR both with and without BOS (p < 0.05). In the BOS group, the percent best FEV1.0 decreased exponentially, in association with increased airway vessel size (r2 = 0.67, p = 0.01). CONCLUSIONS: These findings suggest that increased airway vascularity is a feature of the allograft airways post transplant. This may be a result of the relative hypoxia and hypercarbia in the blood supplying the airways from the pulmonary artery collaterals or of the chronic inflammatory process in the airways. These changes in vascularity could contribute to airflow limitation in BOS.

Adult↗
PubMed1999

An analysis of energy deposition in a tissue equivalent proportional counter onboard the space shuttle.

An improved prediction for space radiations in the lower earth orbits measured by the shuttle TEPC is obtained when energy loss straggling and chord length distribution of the detector are considered. A generalized analytic model is used to describe the energy deposition of direct ion interaction events in a micron-size detector. The transport calculation accounting for the shuttle configuration is accomplished by using a new version of HZETRN that has been extensively verified with laboratory and flight data. The agreement of predicted and measured lineal energy spectra is within 70% for the region above 2 keV/micrometer but within a factor of 2.3 underpredicted for the region below this value. The inclusion of indirect delta ray events in the model is needed before possible causes for the underprediction below 2 keV/micrometer can be assessed.

Cosmic Radiation↗
PubMed1999

Shielding from solar particle event exposures in deep space.

The physical composition and intensities of solar particle event exposures of sensitive astronaut tissues are examined under conditions approximating an astronaut in deep space. Response functions for conversion of particle fluence into dose and dose equivalent averaged over organ tissues are used to establish significant fluence levels and the expected dose and dose rates of the most important events from past observations. The BRYNTRN transport code is used to evaluate the local environment experienced by sensitive tissues and used to evaluate bioresponse models developed for use in tactical nuclear warfare. The present results will help to clarify the biophysical aspects of such exposure in the assessment of RBE and dose rate effects and their impact on design of protection systems for the astronauts. The use of polymers as shielding material in place of an equal mass of aluminum would provide a large safety factor without increasing the vehicle mass. This safety factor is sufficient to provide adequate protection if a factor of two larger event than has ever been observed in fact occurs during the mission.

Bone Marrow↗
PubMed1999

Implication of microdosimetry in estimation of radiation quality in space environment.

Errors introduced using a tissue equivalent proportional counter to estimate radiation quality of an arbitrary ion field as related to space radiations are examined. This is accomplished by using a generalized analytic model to calculate the effect of energy loss straggling, track structure, and pathlength distribution on the microdosimetric distribution. The error can be as large as a factor of two, but no systematic trend could be found.

Extraterrestrial Environment↗
PubMed1999

Beta2-adrenergic receptor agonists and cAMP arrest human cultured airway smooth muscle cells in the G(1) phase of the cell cycle: role of proteasome degradation of cyclin D1.

Hyperplasia of airway smooth muscle (ASM) contributes to the airway hyperresponsiveness that characterizes asthma. We have investigated the relationship between cAMP-induced growth arrest of ASM cells and thrombin-stimulated, extracellular-regulated protein kinase (ERK) activity, cyclin D1, and the restriction protein retinoblastoma. The beta(2)-adrenergic receptor agonist albuterol (100 nM) inhibited DNA synthesis after incubation with ASM for periods as brief as 1 h when these coincided with the timing of the restriction point. Inhibition of thrombin-stimulated DNA synthesis by albuterol (1-100 nM), 8-bromo-cAMP (300 microM), or prostaglandin E(2) (1 microM) was accompanied by a reduction in cyclin D1 protein levels. The ERK kinase inhibitor PD98059 (3-30 microM) attenuated thrombin-stimulated ERK phosphorylation and activity and the increase in cyclin D1 protein levels, as did albuterol (1-100 nM) or 8-bromo-cAMP (300 microM). In contrast, neither albuterol (100 nM) nor PD98059 (30 microM) reduced cyclin D1 mRNA levels between 4 and 20 h after thrombin addition, which suggests that elevation of cAMP regulates cyclin D1 by a post transcriptional mechanism. The proteasome inhibitor MG132 (30 and 100 nM) and the calpain I inhibitor N-acetyl-Leu-Leu-leucinal (10 microM) attenuated the reduction in thrombin-stimulated cyclin D1 levels in ASM exposed to albuterol (100 nM), 8-bromo-cAMP (300 microM), or the phosphodiesterase inhibitor isobutylmethylxanthine (100 microM). Thus, the cAMP-induced arrest of ASM in the G(1) phase of the cell cycle is associated with a proteasomal degradation of cyclin D1 protein and a reduced protein retinoblastoma phosphorylation that prevents passage through the restriction point.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Vascularity in asthmatic airways: relation to inhaled steroid dose.

BACKGROUND: There is an increase in vascularity in the asthmatic airway. Although inhaled corticosteroids (ICS) are an effective anti-inflammatory treatment in asthma, there are few data on any effects on structural changes. METHODS: Endobronchial biopsy specimens from seven asthmatic subjects not receiving ICS and 15 receiving 200-1500 microg/day beclomethasone dipropionate (BDP) were immunohistochemically stained with an anti-collagen type IV antibody to outline the endothelial basement membrane of the vessels. These were compared with biopsy tissue from 11 non-asthmatic controls (four atopic and seven non-atopic). RESULTS: There was a significant increase in the density of vessels (number of vessels/mm2 of lamina propria) in the asthmatic subjects not on ICS compared with non-asthmatic controls (mean 485 (interquartile range (IQR) 390-597) versus 329 (IQR 248-376) vessels/mm2, p<0.05; 95% CI for the difference 48 to 286). There was no significant difference between asthmatic subjects on ICS and those not on ICS or control subjects in the number of vessels/mm2 (mean 421 (IQR 281-534)). However, patients who received >/=800 microg/day BDP tended to have a reduced number of vessels/mm2 compared with patients not on ICS and those receiving </=500 microg/day BDP (mean 366 (IQR 153-608) versus 494 (IQR 391-583), p = 0.08; 95% CI for the difference -31 to 288). Similarly, there was an increase in the percentage of lamina propria occupied by vessels in asthmatic patients not on ICS compared with controls (mean 15.6% (IQR 13.1-18.0) versus 10.1% (IQR 8.4-13.3), p<0.01; 95% CI for the difference 2.4 to 9.3) but a significant decrease in the percentage of lamina propria occupied by vessels was detected in asthmatic patients on ICS (mean 11.4% (IQR 9.1-14.9), p<0.01; 95% CI for the difference 0.7 to 7.7) compared with those not on ICS. The density of vessels correlated significantly with both airway hyperresponsiveness and percentage change in forced expiratory volume in one second (FEV1) after bronchodilator (r = -0. 38 for PD20 methacholine and r = 0.49 for change in percentage FEV1 after bronchodilator versus number of vessels/mm2, p<0.05). CONCLUSION: These findings suggest that ICS, especially at higher doses, may reduce airway wall vascularity in asthmatic subjects but further longitudinal intervention studies are required to confirm this suggestion.

Administration, Inhalation↗
PubMed1999

An antiinflammatory effect of salmeterol, a long-acting beta(2) agonist, assessed in airway biopsies and bronchoalveolar lavage in asthma.

The addition of long-acting beta(2) agonists to inhaled corticosteroid (ICS) therapy in symptomatic patients with asthma improves clinical status more than increasing the dose of ICS. It has been suggested that these benefits could be at the cost of an increase in airway inflammation, but few histopathological studies have been performed in the relevant group. In a double-blind, parallel-group, placebo-controlled study, we randomly assigned 50 symptomatic patients with asthma who were receiving ICS (range, 100 -500 microgram/d) to 12 wk of supplementary treatment with salmeterol (50 microgram twice daily) or fluticasone (100 microgram twice daily) or placebo. Bronchial biopsies and BAL were obtained from 45 patients before and after treatment and analyzed. After treatment with salmeterol there was no deterioration of airway inflammation as assessed by mast cells, lymphocytes, or macrophages in BAL or biopsies, but rather a significant fall in EG1-positive eosinophils in the lamina propria (from a median 18.3 to 7.6 cells/mm, p = 0.01), which was not seen after treatment with fluticasone. The only cellular effect of added fluticasone was a decrease in BAL lymphocyte activation. There was a concurrent improvement in clinical status, more marked with salmeterol than with increased ICS. Thus, adding salmeterol to ICS is not associated with increased "allergic" airway inflammation, but conversely with a complementary antieosinophil effect.

Adrenergic beta-Agonists↗