43 results on '"Wheeler JA"'
Search Results
2. A comparison of the Integrated Uptake Biokinetic Model to Traditional Risk Assessment Approaches for Environmental Lead
- Author
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Chrostowski, PC, primary and Wheeler, JA, additional
- Published
- 1992
- Full Text
- View/download PDF
3. Small-scale drivers : the importance of nutrient availability and snowmelt timing on performance of the alpine shrub Salix herbacea
- Author
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Little, CJ, Wheeler, JA, Sedlacek, J, Cortés, Andrés J., Rixen, C, Little, CJ, Wheeler, JA, Sedlacek, J, Cortés, Andrés J., and Rixen, C
- Abstract
Alpine plant communities are predicted to face range shifts and possibly extinctions with climate change. Fine-scale environmental variation such as nutrient availability or snowmelt timing may contribute to the ability of plant species to persist locally; however, variation in nutrient availability in alpine landscapes is largely unmeasured. On three mountains around Davos, Switzerland, we deployed Plant Root Simulator probes around 58 Salix herbacea plants along an elevational and microhabitat gradient to measure nutrient availability during the first 5 weeks of the summer growing season, and used in situ temperature loggers and observational data to determine date of spring snowmelt. We also visited the plants weekly to assess performance, as measured by stem number, fruiting, and herbivory damage. We found a wide snowmelt gradient which determined growing season length, as well as variations of an order of magnitude or more in the accumulation of 12 nutrients between different microhabitats. Higher nutrient availability had negative effects on most shrub performance metrics, for instance decreasing stem number and the proportion of stems producing fruits. High nutrient availability was associated with increased herbivory damage in early-melting microhabitats, but among late-emerging plants this pattern was reversed. We demonstrate that nutrient availability is highly variable in alpine settings, and that it strongly influences performance in an alpine dwarf shrub, sometimes modifying the response of shrubs to snowmelt timing. As the climate warms and human-induced nitrogen deposition continues in the Alps, these factors may contribute to patterns of local plants persistence.
- Published
- 2016
- Full Text
- View/download PDF
4. Hemarthrosis in a Pediatric Patient With Immune Thrombocytopenia and Lyme Arthritis.
- Author
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Wheeler JA, Rodriguez V, and Jacobson-Kelly AE
- Subjects
- Humans, Child, Hemarthrosis complications, Hemarthrosis diagnosis, Anti-Bacterial Agents therapeutic use, Purpura, Thrombocytopenic, Idiopathic complications, Lyme Disease complications, Lyme Disease diagnosis, Lyme Disease drug therapy, Hemophilia A complications
- Abstract
The presentation of immune thrombocytopenia is dependent on the degree of thrombocytopenia, with no to mild bleeding symptoms, primarily mucocutaneous bleeding. Severe bleeding in other organ systems is a rare complication. Spontaneous hemarthrosis is rare in patients without hemophilia. We report a child presenting with oral and cutaneous petechial lesions and left knee hemarthrosis without trauma. Laboratory findings showed severe thrombocytopenia consistent with immune thrombocytopenia. Serologic tests were consistent with Lyme disease. Hemarthrosis was presumed secondary to Lyme disease monoarticular joint inflammation with bleeding exacerbated by severe thrombocytopenia. Hemarthrosis resolved and platelet counts normalized following immunoglobulin infusion, steroid course, and antibiotics., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
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- View/download PDF
5. Proximal tibia fracture dislocations: Management and outcomes of a severe and under-recognized injury.
- Author
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Keil LG, Mullis BH, Iii PT, Alley MC, Olszewski NP, Wheeler JA, von Kaeppler EP, Morshed S, Matar RN, Archdeacon MT, Smith TW, Miller AN, Horwitz DS, Baig MS, Telgheder ZL, Azer E, Manzano GW, Vallier HA, Barnett SA, Krause PC, Bornes TD, Ricci WM, Dunne PJ, Yarboro SR, Ment AJ, Marcantonio AJ, Alqudhaya RS, Leighton RK, and Ostrum RF
- Subjects
- Fracture Fixation, Internal, Humans, Reproducibility of Results, Retrospective Studies, Tibia, Tibial Fractures diagnostic imaging, Tibial Fractures surgery
- Abstract
Introduction: Proximal tibia fracture dislocations (PTFDs) are a subset of plateau fractures with little in the literature since description by Hohl (1967) and classification by Moore (1981). We sought to evaluate reliability in diagnosis of fracture-dislocations by traumatologists and to compare their outcomes with bicondylar tibial plateau fractures (BTPFs)., Methods: This was a retrospective cohort study at 14 level 1 trauma centers throughout North America. In all, 4771 proximal tibia fractures were reviewed by all sites and 278 possible PTFDs were identified using the Moore classification. These were reviewed by an adjudication board of three traumatologists to obtain consensus. Outcomes included inter-rater reliability of PTFD diagnosis, wound complications, malunion, range of motion (ROM), and knee pain limiting function. These were compared to BTPF data from a previous study., Results: Of 278 submitted cases, 187 were deemed PTFDs representing 4% of all proximal tibia fractures reviewed and 67% of those submitted. Inter-rater agreement by the adjudication board was good (83%). Sixty-one PTFDs (33%) were unicondylar. Eleven (6%) had ligamentous repair and 72 (39%) had meniscal repair. Two required vascular repair. Infection was more common among PTFDs than BTPFs (14% vs 9%, p = 0.038). Malunion occurred in 25% of PTFDs. ROM was worse among PTFDs, although likely not clinically significant. Knee pain limited function at final follow-up in 24% of both cohorts., Conclusions: PTFDs represent 4% of proximal tibia fractures. They are often unicondylar and may go unrecognized. Malunion is common, and PTFD outcomes may be worse than bicondylar fractures., Competing Interests: Declarations of Competing Interest None, (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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6. Successful Rapid Oral Desensitization to Sulfasalazine: An 11-Step Protocol.
- Author
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Bojanini L, Sacco K, Maya Villamizar JJ, Wheeler JA, Ahmed NH, and Gonzalez-Estrada A
- Subjects
- Administration, Oral, Desensitization, Immunologic, Humans, Drug Hypersensitivity diagnosis, Drug Hypersensitivity etiology, Sulfasalazine adverse effects
- Abstract
Competing Interests: The authors declare no conflict of interest.
- Published
- 2021
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7. Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation.
- Author
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Prideaux M, Wright CS, Noonan ML, Yi X, Clinkenbeard EL, Mevel E, Wheeler JA, Byers S, Wijenayaka AR, Gronthos S, Sankar U, White KE, Atkins GJ, and Thompson WR
- Subjects
- Animals, Cell Differentiation, Cell Line, Cell Lineage, Cell Proliferation, Fibroblast Growth Factor-23 metabolism, Immunophenotyping, Male, Mice, Mice, Inbred C57BL, RNA, Messenger metabolism, Adipocytes cytology, Cell Culture Techniques, Chondrocytes cytology, Mesenchymal Stem Cells cytology, Osteocytes cytology
- Abstract
Mesenchymal progenitors differentiate into several tissues including bone, cartilage, and adipose. Targeting these cells in vivo is challenging, making mesenchymal progenitor cell lines valuable tools to study tissue development. Mesenchymal stem cells (MSCs) can be isolated from humans and animals; however, obtaining homogenous, responsive cells in a reproducible fashion is challenging. As such, we developed two mesenchymal progenitor cell (MPC) lines, MPC1 and MPC2, generated from bone marrow of male C57BL/6 mice. These cells were immortalized using the temperature sensitive large T-antigen, allowing for thermal control of proliferation and differentiation. Both MPC1 and MPC2 cells are capable of osteogenic, adipogenic, and chondrogenic differentiation. Under osteogenic conditions, both lines formed mineralized nodules, and stained for alizarin red and alkaline phosphatase, while expressing osteogenic genes including Sost, Fgf23, and Dmp1. Sost and Dmp1 mRNA levels were drastically reduced with addition of parathyroid hormone, thus recapitulating in vivo responses. MPC cells secreted intact (iFGF23) and C-terminal (cFGF23) forms of the endocrine hormone FGF23, which was upregulated by 1,25 dihydroxy vitamin D (1,25D). Both lines also rapidly entered the adipogenic lineage, expressing adipose markers after 4 days in adipogenic media. MPC cells were also capable of chondrogenic differentiation, displaying increased expression of cartilaginous genes including aggrecan, Sox9, and Comp. With the ability to differentiate into multiple mesenchymal lineages and mimic in vivo responses of key regulatory genes/proteins, MPC cells are a valuable model to study factors that regulate mesenchymal lineage allocation as well as the mechanisms that dictate transcription, protein modification, and secretion of these factors., (© 2021. The Author(s).)
- Published
- 2021
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8. Compression of high-power laser pulses using only multiple ultrathin plane plates.
- Author
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Mironov SY, Wheeler JA, Khazanov EA, and Mourou GA
- Abstract
A proposal for additional temporal compression and peak power enhancement of intense (> T W / c m
2 ) femtosecond laser pulses using two thin plane-parallel plates is presented. The first ultrathin plate (order of mm) induces spectral broadening due to self-phase modulation, and the second ultrathin plate (order of micron) corrects the spectral phase. The elimination of the negative dispersive multilayer coating from the scheme offers an improved laser-induced damage threshold for the post-compression process.- Published
- 2021
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9. The HIF-PHI BAY 85-3934 (Molidustat) Improves Anemia and Is Associated With Reduced Levels of Circulating FGF23 in a CKD Mouse Model.
- Author
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Noonan ML, Ni P, Agoro R, Sacks SA, Swallow EA, Wheeler JA, Clinkenbeard EL, Capitano ML, Prideaux M, Atkins GJ, Thompson WR, Allen MR, Broxmeyer HE, and White KE
- Subjects
- Animals, Fibroblast Growth Factor-23, Fibroblast Growth Factors, Humans, Mice, Pyrazoles, Triazoles, Anemia drug therapy, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic drug therapy
- Abstract
Fibroblast growth factor-23 (FGF23) is a critical factor in chronic kidney disease (CKD), with elevated levels causing alterations in mineral metabolism and increased odds for mortality. Patients with CKD develop anemia as the kidneys progressively lose the ability to produce erythropoietin (EPO). Anemia is a potent driver of FGF23 secretion; therefore, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) currently in clinical trials to elevate endogenous EPO to resolve anemia was tested for effects on iron utilization and FGF23-related parameters in a CKD mouse model. Mice were fed either a casein control diet or an adenine-containing diet to induce CKD. The CKD mice had markedly elevated iFGF23 and blood urea nitrogen (BUN), hyperphosphatemia, and anemia. Cohorts of mice were then treated with a patient-equivalent dose of BAY 85-3934 (BAY; Molidustat), which elevated EPO and completely resolved aberrant complete blood counts (CBCs) in the CKD mice. iFGF23 was elevated in vehicle-treated CKD mice (120-fold), whereas circulating iFGF23 was significantly attenuated (>60%) in the BAY-treated CKD mice. The BAY-treated mice with CKD also had reduced BUN, but there was no effect on renal vitamin D metabolic enzyme expression. Consistent with increased EPO, bone marrow Erfe, Transferrin receptor (Tfrc), and EpoR mRNAs were increased in BAY-treated CKD mice, and in vitro hypoxic marrow cultures increased FGF23 with direct EPO treatment. Liver Bmp-6 and hepcidin expression were downregulated in all BAY-treated groups. Femur trabecular parameters and cortical porosity were not worsened with BAY administration. In vitro, differentiated osteocyte-like cells exposed to an iron chelator to simulate iron depletion/hypoxia increased FGF23; repletion with holo-transferrin completely suppressed FGF23 and normalized Tfrc1. Collectively, these results support that resolving anemia using a HIF-PHI during CKD was associated with lower BUN and reduced FGF23, potentially through direct restoration of iron utilization, thus providing modifiable outcomes beyond improving anemia for this patient population. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)
- Published
- 2021
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10. Heart failure is not a determinant of central sleep apnea in the pediatric population.
- Author
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Wheeler JA, Tutrow KD, Ebenroth ES, Gaston B, and Bandyopadhyay A
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Retrospective Studies, Stroke Volume, Ventricular Function, Left, Heart Failure epidemiology, Sleep Apnea, Central epidemiology
- Abstract
Background/objectives: Adults with heart failure (HF) have high prevalence of central sleep apnea (CSA). While this has been repeatedly investigated in adults, there is a deficiency of similar research in pediatric populations. The goal of this study was to compare prevalence of CSA in children with and without HF and correlate central apneic events with heart function., Methods: Retrospective analysis of data from children with and without HF was conducted. Eligible children were less than 18 years old with echocardiogram and polysomnogram within 6 months of each other. Children were separated into groups with and without HF based on left ventricular ejection fraction (LVEF). Defining CSA as central apnea-hypopnea index (CAHI) more than 1/hour, the cohort was also classified into children with and without CSA for comparative study., Results: A total of 120 children (+HF: 19, -HF: 101) were included. The +HF group was younger, with higher prevalence of trisomy 21, muscular dystrophy, oromotor incoordination, and structural heart disease. The +HF group had lower apnea-hypopnea index (median: 3/hour vs. 8.6/hour) and lower central apnea index (CAI) (median: 0.2/hour vs. 0.55/hour). Prevalence of CSA was similar in both groups (p = .195). LogCAHI was inversely correlated to age (Pearson correlation coefficient: -0.245, p = .022). Children with CSA were younger and had higher prevalence of prematurity (40% vs. 5.3%). There was no significant difference in LVEF between children with and without CSA. After excluding children with prematurity, relationship between CAHI and age was no longer sustained., Conclusions: In contrast to adults, there is no difference in prevalence of CSA in children with and without HF. Unlike in adults, LVEF does not correlate with CAI in children. Overall, it appears that central apneic events may be more a function of age and prematurity rather than of heart function., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
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11. Radiation Exposure in Patients with Isolated Limb Trauma: Acceptable or Are We Imaging Too Much?
- Author
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Wheeler JA, Weaver N, Balogh ZJ, Drobetz H, Kovendy A, and Enninghorst N
- Abstract
The aim of our study was to investigate the cumulative effective dose of radiation resulting from medical imaging in orthopaedic patients with isolated extremity trauma. Deidentified radiology records of consecutive patients without age restriction with isolated extremity trauma requiring operative treatment at a regional hospital were reviewed retrospectively over a 1-year period, and the effective dose per patient for each study type of plain film X-ray, computed tomography, and operative fluoroscopy was used to calculate cumulative effective dose. Values were summarised as mean, ± standard deviation, maximum, and proportion with overdose (>20 mSv). The study cohort included 428 patients (193 male and 235 female) with an average age of 44 years (±28). There were 447 procedures performed, i.e., all involved operative fluoroscopy, 116 involved computed tomography, and 397 involved X-ray. The mean cumulative effective dose per patient was 1.96 mSv (±4.98, 45.12). The mean cumulative effective dose for operative fluoroscopy was 0.32 mSv (±0.73, 5.91), for X-ray was 1.12 mSv (±3.6, 39.23) and for computed tomography was 2.22 mSv (±4.13, 20.14). The mean cumulative effective dose of 1.96 mSv falls below the recommended maximum annual exposure of 20 mSv. This study can serve as a guide for informing clinicians and patients of the acceptable radiation risk in the context of isolated extremity trauma.
- Published
- 2020
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12. Oral desensitization to entecavir: An 11-step protocol.
- Author
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Mechtler A, Ahmed NH, Wheeler JA, and Gonzalez-Estrada A
- Subjects
- Administration, Oral, Antiviral Agents therapeutic use, Clinical Protocols, Female, Guanine immunology, Guanine therapeutic use, Humans, Middle Aged, Self Report, Antiviral Agents immunology, Desensitization, Immunologic methods, Guanine analogs & derivatives, Hepatitis B, Chronic drug therapy
- Published
- 2019
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13. Regulation of Fibroblast Growth Factor 23 by Iron, EPO, and HIF.
- Author
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Wheeler JA and Clinkenbeard EL
- Abstract
Purpose of Review: Fibroblast growth factor-23 (FGF23) is the key hormone produced in bone critical for phosphate homeostasis. Elevated serum phosphorus and 1,25dihydroxyvitaminD stimulates FGF23 production to promote renal phosphate excretion and decrease 1,25dihydroxyvitaminD synthesis. Thus completing the feedback loop and suppressing FGF23. Unexpectedly, studies of common and rare heritable disorders of phosphate handling identified links between iron and FGF23 demonstrating novel regulation outside the phosphate pathway., Recent Findings: Iron deficiency combined with an FGF23 cleavage mutation was found to induce the autosomal dominant hypophosphatemic rickets phenotype. Physiological responses to iron deficiency, such as erythropoietin production as well as hypoxia inducible factor activation, have been indicated in regulating FGF23. Additionally, specific iron formulations, used to treat iron deficiency, alter post-translational processing thereby shifting FGF23 protein secretion., Summary: Molecular and clinical studies revealed that iron deficiency, through several mechanisms, alters FGF23 at the transcriptional and post-translational level. This review will focus upon the novel discoveries elucidated between iron, its regulators, and their influence on FGF23 bioactivity., Competing Interests: Conflict of Interest Jonathan A. Wheeler and Erica L. Clinkenbeard each declare no potential conflicts of interest.
- Published
- 2019
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14. Extracorporeal membrane oxygenation in acute respiratory distress syndrome due to influenza A (H1N1)pdm09 pneumonia. A single-center experience during the 2013-2014 season.
- Author
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Menon N, Perez-Velez CM, Wheeler JA, Morris MF, Amabile OL, Tasset MR, and Raschke RA
- Subjects
- Adult, Aged, Blood Gas Analysis, Female, Humans, Influenza A Virus, H1N1 Subtype isolation & purification, Influenza, Human therapy, Intensive Care Units, Length of Stay, Male, Middle Aged, Pneumonia, Viral therapy, Quality-Adjusted Life Years, Respiration, Artificial, Respiratory Distress Syndrome etiology, Retrospective Studies, Treatment Outcome, Extracorporeal Membrane Oxygenation methods, Influenza, Human complications, Pneumonia, Viral complications, Respiratory Distress Syndrome therapy
- Abstract
Objective: This report aimed to describe the outcomes of the patients with severe H1N1 associated acute respiratory distress syndrome who were treated with extracorporeal membrane oxygenation therapy., Methods: This retrospective review analyzed a single-center cohort of adult patients with H1N1-related acute respiratory distress syndrome who were managed with veno-venous extracorporeal membrane oxygenation during the winter of 2013/2014., Results: A total of 10 patients received veno-venous extracorporeal membrane oxygenation for H1N1 influenza between January 2013 and March 2014. Seven patients were transferred to our center for extracorporeal membrane oxygenation consideration (all within 72 hours of initiating mechanical ventilation). The median patient age was forty years, and 30% were female. The median arterial oxygen partial pressure to fraction of inspired oxygen ratio was 62.5, and the median RESP score was 6. Three patients received inhaled nitric oxide, and four patients were proned as rescue therapy before extracorporeal membrane oxygenation was initiated. The median duration of mechanical ventilation was twenty-two days (range, 14 - 32). The median length of stay in the intensive care unit was twenty-seven days (range, 14 - 39). The median hospital length of stay was 29.1 days (range, 16.0 - 46.9). Minor bleeding complications occurred in 6 of 10 patients. Eight of the ten patients survived to hospital discharge., Conclusion: The survivors were relatively young and discharged with good functional status (i.e., enhancing quality-adjusted life-years-saved). Our experience shows that even a relatively new extracorporeal membrane oxygenation program can play an important role in that capacity and provide excellent outcomes for the sickest patients.
- Published
- 2017
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15. Small-scale drivers: the importance of nutrient availability and snowmelt timing on performance of the alpine shrub Salix herbacea.
- Author
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Little CJ, Wheeler JA, Sedlacek J, Cortés AJ, and Rixen C
- Subjects
- Climate Change, Nitrogen metabolism, Principal Component Analysis, Reproduction physiology, Salix growth & development, Seasons, Snow, Switzerland, Time Factors, Ecosystem, Nitrogen analysis, Salix physiology
- Abstract
Alpine plant communities are predicted to face range shifts and possibly extinctions with climate change. Fine-scale environmental variation such as nutrient availability or snowmelt timing may contribute to the ability of plant species to persist locally; however, variation in nutrient availability in alpine landscapes is largely unmeasured. On three mountains around Davos, Switzerland, we deployed Plant Root Simulator probes around 58 Salix herbacea plants along an elevational and microhabitat gradient to measure nutrient availability during the first 5 weeks of the summer growing season, and used in situ temperature loggers and observational data to determine date of spring snowmelt. We also visited the plants weekly to assess performance, as measured by stem number, fruiting, and herbivory damage. We found a wide snowmelt gradient which determined growing season length, as well as variations of an order of magnitude or more in the accumulation of 12 nutrients between different microhabitats. Higher nutrient availability had negative effects on most shrub performance metrics, for instance decreasing stem number and the proportion of stems producing fruits. High nutrient availability was associated with increased herbivory damage in early-melting microhabitats, but among late-emerging plants this pattern was reversed. We demonstrate that nutrient availability is highly variable in alpine settings, and that it strongly influences performance in an alpine dwarf shrub, sometimes modifying the response of shrubs to snowmelt timing. As the climate warms and human-induced nitrogen deposition continues in the Alps, these factors may contribute to patterns of local plants persistence.
- Published
- 2016
- Full Text
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16. The Response of the Alpine Dwarf Shrub Salix herbacea to Altered Snowmelt Timing: Lessons from a Multi-Site Transplant Experiment.
- Author
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Sedlacek J, Wheeler JA, Cortés AJ, Bossdorf O, Hoch G, Lexer C, Wipf S, Karrenberg S, van Kleunen M, and Rixen C
- Subjects
- Confidence Intervals, Flowers physiology, Likelihood Functions, Plant Leaves anatomy & histology, Plant Stems anatomy & histology, Reproduction, Time Factors, Ecosystem, Salix physiology, Snow
- Abstract
Climate change is altering spring snowmelt patterns in alpine and arctic ecosystems, and these changes may alter plant phenology, growth and reproduction. To predict how alpine plants respond to shifts in snowmelt timing, we need to understand trait plasticity, its effects on growth and reproduction, and the degree to which plants experience a home-site advantage. We tested how the common, long-lived dwarf shrub Salix herbacea responded to changing spring snowmelt time by reciprocally transplanting turfs of S. herbacea between early-exposure ridge and late-exposure snowbed microhabitats. After the transplant, we monitored phenological, morphological and fitness traits, as well as leaf damage, during two growing seasons. Salix herbacea leafed out earlier, but had a longer development time and produced smaller leaves on ridges relative to snowbeds. Longer phenological development times and smaller leaves were associated with reduced sexual reproduction on ridges. On snowbeds, larger leaves and intermediate development times were associated with increased clonal reproduction. Clonal and sexual reproduction showed no response to altered snowmelt time. We found no home-site advantage in terms of sexual and clonal reproduction. Leaf damage probability depended on snowmelt and thus exposure period, but had no short-term effect on fitness traits. We conclude that the studied populations of S. herbacea can respond to shifts in snowmelt by plastic changes in phenology and leaf size, while maintaining levels of clonal and sexual reproduction. The lack of a home-site advantage suggests that S. herbacea may not be adapted to different microhabitats. The studied populations are thus unlikely to react to climate change by rapid adaptation, but their responses will also not be constrained by small-scale local adaptation. In the short term, snowbed plants may persist due to high stem densities. However, in the long term, reduction in leaf size and flowering, a longer phenological development time and increased exposure to damage may decrease overall performance of S. herbacea under earlier snowmelt.
- Published
- 2015
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17. Small-scale patterns in snowmelt timing affect gene flow and the distribution of genetic diversity in the alpine dwarf shrub Salix herbacea.
- Author
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Cortés AJ, Waeber S, Lexer C, Sedlacek J, Wheeler JA, van Kleunen M, Bossdorf O, Hoch G, Rixen C, Wipf S, and Karrenberg S
- Subjects
- Climate Change, Ecosystem, Flowers genetics, Population Density, Population Dynamics, Seasons, Seeds genetics, Gene Flow genetics, Genetic Variation genetics, Salix genetics
- Abstract
Current threats to biodiversity, such as climate change, are thought to alter the within-species genetic diversity among microhabitats in highly heterogeneous alpine environments. Assessing the spatial organization and dynamics of genetic diversity within species can help to predict the responses of organisms to environmental change. In this study, we evaluated whether small-scale heterogeneity in snowmelt timing restricts gene flow between microhabitats in the common long-lived dwarf shrub Salix herbacea L. We surveyed 273 genets across 12 early- and late-snowmelt sites (that is, ridges and snowbeds) in the Swiss Alps for phenological variation over 2 years and for genetic variation using seven SSR markers. Phenological differentiation triggered by differences in snowmelt timing did not correlate with genetic differentiation between microhabitats. On the contrary, extensive gene flow appeared to occur between microhabitats and slightly less extensively among adjacent mountains. However, ridges exhibited significantly lower levels of genetic diversity than snowbeds, and patterns of effective population size (Ne) and migration (Nem) between microhabitats were strongly asymmetric, with ridges acting as sources and snowbeds as sinks. As no recent genetic bottlenecks were detected in the studied sites, this asymmetry is likely to reflect current meta-population dynamics of the species dominated by gene flow via seeds rather than ancient re-colonization after the last glacial period. Overall, our results suggest that seed dispersal prevents snowmelt-driven genetic isolation, and snowbeds act as sinks of genetic diversity. We discuss the consequences of such small-scale variation in gene flow and diversity levels for population responses to climate change.
- Published
- 2014
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18. Increased spring freezing vulnerability for alpine shrubs under early snowmelt.
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Wheeler JA, Hoch G, Cortés AJ, Sedlacek J, Wipf S, and Rixen C
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- Altitude, Biomass, Climate, Ecosystem, Plant Leaves, Switzerland, Ericaceae physiology, Freezing, Salix physiology, Seasons, Snow, Vaccinium physiology
- Abstract
Alpine dwarf shrub communities are phenologically linked with snowmelt timing, so early spring exposure may increase risk of freezing damage during early development, and consequently reduce seasonal growth. We examined whether environmental factors (duration of snow cover, elevation) influenced size and the vulnerability of shrubs to spring freezing along elevational gradients and snow microhabitats by modelling the past frequency of spring freezing events. We sampled biomass and measured the size of Salix herbacea, Vaccinium myrtillus, Vaccinium uliginosum and Loiseleuria procumbens in late spring. Leaves were exposed to freezing temperatures to determine the temperature at which 50% of specimens are killed for each species and sampling site. By linking site snowmelt and temperatures to long-term climate measurements, we extrapolated the frequency of spring freezing events at each elevation, snow microhabitat and per species over 37 years. Snowmelt timing was significantly driven by microhabitat effects, but was independent of elevation. Shrub growth was neither enhanced nor reduced by earlier snowmelt, but decreased with elevation. Freezing resistance was strongly species dependent, and did not differ along the elevation or snowmelt gradient. Microclimate extrapolation suggested that potentially lethal freezing events (in May and June) occurred for three of the four species examined. Freezing events never occurred on late snow beds, and increased in frequency with earlier snowmelt and higher elevation. Extrapolated freezing events showed a slight, non-significant increase over the 37-year record. We suggest that earlier snowmelt does not enhance growth in four dominant alpine shrubs, but increases the risk of lethal spring freezing exposure for less freezing-resistant species.
- Published
- 2014
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19. Safety studies conducted on a sanitizing agent containing benzalkonium chloride.
- Author
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Dolan LC, Wheeler JA, and Burdock GA
- Subjects
- Acetic Acid adverse effects, Acetic Acid analysis, Animals, Benzalkonium Compounds analysis, DNA Damage drug effects, Dose-Response Relationship, Drug, Female, Food Contamination prevention & control, Food Microbiology, Food Preservatives analysis, Guidelines as Topic, Male, Micronucleus Tests, Mutagens adverse effects, Mutagens analysis, Parabens adverse effects, Parabens analysis, Rats, Rats, Sprague-Dawley, Toxicity Tests, Benzalkonium Compounds adverse effects, Consumer Product Safety, Food Preservatives adverse effects
- Abstract
Unlabelled: Free N Clear is a sanitizing agent composed of United States Pharmacopeial Convention grade benzalkonium chloride (BAC), acetic acid, and methylparaben. Free N Clear is proposed for use as a sanitizing agent at a 1: 50 dilution (2% solution), which contains approximately 100 ppm BAC. As part of a program to assess its safety, a 2% solution of Free N Clear (diluted Free N Clear) was administered by gavage to Sprague-Dawley rats for 91d and tested for genetic toxicity in vitro and in vivo. In the 91d study, the no observable adverse-effect level of diluted Free N Clear in male and female Sprague-Dawley rats is 5000 mg/kg bw/day, the highest dose administered. Diluted Free N Clear was not mutagenic in a bacterial reverse mutation assay that tested concentrations extending into the toxic range, and did not increase the frequency of micronucleated polychromatic erythrocytes in bone marrow cells of male or female Sprague-Dawley rats when tested at the maximum permissible dose volume of 20 mL/kg bw. The results support safety of Free N Clear, when used at the concentration proposed for use., Practical Application: The significance of these findings will allow for the development of Free N Clear as a potential sanitizing agent for food., (© 2012 Institute of Food Technologists®)
- Published
- 2013
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20. Interpretation domestic and foreign.
- Author
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Vega JA
- Subjects
- Adolescent, Adult, Female, Humans, Male, Semantics, Movement, Nonverbal Communication, Psychoanalytic Interpretation, Psychotherapy, Verbal Behavior
- Abstract
Verbal and nonverbal behavior are on all fours when it comes to interpretation. This idea runs counter to an intuition that, to borrow a phrase, speech is cooked but action is raw. The author discusses some of the most compelling psychoanalytic work on the interpretation of action and presents empirical and philosophical findings about understanding speech. These concepts generate reciprocal implications about the possibility of interpreting the exotics of action and the necessity of interpreting the domestics of speech, treating both as equally dignified aspects of human behavior. The author presents a number of clinical examples to further illustrate these ideas.
- Published
- 2012
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21. Three varieties of authority.
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Vega JA
- Subjects
- Humans, Professional-Patient Relations, Psychotherapeutic Processes, Self Disclosure, Knowledge, Psychoanalytic Interpretation, Psychoanalytic Therapy
- Abstract
Doubts about what can be known may hide what can be said. A focus on knowledge claims and norms that order them--first-, second-, and third-person authority--can replace epistemological projects of all stripes. Further, skeptical worries can be alleviated by attention to the way in which competent language users are secured from radical error by the intersubjective origin and refinement of our thought. Clinical examples, brief outlines of applications, and closer examination of two topics--the assertion of interpretive authority and therapeutic self-disclosure-illustrate some practical uses of these ideas.
- Published
- 2009
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22. Assessment of quality of life and oral function of patients participating in a phase II study of radioprotection of oral and pharyngeal mucosa by the prostaglandin E(1) analog misoprostol (RTOG 96-07).
- Author
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Johnson DJ, Scott CB, Marks JE, Seay TE, Atkins JN, Berk LB, Meoz RT, and Wheeler JA
- Subjects
- Adult, Aged, Antineoplastic Agents therapeutic use, Female, Humans, Laryngeal Neoplasms radiotherapy, Male, Middle Aged, Mouth Neoplasms radiotherapy, Neoplasm Metastasis prevention & control, Pharyngeal Neoplasms radiotherapy, Quality of Life, Surveys and Questionnaires, Time Factors, Alprostadil analogs & derivatives, Misoprostol therapeutic use, Mouth Mucosa radiation effects, Mouth Neoplasms prevention & control, Mucous Membrane radiation effects, Pharynx radiation effects
- Abstract
Purpose: The oral complications associated with radiotherapy to the head and neck are a significant dose-limiting factor. The goals of this study were to determine whether oropharyngeal rinsing and ingestion of misoprostol protect mucous membranes from the acute effects of irradiation, and to evaluate the quality-of-life (QOL) outcomes of patients receiving misoprostol. We report the results of the QOL outcomes of patients in this study., Methods and Materials: A total of 33 patients with resected or intact cancer of the oral cavity, oropharynx, supraglottic larynx, or hypopharynx were registered to receive postoperative radiotherapy plus misoprostol or primary radiotherapy plus misoprostol. All patients were scheduled to receive 60-70 Gy at 2 Gy/d within 6-7 weeks. QOL and function were evaluated., Results: A decrease in the QOL and function occurred in all areas covered by the questionnaire at the 6-week interval. This decrease was significant for eating, saliva, taste, and mucous. Of these significant factors, taste, saliva, and mucous consistency had not resolved by 12 weeks., Conclusion: Increased understanding of the impact of treatment on QOL and symptoms will formulate the rational design of toxicity interventions and enhance the multidisciplinary care of head-and-neck patients.
- Published
- 2002
- Full Text
- View/download PDF
23. Expression of the RNA binding proteins, Mel-N1, Mel-N2, and Mel-N3 in adipose cells.
- Author
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Qi C, Wheeler JA, Pruett A, and Pekala PH
- Subjects
- 3T3 Cells, Adipocytes cytology, Alternative Splicing, Amino Acid Sequence, Animals, Base Sequence, Blotting, Western, Brain metabolism, Cell Differentiation physiology, Down-Regulation, ELAV Proteins, ELAV-Like Protein 2, Electrophoresis, Gel, Two-Dimensional, Fibroblasts cytology, Fibroblasts metabolism, Mice, Molecular Sequence Data, Nerve Tissue Proteins genetics, Organ Specificity, Polyribosomes metabolism, Protein Isoforms biosynthesis, Protein Isoforms genetics, RNA, Messenger metabolism, RNA-Binding Proteins genetics, Adipocytes metabolism, Nerve Tissue Proteins biosynthesis, RNA-Binding Proteins biosynthesis
- Abstract
Mel-N1 (murine embryonic lethal abnormal vision [ELAV]), a mammalian homolog of Drosophila ELAV, is an mRNA binding protein of the RNA Recognition Motif family. Studies with the human homolog, Hel-N1 have supported the hypothesis that Hel-N1, and its splice variant, Hel-N2 play a role in mRNA metabolism. Thus it becomes logical to extend this hypothesis to the murine variant Mel-N1 which has been described as a neuronal protein with a minor level of expression in the testis. Our current work expands the potential function for this protein through demonstration of expression of the full-length message and splice variants in adipose tissue as well as preadipocyte and adipocyte cell lines., ((c) 2002 Elsevier Science (USA).)
- Published
- 2002
- Full Text
- View/download PDF
24. The beneficial effects of volunteering for older volunteers and the people they serve: a meta-analysis.
- Author
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Wheeler JA, Gorey KM, and Greenblatt B
- Subjects
- Female, Humans, Male, North America, Aged psychology, Personal Satisfaction, Volunteers psychology
- Abstract
The current political-economic climate, which is generally supportive of both private and public sector down-sizing, increasingly demands that human service workers assess, engage, and creatively use consumer strengths and resources. This meta-analysis of thirty-seven independent studies provided the means of inferring not only that elder volunteers' sense of well-being seemed to be significantly bolstered through volunteering, but also that such relatively healthy older people represent a significant adjunct resource for meeting some of the service needs of more vulnerable elders, as well as those of other similarly vulnerable groups such as disabled children. Averaging across studies, 85 percent of the "clients" who received service from an older volunteer (e.g., peer-counseling of nursing home residents) scored better on dependent measures (e.g., diminished depression) than the average person in comparison conditions did (U3 = .847 [Cohen, 1988], combined p < .001). The policy implications of such beneficial effects among both older volunteers and the people they serve are discussed.
- Published
- 1998
- Full Text
- View/download PDF
25. About the cellular tropism of the gammaherpesvirus bovine herpesvirus type 4.
- Author
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Osorio FA, Galeota-Wheeler JA, Reed DE, and Lopez O
- Subjects
- Animals, Cattle, Cell Separation, DNA, Viral isolation & purification, Herpesviridae Infections virology, Lymphocytes virology, Monocytes virology, Organ Specificity, Cattle Diseases virology, Gammaherpesvirinae isolation & purification, Herpesviridae Infections veterinary
- Published
- 1996
- Full Text
- View/download PDF
26. Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay.
- Author
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Mayr NA, Yuh WT, Magnotta VA, Ehrhardt JC, Wheeler JA, Sorosky JI, Davis CS, Wen BC, Martin DD, Pelsang RE, Buller RE, Oberley LW, Mellenberg DE, and Hussey DH
- Subjects
- Adenocarcinoma pathology, Adenocarcinoma radiotherapy, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell radiotherapy, Disease-Free Survival, Female, Humans, Neoplasm Staging, Prognosis, Prospective Studies, Radiotherapy Dosage, Treatment Outcome, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms radiotherapy, Adenocarcinoma blood supply, Carcinoma, Squamous Cell blood supply, Magnetic Resonance Imaging methods, Neoplasm Recurrence, Local diagnosis, Uterine Cervical Neoplasms blood supply
- Abstract
Purpose: This study investigated sequential changes in tumor blood supply using magnetic resonance (MR) perfusion imaging and assessed their significance in the prediction of outcome of patients with advanced cervical cancer. The purpose of this project was to devise a simple, noninvasive method to predict early signs of treatment failure in advanced cervical cancer treated with conventional radiation therapy., Methods and Materials: Sixty-eight MR perfusion studies were performed prospectively in 17 patients with squamous carcinomas (14) and adenocarcinomas (3) of the cervix, Stages bulky IB (1), IIB (5), IIIA (1), IIIB (8), and IVA (1), and recurrent (1). Four sequential studies were obtained in each patient: immediately before radiation therapy (pretherapy), after a dose of 20-22 Gy/ approximately 2 weeks (early therapy), after a dose of 40-45 Gy/ approximately 4-5 weeks (midtherapy), and 4-6 weeks after completion of therapy (follow-up). Perfusion imaging of the tumor was obtained at 3-s intervals in the sagittal plane. A bolus of 0.1 mmol/kg of MR contrast material (gadoteridol) was injected intravenously 30 s after beginning image acquisition at a rate of 9 ml/s using a power injector. Time/signal-intensity curves to reflect the onset, slope, and relative signal intensity (rSI) of contrast enhancement in the tumor region were generated. Median follow-up was 8 months (range 3-18 months)., Results: Tumors with a higher tissue perfusion (rSI > or = 2.8) in the pretherapy and early therapy (20-22 Gy) studies had a lower incidence of local recurrence than those with a rSI of < 2.8, but this was not statistically significant (13% vs. 67%; p = 0.05). An increase in tumor perfusion early during therapy (20-22 Gy), particularly to an rSI of > or = 2.8, was the strongest predictor of local recurrence (0% vs. 78%; p = 0.002). However, pelvic examination during early therapy (20-22 Gy) commonly showed no appreciable tumor regression. The slope of the time/signal-intensity curve obtained before and during radiation therapy also correlated with local recurrence. Follow-up perfusion studies did not provide information to predict recurrence., Conclusion: These preliminary results suggest that two simple MR perfusion studies before and early in therapy can offer important information on treatment outcome within the first 2 weeks of radiation therapy before response is evident by clinical examination. High tumor perfusion before therapy and increasing or persistent high perfusion early during the course of therapy appear to be favorable signs. High perfusion suggests a high blood and oxygen supply to the tumor. The increase in tumor perfusion seen in some patients early during radiation therapy suggests improved oxygenation of previously hypoxic cells following early cell kill. Radiation therapy is more effective in eradicating these tumors, resulting in improved local control. Our technique may be helpful in identifying early-while more aggressive therapy can still be implemented-those patients who respond poorly to conventional radiation therapy.
- Published
- 1996
- Full Text
- View/download PDF
27. Definitive radiotherapy for carcinoma of the vagina: outcome and prognostic factors.
- Author
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Chyle V, Zagars GK, Wheeler JA, Wharton JT, and Delclos L
- Subjects
- Adenocarcinoma epidemiology, Adenocarcinoma pathology, Adenocarcinoma secondary, Adolescent, Adult, Aged, Aged, 80 and over, Brachytherapy, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell secondary, Female, Humans, Inguinal Canal, Lymphatic Metastasis, Middle Aged, Neoplasm Recurrence, Local epidemiology, Neoplasm Recurrence, Local mortality, Pelvis, Radiation Injuries epidemiology, Radioisotope Teletherapy, Retrospective Studies, Salvage Therapy, Survival Rate, Treatment Outcome, Vaginal Neoplasms epidemiology, Vaginal Neoplasms pathology, Adenocarcinoma radiotherapy, Carcinoma, Squamous Cell radiotherapy, Vaginal Neoplasms radiotherapy
- Abstract
Purpose: Primary carcinoma of the vagina is an uncommon tumor. Because of the long-standing interest in this disease at our institution a substantial number of patients with this disease has been accumulated, and this retrospective review was performed to define disease outcome, to delineate significant prognostic factors, and to provide treatment guidelines., Methods and Materials: This was a retrospective review of 301 patients with vaginal carcinoma (271 with squamous cell and 30 with adenocarcinoma) who received definitive radiotherapy between 1953 and 1991. Prognostic factors for outcome (local control, pelvic control, metastatic relapse, survival, and complications) were evaluated using univariate and multivariate techniques., Results: Patients disease was staged using the International Federation of Gynecology and Obstetrics (FIGO) system, and stages were distributed as follows: 0, 37 (12%); I, 65 (22%); II, 122 (40%); III, 60 (20%); and, IVA, 17 (6%). Treatment varied according to stage, with brachytherapy predominating for early disease but external beam playing a prominent role for more advanced disease. Patients with in situ disease received brachytherapy alone or transvaginal orthovoltage irradiation. For Stage I, brachytherapy alone was used in 25, external beam and brachytherapy in 38, and transvaginal alone in 2. For Stage II, brachytherapy alone was used in 20, external and brachytherapy in 66, and external irradiation alone in 36. For Stage III, external and brachytherapy was used in 15, and external alone in 45. Two patients with Stage IVA received brachytherapy alone, 10 received a combination of external and brachytherapy, and 6 received external irradiation alone. Total doses ranged from 10 to 154 Gy (mean 74.7 Gy, median 70.0 Gy), but only 18 (6%) received less than 55 Gy. At a median follow-up of 13 years, the 5-, 10-, 15-, 20-, and 25-year survival rates were 60%, 49%, 38%, 29%, and 23%, respectively. Beyond 5 years the survival rates relative to those for age-matched females in the general population were between 50 and 65%. Actuarial local recurrence rates were 23%, 26%, and 26% at 5, 10, and 15 years. Actuarial pelvic relapse rates were 26%, 30%, and 31% at 5, 10, and 15 years, and metastatic rates at those times were 15%, 18%, and 18%. Adenocarcinoma (nonclear cell) was a significantly worse disease than squamous cell carcinoma. The major determinants of local control for squamous carcinoma were tumor bulk (specified by size in centimeters, or by FIGO stage), tumor site (upper lesions faring better than others), and tumor circumferential location (lesions involving the posterior wall faring worse). Tumor bulk was an important determinant of metastatic relapse, but failure to achieve local control was also an independently significant determinant of metastases. Salvage after first relapse was uncommon and the survival rate at 5 years after relapse was only 12%. Serious complications occurred in 39 patients with an actuarial incidence of 19% at 20 years., Conclusion: Vaginal carcinoma poses a formidable therapeutic challenge. The disease is heterogeneous with respect to its prognostic factors. Nonclear cell adenocarcinoma has an extremely poor prognosis and should be distinguished from squamous carcinoma. Both external beam and brachytherapy play crucial roles in management and most patients with disease beyond in situ should receive a significant component of external irradiation prior to brachytherapy.
- Published
- 1996
- Full Text
- View/download PDF
28. Usefulness of tumor volumetry by magnetic resonance imaging in assessing response to radiation therapy in carcinoma of the uterine cervix.
- Author
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Mayr NA, Magnotta VA, Ehrhardt JC, Wheeler JA, Sorosky JI, Wen BC, Davis CS, Pelsang RE, Anderson B, Doornbos JF, Hussey DH, and Yuh WT
- Subjects
- Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Neoplasm, Residual, Prospective Studies, Remission Induction, Magnetic Resonance Imaging, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms radiotherapy
- Abstract
Purpose: Clinical evaluation of tumor size in cervical cancer is often difficult, and clinical signs of radiation therapy failure may not be present until well after completion of treatment. The purpose of this study is to investigate early indicators of treatment response using magnetic resonance (MR) imaging for quantitative assessment of tumor volume and tumor regression rate before, during, and after radiation therapy., Methods and Materials: Thirty-four patients with cervical cancer Stages IB [5], IIB [8], IIIA [1], IIIB [14], IVA [3], IVB [1], and recurrent [2] were studied prospectively with four serial MR examinations obtained at the start of radiation therapy, at 2-2.5 weeks (20-24 Gy), at 4-5 weeks (40-50 Gy), and 1-2 months after treatment completion. Tumor volume was assessed by three-dimensional volumetric measurements using T2-weighted images of each MR examination. The volume regression rate was generated based on the four sequential MR studies. These findings were correlated with local control, metastasis rate, and disease-free survival. Median follow-up was 18 months (range: 9-43 months)., Results: The tumor regression rate after a dose of 40-50 Gy correlated significantly with treatment outcome. The actuarial 2-year disease-free survival was 88.4% in patients with tumors regressing to < 20% of the initial volume compared with 45.4% in those with > or = 20% residual (p = 0.007). The incidence of local recurrence was 9.5% (2 out of 21) and 76.9% (10 out of 13), respectively (p < 0.001). Analysis by initial tumor volume showed that this observation was valid in patients with initial volumes between 40 and 100 cm3. Analysis by FIGO stage confirmed this observation in all patients except those with Stage IB., Conclusion: Sequential tumor volumetry using MR imaging appears to be a sensitive measure of the responsiveness of cervical cancer to irradiation. Treatment response can be assessed as early as during the course of radiation therapy by measurement of initial tumor volume and regression rate at 40-50 Gy. In patients with large (> 40 cm3) and advanced (Stage > or = IIIA) tumors, this technique may be helpful in supplementing the clinical examination for response assessment. The identification of patients at high risk for treatment failure may ultimately lead to improved clinical outcome.
- Published
- 1996
- Full Text
- View/download PDF
29. Brachytherapy and continuous infusion 5-fluorouracil for treatment of locally advanced, lymph node negative, prostate cancer: a phase I trial.
- Author
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See WA, Dreicer R, Wheeler JA, Forest PK, and Loening S
- Subjects
- Aged, Combined Modality Therapy, Humans, Infusions, Intravenous, Lymphatic Metastasis, Male, Middle Aged, Radiotherapy Dosage, Antineoplastic Agents therapeutic use, Brachytherapy, Fluorouracil therapeutic use, Gold Radioisotopes therapeutic use, Prostatic Neoplasms drug therapy, Prostatic Neoplasms radiotherapy, Radiation-Sensitizing Agents therapeutic use
- Abstract
Background: 5-fluorouracil (5-FU) is a known radiosensitizer that enhances efficacy, in vivo and in vitro, when administered during radiotherapy. The following study was performed to evaluate the toxicity of continuous infusion 5-FU administered concomitant with brachytherapy in patients with locally advanced prostate cancer., Methods: Over a 26-month period, a total of 25 patients with newly diagnosed, locally advanced prostate cancer underwent radioactive gold (Au198) brachytherapy. Twenty-four of 25 patients were surgically staged and confirmed node negative. Au198 seed placement was performed transperineally under fluoroscopic and ultrasonographic guidance using an average of 195 mCi of Au198. Within 4 hours after seed placement, 25 patients received 5-FU administered as a continuous infusion over 4 days, at 1 of 8 dose levels ranging from 200-1100 mg/m2/day. Patients had clinical follow-up for a minimum of 1 year. Decreases in serum prostate specific antigen (PSA) and prostate volume (normalized to pretreatment values) were determined at 12 months., Results: 5-FU associated toxicity was negligible, with Grade 1 nausea in four patients and no Grade 2 or higher toxicity. No unique locoregional toxicity was noted. At 12 months after treatment, PSA values decreased on average to 16.4% of pretreatment values. Twelve-month prostate volumes decreased to 55% of the pretreatment values., Conclusions: These findings suggest that continuous infusion 5-FU can be administered safely concomitant with brachytherapy at doses up to 1100 mg/m2 per day for 4 days.
- Published
- 1996
30. ASTRO Research Fellowship: apoptosis as a predictor of tumor response to radiation in stage IB cervical carcinoma. American Society for Therapeutic Radiology and Oncology.
- Author
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Wheeler JA, Stephens LC, Tornos C, Eifel PJ, Ang KK, Milas L, Allen PK, and Meyn RE Jr
- Subjects
- Adenocarcinoma mortality, Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Predictive Value of Tests, Radiotherapy methods, Retrospective Studies, Survival Rate, Time Factors, Treatment Failure, Uterine Cervical Neoplasms mortality, Adenocarcinoma pathology, Adenocarcinoma radiotherapy, Apoptosis radiation effects, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms radiotherapy
- Abstract
Purpose: Levels of apoptosis predict for tumor responsiveness to radiation in various animal systems. To investigate the potential role of apoptosis as a predictor of response in human tumors, a retrospective review was undertaken of patients with adenocarcinoma of the cervix whose primary lesion at presentation measured at least 4 cm and who underwent definitive radiation therapy. A previous report had indicated that roughly half this group of patients should have a long-term relapse free survival., Methods and Materials: Pretreatment biopsy specimens of 44 patients with Stage IB adenocarcinoma of the cervix, whose primary lesion at presentation measured at least 4 cm in greatest dimension, were scored for apoptosis by two independent investigators without knowledge of the treatment outcome, and the results were averaged. Actuarial methods were used to assess overall survival, disease-free survival, determinate survival, and local control as a function of the baseline level of apoptosis. Patients ranged in age from 21 to 87 years and were treated with definitive radiotherapy between 1964 and 1989. Follow-up for the surviving patients ranged from 1 to 278 months, with a mean of 101 months., Results: Patients whose tumors had a baseline level of apoptosis above the median value (2%) had a better overall survival than those with lower levels of apoptosis (p = 0.056). A similar trend for disease-free survival (p = 0.32) and determinate survival (p = 0.27) did not reach statistical significance, perhaps because of the small number of patients. Because only 6 of the 44 patients (13%) had a local tumor failure, it was not possible to establish a correlation between the pretreatment level of apoptosis and the local tumor control by radiation., Conclusion: The baseline level of apoptosis predicted for survival in patients with Stage IB cervical adenocarcinoma. Further investigation of the measurement of apoptosis as a potential predictive assay is warranted in other human tumor systems.
- Published
- 1995
- Full Text
- View/download PDF
31. Dedifferentiation of locally recurrent prostate cancer after radiation therapy. Evidence for tumor progression.
- Author
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Wheeler JA, Zagars GK, and Ayala AG
- Subjects
- Aged, Humans, Male, Middle Aged, Neoplasm Recurrence, Local mortality, Prostatic Neoplasms mortality, Prostatic Neoplasms radiotherapy, Survival Analysis, Cell Differentiation radiation effects, Neoplasm Recurrence, Local pathology, Prostatic Neoplasms pathology
- Abstract
Background: Untreated or unsuccessfully treated prostatic adenocarcinoma may develop more malignant characteristics as time passes--the phenomenon of tumor progression. Whether this occurs after unsuccessful radiation therapy has not been answered. This study was designed to address that issue., Methods: The histologic grades at initial diagnosis and at local recurrence were compared in 49 patients who experienced local recurrence after external beam radiation therapy., Results: Tumor grades were assigned using the M. D. Anderson grading system. At the initial diagnosis, the grades were distributed as follows: Grade 1, 18 (37%), Grade 2, 22 (45%); Grade 3, 8 (16%); and Grade 4, 1 (2%). At recurrence, the grades were: Grade 1, 3 (6%); Grade 2, 14 (29%); Grade 3, 14 (29%); and Grade 4, 18 (37%). The shift to higher grades at recurrence was highly significant (P < 0.001). This dedifferentiation could not be accounted for by possible tissue sampling variability, and stepwise multiple variable logistic regression revealed that the only factor predicting for dedifferentiation was the time since treatment. The tumors that recurred later had a significantly higher likelihood to be dedifferentiated than those that recurred early. Patients whose tumors dedifferentiated had a poorer survival than those whose tumors retained their original grade., Conclusions: The possibilities were considered that the dedifferentiation could arise by tissue sampling error, by persistence and regrowth of high-grade components, by the development of new tumors, or by radiation-induced transformation. None of these mechanisms appeared to explain the data adequately, and it was concluded that the observed dedifferentiation was indeed a manifestation of time-dependent tumor progression. Eradication of the primary tumor is therefore important, not only to allay local symptoms, but also to prevent the emergence of more virulent and potentially lethal tumors.
- Published
- 1993
- Full Text
- View/download PDF
32. Area of overlap and interference in phase space versus Wigner pseudoprobabilities.
- Author
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Schleich W, Walls DF, and Wheeler JA
- Published
- 1988
- Full Text
- View/download PDF
33. Null-strut calculus: The first test.
- Author
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Kheyfets A, Miller WA, and Wheeler JA
- Published
- 1988
- Full Text
- View/download PDF
34. Guide to literature of elementary particle physics, including cosmic rays.
- Author
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TIOMNO J and WHEELER JA
- Subjects
- Humans, Cosmic Radiation, Crystallization, Elementary Particles, Physics, Publications
- Published
- 1949
35. Joseph Henry (1797-1878) architect of organized science.
- Author
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WHEELER JA and BAILEY HS Jr
- Subjects
- History, 18th Century, History, 19th Century, Science
- Published
- 1946
36. Elementary particle physics.
- Author
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WHEELER JA
- Subjects
- Elementary Particles, Nuclear Energy, Physics
- Published
- 1947
37. Trichinosis; with report of a case.
- Author
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TATE WM and WHEELER JA
- Subjects
- Humans, Trichinellosis
- Published
- 1950
38. Correspondence principle analysis of double-photon emission.
- Author
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WHEELER JA
- Subjects
- Humans, Photons
- Published
- 1947
- Full Text
- View/download PDF
39. Problems and prospects in elementary particle research.
- Author
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WHEELER JA
- Subjects
- Elementary Particles, Nuclear Energy, Research
- Published
- 1946
40. Temporal arteritis: report of a case with ACTH therapy.
- Author
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TATE WM and WHEELER JA
- Subjects
- Humans, Adrenocorticotropic Hormone, Arteritis, Giant Cell Arteritis, Temporal Arteries
- Published
- 1951
41. Maria Sklodowska Curie: Copernicus of the World of the Small: The last century of physics is examined, some of its achievements are assessed, and the road ahead is surveyed.
- Author
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Wheeler JA
- Published
- 1968
- Full Text
- View/download PDF
42. Herbicides in the perspectives of 20 months and 20 yeatrs.
- Author
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Wheeler JA
- Subjects
- Arsenicals, Ecology, United States, Vietnam, Chemical Warfare, Herbicides
- Published
- 1968
- Full Text
- View/download PDF
43. How mesons disappear.
- Author
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WHEELER JA
- Subjects
- Humans, Mesons
- Published
- 1948
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