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71.
R P Witherspoon R Storb H D Ochs N Fluornoy K J Kopecky K M Sullivan J H Deeg R Sosa D R Noel K Atkinson E D Thomas 《Blood》1981,58(2):360-368
One-hundred fifty-three recipients of HLA-identical sibling marrow transplants for aplastic anemia or hematologic malignancy were injected with bacteriophage phi X174 (phage), pneumococcal polysaccharide antigen (PPA), or keyhole limpet hemocyanin (KLH). Antibody levels were determined several times in the 6 wk after injection. Multiple regression techniques were used to determine what factors played significant roles in the antibody response. The most significant factors were the time elapsed from transplantation, chronic graft- versus-host disease (GVHD), and antithymocyte globulin (ATG) treatment. All patients had low antibody responses to all antigens in the first 180 days from transplant. Beyond 180 days patients without chronic GVHD showed antibody responses indistinguishable from those of normal donors. However, patients with chronic GVHD had the following impairments: (1) primary response to phage, (2) conversion from IgM to IgG in secondary response to phage, (3) secondary response to KLH, and (4) response to PPA. ATG treatment given to patients either prophylactically or therapeutically for acute GVHD was followed by lower primary responses to phage in the first 180 days and poor ability to switch from IgM to IgG antibody in the secondary response beyond 180 days postgrafting. Other factors did not yield additional significant information about ability to predict antibody responses including diagnosis, conditioning regimen, treatment in or out of laminar air flow rooms, transplantation, pretransplant refractoriness of the recipient to platelet transfusions from random donors, donor age or donor sex, and steroid administration for treatment for prevention of GVHD. The data indicate that, given enough time after transplantation, the ability to produce normal antibody function recovers except in those patients experiencing chronic GVHD. 相似文献
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Brandon P. Verdoorn MD Tamara K. Evans BS Gregory J. Hanson MD Yi Zhu PhD Larissa G. P. Langhi Prata PhD Robert J. Pignolo MD PhD Elizabeth J. Atkinson MS Erin O. Wissler-Gerdes MA George A. Kuchel MD Joan B. Mannick MD Stephen B. Kritchevsky PhD Sundeep Khosla MD Stacey A. Rizza MD Jeremy D. Walston MD Nicolas Musi MD Lewis A. Lipsitz MD Douglas P. Kiel MD Raymond Yung MB ChB Nathan K. LeBrasseur PhD Ravinder J. Singh PhD Teresa McCarthy MD MS Michael A. Puskarich MD Laura J. Niedernhofer MD PhD Paul D. Robbins PhD Matthew Sorenson JD MA Tamara Tchkonia PhD James L. Kirkland MD PhD 《Journal of the American Geriatrics Society》2021,69(11):3023-3033
The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials. 相似文献
74.
Correct allometric analysis is always helpful for scaling flow‐mediated dilation in research and individual patient contexts 下载免费PDF全文
Lorenzo Lolli Alan M. Batterham Greg Atkinson 《Clinical physiology and functional imaging》2018,38(5):907-910
McLay et al. (Clin Physiol Funct Imaging (2017); DOI: 10.1111/cpf.12465 ) recently examined whether the allometric scaling of flow‐mediated dilation influenced the mean difference between samples of young and older adults compared with the traditional percentage change approach. They also explored whether a new scaling calculation improved the ability to obtain individually scaled flow‐mediated dilation. In our response to their study, we can demonstrate that McLay et al. (Clin Physiol Funct Imaging, 2017) have (i) managed to formulate a new scaling index which does nothing to remove the dependency of that index on baseline diameter and (ii) suggested, incorrectly, that the original allometric approach cannot be used to derive individually‐adjusted values of flow‐mediated dilation, which can be interpreted in a similar way to a percentage change. 相似文献
75.
Desmond A. Brown Benjamin T. Himes Brittny T. Major Benjamin F. Mundell Ravi Kumar Bruce Kall Fredric B. Meyer Michael J. Link Bruce E. Pollock John D. Atkinson Jamie J. Van Gompel W. Richard Marsh Giuseppe Lanzino Mohamad Bydon Ian F. Parney 《Mayo Clinic proceedings. Mayo Clinic》2018,93(1):16-24
Objective
To determine adverse event rates for adult cranial neuro-oncologic surgeries performed at a high-volume quaternary academic center and assess the impact of resident participation on perioperative complication rates.Patients and Methods
All adult patients undergoing neurosurgical intervention for an intracranial neoplastic lesion between January 1, 2009, and December 31, 2013, were included. Cases were categorized as biopsy, extra-axial/skull base, intra-axial, or transsphenoidal. Complications were categorized as neurologic, medical, wound, mortality, or none and compared for patients managed by a chief resident vs a consultant neurosurgeon.Results
A total of 6277 neurosurgical procedures for intracranial neoplasms were performed. After excluding radiosurgical procedures and pediatric patients, 4151 adult patients who underwent 4423 procedures were available for analysis. Complications were infrequent, with overall rates of 9.8% (435 of 4423 procedures), 1.7% (73 of 4423), and 1.4% (63 of 4423) for neurologic, medical, and wound complications, respectively. The rate of perioperative mortality was 0.3% (14 of 4423 procedures). Case performance and management by a chief resident did not negatively impact outcome.Conclusion
In our large-volume brain tumor practice, rates of complications were low, and management of cases by chief residents in a semiautonomous manner did not negatively impact surgical outcomes. 相似文献76.
Stephen E. Daniels Hartley C. Atkinson Ioana Stanescu Chris Frampton 《Clinical therapeutics》2018,40(10):1765-1776.e5
Purpose
Acute pain is a significant burden to the individual and to society. There is a clear need for a pain medication that provides improved analgesia over common analgesics, without compromising tolerability. The goal of this study was to determine the efficacy of a new fixed-dose combination of acetaminophen 975 mg and ibuprofen 292.5 mg (FDC 975/292.5) relative to acetaminophen or ibuprofen monotherapy, or placebo.Methods
This prospective, multicenter, randomized, double-blind, placebo-controlled, Phase III trial included 408 adult volunteers aged 18 to 60 years experiencing moderate to severe pain after surgical removal of at least 2 impacted third molars. Subjects were randomized in a 3:3:3:2 ratio to the following interventions: FDC 975/292.5, acetaminophen 975 mg, ibuprofen 292.5 mg, and placebo. Self-reported pain intensity scores were recorded over a 48-hour double-blind treatment period using a 100-mm visual analog scale. In addition, time to perceptible and meaningful pain relief was assessed by using the two-stopwatch method; use of rescue medication (oxycodone) was recorded; and patients rated their pain relief on a 5-point categorical scale. All adverse events during the 30-day study period were assessed.Findings
The majority of participants were female (67.4%) and white (90.0%), with a mean age of 24.8 years. Demographic and baseline characteristics were balanced across treatment groups, with a mean baseline pain score of 56.4 mm. The primary end point was the time-adjusted sum of pain intensity differences over 48 hours, which was found to be significantly greater for FDC 975/292.5 than for both monotherapies and placebo (all, P < 0.001). The robustness of the procedures used in the calculation of the primary end point was confirmed in a series of sensitivity analyses. Statistical superiority of the combination was evident in all secondary end points (time to meaningful pain relief, maximum pain score, response rate, participants using supplementary analgesia, time to rescue, oxycodone consumption, and categorical pain relief score) with the exception of time to perceptible pain relief versus monotherapies and the time to peak response versus ibuprofen. The percentage of patients reporting adverse events was 37.3% in the FDC 975/292.5 group, with no significant differences between treatment groups. Nausea was the most common adverse event across all groups.Implications
Overall, the fixed-dose combination of acetaminophen and ibuprofen provided greater and more rapid analgesia than comparable doses of either agent alone or placebo in adults after removal of impacted third molars. ClinicalTrials.gov identifier: NCT01420653. 相似文献77.
We present findings from a qualitative, multisite, multi-method, longitudinal study of parents and their preschool-aged children that explores the intersections of marketing influences in the home and in the larger outside world of children. Findings indicate that preschoolers represent complicated and nuanced “consumers in training” beyond predictions based on their “perceptual stage of development.” Specifically, our data revealed interesting ways in which marketing and consumer culture can foster a number of pro-social consumer outcomes (e.g., charity, gift-giving, financial literacy). We also noted an emerging understanding by preschoolers of the social meanings of goods for identity construction and product evaluation. Finally, through a presentation of an idiographic case, we show how consumer socialization cannot be attributed to one factor such as media but is based on multiple and concurrent factors—parents, siblings, peers, and home environment—that act to moderate, mediate, and provide meaning for marketing messages. 相似文献
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Seelig MH Malouf YL Klingler PJ Oldenburg WA Atkinson EJ 《VASA. Zeitschrift für Gef?sskrankheiten》2000,29(4):265-268
BACKGROUND: The aim of this study was to determine the clinical utility of transthoracic echocardiography (TTE) as a screening method for the detection of abdominal aortic aneurysms (AAA). PATIENTS AND METHODS: Each patient who was referred to the echocardiography laboratory TTE was included into the study. After complete cardiac assessment the abdominal aorta was evaluated. Patients with a known, a clinically suspected, or a previously operated AAA were excluded. RESULTS: During the study period, 14,876 patients underwent TTE. 13,166 (88.5%) of the patients were 50 years and older. Of these 6953 (52.8%) were men and 6213 (47.2%) were women. A total of 108 (0.82%; 95% confidence interval (CI) 0.67-0.99) clinically unsuspected AAA of at least 3 cm in diameter (range 3 cm-6.8 cm) were detected. There were 93 (86.1%) men and 15 (13.9%) women with a mean age of 73.8 years (range 59-90). In 7 patients an AAA was suspected by TTE but not verified on subsequent abdominal ultrasound, as the diameter of the abdominal aorta was less than 3 cm. The prevalence of an AAA in patients 50 years and older was 1.34% (95% CI 1.08-1.64) for men and 0.24% (95% CI 0.14-0.40) for women. In patients less than 50 years old no aneurysm was detected. Seventeen patients who were found to have an AAA with a mean diameter of 4.4 cm (range 3-6 cm) underwent successful elective conventional AAA repair after a mean interval of 13.9 months (range 0.2-49 months) following the initial diagnosis. CONCLUSIONS: TTE performed in a highly selected cardiac patient group in a tertiary referral center is not a useful tool to screen for clinically unsuspected abdominal aortic aneurysms due to the low prevalence. The detection of an aneurysm should be confirmed by conventional abdominal ultrasound. 相似文献