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101.
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
102.
David A. Ganz MD PhD Anita H. Yuan PhD MPH Erich J. Greene PhD Nancy K. Latham PT PhD Katy Araujo MPH Albert L. Siu MD MSPH Jay Magaziner MSHyg PhD Jerry H. Gurwitz MD Albert W. Wu MD MPH Neil B. Alexander MD Robert B. Wallace MD MSc Susan L. Greenspan MD Jeremy Rich DPM Elena Volpi MD PhD Stephen C. Waring DVM PhD Patricia C. Dykes RN PhD MA Fred Ko MD MS Neil M. Resnick MD Siobhan K. McMahon PhD MPH GNP Shehzad Basaria MD Rixin Wang PhD Charles Lu MS Denise Esserman PhD James Dziura PhD Michael E. Miller PhD Thomas G. Travison PhD Peter Peduzzi PhD Shalender Bhasin MB BS David B. Reuben MD Thomas M. Gill MD 《Journal of the American Geriatrics Society》2022,70(11):3221-3229
103.
Dr. G. O. Barbezat MD FCP F. S. B. Bowey MB ChB E.R. Kaplan PhD R. Hickman ChM MD 《Digestive diseases and sciences》1978,23(3):222-224
In dogs with gastric fistulae and Heidenhain pouches, inhibition of histamine-stimulated gastric acid secretion by the histamine H2-receptor antagonist metiamide is not increased by the addition of a histamine H1-receptor antagonist (mepyramine maleate). Under the conditions of this study there is no evidence for the presence of histamine H1-receptor sites on the gastric parietal cell.Financial assistance was provided by the South African Medical Research Council. 相似文献
104.
Gluten-sensitive recurrent aphthous stomatitis 总被引:4,自引:0,他引:4
Twenty selected patients with recurrent aphthous stomatitis in whom celiac disease had been specifically excluded were placed on a gluten-free diet. Five patients (25%) showed a favorable response to gluten withdrawal and a positive gluten challenge. Jejunal morphology was normal in all patients indicating gluten sensitivity without enteropathy. Gluten withdrawal provides a further method of treating some patients with recurrent aphthous stomatitis. 相似文献
105.
Clonal dysregulation of the antibody response to tetanus-toxoid after bone marrow transplantation 总被引:2,自引:0,他引:2
Gerritsen EJ; Van Tol MJ; Van 't Veer MB; Wels JM; Khouw IM; Touw CR; Jol-Van Der Zijde CM; Hermans J; Rumke HC; Radl J 《Blood》1994,84(12):4374-4382
After bone marrow transplantation (BMT), a prolonged dysregulation of humoral immunity can be observed. In the present study, we investigated whether this is reflected in an abnormal production of specific antibodies (Ab) to the T-cell-dependent recall antigen tetanus-toxoid (TT). The study group consisted of children receiving transplants of an unmodified allogeneic graft and of adults receiving either a T-cell- depleted allogeneic or an unmodified autologous BM graft. Findings were compared with those in healthy controls. In pediatric graft recipients, who were routinely revaccinated early after BMT, the Ab response was quantitatively superior to that in adult graft recipients who did not receive early revaccination. In the majority of graft recipients, the time period after vaccination required to reach the peak level of antibodies was prolonged and the number of responding TT-specific B- cell clones was markedly decreased in comparison with controls. In controls, a low frequency of dominant B-cell clones may produce low quantities of homogeneous Ab components (H-Ab) against a heterogeneous background. However, in BM graft recipients, "overshooting" of Ab production by separate B-cell clones was observed, resulting in the development of H-Ab at a relatively high concentration. These abnormalities were present up to 10 years after BMT, irrespective of either the age of the recipient, the modulation of the graft, or the vaccination schedule used. It is hypothesized that the dysregulated Ab production is the consequence of activation of a restricted number of resting memory B cells, present in germinal centers, repopulating gradually after BMT. Our data show that routine revaccination early after BMT improves the humoral immune response. However, because of a clonally dysregulated Ab production, long-lasting qualitative defects may be present even after normalization of Ab titers. 相似文献
106.
Outcome and prognostic factors for children with supratentorial primitive neuroectodermal tumors treated with carboplatin during radiotherapy: A report from the Children's Oncology Group
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Regina I. Jakacki MD Peter C. Burger MD Mehmet Kocak PhD James M. Boyett PhD Joel Goldwein MD Minesh Mehta MB eChB Roger J. Packer MD Nancy J. Tarbell MD Ian F. Pollack MD 《Pediatric blood & cancer》2015,62(5):776-783
Background
Supratentorial PNETs (sPNET) are uncommon embryonal malignancies of the central nervous system whose prognosis has historically been poor. We evaluated the outcome and prognostic factors of children with sPNET treated prospectively on a Children's Oncology Group trial.Procedure
Following surgery, patients received craniospinal radiotherapy with concurrent carboplatin followed by six months of maintenance chemotherapy with cyclophosphamide and vincristine.Results
Five‐year overall survival (OS) and progression‐free survival (PFS) for all patients was 58 ± 7% and 48 ± 7%. For patients with pineoblastoma (n = 23), five‐year OS and PFS was 81 ± 9% and 62 ± 11%. Extent of resection but not M‐stage was prognostic. Five‐year OS and PFS for 37 patients with non‐pineal tumors (NPsPNET) was 44 ± 8% and 39 ± 8%, significantly worse than for PB (P = 0.055 and 0.009 respectively). Extent of resection and major radiotherapy deviations were prognostic. Five year OS was 59 +/? 11.4% for those undergoing complete resection versus 10.4 +/? 7% for those who did not (P = 0.017). Central pathologic review called 14 (38%) “classic” sPNET, 8 (22%) “undifferentiated” and 13 (35%) “malignant gliomas.” There was no significant difference between the subgroups, although survival distributions approached significance when the combined “classic” and “undifferentiated” group was compared to the “malignant gliomas.”Conclusions
Carboplatin during RT followed by 6 months of non‐intensive chemotherapy is a feasible treatment strategy for patients with sPNET. Aggressive surgical resection should be attempted if feasible. The classification of supratentorial small cell malignancies can be difficult. Pediatr Blood Cancer 2015;62:776–783. © 2015 Wiley Periodicals, Inc.107.
Determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease: The DOC study
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Sarah J. Ronaldson MSc BSc Lisa Dyson MSc BA Laura Clark MSc BSc Catherine E. Hewitt PhD MSc BSc David J. Torgerson PhD MSc Brendan G. Cooper PhD MSc BSc Matt Kearney MPH MB ChB William Laughey MBChB MSc Raghu Raghunath PhD MD Lisa Steele BSc Rebecca Rhodes BMED Sci Joy Adamson PhD MSc BSc 《Journal of evaluation in clinical practice》2018,24(3):487-495
108.
109.
110.
The effect of unit,depth, and probe load on the reliability of muscle shear wave elastography: Variables affecting reliability of SWE
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