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181.
A. I. DeAngelis A. R. Needle T. W. Kaminski T. R. Royer C. A. Knight C. B. Swanik 《Scandinavian journal of medicine & science in sports》2015,25(4):509-516
Growing evidence suggests that the nervous system contributes to non‐contact knee ligament injury, but limited evidence has measured the effect of extrinsic events on joint stability. Following unanticipated events, the startle reflex leads to universal stiffening of the limbs, but no studies have investigated how an acoustic startle influences knee stiffness and muscle activation during a dynamic knee perturbation. Thirty‐six individuals were tested for knee stiffness and muscle activation of the quadriceps and hamstrings. Subjects were seated and instructed to resist a 40‐degree knee flexion perturbation from a relaxed state. During some trials, an acoustic startle (50 ms, 1000 Hz, 100 dB) was applied 100 ms prior to the perturbation. Knee stiffness, muscle amplitude, and timing were quantified across time, muscle, and startle conditions. The acoustic startle increased short‐range (no startle: 0.044 ± 0.011 N·m/deg/kg; average startle: 0.047 ± 0.01 N·m/deg/kg) and total knee stiffness (no startle: 0.036 ± 0.01 N·m/deg/kg; first startle 0.027 ± 0.02 N·m/deg/kg). Additionally, the startle contributed to decreased [vastus medialis (VM): 13.76 ± 33.6%; vastus lateralis (VL): 6.72 ± 37.4%] but earlier (VM: 0.133 ± 0.17 s; VL: 0.124 ± 0.17 s) activation of the quadriceps muscles. The results of this study indicate that the startle response can significantly disrupt knee stiffness regulation required to maintain joint stability. Further studies should explore the role of unanticipated events on unintentional injury. 相似文献
182.
183.
Role of the coronary sinus in maintenance of atrial fibrillation 总被引:2,自引:0,他引:2
Oral H Ozaydin M Chugh A Scharf C Tada H Hall B Cheung P Pelosi F Knight BP Morady F 《Journal of cardiovascular electrophysiology》2003,14(12):1329-1336
INTRODUCTION: Bursts of tachycardia arising in the pulmonary veins may play an important role in perpetuating atrial fibrillation (AF). However, the role of the coronary sinus (CS) in the perpetuation of AF has been unclear. The aim of this study was to determine whether the CS plays a role in perpetuation of AF. METHODS AND RESULTS: Pulmonary vein isolation was performed by segmental ostial ablation with radiofrequency energy in 22 consecutive patients with paroxysmal AF. Bipolar and unipolar electrograms recorded in the left atrium and CS were analyzed during atrial pacing from the mitral annulus and during AF. There was a mean of 2.5 +/- 0.5 electrical connections between the CS and the left atrium. The electrical connections between the left atrium and CS were ablated with a mean of 6.2 +/- 2.7 minutes of radiofrequency energy applied along the atrial side of the inferior mitral annulus. During AF, episodes of intermittent tachycardia alternated between the left atrium and the CS. Among the 22 patients, sustained AF was still inducible in 9 after pulmonary vein isolation. After electrical disconnection of the CS from the left atrium, sustained AF was inducible in only 3 of these 9 patients. CONCLUSION: The CS may be a source of rapid repetitive electrical activity during AF. The lower probability of inducible sustained AF after electrical disconnection of the CS from the left atrium suggests that the CS may play a role in perpetuating AF. 相似文献
184.
A safety study on intrathecal delivery of autologous mesenchymal stromal cells in rabbits directly supporting Phase I human trials 下载免费PDF全文
185.
Stella E. Hines Elizabeth A. Barker Maura Robinson Vijaya Knight Joanna Gaitens Michael Sills Kirby Duvall Cecile S. Rose 《CTS Clinical and Translational Science》2015,8(6):722-728
Objectives
An epoxy resin worker developed hypersensitivity pneumonitis requiring lung transplantation and had an abnormal blood lymphocyte proliferation test (LPT) to an epoxy hardener. We assessed the prevalence of symptoms, abnormal spirometry, and abnormal epoxy resin LPT results in epoxy resin workers compared to unexposed workers.Methods
Participants completed questionnaires and underwent spirometry. We collected blood for epoxy resin LPT and calculated stimulation indices for five epoxy resin products.Results
We compared 38 exposed to 32 unexposed workers. Higher exposed workers were more likely to report cough (OR 10.86, [1.23‐infinity], p = 0.030) or wheeze (OR 4.44, [1.00‐22.25], p = 0.049) than unexposed workers, even controlling for smoking. Higher exposed workers were more likely to have abnormal FEV1 than unexposed workers (OR 10.51, [0.86‐589.9], p = 0.071), although not statistically significant when adjusted for smoking. There were no differences in proportion of abnormal epoxy resin system LPTs between exposed and unexposed workers.Conclusions
In summary, workers exposed to epoxy resin system chemicals were more likely to report respiratory symptoms and have abnormal FEV1 than unexposed workers. Use of epoxy resin LPT was not helpful as a biomarker of exposure and sensitization. 相似文献186.
187.
Julie C. Sung Ciara Bosh Brooke Wyatt Mark Miller Alyson Harty David Del Bello Sterling Knight Douglas T. Dieterich Ponni V. Perumalswami Andrea D. Branch 《Journal of viral hepatitis》2020,27(4):350-359
Patient‐reported outcomes (PROs) are important measures of quality of life. Direct‐acting antiviral (DAA) drugs for hepatitis C virus (HCV) improved PROs in clinical trials. We prospectively evaluated the impact of DAA‐based HCV cure on PROs and liver‐related outcomes in real‐world patients at a large urban medical center. The short form (SF)‐36 and three additional validated instruments were used. F3‐4 fibrosis was defined as > 9.6 kPa by transient elastography (TE); S2‐3 steatosis was defined as > 270 dB/m by TE‐controlled attenuation parameter (CAP). Data were analysed by paired and unpaired t tests. Patients (n = 16) who did not achieve a sustained virologic response at 12 weeks (SVR12) were excluded. The study achieved its primary endpoint and showed a significant 30% improvement in the SF‐36 vitality score, measured baseline to SVR12: 63 versus 82, P < .001 (n = 111). Scores in 24 of 25 PRO domains improved at SVR12 (P < .05). Nearly all gains exceeded 5%, indicating their clinical significance. Transaminase values and liver stiffness improved (decreased) significantly, baseline to SVR12 (P < .005), but steatosis was unchanged (P = .58). Patients with baseline F0‐2 fibrosis and those with F3‐F4 fibrosis both improved in 22 domains. Patients with baseline S0‐S1 steatosis improved in more domains (23) than patients with S2‐S3 steatosis (19). At baseline, patients with F3‐F4 fibrosis and patients with S2‐3 steatosis had worse scores in certain PRO domains than patients with F0‐2 fibrosis or S0‐S1 steatosis, but this difference resolved by SVR12. HCV cure led to meaningful gains in PROs, and these findings may encourage patients to seek treatment. 相似文献
188.
Peter Newham Daniel Ross Peter Ceuppens Shampa Das James W. T. Yates Catherine Betts Jaimini Reens Kevin J. Randall Richard Knight Jennifer S. McKay 《Inflammation research》2014,63(2):149-160
Objective and design
TNF-α neutralization is associated with increased mortality in mouse cecal ligation puncture (CLP) models. AZD9773 is an ovine polyclonal human TNF-α immune Fab, with pharmacological properties that differ from previously studied anti-TNF-α agents. We explored the safety and efficacy of therapeutically administered AZD9773 in mouse CLP sepsis.Methods
A moderate/severe-grade CLP model resulting in 20–30 % 5-day survival and a mild-grade CLP model resulting in ~70 % 5-day survival were established in human TNF-α transgene/murine TNF null (Tg1278/?/?) mice.Treatment
Mice received saline resuscitation and imipenem administration every 12 h (0–72 h post-CLP). AZD9773 (or DigiFab control) was dosed 24, 36, 48 and 60 h post-CLP.Results
Therapeutic dosing of AZD9773 in moderate/severe-grade CLP resulted in significantly increased survival (>70 %) compared with DigiFab (27 %, P < 0.05). Therapeutic dosing of AZD9773 in mild-grade CLP did not significantly affect survival outcome compared with DigiFab or imipenem alone (~60–70 % survival).Conclusions
These data demonstrate that TNF-α neutralization can improve survival in moderate/severe CLP sepsis. TNF-α suppression in mild-grade models was not associated with survival benefit and did not increase 5-day mortality. These findings suggest that therapeutic benefit following TNF-α attenuation in models of sepsis may depend on model severity. 相似文献189.
190.
Kudrat M. Abdulkadyrov Galina N. Salogub Nuriet K. Khuazheva Matthew L. Sherman Abderrahmane Laadem Rachel Barger Robert Knight Shankar Srinivasan Evangelos Terpos 《British journal of haematology》2014,165(6):814-823
This phase IIa study evaluated the safety and tolerability of sotatercept, and its effects on bone metabolism and haematopoiesis in newly diagnosed and relapsed multiple myeloma (MM) patients. Patients were randomized (4:1) to receive four 28‐d cycles of sotatercept (0·1, 0·3, or 0·5 mg/kg) or placebo. Patients also received six cycles of combination oral melphalan, prednisolone, and thalidomide (MPT). Thirty patients were enrolled; six received placebo and 24 received sotatercept. Overall, 25% of patients received all four sotatercept doses; 71% of sotatercept‐treated patients had ≥1 dose interruption mainly due to increases in haemoglobin levels. Grade ≥3 adverse events (AEs) were reported in 17% of patients receiving placebo and 58% receiving sotatercept. Grade 4 AEs in sotatercept‐treated patients were neutropenia, granulocytopenia, and atrial fibrillation (one patient each). In patients without bisphosphonate use, anabolic improvements in bone mineral density and in bone formation relative to placebo occurred, whereas bone resorption was minimally affected. Increases in haemoglobin levels, versus baseline, and the duration of the increases, were higher in the sotatercept‐treated patients, with a trend suggesting a dose‐related effect. Multiple doses of sotatercept plus MPT appear to be safe and generally well‐tolerated in MM patients. 相似文献