Browsing by Author "Hoffman, Richard"

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    DIFFERENTIAL EFFECTS OF VARYING DOSES OF DIETARY NITRATE ON MUSCLE FUNCTION AND BLOOD PRESSURE IN OLDER SUBJECTS
    (Oxford University Press, 2019-11) Coggan, Andrew R.; Gallardo, Edgar; Gray, Derrick A.; Hoffman, Richard; Moorthi, Ranjani; Kinesiology, School of Physical Education and Tourism Management
    We have recently demonstrated that dietary nitrate, a source of nitric oxide via the enterosalivary pathway, can improve muscle contractile function in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in older individuals. However, the optimal dose for eliciting these beneficial effects is unknown. We therefore performed a randomized, double-blind, crossover study to determine the effects of ingesting 3.3 mL/kg of beetroot juice (BRJ) containing 0, 212, or 425 µmol/kg of nitrate in six healthy older (age 69±3 y) subjects. Maximal knee extensor speed (Vmax) and power (Pmax) were measured 2 h after BRJ ingestion using isokinetic dynamometry; blood pressure was monitored periodically throughout each study. Mean arterial pressure (in mmHg) was lower (P<0.05) after the high (80±4) vs. the low (84±3) or placebo (88±2) doses. Vmax (in rad/s), however, was higher (P<0.05) after the low dose (11.7±0.8), but not the high dose (10.8±1.0), compared to the placebo (10.5±1.0). Pmax (in W/kg) also tended to be higher (P=0.11) in the low (3.9±0.5) compared to the placebo (3.7±0.5) or high (3.7±0.5) trials. Five out of six subjects achieved a higher Vmax and Pmax after the low vs. the high dose. We conclude that dietary nitrate has differential effects on muscle function and blood pressure in older individuals. A high dose of nitrate intake further lowers blood pressure but does not enhance muscle contractility as much as a lower dose. Supported by Indiana University Purdue University Indianapolis and by the NIA (R21 AG053606).
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    Impact of Muscle Measures on Outcome in Patients Receiving Endocrine Therapy for Metastatic Breast Cancer: Analysis of ECOG-ACRIN E2112
    (National Comprehensive Cancer Network, 2023) Ballinger, Tarah J.; Marques, Helga S.; Xue, Gloria; Hoffman, Richard; Gatsonis, Constantine; Zhao, Fengmin; Miller, Kathy D.; Sparano, Joseph; Connolly, Roisin M.; Medicine, School of Medicine
    Background: Observational data investigating the relationship between body habitus and outcomes in breast cancer have been variable and inconsistent, largely centered in the curative setting and focused on weight-based metrics. This study evaluated the impact of muscle measures on outcomes in patients with metastatic breast cancer receiving endocrine-based therapy. Methods: Baseline CT scans were collected from ECOG-ACRIN E2112, a randomized phase III placebo-controlled study of exemestane with or without entinostat. A CT cross-sectional image at the L3 level was extracted to obtain skeletal muscle mass and attenuation. Low muscle mass (LMM) was defined as skeletal muscle index <41 cm2/m2 and low muscle attenuation (LMA) as muscle density <25 HU or <33 HU if overweight/obese by body mass index (BMI). Multivariable Cox proportional hazard models determined the association between LMM or LMA and progression-free survival (PFS) and overall survival (OS). Correlations between LMM, LMA, and patient-reported outcomes were determined using 2-sample t tests. Results: Analyzable CT scans and follow-up data were available for 540 of 608 patients. LMM was present in 39% (n=212) of patients and LMA in 56% (n=301). Those with LMA were more likely to have obesity and worse performance status. LMM was not associated with survival (PFS hazard ratio [HR]: 1.13, P=.23; OS HR: 1.05, P=.68), nor was LMA (PFS HR: 1.01, P=.93; OS HR: 1.00, P=.99). BMI was not associated with survival. LMA, but not LMM, was associated with increased frequency of patient-reported muscle aches. Conclusions: Both low muscle mass and density are prevalent in patients with hormone receptor-positive metastatic breast cancer. Muscle measures correlated with obesity and performance status; however, neither muscle mass nor attenuation were associated with prognosis. Further work is needed to refine body composition measurements and select optimal cutoffs with meaningful endpoints in specific breast cancer populations, particularly those living with metastatic disease.
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    Molecular and clinical effects of aromatase inhibitor therapy on skeletal muscle function in early-stage breast cancer
    (Springer Nature, 2024-01-10) Seibert, Tara A.; Shi, Lei; Althouse, Sandra; Hoffman, Richard; Schneider, Bryan P.; Russ, Kristen A.; Altherr, Cody A.; Warden, Stuart J.; Guise, Theresa A.; Coggan, Andrew R.; Ballinger, Tarah J.; Exercise & Kinesiology, School of Health and Human Sciences
    We evaluated biochemical changes in skeletal muscle of women with breast cancer initiating aromatase inhibitors (AI), including oxidation of ryanodine receptor RyR1 and loss of stabilizing protein calstabin1, and detailed measures of muscle function. Fifteen postmenopausal women with stage I–III breast cancer planning to initiate AI enrolled. Quadriceps muscle biopsy, dual-energy x-ray absorptiometry, isokinetic dynamometry, Short Physical Performance Battery, grip strength, 6-min walk, patient-reported outcomes, and serologic measures of bone turnover were assessed before and after 6 months of AI. Post-AI exposure, oxidation of RyR1 significantly increased (0.23 ± 0.37 vs. 0.88 ± 0.80, p < 0.001) and RyR1-bound calstabin1 significantly decreased (1.69 ± 1.53 vs. 0.74 ± 0.85, p < 0.001), consistent with dysfunctional calcium channels in skeletal muscle. Grip strength significantly decreased at 6 months. No significant differences were seen in isokinetic dynamometry measures of muscle contractility, fatigue resistance, or muscle recovery post-AI exposure. However, there was significant correlation between oxidation of RyR1 with muscle power (r = 0.60, p = 0.02) and muscle fatigue (r = 0.57, p = 0.03). Estrogen deprivation therapy for breast cancer resulted in maladaptive changes in skeletal muscle, consistent with the biochemical signature of dysfunctional RyR1 calcium channels. Future studies will evaluate longer trajectories of muscle function change and include other high bone turnover states, such as bone metastases.