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1.
JAAPA ; 32(1): 23-27, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30589731

ABSTRACT

Levamisole is a veterinary antihelminthic, chemotherapeutic agent, and immunomodulator that also is used as an adulterant and cutting agent in cocaine distribution. This drug may potentiate the sympathomimetic actions of cocaine and can cause neutropenia, agranulocytosis, purpuric retiform lesions, and skin necrosis. This article describes two cases of suspected levamisole-induced vasculitis. No standardized diagnostic or treatment algorithm exists for this challenging condition. Diagnosis and treatment require a multidisciplinary team approach.


Subject(s)
Adjuvants, Immunologic/adverse effects , Anthelmintics/adverse effects , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/chemically induced , Levamisole/adverse effects , Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/therapy , Antibodies, Antineutrophil Cytoplasmic/blood , Biomarkers/blood , Cocaine-Related Disorders , Drug Contamination , Female , Humans , Middle Aged
2.
Exp Gerontol ; 106: 116-124, 2018 06.
Article in English | MEDLINE | ID: mdl-29481967

ABSTRACT

Age-related muscle loss (sarcopenia) is a major clinical problem affecting both men and women - accompanied by muscle weakness, dysfunction, disability, and impaired quality of life. Current definitions of sarcopenia do not fully encompass the age-related changes in skeletal muscle. We therefore examined the influence of aging and sex on elements of skeletal muscle health using a thorough histopathological analysis of myocellular aging and assessments of neuromuscular performance. Two-hundred and twenty-one untrained males and females were separated into four age cohorts [mean age 25 y (n = 47), 37 y (n = 79), 61 y (n = 51), and 72 y (n = 44)]. Total (-12%), leg (-17%), and arm (-21%) lean mass were lower in both 61 y and 72 y than in 25 y or 37 y (P < 0.05). Knee extensor strength (-34%) and power (-43%) were lower (P < 0.05) in the older two groups, and explosive sit-to-stand power was lower by 37 y (P < 0.05). At the histological/myocellular level, type IIx atrophy was noted by 37 y and type IIa atrophy by 61 y (P < 0.05). These effects were driven by females, noted by substantial and progressive type IIa and IIx atrophy across age. Aged female muscle displayed greater within-type myofiber size heterogeneity and marked type I myofiber grouping (~5-fold greater) compared to males. These findings suggest the predominant mechanisms leading to whole muscle atrophy differ between aging males and females: myofiber atrophy in females vs. myofiber loss in males. Future studies will be important to better understand the mechanisms underlying sex differences in myocellular aging and optimize exercise prescriptions and adjunctive treatments to mitigate or reverse age-related changes.


Subject(s)
Aging/pathology , Muscle Fibers, Skeletal/pathology , Muscular Atrophy/pathology , Sex Characteristics , Adult , Aged , Aged, 80 and over , Alabama , Female , Humans , Male , Middle Aged , Muscle Strength , Organ Size , Quality of Life , Young Adult
3.
J Burn Care Res ; 39(3): 345-352, 2018 04 20.
Article in English | MEDLINE | ID: mdl-28570309

ABSTRACT

In trauma, admission rapid thrombelastography (rTEG) has been shown to predict in-hospital thromboembolic events, guide treatment of coagulopathy, and identify likely to require large volume resuscitations. We sought to evaluate the use of rTEG in describing the coagulation status of major burn patients at admission and assess whether rTEG values predicted resuscitation volumes and patient outcomes. This is a retrospective study of all patients admitted to our Burn intensive care unit between January 2010 and December 2012. We excluded those with < 15% TBSA burns, < 18 years of age, and with concomitant injuries requiring admission to the Trauma intensive care unit. Previously published and validated cut points for hypocoagulable (activated clotting time ≥ 128; k-time ≥ 2.5; angle ≤ 60; mA ≤ 55; LY30 ≥ 3%) and hypercoagulable (mA ≥ 65) rTEG values were used. Supra-normal burn resuscitation was defined as ≥ 5.0 mL/kg/TBSA. Statistical analyses were conducted using STATA 13.1. Sixty-five patients met inclusion with a median age of 45 years, 74% male and 49% white. Median TBSA was 38% with 14% having third-degree burns. Sixty percentage of patients were hypercoagulable on admission, while 24% were hypocoagulable. rTEG values predicted increased 24-hour resuscitation volumes, as well as plasma and platelet transfusions (P < 0.05). Controlling for age, TBSA, and base deficit, admission rTEG ≥ 128 predicted a 5-fold increased likelihood of supra-normal resuscitation. In addition, an angle < 60 predicted in-hospital mortality. While the majority of severely burned patients arrive hypercoagulable, one-quarter are hypocoagulable and have increased resuscitation and transfusion requirements. Moreover, those with admission activated clotting time ≥ 128 are at 5-fold increased risk of supra-normal resuscitation.


Subject(s)
Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/prevention & control , Burns/complications , Burns/therapy , Resuscitation/methods , Thrombelastography , Adult , Aged , Blood Coagulation Disorders/mortality , Burns/mortality , Female , Hospital Mortality , Humans , Injury Severity Score , Male , Middle Aged , Predictive Value of Tests , Registries , Retrospective Studies , Texas
4.
Burns ; 42(8): 1704-1711, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27692780

ABSTRACT

RATIONAL: There has been increased focus on hemostatic potential and function in the initial assessment of the patient with traumatic injuries, that not been extensively studied in patients with burns. We proposed to determine the hemostatic potential of patients with burns upon admission to the emergency department and contrasted their condition with that of healthy controls and patients with other traumatic injuries. In addition we assessed differences due to thermal versus electrical injury and evaluated the effect of burn size. METHODS: This is a patient based prospective observational study conducted with delayed consented. Subjects at the highest level of trauma activation upon admission to the ED had a blood sample collected for research purposes and were subsequently consented. Hemostatic potential was measured by rapid thromelastography (r-TEG®), thrombin generation by calibrated automated thrombogram (CAT) and platelet function by Multiplate® using five activators. Burn subjects were compared to subjects with other traumatic injuries and controls. Within the burn subjects additional analysis compared mechanism (thermal vs. electrical) and burn size. Values are medians (IQR). RESULTS: Two hundred and eighty two trauma patients (with burns n=40, 14%) and 27 controls were enrolled. Upon admission, compared to controls, subjects with burns or trauma were hyper-coagulable based on r-TEG and CAT, with increased rates of clot formation and thrombin generation. There were no differences in burns compared to other traumatic injuries. The presence of hyper-coagulation did not appear to be related to the type of burn or the percentage of total body surface area involved. Employing previous defined cut points for R-TEG driven therapeutic interventions burn patients had similar rates of hyper- and hypo-coagulation noted in patients with traumatic injuries. CONCLUSION: Upon admission patients with burns are in a hyper-coagulable state similar to that of other trauma patients. Employing demonstrated cut points of hemostatic potential in trauma patients associated with increased risk of poor outcomes demonstrated the incidence in burn patients to be similar, suggesting that these values could be used in the early assessment of the patient with burns to guide treatment interventions.


Subject(s)
Burns, Electric/blood , Electric Injuries/blood , Thrombophilia/blood , Adult , Blood Coagulation Tests , Burns/blood , Burns/complications , Burns, Electric/complications , Case-Control Studies , Electric Injuries/complications , Female , Humans , Male , Middle Aged , Platelet Adhesiveness , Platelet Aggregation , Platelet Function Tests , Prospective Studies , Thrombelastography , Thrombin , Thrombophilia/complications , Wounds and Injuries/blood , Wounds and Injuries/complications , Young Adult
5.
Front Physiol ; 6: 184, 2015.
Article in English | MEDLINE | ID: mdl-26136691

ABSTRACT

The pathophysiological response to a severe burn injury involves a robust increase in circulating inflammatory/endocrine factors and a hypermetabolic state, both of which contribute to prolonged skeletal muscle atrophy. In order to characterize the role of circulating factors in muscle atrophy following a burn injury, human skeletal muscle satellite cells were grown in culture and differentiated to myoblasts/myotubes in media containing serum from burn patients or healthy, age, and sex-matched controls. While incubation in burn serum did not affect NFκB signaling, cells incubated in burn serum displayed a transient increase in STAT3 phosphorlyation (Tyr705) after 48 h of treatment with burn serum (≈ + 70%; P < 0.01), with these levels returning to normal by 96 h. Muscle cells differentiated in burn serum displayed reduced myogenic fusion signaling (phospho-STAT6 (Tyr641), ≈-75%; ADAM12, ≈-20%; both P < 0.01), and reduced levels of myogenin (≈-75%; P < 0.05). Concomitantly, myotubes differentiated in burn serum demonstrated impaired myogenesis (assessed by number of nuclei/myotube). Incubation in burn serum for 96 h did not increase proteolytic signaling (assessed via caspase-3 and ubiquitin levels), but reduced anabolic signaling [p-p70S6k (Ser421/Thr424), -30%; p-rpS6 (Ser240/244), ≈-50%] and impaired protein synthesis (-24%) (P < 0.05). This resulted in a loss of total protein content (-18%) and reduced cell size (-33%) (P < 0.05). Overall, incubation of human muscle cells in serum from burn patients results in impaired myogenesis and reduced myotube size, indicating that circulating factors may play a significant role in muscle loss and impaired muscle recovery following burn injury.

6.
J Burn Care Res ; 35(3): e172-6, 2014.
Article in English | MEDLINE | ID: mdl-24784904

ABSTRACT

Radiation burn injuries account for 0.2% of burn injury admissions. Treatment of radiation burns remains challenging because of unpredictable inflammatory changes and soft tissue necrosis. Conventional treatment consists of multistaged surgical procedures. Here, we present a case of an Iridium-192 exposure treated nonoperatively. A 23-year-old man presented with a 7-day-old, less than 1% TBSA radiation burn to his right hand. He initially sought treatment at an outside hospital and plastic surgeon's office postinjury days 2 and 3. He later presented to our facility because of worsening pain, edema, and discoloration. He was admitted and hospitalized for 15 days. Narcotics were initiated and wound care consisted of daily antibiotic ointment and petroleum gauze dressings. We continued dexamethasone and pentoxyfilline for 1 week. He underwent nineteen 90-minute treatments of hyperbaric oxygen therapy during an 8-week period. He had complete wound healing 1 month postdischarge. This case report provides background on radiation burn injuries and applicability of nonoperative management in treating radiation burn injuries. Furthermore, it encourages the development of individualized treatment plans, consideration of the use of hyperbaric oxygen therapy, referral to a burn center, and consulting radiation experts for guidance.


Subject(s)
Burns/etiology , Hyperbaric Oxygenation/methods , Iridium/adverse effects , Occupational Exposure/adverse effects , Radiation Injuries/therapy , Burns/physiopathology , Burns/therapy , Combined Modality Therapy , Follow-Up Studies , Hand Injuries/diagnosis , Hand Injuries/therapy , Humans , Injury Severity Score , Male , Occupational Health , Radiation Injuries/diagnosis , Treatment Outcome , Wound Healing/physiology , Young Adult
7.
J Burn Care Res ; 34(5): e297-304, 2013.
Article in English | MEDLINE | ID: mdl-23816995

ABSTRACT

Severe burn induces rapid skeletal muscle proteolysis after the injury, which persists for up to 1 year and results in skeletal muscle atrophy despite dietary and rehabilitative interventions. The purpose of this research was to determine acute changes in gene expression of skeletal muscle mass regulators postburn injury. Specimens were obtained for biopsy from the vastus lateralis of a nonburned leg of eight burned subjects (6M, 2F: 34.8 ± 2.7 years: 29.9 ± 3.1% TBSA burn) at 5.1 ± 1.1 days postburn injury and from matched controls. mRNA expression of cytokines and receptors in the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) families, and the ubiquitin proteasome E3 ligases, atrogin-1 and MuRF-1, was determined. TNF receptor 1A was over 3.5-fold higher in burn. Expression of TNF-like weak inducer of apoptosis and its receptor were over 1.6 and 6.0-fold higher in burn. IL-6, IL-6 receptor, and glycoprotein 130 were elevated in burned subjects with IL-6 receptor over 13-fold higher. The level of suppressor of cytokine signaling-3 was also increased nearly 6-fold in burn. Atrogin-1 and MuRF-1 were more than 4- and 3-fold higher in burn. These results demonstrate for the first time that severe burn in humans has a remarkable impact on gene expression in skeletal muscle of a nonburned limb of genes that promote inflammation and proteolysis. Because these changes likely contribute to the acute skeletal muscle atrophy in areas not directly affected by the burn, in the future it will be important to determine the responsible systemic cues.


Subject(s)
Burns/genetics , Muscle, Skeletal/injuries , Muscular Atrophy/genetics , Tumor Necrosis Factors/genetics , Adult , Biopsy, Needle , Body Surface Area , Burns/pathology , Cytokine TWEAK , Female , Gene Expression Regulation , Humans , Immunohistochemistry , Injury Severity Score , Male , Middle Aged , Muscle Proteins/genetics , Muscle Proteins/metabolism , Muscle, Skeletal/metabolism , RNA, Messenger/analysis , Real-Time Polymerase Chain Reaction/methods , Reference Values , SKP Cullin F-Box Protein Ligases/genetics , SKP Cullin F-Box Protein Ligases/metabolism , Sampling Studies , Sensitivity and Specificity , Tripartite Motif Proteins , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Up-Regulation , Young Adult
8.
J Appl Physiol (1985) ; 115(6): 937-48, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23681911

ABSTRACT

The regenerative response of skeletal muscle to mechanically induced damage is impaired with age. Previous work in our laboratory suggests this may result from higher proinflammatory signaling in aging muscle at rest and/or a greater inflammatory response to damage. We, therefore, assessed skeletal muscle proinflammatory signaling at rest and 24 h after unaccustomed, loaded knee extension contractions that induced modest muscle damage (72% increase in serum creatine kinase) in a cohort of 87 adults across three age groups (AGE40, AGE61, and AGE76). Vastus lateralis muscle gene expression and protein cell signaling of the IL-6 and TNF-α pathways were determined by quantitative PCR and immunoblot analysis. For in vitro studies, cell signaling and fusion capacities were compared among primary myoblasts from young (AGE28) and old (AGE64) donors treated with TNF-α. Muscle expression was higher (1.5- to 2.1-fold) in AGE76 and AGE61 relative to AGE40 for several genes involved in IL-6, TNF-α, and TNF-like weak inducer of apoptosis signaling. Indexes of activation for the proinflammatory transcription factors signal transducer and activator of transcription-3 and NF-κB were highest in AGE76. Resistance loading reduced gene expression of IL-6 receptor, muscle RING finger 1, and atrogin-1, and increased TNF-like weak inducer of apoptosis receptor expression. Donor myoblasts from AGE64 showed impaired differentiation and fusion in standard media and greater NF-κB activation in response to TNF-α treatment (compared with AGE28). We show for the first time that human aging is associated with muscle inflammation susceptibility (i.e., higher basal state of proinflammatory signaling) that is present in both tissue and isolated myogenic cells and likely contributes to the impaired regenerative capacity of skeletal muscle in the older population.


Subject(s)
Aging/physiology , Inflammation/physiopathology , Muscle, Skeletal/physiopathology , Regeneration/physiology , Adult , Aged , Aging/pathology , Female , Humans , Inflammation/pathology , Inflammation Mediators/physiology , Interleukin-6/metabolism , Male , Middle Aged , Muscle, Skeletal/injuries , Muscle, Skeletal/pathology , Muscular Atrophy/pathology , Muscular Atrophy/physiopathology , Myoblasts, Skeletal/physiology , STAT3 Transcription Factor/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism
9.
Expert Rev Respir Med ; 7(2): 159-70, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23547992

ABSTRACT

Inhalation injury is most commonly associated with damage to the mucosal surfaces of the small and large airways after exposure to smoke and other products of incomplete combustion. Yet, there are far deadlier things lurking within the smoke than just the heat and particulate matter: carbon monoxide and cyanide. These two toxic substances are found in varying concentrations within the fire room and are associated with early on-scene death and in-hospital morbidity and mortality. Patients suffering from carbon monoxide and/or cyanide poisoning present with vague symptoms requiring an astute physician to make the diagnosis. Fortunately, the toxic effects related to exposure to these agents can be reversed with readily available antidotes.


Subject(s)
Antidotes/therapeutic use , Carbon Monoxide Poisoning , Carbon Monoxide/adverse effects , Cyanides/adverse effects , Inhalation Exposure/adverse effects , Smoke Inhalation Injury , Carbon Monoxide Poisoning/diagnosis , Carbon Monoxide Poisoning/etiology , Carbon Monoxide Poisoning/mortality , Carbon Monoxide Poisoning/physiopathology , Carbon Monoxide Poisoning/therapy , Humans , Predictive Value of Tests , Smoke Inhalation Injury/diagnosis , Smoke Inhalation Injury/etiology , Smoke Inhalation Injury/mortality , Smoke Inhalation Injury/physiopathology , Smoke Inhalation Injury/therapy , Treatment Outcome
10.
J Burn Care Res ; 33(2): 291-7, 2012.
Article in English | MEDLINE | ID: mdl-22079905

ABSTRACT

Severe burn injuries lead to a prolonged hypercatabolic state resulting in dramatic loss of skeletal muscle mass. Postburn muscle loss is well documented but the molecular signaling cascade preceding atrophy is not. The purpose of this study is to determine the response to burn injury of signaling pathways driving muscle inflammation and protein metabolism. Muscle biopsies were collected in the early flow phase after burn injury from the vastus lateralis of a noninjured leg in patients with 20 to 60% TBSA burns and compared with uninjured, matched controls. Circulating levels of proinflammatory cytokines were also compared. Immunoblotting was performed to determine the protein levels of key signaling components for translation initiation, proteolysis, and tumor necrosis factor/nuclear factor kappa B (NFκB)and interleukin (IL)-6/STAT3 signaling. Burn subjects had significantly higher levels of circulating proinflammatory cytokines, with no difference in muscle STAT3 activity and lower NFκB activity. No differences were found in any translational signaling components. Regarding proteolytic signaling in burn, calpain-2 was 47% higher, calpastatin tended to be lower, and total ubiquitination was substantially higher. Surprisingly, a systemic proinflammatory response 3 to 10 days postburn did not lead to elevated muscle STAT3 or NFκB signaling. Signaling molecules governing translation initiation were unaffected, whereas indices of calcium-mediated proteolysis and ubiquitin-proteasome activity were upregulated. These novel findings are the first in humans to suggest that the net catabolic effect of burn injury in skeletal muscle (ie, atrophy) may be mediated, at least during the early flow phase, almost entirely by an increased proteolytic activity in the absence of suppressed protein synthesis signaling.


Subject(s)
Burns/metabolism , Cytokines/blood , Muscle, Skeletal/metabolism , Adult , Case-Control Studies , Female , Humans , Immunoblotting , Inflammation/metabolism , Male , Muscle Proteins/metabolism , Signal Transduction , Surveys and Questionnaires , Up-Regulation
11.
Expert Rev Respir Med ; 5(5): 663-73, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21955236

ABSTRACT

Infectious complications are a constant threat to thermally injured patients during hospitalizations and are a predominant cause of death. Most of the infections that develop in burn patients are nosocomial and of a pulmonary etiology. The bacteria that cause ventilator associated pneumonia (VAP) take advantage of the fact that uniquely among intensive care unit patients endotracheal intubation allows them a 'free' passage to the sterile lower airways; however, the combination of severe thermal injury (systemic immunosuppression) and inhalation injury (local immunosuppression and tissue injury) create an ideal environment for development of VAP. Thus, strategies directed at preventing and treating VAP in burn patients must address not only rapid extubation and VAP prevention bundles known to work in other intensive care unit populations, but therapies directed to more rapid wound healing and restoration of pulmonary patency.


Subject(s)
Burns/therapy , Intubation, Intratracheal/adverse effects , Pneumonia, Ventilator-Associated/etiology , Respiration, Artificial/adverse effects , Smoke Inhalation Injury/therapy , Anti-Bacterial Agents/therapeutic use , Burns/complications , Critical Illness , Humans , Pneumonia, Ventilator-Associated/diagnosis , Pneumonia, Ventilator-Associated/microbiology , Pneumonia, Ventilator-Associated/therapy , Risk Assessment , Risk Factors , Smoke Inhalation Injury/complications , Time Factors , Treatment Outcome , Wound Healing
13.
Med Sci Sports Exerc ; 43(7): 1177-87, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21131862

ABSTRACT

UNLABELLED: Resistance training (RT) is a proven sarcopenia countermeasure with a high degree of potency. However, sustainability remains a major issue that could limit the appeal of RT as a therapeutic approach without well-defined dosing requirements to maintain gains. PURPOSE: To test the efficacy of two maintenance prescriptions on muscle mass, myofiber size and type distribution, and strength. We hypothesized the minimum dose required to maintain RT-induced adaptations would be greater in the old (60-75 yr) versus young (20-35 yr). METHODS: Seventy adults participated in a two-phase exercise trial that consisted of RT 3 d·wk for 16 wk (phase 1) followed by a 32-wk period (phase 2) with random assignment to detraining or one of two maintenance prescriptions (reducing the dose to one-third or one-ninth of that during phase 1). RESULTS: Phase 1 resulted in expected gains in strength, myofiber size, and muscle mass along with the typical IIx-to-IIa shift in myofiber-type distribution. Both maintenance prescriptions preserved phase 1 muscle hypertrophy in the young but not the old. In fact, the one-third maintenance dose led to additional myofiber hypertrophy in the young. In both age groups, detraining reversed the phase 1 IIx-to-IIa myofiber-type shift, whereas a dose response was evident during maintenance training with the one-third dose better maintaining the shift. Strength gained during phase 1 was largely retained throughout detraining with only a slight reduction at the final time point. CONCLUSIONS: We conclude that older adults require a higher dose of weekly loading than the young to maintain myofiber hypertrophy attained during a progressive RT program, yet gains in specific strength among older adults were well preserved and remained at or above levels of the untrained young.


Subject(s)
Adaptation, Physiological , Resistance Training/methods , Adult , Aged , Aging/physiology , Female , Humans , Male , Middle Aged , Muscle Strength/physiology , Muscle, Skeletal/physiology , Young Adult
14.
Physiol Genomics ; 40(3): 141-9, 2010 Feb 04.
Article in English | MEDLINE | ID: mdl-19903761

ABSTRACT

Across numerous model systems, aging skeletal muscle demonstrates an impaired regenerative response when exposed to the same stimulus as young muscle. To better understand the impact of aging in a human model, we compared changes to the skeletal muscle transcriptome induced by unaccustomed high-intensity resistance loading (RL) sufficient to cause moderate muscle damage in young (37 yr) vs. older (73 yr) adults. Serum creatine kinase was elevated 46% 24 h after RL in all subjects with no age differences, indicating similar degrees of myofiber membrane wounding by age. Despite this similarity, from genomic microarrays 318 unique transcripts were differentially expressed after RL in old vs. only 87 in young subjects. Follow-up pathways analysis and functional annotation revealed among old subjects upregulation of transcripts related to stress and cellular compromise, inflammation and immune responses, necrosis, and protein degradation and changes in expression (up- and downregulation) of transcripts related to skeletal and muscular development, cell growth and proliferation, protein synthesis, fibrosis and connective tissue function, myoblast-myotube fusion and cell-cell adhesion, and structural integrity. Overall the transcript-level changes indicative of undue inflammatory and stress responses in these older adults were not mirrored in young subjects. Follow-up immunoblotting revealed higher protein expression among old subjects for NF-kappaB, heat shock protein (HSP)70, and IL-6 signaling [total and phosphorylated signal transducer and activator of transcription (STAT)3 at Tyr705]. Together, these novel findings suggest that young and old adults are equally susceptible to RL-mediated damage, yet the muscles of older adults are much more sensitive to this modest degree of damage-launching a robust transcriptome-level response that may begin to reveal key differences in the regenerative capacity of skeletal muscle with advancing age.


Subject(s)
Genome, Human , Muscle, Skeletal/metabolism , Resistance Training , Adult , Aged , Aging , Creatine Kinase/blood , Humans , Interleukin-6/blood , Interleukin-8/blood , Male , Physical Exertion , Tumor Necrosis Factor-alpha/blood
15.
J Appl Physiol (1985) ; 107(5): 1655-62, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19589955

ABSTRACT

While skeletal muscle protein accretion during resistance training (RT)-mediated myofiber hypertrophy is thought to result from upregulated translation initiation signaling, this concept is based on responses to a single bout of unaccustomed resistance exercise (RE) with no measure of hypertrophy across RT. Further, aging appears to affect acute responses to RE, but whether age differences in responsiveness persist during RT leading to impaired RT adaptation is unclear. We therefore tested whether muscle protein fractional synthesis rate (FSR) and Akt/mammalian target of rapamycin (mTOR) signaling in response to unaccustomed RE differed in old vs. young adults, and whether age differences in acute responsiveness were associated with differences in muscle hypertrophy after 16 wk of RT. Fifteen old and 21 young adult subjects completed the 16-wk study. The phosphorylation states of Akt, S6K1, ribosomal protein S6 (RPS6), eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP1), eIF4E, and eIF4G were all elevated (23-199%) 24 h after a bout of unaccustomed RE. A concomitant 62% increase in FSR was found in a subset (6 old, 8 young). Age x time interaction was found only for RPS6 phosphorylation (+335% in old subjects only), while there was an interaction trend (P = 0.084) for FSR (+96% in young subjects only). After 16 wk of RT, gains in muscle mass, type II myofiber size, and voluntary strength were similar in young and old subjects. In conclusion, at the level of translational signaling, we found no evidence of impaired responsiveness among older adults, and for the first time, we show that changes in translational signaling after unaccustomed RE were associated with substantial muscle protein accretion (hypertrophy) during continued RT.


Subject(s)
Muscle Proteins/metabolism , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Resistance Training/adverse effects , Signal Transduction , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Hypertrophy/physiopathology , Male , Middle Aged , Protein Modification, Translational , Young Adult
16.
J Burn Care Res ; 30(3): 395-9, 2009.
Article in English | MEDLINE | ID: mdl-19349899

ABSTRACT

Approximately 50% of fatal and 15% of nonfatal burn-injured patients have detectable blood alcohol content (BAC) at the time of admission, and it is hypothesized that alcohol exacerbates burn-related immunosuppression. The purpose of this study was to evaluate the association between BAC and infectious complications in burn patients. The study population consisted of 1161 burn patients admitted to a large academic burn center between January 1998 and June 2007. Patients were categorized into no BAC (0.0 g/100 ml), low/moderate BAC (>0.0 and <0.1 g/100 ml) and high BAC (> or =0.1 g/100 ml) groups based on BAC at time of admission. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for associations between pneumonia, sepsis, urinary tract infection, line infection, and wound infection and BAC, adjusted for total burn surface area and inhalation injury. Relative to no BAC patients, both low/moderate and high BAC patients had nonsignificantly increased risk for most infectious complications. High BAC patients were at significantly increased risk for any infectious complication (RR 2.06, CI 1.25-3.41) and pneumonia (RR 2.06, CI 1.04-4.09) and a nonsignificantly increased risk of urinary tract infection (RR 2.12, CI 0.0.94-4.78). Results suggest that preinjury alcohol consumption places patients at an increased risk for infectious complications, most notably pneumonia. Further studies examining the relationship between alcohol and pneumonia among burn patients will help elucidate the reason for the increased risk observed in the current study and suggest ways to prevent infection for this particular subgroup of burn patients.


Subject(s)
Ethanol/blood , Wound Infection/blood , Adult , Burn Units , Burns/complications , Female , Humans , Length of Stay/statistics & numerical data , Male , Proportional Hazards Models , Retrospective Studies , Risk Factors , Wound Infection/etiology
17.
J Trauma ; 66(2): 358-62; discussion 362-4, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19204508

ABSTRACT

BACKGROUND: Recent studies show an apparent survival advantage associated with the administration of higher cumulative ratios of fresh frozen plasma (FFP) to packed red blood cells (PRBC). It remains unclear how temporal factors and survival bias may influence these results. The objective of this study was to evaluate the temporal relationship between blood product ratios and mortality in massively transfused trauma patients. METHODS: Patients requiring massive transfusion (>10 units of PRBC within 24 hours of admission) between 2005 and 2007 were identified (n = 134). In-hospital mortality was compared between patients receiving high (>1:2) versus low (<1:2) FFP:PRBC ratios with a regression model, using the FFP:PRBC ratio as a fixed value at 24 hours (method I) and as a time-varying covariate (method II). RESULTS: The FFP:PRBC ratio for all patients was low early and increased over time. Sixty-eight percent of total blood products were given and 54% of deaths occurred during the first 6 hours. Using method I, patients receiving a high FFP:PRBC ratio (mean, 1:1.3) by 24 hours had a 63% lower risk of death (RR, 0.37; 95% CI, 0.22-0.64) compared with those receiving a low ratio (mean, 1:3.7). However, this association was no longer statistically significant (RR, 0.84; 95% CI, 0.47-1.50) when the timing of component product transfusion was taken into account (method II). CONCLUSIONS: Similar to previous studies, an association between higher FFP:PRBC ratios at 24 hours and improved survival was observed. However, after adjustment for survival bias in the analysis, the association was no longer statistically significant. Prospective trials are necessary to evaluate whether hemostatic resuscitation is clinically beneficial.


Subject(s)
Erythrocyte Transfusion , Plasma , Resuscitation/mortality , Resuscitation/methods , Adult , Chi-Square Distribution , Cross-Sectional Studies , Female , Hospital Mortality , Humans , Male , Regression Analysis , Survival Analysis , Time Factors , Treatment Outcome
18.
J Appl Physiol (1985) ; 104(6): 1736-42, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18436694

ABSTRACT

A present debate in muscle biology is whether myonuclear addition is required during skeletal muscle hypertrophy. We utilized K-means cluster analysis to classify 66 humans after 16 wk of knee extensor resistance training as extreme (Xtr, n = 17), modest (Mod, n = 32), or nonresponders (Non, n = 17) based on myofiber hypertrophy, which averaged 58, 28, and 0%, respectively (Bamman MM, Petrella JK, Kim JS, Mayhew DL, Cross JM. J Appl Physiol 102: 2232-2239, 2007). We hypothesized that robust hypertrophy seen in Xtr was driven by superior satellite cell (SC) activation and myonuclear addition. Vastus lateralis biopsies were obtained at baseline and week 16. SCs were identified immunohistochemically by surface expression of neural cell adhesion molecule. At baseline, myofiber size did not differ among clusters; however, the SC population was greater in Xtr (P < 0.01) than both Mod and Non, suggesting superior basal myogenic potential. SC number increased robustly during training in Xtr only (117%; P < 0.001). Myonuclear addition occurred in Mod (9%; P < 0.05) and was most effectively accomplished in Xtr (26%; P < 0.001). After training, Xtr had more myonuclei per fiber than Non (23%; P < 0.05) and tended to have more than Mod (19%; P = 0.056). Both Xtr and Mod expanded the myonuclear domain to meet (Mod) or exceed (Xtr) 2,000 mum(2) per nucleus, possibly driving demand for myonuclear addition to support myofiber expansion. These findings strongly suggest myonuclear addition via SC recruitment may be required to achieve substantial myofiber hypertrophy in humans. Individuals with a greater basal presence of SCs demonstrated, with training, a remarkable ability to expand the SC pool, incorporate new nuclei, and achieve robust growth.


Subject(s)
Cell Proliferation , Cluster Analysis , Exercise , Muscle Contraction , Muscle Fibers, Skeletal/pathology , Quadriceps Muscle/pathology , Satellite Cells, Skeletal Muscle/pathology , Adult , Age Factors , Aged , Cohort Studies , Humans , Hypertrophy , Insulin-Like Growth Factor Binding Protein 1/blood , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor Binding Proteins/blood , Insulin-Like Growth Factor I/analysis , Middle Aged , Neural Cell Adhesion Molecules/analysis , Phenotype , Quadriceps Muscle/chemistry , Quadriceps Muscle/physiopathology , Satellite Cells, Skeletal Muscle/chemistry
19.
Burns ; 34(3): 320-7, 2008 May.
Article in English | MEDLINE | ID: mdl-17869427

ABSTRACT

BACKGROUND: Early efforts to predict death following severe burns focused on age and burn size; more recent work incorporated inhalation injury and pneumonia. Gender, co-morbid illness, and co-existent trauma have been implicated in burn mortality but have rarely been incorporated into predictive models. METHODS: The National Burn Repository (NBR) and the National Trauma Data Bank (NTDB) provided data on 68,661 (54,219 and 14,442, respectively) burn patients that was used to develop and validate, respectively, a predictive model of burn mortality. Logistic regression was used to model the odds of mortality with respect to age, gender, % body surface area burned (BSAB), co-existent trauma, inhalation injury, pneumonia, and co-morbid illness. Performance of the predictive model was assessed using a deviance statistic, receiver operating characteristic (ROC) curves, and the Hosmer-Lemeshow (HL) statistic. RESULTS: The predictive model that demonstrated optimal performance included the variables age, percent total BSAB, inhalation injury, co-existent trauma, and pneumonia. The area under the ROC curve for this model was 0.94 and the HL statistic was 16.0. The inclusion of additional variables, i.e., gender, co-morbid illness, did not improve the performance of the model despite reduction in the model deviance. When the predictive model was applied to the validation data source, the area under the ROC curve was 0.87 and the HL statistic was 10.0, indicating good discrimination and calibration. CONCLUSION: The results of this study suggest that a comprehensive predictive model of burn mortality incorporating certain variables not previously considered in other models provides superior predictive ability.


Subject(s)
Burns/mortality , Burns/etiology , Burns/pathology , Cohort Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Risk Factors , Statistics as Topic , United States/epidemiology
20.
J Burn Care Res ; 28(6): 854-8, 2007.
Article in English | MEDLINE | ID: mdl-17925640

ABSTRACT

Acute adrenal insufficiency (AI) is an uncommon disorder among critically ill burn patients, which can often go unrecognized. The goal of the current study is to identify risk factors for AI among patients who have sustained severe thermal injury. A case-control study was conducted among all adult patients admitted to the intensive care unit of the University of Alabama at Birmingham Burn Center during a 7-year period (1997-2003). All burn patients who developed AI were selected as cases (n = 26), and a random sample of those ICU patients who did not develop AI were selected as controls (n = 56). Two variables demonstrated significant independent associations with the risk of AI. Patients who developed AI were older than controls (50 vs. 46 years, respectively) and suffered a significantly greater area of thermal injury when compared with controls (mean percentage of total body surface area burned for cases and controls 45.5% and 25.4%, respectively). Over half (59.1%) of the patients with AI died compared with only 14.6% of controls (P < 0.0001). The development of AI appears to be associated with a greater TBSA burn and older age. After severe thermal injury, the diagnosis of AI substantially increases the risk of death. A better understanding of factors that predispose burn patients to AI may aid in earlier diagnosis, initiation of therapy, and improved outcomes.


Subject(s)
Adrenal Insufficiency/etiology , Burns/complications , Adrenal Insufficiency/mortality , Age Factors , Alabama/epidemiology , Burn Units , Burns/mortality , Case-Control Studies , Female , Humans , Injury Severity Score , Length of Stay/statistics & numerical data , Male , Middle Aged , Multivariate Analysis , Risk Factors
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