Levamisole-induced vasculitis.

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.

Differential genomic responses in old vs. young humans despite similar levels of modest muscle damage after resistance loading.

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.

The relationship of blood product ratio to mortality: survival benefit or survival bias?

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.

Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis.

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.

Improving the ability to predict mortality among burn patients.

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.

Admission Rapid Thrombelastography (rTEG®) Values Predict Resuscitation Volumes and Patient Outcomes After Thermal Injury.

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.

Human neuromuscular aging: Sex differences revealed at the myocellular level.

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.

Load-mediated downregulation of myostatin mRNA is not sufficient to promote myofiber hypertrophy in humans: a cluster analysis.

Myostatin is a potent inhibitor of myogenesis; thus differential expression might be expected across individuals varying in responsiveness to myogenic stimuli. We hypothesized that myostatin would be differentially regulated across humans with markedly different hypertrophic responses to resistance training (RT; 16 wk). Targets were assessed in muscle biopsies at baseline (T1) and 24 h after the first (T2) and last (T3) loading bouts in previously untrained subjects statistically clustered based on mean myofiber hypertrophy as extreme (Xtr; n = 17, 2,475 microm(2)), modest (n = 32, 1,111 microm(2)), and nonresponders (n = 17, -16 microm(2)). We assessed protein levels of latent full-length myostatin protein complex and its propeptide; mRNA levels of myostatin, cyclin D1, p21(cip1), p27(kip1), and activin receptor IIB; and serum myostatin protein concentration. Total RNA concentration increased by T3 in nonresponders (37%) and modest responders (40%), while it increased acutely (T2) only in Xtr (26%), remaining elevated at T3 (40%). Myostatin mRNA decreased at T2 (-44%) and remained suppressed at T3 (-52%), but not differentially across clusters. Cyclin D1 mRNA increased robustly by T2 (38%) and T3 (74%). The increase at T2 was driven by Xtr (62%, P < 0.005), and Xtr had the largest elevation at T3 (82%, P < 0.001). No effects were found for other target transcripts. Myostatin protein complex increased 44% by T3 (P < 0.001), but not differentially by cluster. Myostatin protein complex propeptide and circulating myostatin were not influenced by RT or cluster. Overall, we found no compelling evidence that myostatin is differentially regulated in humans demonstrating robust RT-mediated myofiber hypertrophy vs. those more resistant to growth.

Cluster analysis tests the importance of myogenic gene expression during myofiber hypertrophy in humans.

We applied K-means cluster analysis to test the hypothesis that muscle-specific factors known to modulate protein synthesis and satellite cell activity would be differentially expressed during progressive resistance training (PRT, 16 wk) in 66 human subjects experiencing extreme, modest, and failed myofiber hypertrophy. Muscle mRNA expression of IGF-I isoform Ea (IGF-IEa), mechanogrowth factor (MGF, IGF-IEc), myogenin, and MyoD were assessed in muscle biopsies collected at baseline (T1) and 24 h after the first (T2) and last (T3) loading bouts from previously untrained subjects clustered as extreme responders (Xtr, n=17), modest responders (Mod, n=32), and nonresponders (Non, n=17) based on mean myofiber hypertrophy. Myofiber growth averaged 2,475 microm2 in Xtr, 1,111 microm2 in Mod, and -16 microm2 in Non. Main training effects revealed increases in all transcripts (46-83%, P<0.005). For the entire cohort, IGF-IEa, MGF, and myogenin mRNAs were upregulated by T2 (P<0.05), while MyoD did not increase significantly until T3 (P<0.001). Within clusters, MGF and myogenin upregulation was robust in Xtr (126% and 65%) and Mod (73% and 41%) vs. no changes in Non. While significant in all clusters by T3, IGF-IEa increased most in Xtr (105%) and least in Non (44%). Although MyoD expression increased overall, no changes within clusters were detected. We reveal for the first time that MGF and myogenin transcripts are differentially expressed in subjects experiencing varying degrees of PRT-mediated myofiber hypertrophy. The data strongly suggest the load-mediated induction of these genes may initiate important actions necessary to promote myofiber growth during PRT, while the role of MyoD is less clear.

The descriptive epidemiology of intentional burns in the United States: an analysis of the National Burn Repository.

BACKGROUND: Epidemiologic research on intentional burns in the United States has mainly been based on small, geographically restricted populations. The current study presents the descriptive epidemiology of intentional burns using data from a large, geographically diverse population of burn patients. METHODS: The National Burn Repository (NBR) was queried for patients with intentional burns and analyzed data pertaining to their demographic and medical characteristics; primarily comparing the prevalence proportions of these variables according to specific injury intent. RESULTS: From a total of 54,219 burn patients, 1601 patients who sustained intentional burns were identified; 49% were self-inflicted, and 51% were assault-related. Compared to all other burn patients, intentional burn patients had a larger mean total body surface area (TBSA) burned (22.0% versus 11.3%, p<0.0001), longer hospital stay (19.8 days versus 12.5 days, p<0.0001), and higher mortality (13.9% versus 2.5%, p<0.0001). Self-inflicted compared to assault-related burns were associated with a larger TBSA burned (27.5% versus 16.8%, p<0.0001) and higher mortality (20.8% versus 7.2%, p<0.0001). CONCLUSIONS: Data from this national cohort of burn patients support findings from smaller studies that patients who suffer intentional burns experience excess morbidity and mortality.

Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults.

Resistance training (RT) has shown the most promise in reducing/reversing effects of sarcopenia, although the optimum regime specific for older adults remains unclear. We hypothesized myofiber hypertrophy resulting from frequent (3 days/wk, 16 wk) RT would be impaired in older (O; 60-75 yr; 12 women, 13 men), sarcopenic adults compared with young (Y; 20-35 yr; 11 women, 13 men) due to slowed repair/regeneration processes. Myofiber-type distribution and cross-sectional area (CSA) were determined at 0 and 16 wk. Transcript and protein levels of myogenic regulatory factors (MRFs) were assessed as markers of regeneration at 0 and 24 h postexercise, and after 16 wk. Only Y increased type I CSA 18% (P < 0.001). O showed smaller type IIa (-16%) and type IIx (-24%) myofibers before training (P < 0.05), with differences most notable in women. Both age groups increased type IIa (O, 16%; Y, 25%) and mean type II (O, 23%; Y, 32%) size (P < 0.05). Growth was generally most favorable in young men. Percent change scores on fiber size revealed an age x gender interaction for type I fibers (P < 0.05) as growth among Y (25%) exceeded that of O (4%) men. Myogenin and myogenic differentiation factor D (MyoD) mRNAs increased (P < 0.05) in Y and O, whereas myogenic factor (myf)-5 mRNA increased in Y only (P < 0.05). Myf-6 protein increased (P < 0.05) in both Y and O. The results generally support our hypothesis as 3 days/wk training led to more robust hypertrophy in Y vs. O, particularly among men. However, this differential hypertrophy adaptation was not explained by age variation in MRF expression.

The contribution of opiate analgesics to the development of infectious complications in burn patients.

BACKGROUND: Immune and infectious complications are associated with burn injury. Opiate analgesics also can induce similar complications, however, their impact on postburn infectious complications is unknown. METHODS: A retrospective survey of records from 1997 to 2002 from an academic burn center was conducted. Information on all opiate analgesic use was obtained and expressed as opiate equivalents (OEs). Total OEs were summed for each patient and then compared between cases and controls. RESULTS: Patients who developed infections were more likely to be in the high OE group. This association was modified by burn severity. Patients with small burns and infection were more likely to be in the high OE group, whereas patients with moderate to large burns and infections were not associated significantly with opiate use. CONCLUSIONS: The results of this preliminary study suggest that opiate analgesics can contribute to the development of postburn infectious complications when the burn injury is of a less severe nature.

Upon admission coagulation and platelet function in patients with thermal and electrical injuries.

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.

Resting and load-induced levels of myogenic gene transcripts differ between older adults with demonstrable sarcopenia and young men and women.

Regenerative capacity appears to be impaired in sarcopenic muscle. As local growth factors and myogenic regulatory factors (MRFs) modulate repair/regeneration responses after overload, we hypothesized that resistance loading (RL)-induced expression of MRFs and muscle IGF-I-related genes would be blunted in older (O) males (M) and females (F) with demonstrable sarcopenia vs. young (Y) adults. Y (20-35 yr, 10 YF, 10 YM) and O (60-75 yr, 9 OF, 9 OM) underwent vastus lateralis biopsy before and 24 h after knee extensor RL. Sarcopenia was assessed by cross-sectional area of type I, IIa, and IIx myofibers. Transcript levels were assessed by relative RT-PCR and analyzed by age x gender x load repeated-measures ANOVA. O were sarcopenic based on type II atrophy with smaller type IIa (P < 0.05) and IIx (P < 0.001) myofibers. Within-gender cross-sectional area differences were more marked in F (OF < YF: IIa 21%, IIx 42%). Load effects (P < 0.05) were seen for four of seven mRNAs as IGF-IEa (34%), myogenin (53%), and MyoD (20%) increased, and myf-6 declined 10%. Increased IGF-IEa was driven by O (48%) and/or M (43%). An age x gender x load interaction was found for MyoD (P < 0.05). An age x load interaction for type 1 IGF receptor (P < 0.05) was driven by a small increase in O (16%, P < 0.05). A gender x load interaction (P < 0.05) was noted for IGF binding protein-4. Age effects (P < 0.05) resulted from higher MyoD (54%), myf-5 (21%), and IGF binding protein-4 (17%) in O and were primarily localized to F at baseline (OF > YF; MyoD 94%, myf-5 47%, P < 0.05). We conclude that RL acutely increases mRNA expression of IGF-IEa and myogenin, which may promote growth/regeneration in both Y and O. Higher resting levels of MRFs in OF vs. YF suggest elevated basal regenerative activity in sarcopenic muscle of OF.

The association between sex and mortality among burn patients as modified by age.

Although an increased risk of death among female patients suffering thermal injury has been noted, the differential influence of age has received little attention. Because experimental evidence suggests that sex hormones influence the immune response to thermal injury, an age-related sex influence on patient mortality is biologically plausible as the hormone milieu changes with the onset of menopause. The goal of this study was to estimate the association between sex and mortality after thermal injury in a large, population-based sample. The National Trauma Data Bank yielded data for more than 6200 burn patients 20 years of age or older. Logistic regression was used to calculate mortality odds ratios (OR) with 95% confidence intervals (CIs) for men relative to women, both overall and by age. Adjustments for age, race, burn etiology, percent body surface area burned, comorbid conditions, and inhalation injury were performed. For the overall study population, the adjusted risk of death was approximately 30% lower for males (OR 0.67, 95% CI 0.52-0.87). Within age strata, the adjusted association was statistically significant only in those aged 20 to 34 years (OR 0.45; 95% CI 0.24-0.87); 35 to 49 years (OR 0.71; 95% CI 0.39-1.30); 50 to 64 years (OR 0.55; 95% CI 0.31-1.00); and 65 years or older (OR 0.85; 95% CI 0.57-1.27). The results of the present study not only indicate that women have an increased odds of mortality after thermal injury but also demonstrate a differential effect of age on the association between sex and mortality. On the basis of the findings of the present study as well as the results of experimental studies, further clinical research is needed to investigate the impact of sex hormones on mortality among burn patients.

Serum from human burn victims impairs myogenesis and protein synthesis in primary myoblasts.

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.

Gender differences in mortality following burn injury.

Clinical and experimental studies have demonstrated higher mortality following nonthermal trauma among males compared with females. To date, few clinical retrospective studies have focused on gender differences in outcome following burn injury with respect to age. All patients admitted to the University of Alabama at Birmingham (UAB) Burn Center between January 1994 and December 2000 were selected for inclusion in the study. Gender differences in demographic, clinical, and outcome characteristics were compared. Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between mortality and gender, both overall and stratified by age. Over the 7-year study period, 1229 males and 382 females were admitted to the UAB Burn Center, and mortality rates were 7.2% and 13.4%, respectively (P = 0.0002). Female patients were more likely to be older, of the black race, and in poorer health. In addition, females were more likely to suffer flame and scald burns. The association between mortality and gender was modified by age. Up to age 60, mortality rates among females were over twice that of males (OR 2.3, 95% Cl 1.4-3.8); however, no difference was noted among those 60 and older (OR 0.9, 95% Cl 0.5-1.6). These associations persisted following adjustment for potentially confounding variables. Causes and timing of death were similar for males and females. Women less than 60 years of age who sustain burn injuries have an increased risk of death compared with males. Differences in the natural history of nonthermal trauma and burn injury may provide insight regarding these divergent findings.

Myogenic protein expression before and after resistance loading in 26- and 64-yr-old men and women.

Based on the growing body of evidence implicating an important role for myogenic regulatory factors (MRFs) in the adaptive responses of skeletal muscle to mechanical load, we tested the hypothesis that protein concentrations of MRFs as well as cell cycle proteins (i.e., cyclins and cyclin-dependent kinase inhibitors) would be altered after heavy leg resistance exercise (RE). Because we and others, however, have shown a blunted adaptive response to long-term resistance training in older (O) women [females (F)] compared with men (M), we also tested the hypothesis that these myogenic responses to RE would be influenced by age and gender. Twenty-two younger (Y) adults (20-35 yr, 11 YF, 11 YM) and 20 O adults (60-75 yr, 9 OF, 11 OM) consented to vastus lateralis muscle biopsy before and 24 h after a bout of RE using a regimen known to induce myofiber hypertrophy when performed 2-3 days/wk for several weeks (3 sets of 80% one-repetition maximum for squat, leg press, and knee extension). Protein concentrations of MRFs (MyoD, myogenin, myf-6), cyclin D1, cyclin B1, alpha-actin, and the cyclin-dependent kinase inhibitor p27kip were determined by immunoblotting. Data were analyzed by using age x gender x load repeated-measures ANOVA. Myogenin expression was 44% higher (P <0.05) in O compared with Y, and myf-6 tended to be higher in OF compared with YF (95%, P=0.059). A significant gender x load interaction indicated that, in F, RE led to a reduction in p27kip (20%; P<0.05), which was driven mainly by a 27% drop in OF. Levels of cyclin D1, cyclin B1, MyoD, myf-6, and alpha-actin were not influenced by age, gender, or loading. We report a novel finding in humans of markedly higher myogenin protein content in older sedentary muscle. The results do not, however, support the hypothesis that myogenic protein expression is altered 24 h after RE, irrespective of age or gender. Although the time point of postexercise muscle biopsy could be viewed as too early to capture maximal effects for most of these proteins, the significant decline in p27kip concentration found in OF suggests that mechanical load may provide one means of overcoming the inhibitory influence of p27kip.

Long-term trends in mortality according to age among adult burn patients.

The purpose of this study was to evaluate differences in mortality among adult burn patients over a 25-year period according to age. All patients admitted to a regional burn center between 1973 and 1997 were divided into three age groups (18-34, 35-54, and 55 and older), and mortality rates were compared over time. Between 1973 and 1997, the proportion of patients in each age group remained consistent, as did the type of burns. The average total body surface area burned declined steadily from 31.6% in the 1970s to 18.2% in the late 1990s. The absolute change in mortality was small (7.7%), moderate (16.3%), and large (30.2%) in the young, middle-aged, and old, respectively. However, the relative change demonstrated the opposite pattern. The results of this study suggest that declines in mortality among adult burn patients have occurred across the age spectrum over the past 25 years.

Thermal burn fatalities in the workplace, United States, 1992 to 1999.

The purpose of this study was to present the epidemiology of thermal burn fatalities in the workplace in the United States between 1992 and 1999. Data on fatal thermal burn injuries in the United States between 1992 through 1999 were obtained from the Bureau of Labor Statistics Census of Fatal Occupational Injuries. Between 1992 and 1999, 1,189 fatal thermal burns occurred in the workplace (0.11 deaths/100,000 workers per year). Mortality increased with age, with those over 65 years of age having the greatest rate of death (0.20/100,000). Workers in the mining industry and transportation and public utilities had the highest rates of fatal thermal burns. Occupational categories with the highest rates included "extractive occupations" (eg, miners, explosives workers) and "transportation and material movers" (eg, truck drivers). The specific occupations with the highest rates were airplane pilots and navigators, furnace, kiln, and oven operators, and firefighters. Most decedents were operating vehicles or involved in "other transportation operations" at the time of the incident. The majority of injurious incidents occurred on "industrial premises" or the "street and highway." Efforts to prevent fatal occupational thermal burn injuries should focus on older workers and those in occupations with frequent exposure to potential sources of thermal injury. Further study of nonfatal thermal burns in the workplace is needed because patterns of fatal burn injury may not reflect patterns of occupational burn injury overall.