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Biomedical subjects

Charles E Wade

Publications and source records attributed to Charles E Wade.

At least 19 recordsLinked to original sources

Burns sustained in combat explosions in Operations Iraqi and Enduring Freedom (OIF/OEF explosion burns).

BACKGROUND: Burns comprise 5% of casualties evacuated from Operations Iraqi and Enduring Freedom (OIF and OEF). Many OIF/OEF burns result from the enemy's detonation of explosives. We reviewed these to evaluate mission impact and provide recommendations for improved combat burn protection. Data were compared to those from the Vietnam War. METHODS: All OIF/OEF patients with significant burns are treated at the U.S. Army Institute of Surgical Research (ISR). A review from April 2003 to April 2005 was undertaken. Records were obtained and demographics, burn severity and pattern, and early outcomes recorded. RESULTS: Two hundred and seventy-four OIF/OEF burn patients were treated, 142 (52%) sustained burns in explosions from hostile action. Age was 26+/-7 years (mean+/-S.D.). Mortality was 4%. The annual rate of combat explosion as a cause for burns increased from 18% to 69%, total body surface area burned increased from 15+/-12 to 21+/-23%, injury severity score rose from 8+/-11 to 17+/-18, and frequency of inhalation injury rose from 5% to 26%. Improvised explosive devices caused 55% of casualties, car bombs 16%, rocket-propelled grenades 15% and 14% other. The hands (80% of patients) and the face (77%) were the most frequently burned body areas. Burns were isolated to the hands in 6% of patients and to the face and hands in 15%. An average of 52+/-30% of the surface area of the hands and 45+/-26% of the face was burned. Mean length of stay was 24+/-25 days (median 14). Though 77% of patients were discharged without global disability, only 36% returned to full military duty. A similar pattern of injury and disposition was seen at the Army burn center in Vietnam (1966-1968), but mortality was higher (7.9%). CONCLUSION: Burns resulting from combat explosions increased in frequency, size and injury severity. Burns were concentrated on areas not protected by clothing or equipment. These injuries created long hospital stays and frequently prevented soldiers from returning to duty. While wound distribution has not changed, combat burn care has improved, and continued emphasis on military protective equipment for the hands and face is warranted.

Adolescent↗

Comparison of combat and non-combat burns from ongoing U.S. military operations.

BACKGROUND: Military burns result from either combat or non-combat causes. We compared these etiologies from patients involved in ongoing conflicts to evaluate their impact and provide prevention recommendations. METHODS: All military patients with significant burns treated at the United States Army Institute of Surgical Research from April 2003 to May 2005 were reviewed. Injuries were categorized as having resulted from combat or non-combat causes. Demographics, burn severity and pattern, mortality, and early outcomes were compared. RESULTS: There were 273 burn patients seen with 63% injured in combat. A high early rate of non-combat injuries was noted. Feedback on non-combat burn prevention was provided to the combat theater, and the incidence of non-combat burns decreased. Mean age and time from injury to admission did not differ. The majority of combat injuries resulted from explosive device detonation. Waste burning, ammunition handling, and gasoline caused most non-combat injuries. Combat casualties had more associated and inhalation injuries and greater full-thickness burn size; total body surface area burned was equivalent. The hands and the face were the most frequently burned body areas. Mortality was 5% in combat and 2% in non-combat patients. The majority of survivors in both groups returned to military duty. CONCLUSIONS: The disparity in full-thickness burn size and incidence of inhalation and associated injuries resulted from differing mechanisms of injury, with explosions and penetrating trauma more common in combat wounds. Despite the severity of combat burns, mortality was low and outcomes generally good. Non-combat burns are preventable and have decreased in incidence.

Burn Units↗

Neurobiology of exercise.

Voluntary physical activity and exercise training can favorably influence brain plasticity by facilitating neurogenerative, neuroadaptive, and neuroprotective processes. At least some of the processes are mediated by neurotrophic factors. Motor skill training and regular exercise enhance executive functions of cognition and some types of learning, including motor learning in the spinal cord. These adaptations in the central nervous system have implications for the prevention and treatment of obesity, cancer, depression, the decline in cognition associated with aging, and neurological disorders such as Parkinson's disease, Alzheimer's dementia, ischemic stroke, and head and spinal cord injury. Chronic voluntary physical activity also attenuates neural responses to stress in brain circuits responsible for regulating peripheral sympathetic activity, suggesting constraint on sympathetic responses to stress that could plausibly contribute to reductions in clinical disorders such as hypertension, heart failure, oxidative stress, and suppression of immunity. Mechanisms explaining these adaptations are not as yet known, but metabolic and neurochemical pathways among skeletal muscle, the spinal cord, and the brain offer plausible, testable mechanisms that might help explain effects of physical activity and exercise on the central nervous system.

Adaptation, Physiological↗

Issues of concern regarding the use of hypertonic/hyperoncotic fluid resuscitation of hemorrhagic hypotension.

Small volume resuscitation fluids continue to be of interest to the military and limited volume resuscitation is becoming more common in the treatment of hemorrhage in the civilian community. With renewed interest to undertake a large US-Canada multi-center clinical trial of hypertonic saline alone or combined with dextran (HSD) possibly in 2006, concerns related to the safe use of this product continue to surface. This review addresses the use of these products in uncontrolled hemorrhage models, in dehydration and addresses perceived risks associated with hypernatremia, dextran-associated anaphylactoid reactions and effects on coagulation and renal function.

Animals↗

Comparison between civilian burns and combat burns from Operation Iraqi Freedom and Operation Enduring Freedom.

OBJECTIVE: To assess outcome differences between locally burned civilians and military personnel burned in a distant combat zone treated in the same facility. SUMMARY BACKGROUND DATA: The United States Army Institute of Surgical Research (USAISR) Burn Center serves as a referral center for civilians and is the sole center for significant burns in military personnel. We made the hypothesis that outcomes for military personnel burned in the current conflict in Iraq and Afghanistan would be poorer because of delays to definitive treatment, other associated injury, and distance of evacuation. METHODS: We reviewed the civilian and military records of patients treated at the USAISR from the outset of hostilities in Iraq in April 2003 to May 2005. Demographics, injury data, mortality, and clinical outcomes were compared. RESULTS: : We cared for 751 patients during this time period, 273 of whom were military (36%). Military injuries occurred in a younger population (41 +/- 19 vs. 26 +/- 7 years for civilian and military respectively, P < 0.0001) with a longer time from injury to burn center arrival (1 +/- 5 days vs. 6 +/- 5, P < 0.0001), a higher Injury Severity Score (ISS 5 +/- 8 vs. 9 +/- 11, P < 0.0001), and a higher incidence of inhalation injury (8% vs. 13%, P = 0.024). Total burn size did not differ. Mortality was 7.1% in the civilian and 3.8% in the military group (P = 0.076). When civilians outside the age range of the military cohort were excluded, civilian mortality was 5.0%, which did not differ from the military group (P = 0.57). Total body surface area (TBSA) burned, age > or =40 years, presence of inhalation injury, and ventilator days were found to be important predictors of mortality by stepwise regression, and were used in a final predictive model with the area under receiver operator characteristic curve of 0.97 for both populations considered together. No significant effect of either group was identified during development. CONCLUSIONS: Mortality does not differ between civilians evacuated locally and military personnel injured in distant austere environments treated at the same center.

Adolescent↗

Making sense of the preclinical literature on advanced hemostatic products.

A number of new hemostatic products have been developed recently for use in trauma settings of severe uncontrolled bleeding. Currently, the literature on these products is controversial, with efficacy demonstrated under some circumstances but not others. In this review, we analyze the current literature pertaining to four of the most promising products (dry fibrin sealant dressing, Rapid Deployment Hemostat, HemCon chitosan dressing, and QuikClot) that have been suggested for use in combat casualty care applications. In particular, this analysis takes into account the characteristics of the animal models used for efficacy testing of these products, the desired characteristics of hemostatic dressings, and specific safety considerations. Animal models ranged from those featuring low-pressure/low-flow bleeding to those featuring high-pressure/high-flow bleeding. When data are viewed in the context of the specific characteristics of the differing animal models used, seemingly disparate experimental results related to efficacy and safety become quite complementary and lead to recommendations for the use of different products in different injury scenarios. Mission and training requirements will dictate the use of these products by military and civilian prehospital care providers.

Animals↗

Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations.

The world-wide impact of traumatic injury and associated hemorrhage on human health and well-being cannot be overstated. Twelve percent of the global disease burden is the result of violence or accidental injury. Hemorrhage is responsible for 30 to 40% of trauma mortality, and of these deaths, 33 to 56% occur during the prehospital period. Among those who reach care, early mortality is caused by continued hemorrhage, coagulopathy, and incomplete resuscitation. The techniques of early care, including blood transfusion, may underlie late mortality and long-term morbidity. While the volume of blood lost cannot be measured, physiologic and chemical measures and the number of units of blood given are readily recorded and analyzed. Improvements in early hemorrhage control and resuscitation and the prevention and aggressive treatment of coagulopathy appear to have the greatest potential to improve outcomes in severely injured trauma patients.

Hemorrhage↗

Risk factors for respiratory failure following operative stabilization of thoracic and lumbar spine fractures.

BACKGROUND: Respiratory failure is a serious complication that can adversely affect the hospital course and survival of multiply injured patients. Some studies have suggested that delayed surgical stabilization of spine fractures may increase the incidence of respiratory complications. However, the authors of these studies analyzed small sets of patients and did not assess the independent effects of multiple risk factors. METHODS: A retrospective cohort study was conducted at a regional level-I trauma center to identify risk factors for respiratory failure in patients with surgically treated thoracic and lumbar spine fractures. Demographic, diagnostic, and procedural variables were identified. The incidence of respiratory failure was determined in an adult respiratory distress syndrome registry maintained concurrently at the same institution. Univariate and multivariate analyses were used to determine independent risk factors for respiratory failure. An algorithm was formulated to predict respiratory failure. RESULTS: Respiratory failure developed in 140 of the 1032 patients in the study cohort. Patients with respiratory failure were older; had a higher mean Injury Severity Score (ISS) and Charlson Comorbidity Index Score; had greater incidences of pneumothorax, pulmonary contusion, and thoracic level injury; had a lower mean Glasgow Coma Score (GCS); were more likely to have had a posterior surgical approach; and had a longer mean time from admission to surgical stabilization than the patients without respiratory failure (p < 0.05). Multivariate analysis identified five independent risk factors for respiratory failure: an age of more than thirty-five years, an ISS of > 25 points, a GCS of < or = 12 points, blunt chest injury, and surgical stabilization performed more than two days after admission. An algorithm was created to determine, on the basis of the number of preoperative predictors present, the relative risk of respiratory failure when surgery was delayed for more than two days. CONCLUSIONS: Independent risk factors for respiratory failure were identified in an analysis of a large cohort of patients who had undergone operative stabilization of thoracic and lumbar spine fractures. Early operative stabilization of these fractures, the only risk factor that can be controlled by the physician, may decrease the risk of respiratory failure in multiply injured patients.

Adult↗

The epidemiology and modern management of traumatic hemorrhage: US and international perspectives.

Trauma is a worldwide problem, with severe and wide ranging consequences for individuals and society as a whole. Hemorrhage is a major contributor to the dilemma of traumatic injury and its care. In this article we describe the international epidemiology of traumatic injury, its causes and its consequences, and closely examine the role played by hemorrhage in producing traumatic morbidity and mortality. Emphasis is placed on defining situations in which traditional methods of hemorrhage control often fail. We then outline and discuss modern principles in the management of traumatic hemorrhage and explore developing changes in these areas. We conclude with a discussion of outcome measures for the injured patient within the context of the epidemiology of traumatic injury.

Adolescent↗

Insulin-independent pathways mediating glucose uptake in hindlimb-suspended skeletal muscle.

Insulin resistance accompanies atrophy in slow-twitch skeletal muscles such as the soleus. Using a rat hindlimb suspension model of atrophy, we have previously shown that an upregulation of JNK occurs in atrophic muscles and correlates with the degradation of insulin receptor substrate-1 (IRS-1) (Hilder TL, Tou JC, Grindeland RF, Wade CE, and Graves LM. FEBS Lett 553: 63-67, 2003), suggesting that insulin-dependent glucose uptake may be impaired. However, during atrophy, these muscles preferentially use carbohydrates as a fuel source. To investigate this apparent dichotomy, we examined insulin-independent pathways involved in glucose uptake following a 2- to 13-wk hindlimb suspension regimen. JNK activity was elevated throughout the time course, and IRS-1 was degraded as early as 2 wk. AMP-activated protein kinase (AMPK) activity was significantly higher in atrophic soleus muscle, as were the activities of the ERK1/2 and p38 MAPKs. As a comparison, we examined the kinase activity in solei of rats exposed to hypergravity conditions (2 G). IRS-1 phosphorylation, protein, and AMPK activity were not affected by 2 G, demonstrating that these changes were only observed in soleus muscle from hindlimb-suspended animals. To further examine the effect of AMPK activation on glucose uptake, C2C12 myotubes were treated with the AMPK activator metformin and then challenged with the JNK activator anisomycin. While anisomycin reduced insulin-stimulated glucose uptake to control levels, metformin significantly increased glucose uptake in the presence of anisomycin and was independent of insulin. Taken together, these results suggest that AMPK may be an important mediator of insulin-independent glucose uptake in soleus during skeletal muscle atrophy.

AMP-Activated Protein Kinases↗

Effect of hind limb muscle unloading on liver metabolism of rats.

In response to decreased use, skeletal muscle undergoes an adaptive reductive remodeling. There is a shift in fiber types from slow twitch to fast twitch fiber types. Associated with muscle unloading is an increased reliance on carbohydrate metabolism for energy. The hind limb suspended (HLS) rat model was used as the experimental model to determine whether skeletal muscle unloading had any impact on the liver. We used a combination of actual enzyme assays and microarray mRNA expression to address this question. The GenMAPP program was used to identify altered metabolic pathways. We found that the major changes in the liver with HLS were increases in the expression of genes involved in the generation of energy fuels for export, specifically gluconeogenesis and lipogenesis. The expression of mRNA was increased (P<0.05) for three of the four enzymes involved in the regulation of gluconeogenesis pathway (pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G-6-Pase). Actual assay of enzymatic activity, in micromol . min(-1) . mg protein(-1) showed G-6-Pase (0.14+0.01 vs 0.17+0.01 P<0.05), fructose 1,6, bisphophosphatase (0.048+0.002 vs 0.054+0.002, P<0.07), and PEPCK (0.031+0.002 vs 0.038+0.012 (P<0.05) to be increased. We conclude that 1) atrophied muscle is not the only tissue to be affected by HLS, as there is also a response by the liver; and 2) the major changes in liver substrate metabolism induced by HLS appear to be limited to glucose and triglyceride production. The increase in glycolytic capacity in disused muscle is paralleled by an increase in glucogenic capacity by the liver.

Animals↗

Responses across the gravity continuum: hypergravity to microgravity.

In response to hypergravity, it appears that the larger the animal, the greater the response, if present. Therefore, the response of a rat exceeds that of a mouse in the same hypergravity environment. When investigated in the microgravity environment of space flight, this appears to hold true. The lack of definitive data obtained in space for either species makes the extrapolation of the continuum to levels below Earth-gravity problematic. However, in systems where responses are detected for both space flight and acceleration by centrifugation, a gravitational continuum is present supporting the "principle of continuity". For those and similar systems, it appears that the use of hypergravity could be used to predict responses to space flight.

Animals↗

Benefit of slow infusion of hypertonic saline/dextran in swine with uncontrolled aortotomy hemorrhage.

In laboratory models of uncontrolled hemorrhage, immediate resuscitation from hemorrhage is associated with high mortality. However, in clinical practice, resuscitation is often delayed and the rate of fluid administration is limited. We hypothesized that a slow rate of infusion after delayed resuscitation, reflecting the clinical environment, might improve survival in the presence of uncontrolled hemorrhage. To investigate the rate of administration in the presence of delayed resuscitation, we subjected anesthetized swine weighing 35 to 45 kg to wire suture abdominal aortotomy that resulted in an uncontrolled hemorrhage. After a 30-min delay, hemorrhaged swine were infused i.v. with 4 mL/kg hypertonic saline/Dextran solution (7.5% saline in 6% Dextran 70) administered as a bolus over 1 min or as a slow infusion over 12 min (the time period to administer a similar volume to a human with a gravity feed i.v. and an 18-gauge needle) and were then monitored for another 90 min. Survival increased to 78% (seven of nine) in the slow infusion group compared with a survival rate of 56% (five of nine) in the bolus group and 50% (7/14) in the untreated controls. Blood loss was significantly higher in the bolus group (926 +/- 77 mL) compared with the slow infusion (714 +/- 83 mL) and control groups (604 +/- 46 mL). Hypertonic saline/Dextran administered slowly significantly increased cardiac output and blood pressure. Taken together, these results are consistent with the hypothesis that resuscitation solutions can be effective for treatment of uncontrolled hemorrhage when administered at a slow infusion rate 30 min after the insult.

Anesthesia↗

Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats.

Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.

Adaptation, Physiological↗

Phosphorylation of insulin receptor substrate-1 serine 307 correlates with JNK activity in atrophic skeletal muscle.

c-Jun NH(2)-terminal kinase (JNK) has been shown to negatively regulate insulin signaling through serine phosphorylation of residue 307 within the insulin receptor substrate-1 (IRS-1) in adipose and liver tissue. Using a rat hindlimb suspension model for muscle disuse atrophy, we found that JNK activity was significantly elevated in atrophic soleus muscle and that IRS-1 was phosphorylated on Ser(307) prior to the degradation of the IRS-1 protein. Moreover, we observed a corresponding reduction in Akt activity, providing biochemical evidence for the development of insulin resistance in atrophic skeletal muscle.

Animals↗