Biomedical subjects

D W Mozingo

Publications and source records attributed to D W Mozingo.

At least 19 recordsLinked to original sources

PubMed2000

Glucocorticoid-induced, caspase-dependent organ apoptosis early after burn injury.

Immune suppression and increased apoptotic loss of circulating lymphocytes have been reported after burn injury. However, little is known about the underlying mechanisms responsible for the increased apoptosis of lymphoid and parenchymal cells in solid organs and the role played by inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha) and Fas ligand (FasL), as well as by glucocorticoids. To evaluate the role of endogenously produced glucocorticoids and FasL, mice subjected to a 20% steam burn were pretreated with a glucocorticoid receptor antagonist (mifepristone) or a neutralizing murine Fas fusion protein. Three and twenty-four hours after burn injury, histological analysis, caspase-3 activity, and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and phenotyping of lymphocyte populations for apoptosis were evaluated. Burn injury increased the number of apoptotic cells and caspase-3 activity in thymus and spleen, but not in other solid organs. Increased apoptosis was seen in several T and B cell populations from both thymus and spleen. Mifepristone pretreatment significantly reduced the apoptosis and caspase-3 activity after burn injury, whereas blocking FasL activity had only minimal effects. We conclude that corticosteroids, and not FasL, are primarily responsible for the increased caspase-3 activity and apoptosis in thymus and spleen cell populations early after burn injury.

Animals↗

PubMed1999

Caspase-3-dependent organ apoptosis early after burn injury.

OBJECTIVE: To examine the role played by endotoxin, tumor necrosis factor-alpha (TNF-alpha), and caspase-3 in the increased apoptosis seen in solid organs in the early period after a burn injury. SUMMARY BACKGROUND DATA: Burn injury is often associated with immune suppression. Bacterial translocation and systemic endotoxemia have been reported after a burn injury, and caspase-3 activation due to TNF-alpha and Fas ligand (FasL) are presumed to initiate apoptosis. We hypothesized that endotoxin-induced TNF-alpha expression and caspase-3 activation could be the stimulus for the apoptosis after burn injury. METHODS: A 20% full-thickness scald burn was used in C57BL/6 mice. Three hours after burn injury, tissue samples were obtained from the thymus, lung, liver, and spleen. Lipopolysaccharide-nonresponsive (C3H/HeJ) and TNFalpha null B6x129tnf-/- mice were also used. To detect apoptosis, hematoxylin and eosin stain, in situ TUNEL, DNA extraction, and gel electrophoresis were all performed. Caspase-3 activity and TNF-alpha and FasL mRNA were also measured. RESULTS: Increased apoptosis and caspase-3 activity were observed in the thymus and spleen 3 hours after burn injury but were not seen in liver or lung. In the thymus and spleen, increased expression of FasL mRNA was also observed, whereas increased TNF-alpha mRNA was not. Increased apoptosis in thymus and spleen were also observed in C3H/HeJ and B6x129tnf-/- mice after burn injury. An inhibitor of the caspase-3 (Z-VAD-fmk) reduced apoptosis in both thymus and spleen. CONCLUSIONS: In the early period after a burn injury, increased apoptosis is observed primarily in the lymphoid organs and is independent of endotoxin or TNF-alpha. The increased caspase-3 activity in thymus and spleen contributes to apoptosis in these organs.

Animals↗

PubMed1999

Effects of long-term hemofiltration on circulating mediators and superoxide production during continuous endotoxin administration.

BACKGROUND: The purpose of this study was to test whether continuous hemofiltration eliminates cytokines and eicosanoids, or stimulates granulocyte function. METHODS: Nineteen pigs were divided into a control group (n = 7), a hemofiltration group (n = 7), and an extracorporeal circuit only group (n = 5). All animals received the same amount of intravenous endotoxin and resuscitation fluid. Zero-balanced hemofiltration was started 30 minutes after initiation of endotoxemia and continued throughout the experiment. Plasma endotoxin, tumor necrosis factor-alpha, eicosanoids, superoxide production, and other physiologic parameters were measured before challenge and at scheduled intervals thereafter. RESULTS: Eicosanoids were filtered but plasma concentrations were not reduced. Tumor necrosis factor-alpha was not filtered or adsorbed. There were no significant differences between groups in any measured parameters. CONCLUSION: Continuous hemofiltration could not efficiently remove tumor necrosis factor-alpha or eicosanoids. Also, continuous hemofiltration did not stimulate production of the proinflammatory mediators measured, nor improve respiratory distress.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Selectin blockade worsened lipopolysaccharide-induced lung injury in a swine model.

BACKGROUND: Polymorphonuclear leukocytes have been reported to play an important role in various acute lung injuries. Neutrophil recruitment into tissues is a multistep process involving sequential engagement of adhesion molecules. The objective of this study was to determine the effect of selectin inactivation with Sulfo Lewis C (SO3-3betaGal1-3betaGlcNAc-O(CH2)8-COOMe) on the pulmonary response to lipopolysaccharide (LPS) infusion. METHODS: All animals (n = 11) were pretreated with an intramuscular injection of a priming dose of Escherichia coli LPS (10 microg/kg). Eighteen hours later, animals received an intravenous infusion of LPS (20 microg/kg) over 20 minutes. All animals were resuscitated with a lactated Ringer's solution. Group I (G1; n = 5) received no additional treatment. Group II (G2; n = 6) received a bolus injection of Sulfo Lewis C (10 mg/kg) 10 minutes before LPS insult followed by a continuous infusion (1 mg/kg per hour) for the rest of the study. Animals were observed for 5 hours from initiation of the LPS infusion and killed. Cardiopulmonary variables and blood gases were measured serially. The multiple inert gas elimination technique (MIGET) was used to evaluate the matching of air flow and blood flow in the lung 5 hours after LPS infusion. Histologic evaluation of the parenchymal injury was performed by using light microscopy. The number of polymorphonuclear leukocytes and red blood cells in the alveolar spaces per field at 400x magnification were counted in 10 randomly selected fields. RESULTS: Hypoxemia, indexed as Pao2/FIO2, was exacerbated by the administration of Sulfo Lewis C (G1:437+/-33 vs. G2: 241+/-63 mm Hg at 5 hours, p<0.03). This finding is supported by the multiple inert gas elimination technique analysis, which demonstrated significantly greater blood flow to true shunt in G2 (G1:4.42+/-1.75 vs. G2:23.2+/-5.69, p<0.02). There was no difference between the two groups in red blood cell counts in the alveolar spaces. However, polymorphonuclear leukocyte counts were significantly greater in G2 (G1:1.8+/-0.58 vs. G2:9.9+/-2.34, p<0.01). CONCLUSION: Selectin blockade significantly worsened lung injury induced by LPS infusion, and greater numbers of neutrophils were observed in alveolar spaces in the group treated with Sulfo Lewis C. These findings are supported by the multiple inert gas elimination technique analysis, which demonstrated significantly greater blood flow to the true shunt compartment in treated animals. Further studies are required to determine the role of selectins in sepsis-induced lung injury.

Animals↗

PubMed1999

Biphasic changes in left ventricular function during hyperdynamic endotoxemia.

Cardiac contractility was studied in a clinically relevant conscious swine model simulating human hemodynamics during endotoxemia. The slope of the end-systolic pressure-volume relationship [end-systolic elastance (EES)] was used as a load-independent contractility index. Chronic instrumentation in 10 pigs included two pairs of endocardial ultrasonic crystals for measuring internal major and minor axial dimensions of the left ventricle, a micromanometer for left ventricular pressure measurement, and a thermodilution pulmonary artery catheter. After a 10-day recovery period, control measurements of cardiac hemodynamic function were obtained. The following week, Escherichia coli endotoxin (10 micrograms . kg-1. h-1) was administered intravenously for 24 h. EES increased 1 h after endotoxin infusion and decreased beyond 7 h. The later hemodynamic changes resembled human cardiovascular performance during endotoxemia more closely than the changes during the acute phase. EES decreased in the later phase. A similar biphasic response of EES has been reported during a tumor necrosis factor-alpha (TNF) challenge. Even though plasma TNF was highest at 1 h and declined thereafter in this study, no consistent relationship between TNF and EES was identified, and TNF levels did not correlate directly with the changes in EES.

Animals↗

PubMed1998

Effect of Sulfo Lewis C on smoke inhalation injury in an ovine model.

OBJECTIVE: To evaluate the effect of Sulfo Lewis C (SO3-3âGal1-3GlcNAc-O(CH2)8-COOMe), a putative ligand of selectins, on smoke inhalation injury. DESIGN: Prospective animal study with concurrent controls. SETTING: An animal laboratory. SUBJECTS: Twelve 1-yr-old female sheep, weighing 24 to 33 kg. INTERVENTIONS: Twelve sheep received nine exposure units of smoke generated by thermolysis of pine woodchips (80 g). Group 1 (n = 6) was untreated. Group 2 (n = 6) was treated with an intravenous infusion of Sulfo Lewis C after smoke exposure. Animals were killed 48 hrs after injury. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary variables and blood gases were measured serially. Granulocyte free-radical production was measured before smoke exposure and at 4 and 48 hrs after injury. Ventilation/perfusion distribution (VA/Q) was analyzed using the multiple inert gas elimination technique. Granulocyte free-radical production was increased after smoke exposure in both groups. Oxygenation was significantly improved by the administration of Sulfo Lewis C. VA/Q analysis demonstrated significantly less blood flow to low VA/Q lung segments in treated animals. CONCLUSIONS: Selectin blockade attenuated lung injury after smoke exposure. These data support the hypothesis that neutrophils play a pivotal role in smoke inhalation injury.

Animals↗

PubMed1998

Factors contributing to delayed extremity amputation in burn patients.

BACKGROUND: Previous series of traumatic amputations have noted that delay in amputation results in prolonged hospital stay and delayed rehabilitation. A series of major extremity amputations after burn injury was analyzed to identify the frequency of delayed amputation and to identify factors resulting in the delay. METHODS: Chart review of burn admissions between January of 1991 and December of 1995. RESULTS: Twenty-eight patients underwent a total of 44 major extremity amputations. Thirty-five amputations in 22 patients were performed by postburn day 16 (mean 4.3). Nine amputations in six patients were delayed beyond postburn day 26 (mean, 48.3). Delayed amputations occurred in the subgroups of deep thermal burns with extensive necrosis and thermal burns complicated by infections. Early amputation was associated with a 13.6% mortality rate, delayed amputation with a 50% mortality rate. CONCLUSION: There is a bimodal distribution of time to amputation determined by mechanism of injury, severity of burn, and infectious complications. Earlier identification of nonsalvageable limbs may decrease infectious complications and improve the chances of patient survival.

Adult↗

PubMed1998

Inhaled nitric oxide prevents left ventricular impairment during endotoxemia.

We evaluated the effect of long-term inhalation of nitric oxide (NO) on cardiac contractility after endotoxemia by using the end-systolic elastance of the left ventricle (LV) as a load-independent contractility index. Chronic instrumentation in 12 pigs included implantation of two pairs of endocardial dimension transducers to measure LV volume and a micromanometer to measure LV pressure. One week later, the animals were divided into a control group (n = 6) or a NO group (n = 6). All animals received intravenous Escherichia coli endotoxin (10 micrograms. kg-1. h-1) and equivalent lactated Ringer solution. NO inhalation (20 parts/million) was begun 30 min after the initiation of endotoxemia and was continued for 24 h. In both groups, tachycardia, pulmonary hypertension, and systemic hyperdynamic changes were noted. The end-systolic elastance in the control group was significantly decreased beyond 7 h. NO inhalation maintained the end-systolic elastance at baseline levels and prevented its impairment. These findings indicate that NO exerts a protective effect on LV contractility in this model of endotoxemia.

Administration, Inhalation↗

PubMed1997

Incidence of bacteremia after burn wound manipulation in the early postburn period.

BACKGROUND: Transient bacteremia associated with burn wound manipulation is considered a frequent occurrence and is commonly cited as an indication for perioperative antibiotic prophylaxis in burn patients. METHODS: In a prospective clinical setting, blood cultures (BC) were obtained from 19 burn patients at the following intervals: 30 minutes before wound cleansing (WC) or wound excision (WE), 30 minutes after the start of WC or WE, hourly until procedure completion, and 1 hour after completion. Burn wound biopsy for histologic grading and microbial culture was performed after the first BC. RESULTS: Twenty-two WC and 20 WE episodes were evaluated by 67 and 76 BC sets, respectively. Patients had a mean age of 42.8 years and mean burn size of 50% of the body surface area. Three WC episodes (13.6%) and four WE procedures (20.0%) were associated with postprocedure bacteremia. Two patients had both preprocedure and postprocedure bacteremia later attributed to nonburn wound infections. Excluding these cases, the bacteremia rate was 12.5% (9.5% from WC and 15% from WE). Wound biopsy culture and histologic analysis did not predict the occurrence of bacteremia. CONCLUSION: Current therapy is associated with a lesser incidence of burn wound manipulation-induced bacteremia than reported in prior series. The discordance between wound biopsy and BC results, the absence of positive histology, and the similarity of bacteremia occurrence rates with WC and WE confirm the effectiveness of current techniques of microbial control in burn wounds and question the need for perioperative antibiotic therapy in patients with burns involving less than 40% of the total body surface during the first 10 postburn days.

Adult↗

PubMed1997

Effects of burns on inhalation injury.

BACKGROUND: There are few studies of smoke injury combined with thermal burn. METHODS: Seven sheep (G1) received smoke injury alone; eight (G2) received a 40% full-thickness scald burn immediately after smoke injury. All animals were resuscitated with lactated Ringer's solution and killed 48 hours after injury. Cardiopulmonary variables and blood gases were measured serially. Ventilation perfusion distribution was analyzed using the multiple inert gas elimination technique. Lung wet to dry weight ratio and malondialdehyde levels were determined. RESULTS: G2 resulted in early significant hemodynamic changes. Serum total protein concentration was significantly lower and malondialdehyde significantly higher in G2. However, PaO2, lung wet to dry weight ratio, and ventilation perfusion mismatching in G2 did not differ from those in G1. CONCLUSIONS: Although the addition of burn injury exaggerated the lung lipid peroxidation and hypoproteinemia in the presence of more pronounced hemodynamic changes, the pulmonary dysfunction was not accentuated.

Animals↗

PubMed1997

Prospective outcome analysis of a protocol for the surgical and rehabilitative management of burns to the hands.

Treatment protocols for the management of burned hands are essential for integrating team efforts and achieving optimal functional results. Standard protocols are especially useful during mass casualty incidents, when the admission of multiple patients with large burns and/or associated injuries may reduce the priority usually accorded the hands. We prospectively evaluated a surgical and rehabilitative treatment protocol for burned hands during a mass casualty incident, after which 43 burn patients with 82 burned hands were admitted to one burn center. Soft-tissue management was individualized to achieve, if possible, wound closure within 14 days, and included the use of topical antimicrobials, cutaneous debridement and/or tangential excision, biologic dressings, and split-thickness autografts. Range of motion therapy was based on daily measurement of active motion of the metacarpophalangealjoints. Static splinting alternating with continuous passive motion every 4 hours was utilized for sedated patients. Continuous passive motion alternating with active ranging and night splinting was utilized for metacarpophalangeal flexion <70 degrees. Active ranging and progressive resistance was utilized for metacarpophalangeal flexion > or =70 degrees. Sixty-four hands required excision and grafting, with 89 percent having at least one autografting procedure completed by postburn day 16. Total active motion of the hands treated averaged 220.6 degrees on discharge and 229.9 degrees at 3 months after injury. Mean hand grip strength was 60.8 pounds at discharge and 66.0 pounds at 3 months after injury. Adherence to a standard hand burn protocol resulted in timely wound coverage and recovery of hand function for a large group of patients treated at a single burn facility after a mass casualty incident.

Accidents, Aviation↗

PubMed1996

Effect of ambient temperature on metabolic rate after thermal injury.

OBJECTIVE: The authors describe the effect of ambient temperature on metabolic rate after thermal injury. SUMMARY BACKGROUND DATA: Thermal injury induces a hypermetabolic state, which is reported to increase with the extent of burn. The magnitude of this response is further influenced by ambient temperature. METHODS: The resting energy expenditure was measured by indirect calorimetry at ambient temperatures of 22, 28, 32, and 35 C. It was indexed to a calculated basal metabolic rate in normal volunteers and adult patients with burns involving at least 20% of the total body surface area who had no evidence of systemic infection. These measurements were performed between postburn days 6 and 21. RESULTS: The effect of ambient temperature on metabolic rate was measured in 44 burn patients and 8 normal volunteers. Burn size ranged from 20 to 97% total body surface area with a mean of 44 +/- 18.5% total body surface area. Metabolic rate did not change significantly in control subjects as ambient temperature was varied (p<0.05). Regression analysis showed that burn size and ambient temperature were significant determinants (p<0.01) of metabolic rate in the patients and that together these factors accounted for 55% of the variation observed (df adj. r(2)=0.55) across the range of ambient temperatures studied. Metabolic rate was independent of burn size at ambient temperatures of 32 and 35 C (p<0.02) and increased by a factor of 1.5 X basal metabolic rate. A further increase in metabolic rate, which was positively correlated with burn size, resulted from nonshivering thermogenesis at ambient temperatures 28 and 22 C. The magnitude of this response was greatest at 22 C. CONCLUSIONS: These findings suggest that the hypermetabolic response to thermal injury is maximal in burns as small as 20% total body surface area and that an additional burn size-dependent increase in metabolic rate results from heat loss at ambient temperatures below thermoneutrality.

Adult↗

PubMed1995

Peritoneal lavage in the diagnosis of acute surgical abdomen following thermal injury.

Intraperitoneal sepsis is difficult to diagnose in thermally injured patients. We reviewed the use of diagnostic peritoneal lavage (DPL) in burn patients suspected of having intraperitoneal infection. Seventeen patients were identified in whom celiotomy, autopsy, or complete recovery could be used to validate the lavage results. A lavage was considered positive if there were greater than 500 white blood cells per mm3 or if microorganisms were present on Gram stain. Six patients had a positive DPL and 11 patients had a negative DPL. There were six true positive, no false positive, ten true negative, and one false negative studies resulting in a sensitivity of 0.86, specificity of 1.00, and diagnostic accuracy of 94%. No complications related to the DPL occurred. This procedure is safe and will rapidly and reliably discriminate between patients needing urgent celiotomy and those requiring further investigation to identify a source of sepsis.

Abdomen, Acute↗

PubMed1992

Properitoneal synthetic mesh repair of recurrent inguinal hernias.

Safe reconstruction of the inguinal floor is the goal of any operation for repair of groin herniation. Operating in the properitoneal space avoids dissection of the scarred cord, and the incidence of testicular complications is markedly lowered. This study reports our experience with placing synthetic mesh between the peritoneum and the deficient inguinal floor for the repair of recurrent hernias of the groin area. During a five year period, 84 men underwent repair of 100 recurrent inguinal hernias using the properitoneal approach. Fifty-four patients had repair of a unilateral recurrent hernia, 16 had repair of a bilateral recurrent hernia and 14 had repair of both a recurrent hernia and a contralateral primary hernia. Postoperative complications occurred in six patients. No testicular complications were observed. Postoperative follow-up study ranged from six months to five years. There were only three recurrent hernias after this repair. All occurred within the first six months postoperatively. The properitoneal approach for repair of recurrent groin hernias using prosthetic mesh safely creates a new "fascia transversalis" with a low rate of recurrence and effectively eliminates testicular complications.

Adult↗

PubMed1991

New modes of mechanical ventilation.

Mechanical ventilation is required by surgical patients for a number of different reasons. The methods available to ventilate patients have increased in the last few years. Some of these techniques have proved helpful, while a few remain investigational searching for an application. Surgeons dealing with critically ill patients must remain current with alternative methods of ventilation.

High-Frequency Ventilation↗

PubMed1989

A comparison of the cerebral and cardiovascular effects of complete resuscitation with isotonic and hypertonic saline, hetastarch, and whole blood following hemorrhage.

Hemorrhagic shock and closed head injury often accompany severe trauma. Hypertonic saline may be beneficial in these patients, but few have examined its properties when sufficient volume is infused to achieve sustained resuscitation. Solutions of 6% NaCl (HS), 0.9% NaCl (NS), 6% hetastarch (HE), and whole blood (WB) were used to resuscitate swine in hemorrhagic shock (MAP less than 30 mm Hg). The endpoint of resuscitation was normal oxygen delivery (DO2). Measurements of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and intracranial elastance (ICE) were made in the absence and presence of an epidural mass, created by inflating an epidural balloon. HS resuscitation resulted in a lower ICP [5 +/- 1 versus 9 +/- 2 (HE), 17 +/- 3 (NS), and 10 +/- 3 (WB) mm Hg; p = 0.016], and normalization of CPP throughout resuscitation. Animals resuscitated with NS had a lower CPP by the end of resuscitation [CPP = 45 +/- 4 for NS group, versus 63 +/- 4 (HE), 66 +/- 4 (HS), and 63 +/- 5 (WB) mm Hg; p = 0.009]. ICE fell markedly in the HS group, [a decrease of 12 +/- 2 vs. a rise of 5 +/- 3 (HE), 2 +/- 3 (NS), and 6 +/- 3 (WB) mm Hg/ml; p = 0.0005]. This improvement was even more dramatic in the presence of an epidural mass [a fall of 21 +/- 3 vs. no change (HE, WB) and a rise of 4 +/- 3 (NS) mm Hg/ml; p = 0.0005]. For hemorrhage accompanied by severe head injury, resuscitation with HS may benefit victims by decreasing ICP and diminishing the effects of an intracranial mass.

Animals↗

PubMed1988

Chemical burns.

In chemical skin injuries, reduction of the time of exposure to the causative agent and recognition of systemic toxicity are necessary to lessen the severity of the insult, reduce morbidity, and maximize survival. During a 17-year period (1969 through 1985), 87 (2.1%) of the 4,212 burned patients admitted to the U.S. Army Institute of Surgical Research sustained chemical burns. Twelve of 87 patients died (13.8%). White phosphorous, the most common causative agent, produced cutaneous injury in 49 patients. Acids (13 patients), alkalies (ten patients), and organic solvents (five patients) were the other common causes of injury. Initial treatment consisted of water lavage. Later wound management was carried out with topical antibiotic therapy and excision and grafting as necessary. Systemic toxicity due to phenol, nitrate, and formate absorption occurred, as did acute tubular necrosis following copper sulfate treatment of white phosphorus burns. Inhalation injury occurred in five patients. A decrease in hospital stay for chemically injured patients was observed. To minimize chemical injury, clothing should be removed promptly and water lavage begun. Systemic toxicity and inhalation injury are rare but often severe and increase mortality.

Adolescent↗

PubMedDate not supplied

Computer-assisted evaluation of hand and arm function after thermal injury.

Comprehensive care of the burned upper extremity requires accurate and complete evaluation of function, including two-point discrimination, active and passive range of motion, and grip strength. These evaluations, when performed serially during a course of therapy, are time-consuming and manpower-intensive. We tested the utility and accuracy of a commercially available computer-assisted impairment evaluation system when used to automate and standardize measurement of upper-extremity function. The function of 80 upper extremities was evaluated with both the conventional and the computer-assisted methods. The time required to perform a complete examination with each method was recorded, and measurements of grip strength and total active motion made with both methods were compared. Complete upper-extremity evaluation required an average of 20.3 minutes with the computer-assisted method, compared to 62.9 minutes with conventional means. Measurements of extremity function with computer-assisted and conventional methods had correlation coefficients of 0.984 for grip strength and 0.996 for total active motion. The computer-assisted impairment evaluation system was found to be a useful and accurate adjunct in the acute and rehabilitative management of burned upper extremities.

Arm Injuries↗