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Biomedical subjects
Publications and source records attributed to J Shelby.
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The effect of opioids (both exogenous and endogenous) on cell-mediated immune response in normal and thermally injured mice was evaluated with a delayed-type hypersensitivity assay. The administration of morphine sulfate to normal mice resulted in decreased delayed-type hypersensitivity response. This morphine sulfate-induced immunosuppression was prevented by concurrent treatment with the opioid antagonist, naloxone; however, naloxone alone did not alter immune response. Thermally injured mice had a suppressed delayed-type hypersensitivity response that was not further affected by morphine sulfate administration. In contrast, the immunosuppressive effects caused by burn injury, alone or in combination with the administration of morphine sulfate, were not observed in the presence of naloxone as measured by delayed-type hypersensitivity response. These results suggest that opioids depress cellular immune response and may play a role in immune dysfunction that follows thermal injury.
Thermally injured mice that were given intraperitoneal injections of murine cytomegalovirus (MCMV) appeared to be clinically septic and to have increased mortality rates. To evaluate the possible role of MCMV infection in promoting bacterial translocation in burned mice, mesenteric lymph nodes were cultured from two strains of mice (BALB/c and CBA) that were given thermal injuries alone, MCMV alone, or both. BALB/c mice injected with 5 X 10(5) plaque-forming units MCMV following a 15% to 16% total body surface area scald injury had increased incidence of positive mesenteric lymph node cultures compared with other groups. No intestinal mucosal histologies, mucosal dry weights, or wet-to-dry weight ratios in any animals were abnormal. Differences in cecal bacterial concentrations were not observed. Murine cytomegalovirus infection appears to enhance bacterial translocation in this model.
Cytomegalovirus is seen frequently in patients with burns and may enhance morbidity and mortality rates. Burned BALB/c mice that were given murine cytomegalovirus by intraperitoneal injection demonstrate increased bacterial translocation, as evidenced by positive mesenteric lymph node culture at 5 days after burn injury. The present experiment was conducted to investigate the time course and mechanism of this effect. A significant delay in the resolution of positive mesenteric lymph node cultures was observed with thermal injury alone. This was further reduced by the addition of murine cytomegalovirus infection to thermal injury. No such delay was seen with murine cytomegalovirus infection alone or in controls.
Allogeneic blood transfusion (Allo/BT) and burn injury modify the cellular immune response in patients under a variety of circumstances. We designed this study to investigate the influence of Allo/BT, burn injury, and the combination of the two on in vivo natural killer (NK) cell activity in a murine model. This study demonstrated significant enhancement of in vivo NK cell activity in noninjured BALB/c mice receiving Allo/BT from C3H mice when compared to both the control and syngeneic blood transfusion group at posttransfusion day 5. When burn-injured mice were compared to sham-stressed mice, the burn-injured mice showed significant suppression of in vivo NK cell activity. Furthermore, in this strain combination model, Allo/BT modulated the suppressive effect of burn injury on in vivo NK cell activity at posttransfusion day 5 and postburn day 7.
Rehabilitation of patients with burn injuries is receiving renewed interest because survival has improved, and health reform has mandated outcomes assessment. To determine factors affecting return to work, a survey was conducted among 234 employed patients treated from 1986 through 1993. The mean burn size was 13.3% total body surface area. Patients returned to work in a mean of 14.3 weeks; a number initially returned to light-duty or part-time jobs as a "bridge" to full-time employment. Length of hospitalization, number of surgeries, total and full-thickness burn size, and subjective assessments by patients of their functional ability correlated with time off work. Patients with health insurance were more likely to resume work than was expected, whereas those covered by Medicaid and those involved in injury-related lawsuits were less likely to return to work. It is hoped that this information can be used to design interventions aimed at improving this outcome of burn treatment.
Resuscitation from shock based on oxygen transport criteria has been widely used in trauma and surgical patients, but has not been examined in thermally injured patients. To study the possible efficacy of this type of resuscitation, the oxygen transport characteristics of burn resuscitation were studied in nine adults, of whom six had inhalation injuries, with a mean burn size of 45% total body surface area and a mean age of 33.4 years, who were resuscitated based on oxygen transport criteria. Pulmonary artery balloon flotation catheters were placed and hemodynamic and oxygen transport parameters (Fick method) were measured hourly for 6 hours. Patients received fluid boluses in addition to resuscitation calculated by the Parkland formula, until the pulmonary artery wedge pressure reached 15 mm Hg, after which dobutamine infusions (5 micrograms/kg/min) were initiated. Cardiac index increased from 2.51 to 6.57 L/min/m2 (p < 0.05), whereas systemic vascular resistance fell from 1534 to 584 dyne sec/cm5 (p < 0.05). Oxygen delivery (DO2I) and oxygen consumption (VO2I) indexes increased significantly during the study period (573 +/- 47 to 1028 +/- 57, and 132 +/- 8 to 172 +/- 16 ml/min/m2, respectively; p < 0.05). VO2I appeared dependent on DO2I at levels of DO2I less than 800 ml/min/m2. In this study, depressed cardiovascular function in patients with burn injuries responded to volume loading and inotropic support much as it does in patients with shock of other etiologies. Whether oxygen transport-based resuscitation is effective in improving survival or the incidence of multiple organ failure is unknown and will need to be evaluated in randomized trials.
Bone growth and remodeling are inhibited by severe burns in adult and pediatric patients, resulting in alterations in linear growth, bone mass, osteoporosis, and increased risk for pathologic fractures. This study of a mouse model of burn injury showed skeletal changes similar to those reported in patients with burn injuries. Baseline, control, sham, and burned mice were injected with fluorescent markers calcein and tetracycline for histomorphometric analysis. Total femur dry and ash weights and total calcium content were significantly lower 10 days after burn injury compared with sham and control animals. There also were decreases in the percentage of fluorochrome-labeled bone surfaces and bone formation rates in the burn-injured mice compared with control and sham mice; however, there were no differences in the mineral apposition rates. This model now provides an opportunity to examine cellular and molecular mechanisms contributing to skeletal pathology in a well-defined burn injury model.
Chemically crosslinked glycosaminoglycan (GAG) hydrogel films were evaluated as biointeractive dressings in a porcine model for donor-site autograft wounds. Multiple 5 x 5 x 0.03 cm wounds were created on the dorsum of pigs. Half of the wounds were treated with a GAG film plus an occlusive dressing (Tegaderm), whereas the other half were treated with Tegaderm alone. At 3, 5, or 7 days after surgery, the partially healed wounds were excised and evaluated histologically for three animals at each time point. By day 3, epithelial cells had proliferated and migrated from wound edges and from epithelial islands associated with residual hair follicles to begin to cover the wound bed. A statistically significant increase in coverage was observed for GAG + Tegaderm-dressed wounds than for those with Tegaderm alone at day 3 and day 5 post-surgery. By day 7, all treatment groups were completely healed. Thus, GAG hydrogels accelerated wound healing by enhancing re-epithelialization.
The crucial role of close relative care givers in the rehabilitation of the patient with burns indicates that the psychologic adjustment of noninjured relatives is of concern. This study examined the stress profiles of 14 spouses and parents of patients with burns of greater than 20% total body surface area. Four standardized measures of depression, anxiety, and cell-mediated immunity were used. Tests were given at two time intervals: less than 72 hours after admission and 2 to 5 weeks later. Depression and anxiety were high at the first test period; there was a significant drop in depression (p less than 0.05) but not in anxiety at the second testing. Immune function was suppressed at the first test but improved at the second test (p less than 0.05). There were significant negative correlations between immune response and psychologic distress, indicating that immune function declined as depressive symptoms increased. These results support an interaction between psychologic distress and immunity, and provide further evidence of the stressful nature of severe burn injury on close noninjured relatives.
Therapeutic interventions after traumatic injury often include components that may affect the immune response, including administration of blood transfusions. Recent efforts focused on the effect of transfusion on cell-mediated immune response (CMI) in mice. Antigen-specific and third-party allogeneic blood suppressed CMI response, indicating a nonspecific component of transfusion-induced immunosuppression. A larger volume of allogeneic blood given once was more suppressive than a smaller amount, while administration of syngeneic blood had no effect. The observed blood-induced suppression was indomethacin-sensitive, and antiprostaglandin E antibody given to transfused mice resulted in an augmented CMI. Prostaglandin E appears to play a mechanistic role in transfusion-induced suppression.
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