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Biomedical subjects

J Hansbrough

Publications and source records attributed to J Hansbrough.

At least 19 recordsLinked to original sources

Effects of recombinant bactericidal/permeability-increasing protein (rBPI23) on neutrophil activity in burned rats.

Bactericidal/permeability-increasing protein (BPI) is a neutrophil granule protein with potent bactericidal and lipopolysaccharide (LPS)-neutralizing activities. The purpose of this study was to determine if a human recombinant BPI product, rBPI23, would influence neutrophil (PMN) sequestration into various tissues in a rat burn injury model. Leukosequestration may produce local tissue injury from proteases and high-energy oxygen species released from PMNs. Rats received tracheostomy and venous cannulation, then received 17 to 20% total body surface area full-thickness contact burns and resuscitation with 20 ml, of intraperitoneal saline. Ten mg/kg body weight rBPI23 in saline was given by intravenous injection immediately after burn injury, followed by intravenous doses of 2 mg/kg at 2 and 4 hours. Control animals received intravenous saline only. PMN retention in lung, liver, spleen, gut, skin, muscle, kidney, and brain tissues was determined by removing (before burn injury) and differentially radiolabeling PMNs (111In) and erythrocytes (51Cr), reinfusing cells 4.5 hours after burn injury, and measuring tissue radioactivity 30 minutes later. Edema was estimated by measuring extravasated 125I-labeled albumin in the various tissues, 30 minutes after injection. Peripheral blood PMNS were analyzed for intracellular H2O2 content by flow cytometry using a fluorescent dye that reacts with H2O2. Radioisotope studies demonstrated significant (p < 0.05) leukosequestration into lung, liver, gut, kidney, and skin tissues at 5 hours after burn injury. Tissue edema, manifested by radiolabeled albumin retention, was not observed in any tissues. Postburn PMN deposition in lungs and skin was decreased (p < 0.05) by the immediate administration of rBPI23 after burn injury. Flow cytometry showed increased intracellular H2O2 content in peripheral blood PMNs 5 hours after burn injury (p < 0.05), which was unaffected by administration of rBPI23. Since sequestration of metabolically active PMNs may induce tissue injury, therapies that block leukosequestration after burn injury may improve clinical outcomes by limiting remote tissue injury.

Animals↗

Drug and alcohol abuse in patients with acute burn injuries.

We reviewed records of adult patients admitted to our burn unit who were reported to abuse drugs or alcohol from 1985 to 1988. The proportion of patients reported as abusing drugs increased significantly from 1987 to 1988, compared to previous years. However, there was no increase in the proportion of patients reported to abuse alcohol. Patients identified as abusing drugs had longer hospital stays, compared to patients who were not reported to abuse substances. Methamphetamine and cocaine were the drugs most often abused by patients who abused drugs or both drugs and alcohol. Mechanisms of burn injury in these patients included "accidental" burn injury related to acute intoxication, and self-injury due to psychosis or depression.

Adult↗

The impact of in-house surgeons and operating room resuscitation on outcome of traumatic injuries.

As trauma systems develop, more patients can potentially benefit from immediate surgery. With in-house surgeons available, enthusiasm for direct transfer from the scene to the operating room (OR) has developed in many institutions. The purpose of this study was to define precisely which patients should be taken to the OR for resuscitation. Three hundred twenty-three patients were taken to the OR directly from the field during a 4-year period (6.9% of trauma activations). Indications included the following: (1) cardiac arrest--one vital sign present, (2) persistent hypotension despite field intravenous fluid, and (3) uncontrolled external hemorrhage. A board-certified surgeon and resuscitation team met the field transport team in the OR in all cases. Cardiopulmonary resuscitation for patients with blunt trauma was not accompanied by survival even with immediate surgery by a trained surgeon and it wastes valuable OR resources. Patients with prehospital hypotension unresponsive to fluid resuscitation indicate the need for rapid surgery. Patients with blunt injuries even with hypotension infrequently undergo operations in less than 20 minutes and can be resuscitated in traditional areas where better roentgenograms are obtained. Penetrating injuries to the chest and abdomen with hypotension are the primary indications for OR resuscitation. It can be anticipated with field communication and accompanied by enhanced survival.

Heart Arrest↗

Elastase and suppressor active peptide activity following burn injury.

Proteolytic enzyme activity following trauma and inflammation plays a key role in the pathophysiology of injury. The precise mechanisms involved in the induction of protease release has not been determined. We show here that sera from burn patients with greater than 40% TBSA have significantly elevated levels of active elastase which correspond with significantly increased levels of suppressor active peptide (SAP) and suppression of neutrophil chemotaxis. The elastase inhibitory capacity of serum from burned or blunt trauma patients was within normal range, suggesting that the primary elastase inhibitor, alpha-1-proteinase inhibitor, is functionally active. Additionally, granulocytes exposed to suppressor active peptide in vitro resulted in a markedly elevated release of elastase into the culture supernatants. These data suggest that the suppressor peptide is capable of not only suppressing immune function but is also a potent mediator for the induction of proteolytic enzyme release from leukocytes.

Burns↗

The neurohumoral response to burn injury in patients resuscitated with hypertonic saline.

Fourteen adult patients (mean age, 35 yrs) with 20-60% total body surface area (TBSA) burns (mean, 35%) were resuscitated using hypertonic sodium lactate (HSL: sodium = 250 mEq/L). Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), angiotensin II (A-II), epinephrine (E) and norepinephrine (NE) were measured on admission and for 7 days following burn injury. Serum sodium concentrations and osmolalities were lowest on admission, and were persistently elevated following HSL resuscitation. Plasma AVP levels were highest on admission and correlated with the size of the burn injury. Between days 4 and 5 plasma ANP levels rose while plasma AVP levels returned to normal. Plasma concentrations of AVP and ANP did not correlate with serum osmolality or serum sodium concentrations on admission or after HSL resuscitation. Plasma levels of A-II, NE and E were elevated throughout the 7-day period and were unrelated to the size of the burn.

Adult↗

Beach-fire burns in San Diego County.

In September and October 1986, seven patients were burned in beach fires in San Diego County; this prompted us to review our past patients who suffered beach-fire burns. A review of our registry revealed an additional 15 patients who had been burned in beach fires in the past 2 years. Four such cases are summarized, and common features are described.

Adult↗

Contact dermatitis to Biobrane.

Contact dermatitis to Biobrane has not been reported previously. We report a patient who developed a bullous skin reaction directly related to a second exposure to Biobrane. The second exposure occurred 18 days after initial use of Biobrane, and the bullous reaction developed within 48 hours of repeat exposure. Sensitivity was confirmed by patch testing. Clinicians should be aware of the possibility of contact dermatitis to Biobrane.

Adult↗

Vitamin E improves cell-mediated immunity in the burned mouse: a preliminary study.

Profound immunosuppression occurs after major burn injuries. The ability of vitamin E to prevent post-burn immunosuppression was tested in mice using ear swelling in response to a challenge with 2,4-dinitrofluorobenzene (DNFB) as an in vivo measure of cell-mediated immunity (CMI). Vitamin E was administered to burned mice every other day for 14 days by either the topical or intraperitoneal route. Dimethyl sulphoxide (DMSO) was compared to white petroleum jelly (VAS) as a vehicle for topically administered vitamin E. Mean CMI +/- the standard error of the mean (SEM) was depressed to 55 +/- 4 per cent of normal control in untreated burned mice. Treatment with either parenteral vitamin E in corn oil or topical vitamin E in DMSO improved CMI dramatically compared to burned controls (P less than 0.005) while vitamin E in VAS had a less beneficial effect on CMI (P less than 0.05). We conclude that vitamin E is an effective immunomodulator in burned mice.

Administration, Topical↗

Rapid volume replacement for hypovolemic shock: a comparison of techniques and equipment.

The achievement of a very rapid fluid infusion rate may be critical in the resuscitation of the patient in hypovolemic shock. We studied flow rates of crystalloid and whole blood through various intravenous catheters and tubing systems. The 10-gauge Angiocath and the 8 Fr pulmonary artery introducer catheter provide flow rates equivalent to intravenous tubing (3.2 mm I.D.) inserted directly into the vein. Substantially higher flow rates can be achieved with the use of large-bore intravenous tubing (5.0 mm I.D.) connected to these catheters in place of standard intravenous tubing, allowing the infusion of 1,200-1,400 cc/minute of crystalloid and whole blood into the patient in hypovolemic shock through one intravenous catheter. Clinical trials with larger bore intravenous tubing are probably indicated.

Blood Transfusion↗

Postburn immunosuppression in an animal model. II. Restoration of cell-mediated immunity by immunomodulating drugs.

We used a model of full-thickness burn injury in the mouse and quantitated cell-mediated immunity (CMI) by measuring the degree of sensitization to the contact antigen, 2,4-dinitrofluorobenzene (DNFB). Our previous studies have shown that CMI in the burned mouse is severely suppressed. Using this immunosuppression model, we were able to significantly restore CMI by treating animals following the burn injury either with one of the nonsteroidal anti-inflammatory drugs ibuprofen or indomethacin or with the cytotoxic alkylating agent cyclophosphamide. These drugs probably restore CMI by inhibiting generation of suppressor T lymphocytes in the burned host.

Animals↗

Regulation of granulopoiesis following severe thermal injury.

Neutropenia often accompanies septicemia in burned patients. This paradox suggests a defect in the regulation of granulopoiesis. Colony stimulating factor (CSF) produced by the monocyte-macrophage system is an important regulator of granulocyte production. We followed serial serum CSF levels and peripheral blood leukocyte differential counts in 22 patients with greater than 30% burns. Six patients (mean burn, 58%) developed Gram-negative septicemia and died (Group I). Sixteen patients (mean burn, 38%) had no fatal septicemias (Group II). Nonsurvivors had initially low levels of CSF and developed persistent monocytopenia. Survivors, in contrast, had prompt rises in CSF and developed monocytosis. The presence of monocytopenia and low CSF levels in Group I suggests an abnormality in the stimulatory arm regulating granulopoiesis. Such a defect may play a role in the development of fatal septicemia following severe thermal injury.

Adult↗

Multiple organ failure: clinical and experimental.

The clinical scenario of multiple organ failure (MOF) is reviewed and its frequent correlation with sepsis emphasized. It is hypothesized that MOF is produced by the formation of immune complexes (IC) in response to infection with deposition on organs such as the liver, lung, and kidney. Such immune complexes trap macrophages which can directly damage endothelium. Such a pathologic picture is in keeping with that of MOF. Granular deposits of IgG, IgM, C3, C5, and fibrinogen have been identified in the organs of four patients dying of MOF and sepsis. Similar deposits have been identified using fluorescent antibody stains in the organs of rabbits following cecal perforation. It is hypothesized that sepsis may produce organ failure at a distance from the site of infection via deposits of immune complexes.

Acute Kidney Injury↗

New approaches for immunosuppression.

New approaches for experimental immunosuppression have been reviewed. These include the following: 1) cyclosporin A, a metabolite from fungus that suppresses multiplying but not resting T and B lymphocytes and can be used in pulsed manner with interspersed drug-free periods; 2) total lymphoid irradiation (transplantation tolerance in rats has been achieved by pretransplant radiation); 3) thoracic duct drainage, which is being revived following its demonstrated effectiveness in the treatment of some autoimmune disease; 4) hyperbaric oxygen (HBOX). We have found that HBOX 2 1/2 ATA for five hours daily depresses cell-mediated immunity in mice and that this can be reversed by intravenous administration of autologous macrophages.

Animals↗

Preexisting psychiatric disorders in burn patients.

The authors studied 51 of 56 consecutive eligible patients admitted to a burn unit. Sixty-nine percent of the patients had a preburn psychiatric diagnosis. Depression alone was present in more than half the sample. Few burns were strictly accidental; 68% involved some degree of complicity on the victim's part, but intentional burns were rare. Patients with depression were more likely to sustain their burns in a setting of risk-enhancing behavior.

Adult↗

Sildimac: a new delivery system for silver sulfadiazine in the treatment of full-thickness burn injuries.

Wound care is painful for the patient with a burn injury and tedious for the burn unit staff but necessary to remove exudates and debris and to limit infections. In an effort to circumvent daily dressing changes while ensuring optimal wound protection, Sildimac (Marion Laboratories, Kansas City, Mo.), a new drug delivery system for silver sulfadiazine, was developed. When silver sulfadiazine, a topical antimicrobial commonly used for the treatment of burns, is incorporated into the delivery system, the drug is released in a sustained fashion. We report here the results of a multicenter evaluation of the safety and efficiency of Sildimac for treatment of full-thickness burn wounds. Sildimac, when left in place for up to 4 days, appears to be as effective as twice-daily wound cleansing and application of Silvadene cream 1% (Marion Laboratories, Kansas City, Mo.) for the treatment of full-thickness burns.

Acrylates↗

Effects of recombinant bactericidal, permeability-increasing protein on bacterial translocation and pulmonary neutrophil sequestration in burned mice.

Burn injury induces bacterial translocation (BT) from the gut in multiple animal models. Etiologic factors contributing to BT may be an ischemia-reperfusion injury to the gut, the release of inflammatory cytokines, oxygen metabolites and other mediators, and cytotoxic effects mediated by endotoxin (lipopolysaccharide). Bactericidal, permeability-increasing protein is a neutrophil granule protein with potent bactericidal and lipopolysaccharide-neutralizing activities. The use of this protein has not been previously reported in a burn-injury model. The purpose of this study was to determine whether recombinant bactericidal, permeability-increasing protein (rBPI23) affects the incidence of BT and myeloperoxidase content in lung tissue (a measure of leukocyte sequestration) in a burn-injury model. Mice received a 32% total body surface area, full-thickness, scald burn, and 10 mg/kg body weight rBPI23 in saline solution was given by intraperitoneal injection at 0, 3, and 6 hours after the burn. Control animals received intraperitoneal saline solution only. All animals received a total of 1 ml saline solution intraperitoneally immediately after burn injury for fluid resuscitation. At 24 hours after burn injury, mesenteric lymph nodes (MLN) were harvested, homogenized, and plated. Lung tissue was harvested and assayed for myeloperoxidase. Burned mice treated with rBPI23 had significantly (p = 0.005, Fisher's Exact Test, two-tailed) decreased incidence of BT, compared to burned mouse controls. Leukosequestration into lung tissues was not affected by rBPI23. Postburn administration of rBPI23 reduces but does not abolish the incidence of BT after burn injury in mice, perhaps by reducing intestinal injury during burn shock and the ischemia-reperfusion period by inhibiting the effects of lipopolysaccharide. An alternate explanation may be that rBPI23 could increase clearance and killing of bacteria by host defenses.

Animals↗