Progress in burn treatment and the use of artificial skin.

Recently improved survival from thermal injuries has been demonstrated both in children and adults. This increase in burn injury survival rates is the result of multiple changes in treatment; probably the most important changes are, first, a more aggressive management of the wound with prompt excision of devitalized tissues and immediate closure of the wound, and, second, a better understanding and management of metabolic, immunologic, and nutritional aspects of the injured patient. Artificial skin is a very important additional treatment modality that has more recently become available and promises to contribute significantly to improvements in wound management and survival rates by its ability to physiologically close a burn wound immediately after its excision.

A new approach to the cryopreservation of hepatocytes in a sandwich culture configuration.

Current methods of cryopreservation of hepatocytes in single cell suspensions result in low overall yields of hepatocytes, demonstrating long-term preservation of hepatocellular functions. A novel culture method has recently been developed to culture liver cells in a sandwich configuration of collagen layers in order to stabilize the phenotypic expression of these cells in vitro (J. C.

Imaging infections with antibodies. A quantitative autoradiographic analysis.

Radiolabeled IgG has recently been demonstrated to effectively image infections. A potential but unproven mechanism for this localization is the specific binding of IgG to Fc receptors on the surface of inflammatory cells in infections. In an animal model of soft tissue infection, quantitative autoradiography was used to measure 125I-labeled IgG and albumin in tissues with a spatial resolution sufficient to associate these proteins with cellular morphology.

Antibody-targeted photolysis: in vitro studies with Sn(IV) chlorin e6 covalently bound to monoclonal antibodies using a modified dextran carrier.

A monoclonal antibody-dextran-Sn(IV) chlorin e6 immunoconjugate was prepared by a technique involving the site-specific covalent modification of the monoclonal antibody oligosaccharide moiety. Dextran carriers were synthesized with a single chain-terminal hydrazide group, which was used as the coupling point between the carrier and the monoclonal antibody carbohydrate. Selective in vitro photolysis of SK-MEL-2 human malignant melanoma cells was accomplished using several conjugates prepared from anti-melanoma 2.

Injury-induced inhibition of small intestinal protein and nucleic acid synthesis.

Small intestinal mucosal weight and nutrient absorption are significantly diminished early after cutaneous thermal injuries. Because these intestinal properties are highly dependent on rates of nucleic acid and protein synthesis, in vivo incorporation of thymidine, uridine, and leucine into small intestinal deoxyribonucleic acid, ribonucleic acid, and proteins were measured. Deoxyribonucleic acid synthesis was markedly decreased with the lowest thymidine incorporation in the jejunum (p less than 0.

Changing patterns in diagnosis and management of bile duct cancer.

An analysis of 186 patients treated for bile duct cancer at UCLA Medical Center from November 1954 to December 1988 demonstrated improvements in several areas of diagnosis and management. Comparison of 96 patients treated between 1954 and 1978 (group 1) with 90 patients treated between 1978 and 1988 (group 2) showed earlier diagnosis and treatment in group 2 (2.1 months from onset of symptoms) than in group 1 (4.

Preparation and characterization of immunoconjugates for antibody-targeted photolysis.

Monoclonal antibody (MAb)-dextran-tin(IV) chlorin e6 (SnCe6) immunoconjugates were prepared by a new technique involving the use of reducing, terminal-modified dextran carriers and site-specific modification of the Fc oligosaccharide moiety on the antibodies. Dextran carriers were synthesized to increase the number of SnCe6 molecules attached to a MAb. The dextran carriers were coupled to the MAb via a single, chain-terminal hydrazide group to prevent aggregation of MAbs.

Cutaneous thermal injury alters macromolecular permeability of rat small intestine.

The intestinal epithelium normally provides a barrier function that prevents absorption of potentially harmful materials from the intestinal lumen. It has been postulated but never demonstrated that a cutaneous thermal injury will result in increased small-intestinal permeability. In a standardized 20% body surface area full-thickness scald injury, with polyethylene glycol 3350 and horseradish peroxidase used as permeability probes, small-intestinal permeability was examined regionally in an everted intestinal sac model.

Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever.

Interleukins (IL) -1 beta and -1 alpha and tumor necrosis factor (TNF-alpha) were measured by radioimmunoassay in plasma samples from 44 healthy individuals, 15 patients in septic shock, and 6 volunteers infused with endotoxin. Plasma IL-1 alpha levels were low (40 pg/ml) or undetectable in all situations. In 67% of the healthy subjects, plasma IL-1 beta levels were less than 70 pg/ml.

Unique urinary-fecal calculus after cystectomy and ureterosigmoidostomy.

A 36-year-old m an had stage B1 bladder cancer-treated by cystectomy and ureterosigmoidostomy. Postoperatively, a urinary leak was managed successfully by transureteroureterostomy and temporary colostomy. In succeeding years a large calculus developed in the region where the bladder had been and it also involved the sigmoid colon.

Temperature dependence of the maternal-fetal electrical potential difference in guinea pigs.

An electrical potential difference (PD) is measured between maternal organism and fetus in the pregnant guinea pig. To investigate whether the PD is generated by active or passive forces these studies examined the temperature dependence of the PD in guinea pigs at 55-61 days gestation. Anesthesia was induced (ketamine, 44 mg/kg) and maintained (halothane, 1.

Autoradiographic method for quantitation of radiolabeled proteins in tissues using indium-111.

A quantitative autoradiographic method was developed to measure 111In-labeled proteins in extravascular tissues with a spatial resolution sufficient to associate these proteins with tissue morphology. A linear relationship between measured grain density and isotope concentration was demonstrated with uniformly-labeled standard sources of epoxy-embedded gelatin containing [111In]albumin; half-distance of spatial resolution was 0.6 micron.

Low-density lipoprotein transport in blood vessel walls of squirrel monkeys.

Transmural accumulations of low-density lipoprotein (LDL) were examined in the blood vessel walls of four squirrel monkeys. Vascular wall concentrations of LDL were measured using quantitative autoradiography after 125I-labeled LDL circulation for 30 min. Profiles of relative tissue concentration from different sections in the same region were similar to each other, and there was little animal-to-animal variation.

Increased survival after massive thermal injuries in adults: preliminary report using artificial skin.

Survival of major burn injuries has improved markedly from an expected survival of 10% to 20% in both children and adults to an expected survival of 60% in children with burns greater than 70% BSA. Increased survival for adults after similar burn injuries has been less dramatic than in children because of the profound influences of advancing age and the coexistent processes of aging upon survival after a major injury. Consecutive admissions of patients with massive burn injuries (greater than or equal to 70% BSA) to the Massachusetts General Hospital Adult Burn Unit from 1974 to 1986 were analyzed statistically using univariate and multiple logistic regression analysis to identify factors associated with survival and to identify patient characteristics associated with increases in expected survival.

Macromolecular transport within heart valves.

The present study documents the permeability characteristics of heart valvular endothelium to low-density lipoprotein (LDL), albumin, and horseradish peroxidase (HRP). Using quantitative autoradiography, LDL and albumin concentrations were measured within aortic valves of squirrel monkeys and rabbits after 30 minutes of in vivo circulation. The valvular concentration profiles were analyzed using theoretical mathematical models based on fundamental transport principles.

Inhibition of in vivo DNA synthesis in regenerating rat liver following thermal injury.

Hepatic repair and regeneration which is extremely important after thermal injuries can be inhibited by the acute inflammatory reaction. Since thermal injury initiates this acute inflammatory reaction, DNA synthesis was studied in the regenerating liver following this injury. In vivo incorporation of [3H]-thymidine into hepatic DNA, autoradiographic determination of a labeling index, and thymidine kinase activity were determined.

Management of cystic disease of the liver.

The management of cystic diseases of the liver requires an understanding of their pathophysiology and natural history. Surgery for congenital solitary cysts and polycystic disease should be reserved for patients with significant symptoms. Caroli's disease requires careful preoperative evaluation and planning and long-term follow-up.

Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration.

Adult rat hepatocytes cultured in a collagen sandwich system maintained normal morphology and a physiological rate of albumin secretion for at least 42 days. Hepatocytes cultured on a single layer of collagen gel essentially ceased albumin secretion within 1 wk but could recover function with the overlay of a second layer of collagen gel. This culture configuration more closely mimics the hepatocytes' in vivo environment and provides a simple method for their long-term maintenance.

Occult gastrointestinal bleeding: newer techniques and diagnosis and therapy.

Complex problems occur concerning the diagnosis and treatment of GI bleeding. How often can the exact cause and site of the bleeding be determined? What are the advantages and complications of various forms of treatment? There are no universal answers, applicable to all situations. Nevertheless, certain assumptions seem to be justified.

Significant reductions in mortality for children with burn injuries through the use of prompt eschar excision.

During the past 19 years, mortality due to burn injuries has markedly declined for children at the Boston Unit of the Shriners Burns Institute (SBI), dropping from an average of 9% of SBI admissions during 1968-1970 to an average of 1% during 1981-1986. Detailed statistical analysis using logistic regression was necessary for determining whether this decline in mortality was explained by changes in patient characteristics, such as age or burn size, which are known to strongly influence the outcome of burn injuries. This dramatic decline in mortality during the past 19 years was not the result of change in the age of the patients or their burn sizes; rather, it may be attributed to improvements in burn care.