A bilayer artificial skin composed of a temporary Silastic epidermis and a porous collagen-chondroitn 6-sulfate fibrillar dermis, which is not removed, has been used to physiologically close up to 60% of the body surface following prompt excision of burn wounds in ten patients whose total burn size covered 50--95% body surface area (BSA). Following grafting, the dermal portion is populated with fibroblasts and vessels from the wound bed. The anatomic structure of the artificial dermis resembles normal dermis and serves as a template for the synthesis of new connective tissue and the formation of a "neodermis," while it is slowly biodegraded. This artificial skin has physiologically closed excised burn wounds for periods of time up to 46 days before the Silastic epidermis was removed. At the time of election when donor sites are ready for reharvesting, the Silastic epidermis is removed from the vascularized artificial dermis and replaced with 0.004 autoepidermal graft in sheet or meshed form. Clinical and histologic experience in a relatively short follow-up period (2--16 months) indicates that "neodermis" retains some of the anatomic characteristics and behavior of normal dermis, thus promising improvement in the functional and cosmetic results, as well as providing physiologic function as a skin substitute. The artificial skin is easily sterilized and stored at room temperature, capable of large scale production, and immediately available for grafting, indicating its potential for easy and relatively economic use in the burn patient.

Grid cells in the entorhinal cortex appear to represent spatial location via a triangular coordinate system. Such cells, which have been identified in rats, bats, and monkeys, are believed to support a wide range of spatial behaviors. By recording neuronal activity from neurosurgical patients performing a virtual-navigation task we identified cells exhibiting grid-like spiking patterns in the human brain, suggesting that humans and simpler animals rely on homologous spatial-coding schemes.

Individuals who suffer extensive loss of skin, commonly in fires, are acutely ill, in danger of succumbing either to massive infection of to severe fluid loss. Patients who survive these early threats must often cope with problems of rehabilitation arising from deep, disfiguring scars and crippling contractures. In this report we describe the physiocochemical, biochemical, and mechanical considerations that form the basis for two-stage design of a membrane useful as an experimental wound closure. Stage I of the design, applicable to short-term acute use, calls for a membrane which displaces efficiently air pockets from a carefully prepared woundbed, free of weak boundary layers, and maintains the moisture flux through the wound at an optimal level. Optimization of the surface energy, modulus of elasticity, energy to fracture and moisture permeability of the membrane are among the essential attributes of Stage I design. Stage 2 of the design, applicable to long-term, chronic use, focuses on a nonantigenic membrane which performs as a biodegradable template for synthesis of neodermal tissue. A survey of candidate materials suggests reasons for selection of a porous, crosslinked collagen-glycosaminoglycan coprecipitate as the chemical basis of an evolving design which was initiated 10 years ago. Over the past several years a set of membranes has been iteratively designed on this basis and has been used to cover satisfactorily large experimental full-thickness skin wounds in guinea pigs. Such membranes have effectively protected these wounds from infection and fluid loss for over 25 days without rejection and without requiring change or other invasive manipulation. When appropriately designed for the purpose, the membranes have also strongly retarded wound contraction and have become replaced by newly synthesized, stable connective tissue. Several rules relating the molecular structure and morphology of these membranes to cellular response of adjacent tissue have also been derived. This report is the first in a series which details the methodology of preparation and the record of performance.

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. Septic patients had higher plasma IL-1 beta levels (120 +/- 17 pg/ml, P = .001); those of surviving patients were higher than those of patients who died (P = .05). Plasma TNF-alpha concentrations in septic individuals were elevated (119 +/- 30 pg/ml) and correlated with severity of illness (r = .73, P = .003), but no correlation was observed between plasma IL-1 beta and TNF-alpha concentrations in individual samples. Infusion of endotoxin caused a twofold elevation of IL-1 beta, from a baseline of 35 +/- 5 pg/ml to a maximum of 69 +/- 27 pg/ml at 180 min (P less than .05). Peak TNF-alpha levels after endotoxin infusion were 15 times higher than IL-1 beta levels, were attained more rapidly (90 min), and as with the septic patients, did not correlate with IL-1 beta levels. These data support the concept that plasma IL-1 beta and TNF-alpha concentrations are regulated independently and are associated with different clinical outcomes.

Leucine metabolism in vivo can be determined from a primed, continuous infusion of L-[1-13C]leucine by measuring, at isotopic steady state, plasm [-13C]leucine enrichment, expired 13CO2 enrichment, and CO2 production rate. With an appropriate priming dose of L-[1-13C]leucine and NaH13CO3, isotopic steady state is reached in less than 2 h, and the infusion is completed in 4 h. The method can determine rates of leucine turnover, oxidation, and incorporation into protein with typical relative uncertainties of 2, 10, and 4%, respectively. The method requires no more than 1 ml of blood and uses stable isotope rather than radioisotope techniques. Thus, the method is applicable to studies of human beings of all ages. L-[1-13C]leucine may be infused with a second amino acid labeled with 15N for simultaneous determination of the kinetics of two amino acids.

To test the hypothesis that neural oscillations synchronize to mediate memory encoding, we analyzed electrocorticographic recordings taken as 68 human neurosurgical patients studied and subsequently recalled lists of common words. To the extent that changes in spectral power reflect synchronous oscillations, we would expect those power changes to be accompanied by increases in phase synchrony between the region of interest and neighboring brain areas. Contrary to the hypothesized role of synchronous gamma oscillations in memory formation, we found that many key regions that showed power increases during successful memory encoding also exhibited decreases in global synchrony. Similarly, cortical theta activity that decreases during memory encoding exhibits both increased and decreased global synchrony depending on region and stage of encoding. We suggest that network synchrony analyses, as used here, can help to distinguish between two major types of spectral modulations: (1) those that reflect synchronous engagement of regional neurons with neighboring brain areas, and (2) those that reflect either asynchronous modulations of neural activity or local synchrony accompanied by global disengagement from neighboring regions. We show that these two kinds of spectral modulations have distinct spatiotemporal profiles during memory encoding.

People often forget information because they fail to effectively encode it. Here, we test the hypothesis that targeted electrical stimulation can modulate neural encoding states and subsequent memory outcomes. Using recordings from neurosurgical epilepsy patients with intracranially implanted electrodes, we trained multivariate classifiers to discriminate spectral activity during learning that predicted remembering from forgetting, then decoded neural activity in later sessions in which we applied stimulation during learning. Stimulation increased encoding-state estimates and recall if delivered when the classifier indicated low encoding efficiency but had the reverse effect if stimulation was delivered when the classifier indicated high encoding efficiency. Higher encoding-state estimates from stimulation were associated with greater evidence of neural activity linked to contextual memory encoding. In identifying the conditions under which stimulation modulates memory, the data suggest strategies for therapeutically treating memory dysfunction.

Successful memory encoding is marked by increases in 30-100 Hz gamma-band activity in a broad network of brain regions. Activity in the 3-8 Hz theta band has also been shown to modulate memory encoding, but this effect has been found to vary in direction across studies. Because of the diversity in memory tasks, and in recording and data-analytic methods, our knowledge of the theta frequency modulations remains limited. The difference in the directionality of these theta effects could arise from a distinction between global cortical and deeper subcortical effects. To address this issue, we examined the spectral correlates of successful memory encoding using intracranial EEG recordings in neurosurgical patients and scalp EEG recordings in healthy controls. We found significant theta (3-8 Hz) power modulations (both increases and decreases) and high gamma (44 - 100 Hz) power increases in both samples of participants. These results suggest that (1) there are two separate theta mechanisms supporting memory success, a broad theta decrease present across both the cortex and hippocampus as well as a theta power increase in the frontal cortex, (2) scalp EEG is capable of resolving high frequency gamma activity, and (3) iEEG theta effects are likely not the result of epileptic pathology.