Where is the "neuro" in psychoneuroimmunology? A commentary on increasing research on the "neuro" component of psychoneuroimmunology.

The role of the central nervous system in generating the interrelationships among stress, endocrine and peripheral immune function, and disease receives relatively little experimental attention. This commentary encourages a greater emphasis on such research with a particular emphasis on the use of electrophysiological and neural imaging techniques.

The effects of forced-air warming on postbypass central and skin temperatures and shivering activity.

STUDY OBJECTIVE: To test the hypothesis that forced-air skin-surface warming used prophylactically after hypothermic cardiopulmonary bypass (CPB) would: (1) decrease the incidence and severity of postbypass shivering, (2) rapidly increase skin-surface temperatures when compared with standard warmed cotton blankets, and (3) not contribute to excessive central temperature elevation. DESIGN: Prospective, randomized, nonblinded comparison of two rewarming techniques. SETTING: Multidisciplinary intensive care unit at a tertiary care, private teaching hospital. PATIENTS: Following hypothermic CPB, 47 patients underwent postoperative rewarming by using either conduction (warmed cotton blankets) or convection (forced-air cover) techniques. MEASUREMENTS AND MAIN RESULTS: Central and skin temperatures were measured at 30-minute intervals for 5.5 hours postoperatively. Four lead electromyographic recordings were used to objectively document shivering activity. Antihypertensives, opioids, sedatives, and muscle relaxants were administered per patient need and recorded. The forced-air cover markedly decreased the overall incidence, duration, and magnitude of significant shivering compared with the warmed cotton blankets. Forced-air therapy produced clinically significant increases in skin surface temperatures, but avoided excessive central temperature elevation when compared with passive rewarming with cotton blankets. CONCLUSION: Convection warming, when compared with conductive warming with cotton blankets, limited the incidence, magnitude, and duration of shivering following hypothermic cardiac surgery. This suggests an important role of cutaneous thermal input in the mediation of the shivering response. The central tissue compartment is buffered from the effects of skin-surface warming and, thus, forced-air therapy will not lead to excessive central temperature elevation in this patient population when compared with cotton blanket rewarming.

Prophylactic strategies for hospitalized patients at risk for pneumonia.

Thirty-five years ago pneumonia prophylaxis failed because the agents available then did not have the antibacterial spectrum necessary to prevent colonization and infection with multiple gram-negative bacteria. Combinations of the newer antibiotics delivered intratracheally do cover most common organisms and they may be sufficient for prophylaxis. Careful monitoring is necessary because a number of unusual pathogens have the potential to circumvent the prophylactic regimen. Widespread use of topical antibiotics may result in the emergence of antimicrobial resistance in intensive care unit areas. The magnitude of this risk is difficult to calculate and some maneuvers are available to decrease the likelihood that this will occur. Nevertheless, at present these uncertainties are sufficient to prevent the routine clinical use of antibiotics for pneumonia prophylaxis. There are now eight studies showing that prophylaxis can decrease the incidence of pneumonia by greater than 50%. These should stimulate further clinical research designed to minimize the problems with bacterial resistance.

Enzyme histochemical changes in murine osteoarthritis.

Male mice of the STR/ORT strain spontaneously develop an osteoarthritic lesion in the medial tibial condyles. Histochemical studies of lactate dehydrogenase have previously shown that a region of completely inactive chondrocytes develops in the cartilage prior to degenerative changes. The present studies have shown a nearly parallel time course for the development of inactive cells and cartilage damage, except that there is a delay of four to five weeks between these two events. It is considered that the latter is a consequence of the former. The mechanism of the enzyme depletion is not known, but it probably extends to many, if not all, oxidative enzymes, and it is suggested that a disturbance in a hydrogen transport (cytochrome) system could account for the apparent lack of activity of many dehydrogenases as demonstrated by tetrazolium salt techniques.

A metabolic dysfunction in early murine osteoarthritis.

Male mice of the STR/ORT strain spontaneously develop an osteoarthritis lesion in the medial tibial condyle. The appearance of the lesion is age-related and by about 15 months has affected almost all animals. Histochemical studies of lactate dehydrogenase and succinate dehydrogenase activities have shown that a region of inactive chondrocytes appears in the cartilage of these mice before major histological evidence of degeneration. It is suggested that this may be an early metabolic dysfunction, which subsequently leads to matrix breakdown due to the lack of essential enzyme cofactors.

Some aspects of the use of tetrazolium salts in quantitative histochemistry.

The reduction of tetrazolium salts to highly coloured insoluble formazans is a reaction which has been widely exploited in histochemistry. This presentation considers three important aspects of the use of these compounds in quantitative studies, namely purity, intermediate reduction products, and calibration and measurement. Thin layer chromatography of tetrazolium salts from different suppliers has shown that standards of purity can vary widely, and that some samples are seriously contaminated. Studies with chromatographically pure compounds have demonstrated that the red diffuse colour seen in some reactions with di-tetrazolium salts is due to a half-reduced reduction intermediate. This "half-formazan" is part of the total activity, and cannot be disregarded in quantitative work. An understanding of the chemical nature of formazan end-products in tissue sections has made it possible to calibrate these reactions for microdensitometry.

Tissue stabilizer methods in histochemistry.

Quantitative studies in the 1960s established that the tissue disruption and enzyme loss which occurs when unfixed cryostat sections are incubated could be prevented with high concentrations of polyvinyl alcohol without inhibition of enzyme activity. This use of polymeric stabilizers has been largely confined to studies of 'soluble' dehydrogenases in tissue sections. However, optimum conditions for 'soluble' enzymes in cut sections may not be ideal for membrane-bound enzymes or for whole cells, where an over-stabilization of membranes can lead to restricted entry of reagents and thereby low activities. Lower concentrations, or other stabilizers such as Ficoll (a synthetic polysucrose) and collagen polypeptides, have been used in such cases. Suggested criteria for a tissue stabilizer are: (i) The stabilizer should be chemically inert, of defined and constant composition, and generally available; (ii) The tissue must remain structurally intact during the incubation, and the final preparation should look 'clean' and have the proper morphology; (iii) The component being assayed must remain inside the section, and not diffuse into the incubation medium. Ideally, it and any reaction product should remain at their original loci, although it may not always be possible to verify this; (iv) Recorded activities should be comparable to those found in biochemical systems under similar conditions.

Quantitative microscopy of enzyme reactions in tissue sections.

Microdensitometry makes it possible to measure reaction products in discrete regions of tissue sections. Single cells, or groups of cells, can be selected for measurement. In this way, it is possible to obtain quantitative data from enzyme reactions, and to relate activities to histology. Some examples are given to illustrate the application of this technique.