Is performance of intermittent intense exercise enhanced by use of a commercial palm cooling device?

The purpose of this study was to determine if using the CoreControl Rapid Thermal Exchange (RTX), a commercial palm cooling device, during active rest periods of multiple set training is an effective means to increase performance. Ten volunteers (5 men, 5 women) completed a VO2max test on a motorized treadmill and 3 interval running tests on a human powered treadmill. This treadmill allowed the subjects to quickly reach their running speed while allowing for measurement of distance, speed, and force. During the interval running tests the subjects completed eight 30-second intervals at a hard/fast pace followed by a 90-second walking or light jogging recovery period. During the recovery period, the subjects placed their left hand on 1 of 3 media: the RTX held at 15 degrees C (R), a 15 degrees C standard refrigerant gel pack (P), or nothing at all (C). Although there were differences in core temperature (Tc), subjective heat stress ratings, distance, and power generated between intervals, there were no significant differences (p < 0.05) found between treatments for any of these variables, nor was the interaction effect of interval*treatment found to be significant. Mean distance completed per trial was 717.1 m +/- 124.4 m (R), 724.8 m +/- 130.3 m (P), and 728.6 m +/- 110.6 m (C). Change in Tc from baseline to end-test averaged 1.41 degrees C +/- 0.37 degrees C (R), 1.41 degrees C +/- 0.39 degrees C (P), and 1.41 degrees C +/- 0.59 degrees C (C). There were no significant differences (p < 0.05) in Tc, heart rate (HR), or VO2 between intervals or treatments. We conclude that the RTX, in its current iteration, is ineffective at improving performance and/or mitigating thermal stress during high-intensity intermittent exercise.

TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation.

The pleiotropic activities of the potent proinflammatory cytokine TNF are mediated by two structurally related, but functionally distinct, receptors, p55 and p75, that are coexpressed on most cell types. The majority of biologic responses classically attributed to TNF are mediated by p55. In contrast, p75 has been proposed to function as both a TNF antagonist by neutralizing TNF and as a TNF agonist by facilitating the interaction between TNF and p55 at the cell surface. We have examined the roles of p55 and p75 in mediating and modulating the activity of TNF in vivo by generating and examining mice genetically deficient in these receptors. Selective deficits in several host defense and inflammatory responses are observed in mice lacking p55 or both p55 and p75, but not in mice lacking p75. In these models, the activity of p55 is not impaired by the absence of p75, arguing against a physiologic role for p75 as an essential element of p55-mediated signaling. In contrast, exacerbated pulmonary inflammation and dramatically increased endotoxin induced serum TNF levels in mice lacking p75 suggest a dominant role for p75 in suppressing TNF-mediated inflammatory responses. In summary, these data help clarify the biologic roles of p55 and p75 in mediating and modulating the biologic activity of TNF and provide genetic evidence for an antagonistic role of p75 in vivo.

Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors.

Poxvirus genomes encode several proteins which inhibit specific elements of the host immune response. We show the "35K" virulence gene in variola and cowpox viruses, whose vaccinia and Shope fibroma virus equivalents are strongly conserved in sequence, actually encodes a secreted soluble protein with high-affinity binding to virtually all known beta chemokines, but only weak or no affinity to the alpha and gamma classes. The viral protein completely inhibits the biological activity of monocyte chemotactic protein-1 (MCP-1) by competitive inhibition of chemokine binding to cellular receptors. As all beta chemokines are also shown to cross-compete with MCP1 binding to the viral protein, we conclude that this viral chemokine inhibitor (vCCI) not only interacts through a common binding site, but is likely a potent general inhibitor of beta chemokine activity. Unlike many poxvirus virulence genes to date, which are clearly altered forms of acquired cellular genes of the vertebrate immune system, this viral chemokine inhibitor (vCCI) shares no sequence homology with known proteins, including known cellular chemokine receptors, all of which are multiple membrane-spanning proteins. Thus, vCCI presumably has no cellular analogue and instead may be the product of unrelenting sequence variations which gave rise to a completely new protein with similar binding properties to native chemokine receptors. The proposed function of vCCI is inhibition of the proinflammatory (antiviral) activities of beta chemokines.

Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing.

Tumour necrosis factor (tumour necrosis factor-alpha/cachectin) plays a critical role in certain physiological defensive responses but causes severe damage to the host organism when produced in excess. There are two forms of tumour necrosis factor, a type II membrane protein of relative molecular mass 26,000 (26K) and a soluble, 17K form generated from the cell-bound protein by proteolytic cleavage. The two forms of tumour necrosis factor and lymphotoxin-alpha (tumour necrosis factor-beta/lymphotoxin), a related protein, have similar but apparently not identical biological activities. A therapeutic agent which inhibited the release of tumour necrosis factor, but did not reduce the cell-associated activity or the level of lymphotoxin-alpha, might preserve the benefits of these cytokines while preventing tumour necrosis factor-induced damage. Here we describe a potent inhibitor of tumour necrosis factor processing and report that it protects mice from a lethal dose of endotoxin.

Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists.

Two forms (monomeric or dimeric) of the extracellular, ligand-binding portion of the human p80 cell-surface receptor for TNF were used to antagonize TNF activity in vitro and in vivo. The dimeric sTNFR:Fc molecule was a more potent inhibitor of TNF than the monomeric sTNFR (50 to 1000x), as assessed in vitro by inhibition of TNF binding or bioactivity and in vivo by protection of mice from an otherwise lethal injection of LPS. Surprisingly, the dimeric sTNFR:Fc construct demonstrated a beneficial effect even when administered 3 h after a lethal LPS injection (i.e., after serum TNF levels had peaked and receded). To study the mechanism by which the soluble TNFR functions in vivo, serum TNF levels were examined in mice given LPS in the presence or absence of soluble receptor. Administration of a mortality-reducing dose of sTNFR:Fc ablated the rise in serum TNF bioactivity that normally occurs in response to LPS. However, TNF bioactivity was revealed in these "TNF-negative" serum samples when the L929 bioassay was modified by inclusion of a mAb that blocks the binding of murine TNF to the human soluble TNFReceptor. These results indicate that the absence of direct cytolytic activity in the L929 assay was caused by neutralization of TNF, rather than to an absence of TNF in the serum. Moreover, administration of either monomeric sTNFR or low doses of dimeric sTNFR:Fc actually resulted in increased serum TNF levels compared to mice given LPS but no soluble receptor. However, these "agonistic" doses of soluble receptor did not lead to increased mortality when an LD60 dose of LPS was given. Thus, dimeric sTNFR are effective inhibitors of TNF and under some circumstances function simultaneously as both TNF "carriers" and antagonists of TNF biologic activity.

Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery.

Experimental autoimmune encephalomyelitis (EAE) serves as an important animal model for understanding the events that lead to immune-mediated inflammation and tissue destruction within the central nervous system. We have utilized a murine adoptive transfer model of EAE and semiquantitative reverse transcriptase-polymerase chain reaction analysis to examine cytokine mRNA expression within the central nervous system in relation to the onset and resolution of paralysis associated with EAE. Spinal cord samples, obtained from mice as they progressed through discrete clinical stages of EAE, were examined for the expression of six cytokine genes (IL-1 alpha, IL-2, IL-4, IL-6, IL-10, and IFN-gamma). Distinct patterns of cytokine gene expression were observed during the acute, recovery, and chronic phases of EAE. The acute phase of disease was characterized by rapid increases in the levels of mRNA for IL-2, IL-4, IL-6, IFN-gamma, and IL-1 alpha. In fact, peak expression of several cytokine mRNA (e.g., IL-2, IL-4, IL-6, and IFN-gamma) occurred before the peak in clinical severity. In contrast, IL-1 alpha mRNA levels were elevated throughout the initial disease course. IL-10 mRNA demonstrated only modest increases during the acute phase of EAE. Stabilization of the clinical symptoms was characterized by rapid declines in the mRNA levels of IL-2, IL-4, IL-6, and IFN-gamma. The decreases in these four cytokine mRNA levels occurred concomitant with a dramatic rise in IL-10 mRNA. Finally, of the six cytokine mRNA examined, only IL-1 alpha, IFN-gamma, and IL-10 mRNA remained elevated during the early chronic stage. These results suggest that local cytokine production varies significantly during the course of EAE and that increases in discrete sets of cytokines are associated with the acute response and the recovery/chronic phase of disease.

The role of exercise testing in impairment evaluation.

To examine the usefulness of exercise testing in impairment evaluation, we reviewed the evaluation of 348 asbestos-exposed shipyard workers. We compared work capacity predicted from history, physical examination, chest roentgenogram, resting electrocardiogram, and resting pulmonary function tests with measured work capacity during an incremental cycle exercise test. The predicted work capacity was often incorrect when compared with measured maximal oxygen uptake (VO2). One third (22 of 66) of those predicted to have reduced work capacity had normal measured work capacity, and 46 of 148 workers (31%) predicted to have normal work capacity were found to have low maximal VO2 during exercise. Of 134 men for whom predicted work capacity was uncertain, maximal VO2 during exercise was low in 49 (37%), normal in 81 (60%), and remained indeterminate in 4 (3%). Thus, of the 138 workers who had low measured VO2, 43 were correctly predicted to have normal work capacity, 46 were incorrectly predicted, and the prediction was uncertain in 49. Only a few were limited by respiratory disease, and cardiovascular disorders limited 69% of those with a low maximal VO2 during exercise. Accordingly, resting VC, FEV1, and DLCO had a poor correlation with exercise performance. Finally, we found that resting DLCO was a poor predictor of abnormal exercise AaPO2, dead-space/tidal volume ratio, or arterial end-tidal PCO2 difference. We conclude that exercise testing is needed for accurate work capacity assessment in impairment evaluation. Exercise testing also facilitates the identification of the major limiting system in those with low work capacity.

Mobile 240 kVp phototimed chest radiography.

Chest radiographs obtained with mobile equipment for 240 kVp phototimed technique and conventional technique were compared in 161 patients. Features of interest were visualization of air space, interstitium, mediastinum, pleura and vessels, tracheobronchial tree, catheters and tubes. The 240 kVp system demonstrated consistently good visualization of central air passages, hilar contours, and pulmonary detail. It was superior to the conventional portable in eliminating respiratory motion, defining lung infiltrates, and localizing the endotracheal tube relation to the carina. The 240 kVp system had noticeable deficiencies in depicting calcifications, bone detail, and fat planes. These deficiencies were not of clinical significance. Although the equipment was compact, easily maneuverable, and simple to operate, the cassette holder was somewhat heavy--a detrimental but manageable factor. Another shortcoming was poor visualization of homogeneously opacified catheters within the mediastinum, although catheters with a dense radiopaque stripe alleviated this problem.