A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma

The addition of concanavalin A-stimulated supernatants of the helper T cell clone, D9.1, to cultures of lipopolysaccharide (LPS)-stimulated T-depleted mouse spleen cells caused more than a 100-fold increase in immunoglobulin (Ig) E production. These supernatants cause a 10-fold to 15-fold increase in IgG1, a fivefold to 10-fold increase in IgA, and a fivefold to 10-fold decrease in IgG3. These effects are optimal when the supernatants are added 1 to 2 days after stimulation with LPS. Cells from mouse strains that normally give little or no IgE response in vivo give normal IgE levels in response to LPS plus the supernatant of Concanavalin A-stimulated D9.1 cells in vitro. The enhancement of both IgE and IgG1 can be completely inhibited by relatively low concentrations of interferon-gamma (IFN-gamma). Both the IgE-enhancing activity and IFN-gamma act directly upon purified B cells.     

Piroxicam, a structurally novel anti-inflammatory compound. Mode of prostaglandin synthesis inhibition

Piroxicam is a potent inhibitor of prostaglandin biosynthesis. Experiments utilizing cell culture and microsomes derived from various sources have demonstrated that piroxicam is a selective inhibitor of the cyclooxygenase step of arachidonic acid metabolism. Little blocking activity is observed at the phospholipase, thromboxane or prostacyclin synthetase, and arachidonic acid lipoxygenase steps.     

Conformational effects of the substitution of Arg for Gly 13 in the ras oncogene-encoded P21 protein

The effect of the substitution of Arg for Gly 13 on the structure of the transforming region decapeptide (Leu 6-Gly 15) of the ras oncogene encoded P21 protein has been investigated using conformational energy analysis. A human malignancy has been identified that contains a ras gene with a single mutation in the thirteenth codon such that the encoded protein would have Arg substituted for Gly at this position, and transfection of cells in culture with this gene results in malignant transformation. Conformational analysis demonstrates that the Arg 13 decapeptide adopts a conformation identical to that for other peptides with substitutions at position 13 (Asp 13, Val 13) from transforming proteins that is distinctively different from that for peptides (Gly 13, Ser 13) from normal, nontransforming proteins. This is found to be an indirect effect resulting from changes in the conformation of Gly 12 produced by substitutions at position 13. These results are consistent with recent analysis of crystallographic data of proteins on conformational preferences for glycine in tripeptide sequences.     

Antimicrobial Activity of a Novel Vascular Access Film Dressing Containing Chlorhexidine Gluconate

Background

Covering insertion sites with chlorhexidine impregnated dressings has been proven to be clinically effective in reducing catheter related blood stream infections (CR-BSI). Two chlorhexidine gluconate (CHG)-impregnated dressings are commercially available, a polyurethane foam disk and a film dressing containing a chlorhexidine gluconate-impregnated gel pad. While both have demonstrated efficacy in clinical settings, the major drawback of high cost and impaired IV insertion site visibility limits their usage. A new, simple film dressing containing CHG within its adhesive layer is now available. The objective of this study was to test the in vitro antimicrobial efficacy of the new dressing in comparison to the CHG-impregnated gel dressing.

Methods

Quantitative aliquots of suspensions (concentration of 1.0x10⁶ to 5.0x10⁶ cfu/sample) of clinically relevant challenge organisms (Staphylococcus species, gram-negative bacilli, Candida albicans) were incubated in contact with the new CHG-containing film dressing, a placebo version of the same (negative control) and the commercially available CHG-impregnated gel dressing (positive control). Serial dilutions of the surviving organisms were quantified using the pour plate after 1, 3, 5, and 7 days of incubation in order to calculate an antimicrobial log₁₀ reduction for each organism/dressing combination at each point in time.

Results

The new CHG-containing film dressing delivered greater than 5.0 log₁₀ reduction throughout the 7 days on all aerobic gram-negative bacilli and Staphylococcus species tested. As of day 1 the CHG-containing film dressing provided greater than 5.0 log₁₀ reduction on Candida albicans. There were no statistically significant differences in the log₁₀ reduction between the two dressings tested.

Conclusion

The new CHG-containing film dressing was found to be as effective as the chlorhexidine gluconate-impregnated gel dressing on clinically relevant microbes.     

Surgical Risks Associated with Winter Sport Tourism

BackgroundMass tourism during winter in mountain areas may cause significant clustering of body injuries leading to increasing emergency admissions at hospital. We aimed at assessing if surgical safety and efficiency was maintained in this particular context.MethodsWe selected all emergency admissions of open surgery performed in French hospitals between 2010 and 2012. After identifying mountain areas with increasing volume of surgical stays during winter, we considered seasonal variations in surgical outcomes using a difference-in-differences study design. We computed multilevel regressions to evaluate whether significant increase in emergency cases had an effect on surgical mortality, complications and length of stay. Clustering effect of patients within hospitals was integrated in analysis and surgical outcomes were adjusted for both patient and hospital characteristics.ResultsA total of 381 hospitals had 559,052 inpatient stays related to emergency open surgery over 3 years. Compared to other geographical areas, a significant peak of activity was noted during winter in mountainous hospitals (Alps, Pyrenees, Vosges), ranging 6-77% volume increase. Peak was mainly explained by tourists’ influx (+124.5%, 4,351/3,496) and increased need for orthopaedic procedures (+36.8%, 4,731/12,873). After controlling for potential confounders, patients did not experience increased risk for postoperative death (ratio of OR 1.01, 95%CI 0.89-1.14, p = 0.891), thromboembolism (0.95, 0.77-1.17, p = 0.621) or sepsis (0.98, 0.85-1.12, p = 0.748). Length of stay was unaltered (1.00, 0.99-1.02, p = 0.716).ConclusionSurgical outcomes are not compromised during winter in French mountain areas despite a substantial influx of major emergencies.     

Triceps surae short latency stretch reflexes contribute to ankle stiffness regulation during human running

During human running, short latency stretch reflexes (SLRs) are elicited in the triceps surae muscles, but the function of these responses is still a matter of controversy. As the SLR is primarily mediated by Ia afferent nerve fibres, various methods have been used to examine SLR function by selectively blocking the Ia pathway in seated, standing and walking paradigms, but stretch reflex function has not been examined in detail during running. The purpose of this study was to examine triceps surae SLR function at different running speeds using Achilles tendon vibration to modify SLR size. Ten healthy participants ran on an instrumented treadmill at speeds between 7 and 15 km/h under 2 Achilles tendon vibration conditions: no vibration and 90 Hz vibration. Surface EMG from the triceps surae and tibialis anterior muscles, and 3D lower limb kinematics and ground reaction forces were simultaneously collected. In response to vibration, the SLR was depressed in the triceps surae muscles at all speeds. This coincided with short-lasting yielding at the ankle joint at speeds between 7 and 12 km/h, suggesting that the SLR contributes to muscle stiffness regulation by minimising ankle yielding during the early contact phase of running. Furthermore, at the fastest speed of 15 km/h, the SLR was still depressed by vibration in all muscles but yielding was no longer evident. This finding suggests that the SLR has greater functional importance at slow to intermediate running speeds than at faster speeds.     

Automatic tracking of medial gastrocnemius fascicle length during human locomotion

During human locomotion lower extremity muscle-tendon units undergo cyclic length changes that were previously assumed to be representative of muscle fascicle length changes. Measurements in cats and humans have since revealed that muscle fascicle length changes can be uncoupled from those of the muscle-tendon unit. Ultrasonography is frequently used to estimate fascicle length changes during human locomotion. Fascicle length analysis requires time consuming manual methods that are prone to human error and experimenter bias. To bypass these limitations, we have developed an automatic fascicle tracking method based on the Lucas-Kanade optical flow algorithm with an affine optic flow extension. The aims of this study were to compare gastrocnemius fascicle length changes during locomotion using the automated and manual approaches and to determine the repeatability of the automated approach. Ultrasound was used to examine gastrocnemius fascicle lengths in eight participants walking at 4, 5, 6, and 7 km/h and jogging at 7 km/h on a treadmill. Ground reaction forces and three dimensional kinematics were recorded simultaneously. The level of agreement between methods and the repeatability of the automated method were quantified using the coefficient of multiple correlation (CMC). Regardless of speed, the level of agreement between methods was high, with overall CMC values of 0.90 ± 0.09 (95% CI: 0.86-0.95). Repeatability of the algorithm was also high, with an overall CMC of 0.88 ± 0.08 (95% CI: 0.79-0.96). The automated fascicle tracking method presented here is a robust, reliable, and time-efficient alternative to the manual analysis of muscle fascicle length during gait.     

A position paper in support of hand transplantation in the blind

Blind upper extremity amputees have historically been excluded from consideration for hand allotransplantation. Although no formal position statement regarding their exclusion has been published to date, functional, rehabilitative, and ethical concerns related to blind amputee candidacy for hand transplantation may be inferred. The authors provide a summary of these reservations and a counterargument to their assumptions, drawing on outcomes measures reported for hand transplantations completed to date. The authors therefore provide a rationale for the inclusion of blind amputees in hand transplantation protocols in the future.