Minactivin expression in human monocyte and macrophage populations

Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.     

High abundance of CD271(+) multipotential stromal cells (MSCs) in intramedullary cavities of long bones

Aspiration of iliac crest bone marrow (ICBM) remains the most frequent technique used in harvesting multipotential stromal cells (MSCs) for bone regeneration. Although this tissue type is easily accessed by a surgeon, it has a low frequency of MSCs, which is significant given the high cell numbers required for bone regeneration strategies. Lipoaspirates possess higher MSC frequencies, albeit cells with a differentiation profile less suited to orthopaedic interventions. Intra-medullary cavities of long bones have previously been shown to harbour MSCs in animals, however evaluation of their frequency, differentiation capacity and phenotype in humans had not previously been performed. Long bone fatty bone marrow (LBFBM) was collected prior to harvesting bone graft. Basic cellular compositions of donor-matched LBFBM and ICBM aspirates, including the numbers of CD34(+) hematopoietic stem cells and CD31(+) endothelial cells, were similar. MSCs were enumerated using colony-forming-unit-fibroblast assays and flow cytometry for the presence of a resident LBFBM CD45(-/low) CD271(+) MSC population and revealed a trend for higher MSC numbers (average 5 fold, n=6) per millilitre of LBFBM compared to donor-matched ICBM. Functional characteristics of resident MSCs, including their growth rates, differentiation potentials and surface phenotypes (CD73(+)CD105(+)CD90(+)) before and after culture-amplification, were similar. Enhanced numbers of MSCs could be recovered following brief enzymatic treatment of solid fragments of LBFBM. Our findings therefore reveal that the intramedullary cavity of the human femur is a depot of MSCs, which, although closely associated with fat, have a differentiation profile equivalent to ICBM. This anatomical site is frequently accessed by the orthopaedic/trauma surgeon and aspiration of the intramedullary cavity represents a 'low-tech' method of harvesting potentially large numbers of MSCs for regenerative therapies and research.     

Reliability of Infrared Thermometric Measurements of Skin Temperature in the Hand

Study DesignClinical measurement study.IntroductionSkin temperature asymmetries (STAs) are used in the diagnosis of complex regional pain syndrome (CRPS), but little evidence exists for reliability of the equipment and methods.PurposeThis study examined the reliability of an inexpensive infrared (IR) thermometer and measurement points in the hand for the study of STA.MethodsST was measured three times at five points on both hands with an IR thermometer by two raters in 20 volunteers (12 normals and 8 CRPS).ResultsST measurement results using IR thermometers support inter-rater reliability: intraclass correlation coefficient (ICC) estimate for single measures 0.80; all ST measurement points were also highly reliable (ICC single measures, 0.83–0.91).ConclusionsThe equipment demonstrated excellent reliability, with little difference in the reliability of the five measurement sites. These preliminary findings support their use in future CRPS research.Level of EvidenceNot applicable.     

Efficacy of nasal continuous positive airway pressure therapy in chronic heart failure: importance of underlying cardiac rhythm

BACKGROUND: Some previous reports have indicated beneficial cardiac effects of nasal continuous positive airway pressure (NCPAP) in patients with severe congestive heart failure (CHF), but others have reported deleterious cardiac effects, particularly among patients in atrial fibrillation (AF). The aim of this study was to determine if differences in cardiac rhythm influence the acute cardiac response to NCPAP. METHODS: Eleven consecutive patients with CHF were recruited, six in atrial fibrillation (AF) and five with sinus rhythm (SR). Cardiac index was measured during awake NCPAP application by the thermodilution technique during cardiac catheterisation. NCPAP was applied in a randomised sequence at pressures of 0, 5, and 10 cm H2O with three 30 minute applications separated by 20 minute recovery periods without NCPAP. RESULTS: Significant differences were found between the AF and SR groups for cardiac index responses to NCPAP (p = 0.004, ANOVA) with a fall in cardiac index in the AF group (p = 0.02) and a trend towards an increase in the SR group (p = 0.10). Similar differences were seen between the groups in stroke volume index responses but not in heart rate responses. Changes in systemic vascular resistance were also significantly different between the two groups (p < 0.005, ANOVA), rising in the AF group but falling in the SR group. CONCLUSIONS: These data indicate an important effect of underlying cardiac rhythm on the awake haemodynamic effects of NCPAP in patients with CHF.     

Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a major therapeutic target in a range of chronic inflammatory disorders characterised by a Th1 type immune response in which TNFalpha is generated in excess. By contrast, asthma is regarded as a Th2 type disorder, especially when associated with atopy. However, as asthma becomes more severe and chronic, it adopts additional characteristics including corticosteroid refractoriness and involvement of neutrophils suggestive of an altered inflammatory profile towards a Th1 type response, incriminating cytokines such as TNFalpha. METHODS: TNFalpha levels in bronchoalveolar lavage (BAL) fluid of 26 healthy controls, 42 subjects with mild asthma and 20 with severe asthma were measured by immunoassay, and TNFalpha gene expression was determined in endobronchial biopsy specimens from 14 patients with mild asthma and 14 with severe asthma. The cellular localisation of TNFalpha was assessed by immunohistochemistry. An open label uncontrolled clinical study was then undertaken in 17 subjects with severe asthma to evaluate the effect of 12 weeks of treatment with the soluble TNFalpha receptor-IgG1Fc fusion protein, etanercept. RESULTS: TNFalpha levels in BAL fluid, TNFalpha gene expression and TNFalpha immunoreative cells were increased in subjects with severe corticosteroid dependent asthma. Etanercept treatment was associated with improvement in asthma symptoms, lung function, and bronchial hyperresponsiveness. CONCLUSIONS: These findings may be of clinical significance in identifying TNFalpha as a new therapeutic target in subjects with severe asthma. The effects of anti-TNF treatment now require confirmation in placebo controlled studies.     

Quantifying the amount of padding improves the comfort and function of a fibreglass below-elbow cast

Aim

To determine the quantity of cotton underpadding needed for a comfortable, functional, below-elbow fibreglass cast.

Methods

In this randomised, prospective, crossover, clinical trial, 45 people with minimally displaced distal radial fractures were enrolled to randomly receive, 14 days after injury, a fibreglass below-elbow cast with either two or four layers of cotton underpadding. The characteristics of the recipients were recorded. After 2 weeks of immobilisation, participants completed a numerical survey evaluating parameters of comfort and underwent clinical and radiographic assessment. They then crossed over to receive the other fibreglass cast design, the process was repeated, and they indicated their cast preference, if any.

Results

Of 37 people who completed the study, 20 preferred the two-layer model, 13 the four-layer model and 4 had no preference. No significant trend for one design over the other was shown (p = 0.1), nor any statistical association between preference and participant characteristics or the order in which cast models were received.

Conclusions

Participants did state a preference, but this was not related to recipient characteristics. Neither cast design was significantly the more comfortable; and both models were safe and functionally satisfactory.