Spontaneous generation of functional osteoclasts from synovial fluid mononuclear cells as a model of inflammatory osteoclastogenesis

In osteoimmunology, osteoclastogenesis is understood in the context of the immune system. Today, the in vitro model for osteoclastogenesis necessitates the addition of recombinant human receptor activator of nuclear factor kappa‐B ligand (RANKL) and macrophage colony‐stimulating factor (M‐CSF). The peripheral joints of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are characterized by an immune‐mediated inflammation that can lead to bone destruction. Here, we evaluate spontaneous in vitro osteoclastogenesis in cultures of synovial fluid mononuclear cells (SFMCs) activated only in vivo. SFMCs were isolated and cultured for 21 days at 0.5–1.0 × 10⁶ cells/mL in culture medium. SFMCs and healthy control peripheral blood monocytes were cultured with RANKL and M‐CSF as controls. Tartrate‐resistant acid phosphatase (TRAP) positive multinucleated cells were found in the SFMC cultures after 21 days. These cells expressed the osteoclast genes calcitonin receptor, cathepsin K, and integrin β3, formed lacunae on dentin plates and secreted matrix metalloproteinase 9 (MMP9) and TRAP. Adding RANKL and M‐CSF potentiated this secretion. In conclusion, we show that SFMCs from inflamed peripheral joints can spontaneously develop into functionally active osteoclasts ex vivo. Our study provides a simple in vitro model for studying inflammatory osteoclastogenesis.     

Distraction effects on muscle: Leg lengthening studied in rabbits

We investigaed changes in the anterior tibial muscle during lengthening of the lower leg in rabbits. In 37 rabbits, an osteotomy of the right middle tibia was performed and was fixed by a unilateral external fixator. The rabbits were randomized into 6 groups. In groups 1, 2, and 3 the tibiae were distracted 0.5 mm/day. In groups 1 and 2, the rabbits were killed after 14 and 28 days of distraction, respectively, and in group 3 after 28 days of distraction, followed by 14 days of rest. Groups 1a, 2a, and 3a served as controls. They were treated similarly as groups 1, 2, and 3, but no distracton was performed. Proliferating cell nuclei were labeled with 5-bromo-2-deoxyuridine and were identified by immunohistochemical staining. The weight of the muscle was measured. During bone lengthening the muscle showed signs of growth, as indicated by increasing weight and number of proliferating cell nuclei. This was observed only during lengthening and it ceased when the lengthening was stopped.     

Bilateral hallux saltans. Report of a case

A case of bilateral hallux saltans in a 13-year-old girl is reported. The signs and symptoms were a tender nodule behind the medial malleolus and a "trigger toe" as well as pain radiating up the lower leg. Operation revealed thickening of the flexor retinaculum superficially to the flexor hallucis longus tendon which showed compression and proximal thickening. Resection of the retinaculum afforded a satisfactory result.     

Properties of growing trabecular ovine bone. Part I: mechanical and physical properties

Our aim was to determine the relationship between age and the mechanical and physical properties of trabecular bone, to describe the patterns in which the variations in these properties take place, and to investigate the influence of the physical properties on the mechanical characteristics of trabecular bone during growth. We used 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. We performed non-destructive compression tests of the specimens in three orthogonal directions and compression tests to failure in the axial direction. The physical properties of the specimens were also determined. The data were correlated with age and compared in skeletally immature and mature animals. Multiple regression analyses were performed between the mechanical and the physical properties. Age correlated positively with elastic modulus, bone strength, energy absorption to failure, elastic energy, mechanical anisotropy ratio, tissue density, apparent density, apparent ash density, and bone mineral content, and inversely with ultimate strain, viscoelastic energy absorption, relative energy loss, the collagen content of bone and the percentage porosity. The values of all variables were significantly different in the skeletally mature and immature groups. The apparent density of trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the content of bone muscle and bone collagen, the apparent density could explain 84% of the variation in the elastic modulus, whereas only a small portion of the variation in ultimate strain could be explained by the variation in apparent density.     

Telemedicine support shortens length of stay after fast-track hip replacement

Background and purpose — Telemedicine could allow patients to be discharged more quickly after surgery and contribute to improve fast-track procedures without compromising quality, patient safety, functionality, anxiety, or other patient-perceived parameters. We investigated whether using telemedicine support (TMS) would permit hospital discharge after 1?day without loss of self-assessed quality of life, loss of functionality, increased anxiety, increased rates of re-admission, or increased rates of complications after hip replacement.

Patients and methods — We performed a randomized controlled trial involving 72 Danish patients in 1 region who were referred for elective fast-track total hip replacement between August 2009 and March 2011 (654 were screened for eligibility). Half of the patients received a telemedicine solution connected to their TV. The patients were followed until 1 year after surgery.

Results — Length of stay was reduced from 2.1 days (95% CI: 2.0–2.3) to 1.1?day (CI: 0.9–1.4; p < 0.001) with the TMS intervention. Health-related quality of life increased in both groups, but there were no statistically significant differences between groups. There were also no statistically significant differences between groups regarding timed up-and-go test and Oxford hip score at 3-month follow-up. At 12-month follow-up, the rates of complications and re-admissions were similar between the groups, but the number of postoperative hospital contacts was lower in the TMS group.

Interpretation — Length of postoperative stay was shortened in patients with the TMS solution, without compromising patient-perceived or clinical parameters in patients undergoing elective fast-track surgery. These results indicate that telemedicine can be of value in fast-track treatment of patients undergoing total hip replacement.     

Antibacterial Activity of Pepducins,Allosterical Modulators of Formyl Peptide Receptor Signaling

Pepducins containing a fatty acid linked to an amino acid sequence derived from cytosolic parts of a G-protein-coupled receptor (GPCR) constitute a new group of lipopeptide tools in GPCR studies. Pepducins corresponding to the third intracellular loop of formyl peptide receptor 2 (FPR2) activate human neutrophils, and we show here that, in addition, these allosteric modulators of receptor activity also kill bacteria. The functional dualism of FPR2 pepducins could potentially be explored as a novel class of antibacterial drugs with immunomodulatory properties.     

Ear measurement of temperature is only useful for screening for fever in an adult emergency department

Background

A new generation of ear thermometers with preheated tips and several measurements points should allow a more precise temperature measurement. The aim of the study was to evaluate if the ear temperature measured by this ear thermometer can be used to screen for fever and whether the thermometer is in agreement with the rectal temperature and if age, use of hearing devices or time after admission influences the temperature measurements.

Methods

Open cross-sectional clinical single site study patients, >?18?years old, who were acutely admitted to the short stay unit at the ED. A sample size of 99 patient per subgroup was recruited as random convenience series. As ear thermometer Braun Thermoscan Pro 4000® and as rectal thermometer Omron Flex Temp Smart ® was used. For different cut off of temperature the AUC was calculated and Bland-Altman analysis for calculation of 95% limits of agreement with rectal temperature, with subgroup analysis concerning age, time span from admission time and use of hearing aid.

Results

Among 599 patients the sensitivity to detect fever with an ear thermometer varied between 68 and 70% with AUC from 0.88–0.97. If the ear temperature was ≥37.5 oC, the sensitivity to detect patients with ≥38.0 oC rectally was 95% which raised to 100% for a rectal temperature of ≥38.3 oC. For the ear thermometer’s ability to determine the exact temperature the 95% limits of agreement were +/??0.8 oC. with no influence from age, duration of hospital stay or hearing aids.

Conclusion

The examined ear thermometer is able to detect fever, defined as ≥38 oC rectally in an adult ED population by using an ear cut-point of 37.5 oC, but not to measure the exact temperature. Used in this way around a fifth of the patients will still be in need of a rectal temperature measurement, but less than 5% with fever ≥38.0 oC will remain undetected and none with fever ≥38.3 oC. Age, admission time and use of hearing aid did not influence the temperature measurements.

Trial registration

Clinical Trials: ID NCT02977481, date 11/18/2016.

     

Thyroid effects of endocrine disrupting chemicals

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties.