In vivo fluoroscopic studies of patients with total knee replacements (TKRs) have shown lift-off of the femoral condyles from the tibial insert. This study investigated the influence of femoral condylar lift-off on the ultra-high molecular weight polyethylene (UHMWPE) wear of fixed bearing (FB) and rotating platform mobile bearing (RP MB) total knee replacements, using a physiological knee joint simulator. In the absence of lift-off, the RP MB knees exhibited a lower wear rate of 5.2;;2.2 mm3 per million cycles (mm3/MC) compared with 8.8;;4.8 mm3/MC for the FB knees. The presence of femoral condylar lift-off was found to accelerate the wear of the FB and RP MB knees tested in this study to 16.4;;2.9 and 16.9;;2.9 mm3/MC respectively. For the RP MB knees the increase in wear rate was more marked, resulting in a similar wear rate for both designs of knee under lift-off conditions. In both cases the medial condyle displayed more wear damage. This study has shown that a small amount of abduction/adduction lift-off and medial-lateral shift increases wear and that the increase in wear is design dependent. In this simulator test, lift-off was simulated on every cycle, whereas the amount of wear and effect of lift-off clinically would depend on the frequency of occurrence of lift-off in vivo.

The self-assembly of peptides is explored as an alternative route towards the development of new injectable joint lubricants for osteoarthritis (OA). The versatility of the peptide chemistry allows the incorporation of behavior reminiscent of hyaluronic acid (HA), while the triggered in situ self-assembly provides easy delivery of the samples by injection due to the low viscosity of the peptide solutions (that are initially monomeric). Using design criteria based on the chemical properties of HA, a range of de novo peptides were prepared with systematic alterations of charge and hydrophilicity that self-assembled into nematic fluids and gels in physiological solution conditions. The frictional characteristics of the peptides were evaluated using cartilage on cartilage sliding contacts along with their rheological characteristics. Peptide P(11)-9, whose molecular, mesoscopic, and rheological properties most closely resembled HA was found to be the most effective lubricant amongst the peptides. In healthy static and dynamic friction testing (corresponding to healthy joints) P(11)-9 at 20-40 mg/mL performed similar to HA at 10 mg/mL. In friction tests with damaged cartilage (corresponding to early stage OA) P(11)-9 was a less efficient lubricant than HA, but still the best among all the peptides tested. The results indicate that de novo self-assembling peptides could be developed as an alternate therapeutic lubricant for early stage OA.

Therapeutic lubricant injections of hyaluronic acid are a relatively recent treatment for osteoarthritis. Their efficacy however, in vivo has been subject to much debate. Frictional properties of cartilage-cartilage contacts under both static and dynamic loading conditions have been investigated, using healthy cartilage and cartilage with a physically disrupted surface, with and without the addition of a therapeutic lubricant, hyaluronic acid. Most of the cartilage friction models produced typical time-dependent loading curves, with a rise in static friction with loading time. For the dynamic loading conditions the rise in friction with loading time was dependent on the spatial (and time) variation in the load on the cartilage plate. For sliding distances of 4 mm or greater, when the cartilage plate was unloaded during sliding, the dynamic friction remained low whereas, with shorter sliding distances, the dynamic friction increased with increasing loading time. Static friction was higher than dynamic friction (under the same tribological conditions). The ‘damaged’ cartilage models produced higher friction than healthy cartilage under equivalent tribological conditions. It was shown that hyaluronic acid was an effective boundary lubricant for articular cartilage under static conditions with both healthy and damaged cartilage surfaces. Hyaluronic acid was less effective under dynamic conditions. However, these dynamic conditions had low friction values with the control lubricant because of the effectiveness of the intrinsic biphasic lubrication of the cartilage. It was only under the tribological conditions in which the cartilage friction was higher and rising with increasing loading time because of depletion of the intrinsic biphasic lubrication, that the role of hyaluronic acid as an effective therapeutic lubricant was demonstrated.

Debris-induced osteolysis due to surface wear of ultra high molecular weight polyethylene (UHMWPE) bearings is a potential long-term failure mechanism of total knee replacements (TKR). This study investigated the effect of prosthesis design, kinematics and bearing material on the wear of UHMWPE bearings using a physiological knee simulator. The use of a curved fixed bearing design with stabilised polyethylene bearings reduced wear in comparison to more flat-on-flat components which were sterilised by gamma irradiation in air. Medium levels of crosslinking further improved the wear resistance of fixed bearing TKR due to resistance to strain softening when subjected to multidirectional motion at the femoral-insert articulating interface. Backside motion was shown to be a contributing factor to the overall rate of UHMWPE wear in fixed bearing components. Wear of fixed bearing prostheses was reduced significantly when anterior-posterior displacement and internal-external rotation kinematics were reduced due to decreased cross shear on the articulating surface and a reduction in AP displacement. Rotating platform mobile bearing prostheses exhibited reduced wear rates in comparison to fixed bearing components in these simulator studies due to redistribution of knee motion to two articulating interfaces with more linear motions at each interface. This was observed in two rotating platform designs with different UHMWPE bearing materials. In knee simulator studies, wear of TKR bearings was dependent on kinematics at the articulating surfaces and the prosthesis design, as well as the type of material.

Although rare, night terrors are difficult to treat and a major management problem, especially when accompanied by sleepwalking or other automatic behaviours. Severe injury (sometimes death) during the period of confusion following the rise from bed has been reported,1 and more frequent attacks lead to serious disruption of sleep, which may impair subsequent daytime functioning and result in psychiatric comorbidity. Night terrors can thus cause severe disability, and effective therapy would be of benefit to patients and their families.

We studied reported withdrawal symptoms in a retrospective chart review of 352 patients treated in an outpatient clinic with the nonselective serotonin reuptake inhibitor clomipramine or with one of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine, fluvoxamine, paroxetine, or sertraline. In 171 patients who were supervised during medication tapering and discontinuation, the most common symptoms were dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability, and lowered mood. When patients with at least one qualitatively new symptom were defined as cases, these symptoms occurred significantly more frequently in patients who had been treated either with one of the shorter half-life SSRIs, fluvoxamine or paroxetine (17.2%), or with clomipramine (30.8%), than in patients taking one of the SSRIs with longer half-life metabolites, sertraline or fluoxetine (1.5%). The rate was not significantly different between the different shorter half-life treatments. Cases treated with fluvoxamine or paroxetine had received a significantly longer period of treatment (median 28 weeks) than noncases (16 weeks), but there were no significant associations with age or with diagnostic grouping. There was a trend toward an association with male sex. The majority of cases occurred despite slowly tapered withdrawal. Symptoms persisted for up to 21 days (mean = 11.8 days) after onset. These symptoms were relieved within 24 hours by restarting the medication, but were not relieved by benzodiazepines or by moclobemide. A role has been suggested for serotonin in coordinating sensory and autonomic function with motor activity. We suggest that this may lead to useful hypotheses about the pathophysiology of withdrawal symptoms from serotonin reuptake inhibitors.

The relative roles of heat storage, evaporative, and non-evaporative heat loss were examined in the brushtail possum, Trichosurus vulpecula, and the Tasmanian devil, Sarcophilus harrisii, during exercise. Rates of water conductance across the skin were also measured at rest and while running at two ambient temperatures. Evaporative heat loss from the general body surface in S. harrisii is a minor contribution to the overall heat balance, and sweat gland function is not apparent. T. vulpecula relies more on heat loss mediated by cutaneous evaporation than from respiratory routes, but changes in cutaneous blood flow are more important than glandular activity in augmenting this response. These results and earlier reports in the literature suggest that the occurrence and function of cutaneous evaporation varies among marsupial species.