Estrogen effects on object memory and cholinergic receptors in young and old female mice.

We investigated whether object recognition memory is modulated by estrogen in young (5 month) and aged (24 month) female C57Bl/6J mice, and if cholinergic muscarinic receptors might contribute to this response. Mice that were ovariectomized, or ovariectomized plus estradiol-treated three weeks before behavioral testing or quantitative autoradiography were compared to intact mice. Memory for a previously encountered object deteriorated significantly between 3 and 6h after initial exposure, regardless of animal age. In both young and aged mice, estradiol-treated mice showed significantly greater recall than did ovariectomized mice. In both age groups, the apparent number of [(3)H]pirenzepine/M(1)-like and [(3)H]AFDX384/M(2)-like muscarinic receptor binding sites was reduced in the basal forebrain as well as its projection areas following ovariectomy, but this decrease was not alleviated by estrogen. Aging poorly affected object memory, but reduced muscarinic binding in some cortical subregions and in the caudate nucleus. These findings suggest that estrogen effects on memory in C57Bl/6J mice are not due to changes in the number of muscarinic receptors.     

Total knee arthroplasty of the stiff knee: three hundred and four cases

Purpose

The purpose of this study was to analyse the results of total knee arthroplasty (TKA) in stiff knees (flexion ≤90° and/or flexion contracture ≥20°). Our hypothesis was that despite having poorer results than those obtained in a “standard” population and a high rate of complications, TKA was a satisfactory treatment in patients with osteoarthritis of the knee associated with significant stiffness.

Methods

Three hundred and four consecutive primary HLS TKAs (Tornier), whose data were prospectively collected between October 1987 and October 2012, were retrospectively analysed at a mean of 60 months (range, 12–239) postoperatively. Two groups, those with a “flexion contracture” and those with a “flexion deficit”, were assessed for postoperative range of motion (as integrated to the Knee Society score [KSS]), physical activity level and patient satisfaction.

Results

At the latest follow-up, range of motion was significantly improved, as was the KSS. Ninety-four percent of patients were satisfied or very satisfied, and activity levels were increased after surgery. The complication rate, however, was high in patients with a preoperative flexion deficit (17 %). Pain and residual stiffness were the most common complications.

Conclusion

TKA provides satisfactory results in patients with knee osteoarthritis associated with significant pre-operative stiffness. The surgical plan should be adapted to anticipate complications, which are particularly frequent in the presence of a flexion deficit.     

Treatment of chronic disruption of the patellar tendon in Osteogenesis Imperfecta with allograft reconstruction

We present a case of chronic disruption of the patellar tendon in a patient with Osteogenesis Imperfecta. This patient was treated with a customized extensor mechanism allograft. Results were excellent at 5 years follow up. To our knowledge this treatment has not previously been published in this situation. We present this as a reliable treatment option.     

A natural protective function of invariant NKT cells in a mouse model of innate-cell-driven lung inflammation

Activation of invariant natural killer T (iNKT) cells by treatment with their α-galactosyl ceramide ligand provides therapeutic benefits in several immune inflammatory settings. Given the artificial nature of this stimulation, the natural regulatory functions of iNKT remain uncertain. Addressing this issue in a mouse model of innate-cell-driven lung inflammation induced by the cytokine/alarmin IL-33 that targets iNKT cells, we found that eosinophil and neutrophil recruitment was markedly increased in treated iNKT cell-deficient (Jα18 KO) mice, as was the local production of eotaxin and keratinocyte chemoattractant chemokines. By contrast, lung inflammation decreased after adoptive transfer of iNKT cells, which restored the WT inflammatory response in Jα18 KO mice. Finally, we established that this natural anti-inflammatory function of iNKT cells depends on their IFN-γ production and on endogenous IL-12. Our study provides the first evidence of a protective role of iNKT cells during lung inflammation that does not require pharmacological TCR engagement.     

The pro‐Th2 cytokine IL‐33 directly interacts with invariant NKT and NK cells to induce IFN‐γ production

IL‐33 has recently been identified as a cytokine endowed with pro‐Th2 functions, raising the question of its effect on invariant natural killer T cell (iNKT), which are potent IL‐4 producers. Here, we report a two‐fold increase of iNKT‐cell counts in spleen and liver after a 7‐day treatment of mice with IL‐33, which results from a direct effect, given that purified iNKT cells express the T1/ST2 receptor constitutively and respond to IL‐33 by in vitro expansion and functional activation. Conversely to the expected pro‐Th2 effect, IL‐33 induced a preferential increase in IFN‐γ rather than IL‐4 production upon TCR engagement that depended on endogenous IL‐12. Moreover, in combination with the pro‐inflammatory cytokine IL‐12, IL‐33 enhanced IFN‐γ production by both iNKT and NK cells. Taken together these data support the conclusion that IL‐33 can contribute as a co‐stimulatory factor to innate cellular immune responses.     

A CT-based classification of prior ACL femoral tunnel location for planning revision ACL surgery

Purpose

The purposes of this study are to describe an ACL femoral tunnel classification system for use in planning revision ACL reconstruction based on 3-D computed tomography (CT) reconstructions and to evaluate its inter- and intra-rater reliability.

Methods

A femoral tunnel classification system was developed based on the location of the femoral tunnel relative to the lateral intercondylar ridge. The femoral tunnel was classified as Type I if it was located entirely below and posterior to the ridge as viewed from distally, Type II if it was slightly malpositioned (either vertically, anteriorly, or both), and Type III if it was significantly malpositioned. To evaluate the reproducibility of the classification system, CT scans of 27 knees were obtained from patients scheduled for revision ACL reconstruction, and 3-D reconstructions were created. Four views of the 3-D reconstruction of each femur were then obtained, and inter- and intra-observer reliability was determined following classification of the tunnels by eight observers.

Results

Twenty-five tunnels were classified as Type I (5 tunnels), Type II (9 tunnels), or type III (11 tunnels) by at least 5 of 8 observers, while insufficient agreement was noted to classify two tunnels. The interobserver reliability of tunnel classification as type I, II, or III yielded a κ coefficient of 0.57, while intra-observer reliability yielded a κ coefficient of 0.67. Subclassification of type II femoral tunnels into the subgroups anterior, vertical, and both was possible in four of the nine type II patients. The interobserver reliability of the complete classification system yielded a κ coefficient of 0.50, while the intra-observer reliability yielded a κ coefficient of 0.54.

Conclusion

Classification of the location of ACL femoral tunnels utilizing 3-D reconstructions of CT data yields moderate to substantial inter- and intra-observer reliability.

Level of evidence

Diagnostic Level III.     

Gene therapy for rheumatoid arthritis

Rheumatoid arthritis (RA) is a painful chronic disorder. Conventional therapies are palliative, not curative. Advances in the understanding of the pathophysiology of RA have led to the development of new therapeutic strategies, including gene therapy. Multiple studies in several different animal models provide proof supporting the use of gene therapy in arthritis. A phase I clinical trial has already been performed successfully on nine women with end-stage RA in the United States, and two other trials are in progress. Limited duration of gene expression impedes the development of a clinically useful genetic treatment for arthritis.     

Iatrogenic popliteus tendon injury during total knee arthroplasty results in decreased knee function two to three years postoperatively

Purpose

The popliteus tendon is known to play a key role in the stability of the posterolateral corner of the knee. While prior work suggests that isolated sectioning of the popliteus tendon has little consequence for the static stability of the knee following TKA, no studies have evaluated the effect of iatrogenic popliteal tendon injury on patient oriented outcome and knee function following TKA. The aims of this study are (1) to compare patient-oriented outcome scores of patients who suffered an iatrogenic injury to the popliteus tendon with a control group without such an injury and (2) to identify risk factors associated with iatrogenic injury to the popliteus tendon.

Methods

Fifteen patients with an iatrogenic complete transection of the popliteus tendon during TKA were compared to the 666 patients who underwent TKA during the same time period without popliteus tendon injury.

Results

Postoperatively, IKS knee scores were similar between the two groups; however, significantly lower IKS function scores were noted in the study group (71?±?31) compared to the control group (86?±?19) (p?=?0.0036). Iatrogenic popliteal tendon injury was only noted to occur in patients in whom components of size four or smaller were used.

Conclusions

Intraoperative complete section of the popliteus tendon during the performance of TKA results in decreased IKS functional scores two to three?years postoperatively. Patients with smaller knees may be at higher risk for this complication.