The anatomy of the anterior inferior tibiofibular ligament and its relationship with the Wagstaffe fracture

BackgroundOur aim in this study was to identify the fibular footprint of the Anterior Inferior Tibiofibular Ligament (AITFL) and its relation to Wagstaffe fracture fragment size.MethodsWe examined 25 cadaveric lower limbs which were carefully dissected to identify the lateral ankle ligaments. The AITFL anatomy was compared to 40 Wagstaffe fractures identified from our ankle fracture database.ResultsThe AITFL origin was from the anterior fibular tubercle with an average length of 21.61 mm (95% CI 20.22, 22.99). The average distance of the distal aspect of the AITFL footprint to the distal fibula margin was 11.60 mm (95% CI 10.49, 12.71). In the ankle fractures analyzed, the average length of the Wagstaffe fragment was 17.88 mm (95% CI 16.21, 19.54). The average distance from the distal tip of the fibula to the Wagstaffe fracture fragment was 21.40 mm (95% CI 19.78, 23.01).In total there were 22 syndesmosis injuries. There was no statistical difference in Wagstaffe fragment size between stable and unstable groups.ConclusionThe AITFL fibular origin was both larger and more distal than the Wagstaffe fracture fragments seen in our institution. Therefore, this suggests that a ligamentous failure will also have to occur to result in syndesmotic instability. The size of fracture fragment also did not confer to syndesmotic instability on testing.Level of Evidence - 3     

Impact of donor extracellular vesicle release on recipient cell “cross-dressing” following clinical liver and kidney transplantation

In several murine models of transplantation, the “cross-dressing” of recipient antigen presenting cells (APCs) with intact donor major histocompatibility complex (MHC) derived from allograft-released small extracellular vesicles (sEVs) has been recently described as a key mechanism in eliciting and sustaining alloimmune responses. Investigation of these processes in clinical organ transplantation has, however, been hampered by the lack of sensitivity of conventional instruments and assays. We have employed advanced imaging flow cytometry (iFCM) to explore the kinetics of allograft sEV release and the extent to which donor sEVs might induce cross-dressing following liver and kidney transplantation. We report for the first time that recipient APC cross-dressing can be transiently detected in the circulation shortly after liver, but not kidney, transplantation in association with the release of HLA-bearing allograft-derived sEVs. In liver transplant recipients the majority of circulating cells exhibiting donor HLA are indeed cross-dressed cells and not passenger leukocytes. In keeping with experimental animal data, the downstream functional consequences of the transfer of circulating sEVs harvested from human transplant recipients varies depending on the type of transplant and time posttransplant. sEVs released shortly after liver, but not kidney, transplantation exhibit immunoinhibitory effects that could influence liver allograft immunogenicity.     

Anhedonia,positive affect dysregulation,and risk and maintenance of binge-eating disorder

Low positive affect has been identified as an antecedent of binge-eating episodes among individuals with binge-eating disorder (BED), yet positive affect has received far less attention in eating disorders research than its counterpart, negative affect. In this article, we argue that the low levels of positive affect which occur with anhedonia (i.e., loss of interest or pleasure in activities) may contribute to the onset and maintenance of BED. We introduce a theoretical model in which anhedonia increases the risk for BED through its interrelationships with dysregulated eating and weight gain, and we describe potential direct (e.g., reward-related processes) as well as indirect (e.g., influences on depressive symptoms and physical activity) pathways by which anhedonia may lead to adverse eating- and weight-related outcomes. We also propose a momentary maintenance model in which low positive affect and positive affect dysregulation occurring with anhedonia maintain binge eating directly and indirectly through maladaptive health behaviors, such as decreased physical activity, less healthy eating, and fewer social interactions, which in turn maintain anhedonia. We draw upon outside literature to present evidence that aligns with the proposed risk and maintenance models and conclude by outlining avenues for future research—including methodological/measurement, theoretical, and clinical research directions.     

An immunocytochemical study of malignant melanoma and its differential diagnosis from other malignant tumours.

A series of 41 fresh and 36 routinely processed malignant melanomas were immunostained with a panel of 12 monoclonal antibodies reactive against a range of epithelial, lymphoid, and melanoma associated antigens. The aim of the study was to determine whether this panel of antibodies would be useful in diagnostically difficult cases for differentiating melanomas from other tumours, particularly carcinomas and lymphomas. The results confirmed that most unequivocal malignant melanomas can be identified by positivity for S100 protein and for the antigen recognised by antibody NK1/C3, and by negativity for epithelial and lymphoid antigens. The incidence of melanomas expressing cytokeratin antigens was higher, however, particularly in cryostat sections than has previously been reported. It is therefore suggested that a panel of antibodies with more than one marker in each category should be used for identifying melanomas in clinical practice.     

Automation of APAAP immunocytochemical technique.

A tissue processing instrument (the Histokinette) was modified by the addition of an electronic timing device which allows an immunocytochemical staining technique (the APAAP method) to be performed as a semiautomated procedure. After incubation with primary monoclonal antibodies (applied by hand) slides (up to 72 in a batch) are placed in racks and cycled through tanks of reagents, comprising anti-mouse Ig followed by APAAP complexes with intervening timed draining and washing stages. This semiautomated process gave consistent staining results and offered considerable savings in time compared with conventional methods. The same reagent baths were used over four months on an almost daily basis without deterioration in staining intensity, and consequently the calculated overall cost of the staining procedure was less than if the reagents had been applied by hand and then discarded. The machine is now into its eleventh month of operation; the reagents have been changed twice. It is suggested that this approach, because of savings in time and increased consistency, may be an attractive technique for the routine immunocytochemical staining of slides, and that the nature of the APAAP method is particularly suitable for automation as the necessary reagents can be produced at low cost.     

Exercise, training and neutrophil microbicidal activity

The concentration in human plasma of putative neutrophil-"priming" cytokines like endogenous pyrogens is known to increase significantly in response to moderate exercise (11). This is characteristic of an acute-phase response. The ability of blood neutrophils isolated from both trained and untrained human subjects (n = 11, 9) to produce microbicidal reactive oxygen species was determined using luminol-enhanced chemiluminescence both before and after one hour of aerobic exercise at 60% VO2max. Irrespective of training and stimulus concentration, exercise nearly always caused significant "priming" of the capacity of neutrophils to produce H2O2 and HOCl upon stimulation with opsonized zymosan (P less than 0.01); however, compared to their untrained counterparts, the activity of cells isolated from trained individuals was depressed about 50% at unit stimulus concentration, both before and after exercise (P less than 0.075), whilst remaining unaltered at saturating concentrations. Although neutrophil oxygenation activity is only one parameter that contributes to immunological status, regular episodes of moderate exercise may increase resistance to infection by priming the "killing capacity" of neutrophils. In contrast, prolonged periods of intensive training may lead to increased susceptibility to common infections by diminishing this activity.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Prioritising waiting lists

The 'top 22' patient conditions on the general surgical waiting list at Guy's Hospital were rated independently by five general surgeons. Each surgeon estimated the peri-operative mortality rates associated with each treatment; the proportion of patients who failed to benefit; the effect of successful treatment on life expectancy and on the patients' quality of life. the mean values were used to estimate the expected net benefits (in terms of quality-adjusted life-years) from treatment one year earlier than might otherwise have been the case. These benefits were then related to the operating times and length of stay associated with each treatment; this identified which treatments offered the greatest benefit per unit of each constrained resource. Of all conditions examined anal fissures where shown to be the least resource intensive in relation to the benefits generated, whilst varicose veins and epigastric hernias proved otherwise. For the full potential of this approach to be realised it needs to be repeated in other places and in other specialties. It nevertheless offers a more rational basis for interpreting waiting list data than presently exists and by using the short-cut methods is a relatively cheap way of generating much useful data.     

Characterization of chimeric proteins constructed from human epidermal growth factor (EGF) and the Drosophila EGF-receptor antagonist argos

The Drosophila argos protein is a natural ligand antagonist of Drosophila EGF receptor (DER), but does not interact with the human EGF receptor (EGFR). With a view to generating a corresponding EGFR antagonist, we, have designed five chimeric proteins featuring selected characteristic parts of argos within the framework of the human EGF ligand. These chimeras were expressed in bacteria, purified, refolded and characterized. We tested their ability to bind to EC;FR, to effect receptor tyrosine phosphorylation and to inhibit EGF-induced EGFR phosphorylation.