How Should We Investigate Breast Implant Rupture?

We aimed to examine a cohort of patients presenting with breast implant complications to establish the sensitivity and specificity of clinical examination, Ultrasound Scanning (US) and Magnetic Resonance Imaging (MRI) in the diagnosis of implant rupture, and to examine the correlation between US and MRI. We performed a 26-month retrospective review. Patients underwent US and MRI to exclude rupture. Results of US and MRI were compared prospectively for concordance, then retrospectively to clinical findings and surgical diagnosis. Thirty-four patients with 60 implants were reviewed. The sensitivities of clinical diagnosis, US, and MRI for rupture was 42%, 50%, and 83%, respectively, while the specificities were 50%, 90%, and 90%. The concordance between US and MRI was 87%. MRI is the investigation of choice for implant rupture. US is a valuable alternative with good concordance with MRI. When US is positive for implant rupture an MRI is not necessary to confirm the diagnosis. Knowledge of the sensitivity and specificity as well as the concordance between the two investigations is useful to ensure the appropriate use of available resources.     

Orbital exenteration in periorbital malignancies

BackgroundOrbital exenteration is a disfiguring procedure most commonly performed for locally advanced or recurrent periorbital malignancies.¹MethodsWe performed a retrospective review of 22 patients who underwent orbital exenteration for advanced periorbital malignancy at our institution, by the senior author over a seventeen-year period. Specifically, we have reviewed the tumour histology along with stage at presentation, patient age, history of previous surgical intervention and surgical outcomes. The review highlighted two main groups who required orbital exenteration – patients with recurrent or locally advanced periorbital skin cancers, and patients with malignancy of the sinus.ConclusionWe discuss the presentation and management of the two pathological processes and highlight the importance of aggressive early management of periorbital malignancy with a view to prevention of exenteration and improving survival.     

Mice with defective Fas ligand are protected from crescentic glomerulonephritis

Fas ligand is a well-known inducer of apoptosis in cells expressing its receptor Fas; it also prevents autoimmunity by inducing apoptosis of activated T cells. However, Fas ligand also mediates non-apoptotic functions involving inflammatory cell migration and cytokine responses. We sought here to study the role of Fas ligand in nephrotoxic nephritis, a model of crescentic glomerulonephritis, using generalized lymphoproliferative disorder (GLD) mice on a C57BL/6 background, which have defective Fas ligand and display only mild autoimmunity. These mice were significantly protected from glomerular crescent formation, glomerular thrombosis, renal impairment, and albuminuria 15 days after the induction of glomerulonephritis in comparison with wild-type mice. There were a reduced number of apoptotic cells in the glomeruli of nephritic GLD mice but no defect in their antibody responses or splenocyte proliferation at 15 days following the induction of glomerulonephritis. Bone marrow transplantation from wild-type mice restored disease susceptibility to GLD mice; however, wild-type mice were not protected when transplanted with bone marrow from GLD mice. Mesangial cells express Fas ligand in vitro, and these cells isolated from GLD mice produced lower amounts of monocyte chemoattractive protein-1 following interleukin-1 stimulation compared with cells from wild-type mice. Thus, Fas ligand-defective mice are protected from nephrotoxic nephritis, a disease in which both circulating and intrinsic renal cells appear to have a role.     

A comparison of the clinical and experimental characteristics of four acute surgical pain models: Dental extraction,bunionectomy, joint replacement,and soft tissue surgery

When a clinical trial of an analgesic produces a negative finding, it is important to consider the influence (if any) of experimental error on the validity of that result. Although efforts to identify and minimize experimental error in chronic pain investigations have begun in earnest, less work has been performed on the optimization of acute pain methodology. Of the acute surgical pain methodology articles that have been published over the last decade, almost all focus on either the dental or bunion model. Analgesics are typically evaluated in a variety of surgical models that eventually include hospital-based models (eg, joint replacement and soft tissue surgery). Every surgical procedure has unique clinical characteristics that must be considered to optimize study design and conduct. Much of the methodological knowledge garnered from bunion and dental studies is applicable to other surgical models, but some extrapolations are hazardous. The purposes of this review were (1) to qualitatively describe the clinical and experimental characteristics of the 4 classic surgical models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery; and (2) to quantitatively compare the models by analyzing 3 factors: effect size, enrollment rate, and demographics. We found that the dental extraction and bunionectomy models had higher assay sensitivity than the joint replacement and soft tissue surgery models. It is probable that this finding is secondary to the superior experimental conditions under which the dental and bunion models are executed (utilization of few centers that have the ability to reduce surgical, anesthetic, and postoperative confounders).     

Mutation R120G in αB-crystallin, which is linked to a desmin-related myopathy, results in an irregular structure and defective chaperone-like function

alphaB-crystallin, a member of the small heat shock protein family, possesses chaperone-like function. Recently, it has been shown that a missense mutation in alphaB-crystallin, R120G, is genetically linked to a desmin-related myopathy as well as to cataracts [Vicart, P., Caron, A., Guicheney, P., Li, A., Prevost, M.-C., Faure, A., Chateau, D., Chapon, F., Tome, F., Dupret, J.-M., et al. (1998) Nat. Genet. 20, 92-95]. By using alpha-lactalbumin, alcohol dehydrogenase, and insulin as target proteins, in vitro assays indicated that R120G alphaB-crystallin had reduced or completely lost chaperone-like function. The addition of R120G alphaB-crystallin to unfolding alpha-lactalbumin enhanced the kinetics and extent of its aggregation. R120G alphaB-crystallin became entangled with unfolding alpha-lactalbumin and was a major portion of the resulting insoluble pellet. Similarly, incubation of R120G alphaB-crystallin with alcohol dehydrogenase and insulin also resulted in the presence of R120G alphaB-crystallin in the insoluble pellets. Far and near UV CD indicate that R120G alphaB-crystallin has decreased beta-sheet secondary structure and an altered aromatic residue environment compared with wild-type alphaB-crystallin. The apparent molecular mass of R120G alphaB-crystallin, as determined by gel filtration chromatography, is 1.4 MDa, which is more than twice the molecular mass of wild-type alphaB-crystallin (650 kDa). Images obtained from cryoelectron microscopy indicate that R120G alphaB-crystallin possesses an irregular quaternary structure with an absence of a clear central cavity. The results of this study show, through biochemical analysis, that an altered structure and defective chaperone-like function of alphaB-crystallin are associated with a point mutation that leads to a desmin-related myopathy and cataracts.