Accumulating epidemiological evidence shows that obesity is associated with an increased risk of several types of adult cancers, including endometrial cancer. Chronic hyperinsulinemia, a typical hallmark of diabetes, is one of the leading factors responsible for the obesity-cancer connection. Numerous cellular and circulating factors are involved in the biochemical chain of events leading from hyperinsulinemia and insulin resistance to increased cancer risk and, eventually, tumor development. Metformin is an oral anti-diabetic drug of the biguanide family used for treatment of type 2 diabetes. Recently, metformin was shown to exhibit anti-proliferative effects in ovarian and Type I endometrial cancer, although the mechanisms responsible for this non-classical metformin action remain unclear. The insulin-like growth factors (IGFs) play a prominent role in cancer biology and their mechanisms of action are tightly interconnected with the insulin signaling pathways. Given the cross-talk between the insulin and IGF signaling pathways, the aim of this study was to examine the hypothesis that the anti-proliferative actions of metformin in uterine serous carcinoma (USC) are potentially mediated via suppression of the IGF-I receptor (IGF-IR) pathway. Our results show that metformin interacts with the IGF pathway, and induces apoptosis and inhibition of proliferation and migration of USC cell lines with both wild type and mutant p53. Taken together, our results suggest that metformin therapy could be a novel and attractive therapeutic approach for human USC, a highly aggressive variant of endometrial cancer.
Guillain-Barré syndrome (GBS) is a subacutely evolving paralysis with variable sensory involvement accompanied by hyporeflexia, and typically, albuminocytologic dissociation in cerebrospinal fluid. Abnormal nerve conductions and pathological descriptions of lymphocytic and macrophage infiltration of the peripheral nerve with segmental myelin destruction 1-3 have been well-described. Axonal loss can be present, and is usually secondary to demyelination. Among the intriguing aspects of this syndrome are the variations in clinical course, with severity ranging from trivial limb weakness to total paralysis requiring ventilatory assistance. The majority of patients (75-80%) recover fully (or almost so), but a small percentage (3-8%) still die secondary to sepsis, pulmonary ABSTRACT: Background: Guillain-Barré syndrome (GBS) classically presents with a subacutely evolving areflexic paralysis, with typical laboratory findings of elevated cerebrospinal fluid protein and abnormal nerve conduction studies. There is now an increasing recognition of GBS variants that differ in clinical presentation, prognosis, electrophysiology and presumed pathogenesis. Fulminant cases of GBS have been reported in which a rapid deterioration evolves to a clinical state resembling "brain death". Methods: A retrospective analysis of two such cases of fulminant neuropathy are described, that includes the clinical course, electrophysiology and neuropathology where available. Results: We describe two patients that presented with a rapid course of neurological deterioration, lapsing into what resembled a "clinically brain-dead" state that was subsequently ascribed to a fulminant polyneuropathy. Investigations (electrophysiological, pathological) and the clinical course suggested an axonal neuropathy. Conclusions: A fulminant neuropathy can result in a clinical state resembling "brain death" through diffuse de-efferentation. Although generally attributed to aggressive demyelination with secondary axonal degeneration, a primary axonopathy can also lead to a similar clinical presentation. RÉSUMÉ: Simulation de la mort cérébrale par de-efférentation fulminante. Introduction: La présentation classique du syndrome de Guillain-Barré (SGB) consiste en une paralysie aréflexique évoluant de façon subaiguë accompagnée d'anomalies biochimiques typiques, soit une augmentation des protéines dans le liquide céphalorachidien et des anomalies de conduction nerveuse. On reconnaît maintenant qu'il existe des variantes du SGB qui diffèrent par leur présentation clinique, leur pronostic, les constatations électrophysiologiques et la pathogenèse présumée. Des cas fulminants de SGB chez qui une détérioration rapide évolue vers un état clinique ressemblant à la mort cérébrale ont été rapportés. Méthodes: Nous présentons une analyse rétrospective de deux cas de neuropathie fulminante, leur évolution clinique, ainsi que les constatations électrophysiologiques et neuropathologiques si elles étaient disponibles. Résultats: Nous décrivons deux patients qui ont consulté pour...
A 74-year-old man presented with progressive weakness involving only his back muscles. Serum protein electrophoresis revealed the presence of a monoclonal gammopathy. Muscle biopsy of affected muscles demonstrated amyloid light chain deposition surrounding individual muscle fibers as well as in the walls of blood vessels in association with vasculitis. Selective involvement of axial muscles in isolated amyloid myopathy has not been previously described. We report the occurrence of axial myopathy with associated vasculitis as a presenting feature of primary (AL) amyloidosis. Amyloidosis should be considered in the differential diagnosis of focal myopathies, since the condition may be responsive to chemotherapy.
A comparison of true (assigned) VA to measured VA, demonstrated, on average, better accuracy and reproducibility of the ETDRS chart, but at the penalty of significantly longer test duration. These differences were most pronounced in the low VA range. The reproducibility using a simulation approach is in line with reproducibility values found in several clinical studies.
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