Spiking of the tubercles of the intercondylar eminence of the tibial plateau in osteoarthritis

"Spiking", "sharpening" or "peaking" of the tubercles of the intercondylar eminence of the tibial plateau has been described as an early sign of osteoarthritis of the knee joint, but there are no reports confirming this association. The radiographs of 55 patients with established osteoarthritis of the knee joint and 36 controls were reviewed. Measurements were made of the angulation of the tips of the medial and lateral tubercles, and the ratio of the tubercle height to the width of the tibial plateau was calculated. There was a significant difference in both these parameters between the two groups, confirming that lengthening and sharpening of the angles of the tubercles are features of osteoarthritis of the knee joint.     

Loss of RhoB expression in human lung cancer progression.

PURPOSE: RhoB is a low molecular weight GTPase belonging to the Ras protein superfamily. Whereas most Rho proteins have been shown to have a positive role in proliferation and malignant transformation, the specific role of RhoB appears more divergent. We reported previously that RhoB inhibits cell proliferation in various human cancer cells. Here, we studied the specific role played by RhoB in human lung cancer. EXPERIMENTAL DESIGN: We analyzed the expression of RhoB protein by immunostaining in human lung tissues ranging from normal to invasive carcinoma from different histological types in two large independent studies of, respectively, 94 and 45 samples. We then studied the cellular effect of RhoB overexpression in a model of lung cancer (A549, adenocarcinoma) and tumorigenicity in nude mice. RESULTS: We showed in both studies that RhoB protein was expressed in normal lung and decreased dramatically through lung cancer progression (P < 0.01). Interestingly, RhoB expression was lost in 96% of invasive tumors and reduced by 86% in poorly differentiated tumors compared with the nonneoplastic epithelium. Moreover, the loss of expression of RhoB correlated significantly with tumor stage and proliferative index, whereas no correlation was found between RhoB and p53 or Bcl-2 expression. We then showed that ectopic expression of RhoB in lung cancer cell line A549 suppressed cell proliferation, anchorage-independent growth, and xenograft tumor growth in nude mice. CONCLUSIONS: RhoB loss of expression occurs very frequently in lung carcinogenesis, reinforcing its putative tumor suppressive activity, and raising the value of its potential use in cancer therapy.     

Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia.

PURPOSE: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO. PATIENTS AND METHODS: Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response. RESULTS: The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity. CONCLUSION: ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested.     

Gaze anticipation during human locomotion

During locomotion, a top-down organization has been previously demonstrated with the head as a stabilized platform and gaze anticipating the horizontal direction of the trajectory. However, the quantitative assessment of the anticipatory sequence from gaze to trajectory and body segments has not been documented. The present paper provides a detailed investigation into the spatial and temporal anticipatory relationships among the direction of gaze and body segments during locomotion. Participants had to walk along several mentally simulated complex trajectories, without any visual cues indicating the trajectory to follow. The trajectory shapes were presented to the participants on a sheet of paper. Our study includes an analysis of the relationships between horizontal gaze anticipatory behavior direction and the upcoming changes in the trajectory. Our findings confirm the following: 1) The hierarchical ordered organization of gaze and body segment orientations during complex trajectories and free locomotion. Gaze direction anticipates the head orientation, and head orientation anticipates reorientation of the other body segments. 2) The influence of the curvature of the trajectory and constraints of the tasks on the temporal and spatial relationships between gaze and the body segments: Increased curvature resulted in increased time and spatial anticipation. 3) A different sequence of gaze movements at inflection points where gaze plans a much later segment of the trajectory.     

Age determination of adult individuals by three-dimensional modelling of canines

Accurate age determination is fundamental in both forensic medicine and anthropology. Many methods that relate dental characteristics to adult age have been proposed, but there is still no simple and reliable method that does not damage the study material. The aim of this work was to propose a relevant and practical technique for determining age in adults that could be used in both living and deceased individuals. The sample was composed of 210 CT scans from individuals aged from 15 to 85 years old, with four healthy canines present in the mouth. The 840 canines were modelled using Mimics® 10.01 software. The pulp volume/total volume ratio ×100 was determined for each tooth. Seven mathematical models, corresponding to all possible real situations, were determined by the weighted least squares method and ranked in order of relative performance. The adequacy of the seven models to the data was very high with the regressions proposed (0.915?<?R ² _adjusted?<?0.964). Ranked in order of performance, the maxillary model was the most powerful of the seven models for age determination, followed by the 4 canines model, the 13 model and the 23 model.     

Novel Linker Variants of Antileishmanial/Antitubercular 7-Substituted 2-Nitroimidazooxazines Offer Enhanced Solubility

Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, culminating in a new clinical investigational drug for visceral leishmaniasis (DNDI-0690). To offset development risks, we continued to seek further leads with divergent candidate profiles, especially analogues possessing greater aqueous solubility. Starting from an efficacious monoaryl derivative, replacement of the side chain ether linkage by novel amine, amide, and urea functionality was first explored; the former substitution was well-tolerated in vitro and in vivo but elicited marginal alterations to solubility (except through a less stable benzylamine), whereas the latter groups resulted in significant solubility improvements (up to 53-fold) but an antileishmanial potency reduction of at least 10-fold. Ultimately, we discovered that O-carbamate 66 offered a more optimal balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).     

Angiofibroma celular de vulva: una entidad a investigar

Cellular angiofibroma of the vulva is a well-circumscribed tumor that occurs in men and women. This tumor has histological and immunohistochemical features that distinguish it from other vulvar tumors. The prognosis is good, although there is a risk of recurrence. We report the case of a woman with this diagnosis.