Imaging the Impact of Chemically Inducible Proteins on Cellular Dynamics In Vivo

The analysis of dynamic events in the tumor microenvironment during cancer progression is limited by the complexity of current in vivo imaging models. This is coupled with an inability to rapidly modulate and visualize protein activity in real time and to understand the consequence of these perturbations in vivo. We developed an intravital imaging approach that allows the rapid induction and subsequent depletion of target protein levels within human cancer xenografts while assessing the impact on cell behavior and morphology in real time. A conditionally stabilized fluorescent E-cadherin chimera was expressed in metastatic breast cancer cells, and the impact of E-cadherin induction and depletion was visualized using real-time confocal microscopy in a xenograft avian embryo model. We demonstrate the assessment of protein localization, cell morphology and migration in cells undergoing epithelial-mesenchymal and mesenchymal-epithelial transitions in breast tumors. This technique allows for precise control over protein activity in vivo while permitting the temporal analysis of dynamic biophysical parameters

Revision anterior cruciate ligament reconstruction using a 2-stage technique with bone grafting of the tibial tunnel.

BACKGROUND: Revision anterior cruciate ligament surgery is often considered a salvage procedure with limited goals. However, this limitation need not be the case. Similar to primary reconstruction, the goal should be to choose an appropriate graft and place it in an anatomical position in a good quality bone. The issue of good quality bone seems to have been ignored. HYPOTHESIS: A 2-stage anterior cruciate ligament revision reconstruction with bone grafting of the tibial tunnel and the use of a different femoral tunnel will produce measured knee laxity and International Knee Documentation Committee scores similar to a primary anterior cruciate ligament reconstruction. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: This prospective study involved 49 consecutive 2-stage anterior cruciate ligament revisions (group R) performed by a single surgeon from 1993 to 2000. Two-stage revision surgery was performed if the tibial tunnel from a previous reconstruction surgery would overlap (either partially or fully) the correctly placed revision tunnel. The first stage consisted of removal of the old graft and interfering metalwork, together with bone grafting of the tibial tunnel. After ensuring adequate bone graft incorporation using computed tomography scan, the second stage revision was undertaken. This stage comprised harvesting the autograft, its anatomical placement, and its adequate fixation. The results were compared with the results of a matched group of patients with primary anterior cruciate ligament reconstruction (group P). RESULTS: In group R, as meniscal and chondral lesions were more common, the International Knee Documentation Committee scores were lower than those of group P (61.2 for group R and 72.8 for group P; P = .006). Objective laxity measurement was similar in both groups (1.36 mm for group R and 1.2 mm for group P; P = .25). CONCLUSION: This study establishes that the laxity measurements achieved with a 2-stage revision anterior cruciate ligament reconstruction can be similar to those achieved after primary anterior cruciate ligament reconstruction, although the International Knee Documentation Committee rating is lower

Smoking and reconstruction of the anterior cruciate ligament

We sought to determine whether smoking affected the outcome of reconstruction of the anterior cruciate ligament. We analysed the results of 66 smokers (group 1 with a mean follow-up of 5.67 years (1.1 to 12.7)) and 238 non-smokers (group 2 with a mean follow-up of 6.61 years (1.2 to 11.5)), who were statistically similar in age, gender, graft type, fixation and associated meniscal and chondral pathology. The assessment was performed using the International Knee Documentation Committee form and serial cruciometer readings. Poor outcomes were reported in group 1 for the mean subjective International Knee Documentation Committee score (p < 0.001), the frequency (p = 0.005) and intensity (p = 0.005) of pain, a side-to-side difference in knee laxity (p = 0.001) and the use of a four-strand hamstring graft (p = 0.015). Patients in group 1 were also less likely to return to their original level of pre-injury sport (p = 0.003) and had an overall worse final 7 International Knee Documentation Committee grade score (p = 0.007). Despite the well-known negative effects of smoking on tissue healing, the association with an inferior outcome after reconstruction of the anterior cruciate ligament has not previously been described and should be included in the pre-operative counselling of patients undergoing the procedure. ©2006 British Editorial Society of Bone and Joint Surgery

Cimetidine induced postural and action tremor.

Letter to the Edito

Meniscal repair in anterior cruciate ligament reconstruction: A long-term outcome study

Purpose: To study the long-term outcome of patients who have undergone inside-out, vertical stacked mattress suture repair of meniscal tears combined with anterior cruciate ligament (ACL) reconstruction. Methods: From a database of ACL reconstructed patients, consecutive patients undergoing concomitant meniscal repair and ACL reconstruction between 1991 and 1999 were identified. Patients with previous ACL or meniscal pathology were excluded. Two age- and sex-matched cohorts who had undergone combined ACL reconstruction and menisectomy and who had undergone ACL reconstruction with normal menisci were identified for comparison. Outcome scoring included IKDC and Lysholm scores for the meniscal repair group. Two sample t-tests and chi-square tests were used to compare the IKDC subjective scores, with a minimum level of significance set at 5% (P = 0.05). Results: Fourty-four patients were identified for analysis with a median follow-up of 10 years (7.7-12.6). Patients undergoing ACL reconstruction combined with meniscal repair had a mean IKDC of 84.2 compared with a mean score of 70.5 (P = 0.008) in patients who had undergone menisectomy and 88.2 (P = 0.005) in patients with intact menisci. 86.2% of patients with ACL reconstruction and meniscal repair had Lysholm score of between 80 and 100%. Sixty-nine percent follow-up was achieved. Survival analysis by life table method shows a best case of 89% 10-years survival. Conclusions: This study demonstrates that good long-term outcomes can be obtained in patients up to over 12 years after combined ACL reconstruction and meniscal repair. Improved functional scores can be achieved when compared with ACL reconstruction and menisectomy. The authors advocate repair of meniscal tears during ACL reconstruction unless there is complex tearing, radial tearing or plastic deformation of the remaining meniscus. Level of evidence: III. © 2011 Springer-Verlag