Changes of cerebral blood flow during the secondary expansion of a cortical contusion assessed by 14C-iodoantipyrine autoradiography in mice using a non-invasive protocol

Although changes of cerebral blood flow (CBF) in and around traumatic contusions are well documented, the role of CBF for the delayed death of neuronal cells in the traumatic penumbra ultimately resulting in secondary contusion expansion remains unclear. The aim of the current study was therefore to investigate the relationship between changes of CBF and progressive peri-contusional cell death following traumatic brain injury (TBI). CBF and contusion size were measured in C57Bl6 mice under continuous on-line monitoring of (ETp)CO2 before, and at 15 min and 24 h following controlled cortical impact by 14C-iodoantipyrine autoradiography (IAP-AR; n = 5-6 per group) and by Nissl staining, respectively. Contused and ischemic (CBF < 10%) tissue volumes were calculated and compared over time. Cortical CBF in not injured mice varied between 69 and 93 mL/100mg/min depending on the anatomical location. Fifteen minutes after trauma, CBF decreased in the whole brain by approximately 50% (39 +/- 18 mL/100mg/min; p < 0.05), except in contused tissue where it fell by more than 90% (3 +/- 2 mL/100mg/min; p < 0.001). Within 24 h after TBI, CBF recovered to normal values in all brain areas except the contusion where it remained reduced by more than 90% (p < 0.001). Contusion volume expanded from 24.9 to 35.5 mm3 (p < 0.01) from 15 min to 24 h after trauma (+43%), whereas the area of severe ischemia (CBF < 10%) showed only a minimal (+13%) and not significant increase (22.3 to 25.1 mm3). The current data therefore suggest that the delayed secondary expansion of a cortical contusion following traumatic brain injury may not be caused by a reduction of CBF alone.     

Differences in CMV-Specific T-Cell Levels and Long-Term Susceptibility to CMV Infection after Kidney, Heart and Lung Transplantation

Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV-specific T-cell responses were characterized in long-term transplant recipients and associated with the frequency of infectious complications. CMV-reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation. Moreover, the immunosuppressive effect of calcineurin inhibitors on specific T-cell reactivity was quantified in vitro and compared with responses in vivo. Median CMV-specific T-cell frequencies in long-term renal (1.48%; range 0.06-17.26%) and heart transplant recipients (0.90%; 0.13-12.49%) did not differ from controls (1.82%; 0.26-21.00%). In contrast, CMV-specific T-cell levels were significantly lower in lung transplant recipients (0.50%; <0.05-4.98%) and showed a significant correlation with the frequency of infectious episodes (r =-0.57, p = 0.005). The differences within the groups were associated with increasing dosages of immunosuppressive drugs, as exemplified for calcineurin inhibitors that dose dependently reduced specific T-cell reactivity in vitro. In conclusion, monitoring CMV-specific CD4 T cells may serve as a measure for long-term disease susceptibility and may contribute to an improved management of CMV complications after lung transplantation.     

Accuracy assessment of cone beam computed tomography-derived laboratory-based surgical templates on partially edentulous patients

Objectives: The aim of the present prospective clinical study was to evaluate the match between the positions and axes of the virtually planned and the placed implants using laboratory‐based surgical guides generated from cone beam computed tomography (CBCT). Materials and methods: A total of 132 implants were placed with the aid of 3D‐based transfer templates in 52 consecutive partially edentulous patients between April 2008 and March 2010. After individual adaptation of the scan templates and CBCT scanning, the acquired data for virtual implant planning and simulation were processed using the med3D software program. After finalizing the virtual placement of the implants the radiographic templates were converted into operative guides containing titanium sleeves for cavity preparation. Preoperative planning was merged with postoperative CBCT data to identify linear and angular deviations between virtually planned and placed implants. Results: Compared with the planned implants the installed implants showed linear deviations in the median at the neck and apex of 0.27 mm (range 0.01–0.97 mm), and of 0.46 mm (range 0.03–1.38 mm), respectively. The angle deviation was 1.84° in median, with a range of 0.07–6.26°. The extent of deviation depends on the size of the tooth gap and the distribution of the remaining teeth. Conclusion: The results of this study suggested that laboratory‐fabricated surgical guides using CBCT data may be reliable in implant placement under prosthodontic considerations in partial edentulism. To cite this article:
Behneke A, Burwinkel M, Knierim K, Behneke N. Accuracy assessment of cone beam computed tomography‐derived laboratory‐based surgical templates on partially edentulous patients.
Clin. Oral Impl. Res. 23 , 2012; 137–143.
doi: 10.1111/j.1600‐0501.2011.02176.x     

Effect of intravitreal injections and volume changes on intraocular pressure: clinical results and biomechanical model

PURPOSE: Intravitreal injections are used extensively to treat retinal diseases. Performing an intravitreal injection increases intraocular volume by the amount of fluid brought into the eye. Whether this influences intraocular pressure (IOP) was investigated here. METHODS: A biomechanical model relying on 3-dimensional elasticity theory was developed to determine the short-term effect of volume changes on IOP. We calculated the effect for intravitreal injections of 0.1 ml in myopic, emmetropic and hyperopic eyes. Our calculations were compared with IOP measurements obtained immediately after intravitreal injection of 4 mg triamcinolone in 0.1 ml solution (IVTA) in 22 patients. Shortly after the measurement had been taken, IOP was reduced by paracentesis. RESULTS: Immediately after IVTA, measured IOP was elevated by a mean of 40.6 +/- 12.1 mmHg compared with initial pressure (p < 0.001). Measured and calculated IOP were comparable. Eyes with shorter axial length had higher IOP immediately after the injection (p < 0.05). CONCLUSIONS: The effect of injected volumes on IOP can be calculated with a biomechanical model. Our results show that paracentesis might be recommended when injecting 0.1 ml of a substance to avoid a short-term increase in IOP. As intravitreal injections are mostly applied in diseases that are due to vascular compromise, it might be prudent not to impair perfusion in those eyes, even for short periods of time.     

Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation

Caspase-3 is a major cell death effector protease in the adult and neonatal nervous system. We found a greater number and higher density of cells in the cortex of caspase-3(-/-) adult mice, consistent with a defect in developmental cell death. Caspase-3(-/-) mice were also more resistant to ischemic stress both in vivo and in vitro. After 2 h of ischemia and 48 h of reperfusion, cortical infarct volume was reduced by 55%, and the density of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive cells was decreased by 36% compared with wild type. When subjected to oxygen-glucose deprivation (2 h), cortical neurons cultured from mice deficient in caspase-3 expression were also more resistant to cell death by 59%. Mutant brains showed caspase-specific poly(ADP-ribose) polymerase cleavage product (85-kDa fragment) in vivo and in vitro, suggesting redundant mechanisms and persistence of caspase-mediated cell death. In the present study, we found that caspase-8 mediated poly(ADP-ribose) polymerase cleavage in caspase-3(-/-) neurons in vivo and in vitro. In addition, mutant neurons showed no evidence of compensatory activation by caspase-6 or caspase-7 after ischemia. Taken together, these data extend the pharmacological evidence supporting an important role for caspase-3 and caspase-8 as cell death mediators in mammalian cortex and indicate the potential advantages of targeting more than a single caspase family member to treat ischemic cell injury.     

Adapting to inversion of the visual field: a new twist on an old problem

While sensorimotor adaptation to prisms that displace the visual field takes minutes, adapting to an inversion of the visual field takes weeks. In spite of a long history of the study, the basis of this profound difference remains poorly understood. Here, we describe the computational issue that underpins this phenomenon and presents experiments designed to explore the mechanisms involved. We show that displacements can be mastered without altering the updated rule used to adjust the motor commands. In contrast, inversions flip the sign of crucial variables called sensitivity derivatives—variables that capture how changes in motor commands affect task error and therefore require an update of the feedback learning rule itself. Models of sensorimotor learning that assume internal estimates of these variables are known and fixed predicted that when the sign of a sensitivity derivative is flipped, adaptations should become increasingly counterproductive. In contrast, models that relearn these derivatives predict that performance should initially worsen, but then improve smoothly and remain stable once the estimate of the new sensitivity derivative has been corrected. Here, we evaluated these predictions by looking at human performance on a set of pointing tasks with vision perturbed by displacing and inverting prisms. Our experimental data corroborate the classic observation that subjects reduce their motor errors under inverted vision. Subjects’ accuracy initially worsened and then improved. However, improvement was jagged rather than smooth and performance remained unstable even after 8 days of continually inverted vision, suggesting that subjects improve via an unknown mechanism, perhaps a combination of cognitive and implicit strategies. These results offer a new perspective on classic work with inverted vision.