Comparative Effectiveness of Structural versus Regulatory Protein Gene Transfer on Articular Chondrocyte Matrix Gene Expression

OBJECTIVE: The production of extracellular matrix is a necessary component of articular cartilage repair. Gene transfer is a promising method to improve matrix biosynthesis by articular chondrocytes. Gene transfer may employ transgenes encoding regulatory factors that stimulate the production of matrix proteins, or may employ transgenes that encode the proteins themselves. The objective of this study was to determine which of these 2 approaches would be the better choice for further development. We compared these 2 approaches using the transgenes encoding the structural matrix proteins, aggrecan or type II collagen, and the transgene encoding the anabolic factor, insulin-like growth factor I (IGF-I). METHODS: We transfected adult bovine articular chondrocytes with constructs encoding type II collagen, aggrecan, or IGF-I, and measured the expression of type II collagen ( COL2A1) and aggrecan ( ACAN) from their native genes and from their transgenes. RESULTS: IGF-I gene ( IGF1) transfer increased the expression of the native chondrocyte COL2A1 and ACAN genes 2.4 and 2.9 times control, respectively. COL2A1 gene transfer did not significantly increase COL2A1 transcripts, even when the transgene included the genomic COL2A1 regulatory sequences stimulated by chondrogenic growth factors. In contrast, ACAN gene transfer increased ACAN transcripts up to 3.4 times control levels. IGF1, but not ACAN, gene transfer increased aggrecan protein production. CONCLUSION: Taken together, these results suggest that the type II collagen and aggrecan production required for articular cartilage repair will be more effectively achieved by genes that encode anabolic regulatory factors than by genes that encode the matrix molecules themselves

REGRESSIONS FOR SUMS OF SQUARES OF SPACINGS

Abstract. Starting with a new formula for the regression of sum of squares of spacings (SSS) with respect to the maximum we present a characterization of a family of beta type mixtures in terms of the constancy of regression of normalized SSS of order statistics. Related characterization for records describes a family of minima of independent Weibull distributions

Blood loss following medial unicondylar knee replacements without a tourniquet: is there a need to group and save?

Background: There are current trends towards not using a tourniquet in total knee replacement (TKR), but there is nothing published on what the effects of not using a tourniquet on unicondylar knee replacements (UKR) may be in terms of blood loss.Methods: A retrospective case series of 36 consecutive UKR from our institution were analysed. All procedures were carried out without a tourniquet and also utilised a standardised interventions protocol including withholding of anticoagulants and antiplatelet medications, administration of periarticular local anaesthetic and adrenaline injection, and both IV and topical tranexamic acid. Outcomes measured were estimated intra-operative blood loss, overall blood loss through comparison of pre and post-operative haemoglobin laboratory values, and the need for post-operative blood transfusion.Results: Most patients (61.1%) experienced an estimated intra-operative blood loss of less than100 mls. There was a mean haemoglobin drop of 16.1 g/l (range 1–26, SD ±5.9), with a mean post operatively haemoglobin level of 125.1 g/l (range 107-142, SD ±8.7). No patients required a blood transfusion.Conclusions: A low level of blood loss is encountered when UKR is undertaken without a tourniquet and with our standard interventions to reduce bleeding. The level of post-operative haemoglobin and absence of requirement for blood transfusion suggests that this operation can be undertaken without the need for a group and save. It is our hope that surgeons will be encouraged to perform this procedure without a tourniquet and benefit from the cost-saving opportunity of not performing a group and save

A comparison of blood loss and the need for transfusion following primary total knee replacement with or without the use of a tourniquet

Background: Primary total knee replacement (TKR) has traditionally been carried out with the use of a tourniquet. More recent trends towards performing the surgery without a tourniquet have had some support in the literature and may improve patient recovery.Methods: A retrospective cohort of 198 consecutive primary TKRs from our institution were identified and analysed, 52 used a tourniquet and 146 did not. All TKRs also utilised a standardised interventions protocol including withholding of anticoagulants and antiplatelet medications, topical adrenaline injection, and both IV and topical tranexamic acid. Outcomes measured were estimated intra-operative blood loss, overall blood loss through comparison of pre and post-operative haemoglobin laboratory values, and the need for post-operative blood transfusion.Results: Analysis demonstrated a statistically significant reduction in estimated intra-operative blood loss when a tourniquet was used (p<0.001). However, overall blood loss indicated by the haemoglobin drop after surgery was not significantly affected by tourniquet use (p=0.342). Transfusion requirements were also similar among the groups (4.8% vs. 5.8%) and no tendency was suggested towards an increased rate of transfusion in the non-tourniquet group.Conclusions: Our study shows that although estimated intra-operative blood loss is increased without a tourniquet, total blood loss as measured by haemoglobin levels is no different for primary TKRs that use a tourniquet and those that do not. Furthermore there is no difference in post-operative blood transfusion rates. It is our hope that this study will add to the body of evidence for surgeons to consider no longer using a tourniquet for primary TKR

Single view reflectance capture using multiplexed scattering and time-of-flight imaging

This paper introduces the concept of time-of-flight reflectance estimation, and demonstrates a new technique that allows a camera to rapidly acquire reflectance properties of objects from a single view-point, over relatively long distances and without encircling equipment. We measure material properties by indirectly illuminating an object by a laser source, and observing its reflected light indirectly using a time-of-flight camera. The configuration collectively acquires dense angular, but low spatial sampling, within a limited solid angle range - all from a single viewpoint. Our ultra-fast imaging approach captures space-time "streak images" that can separate out different bounces of light based on path length. Entanglements arise in the streak images mixing signals from multiple paths if they have the same total path length. We show how reflectances can be recovered by solving for a linear system of equations and assuming parametric material models; fitting to lower dimensional reflectance models enables us to disentangle measurements. We demonstrate proof-of-concept results of parametric reflectance models for homogeneous and discretized heterogeneous patches, both using simulation and experimental hardware. As compared to lengthy or highly calibrated BRDF acquisition techniques, we demonstrate a device that can rapidly, on the order of seconds, capture meaningful reflectance information. We expect hardware advances to improve the portability and speed of this device.National Science Foundation (U.S.) (Award CCF-0644175)National Science Foundation (U.S.) (Award CCF-0811680)National Science Foundation (U.S.) (Award IIS-1011919)Intel Corporation (PhD Fellowship)Alfred P. Sloan Foundation (Research Fellowship

Paraganglioma of the tongue with SDHB gene mutation in a patient with Graves' disease

The authors want to thank Mr. Jose Eduardo Matos (photog-rapher) for his technical assistance.We report a case of an apparently sporadic paraganglioma of the tongue with a germ-line mutation in a female patient with asymptomatic Graves' disease. The tongue is an unusual primary location. Genetic testing is mandatory in all cases. Thyroid gland dysfunction and autoimmune phenomena could be associated with some paragangliomas.S