Retroperitoneal Repair of Abdominal Aortic Aneurysm Reduces Bowel Dysfunction

Objective: To assess the effect of intestinal manipulation and mesenteric traction on gastro-intestinal function and postoperative recovery in patients undergoing abdominal aortic aneurysm (AAA) repair. Methods: Thirty-five patients undergoing AAA repair were randomised into 3 groups. Group I (n = II) had repair via retroperitoneal approach while Group II (n = 12) and Group III (n = 12) were repaired via transperitoneal approach with bowel packed within the peritoneal cavity or exteriorised in a bowel bag respectively. Gastric emptying was measured pre-operatively (day 0), day 1 and day 3 using paracetamol absorption test (PAT) and area under curve (P-AUC) was calculated. Intestinal permeability was measured using the Lactulose-Mannitol test. Results: Aneurysm size, operation time and PAT (on day 0 and day 3) were similar in the three groups. On day 1, the P-AUC was significantly higher in Group I, when compared with Group II and Group III (P = .02). Resumption of diet was also significantly earlier in Group I as compared to Group II and Group III. The intestinal permeability was significantly increased in Group II and Group III at day 1 when compared with day 0, with no significant increase in Group I. Retroperitoneal repair was also associated with significantly shorter intensive care unit (P = .04) and hospital stay (P = .047), when compared with the combined transperitoneal repair group (Group II and III). Conclusion: Retroperitoneal AAA repair minimises intestinal dysfunction and may lead to quicker patient recovery when compared to transperitoneal repair.

Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance

Purpose: To determine whether repression of a recently isolated, X-ray-responsive gene, DIR1, using antisense oligonucleotides could affect clonogenic cell survival and repair of DNA strand breaks and have a possible role in the mechanism underlying the phenomenon of 'induced radioresistance' (IRR).

A study of the relationship between process conditions and mechanical strength of mineralized red algae in the preparation of a marine-derived bone void filler

Bone void fillers that can enhance biological function to augment skeletal repair have significant therapeutic potential in bone replacement surgery. This work focuses on the development of a unique microporous (0.5-10 mu m) marine-derived calcium phosphate bioceramic granule. It was prepared fro Corallina officinalis, a mineralized red alga, using a novel manufacturing process. This involved thermal processing, followed by a low pressure-temperature chemical synthesis reaction. The study found that the ability to maintain the unique algal morphology was dependent on the thermal processing conditions. This study investigates the effect of thermal heat treatment on the physiochemical properties of the alga. Thermogravimetric analysis was used to monitor its thermal decomposition. The resultant thermograms indicated the presence of a residual organic phase at temperatures below 500 degrees C and an irreversible solid-state phase transition from mg-rich-calcite to calcium oxide at temperatures over 850 degrees C. Algae and synthetic calcite were evaluated following heat treatment in an air-circulating furance at temperatures ranging from 400 to 800 degrees C. The highest levels of mass loss occurred between 400-500 degrees C and 700-800 degrees C, which were attributed to the organic and carbonate decomposition respectively. The changes in mechanical strength were quantified using a simple mechanical test, which measured the bulk compressive strength of the algae. The mechanical test used may provide a useful evaluation of the compressive properties of similar bone void fillers that are in granular form. The study concluded that soak temperatures in the range of 600 to 700 degrees C provided the optimum physiochemical properties as a precursor to conversion to hydroxyapatite (HA). At these temperatures, a partial phase transition to calcium oxide occurred and the original skeletal morphology of the alga remained intact.

Wear paths produced by individual hip-replacement patients— A large-scale, long-term follow-up study

Wear particle accumulation is one of the main contributors to osteolysis and implant failure in hip replacements. Altered kinematics produce significant differences in wear rates of hip replacements in simulator studies due to varying degrees of multidirectional motion. Gait analysis data from 153 hip-replacement patients 10-years post-operation were used to model two- and three-dimensional wear paths for each patient. Wear paths were quantified in two dimensions using aspect ratios and in three dimensions using the surface areas of the wear paths, with wear-path surface area correlating poorly with aspect ratio. The average aspect ratio of the patients wear paths was 3.97 (standard deviation ¼ 1.38), ranging from 2.13 to 10.86. Sixty percent of patients displayed aspect ratios between 2.50 and 3.99. However, 13% of patients displayed wear paths with aspect ratios 45.5, which indicates reduced multidirectional motion. The majority of total hip replacement (THR) patients display gait kinematics which produce multidirectional wear paths, but a significant minority display more linear paths.

The influence of wear paths produced by hip replacement patients during normal walking on wear rates

Variation in wear paths is known to greatly affect wear rates in vitro, with multidirectional paths producing much greater wear than unidirectional paths. This study investigated the relationship between multidirectional motion at the hip joint, as measured by aspect ratio, sliding distance, and wear rate for 164 hip replacements. Kinematic input from three-dimensional gait analysis was used to determine the wear paths. Activity cycles were determined for a subgroup of 100 patients using a pedometer study, and the relationship between annual sliding distance and wear rate was analyzed. Poor correlations were found between both aspect ratio and sliding distance and wear rate for the larger group and between annual sliding distance and wear rate for the subgroup. However, patients who experienced a wear rate <0.08 mm/year showed a strong positive correlation between the combination of sliding distance, activity levels, and aspect ratio and wear rate (adjusted r2?=?55.4%). This group may represent those patients who experience conditions that most closely match those that prevail in simulator and laboratory tests. Although the shape of wear paths, their sliding distance, and the number of articulation cycles at the hip joint affect wear rates in simulator studies, this relationship was not seen in this clinical study. Other factors such as lubrication, loading conditions and roughness of the femoral head may influence the wear rate.

Cells deficient in the base excision repair protein, DNA polymerase beta, are hypersensitive to oxaliplatin chemotherapy

A significant proportion of human cancers overexpress DNA polymerase beta (Pol beta), the major DNA polymerase involved in base excision repair. The underlying mechanism and biological consequences of overexpression of this protein are unknown. We examined whether Pol beta, expressed at levels found in tumor cells, is involved in the repair of DNA damage induced by oxaliplatin treatment and whether the expression status of this protein alters the sensitivity of cells to oxaliplatin. DNA damage induced by oxaliplatin treatment of HCT116 and HT29 colon cancer cells was observed to be associated with the stabilization of Pol beta protein on chromatin. In comparison with HCT116 colon cancer cells, isogenic oxaliplatin-resistant (HCT-OR) cells were found to have higher constitutive levels of Pol beta protein, faster in vitro repair of a DNA substrate containing a single nucleotide gap and faster repair of 1,2-GG oxaliplatin adduct levels in cells. In HCT-OR cells, small interfering RNA knockdown of Pol beta delayed the repair of oxaliplatin-induced DNA damage. In a different model system, Pol beta-deficient fibroblasts were less able to repair 1,2-GG oxaliplatin adducts and were hypersensitive to oxaliplatin treatment compared with isogenic Pol beta-expressing cells. Consistent with previous studies, Pol beta-deficient mouse fibroblasts were not hypersensitive to cisplatin treatment. These data provide the first link between oxaliplatin sensitivity and DNA repair involving Pol beta. They demonstrate that Pol beta modulates the sensitivity of cells to oxaliplatin treatment. Oncogene (2010) 29, 463-468; doi:10.1038/onc.2009.327; published online 19 October 2009

Fabrication and Repair of Cartilage Defects with a Novel Acellular Cartilage Matrix Scaffold

The objectives of this study were to develop a three-dimensional acellular cartilage matrix (ACM) and investigate its possibility for use as a scaffold in cartilage tissue engineering. Bovine articular cartilage was decellularized sequentially with trypsin, nuclease solution, hypotonic buffer, and Triton x 100 solution; molded with freeze-drying process; and cross-linked by ultraviolet irradiation. Histological and biochemical analysis showed that the ACM was devoid of cells and still maintained the collagen and glycosaminoglycan components of cartilage. Scanning electronic microscopy and mercury intrusion porosimetry showed that the ACM had a sponge-like structure of high porosity. The ACM scaffold had good biocompatibility with cultured rabbit bone marrow mesenchymal stem cells with no indication of cytotoxicity both in contact and in extraction assays. The cartilage defects repair in rabbit knees with the mesenchymal stem cell-ACM constructs had a significant improvement of histological scores when compared to the control groups at 6 and 12 weeks. In summary, the ACM possessed the characteristics that afford it as a potential scaffold for cartilage tissue engineering.

Spatio-temporal analysis of DNA damage repair using the X-ray microbeam

Cellular response to radiation damage is made by a complex network of pathways and feedback loops whose spatiotemporal organization is still unclear despite its decisive role in determining the fate of the damaged cell. The single-cell approach and the high spatial resolution offered by microbeams provide the perfect tool to study and quantify the dynamic processes associated with the induction and repair of DNA damage. The soft X-ray microbeam has been used to follow the development of radiation induced foci in live cells by monitoring their size and intensity as a function of dose and time using yellow fluorescent protein (YFP) tagging techniques. Preliminary data indicate a delayed and linear rising of the intensity signal indicating a slow kinetic for the accumulation of DNA repair protein 53BP1. A slow and limited foci diffusion has also been observed. Further investigations are required to assess whatever such diffusion is consistent with a random walk pattern or if it is the result of a more structured lesion processing phenomenon. In conclusion, our data indicates that the use of microbeams coupled to live cell microscopy represent a sophisticated approach for visualizing and quantifying the dynamics changes of DNA proteins at the damaged sites.

Cement mantle fatigue failure in total hip replacement: Experimental and computational testing

One possible loosening mechanism of the femoral component in total hip replacement is fatigue cracking of the cement mantle. A computational method capable of simulating this process may therefore be a useful tool in the preclinical evaluation of prospective implants. In this study, we investigated the ability of a computational method to predict fatigue cracking in experimental models of the implanted femur construct. Experimental specimens were fabricated such that cement mantle visualisation was possible throughout the test. Two different implant surface finishes were considered: grit blasted and polished. Loading was applied to represent level gait for two million cycles. Computational (finite element) models were generated to the same geometry as the experimental specimens, with residual stress and porosity simulated in the cement mantle. Cement fatigue and creep were modelled over a simulated two million cycles. For the polished stem surface finish, the predicted fracture locations in the finite element models closely matched those on the experimental specimens, and the recorded stem displacements were also comparable. For the grit blasted stem surface finish, no cement mantle fractures were predicted by the computational method, which was again in agreement with the experimental results. It was concluded that the computational method was capable of predicting cement mantle fracture and subsequent stem displacement for the structure considered. (C) 2006 Elsevier Ltd. All rights reserved.