Biomedical subjects
Publications and source records attributed to Ashish D Diwan.
Image intensifier (C-arm) guided facet infiltration of a mixture of long acting local anaesthetic and corticosteroid is a safe and effective office procedure for cervical spondylosis. Visualisation of lower cervical anatomy using C-arm may not always be possible due to the shadow cast by the shoulders. We describe the successful adaptation of swimmer's view in such cases to carry out the injections.
Nitric oxide (NO) is a signaling molecule synthesized from l-arginine by nitric oxide synthases (NOSs). NOS isoforms are either constitutive (endothelial NOS [eNOS] and neuronal NOS [nNOS]) or inducible NOS (iNOS). Previously, our group has reported that NO is expressed during and modulates fracture healing. In this study, we evaluated the specific contribution of iNOS to fracture healing by using iNOS gene therapy in iNOS-deficient mice. Twelve-week-old female wild-type mice and iNOS-KO mice had a right femoral midshaft osteotomy fixed with an intramedullary 0.5-mm-diameter needle. A gelatine sponge was implanted across the fracture site. The gelatine sponge received either Ad5-CMViNOS (in iNOS-deficient mice; n=16) or Ad5-CMVempty (in wild-type mice; n=15, and iNOS-deficient mice; n=15) at a dose of 10(7) pfu. Mice were sacrificed at day 14, and their right and left hind limbs were harvested. Cross-sectional area (CSA) was determined by measuring the callus diameter across the mediolateral and anteroposterior plane using a vernier caliper. Specimens were loaded to failure torsionally in a biaxial INSTRON testing system, and maximum torque, torsional stiffness, and maximal and total energy were determined. Deletion of the iNOS gene decreased the total and maximum energy absorption of the healing femoral fracture by 30% and by 70% (P<0.01), respectively, in comparison to the wild-type mice. This reduction in energy absorption was reversed by iNOScDNA administration via adenovirus vector. Furthermore, iNOScDNA caused an increase in torsional failure by 20% (P=0.01) in comparison to iNOS(-/-) mice that did not receive the iNOScDNA. There were no significant differences in the biomechanical properties of intact femora. These data indicate that iNOS is important in mouse fracture healing. However, the clinical utility of NOS gene therapy to enhance fracture healing will need further evaluation.
Mechanical articulated device to replace intervertebral disc as a treatment for low back pain secondary to disc degeneration has emerged as a promising tool for selected patients. The potential advantages are prevention of adjacent segment degeneration, maintenance of mobility as well as avoidance of all the complications associated with fusion. The short-term results have been comparable to that of fusion, a few mid-term results have shown mixed outcome, but information on long-term results and performance are not available at present. The rationale for lumbar disc arthroplasty, indications, contraindications, the various artificial devices in the market and the concepts intrinsic to each of them, basic technique of insertion, complications are discussed and a brief summary of our experience with one of the devices is presented.
Although one cannot always determine when a patient's persistent pain is neuropathic, the issues are becoming clearer. Patients with spinal pain need to be examined carefully and the persistence of pain should not necessarily be considered to indicate a continuing search for a nociceptive focus. Similarly, continuing pain following successful surgery may be caused by persistent spinal or central neurologic changes. New methods for characterizing the site of neural changes will develop--functional MRI and PET scanning are now characterizing brain activity and will possibly yield results soon that will be helpful in the clinic. Further work needs to be done to identify which clinical features lead to better responses to agents for the treatment of neuropathic pain. New, more specific agents with actions focused on the specific parts of neural transmission are being developed. These include agents (such as growth factors) that will cure, not just suppress, the pathologic pain generators and pathways in patients with persistent pain.
Disc degeneration is considered a major source of pain in patients with chronic low back pain. Novel strategies to cure or decrease the symptoms and increase the patient's quality of life and function are under development. Until recently conservative treatment and fusion surgery were the main therapeutic options. Disc prostheses are undergoing clinical evaluation. The potential for cell transplantation to the intervertebral disc with mature autologous disc cells, chondrocytes, or stem cells is in early stages of investigation. Cell transplantation potentially can increase proteoglycan production and induce disc regeneration or slow down the degeneration process. In animal models, transplantation of autologous disc cells and chondrocytes (derived from costal cartilage) has been demonstrated to be feasible and may slow disc degeneration.
At present, the molecular evidence involved in the degeneration of the IVD is still in its primitive stage. In general, however, intrinsic, extrinsic, and generic factors all have shown a contribution to the initiation of degeneration. These factors may stimulate cytokines and directly or indirectly generate the cellular events thus far detected and observed. Such changes discussed have been the cellularity, matrix degradation, matrix quality, and synthesis of enzymes involved in the breakdown of the matrix, including fibronectin fragments of the degraded matrix which can contribute to further degradation. The involvement of cytokines and other inflammatory mediators in the generation of vascularization and stimulation of pain receptors are still controversial but may reveal the pathway to the symptomatic conditions of IVD degeneration.
Significant back and leg symptoms develop in approximately 10%-15% of patients who have undergone a spinal decompression procedure and approximately 15%-20% of patients who have had a spinal fusion procedure for degenerative disease of the lumbar spine during the ensuing 3-5 year so that they require revision lumbar surgery. The cause for their symptoms has to be diligently looked for, as that is a main predictor of good outcome following revision surgery. Good history taking, including a detailed old chart review, repeat physical evaluation, and input from therapists--physical and psychological, neurologist, and other caregivers--should be sought. These, together with intelligent use of investigations, go a long way in helping establish a cause for failure. Furthermore, developing a revision surgical strategy is also an intellectual exercise in which a simple algorithmic approach may not always work. The process of evaluation and surgical management for failed lumbar degeneration is a science and an art that requires a great deal of understanding and commitment on the part of the surgeon. The temporal trend of improving outcomes is aided in part by emerging technologies, however, one has to be constantly aware of simple factors that influence outcome. The use of published literature and experiences of peers helps one offer appropriate surgical intervention while improving the long-term results of revision surgery of the lumbar spine.
Lumbar fusion is a common spinal surgery, for which numerous devices have been developed to aid in segment stabilization. A threaded cortical bone dowel is a machined and processed bone allograft which is one such development. Threaded cortical bone dowels are attractive because of their osteoconductive nature and the opportunity to load them with osteogenic morselized bone autograft or osteoinductive growth factors, such as bone morphogenetic proteins. Although threaded cortical bone dowels have been in clinical use for more than 5 years, they have not been the subject of a comprehensive review. The current article covers the history, preparation, uses, safety, and efficacy of threaded cortical bone dowels in lumbosacral interbody fusion.
STUDY DESIGN: In a study investigating the correlation between a set of designed criteria and judgments of surgical experience, 100 cervical magnetic resonance images from different patients were used. OBJECTIVES: To demonstrate reliable and reproducible anatomic measurements that can aid spine surgeons in selecting surgical approaches for anterior spine fusion in the cervicothoracic region. SUMMARY OF BACKGROUND DATA: Surgical approaches to the cervicothoracic junction vary among surgeons. Whereas sternotomy provides maximum exposure, less extensive approaches are preferred to minimize surgical trauma, provided surgical goals are not compromised. No quantitative criteria currently exist to determine before surgery the least invasive surgical approach for sufficiently exposing pertinent anatomy. METHODS: Thirteen geometric variables designed to be clinically practical and to expose important anatomic relations were used to evaluate 100 sagittal scout cervical magnetic resonance image sequences. An experienced spine surgeon independently rated each image for the most appropriate surgical approach to the C5-T2 region. The ratings were tested for interrater reliability using a second spine surgeon. After testing for interrater and intrarater reliability, the geometric measurements were correlated with the surgeon's selected surgical approaches for each intervertebral segment (P < 0.05). RESULTS: Instrument manubrial thoracic distances, reflecting standardized heights of intervertebral discs above or below the superior tip of the manubrium, were the most reliable, reproducible, and correlative with the choice of surgical approach. All the measurements but one, the instrument manubrial thoracic distance for T1/T2, demonstrated interrater and intrarater reliability, with an interclass correlation of at least 0.70. The primary surgeon-investigator indicated the anterior approach with sternotomy (n = 3) or the transverse cervical approach (n = 97) for the C7/T1 exposure, and the anterior approach with sternotomy (n = 43) or the transverse cervical approach (n = 57) for the T1/T2 exposure. The interrater questionnaire reliability results indicated statistical agreement between the primary surgeon-investigator and the second cervical spine surgeon at all vertebral segments evaluated. Instrument manubrial thoracic distances showed the strongest significant correlation with the surgical approach, demonstrating a statistical power of 1. For the C7/T1 exposure, the instrument manubrial thoracic distance for C7/T1 was 1.9 +/- 2 cm (95% confidence interval [CI] = 1.41 to 2.22) for the transverse cervical approach, and -3.3 +/- 1.3 cm (95% CI = -4.79 to -1.75)] for the anterior approach with sternotomy. The instrument manubrial thoracic distance measurements for C5/C6, C6/C7, and T1/T2 also showed nonoverlapping 95% confidence intervals for the transverse cervical versus the anterior approach with sternotomy for the C7/T1 exposure. For the T1/T2 exposure, all four instrument manubrial thoracic distance measurements again showed statistically significant differences between approaches, with nonoverlapping 95% confidence intervals and a statistical power of 1. In addition, the measurements elaborating the anterior-to-posterior distance of the thoracic outlet and the measurements of the angle between the planes of the intervertebral disc and the sternum also showed statistically significant differences between approaches for the T1/T2 segment, with a statistical power of at least 0.9. CONCLUSIONS: Strong correlations exist between objective measurements and the choice of surgical approach for anterior spine fusion. Among investigated anatomic relations, the instrument manubrial thoracic distance correlated most reliably with the surgeons' choice of the anterior approach. Such objective measurements represent tools that cervical spine surgeons can use to determine the surgical approach.
STUDY DESIGN: The sheep anterior lumbar spinal fusion model was used to study the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)-collagen composite in comparison with autograft to enhance spinal interbody fusion. Comparisons were drawn from temporal radiographic and end-point biomechanical and histologic data. OBJECTIVE: To analyze histologically the ability of rhBMP-2 to achieve complete arthrodesis between vertebral bodies. SUMMARY OF BACKGROUND DATA: Studies using rhBMP for enhancement of anterior interbody fusion have used numerous endpoints. However, systematic histologic evaluation of the fusion has not been conducted. METHODS: Twelve sheep underwent single-level anterior lumbar interbody fusion performed with a cylindrical fenestrated titanium interbody fusion device (INTER FIX, Medtronic Sofamor Danek, Inc., Memphis, TN). The device was filled either with rhBMP-2-collagen (n = 6) or autogenous iliac crest bone graft (n = 6). Radiologic evaluation was carried out at 2-month intervals, and all sheep were killed 6 months after surgery. Nondestructive biomechanical testing for stiffness to flexion, extension, and lateral bending moments, un-decalcified histology, and qualitative and quantitative histologic evaluation were performed. RESULTS: Radiographs revealed a bony bridge anterior to the cage in five of six rhBMP-2-treated animals, whereas it was present only in one of five in the autogenous bone graft group. Segments treated with rhBMP-2 were 20% stiffer in flexion than autograft-treated segments at 6 months. Six of six in the rhBMP-2 group and two of six in the autograft group showed complete fusion. There was a significantly higher rate of bony continuity observed at the fenestrations of the rhBMP-2 group. Three times more number of cage fenestrations in the rhBMP-2 group demonstrated "all-bone" when compared with the autograft group (P < 0.001). Further, the scar tissue in and around the autograft-treated cages was 16-fold more (P < 0.01) than that seen for rhBMP-2-treated cages. CONCLUSIONS: The study demonstrates that rhBMP-2 can lead to earlier radiologic fusion and a more consistent increased stiffness of the segments when compared with autograft in sheep anterior lumbar interbody fusion. Furthermore, a three times higher histologic fusion rate is attainable with significantly reduced fibrous tissue around the implant when rhBMP-2 is used.
Our goals in writing this article are to facilitate understanding of issues related to (1) why anterior fixation for thoracolumbar fractures are an important tool for managing these injuries, (2) when to perform these as a single procedure, or in combination with other procedures such as vertebrectomy and/or posterior stabilization and fusion, (3) to appreciate the biomechanical and design-related issues of available systems, and (4) what the clinical outcomes are following these procedures.
Previously, we have reported that nitric oxide synthases (NOSs), which generate NO, modulate fracture healing. However, the cellular sources of the NOS isoforms during the course of fracture healing have not been studied systematically. The purpose of this study was to localize the cellular distribution of NOS isoforms (inducible NOS [iNOS], endothelial NOS [eNOS], and neuronal NOS [bNOS]) by in situ hybridization and immunohistology after femoral fractures in rats. The iNOS signal was detected during the initial stages (on day 4 and day 7) of fracture healing in 52 +/- 2% (mean +/- SE, n = 7) of cells within the intramembranous region, along the edge of the periosteal callus. The iNOS signal in callus cells declined to an undetectable level on day 14. eNOS was detected during the middle stages (on day 7 and day 14) of fracture healing in cells lining the blood vessels and also in 49 +/- 3% of cells in the chondral region. The bNOS signal was found to be increased at the later stages (day 14 and day 21) of fracture healing in 51 +/- 3% of cells at the junction between fibrous tissue and cartilage within the fibrochondral region. In summary, the,expression of NOS isoforms during fracture healing was time dependent and cellular distinctive.
Many approaches are used to repair skeletal defects in reconstructive orthopaedic surgery, and bone grafting is involved in virtually every procedure. The type of bone graft used depends on the clinical scenario and the anticipated final outcome. Autogenous cancellous bone graft, with its osteogenic, osteoinductive, and osteoconductive properties, remains the standard for grafting. However, the high incidence of morbidity during autogenous graft harvest may make the acquisition of grafts from other sources desirable. The clinical applications for each type of bone graft are dictated by the structure and biochemical properties of the graft. An elegant cellular and molecular cascade follows bone transplantation. Bone graft incorporation within the host, whether autogenous or allogeneic, depends on many factors: type of graft (autogenous versus allogeneic, vascular versus nonvascular), site of transplant, quality of transplanted bone and host bone, host bed preparation, preservation techniques, systemic and local disease, and mechanical properties of the graft.