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Biomedical subjects

Safdar N Khan

Publications and source records attributed to Safdar N Khan.

At least 19 recordsLinked to original sources
PubMed2006

Surgical management of metastatic spine tumors.

Recent advances in diagnostic tests and radiologic imaging, and the development of novel chemotherapeutic agents and radiation methods have greatly altered the treatment options in patients who have spinal tumors. Improvements in fundamental understanding of the mechanisms of bone metastases, developments in spinal instrumentation, and recent introduction of recombinant bone morphogenetic proteins for spinal reconstruction offer promising strategies in selected patients. Clear applications of the fundamental surgical oncology still apply to spinal tumors. This article considers recent advances in management of the metastatic tumors to the spine.

Adolescent↗
PubMed2005

Alendronate inhibits spine fusion in a rat model.

STUDY DESIGN: A posterolateral lumbar fusion model in rats. OBJECTIVE: To study the effects of alendronate on posterolateral lumbar fusion in rats. SUMMARY OF BACKGROUND DATA: To our knowledge, there are no studies that show a significant inhibition of manual palpation-assessed spine fusion by alendronate. METHODS: A total of 75 Sprague-Dawley rats underwent intertransverse fusion with 7-tailbone autograft at L4-L5. Animals received saline (control), alendronate equivalent to human dose (dose1, 5 microg/kg/day), or 10 times the human dose (dose10, 50 microg/kg/day) via subcutaneous osmotic pumps starting the day of surgery. Eight weeks after surgery, animals were euthanized, and fusion was assessed by manual palpation. Radiographic area and optical density of fusion masses were calculated. Histomorphometry was used to assess the percentage area of fusion masses occupied by bone or marrow tissues. RESULTS: Manual palpation fusion rates were lower in alendronate groups (50% and 40%, respectively) than in the control group (95%, P = 0.002). Interobserver and intraobserver kappa values were high (0.97-1.00). There were dose-dependent and statistically significant (P < 0.001) increases in fusion mass area and optical density with increasing alendronate dose. Fusion masses in dose10 animals had significantly higher percent area of bone tissue (P = 0.01) and lower percent area of marrow elements (P < 0.001) when compared to control animals. CONCLUSIONS: Alendronate inhibits spine fusion in rats. Fusion masses in alendronate-treated animals appeared radiographically larger and denser than those in control animals despite lower fusion rates. Quantitative histomorphometry confirmed that alendronate inhibited bone graft resorption and incorporation. We recommend that patients undergoing spine arthrodesis should not take alendronate until fusion is achieved.

Alendronate↗
PubMed2005

Application of bone morphogenetic proteins in spinal fusion.

We are now entering an exciting new era in spinal surgery where the inherent osteoinductive capacity of the body has been harnessed for bone formation for therapeutic purposes. Recombinant bone morphogenetic proteins have been extensively studied in both the pre-clinical and clinical arena for spinal fusion with considerable success. The challenges facing spine surgeons now is the development of site-specific carriers and optimal doses for these growth factors. This review highlights the recent advances in this regard.

Animals↗
PubMed2004

Piriformis syndrome and low back pain: a new classification and review of the literature.

Piriformis syndrome is a common cause of low back pain. It is often not included in the differential diagnosis of back, buttock, and leg pain. Additionally it has received minimal recognition because it is often seen as a diagnosis of exclusion. Familiarity with the common elements of the syndrome should increase its recognition and facilitate the appropriate treatment. These include buttock pain and tenderness with or without electrodiagnostic or neurologic signs. Pain is exacerbated in prolonged sitting. Specific physical findings are tenderness in the sciatic notch and buttock pain in flexion, adduction, and internal rotation (FADIR) of the hip. Imaging modalities are rarely helpful, but electrophysiologic studies should confirm the diagnosis, if not immediately, then certainly in a patient re-evaluation and as such should be sought persistently. Physical therapy aims at stretching the muscle and reducing the vicious cycle of pain and spasm. It is a mainstay of conservative treatment, usually enhanced by local injections. Surgery should be reserved as a last resort in case of failure of all conservative modalities. Piriformis syndrome may constitute up to 5% of cases of low back, buttock, and leg pain. Recognition and widespread appreciation of the clinical presentation improves its early detection and accurate treatment.

Buttocks↗
PubMed2004

Spinal fusion surgery: animal models for tissue-engineered bone constructs.

Animal models have been used extensively to investigate the biology of fracture healing and spinal fusion. The goal of each spinal fusion model is to try and reproduce the correct sequence of events during osseous healing in humans. Animal models allow us the capability of dialing in fusion rates and fusion parameters depending upon the study conditions. These models have become invaluable in assessing the clinical potential of emerging technologies such as recombinant growth factors and gene therapy.

Animals↗
PubMed2004

High-dose alendronate uncouples osteoclast and osteoblast function: a study in a rat spine pseudarthrosis model.

The effect of alendronate on osteoclast and osteoblast function was studied in a novel spine pseudarthrosis model in rats. Sixty-three Sprague-Dawley rats were divided into three groups: control group (saline), therapeutic dose group (1 microg/kg/week), and one-log overdose group (10 microg/kg/week). Animals had L4-L5 posterior intertransverse process fusion with limited bone graft and were sacrificed at 2, 4, and 6 weeks. Manual palpation showed no notable differences among groups. Treatment group radiographic scores were equal to or better than control group scores and were higher than the overdose group at 2 and 6 weeks. Qualitatively, limited histologic remodeling and poor osteoclastic and osteoblastic function were noted in the alendronate treated groups. Quantitative histologic analysis showed fewer osteoclasts in the therapeutic and high-dose groups (p < 0.001). The percent osteoblasts per bone surface area was lower in the high-dose group (p < 0.05). The results suggest that the effect of alendronate was dose dependent and animal model dependent and that supranormal doses of alendronate had a deleterious effect on osteoclastic and osteoblastic function in this model.

Alendronate↗
PubMed2004

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in orthopaedic applications.

Preclinical proof-of-concept, feasibility and efficacy studies in lower animals resulted in the accumulation of data that served as a backbone for clinical trials with the recombinant, osteogenic bone morphogenetic protein-2 (BMP-2). Among the important observations was the dependence of dose and carrier on the outcome for osseous union in relation to the animal model used. Clinical outcome data for spinal applications indicate better overall results compared with traditional controls that utilised autogenous iliac crest bone graft for fusion. Parameters include less blood loss, less operating room time and costs, better fusion outcomes and increased patient satisfaction. At this juncture, the long journey from the identification of BMP-2 in demineralised bone fraction to FDA approval for use in a singular orthopaedic application has been completed. It has been demonstrated to be safe, efficacious and cost-effective, leading to increased patient satisfaction and improved clinical outcome.

Bone Development↗
PubMed2003

The molecular basis of intervertebral disk 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.

Humans↗
PubMed2003

Threaded cortical bone dowels in lumbosacral arthrodesis: a review.

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.

Bone Transplantation↗
PubMed2002

Animal models for preclinical assessment of bone morphogenetic proteins in the spine.

STUDY DESIGN: A review of the rationale behind the use of animal models for the assessment of bone morphogenetic proteins (BMPs) in the spine. OBJECTIVE: To summarize the underlying principles of animal experimentation in the context of bone morphogenetic proteins and the spine. SUMMARY OF BACKGROUND DATA: Animal models aid in the collection of important information regarding the precise mechanobiologic events that occur during spinal fusion healing. Reproducible spinal fusion models have been developed in several animal species, leading to experimentation in a controlled fashion. Reliable assessment of outcome measures for osseous healing, including histology and biomechanical testing, has made preclinical testing of innovative growth factors essential before the advance to clinical trials. METHODS: These materials have initially gone through the "burden of proof" steps: proof of concept studies, feasibility studies, and efficacy studies. RESULTS AND CONCLUSIONS: Bone morphogenetic proteins have undergone extensive scrutiny in the preclinical arena. This article summarizes the evolution of animal experimentation with BMP including the background and future directions.

Animals↗
PubMed2002

Factors predicting hospital stay, operative time, blood loss, and transfusion in patients undergoing revision posterior lumbar spine decompression, fusion, and segmental instrumentation.

STUDY DESIGN: A retrospective chart review was conducted for 112 patients who underwent revision posterior lumbar spine decompression, fusion, and segmental instrumentation. OBJECTIVE: To ascertain factors predicting hospital stay, operative time, blood loss, and transfusion in patients undergoing revision posterior lumbar spine decompression, fusion, and segmental instrumentation. SUMMARY OF BACKGROUND DATA: Posterior lumbar spine decompression and fusion with segmental instrumentation is a common procedure in the treatment of degenerative lumbar spine disorders. Many patients undergoing this procedure have had previous lumbar spine surgery, yet little is known about the factors predicting hospital stay, operative time, blood loss, and transfusion. METHODS: The charts of 112 patients (53 men and 59 women) with degenerative lumbar spinal stenosis who underwent revision surgery from March 1992 to June 1999 were reviewed. Their average age was 54 years (range, 27-84 years). All the surgeries included decompression and fusion with segmental instrumentation. The patients' demographics, comorbid conditions, factors related to previous lumbar spine surgery, diagnosis, number of levels fused, and preoperative hemoglobin and hematocrit were collected and used as the independent variables. Multiple regression analysis was used to ascertain factors predicting length of hospital stay, operative time, intraoperative blood loss, and transfusion. RESULTS: The mean length of hospital stay was 6 +/- 2.4 days, the operative time 280 +/- 62 minutes, the estimated intraoperative blood loss 1073 +/- 716 mL, and the total volume of blood transfused 1.04 +/- 1.17 U. For 63% of the patients, a blood transfusion was needed. Increasing age was the significant predictor for hospital stay (P < 0.001). The factors predicting operative time were number of levels fused (P < 0.001), diagnosis of degenerative scoliosis (P < 0.05), and excessive body weight (P < 0.01). The factors predicting intraoperative blood loss were number of levels fused (P < 0.01), body weight (P < 0.001), and high preoperative hemoglobin (P < 0.001). Both logistic and linear regression analysis showed that the factors predicting blood transfusion were number of levels fused (P < 0.01), age (P < 0.05), and low preoperative hemoglobin (P < 0.001). Other factors associated with hospital stay and blood transfusion were unemployment associated with three or more comorbid conditions and complications. The women had less intraoperative blood loss (P < 0.01), but received more transfused blood than the men (P < 0.01). CONCLUSIONS: Number of levels fused and age seem to be the most significant factors predicting hospital stay, operative time, intraoperative blood loss, and transfusion in patients undergoing revision posterior lumbar spine decompression, fusion, and segmental instrumentation.

Adult↗
PubMed2002

Preoperative magnetic resonance imaging screening for a surgical decision regarding the approach for anterior spine fusion at the cervicothoracic junction.

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.

Cervical Vertebrae↗
PubMed2002

Bone morphogenetic proteins: relevance in spine surgery.

Bone morphogenetic proteins (BMPs) are low molecular weight glycoproteins that play a vital role in the development and maturation of skeletal tissue. Bone morphogenetic protein-induced mesenchymal cell recruitment and differentiation leads to the formation of chondroblasts and osteoblasts leading to the formation of de novo bone. Overwhelming pre-clinical and clinical evidence has suggested a promising role for BMPs for anterior and posterolateral spinal fusion. Strength of this approach lies in the potential ability of these growth factors to reverse inhibitory conditions common in the clinical setting and enabling predictable fusion. However, several issues related to carriers, costs, and dosages still need to be consecutively addressed. Gene therapy techniques producing in vivo osteoinductive factors and utilizing minimally invasive approaches are attractive options being developed for the future.

Animals↗
PubMed2002

Computerized frameless stereotactic image guidance in spinal surgery.

Clinical applications of computerized frameless stereotactic image-guided spinal surgery continue to evolve. This article discusses several limiting factors regarding the use of this technology. It discusses the benefits of stereotaxy, which are better realized when there is a distortion of 'normal' anatomy because of previous surgery or severe deformity. The three-dimensional model helps the surgeon navigate the rotated and translated vertebrae. The technology can also be helpful when performing a posterior lumbar interbody fusion, to determine the orientation and depth of placement of the allograft or the cage.

Humans↗
PubMed2002

Gene therapy for spinal applications.

Gene therapy is a promising drug delivery mechanism for the treatment of spinal disorders. Currently, the technique has been most useful in enhancing growth factor therapy for spinal fusion, intervertebral disc regeneration, and spinal cord injury healing. Gene therapy allows for the high-level local production of growth factors, obviating the need for slow release carriers or continuous infusion pumps that are otherwise necessary because of the short half-lives of most peptide growth factors. Although continuous expression is desirable, growth factor therapy is usually intended to be transient. The typical expression profile of Ad vectors--at a high level over 2 weeks or so--has been ideal, leading to its widespread use in these applications. Despite the ability of Ad to deliver genes directly in vivo, however, the cell-based ex vivo approach has been used widely in spinal applications. In spinal cord injury, cells such as peripheral nerve or Schwann cells may provide a permissive substrate for axonal growth [51]. For spinal fusion and IVD regeneration, ex vivo manipulation of cells facilitates gene transfer, because bone and IVD tissue are too dense to be penetrated by injection of Ad or other vectors. The use of cells may be advantageous in these applications in which new tissue formation is the goal. Finally, the use of genetically modified cells may decrease the inflammatory reaction induced by Ad vectors. Although gene therapy for spinal disorders has been centered around Ad-mediated transfer of single growth factor genes, the options for candidate genes and vectors are growing rapidly. Ad vectors are being improved by decreasing their immunogenicity and altering their tropism [2]. Vectors based on other viruses (such as herpes, adeno-associated virus, and lentivirus) are being developed, also with lower immunogenicity and with longer durations of expression [26,67]. Regulated expression, such as with the tetracycline regulated promoter, is being developed so that genes can be turned on or off as needed. Such regulation may be sensitive even to physiologic cues in the future [68,69]. Finally, the high throughput technologies, such as the gene chip, are elucidating thousands of genes that may be good candidates for the enhancement of bone healing and IVD and spinal cord regeneration. Genes whose products not only support bone, fibrocartilage, or axon growth but also neutralize natural inhibitors or promote tissue remodeling and maturation may be good future candidates. In the future, a series of vectors with multiple genes that are regulated by physiologic cues might be used to enhance spinal fusion, restore IVD tissue, or support spinal cord healing.

Adenoviridae↗
PubMed2002

Revision strategies for lumbar pseudarthrosis.

Revision surgery for pseudarthrosis remains costly and complicated. Local and systemic factors should be corrected or improved before further surgery is performed. Careful evaluation is mandatory, and patients' expectations should be addressed fully by the surgeon before undertaking any surgical procedure. The single most important factor in achieving a successful clinical outcome in revision spine surgery is patient selection. Pseudarthrosis is still one of the most difficult conditions to assess as a source of symptoms, and not surprisingly the outcome from repair of pseudarthrosis is the most difficult to predict. In evaluation of a solid fusion, the preliminary test includes plain radiographs that include flexion and extension films. More definitive evaluation of pseudarthrosis usually requires CT with two-dimensional and possibly three-dimensional reconstruction. Adjacent levels and the status of neural structures may be evaluated via MRI scanning, discography, and myelography. After determining the presence of pseudarthrosis and ascertaining through clinical examination and evaluation the level of symptomatic pseudarthrosis, operative intervention may be considered once conservative management has failed. Posterior procedures for revision of a failed lumbar fusion have not yielded reliably successful results; however, this approach does have a significant role in the appropriately selected candidate. A combined anteroposterior approach may be more effective in restoring sagittal balance and enhancing fusion rates. The use of posterior instrumentation in light of an anterior pseudarthrosis or anterior support in light of a posterior pseudarthrosis is a viable option for treatment in these circumstances. Several osteoinductive growth factors, referred to as bone morphogenetic proteins, have been shown to induce transformation of undifferentiated mesenchymal cells into chondroblasts and osteoblasts, which results in the formation of de novo bone. Numerous animal studies have demonstrated the superiority of bone morphogenetic proteins over autogenous bone grafts in various orthopedic settings. Bone morphogenetic protein (by itself or in conjunction with autogenous bone) has been shown repeatedly to produce a better quality of spine fusion in a decreased interval of time when compared with the use of autogenous bone alone. These materials, however, remain investigational and currently are not widely used. Prevention of pseudarthrosis is the most successful treatment, although this is not always possible. Appropriate patient selection, surgical techniques, and the use of biologic implants and gene therapy in the near future will make spinal fusion a more predictable procedure to perform. Undoubtedly there is great difficulty in performing satisfactory and statistically verifiable conclusions from the available published studies. Better prospective outcomes studies are needed to improve our knowledge regarding overall patient satisfaction, function, residual pain, and health impact of the treatment of lumbar spine pseudarthrosis.

Humans↗