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Sample records for degenerative disc disease

  1. MRI Evaluation of Lumbar Disc Degenerative Disease

    PubMed Central

    Patel, Rupal; Mehta, Chetan; Patel, Narrotam

    2015-01-01

    Introduction: Lower back pain secondary to degenerative disc disease is a condition that affects young to middle-aged persons with peak incidence at approximately 40 y. MRI is the standard imaging modality for detecting disc pathology due to its advantage of lack of radiation, multiplanar imaging capability, excellent spinal soft-tissue contrast and precise localization of intervertebral discs changes. Aims and Objective: To evaluate the characterization, extent, and changes associated with the degenerative lumbar disc disease by Magnetic Resonance Imaging. Study Design: Cross-sectional and observational study. Materials and Methods: A total 109 patients of the lumbar disc degeneration with age group between 17 to 80 y were diagnosed & studied on 1.5 Tesla Magnetic Resonance Imaging machine. MRI findings like lumbar lordosis, Schmorl’s nodes, decreased disc height, disc annular tear, disc herniation, disc bulge, disc protrusion and disc extrusion were observed. Narrowing of the spinal canal, lateral recess and neural foramen with compression of nerve roots observed. Ligamentum flavum thickening and facetal arthropathy was observed. Result: Males were more commonly affected in Degenerative Spinal Disease & most of the patients show loss of lumbar lordosis. Decreased disc height was common at L5-S1 level. More than one disc involvement was seen per person. L4 – L5 disc was the most commonly involved. Annular disc tear, disc herniation, disc extrusion, narrowing of spinal canal, narrowing of lateral recess, compression of neural foramen, ligamentum flavum thickening and facetal arthropathy was common at the L4 –L5 disc level. Disc buldge was common at L3 – L4 & L4 – L5 disc level. Posterior osteophytes are common at L3 - L4 & L5 –S1 disc level. L1- L2 disc involvement and spondylolisthesis are less common. Conclusion: Lumbar disc degeneration is the most common cause of low back pain. Plain radiograph can be helpful in visualizing gross anatomic changes in

  2. MR imaging of degenerative disc disease.

    PubMed

    Farshad-Amacker, Nadja A; Farshad, Mazda; Winklehner, Anna; Andreisek, Gustav

    2015-09-01

    Magnet resonance imaging (MRI) is the most commonly used imaging modality for diagnosis of degenerative disc disease (DDD). Lack of precise observations and documentation of aspects within the complex entity of DDD might partially be the cause of poor correlation of radiographic findings to clinical symptoms. This literature review summarizes the current knowledge on MRI in DDD and outlines the diagnostic limitations. The review further sensitizes the reader toward awareness of potentially untended aspects of DDD and the interaction of DDD and endplate changes. A summary of the available classifications for DDD is provided. PMID:26094867

  3. Operative Management of Lumbar Degenerative Disc Disease.

    PubMed

    Lee, Yu Chao; Zotti, Mario Giuseppe Tedesco; Osti, Orso Lorenzo

    2016-08-01

    Lumbar degenerative disc disease is extremely common. Current evidence supports surgery in carefully selected patients who have failed non-operative treatment and do not exhibit any substantial psychosocial overlay. Fusion surgery employing the correct grafting and stabilization techniques has long-term results demonstrating successful clinical outcomes. However, the best approach for fusion remains debatable. There is some evidence supporting the more complex, technically demanding and higher risk interbody fusion techniques for the younger, active patients or patients with a higher risk of non-union. Lumbar disc arthroplasty and hybrid techniques are still relatively novel procedures despite promising short-term and mid-term outcomes. Long-term studies demonstrating superiority over fusion are required before these techniques may be recommended to replace fusion as the gold standard. Novel stem cell approaches combined with tissue engineering therapies continue to be developed in expectation of improving clinical outcomes. Results with appropriate follow-up are not yet available to indicate if such techniques are safe, cost-effective and reliable in the long-term. PMID:27559465

  4. Operative Management of Lumbar Degenerative Disc Disease

    PubMed Central

    Lee, Yu Chao; Osti, Orso Lorenzo

    2016-01-01

    Lumbar degenerative disc disease is extremely common. Current evidence supports surgery in carefully selected patients who have failed non-operative treatment and do not exhibit any substantial psychosocial overlay. Fusion surgery employing the correct grafting and stabilization techniques has long-term results demonstrating successful clinical outcomes. However, the best approach for fusion remains debatable. There is some evidence supporting the more complex, technically demanding and higher risk interbody fusion techniques for the younger, active patients or patients with a higher risk of non-union. Lumbar disc arthroplasty and hybrid techniques are still relatively novel procedures despite promising short-term and mid-term outcomes. Long-term studies demonstrating superiority over fusion are required before these techniques may be recommended to replace fusion as the gold standard. Novel stem cell approaches combined with tissue engineering therapies continue to be developed in expectation of improving clinical outcomes. Results with appropriate follow-up are not yet available to indicate if such techniques are safe, cost-effective and reliable in the long-term. PMID:27559465

  5. Total Disc Arthroplasty for Treating Lumbar Degenerative Disc Disease

    PubMed Central

    2015-01-01

    Study Design Lumber disc arthroplasty is a technological advancement that has occurred in the last decade to treat lumbar degenerative disk diseases. Purpose The aim of this retrospective study was to establish the impact and outcomes of managing patients with lumbar degenerative disk disease who have been treated with lumbar total disc arthroplasty (TDA). Overview of Literature Several studies have shown promising results following this surgery. Methods We reviewed the files of 104 patients at the Department of Neurosurgery in Colmar (France) who had been operated on by lumbar spine arthroplasty (Prodisc) between April 2002 and October 2008. Results Among the 104 patients, 67 were female and 37 were male with an average age of 33.1 years. We followed the cases for a mean of 20 months. The most frequent level of discopathy was L4-L5 with 62 patients (59.6%) followed by L5-S1 level with 52 patients (50%). Eighty-three patients suffered from low back pain, 21 of which were associated with radiculopathy. The status of 82 patients improved after surgery according to the Oswestry Disability Index score, and 92 patients returned to work. Conclusions The results indicate that TDA is a good alternative treatment for lumbar spine disk disease, particularly for patients with disabling and chronic low back pain. This technique contributes to improve living conditions with correct patient selection for surgery. PMID:25705336

  6. Total Disc Replacement in Lumbar Degenerative Disc Diseases

    PubMed Central

    2015-01-01

    More than 10 years have passed since lumbar total disc replacement (LTDR) was introduced for the first time to the world market for the surgical management of lumbar degenerative disc disease (DDD). It seems like the right time to sum up the relevant results in order to understand where LTDR stands on now, and is heading forward to. The pathogenesis of DDD has been currently settled, but diagnosis and managements are still controversial. Fusion is recognized as golden standard of surgical managements but has various kinds of shortcomings. Lately, LTDR has been expected to replace fusion surgery. A great deal of LTDR reports has come out. Among them, more than 5-year follow-up prospective randomized controlled studies including USA IDE trials were expected to elucidate whether for LTDR to have therapeutic benefit compared to fusion. The results of these studies revealed that LTDR was not inferior to fusion. Most of clinical studies dealing with LTDR revealed that there was no strong evidence for preventive effect of LTDR against symptomatic degenerative changes of adjacent segment disease. LTDR does not have shortcomings associated with fusion. However, it has a potentiality of the new complications to occur, which surgeons have never experienced in fusion surgeries. Consequently, longer follow-up should be necessary as yet to confirm the maintenance of improved surgical outcome and to observe any very late complications. LTDR still may get a chance to establish itself as a substitute of fusion both nominally and virtually if it eases the concerns listed above. PMID:26713139

  7. Prosthetic lumbar disc replacement for degenerative disc disease.

    PubMed

    Kulkarni, Arvind G; Diwan, Ashish D

    2005-12-01

    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. PMID:16565543

  8. Prognosis of intervertebral disc loss from diagnosis of degenerative disc disease

    NASA Astrophysics Data System (ADS)

    Li, S.; Lin, A.; Tay, K.; Romano, W.; Osman, Said

    2015-03-01

    Degenerative Disc Disease (DDD) is one of the most common causes of low back pain, and is a major factor in limiting the quality of life of an individual usually as they enter older stages of life, the disc degeneration reduces the shock absorption available which in turn causes pain. Disc loss is one of the central processes in the pathogenesis of DDD. In this study, we investigated whether the image texture features quantified from magnetic resonance imaging (MRI) could be appropriate markers for diagnosis of DDD and prognosis of inter-vertebral disc loss. The main objective is to use simple image based biomarkers to perform prognosis of spinal diseases using non-invasive procedures. Our results from 65 subjects proved the higher success rates of the combination marker compared to the individual markers and in the future, we will extend the study to other spine regions to allow prognosis and diagnosis of DDD for a wider region.

  9. How Does Lumbar Degenerative Disc Disease Affect the Disc Deformation at the Cephalic Levels In Vivo?

    PubMed Central

    Wang, Shaobai; Xia, Qun; Passias, Peter; Li, Weishi; Wood, Kirkham; Li, Guoan

    2013-01-01

    Study Design Case-control study. Objective . To evaluate the effect of lumbar degenerative disc disease (DDD) on the disc deformation at the adjacent level and at the level one above the adjacent level during end ranges of lumbar motion. Summary of Background Data It has been reported that in patients with DDD, the intervertebral discs adjacent to the diseased levels have a greater tendency to degenerate. Although altered biomechanics have been suggested to be the causative factors, few data have been reported on the deformation characteristics of the adjacent discs in patients with DDD. Methods Ten symptomatic patients with discogenic low back pain between L4 and S1 and with healthy discs at the cephalic segments were involved. Eight healthy subjects recruited in our previous studies were used as a reference comparison. The in vivo kinematics of L3–L4 (the cephalic adjacent level to the degenerated discs) and L2–L3 (the level one above the adjacent level) lumbar discs of both groups were obtained using a combined magnetic resonance imaging and dual fluoroscopic imaging technique at functional postures. Deformation characteristics, in terms of areas of minimal deformation (defined as less than 5%), deformations at the center of the discs, and maximum tensile and shear deformations, were compared between the two groups at the two disc levels. Results In the patients with DDD, there were significantly smaller areas of minimal disc deformation at L3–L4 and L2–L3 than the healthy subjects (18% compared with 45% of the total disc area, on average). Both L2–L3 and L3–L4 discs underwent larger tensile and shear deformations in all postures than the healthy subjects. The maximum tensile deformations were higher by up to 23% (of the local disc height in standing) and the maximum shear deformations were higher by approximately 25% to 40% (of the local disc height in standing) compared with those of the healthy subjects. Conclusion Both the discs of the adjacent

  10. Lumbar Degenerative Disc Disease: Current and Future Concepts of Diagnosis and Management

    PubMed Central

    Taher, Fadi; Essig, David; Lebl, Darren R.; Hughes, Alexander P.; Sama, Andrew A.; Cammisa, Frank P.; Girardi, Federico P.

    2012-01-01

    Low back pain as a result of degenerative disc disease imparts a large socioeconomic impact on the health care system. Traditional concepts for treatment of lumbar disc degeneration have aimed at symptomatic relief by limiting motion in the lumbar spine, but novel treatment strategies involving stem cells, growth factors, and gene therapy have the theoretical potential to prevent, slow, or even reverse disc degeneration. Understanding the pathophysiological basis of disc degeneration is essential for the development of treatment strategies that target the underlying mechanisms of disc degeneration rather than the downstream symptom of pain. Such strategies ideally aim to induce disc regeneration or to replace the degenerated disc. However, at present, treatment options for degenerative disc disease remain suboptimal, and development and outcomes of novel treatment options currently have to be considered unpredictable. PMID:22567411

  11. Short aggrecan gene repetitive alleles associated with lumbar degenerative disc disease in Turkish patients.

    PubMed

    Eser, O; Eser, B; Cosar, M; Erdogan, M O; Aslan, A; Yıldız, H; Solak, M; Haktanır, A

    2011-01-01

    We investigated a possible association between aggrecan gene polymorphism and lumbar degenerative disc disease in Turkish patients. One hundred 20-30-year-old patients with or without low back pain were selected for the study. Lumbar magnetic resonance imaging was performed on all patients. The patient group had low back pain clinically and degenerative disc disease radiographically. The control group included patients with and without low back pain: all were negative radiographically for degenerative disc disease. Genomic DNA was extracted from all participants. A PCR assay were used to evaluate variable number of tandem repeat polymorphism of aggrecan gene alleles to determine if there was any correlation with degenerative disc disease. Significant associations were found between short repeated alleles of the aggrecan gene and severe disc degeneration. A significant association was also found between short repeated alleles of the aggrecan gene and multilevel disc herniation as well as extrusion and sequestration types of disc herniation. In Turkish population, short repeated alleles of the aggrecan gene are associated with increased disc degeneration and disc herniation. PMID:21948754

  12. Treatment of multilevel degenerative disc disease with intradiscal electrothermal therapy.

    PubMed

    Malik, K

    2007-04-01

    Intradiscal electrothermal therapy is a frequently performed procedure for the pain of internal disc disruption. It is typically performed on one to two discs; the discal treatment is followed by a long period of rest and rehabilitation. In patients with multilevel disc disease, intradiscal electrothermal therapy is either not contemplated or only one to two discs are treated at a time. This approach therefore either denies these patients the potential benefits of intradiscal electrothermal therapy or significantly prolongs the period of pain and disability. A 25-year-old female patient presented with internal disc disruption at four lumbar disc levels, diagnosed by provocative discography and post discography CT scan. All these discs were treated simultaneously by intradiscal electrothermal therapy. The patient tolerated the procedure well and responded favourably with significant and prolonged decrease in her symptoms. She reported sustained reduction in her pain and showed no clinical evidence of early neurological or infectious complications during 18 months of follow-up. This report indicates that intradiscal electrothermal therapy can be performed at multiple levels at a single sitting, compared to intradiscal electrothermal therapy performed at one to two discs at a time, this approach may obviate the need for surgery and may reduce the duration of pain and disability incurred. However, the influence of multilevel intradiscal electrothermal therapy on long-term complications or outcome is not known. PMID:17444324

  13. Intervertebral Fusion with Mobile Microendoscopic Discectomy for Lumbar Degenerative Disc Disease.

    PubMed

    Xu, Bao-Shan; Liu, Yue; Xu, Hai-Wei; Yang, Qiang; Ma, Xin-Long; Hu, Yong-Cheng

    2016-05-01

    The aim of this article is to introduce a technique for lumbar intervertebral fusion that incorporates mobile microendoscopic discectomy (MMED) for lumbar degenerative disc disease. Minimally invasive transforaminal lumbar interbody fusion is frequently performed to treat degenerative diseases of the lumbar spine; however, the scope of such surgery and vision is limited by what the naked eye can see through the expanding channel system. To expand the visual scope and reduce trauma, we perform lumbar intervertebral fusion with the aid of a MMED system that provides a wide field through freely tilting the surgical instrument and canals. We believe that this technique is a good option for treating lumbar degenerative disc disease that requires lumbar intervertebral fusion. PMID:27384734

  14. Total disc replacement surgery for symptomatic degenerative lumbar disc disease: a systematic review of the literature.

    PubMed

    van den Eerenbeemt, Karin D; Ostelo, Raymond W; van Royen, Barend J; Peul, Wilco C; van Tulder, Maurits W

    2010-08-01

    The objective of this study is to evaluate the effectiveness and safety of total disc replacement surgery compared with spinal fusion in patients with symptomatic lumbar disc degeneration. Low back pain (LBP), a major health problem in Western countries, can be caused by a variety of pathologies, one of which is degenerative disc disease (DDD). When conservative treatment fails, surgery might be considered. For a long time, lumbar fusion has been the "gold standard" of surgical treatment for DDD. Total disc replacement (TDR) has increased in popularity as an alternative for lumbar fusion. A comprehensive systematic literature search was performed up to October 2008. Two reviewers independently checked all retrieved titles and abstracts, and relevant full text articles for inclusion. Two reviewers independently assessed the risk of bias of included studies and extracted relevant data and outcomes. Three randomized controlled trials and 16 prospective cohort studies were identified. In all three trials, the total disc replacement was compared with lumbar fusion techniques. The Charité trial (designed as a non-inferiority trail) was considered to have a low risk of bias for the 2-year follow up, but a high risk of bias for the 5-year follow up. The Charité artificial disc was non-inferior to the BAK Interbody Fusion System on a composite outcome of "clinical success" (57.1 vs. 46.5%, for the 2-year follow up; 57.8 vs. 51.2% for the 5-year follow up). There were no statistically significant differences in mean pain and physical function scores. The Prodisc artificial disc (also designed as a non-inferiority trail) was found to be statistically significant more effective when compared with the lumbar circumferential fusion on the composite outcome of "clinical success" (53.4 vs. 40.8%), but the risk of bias of this study was high. Moreover, there were no statistically significant differences in mean pain and physical function scores. The Flexicore trial, with a high

  15. Total disc replacement surgery for symptomatic degenerative lumbar disc disease: a systematic review of the literature

    PubMed Central

    van den Eerenbeemt, Karin D.; van Royen, Barend J.; Peul, Wilco C.; van Tulder, Maurits W.

    2010-01-01

    The objective of this study is to evaluate the effectiveness and safety of total disc replacement surgery compared with spinal fusion in patients with symptomatic lumbar disc degeneration. Low back pain (LBP), a major health problem in Western countries, can be caused by a variety of pathologies, one of which is degenerative disc disease (DDD). When conservative treatment fails, surgery might be considered. For a long time, lumbar fusion has been the “gold standard” of surgical treatment for DDD. Total disc replacement (TDR) has increased in popularity as an alternative for lumbar fusion. A comprehensive systematic literature search was performed up to October 2008. Two reviewers independently checked all retrieved titles and abstracts, and relevant full text articles for inclusion. Two reviewers independently assessed the risk of bias of included studies and extracted relevant data and outcomes. Three randomized controlled trials and 16 prospective cohort studies were identified. In all three trials, the total disc replacement was compared with lumbar fusion techniques. The Charité trial (designed as a non-inferiority trail) was considered to have a low risk of bias for the 2-year follow up, but a high risk of bias for the 5-year follow up. The Charité artificial disc was non-inferior to the BAK® Interbody Fusion System on a composite outcome of “clinical success” (57.1 vs. 46.5%, for the 2-year follow up; 57.8 vs. 51.2% for the 5-year follow up). There were no statistically significant differences in mean pain and physical function scores. The Prodisc artificial disc (also designed as a non-inferiority trail) was found to be statistically significant more effective when compared with the lumbar circumferential fusion on the composite outcome of “clinical success” (53.4 vs. 40.8%), but the risk of bias of this study was high. Moreover, there were no statistically significant differences in mean pain and physical function scores. The Flexicore trial

  16. Efficacy of a Human Amniotic Tissue-derived Allograft, NuCel, in Patients Undergoing Posteriolateral Lumbar Fusions for Degenerative Disc Disease

    ClinicalTrials.gov

    2016-03-28

    Lumbar Degenerative Disc Disease; Spinal Stenosis; Spondylolisthesis; Spondylosis; Intervertebral Disk Displacement; Intervertebral Disk Degeneration; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Spondylolysis

  17. Artificial Discs for Lumbar and Cervical Degenerative Disc Disease –Update

    PubMed Central

    2006-01-01

    Executive Summary Objective To assess the safety and efficacy of artificial disc replacement (ADR) technology for degenerative disc disease (DDD). Clinical Need Degenerative disc disease is the term used to describe the deterioration of 1 or more intervertebral discs of the spine. The prevalence of DDD is roughly described in proportion to age such that 40% of people aged 40 years have DDD, increasing to 80% among those aged 80 years or older. Low back pain is a common symptom of lumbar DDD; neck and arm pain are common symptoms of cervical DDD. Nonsurgical treatments can be used to relieve pain and minimize disability associated with DDD. However, it is estimated that about 10% to 20% of people with lumbar DDD and up to 30% with cervical DDD will be unresponsive to nonsurgical treatments. In these cases, surgical treatment is considered. Spinal fusion (arthrodesis) is the process of fusing or joining 2 bones and is considered the surgical gold standard for DDD. Artificial disc replacement is the replacement of the degenerated intervertebral disc with an artificial disc in people with DDD of the lumbar or cervical spine that has been unresponsive to nonsurgical treatments for at least 6 months. Unlike spinal fusion, ADR preserves movement of the spine, which is thought to reduce or prevent the development of adjacent segment degeneration. Additionally, a bone graft is not required for ADR, and this alleviates complications, including bone graft donor site pain and pseudoarthrosis. It is estimated that about 5% of patients who require surgery for DDD will be candidates for ADR. Review Strategy The Medical Advisory Secretariat conducted a computerized search of the literature published between 2003 and September 2005 to answer the following questions: What is the effectiveness of ADR in people with DDD of the lumbar or cervical regions of the spine compared with spinal fusion surgery? Does an artificial disc reduce the incidence of adjacent segment degeneration (ASD

  18. Hybrid Surgery of Multilevel Cervical Degenerative Disc Disease : Review of Literature and Clinical Results

    PubMed Central

    Lee, Sang-Bok; Kim, Jong-Youn; Yoo, Do-Sung; Lee, Tae-Gyu; Huh, Pil-Woo

    2012-01-01

    Objective In the present study, we evaluated the effect, safety and radiological outcomes of cervical hybrid surgery (cervical disc prosthesis replacement at one level, and interbody fusion at the other level) on the multilevel cervical degenerative disc disease (DDD). Methods Fifty-one patients (mean age 46.7 years) with symptomatic multilevel cervical spondylosis were treated using hybrid surgery (HS). Clinical [neck disability index (NDI) and Visual Analogue Scale (VAS) score] and radiologic outcomes [range of motion (ROM) for cervical spine, adjacent segment and arthroplasty level] were evaluated at routine postoperative intervals of 1, 6, 12, 24 months. Review of other similar studies that examined the HS in multilevel cervical DDD was performed. Results Out of 51 patients, 41 patients received 2 level hybrid surgery and 10 patients received 3 level hybrid surgery. The NDI and VAS score were significantly decreased during the follow up periods (p<0.05). The cervical ROM was recovered at 6 and 12 month postoperatively and the mean ROM of inferior adjacent segment was significantly larger than that of superior adjacent segments after surgery. The ROM of the arthoplasty level was preserved well during the follow up periods. No surgical and device related complications were observed. Conclusion Hybrid surgery is a safe and effective alternative to fusion for the management of multilevel cervical spondylosis. PMID:23323165

  19. Association between nutritional status and Modic classification in degenerative disc disease.

    PubMed

    Seyithanoglu, Hakan; Aydin, Teoman; Taşpınar, Ozgur; Camli, Adil; Kiziltan, Huriye; Eris, Ali Hikmet; Hocaoglu, Ilknur Turk; Ozder, Aclan; Denizli, Ebru; Kepekci, Muge; Keskin, Yasar; Mutluer, Ahmet Serdar

    2016-04-01

    [Purpose] This study was conducted to examine the association between Modic classification and the eating habits in patients with degenerative disc disease (DDD) and to determine the influence of nutrition on disease severity. [Subjects and Methods] Sixty patients with DDD visiting a low back pain outpatient clinic were enrolled. Through face-to-face interviews, they completed questionnaires regarding their demographics, disease activity, smoking and alcohol use, concomitant diseases, disease duration, and nutritional status.Exclusion criteria were age <20 years or >65 years, other comorbidities, missing MRI data, and inability to speak Turkish. [Results] Forty patients were finally included in the study. The frequency with which they consumed water, salt, fast food, eggs, milk, yogurt, cheese, whole wheat bread, white bread, butter, and margarine was recorded. A weak negative correlation was observed between the Modic types and fish and egg consumption. [Conclusion] Modic changes, which indicate the severity of DDD, seem to be correlated to patients' dietary habits. However, studies with comparison groups and larger samples are needed to confirm our promising results before any cause-and-effect relationship can be proposed. PMID:27190462

  20. Association between nutritional status and Modic classification in degenerative disc disease

    PubMed Central

    Seyithanoglu, Hakan; Aydin, Teoman; Taşpınar, Ozgur; Camli, Adil; Kiziltan, Huriye; Eris, Ali Hikmet; Hocaoglu, Ilknur Turk; Ozder, Aclan; Denizli, Ebru; Kepekci, Muge; Keskin, Yasar; Mutluer, Ahmet Serdar

    2016-01-01

    [Purpose] This study was conducted to examine the association between Modic classification and the eating habits in patients with degenerative disc disease (DDD) and to determine the influence of nutrition on disease severity. [Subjects and Methods] Sixty patients with DDD visiting a low back pain outpatient clinic were enrolled. Through face-to-face interviews, they completed questionnaires regarding their demographics, disease activity, smoking and alcohol use, concomitant diseases, disease duration, and nutritional status.Exclusion criteria were age <20 years or >65 years, other comorbidities, missing MRI data, and inability to speak Turkish. [Results] Forty patients were finally included in the study. The frequency with which they consumed water, salt, fast food, eggs, milk, yogurt, cheese, whole wheat bread, white bread, butter, and margarine was recorded. A weak negative correlation was observed between the Modic types and fish and egg consumption. [Conclusion] Modic changes, which indicate the severity of DDD, seem to be correlated to patients’ dietary habits. However, studies with comparison groups and larger samples are needed to confirm our promising results before any cause-and-effect relationship can be proposed. PMID:27190462

  1. Intervertebral disc disease.

    PubMed

    Simpson, S T

    1992-07-01

    This article describes the functional anatomy of intervertebral discs and their relationship to the vertebrae and spinal cord. The pathologic events and clinical complications of intervertebral disc disease are described. A discussion of proper staging of disc disease and appropriate conservative management of degenerative disc disease is included. PMID:1641922

  2. Degenerative Nerve Diseases

    MedlinePlus

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many ... viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ...

  3. Cost Utility Analysis of the Cervical Artificial Disc vs Fusion for the Treatment of 2-Level Symptomatic Degenerative Disc Disease: 5-Year Follow-up

    PubMed Central

    Yang, Zhuo; Nunley, Pierce; Stone, Marcus B.; Lee, Darrin; Kim, Kee D.

    2016-01-01

    BACKGROUND: The cervical total disc replacement (cTDR) was developed to treat cervical degenerative disc disease while preserving motion. OBJECTIVE: Cost-effectiveness of this intervention was established by looking at 2-year follow-up, and this update reevaluates our analysis over 5 years. METHODS: Data were derived from a randomized trial of 330 patients. Data from the 12-Item Short Form Health Survey were transformed into utilities by using the SF-6D algorithm. Costs were calculated by extracting diagnosis-related group codes and then applying 2014 Medicare reimbursement rates. A Markov model evaluated quality-adjusted life years (QALYs) for both treatment groups. Univariate and multivariate sensitivity analyses were conducted to test the stability of the model. The model adopted both societal and health system perspectives and applied a 3% annual discount rate. RESULTS: The cTDR costs $1687 more than anterior cervical discectomy and fusion (ACDF) over 5 years. In contrast, cTDR had $34 377 less productivity loss compared with ACDF. There was a significant difference in the return-to-work rate (81.6% compared with 65.4% for cTDR and ACDF, respectively; P = .029). From a societal perspective, the incremental cost-effective ratio (ICER) for cTDR was −$165 103 per QALY. From a health system perspective, the ICER for cTDR was $8518 per QALY. In the sensitivity analysis, the ICER for cTDR remained below the US willingness-to-pay threshold of $50 000 per QALY in all scenarios (−$225 816 per QALY to $22 071 per QALY). CONCLUSION: This study is the first to report the comparative cost-effectiveness of cTDR vs ACDF for 2-level degenerative disc disease at 5 years. The authors conclude that, because of the negative ICER, cTDR is the dominant modality. ABBREVIATIONS: ACDF, anterior cervical discectomy and fusion AWP, average wholesale price CE, cost-effectiveness CEA, cost-effectiveness analysis CPT, Current Procedural Terminology cTDR, cervical total disc

  4. One decade follow up after nucleoplasty in the management of degenerative disc disease causing low back pain and radiculopathy

    PubMed Central

    Cincu, Rafael; Lorente, Francisco de Asis; Gomez, Joaquin; Eiras, Jose; Agrawal, Amit

    2015-01-01

    Objectives: Nucleoplasty is a minimally invasive procedure that is developed to treat patients with symptomatic, but contained disc herniations or bulging discs. The purpose of this study was to evaluate a decade follow-up of coblation nucleoplasty treatment for protruded lumbar intervertebral disc. Methods: In this retrospective study there a total 50 patients who underwent intradiscal coblation therapy for symptomatic, but contained lumbar degenerative disc disease were included. Relief of low back pain, leg pain and numbness after the operation were assessed by visual analog pain scale (VAS). Function of lower limb and daily living of patients were evaluated by the Oswestry disability index (ODI) and subjective global rating of overall satisfaction were recorded and analyzed. Results: There were 27 male and 23 female with followup mean follow up of 115 months (range 105–130 months) with a mean age was 52 years (range 26–74 years). Analgesic consumption was reduced or stopped in 90% of these cases after 1 year. At 24 months follow up VAS was four points and ODI was 7.2. In three patients, we repeated the cool ablation after 36 months, at L3–4 level in two cases. Ten patients continue to be asymptomatic after 114 months of intervention. There were no complications with the procedure including nerve root injury, discitis or allergic reactions. Conclusions: Nucleoplasty may provide intermittent relief in contained disc herniation without significant complications and minimal morbidity. In accordance with the literature the evidence for intradiscal coablation therapy is moderate in managing chronic discogenic low back pain; nucleoplasty appears to be safe and effective. PMID:25767571

  5. Degenerative Nerve Diseases

    MedlinePlus

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...

  6. Hybrid surgery versus anterior cervical discectomy and fusion for multilevel cervical degenerative disc diseases: a meta-analysis.

    PubMed

    Tian, Peng; Fu, Xin; Li, Zhi-Jun; Sun, Xiao-Lei; Ma, Xin-Long

    2015-01-01

    The objective of this meta-analysis is to compare hybrid surgery (HS) and cervical discectomy and fusion (ACDF) for multilevel cervical degenerative disc diseases (DDD). Systematic searches of all published studies through March 2015 were identified from Cochrane Library, Medline, PubMed, Embase, ScienceDirect, CNKI, WANFANG DATA and CQVIP. Randomized controlled trials (RCTs) and non-RCTs involving HS and ACDF for multilevel DDD were included. All literature was searched and assessed by two independent reviewers according to the standard of Cochrane systematic review. Data of functional and radiological outcomes in two groups were pooled, which was then analyzed by RevMan 5.2 software. One RCT and four non-RCTs encompassing 160 patients met the inclusion criteria. Meta-analysis revealed significant differences in blood loss (p = 0.005), postoperative C2-C7 ROM (p = 0.002), ROM of superior adjacent segment (p < 0.00001) and ROM of inferior adjacent segment (p = 0.0007) between the HS group and the ACDF group. No significant differences were found regarding operation time (p = 0.75), postoperative VAS (p = 0.18) and complications (p = 0.73) between the groups. Hybrid surgery demonstrated excellent clinical efficacy and radiological results. Postoperative C2-C7 ROM was closer to the physiological status. No decrease in the ROM of the adjacent segment was noted in the hybrid surgery group. PMID:26307360

  7. Association of rs2228570 polymorphism of vitamin D receptor gene with degenerative disc disease: a meta-analysis involving 2947 subjects

    PubMed Central

    Zong, Qiang; Ni, Dongkui; Li, Lijun; Shi, Yubo

    2015-01-01

    This study aimed to explore the association between the rs2228570 polymorphism in the vitamin D receptor gene and degenerative disc disease (IDD), especially in European. We perform a meta-analysis to analyze the association after searching the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed, Medline and EMBASE databases. And odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. A total of 10 studies involving 1,465 cases and 1,482 controls were included in the meta-analysis. Overall, there was not significant risk between rs2228570 polymorphism and degenerative disc disease in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by others indicates an association between IDD and the FF genotype (OR=0.62, 95% CI=0.43- 0.90, P=0.486) in age =40, and the F allele (OR=0.84, 95% CI=0.73-0.96, P=0.992), FF genotype (OR=0.78, 95% CI=0.65-0.93, P=0.853) in sample size > 300, and ff genotype (OR=0.91, 95% CI=1.11-3.29, P=0.783), FF genotype (OR=0.70, 95% CI=0.51-0.96, P=0.258) in Northern European. This meta-analysis suggested that the rs2228570 polymorphism may not be associated with degenerative disc disease. However, there existed some diversities, especially in age < 40, sample size > 300, countries in Northern Europe, suggesting that carrying the VDR FokI F allele may be a protective factor against IDD development. But a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease. PMID:26885185

  8. Clinical and radiologic comparison of dynamic cervical implant arthroplasty and cervical total disc replacement for single-level cervical degenerative disc disease.

    PubMed

    Shichang, Liu; Yueming, Song; Limin, Liu; Lei, Wang; Zhongjie, Zhou; Chunguang, Zhou; Xi, Yang

    2016-05-01

    Anterior cervical discectomy and fusion, to date the most successful spine procedure for the surgical treatment of cervical radiculopathy, has limitations that have led to the development of non-fusion cervical procedures, such as cervical total disc replacement (TDR) and dynamic cervical implant (DCI) arthroplasty. We compared the clinical and radiological results of DCI and cervical TDR for the treatment of single-level cervical degenerative disc disease in Chinese patients. A retrospective review of 179 patients with cervical spondylotic myelopathy who underwent DCI or TDR between April 2010 and October 2012 was conducted, and 152 consecutive patients (67 patients single-level DCI and 85 single-level TDR) who completed at least 2years of follow-up were included. Clinical and radiological assessments were performed preoperatively and at 1week and 3, 6, 12, and 24months postoperatively. The most common operative level was C5/C6 (49.3%). The differences in blood loss, duration of surgery, and duration of hospitalization were not statistically significant. The Japanese Orthopaedic Association scale, Visual Analog Scale, Neck Disability Index, and Short Form-36 scores improved significantly after surgery in both the DCI and TDR groups (P<0.05), but the differences were not statistically significant at the final follow-up. The rate of occurrence of heterotopic ossification was 22.4% and 28.2% in the DCI and TDR groups, respectively. As an effective non-fusion technique, DCI is a more economical procedure. Further prospective, randomized studies with long-term follow-up periods are needed to determine the long-term effects. PMID:26928156

  9. Clinical and radiologic comparison of dynamic cervical implant arthroplasty versus anterior cervical discectomy and fusion for the treatment of cervical degenerative disc disease.

    PubMed

    Li, Zhonghai; Yu, Shunzhi; Zhao, Yantao; Hou, Shuxun; Fu, Qiang; Li, Fengning; Hou, Tiesheng; Zhong, Hongbin

    2014-06-01

    This study compared the clinical and radiological outcomes of dynamic cervical implant (DCI; Scient'x, Villers-Bretonneux, France) arthroplasty versus anterior cervical discectomy and fusion (ACDF) for the treatment of cervical degenerative disc disease. This prospective cohort study enrolled patients with single-level cervical degenerative disc disease who underwent DCI arthroplasty or ACDF between September 2009 and June 2011. Patients were followed up for more than 2years. Clinical evaluation included the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), Neck Disability Index (NDI), Japan Orthopedic Association (JOA) score, and visual analog scale (VAS) scores for neck and arm pain. Radiological assessments included segmental range of motion (ROM), overall ROM (C2-C7), disc height (DHI), and changes in adjacent disc spaces. The VAS, SF-36, JOA, and NDI scores improved significantly after surgery in both the DCI and ACDF groups. The VAS, JOA, and SF-36 scores were not significantly different between the DCI and ACDF groups at the final follow-up. The segmental ROM at the treated level and overall ROM increased significantly after surgery in the DCI group, but the ROM in the adjacent cephalad and caudal segments did not change significantly. The mean DHI at the treated level was significantly restored after surgery in both groups. Five patients (12.8%) in the DCI group showed new signs of adjacent segment degeneration. These results indicate that DCI is an effective, reliable, and safe procedure for the treatment of cervical degenerative disc disease. However, there is no definitive evidence that DCI arthroplasty has better intermediate-term results than ACDF. PMID:24411326

  10. Hybrid surgery versus anterior cervical discectomy and fusion for multilevel cervical degenerative disc diseases: a meta-analysis

    PubMed Central

    Tian, Peng; Fu, Xin; Li, Zhi-Jun; Sun, Xiao-Lei; Ma, Xin-Long

    2015-01-01

    The objective of this meta-analysis is to compare hybrid surgery (HS) and cervical discectomy and fusion (ACDF) for multilevel cervical degenerative disc diseases (DDD). Systematic searches of all published studies through March 2015 were identified from Cochrane Library, Medline, PubMed, Embase, ScienceDirect, CNKI, WANFANG DATA and CQVIP. Randomized controlled trials (RCTs) and non-RCTs involving HS and ACDF for multilevel DDD were included. All literature was searched and assessed by two independent reviewers according to the standard of Cochrane systematic review. Data of functional and radiological outcomes in two groups were pooled, which was then analyzed by RevMan 5.2 software. One RCT and four non-RCTs encompassing 160 patients met the inclusion criteria. Meta-analysis revealed significant differences in blood loss (p = 0.005), postoperative C2–C7 ROM (p = 0.002), ROM of superior adjacent segment (p < 0.00001) and ROM of inferior adjacent segment (p = 0.0007) between the HS group and the ACDF group. No significant differences were found regarding operation time (p = 0.75), postoperative VAS (p = 0.18) and complications (p = 0.73) between the groups. Hybrid surgery demonstrated excellent clinical efficacy and radiological results. Postoperative C2–C7 ROM was closer to the physiological status. No decrease in the ROM of the adjacent segment was noted in the hybrid surgery group. PMID:26307360

  11. Effects of age, replicative lifespan and growth rate of human nucleus pulposus cells on selecting age range for cell-based biological therapies for degenerative disc diseases.

    PubMed

    Lee, J S; Lee, S M; Jeong, S W; Sung, Y G; Lee, J H; Kim, K W

    2016-07-01

    Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases. PMID:27149303

  12. Early results and review of the literature of a novel hybrid surgical technique combining cervical arthrodesis and disc arthroplasty for treating multilevel degenerative disc disease: opposite or complementary techniques?

    PubMed Central

    Assietti, Roberto; Corbino, Leonardo; Olindo, Giuseppe; Foti, Pietro V.; Russo, Vittorio; Albanese, Vincenzo

    2009-01-01

    We report the clinical and radiological results on the safety and efficacy of an unusual surgical strategy coupling anterior cervical discectomy and fusion and total disc replacement in a single-stage procedure, in patients with symptomatic, multilevel cervical degenerative disc disease (DDD). The proposed hybrid, single-stage, fusion–nonfusion technique aims either at restoring or maintaining motion where appropriate or favouring bony fusion when indicated by degenerative changes. Twenty-four patients (mean age 46.7 years) with symptomatic, multilevel DDD, either soft disc hernia or different stage spondylosis per single level, with predominant anterior myeloradicular compression and absence of severe alterations of cervical spine sagittal alignment, have been operated using such hybrid technique. Fifteen patients underwent a two-level surgery, seven patients received a three-level surgery and two a four-level procedure, for a total of 59 implanted devices (27 disc prostheses and 32 cages). Follow-up ranged between 12 and 40 months (mean 23.8 months). In all but one patient clinical follow-up (neurological examination, Nurick scale, NDI, SF-36) demonstrated significant improvement; radiological evaluation showed functioning disc prostheses (total range of motion 3–15°) and fusion through cages. None of the patients needed revision surgery for persisting or recurring symptoms, procedure-related complications or devices dislocations. To the authors’ best knowledge, this is the first study with the longest available follow-up describing a different concept in the management of cervical multilevel DDD. Although larger series with longer follow-up are needed, in selected cases of symptomatic multilevel DDD, the proposed surgical strategy appears to be a safe and reliable application of combined arthroplasty and arthrodesis during a single surgical procedure. PMID:19415346

  13. Combined transforaminal lumbar interbody fusion with posterolateral instrumented fusion for degenerative disc disease can be a safe and effective treatment for lower back pain

    PubMed Central

    Deukmedjian, Ara J; Cianciabella, Augusto J; Cutright, Jason; Deukmedjian, Arias

    2015-01-01

    Background: Lumbar fusion is a proven treatment for chronic lower back pain (LBP) in the setting of symptomatic spondylolisthesis and degenerative scoliosis; however, fusion is controversial when the primary diagnosis is degenerative disc disease (DDD). Our objective was to evaluate the safety and effectiveness of lumbar fusion in the treatment of LBP due to DDD. Materials and Methods: Two-hundred and five consecutive patients with single or multi-level DDD underwent lumbar decompression and instrumented fusion for the treatment of chronic LBP between the years of 2008 and 2011. The primary outcome measures in this study were back and leg pain visual analogue scale (VAS), patient reported % resolution of preoperative back pain and leg pain, reoperation rate, perioperative complications, blood loss and hospital length of stay (LOS). Results: The average resolution of preoperative back pain per patient was 84% (n = 205) while the average resolution of preoperative leg pain was 90% (n = 190) while a mean follow-up period of 528 days (1.5 years). Average VAS for combined back and leg pain significantly improved from a preoperative value of 9.0 to a postoperative value of 1.1 (P ≤ 0.0001), a change of 7.9 points for the cohort. The average number of lumbar disc levels fused per patient was 2.3 (range 1-4). Median postoperative LOS in the hospital was 1.2 days. Average blood loss was 108 ml perfused level. Complications occurred in 5% of patients (n = 11) and the rate of reoperation for symptomatic adjacent segment disease was 2% (n = 4). Complications included reoperation at index level for symptomatic pseudoarthrosis with hardware failure (n = 3); surgical site infection (n = 7); repair of cerebrospinal fluid leak (n = 1), and one patient death at home 3 days after discharge. Conclusion: Lumbar fusion for symptomatic DDD can be a safe and effective treatment for medically refractory LBP with or without leg pain. PMID:26692696

  14. Sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life in patients with lumbar degenerative disc disease.

    PubMed

    Gautschi, Oliver P; Corniola, Marco V; Smoll, Nicolas R; Joswig, Holger; Schaller, Karl; Hildebrandt, Gerhard; Stienen, Martin N

    2016-05-01

    Sex differences in pain perception are known to exist; however, the exact pathomechanism remains unclear. This work aims to elucidate sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life (HRQoL) in patients with lumbar degenerative disc disease. In a prospective 2-center study, back and leg pain (visual analogue scale [VAS]), functional disability (Oswestry Disability Index and Roland-Morris Disability Index), and HRQoL (EuroQol-5D and Short Form [SF12]) were collected for consecutive patients undergoing lumbar spine surgery. Objective functional impairment (OFI) was estimated using age-adjusted and sex-adjusted cutoff values for the timed-up-and-go (TUG) test. A healthy cohort of n = 110 subjects served as the control group. Univariate and multivariate analyses were performed to test the association between sex and pain, subjective and OFIs, and HRQoL. The study comprised n = 305 patients (41.6% females). Female patients had more VAS back pain (P = 0.002) and leg pain (P = 0.014). They were more likely to report higher functional impairment in terms of Oswestry Disability Index (P = 0.005). Similarly, HRQoL measured with the EuroQol-5D index (P = 0.012) and SF12 physical composite score (P = 0.005) was lower in female patients. Female patients reported higher VAS back and leg pain, functional impairment, and reduced HRQoL than male patients. However, there were no sex differences with respect to the presence and degree of OFI measured by the TUG test using age-adjusted and sex-adjusted cutoff values. As such, the TUG may be a good test to overcome sex bias for the clinical assessment of patients with degenerative disc disease. PMID:26761383

  15. Comparative Analysis of Interbody Cages Versus Tricortical Graft with Anterior Plate Fixation for Anterior Cervical Discectomy and Fusion in Degenerative Cervical Disc Disease

    PubMed Central

    Singh, Pritish; Shekhawat, Vishal

    2016-01-01

    Introduction Multiple techniques and modalities of fixation are used in Anterior Cervical Discectomy and interbody Fusion (ACDF), each with some merit and demerit against others. Such pool of techniques reflects lack of a consensus method conducive to uniformly good results. Aim A prospective study was done to analyse safety and efficacy of tricortical autograft and anterior cervical plate (Group A) with cylindrical titanium cage filled with cancellous bone (Group B) in procedure of ACDF for single level degenerative cervical disc disease. Materials and Methods Twenty patients with degenerative cervical disc disease were included in study for ACDF. After a computer generated randomisation, ten patients (10 segments) were operated with anterior locking plating and tricortical iliac crest graft (Group A, Tricortical graft group), while ten patients(10 segments) were operated with standalone cylindrical titanium cages filled with cancellous bone harvested using minimally invasive methods (Group B, Cage group) from April 2012 to May 2015. Odoms’s criteria, visual pain analogue score and sequential plain radiographs were obtained to assess for clinic-radiological outcome. Results According to Odom’s system of functional assessment, 9 patients from each group (90%) experienced good to excellent functional recovery and 9 of 10 (90%) patients of each groups were satisfied with outcome. In both groups, relief in neck pain or arm pain was similar without any statistical difference as assessed by visual analogue score. Fusion was present in 10 of 10 (100%) patients in tricortical graft group and 10 of 10 (100%) in cage group at the end of 6 months. There was no implant related complications in cage group. Transient postoperative dysphagia was recorded in 3 patients (2 in Group A and 1 in group B), which resolved within 3 days. In tricortical graft group, graft collapse and partial extrusion was detected in one patient, which did not correspond with good results obtained

  16. Measurement of Intervertebral Motion Using Quantitative Fluoroscopy: Report of an International Forum and Proposal for Use in the Assessment of Degenerative Disc Disease in the Lumbar Spine

    PubMed Central

    Breen, Alan C.; Teyhen, Deydre S.; Mellor, Fiona E.; Breen, Alexander C.; Wong, Kris W. N.; Deitz, Adam

    2012-01-01

    Quantitative fluoroscopy (QF) is an emerging technology for measuring intervertebral motion patterns to investigate problem back pain and degenerative disc disease. This International Forum was a networking event of three research groups (UK, US, Hong Kong), over three days in San Francisco in August 2009. Its aim was to reach a consensus on how best to record, analyse, and communicate QF information for research and clinical purposes. The Forum recommended that images should be acquired during regular trunk motion that is controlled for velocity and range, in order to minimise externally imposed variability as well as to correlate intervertebral motion with trunk motion. This should be done in both the recumbent passive and weight bearing active patient configurations. The main recommended outputs from QF were the true ranges of intervertebral rotation and translation, neutral zone laxity and the consistency of shape of the motion patterns. The main clinical research priority should initially be to investigate the possibility of mechanical subgroups of patients with chronic, nonspecific low back pain by comparing their intervertebral motion patterns with those of matched healthy controls. PMID:22666606

  17. A 6.5-year follow-up of 14 patients who underwent ProDisc total disc arthroplasty for combined long-standing degenerative lumbar disc disease and recent disc herniation.

    PubMed

    Markwalder, Thomas-Marc; Wenger, Markus; Marbacher, Serge

    2011-12-01

    A highly selected cohort of nine women and five men (mean age±standard error of the mean, 39.6±10.2 years) with discogenic low-back pain (duration: 75.4±97.5 months) and radiculopathy due to disc herniation (duration: 9.4±11.8 months) underwent anterior microdiscectomy and ProDisc-L II arthroplasty (Synthes, Oberdorf, Switzerland) (L5/S1 in 13 patients, L4/5 in one). As reported earlier, initial results were excellent in 11 and good in three patients at 17.8±4.7 months. At an average of 6.5 years after surgery, all were reassessed using the SWISSDISC-questionnaire, which involves the EuroQol-5D and North American Spine Society evaluations (general health, low-back and lower limb status), and a telephone call. Patients reporting an unsatisfactory outcome were re-examined clinically and radiologically. Results were excellent for 10, good for two, satisfactory for one, and poor for one patient. Visual analog scores for back and leg pain at 6.5 years had improved significantly relative to preoperative values (p<0.01), and were only slightly higher than at 1.48 years (p=0.3). This study confirms the initial favorable results. PMID:22099076

  18. [Current research status and progress of stem cells therapy for degenerative intervertebral disc regeneration].

    PubMed

    Xie, Guangyou; Lu, Furong; Yang, Haitao

    2014-12-01

    Low back pain caused by intervertebral disc degeneration is a common clinical chronic disease. The regenerative ability of intervertebral disc tissue is extremely poor. Meanwhile, current treating methods can not fundamentally solve such problems. With the increasing awareness of the mechanism of disc degeneration and the rapid development of the fields of cellular and molecular biology, gene and materials engineering, using stem cells and tissue engineering technology to slow down or reverse the progress of disc degeneration may become possible. The author reviewed the application of stem cells for treating degenerative discs from present researching status and concepts for the future in the combination of researches reported both at home and abroad. PMID:25868271

  19. Does 360° lumbar spinal fusion improve long-term clinical outcomes after failure of conservative treatment in patients with functionally disabling single-level degenerative lumbar disc disease? Results of 5-year follow-up in 75 postoperative patients

    PubMed Central

    Zigler, Jack E.; Delamarter, Rick B.

    2013-01-01

    Background Surgical treatment of patients with mechanical degenerative disc disease has been controversial, but improvements in clinical outcomes have been shown in properly selected patients with disease-specific diagnoses, with fusion arguably now becoming the “gold standard” for surgical management of these patients. No published study thus far has been designed for prospective enrollment of patients with specific inclusion/exclusion criteria in whom at least 6 months of conservative therapy has failed and who are then offered a standardized surgical procedure and are followed up for 5 years. Methods The study group was composed of the patients in the prospective, randomized Food and Drug Administration Investigational Device Exemption trial comparing ProDisc-L (Synthes Spine, West Chester, Pennsylvania) with 360° fusion for the treatment of single-level symptomatic disc degeneration. Of 80 patients randomized to 360° fusion after failure of non-operative care, 75 were treated on protocol with single-level fusions. Follow-up of this treatment cohort was 97% at 2 years and 75% at 5 years and serves as the basis for this report. Patients in the trial were required to have failure of at least 6 months of nonoperative care and in fact had failure of an average of 9 months of nonoperative treatment. The mean Oswestry Disability Index score indicated greater than 60% impairment. The mean entry-level pain score on a visual analog scale was greater than 8 of 10. Results After fusion, not only did patients have significant improvements in measurable clinical outcomes such as the Oswestry Disability Index score and pain score on a visual analog scale but there were also substantial improvements in their functional status and quality of life. Specifically, over 80% of patients in this study had improvements in recreational status that was maintained 5 years after index surgery, indicating substantial improvements in life quality that were not afforded by months of

  20. Five-year clinical results of cervical total disc replacement compared with anterior discectomy and fusion for treatment of 2-level symptomatic degenerative disc disease: a prospective, randomized, controlled, multicenter investigational device exemption clinical trial.

    PubMed

    Radcliff, Kris; Coric, Domagoj; Albert, Todd

    2016-08-01

    OBJECTIVE The purpose of this study was to report the outcome of a study of 2-level cervical total disc replacement (Mobi-C) versus anterior cervical discectomy and fusion (ACDF). Although the long-term outcome of single-level disc replacement has been extensively described, there have not been previous reports of the 5-year outcome of 2-level cervical disc replacement. METHODS This study reports the 5-year results of a prospective, randomized US FDA investigational device exemption (IDE) study conducted at 24 centers in patients with 2-level, contiguous, cervical spondylosis. Clinical outcomes at up to 60 months were evaluated, including validated outcome measures, incidence of reoperation, and adverse events. The complete study data and methodology were critically reviewed by 3 independent surgeon authors without affiliation with the IDE study or financial or institutional bias toward the study sponsor. RESULTS A total of 225 patients received the Mobi-C cervical total disc replacement device and 105 patients received ACDF. The Mobi-C and ACDF follow-up rates were 90.7% and 86.7%, respectively (p = 0.39), at 60 months. There was significant improvement in all outcome scores relative to baseline at all time points. The Mobi-C patients had significantly more improvement than ACDF patients in terms of Neck Disability Index score, SF-12 Physical Component Summary, and overall satisfaction with treatment at 60 months. The reoperation rate was significantly lower with Mobi-C (4%) versus ACDF (16%). There were no significant differences in the adverse event rate between groups. CONCLUSIONS Both cervical total disc replacement and ACDF significantly improved general and disease-specific measures compared with baseline. However, there was significantly greater improvement in general and disease-specific outcome measures and a lower rate of reoperation in the 2-level disc replacement patients versus ACDF control patients. Clinical trial registration no. NCT00389597

  1. Cells from Degenerative Intervertebral Discs Demonstrate Unfavorable Responses to Mechanical and Inflammatory Stimuli: A Pilot Study

    PubMed Central

    Sowa, Gwendolyn A.; Coelho, J. Paulo; Vo, Nam V.; Pacek, Corey; Westrick, Edward; Kang, James D.

    2016-01-01

    Objective Mechanical forces and inflammatory signaling influence intervertebral disc matrix homeostasis. We hypothesized that annulus fibrosus cells from degenerative discs would have altered responses to mechanical and inflammatory stimuli compared with cells isolated from normal discs. Design Annulus fibrosus cells were isolated from New Zealand White rabbits with normal and magnetic resonance imaging-confirmed degenerative discs created by annular stab. Cells were cultured with and without inflammatory and mechanical stimuli (tensile strain). After 4 or 24 hrs, the mRNA expression of inflammatory, catabolic, and anabolic genes was measured by reverse transcription polymerase chain reaction. Results Baseline gene expression differences were noted between cells from normal and degenerative discs. Degenerative cells demonstrated a more proinflammatory response profile to inflammatory and mechanical stimuli and loss of the beneficial effects of mechanical signaling. Decreased expression of catabolic and anabolic genes was observed in degenerative cells under conditions of inflammatory and mechanical stimuli. Conclusions These data demonstrate that degenerative cells have a decreased capacity to respond positively to beneficial levels of mechanical strain and demonstrate an exaggerated response to an inflammatory stimulus. This may, in part, help to explain differential responses to motion-based therapies in patients with intervertebral disc degeneration. PMID:22760106

  2. Temporal changes of mechanical signals and extracellular composition in human intervertebral disc during degenerative progression

    PubMed Central

    Zhu, Qiaoqiao; Gao, Xin; Gu, Weiyong

    2014-01-01

    In this study, a three-dimensional finite element model was used to investigate the changes in tissue composition and mechanical signals within human lumbar intervertebral disc during the degenerative progression. This model was developed based on the cell-activity coupled mechano-electrochemical mixture theory. The disc degeneration was simulated by lowering nutrition levels at disc boundaries, and the temporal and spatial distributions of the fixed charge density, water content, fluid pressure, Von Mises stress, and disc deformation were analyzed. Results showed that fixed charge density, fluid pressure, and water content decreased significantly in the nucleus pulposus (NP) and the inner to middle annulus fibrosus (AF) regions of the degenerative disc. It was found that, with degenerative progression, the Von Mises stress (relative to that at healthy state) increased within the disc, with a larger increase in the outer AF region. Both the disc volume and height decreased with the degenerative progression. The predicted results of fluid pressure change in the NP were consistent with experimental findings in the literature. The knowledge of the variations of temporal and spatial distributions of composition and mechanical signals within the human IVDs provide a better understanding of the progression of disc degeneration. PMID:25305690

  3. Inherited Retinal Degenerative Disease Registry

    ClinicalTrials.gov

    2016-03-21

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  4. Physiochemical basis of human degenerative disease

    PubMed Central

    Lipinski, Boguslaw

    2015-01-01

    The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers. PMID:27486355

  5. Degenerative diseases of the vertebral column.

    PubMed

    Resnick, D

    1985-07-01

    Several distinct degenerative processes affect the articulations of the vertebral column; each is associated with characteristic radiographic and pathologic abnormalities, and many are accompanied by significant clinical manifestations. A discussion of these processes is best accomplished according to the type of joint that is involved. With regard to cartilaginous articulations, of which the intervertebral disk is most important, intervertebral (osteo)chondrosis, spondylosis deformans, and, in the cervical spine, uncovertebral arthrosis are the major degenerative disorders. Osteoarthritis (osteoarthrosis) affects any of the synovium-lined joints of the vertebral column, including the apophyseal, costovertebral, transitional lumbosacral, median atlantoaxial, and sacroiliac articulations. Fibrous articulations, ligaments, or entheses (sites of tendon or ligament attachment to bone) are involved in diffuse idiopathic skeletal hyperostosis, ossification of the posterior spinal ligaments, and Baastrup disease. Of the many complications of these degenerative processes, alignment abnormalities (including segmental instability, degenerative spondylolisthesis, senile kyphosis, and degenerative scoliosis), intervertebral disk displacement, calcification or ossification, and spinal stenosis are the most important. PMID:3923556

  6. Is running associated with degenerative joint disease

    SciTech Connect

    Panush, R.S.; Schmidt, C.; Caldwell, J.R.; Edwards, N.L.; Longley, S.; Yonker, R.; Webster, E.; Nauman, J.; Stork, J.; Pettersson, H.

    1986-03-07

    Little information is available regarding the long-term effects, if any, of running on the musculoskeletal system. The authors compared the prevalence of degenerative joint disease among 17 male runners with 18 male nonrunners. Running subjects (53% marathoners) ran a mean of 44.8 km (28 miles)/wk for 12 years. Pain and swelling of hips, knees, ankles and feet and other musculoskeletal complaints among runners were comparable with those among nonrunners. Radiologic examinations (for osteophytes, cartilage thickness, and grade of degeneration) also were without notable differences among groups. They did not find an increased prevalence of osteoarthritis among the runners. Our observations suggest that long-duration, high-mileage running need to be associated with premature degenerative joint disease in the lower extremities.

  7. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body. PMID:25026144

  8. Multi-center, Prospective, Randomized, Controlled Investigational Device Exemption Clinical Trial Comparing Mobi-C Cervical Artificial Disc to Anterior Discectomy and Fusion in the Treatment of Symptomatic Degenerative Disc Disease in the Cervical Spine

    PubMed Central

    Bae, Hyun W.; Davis, Reginald; Gaede, Steven; Hoffman, Greg; Kim, Kee; Nunley, Pierce D.; Peterson, Daniel; Rashbaum, Ralph; Stokes, John

    2014-01-01

    Background Anterior cervical discectomy and fusion (ACDF) is the gold standard for treating symptomatic cervical disc degeneration. Cervical total disc replacements (TDRs) have emerged as an alternative for some patients. The purpose of this study was to evaluate the safety and effectiveness of a new TDR device compared with ACDF for treating single-level cervical disc degeneration. Methods This was a prospective, randomized, controlled, multicenter Food and Drug Administration (FDA) regulated Investigational Device Exemption (IDE) study. A total of 245 patients were treated (164 TDR: 81 ACDF). The primary outcome measure was overall success based on improvement in Neck Disability Index (NDI), no subsequent surgical interventions, and no adverse events (AEs) classified as major complications. Secondary outcome measures included SF-12, visual analog scale (VAS) assessing neck and arm pain, patient satisfaction, radiographic range of motion, and adjacent level degeneration. Patients were evaluated preoperatively and postoperatively at 6 weeks, 3, 6, 12, 18, and 24 months. The hypothesis was that the TDR success rate was non-inferior to ACDF at 24 months. Results Overall success rates were 73.6% for TDR and 65.3% for ACDF, confirming non-inferiority (p < 0.0025). TDR demonstrated earlier improvements with significant differences in NDI scores at 6 weeks and 3 months, and VAS neck pain and SF-12 PCS scores at 6 weeks (p<0.05). Operative level range of motion in the TDR group was maintained throughout follow-up. Radiographic evidence of inferior adjacent segment degeneration was significantly greater with ACDF at 12 and 24 months (p < 0.05). AE rates were similar. Conclusions Mobi-C TDR is a safe and effective treatment for single-level disc degeneration, producing outcomes similar to ACDF with less adjacent segment degeneration. Level of Evidence: Level I. Clinical relevance: This study adds to the literature supporting cervical TDR as a viable option to ACDF in

  9. Developing Cellular Therapies for Retinal Degenerative Diseases

    PubMed Central

    Bharti, Kapil; Rao, Mahendra; Hull, Sara Chandros; Stroncek, David; Brooks, Brian P.; Feigal, Ellen; van Meurs, Jan C.; Huang, Christene A.; Miller, Sheldon S.

    2014-01-01

    Biomedical advances in vision research have been greatly facilitated by the clinical accessibility of the visual system, its ease of experimental manipulation, and its ability to be functionally monitored in real time with noninvasive imaging techniques at the level of single cells and with quantitative end-point measures. A recent example is the development of stem cell–based therapies for degenerative eye diseases including AMD. Two phase I clinical trials using embryonic stem cell–derived RPE are already underway and several others using both pluripotent and multipotent adult stem cells are in earlier stages of development. These clinical trials will use a variety of cell types, including embryonic or induced pluripotent stem cell–derived RPE, bone marrow– or umbilical cord–derived mesenchymal stem cells, fetal neural or retinal progenitor cells, and adult RPE stem cells–derived RPE. Although quite distinct, these approaches, share common principles, concerns and issues across the clinical development pipeline. These considerations were a central part of the discussions at a recent National Eye Institute meeting on the development of cellular therapies for retinal degenerative disease. At this meeting, emphasis was placed on the general value of identifying and sharing information in the so-called “precompetitive space.” The utility of this behavior was described in terms of how it could allow us to remove road blocks in the clinical development pipeline, and more efficiently and economically move stem cell–based therapies for retinal degenerative diseases toward the clinic. Many of the ocular stem cell approaches we discuss are also being used more broadly, for nonocular conditions and therefore the model we develop here, using the precompetitive space, should benefit the entire scientific community. PMID:24573369

  10. Biomechanical analysis of press-extension technique on degenerative lumbar with disc herniation and staggered facet joint.

    PubMed

    Du, Hong-Gen; Liao, Sheng-Hui; Jiang, Zhong; Huang, Huan-Ming; Ning, Xi-Tao; Jiang, Neng-Yi; Pei, Jian-Wei; Huang, Qin; Wei, Hui

    2016-05-01

    This study investigates the effect of a new Chinese massage technique named "press-extension" on degenerative lumbar with disc herniation and facet joint dislocation, and provides a biomechanical explanation of this massage technique. Self-developed biomechanical software was used to establish a normal L1-S1 lumbar 3D FE model, which integrated the spine CT and MRI data-based anatomical structure. Then graphic technique is utilized to build a degenerative lumbar FE model with disc herniation and facet joint dislocation. According to the actual press-extension experiments, mechanic parameters are collected to set boundary condition for FE analysis. The result demonstrated that press-extension techniques bring the annuli fibrosi obvious induction effect, making the central nucleus pulposus forward close, increasing the pressure in front part. Study concludes that finite element modelling for lumbar spine is suitable for the analysis of press-extension technique impact on lumbar intervertebral disc biomechanics, to provide the basis for the disease mechanism of intervertebral disc herniation using press-extension technique. PMID:27275119

  11. The Changes in the Expression of NF-KB in a Degenerative Human Intervertebral Disc model.

    PubMed

    Sun, Zhongyi; Yin, Zhanmin; Liu, Chao; Tian, Jiwei

    2015-05-01

    We aim at determining the changes in the expression of NF-kB signaling pathway in degenerative intervertebral discs. We collected normal and degenerated intervertebral discs tissues. The normal and degenerated cells were cultivated and their histopathology and immunofluoresence studies were used to observe the position of NF-kB p65 in the cell. We also treated the nucleus pulposus cells with inflammatory factors and inhibitors. Western blot was used to analyze the expression of different proteins. Real time fluorescence-based quantitative PCR was used for observation of NF-kB regulation of change in gene expression. Immunofluorescence showed that in the non-degenerative group the p65 was found in the cytoplasm of the nucleus pulposus cell while in the degenerated cell group the p65 protein was found in the nucleus of the cell. The expression of p65 increased with increase in the degree of degenerative change of the nucleus pulposus cell. RT-PCR showed that the expression of matrix metalloproteinases, aggrecanases and IL-6 was higher in the degenerative group. The amount of aggrecan and type II collagen was significantly decreased in the degenerative group. IL-1β was able to upregulate the activation of NF-kB and the expression of MMP-13 and ADAMTS-4 was also significantly increased. The effect of these proteins can be inhibited by the NF-kB inhibitor, BAY11-7082. The activation of the NK-kB signaling pathway in a degenerative intervertebral disc is gradually increased, regulating the over-expression of matrix-degrading enzymes. It plays an important role in the degradation of extracellular matrix. PMID:25433723

  12. Degenerative disease of the lumbar spine.

    PubMed

    Kovacs, F M; Arana, E

    2016-04-01

    In the last 25 years, scientific research has brought about drastic changes in the concept of low back pain and its management. Most imaging findings, including degenerative changes, reflect anatomic peculiarities or the normal aging process and turn out to be clinically irrelevant; imaging tests have proven useful only when systemic disease is suspected or when surgery is indicated for persistent spinal cord or nerve root compression. The radiologic report should indicate the key points of nerve compression, bypassing inconsequential findings. Many treatments have proven inefficacious, and some have proven counterproductive, but they continue to be prescribed because patients want them and there are financial incentives for doing them. Following the guidelines that have proven effective for clinical management improves clinical outcomes, reduces iatrogenic complications, and decreases unjustified and wasteful healthcare expenditures. PMID:26872873

  13. Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

    PubMed Central

    Zhou, Ren-Peng; Wu, Xiao-Shan; Wang, Zhi-Sen; Xie, Ya-Ya; Ge, Jin-Fang; Chen, Fei-Hu

    2016-01-01

    Degenerative diseases often strike older adults and are characterized by progressive deterioration of cells, eventually leading to tissue and organ degeneration for which limited effective treatment options are currently available. Acid-sensing ion channels (ASICs), a family of extracellular H+-activated ligand-gated ion channels, play critical roles in physiological and pathological conditions. Aberrant activation of ASICs is reported to regulate cell apoptosis, differentiation and autophagy. Accumulating evidence has highlighted a dramatic increase and activation of ASICs in degenerative disorders, including multiple sclerosis, Parkinson’s disease, Huntington’s disease, intervertebral disc degeneration and arthritis. In this review, we have comprehensively discussed the critical roles of ASICs and their potential utility as therapeutic targets in degenerative diseases. PMID:27493834

  14. Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases.

    PubMed

    Zhou, Ren-Peng; Wu, Xiao-Shan; Wang, Zhi-Sen; Xie, Ya-Ya; Ge, Jin-Fang; Chen, Fei-Hu

    2016-08-01

    Degenerative diseases often strike older adults and are characterized by progressive deterioration of cells, eventually leading to tissue and organ degeneration for which limited effective treatment options are currently available. Acid-sensing ion channels (ASICs), a family of extracellular H(+)-activated ligand-gated ion channels, play critical roles in physiological and pathological conditions. Aberrant activation of ASICs is reported to regulate cell apoptosis, differentiation and autophagy. Accumulating evidence has highlighted a dramatic increase and activation of ASICs in degenerative disorders, including multiple sclerosis, Parkinson's disease, Huntington's disease, intervertebral disc degeneration and arthritis. In this review, we have comprehensively discussed the critical roles of ASICs and their potential utility as therapeutic targets in degenerative diseases. PMID:27493834

  15. Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs.

    PubMed

    Nasto, Luigi A; Wang, Dong; Robinson, Andria R; Clauson, Cheryl L; Ngo, Kevin; Dong, Qing; Roughley, Peter; Epperly, Michael; Huq, Saiful M; Pola, Enrico; Sowa, Gwendolyn; Robbins, Paul D; Kang, James; Niedernhofer, Laura J; Vo, Nam V

    2013-01-01

    Intervertebral disc degeneration (IDD) is the leading cause of debilitating spinal disorders such as chronic lower back pain. Aging is the greatest risk factor for IDD. Previously, we demonstrated IDD in a murine model of a progeroid syndrome caused by reduced expression of a key DNA repair enzyme. This led us to hypothesize that DNA damage promotes IDD. To test our hypothesis, we chronically exposed adult wild-type (Wt) and DNA repair-deficient Ercc1(-/Δ) mice to the cancer therapeutic agent mechlorethamine (MEC) or ionization radiation (IR) to induce DNA damage and measured the impact on disc structure. Proteoglycan, a major structural matrix constituent of the disc, was reduced 3-5× in the discs of MEC- and IR-exposed animals compared to untreated controls. Expression of the protease ADAMTS4 and aggrecan proteolytic fragments was significantly increased. Additionally, new PG synthesis was reduced 2-3× in MEC- and IR-treated discs compared to untreated controls. Both cellular senescence and apoptosis were increased in discs of treated animals. The effects were more severe in the DNA repair-deficient Ercc1(-/Δ) mice than in Wt littermates. Local irradiation of the vertebra in Wt mice elicited a similar reduction in PG. These data demonstrate that genotoxic stress drives degenerative changes associated with IDD. PMID:23262094

  16. Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs

    PubMed Central

    Nasto, Luigi A.; Wang, Dong; Robinson, Andria R.; Clauson, Cheryl L.; Ngo, Kevin; Dong, Qing; Roughley, Peter; Epperly, Michael; Huq, Saiful M.; Pola, Enrico; Sowa, Gwendolyn; Robbins, Paul D.; Kang, James; Niedernhofer, Laura J.; Vo, Nam V.

    2013-01-01

    Intervertebral disc degeneration (IDD) is the leading cause of debilitating spinal disorders such as chronic lower back pain. Aging is the greatest risk factor for IDD. Previously, we demonstrated IDD in a murine model of a progeroid syndrome caused by reduced expression of a key DNA repair enzyme. This led us to hypothesize that DNA damage promotes IDD. To test our hypothesis, we chronically exposed adult wild-type (Wt) and DNA repair-deficient Ercc1−/Δ mice to the cancer therapeutic agent mechlorethamine (MEC) or ionization radiation (IR) to induce DNA damage and measured the impact on disc structure. Proteoglycan, a major structural matrix constituent of the disc, was reduced 3-5x in the discs of MEC- and IR-exposed animals compared to untreated controls. Expression of the protease ADAMTS4 and aggrecan proteolytic fragments were significantly increased. Additionally, new PG synthesis was reduced 2-3x in MEC- and IR-treated discs compared to untreated controls. Both cellular senescence and apoptosis were increased in discs of treated animals. The effects were more severe in the DNA repair-deficient Ercc1−/Δ mice than in Wt littermates. Local irradiation of the vertebra in Wt mice elicited a similar reduction in PG. These data demonstrate that genotoxic stress drives degenerative changes associated with IDD. PMID:23262094

  17. Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

    PubMed Central

    Madeira, Maria H.; Boia, Raquel; Santos, Paulo F.; Ambrósio, António F.; Santiago, Ana R.

    2015-01-01

    Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy. PMID:25873768

  18. [Etiology, pathophysiology and conservative therapy of degenerative rheumatic diseases].

    PubMed

    Jandrić, Slavica

    2002-01-01

    ETIOLOGY OF DEGENERATIVE JOINT DISEASES: Etiology of degenerative joint diseases is still not clearly understood and there is no specific management for this group of diseases. Various pathological conditions cause damage of the articular cartilage and lead to clinically and radiographically recognized impairment. Biomechanical, metabolic, genetic factors, inflammation and other risk factors contribute to development of osteoarthrosis. PATHOPHYSIOLOGY OF DEGENERATIVE JOINT DISEASES: Osteoarthrosis is characterized by progressive erosion of articular cartilage and bone overgrowth at the joint margins. Cartilage integrity requires balance between synthesis and degradation of matrix components. Chondrocytes react to various mechanical and chemical stresses in order to stabilize and restore the tissue. Failures in stabilizing and restoring the tissue lead to cartilage degeneration that may be irreversibile. For better understanding of conservative management of degenerative joint diseases it is important to know the impact of pathophysiology mechanisms on development of degenerative joint diseases. There is great variability in the rate of progression of erosive processes in articular cartilage in clinical, radiographic signs and course of the disease. This is in relation with many factors, as well as with management and response to therapy. TREATMENT OF DEGENERATIVE JOINT DISEASES: Treatment should vary depending on the severity of disease and patient's expectations and level of activity. Besides analgesic and anti-inflammatory drugs, conventional and not conventional treatment and techniques can be used for management of osteoarthrosis. Physical therapy and exercises are very important for maintaining muscle strength, joint stability and mobility, but should be closely monitored for optimal efficacy. PMID:12037935

  19. Fibronectin fragments and the cleaving enzyme ADAM-8 in the degenerative human intervertebral disc

    PubMed Central

    Ruel, Nancy; Markova, Dessislava Z.; Adams, Sherrill L.; Scanzello, Carla; Cs-Szabo, Gabriella; Gerard, David; Shi, Peng; Anderson, D. Greg; Zack, Marc; An, Howard S.; Chen, Di; Zhang, Yejia

    2014-01-01

    Study Design The presence fibronectin fragments (FN-fs) and the cleaving enzyme, A disintegrin and metalloproteinase domain-containing protein (ADAM)-8 were examined in human intervertebral disc (IVD) tissue in vitro. Objective To investigate the presence and pathophysiological concentration of FN-fs and their cleaving enzyme, ADAM-8, in the human IVD tissue. Summary of Background Data The 29kDa FN-f has been shown to result in extracellular matrix loss in rabbit IVDs. However, the concentration of this biologically active fragment in the degenerative human IVD tissue has previously not been determined. Further, it is critical to identify the enzyme(s) responsible for FN cleavage in the IVD. Methods Human degenerative IVD tissues were removed during spinal surgery. A normal appearing young adult and an infant human cadaveric sample were obtained as controls. Soluble proteins were extracted, and analyzed by Western blotting utilizing antibodies specific for the human FN neoepitope VRAA271. A purified 29 kDa FN-f was used to allow estimation of the concentration of FN-fs in the tissues. ADAM-8, a FN-cleaving enzyme, was analyzed by Western blotting and immunostaining. Results All adult IVD tissues contain many FN-f species, but these species were absent from the infant disc tissue. Moderately degenerative discs contained the highest amount of FN-fs; the concentration was estimated to be in the nanomolar range per gram of tissue. ADAM-8, known to cleave FN resulting in the VRAA271 neoepitope, was present in the human disc. ADAM-8 primarily localized in the pericellular matrix of the nucleus pulposus (NP) tissue, as determined by immunostaining. Conclusion This is the first report that N-terminal FN-fs are consistently present in IVD tissues from adult subjects. The pathophysiological concentration of these fragments is estimated to be at nanomolar range per gram of IVD tissue. Further, ADAM-8, known to cleave FN, is present at the pericellular matrix of disc cells

  20. The Effect of Sustained Compression on Oxygen Metabolic Transport in the Intervertebral Disc Decreases with Degenerative Changes

    PubMed Central

    Malandrino, Andrea; Noailly, Jérôme; Lacroix, Damien

    2011-01-01

    Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance. Disc degenerative changes alter the tissue mechanics, but interactions between mechanical loading and disc transport are still an open issue. A poromechanical finite element model of the human disc was coupled with oxygen and lactate transport models. Deformations and fluid flow were linked to transport predictions by including strain-dependent diffusion and advection. The two solute transport models were also coupled to account for cell metabolism. With this approach, the relevance of metabolic and mechano-transport couplings were assessed in the healthy disc under loading-recovery daily compression. Disc height, cell density and material degenerative changes were parametrically simulated to study their influence on the calculated solute concentrations. The effects of load frequency and amplitude were also studied in the healthy disc by considering short periods of cyclic compression. Results indicate that external loads influence the oxygen and lactate regional distributions within the disc when large volume changes modify diffusion distances and diffusivities, especially when healthy disc properties are simulated. Advection was negligible under both sustained and cyclic compression. Simulating degeneration, mechanical changes inhibited the mechanical effect on transport while disc height, fluid content, nucleus pressure and overall cell density reductions affected significantly transport predictions. For the healthy disc, nutrient concentration patterns depended mostly on the time of sustained compression and recovery. The relevant effect of cell density on the metabolic transport indicates the disturbance of cell number as a possible onset for disc degeneration via alteration of the metabolic balance. Results also suggest that healthy disc properties have a positive effect of loading on metabolic transport. Such

  1. Reliability of the modified Tufts Lumbar Degenerative Disc Classification between neurosurgeons and neuroradiologists.

    PubMed

    Burke, Shane M; Hwang, Steven W; Mehan, William A; Bedi, Harprit S; Ogbuji, Richard; Riesenburger, Ron I

    2016-07-01

    Cross-specialty inter-rater reliability has not been explicitly reported for imaging characteristics that are thought to be important in lumbar intervertebral disc degeneration. Sufficient cross-specialty reliability is an essential consideration if radiographic stratification of symptomatic patients to specific treatment modalities is to ever be realized. Therefore the purpose of this study was to directly compare the assessment of such characteristics between neurosurgeons and neuroradiologists. Sixty consecutive patients with a diagnosis of lumbago and appropriate imaging were selected for inclusion. Lumbar MRI were evaluated using the Tufts Degenerative Disc Classification by two neurosurgeons and two neuroradiologists. Inter-rater reliability was assessed using Cohen's κ values both within and between specialties. A sensitivity analysis was performed for a modified grading system, which excluded high intensity zones (HIZ), due to poor cross-specialty inter-rater reliability of HIZ between specialties. The reliability of HIZ between neurosurgeons and neuroradiologists was fair in two of the four cross-specialty comparisons in this study (neurosurgeon 1 versus both radiologists κ=0.364 and κ=0.290). Removing HIZ from the classification improved inter-rater reliability for all comparisons within and between specialties (0.465⩽κ⩽0.576). In addition, intra-rater reliability remained in the moderate to substantial range (0.523⩽κ⩽0.649). Given our findings and corroboration with previous studies, identification of HIZ seems to have a markedly variable reliability. Thus we recommend modification of the original Tufts Degenerative Disc Classification by removing HIZ in order to make the overall grade provided by this classification more reproducible when scored by practitioners of different training backgrounds. PMID:27021223

  2. Imaging diagnosis--degenerative intraspinal cyst associated with an intervertebral disc.

    PubMed

    Penning, Victoria A; Benigni, Livia; Steeves, Elizabeth; Cappello, Rodolfo

    2007-01-01

    A 6-year-old neutered male Rottweiler had chronic episodic signs of thoracolumbar pain and inability to stand that did not improve after rest and nonsteroidal antiinflammatory medication. In magnetic resonance images, an extradural mass was identified between the spinal cord and the T13/L1 intervertebral disc; the mass was compressing the cord in a dorsoventral direction. The lesion had a low signal intensity rim that enhanced slightly after gadolinium administration, and contents with similar signal intensity to cerebrospinal fluid. The lesion was removed surgically by severing its attachments to the annulus fibrosus. The histologic diagnosis was degenerative intraspinal cyst. The origin of such cysts, and their relationship to synovial and ganglion cysts is discussed. PMID:17899976

  3. Anabolic factors in degenerative joint disease.

    PubMed

    Sandell, L J

    2007-02-01

    While a great deal of information is available on the cellular and molecular biology of cartilage degradation, less is known about anabolism in normal cartilage and degenerating cartilage. A consistent amount of evidence is now available on the neo-synthesis of matrix molecules and enzymes in OA: the entire cell metabolism appears to be increased leading to the hypothesis that chondrocytes in OA are actually "activated". This chapter will focus on anabolic events that are now known to occur in articular cartilage. We will begin to view articular cartilage as a complex three-dimensional tissue in which local events may be different. We will also be interested in viewing the development of degenerative arthritis as a continuum from functionally normal tissue to degeneration. PMID:17305513

  4. Oxygen-ozone therapy for degenerative spine disease in the elderly: a prospective study.

    PubMed

    Bonetti, Matteo; Fontana, Alessandro; Martinelli, Francesco; Andreula, Cosma

    2011-01-01

    We describe our experience of oxygen-ozone therapy to treat degenerative spine disease in the elderly. From April 2004 to March 2008 we selected 129 patients with CT and/or MR evidence of spondyloarthrosis and disc degeneration of the lumbar spine. All patients enrolled in the study had contraindications to the administration of commonly used analgesic and anti-inflammatory drugs.Oxygen-ozone therapy was given by CT-guided intraforaminal injection as the first treatment followed by 4 weekly paralumbar infiltrations on an outpatient basis. The full treatment lasted a month. Clinical outcome was assessed 3 months and 1 year after treatment. The good results obtained indicate that oxygen-ozone therapy is an ideal treatment with no side-effects in elderly patients with degenerative spine disease. PMID:21107950

  5. Anterior Cervical Spine Surgery for Degenerative Disease: A Review

    PubMed Central

    SUGAWARA, Taku

    Anterior cervical spine surgery is an established surgical intervention for cervical degenerative disease and high success rate with excellent long-term outcomes have been reported. However, indications of surgical procedures for certain conditions are still controversial and severe complications to cause neurological dysfunction or deaths may occur. This review is focused mainly on five widely performed procedures by anterior approach for cervical degenerative disease; anterior cervical discectomy, anterior cervical discectomy and fusion, anterior cervical corpectomy and fusion, anterior cervical foraminotomy, and arthroplasty. Indications, procedures, outcomes, and complications of these surgeries are discussed. PMID:26119899

  6. Dynamic and Static Overloading Induce Early Degenerative Processes in Caprine Lumbar Intervertebral Discs

    PubMed Central

    Paul, Cornelis P. L.; Schoorl, Tom; Zuiderbaan, Hendrik A.; Zandieh Doulabi, Behrouz; van der Veen, Albert J.; van de Ven, Peter M.; Smit, Theo H.; van Royen, Barend J.; Helder, Marco N.; Mullender, Margriet G.

    2013-01-01

    Mechanical overloading of the spine is associated with low back pain and intervertebral disc (IVD) degeneration. How excessive loading elicits degenerative changes in the IVD is poorly understood. Comprehensive knowledge of the interaction between mechanical loading, cell responses and changes in the extracellular matrix of the disc is needed in order to successfully intervene in this process. The purpose of the current study was to investigate whether dynamic and static overloading affect caprine lumbar discs differently and what mechanisms lead to mechanically induced IVD degeneration. Lumbar caprine IVDs (n = 175) were cultured 7, 14 and 21 days under simulated-physiological loading (control), high dynamic or high static loading. Axial deformation and stiffness were continuously measured. Cell viability, cell density, and gene expression were assessed in the nucleus, inner- and outer annulus. The extracellular matrix (ECM) was analyzed for water, glycosaminoglycan and collagen content. IVD height loss and changes in axial deformation were gradual with dynamic and acute with static overloading. Dynamic overloading caused cell death in all IVD regions, whereas static overloading mostly affected the outer annulus. IVDs expression of catabolic and inflammation-related genes was up-regulated directly, whereas loss of water and glycosaminoglycan were significant only after 21 days. Static and dynamic overloading both induced pathological changes to caprine lumbar IVDs within 21 days. The mechanism by which they inflict biomechanical, cellular, and extracellular changes to the nucleus and annulus differed. The described cascades provide leads for the development of new pharmacological and rehabilitative therapies to halt the progression of DDD. PMID:23638074

  7. SIRT1 alleviates senescence of degenerative human intervertebral disc cartilage endo-plate cells via the p53/p21 pathway.

    PubMed

    Zhou, Nian; Lin, Xin; Dong, Wen; Huang, Wei; Jiang, Wei; Lin, Liangbo; Qiu, Quanhe; Zhang, Xiaojun; Shen, Jieliang; Song, Zhaojun; Liang, Xi; Hao, Jie; Wang, Dawu; Hu, Zhenming

    2016-01-01

    Cartilage end plates (CEP) degeneration plays an integral role in intervertebral disc (IVD) degeneration resulting from nutrient diffusion disorders. Although cell senescence resulting from oxidative stress is known to contribute to degeneration, no studies concerning the role of senescence in CEP degeneration have been conducted. SIRT1 is a longevity gene that plays a pivotal role in many cellular functions, including cell senescence. Therefore, the aim of this study was to investigate whether senescence is more prominent in human degenerative CEP and whether SIRT1-regulated CEP cells senescence in degenerative IVD as well as identify the signaling pathways that control that cell fate decision. In this study, the cell senescence phenotype was found to be more prominent in the CEP cells obtained from disc degenerative disease (DDD) patients than in the CEP cells obtained from age-matched lumbar vertebral fractures (LVF) patients. In addition, the results indicated that p53/p21 pathway plays an important role in the senescence of CEP cells in vivo and vitro. Furthermore, SIRT1 was found to be capable of alleviating the oxidative stress-induced senescence of CEP cells in humans via p53/p21 pathway. Thus, the information presented in this study could be used to further investigate the underlying mechanisms of CEP. PMID:26940203

  8. Initial clinical experience with a next-generation artificial disc for the treatment of symptomatic degenerative cervical radiculopathy

    PubMed Central

    Reyes-Sanchez, Alejandro; Miramontes, Victor; Olivarez, Luis M. Rosales; Aquirre, Armando Alpizar; Quiroz, Alfredo Ortega; Zarate-Kalfopulos, Baron

    2010-01-01

    Background A feasibility trial was conducted to evaluate the initial safety and clinical use of a next-generation artificial cervical disc (M6-C artificial cervical disc; Spinal Kinetics, Sunnyvale, CA) for the treatment of patients with symptomatic degenerative cervical radiculopathy. A standardized battery of validated outcome measures was utilized to assess condition-specific functional impairment, pain severity, and quality of life. Methods Thirty-six consecutive patients were implanted with the M6-C disc and complete clinical and radiographic outcomes for 25 patients (mean age, 44.5 ± 10.1 years) with radiographically-confirmed cervical disc disease and symptomatic radiculopathy unresponsive to conservative medical management are included in this report. All patients had disc-osteophyte complex causing neural compression and were treated with discectomy and artificial cervical disc replacement at either single level (n = 12) or 2-levels (n = 13). Functional impairment was evaluated using the Neck Disability Index (NDI). Evaluation of arm and neck pain severity utilized a standard 11-point numeric scale, and health-related quality of life was evaluated with the SF-36 Health Survey. Quantitative radiographic assessments of intervertebral motion were performed using specialized motion analysis software, QMA (Quantitative Motion Analysis; Medical Metrics, Houston, TX). All outcome measures were evaluated pre-treatment and at 6 weeks, 3, 6, 12, and 24 months. Results The mean NDI score improved from 51.6 ± 11.3% pre-treatment to 27.9 ± 16.9% at 24 months, representing an approximate 46% improvement (P <.0001). The mean arm pain score improved from 6.9 ± 2.5 pre-treatment to 3.9 ± 3.1 at 24 months (43%, P =.0006). The mean neck pain score improved from 7.8 ± 2.0 pre-treatment to 3.8 ± 3.0 at 24 months (51%, P <.0001). The mean PCS score of the SF-36 improved from 34.8 ± 7.8 pre-treatment to 43.8 ± 9.3 by 24 months (26%, P =.0006). Subgroup analyses found

  9. [Degenerative disorders of the lumbar spine Total disc replacement as an alternative to lumbar fusion?].

    PubMed

    Mayer, H M

    2005-10-01

    Spinal fusion is accepted worldwide as a therapeutic option for the treatment of degenerative disorders of the lumbar spine. Because there are only few evidence-based data available supporting the usefulness of lumbar spinal fusion, its questionable benefit as well as the potential for complications are the reasons for an ongoing discussion. In recent years, total disc replacement with implants has emerged as an alternative treatment. Although early results are promising, there is still a lack of evidence-based data as well as of long-term results for this technology. This article gives a critical update on the implant systems currently in use (SB Charité, Prodisc II L, Maverick, Flexicore, Mobidisc), which all have to be considered as "first-generation" implants. Morphological and clinical sequelae of the different biomechanical properties, designs, and materials have not yet been sufficiently investigated. There is no international consensus on the indication spectrum and on the preoperative diagnosis of discogenic low back pain. The same is true for the (minimally invasive) surgical access strategies. Complication rates seem to be somewhat lower compared to spinal fusion techniques. There are no standardized revision concepts in cases of implant failure. Lumbar disc replacement has opened a new era in spinal surgery with a still unproven benefit for the patient. It is strongly recommended that these techniques should only be applied by experienced and well-trained spine surgeons. Until evidence-based data are available, all patients should be treated under scientific study conditions with close postoperative follow-up. PMID:16034627

  10. Immune Mechanisms in Inflammatory and Degenerative Eye Disease

    PubMed Central

    Perez, Victor L.; Caspi, Rachel R.

    2015-01-01

    It has recently been recognized that pathology of age-associated degenerative eye diseases such as adult macular degeneration (AMD), glaucoma and diabetic retinopathy, have strong immunological underpinnings. Attempts have been made to extrapolate to age-related degenerative disease insights from inflammatory processes associated with non-infectious uveitis, but these have not yet been sufficiently informative. Here we review recent findings on the immune processes underlying uveitis and those that have been shown to contribute to AMD, discussing in this context parallels and differences between overt inflammation and para-inflammation in the eye. We propose that mechanisms associated with ocular immune privilege, in combination with paucity of age-related antigen(s) within the target tissue, dampen what could otherwise be overt inflammation and result in the para-inflammation that characterizes age-associated neurodegenerative disease. PMID:25981967

  11. Revisiting the Term Neuroprotection in Chronic and Degenerative Diseases.

    PubMed

    Orsini, Marco; Nascimento, Osvaldo J M; Matta, Andre P C; Reis, Carlos Henrique Melo; de Souza, Olivia Gameiro; Bastos, Victor Hugo; Moreira, Rayele; Ribeiro, Pedro; Fiorelli, Stenio; Novellino, Pietro; Pessoa, Bruno; Cunha, Mariana; Pupe, Camila; Morales, Pedro S; Filho, Pedro F Moreira; Trajano, Eduardo Lima; Oliveira, Acary Bulle

    2016-04-01

    Thanks to the development of several new researches, the lifetime presented a significant increase, even so, we still have many obstacles to overcome - among them, manage and get responses regarding neurodegenerative diseases. Where we are in the understanding of neuroprotection? Do we really have protective therapies for diseases considered degeneratives such as amyotrophic lateral sclerosis and its variants, Parkinson's disease, Alzheimer's disease and many others? Neuroprotection is defined by many researches as interactions and interventions that can slow down or even inhibit the progression of neuronal degeneration process. We make some considerations on this neuroprotective effect. PMID:27127599

  12. Revisiting the Term Neuroprotection in Chronic and Degenerative Diseases

    PubMed Central

    Orsini, Marco; Nascimento, Osvaldo J.M.; Matta, Andre P.C.; Reis, Carlos Henrique Melo; de Souza, Olivia Gameiro; Bastos, Victor Hugo; Moreira, Rayele; Ribeiro, Pedro; Fiorelli, Stenio; Novellino, Pietro; Pessoa, Bruno; Cunha, Mariana; Pupe, Camila; Morales, Pedro S.; Filho, Pedro F. Moreira; Trajano, Eduardo Lima; Oliveira, Acary Bulle

    2016-01-01

    Thanks to the development of several new researches, the lifetime presented a significant increase, even so, we still have many obstacles to overcome – among them, manage and get responses regarding neurodegenerative diseases. Where we are in the understanding of neuroprotection? Do we really have protective therapies for diseases considered degeneratives such as amyotrophic lateral sclerosis and its variants, Parkinson’s disease, Alzheimer’s disease and many others? Neuroprotection is defined by many researches as interactions and interventions that can slow down or even inhibit the progression of neuronal degeneration process. We make some considerations on this neuroprotective effect. PMID:27127599

  13. Vitiligo: A Possible Model of Degenerative Diseases

    PubMed Central

    Bellei, Barbara; Pitisci, Angela; Ottaviani, Monica; Ludovici, Matteo; Cota, Carlo; Luzi, Fabiola; Dell'Anna, Maria Lucia; Picardo, Mauro

    2013-01-01

    Vitiligo is characterized by the progressive disappearance of pigment cells from skin and hair follicle. Several in vitro and in vivo studies show evidence of an altered redox status, suggesting that loss of cellular redox equilibrium might be the pathogenic mechanism in vitiligo. However, despite the numerous data supporting a pathogenic role of oxidative stress, there is still no consensus explanation underlying the oxidative stress-driven disappear of melanocytes from the epidermis. In this study, in vitro characterization of melanocytes cultures from non-lesional vitiligo skin revealed at the cellular level aberrant function of signal transduction pathways common with neurodegenerative diseases including modification of lipid metabolism, hyperactivation of mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB), constitutive p53-dependent stress signal transduction cascades, and enhanced sensibility to pro-apoptotic stimuli. Notably, these long-term effects of subcytotoxic oxidative stress are also biomarkers of pre-senescent cellular phenotype. Consistent with this, vitiligo cells showed a significant increase in p16 that did not correlate with the chronological age of the donor. Moreover, vitiligo melanocytes produced many biologically active proteins among the senescence-associated secretory phenotype (SAPS), such as interleukin-6 (IL-6), matrix metallo proteinase-3 (MMP3), cyclooxygenase-2 (Cox-2), insulin-like growth factor-binding protein-3 and 7 (IGFBP3, IGFBP7). Together, these data argue for a complicated pathophysiologic puzzle underlying melanocytes degeneration resembling, from the biological point of view, neurodegenerative diseases. Our results suggest new possible targets for intervention that in combination with current therapies could correct melanocytes intrinsic defects. PMID:23555779

  14. Cell Therapy Using Bone Marrow-Derived Stem Cell Overexpressing BMP-7 for Degenerative Discs in a Rat Tail Disc Model.

    PubMed

    Liao, Jen-Chung

    2016-01-01

    Degenerative discs can cause low back pain. Cell-based transplantation or growth factors therapy have been suggested as a strategy to stimulate disc regeneration. Bone marrow-derived mesenchymal stem cells (BMDMSC) containing bone morphogenetic protein-7 (BMP-7) gene were constructed. We evaluated the effectiveness of these BMP-7 overexpressing cells on degenerative discs in rat tails. In vitro and in vivo studies were designed. In the first stage, the rats were divided into two group according to discs punctured by different needle gauges (18 gauge and 22 gauge). In the second stage, the ideal size of needle was used to induce rat tail disc degeneration. These animals are divided into three groups according to timing of treatment (zero-week, two-week, four-week). Each group was divided into three treating subgroups: control group, BMDMSC group, and Baculo-BMP-7-BMDMSC group. Each rat undergoes radiography examination every two weeks. After eight weeks, the discs were histologically examined with hematoxylin and eosin stain and Alcian blue stain. The 18-gauge group exhibited significant decrease in disc height index (%) than 22-gauge group at eight weeks at both Co6-7 (58.1% ± 2.8% vs. 63.7% ± 1.0%, p = 0.020) and Co8-9 discs (62.7% ± 2.8% vs. 62.8% ± 1.5%, p = 0.010). Baculo-BMP-7-BMDMSCs group showed significant difference in disc height index compared to the BMDMSCs group at both Co6-7 (93.7% ± 1.5% vs. 84.8% ± 1.0%, p = 0.011) and Co8-9 (86.0% ± 2.1% vs. 81.8% ± 1.7%, p = 0.012). In Baculo-BMP-7-BMDMSCs group, the zero-week treatment subgroup showed significant better in disc height index compared to two-week treatment group (p = 0.044), and four-week treatment group (p = 0.011). The zero-week treatment subgroup in Baculo-BMP-7-BMDMSCs group also had significant lower histology score than two-week treatment (4.3 vs. 5.7, p = 0.045) and four-week treatment (4.3 vs. 6.0, p = 0.031). In conclusion, Baculo-BMP-7-BMDMSC can slow down the progression of disc

  15. Cell Therapy Using Bone Marrow-Derived Stem Cell Overexpressing BMP-7 for Degenerative Discs in a Rat Tail Disc Model

    PubMed Central

    Liao, Jen-Chung

    2016-01-01

    Degenerative discs can cause low back pain. Cell-based transplantation or growth factors therapy have been suggested as a strategy to stimulate disc regeneration. Bone marrow-derived mesenchymal stem cells (BMDMSC) containing bone morphogenetic protein-7 (BMP-7) gene were constructed. We evaluated the effectiveness of these BMP-7 overexpressing cells on degenerative discs in rat tails. In vitro and in vivo studies were designed. In the first stage, the rats were divided into two group according to discs punctured by different needle gauges (18 gauge and 22 gauge). In the second stage, the ideal size of needle was used to induce rat tail disc degeneration. These animals are divided into three groups according to timing of treatment (zero-week, two-week, four-week). Each group was divided into three treating subgroups: control group, BMDMSC group, and Baculo-BMP-7-BMDMSC group. Each rat undergoes radiography examination every two weeks. After eight weeks, the discs were histologically examined with hematoxylin and eosin stain and Alcian blue stain. The 18-gauge group exhibited significant decrease in disc height index (%) than 22-gauge group at eight weeks at both Co6-7 (58.1% ± 2.8% vs. 63.7% ± 1.0%, p = 0.020) and Co8-9 discs (62.7% ± 2.8% vs. 62.8% ± 1.5%, p = 0.010). Baculo-BMP-7-BMDMSCs group showed significant difference in disc height index compared to the BMDMSCs group at both Co6-7 (93.7% ± 1.5% vs. 84.8% ± 1.0%, p = 0.011) and Co8-9 (86.0% ± 2.1% vs. 81.8% ± 1.7%, p = 0.012). In Baculo-BMP-7-BMDMSCs group, the zero-week treatment subgroup showed significant better in disc height index compared to two-week treatment group (p = 0.044), and four-week treatment group (p = 0.011). The zero-week treatment subgroup in Baculo-BMP-7-BMDMSCs group also had significant lower histology score than two-week treatment (4.3 vs. 5.7, p = 0.045) and four-week treatment (4.3 vs. 6.0, p = 0.031). In conclusion, Baculo-BMP-7-BMDMSC can slow down the progression of disc

  16. Health assessment of environmental pollutants; Proliferative and degenerative diseases

    SciTech Connect

    Stuart, B.O. )

    1987-01-01

    The health assessments of environmental air contaminants are at present frequently based upon probability of cancer, if this has been identified as a potential result of prolonged exposure to the particular inhalation hazard. However, for many airborne hazards chronic inhalation exposure may result in morbidity or mortality risks due to chronic degenerative diseases such as emphysema, fibrosis, or chronic obstructive pulmonary disease that may be nearly as great or greater than those of more widely recognized neoplastic or proliferative disease. The relative hazards of environmentally released radioactive and chemical air contaminants, i.e., radon daughters and diesel engine exhaust, are discussed as examples.

  17. Nanoneuromedicines for Degenerative, Inflammatory, and Infectious Nervous System Diseases

    PubMed Central

    Gendelman, Howard E.; Anantharam, Vellareddy; Bronich, Tatiana; Ghaisas, Shivani; Jin, Huajun; Kanthasamy, Anumantha G.; Liu, Xinming; McMillan, JoEllyn; Mosley, R. Lee; Narasimhan, Balaji; Mallapragada, Surya K.

    2015-01-01

    Interest in nanoneuromedicine has grown rapidly due to the immediate need for improved biomarkers and therapies for psychiatric, developmental, traumatic, inflammatory, infectious and degenerative nervous system disorders. These, in whole or in part, are a significant societal burden due to growth in numbers of affected people and in disease severity. Lost productivity of the patient and his or her caregiver, and the emotional and financial burden cannot be overstated. The need for improved health care, treatment and diagnostics are immediate. A means to such an end is nanotechnology. Indeed, recent developments of health-care enabling nanotechnologies and nanomedicines range from biomarker discovery including neuroimaging to therapeutic applications for degenerative, inflammatory and infectious disorders of the nervous system. This review focuses on the current and future potential of the field to positively affect clinical outcomes. PMID:25645958

  18. An organ culture system to model early degenerative changes of the intervertebral disc II: profiling global gene expression changes

    PubMed Central

    2013-01-01

    Introduction Despite many advances in our understanding of the molecular basis of disc degeneration, there remains a paucity of preclinical models which can be used to study the biochemical and molecular events that drive disc degeneration, and the effects of potential therapeutic interventions. The goal of this study is to characterize global gene expression changes in a disc organ culture system that mimics early nontraumatic disc degeneration. Methods To mimic a degenerative insult, rat intervertebral discs were cultured in the presence of TNF-α, IL-1β and serum-limiting conditions. Gene expression analysis was performed using a microarray to identify differential gene expression between experimental and control groups. Differential pattern of gene expression was confirmed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or Western blot. Results Treatment resulted in significant changes in expression of more than 1,000 genes affecting many aspects of cell function including cellular movement, the cell cycle, cellular development, and cell death and proliferation. Many of the most highly upregulated and downregulated genes have known functions in disc degeneration and extracellular matrix hemostasis. Construction of gene networks based on known cellular pathways and expression data from our analysis demonstrated that the network associated with cell death, cell cycle regulation and DNA replication and repair was most heavily affected in this model of disc degeneration. Conclusions This rat organ culture model uses cytokine exposure to induce wide gene expression changes with the most affected genes having known reported functions in disc degeneration. We propose that this model is a valuable tool to study the etiology of disc degeneration and evaluate potential therapeutic treatments. PMID:24171898

  19. Oxidants, antioxidants, and the degenerative diseases of aging.

    PubMed Central

    Ames, B N; Shigenaga, M K; Hagen, T M

    1993-01-01

    Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great. Images Fig. 1 PMID:8367443

  20. Role of Oxidative RNA Damage in Chronic-Degenerative Diseases

    PubMed Central

    2015-01-01

    Normal cellular metabolism and exposure to ionizing and ultraviolet radiations and exogenous agents produce reactive oxygen species (ROS). Due to their reactivity, they can interact with many critical biomolecules and induce cell damage. The reaction of ROS with free nucleobases, nucleosides, nucleotides, or oligonucleotides can generate numerous distinct modifications in nucleic acids. Oxidative damage to DNA has been widely investigated and is strongly implicated in the development of many chronic-degenerative diseases. In contrast, RNA damage is a poorly examined field in biomedical research. In this review, I discuss the importance of RNA as a target of oxidative damage and the role of oxidative damage to RNA in the pathogenesis of some chronic-degenerative diseases, such as neurological disorders, atherosclerosis, and cancer. Furthermore, I review recent evidence suggesting that RNA may be the target for toxic agents and indicating RNA degradation as a powerful tool to treat any pathology in which there is an aberrant expression of mRNA and/or its gene products. PMID:26078805

  1. A Degenerative/Proinflammatory Intervertebral Disc Organ Culture: An Ex Vivo Model for Anti-inflammatory Drug and Cell Therapy.

    PubMed

    Teixeira, Graciosa Q; Boldt, Antje; Nagl, Ines; Pereira, Catarina Leite; Benz, Karin; Wilke, Hans-Joachim; Ignatius, Anita; Barbosa, Mário A; Gonçalves, Raquel M; Neidlinger-Wilke, Cornelia

    2016-01-01

    Resolution of intervertebral disc (IVD) degeneration-associated inflammation is a prerequisite for tissue regeneration and could possibly be achieved by strategies ranging from pharmacological to cell-based therapies. In this study, a proinflammatory disc organ culture model was established. Bovine caudal disc punches were needle punctured and additionally stimulated with lipopolysaccharide (10 μg/mL) or interleukin-1β (IL-1β, 10-100 ng/mL) for 48 h. Two intradiscal therapeutic approaches were tested: (i) a nonsteroidal anti-inflammatory drug, diclofenac (Df) and (ii) human mesenchymal stem/stromal cells (MSCs) embedded in an albumin/hyaluronan hydrogel. IL-1β-treated disc organ cultures showed a statistically significant upregulation of proinflammatory markers (IL-6, IL-8, prostaglandin E2 [PGE2]) and metalloproteases (MMP1, MMP3) expression, while extracellular matrix (ECM) proteins (collagen II, aggrecan) were significantly downregulated. The injection of the anti-inflammatory drug, Df, was able to reduce the levels of proinflammatory cytokines and MMPs and surprisingly increase ECM protein levels. These results point the intradiscal application of anti-inflammatory drugs as promising therapeutics for disc degeneration. In parallel, the immunomodulatory role of MSCs on this model was also evaluated. Although a slight downregulation of IL-6 and IL-8 expression could be found, the variability among the five donors tested was high, suggesting that the beneficial effect of these cells on disc degeneration needs to be further evaluated. The proinflammatory/degenerative IVD organ culture model established can be considered a suitable approach for testing novel therapeutic drugs, thus reducing the number of animals in in vivo experimentation. Moreover, this model can be used to address the cellular and molecular mechanisms that regulate inflammation in the IVD and their implications in tissue degeneration. PMID:26565141

  2. Complement, a target for therapy in inflammatory and degenerative diseases.

    PubMed

    Morgan, B Paul; Harris, Claire L

    2015-12-01

    The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies. PMID:26493766

  3. MRI features of cervical articular process degenerative joint disease in Great Dane dogs with cervical spondylomyelopathy.

    PubMed

    Gutierrez-Quintana, Rodrigo; Penderis, Jacques

    2012-01-01

    Cervical spondylomyelopathy or Wobbler syndrome commonly affects the cervical vertebral column of Great Dane dogs. Degenerative changes affecting the articular process joints are a frequent finding in these patients; however, the correlation between these changes and other features of cervical spondylomyelopathy are uncertain. We described and graded the degenerative changes evident in the cervical articular process joints from 13 Great Danes dogs with cervical spondylomyelopathy using MR imaging, and evaluated the relationship between individual features of cervical articular process joint degeneration and the presence of spinal cord compression, vertebral foraminal stenosis, intramedullary spinal cord changes, and intervertebral disc degenerative changes. Degenerative changes affecting the articular process joints were common, with only 13 of 94 (14%) having no degenerative changes. The most severe changes were evident between C4-C5 and C7-T1 intervertebral spaces. Reduction or loss of the hyperintense synovial fluid signal on T2-weighted MR images was the most frequent feature associated with articular process joint degenerative changes. Degenerative changes of the articular process joints affecting the synovial fluid or articular surface, or causing lateral hypertrophic tissue, were positively correlated with lateral spinal cord compression and vertebral foraminal stenosis. Dorsal hypertrophic tissue was positively correlated with dorsal spinal cord compression. Disc-associated spinal cord compression was recognized less frequently. PMID:22236021

  4. [Lumbar disc herniation and andrological diseases].

    PubMed

    Jin, Bao-fang

    2015-10-01

    Lumbar disc herniation is a common male disease. In the past, More academic attention was directed to its relationship with lumbago and leg pain than to its association with andrological diseases. Studies show that central lumber intervertebral disc herniation may cause cauda equina injury and result in premature ejaculation, erectile dysfunction, chronic pelvic pain syndrome, priapism, and emission. This article presents an overview on the correlation between central lumbar intervertebral disc herniation and andrological diseases, focusing on the aspects of etiology, pathology, and clinical progress, hoping to invite more attention from andrological and osteological clinicians. PMID:26665671

  5. Controversies about Interspinous Process Devices in the Treatment of Degenerative Lumbar Spine Diseases: Past, Present, and Future

    PubMed Central

    Galarza, Marcelo

    2014-01-01

    A large number of interspinous process devices (IPD) have been recently introduced to the lumbar spine market as an alternative to conventional decompressive surgery in managing symptomatic lumbar spinal pathology, especially in the older population. Despite the fact that they are composed of a wide range of different materials including titanium, polyetheretherketone, and elastomeric compounds, the aim of these devices is to unload spine, restoring foraminal height, and stabilize the spine by distracting the spinous processes. Although the initial reports represented the IPD as a safe, effective, and minimally invasive surgical alternative for relief of neurological symptoms in patients with low back degenerative diseases, recent studies have demonstrated less impressive clinical results and higher rate of failure than initially reported. The purpose of this paper is to provide a comprehensive overview on interspinous implants, their mechanisms of action, safety, cost, and effectiveness in the treatment of lumbar stenosis and degenerative disc diseases. PMID:24822224

  6. Regenerative nanomedicine and the treatment of degenerative retinal diseases.

    PubMed

    Zarbin, Marco A; Montemagno, Carlo; Leary, James F; Ritch, Robert

    2012-01-01

    Regenerative medicine deals with the repair or the replacement of tissues and organs using advanced materials and methodologies. Regenerative nanomedicine uses nanoparticles containing gene transcription factors and other modulating molecules that allow reprogramming of cells in vivo as well as nanomaterials to induce selective differentiation of neural progenitor cells and to create neural-mechanical interfaces. In this article, we consider some applications of nanotechnology that may be useful for the treatment of degenerative retinal diseases, for example, use of nanoparticles for drug and gene therapy, use of nanomaterials for neural interfaces and extracellular matrix construction for cell-based therapy and neural prosthetics, and the use of bionanotechnology to re-engineer proteins and cell behavior for regenerative medicine. PMID:22170869

  7. The Degenerative Spine.

    PubMed

    Clarençon, Frédéric; Law-Ye, Bruno; Bienvenot, Peggy; Cormier, Évelyne; Chiras, Jacques

    2016-08-01

    Degenerative disease of the spine is a leading cause of back pain and radiculopathy, and is a frequent indication for spine MR imaging. Disc degeneration, disc protrusion/herniation, discarhtrosis, spinal canal stenosis, and facet joint arthrosis, as well as interspinous processes arthrosis, may require an MR imaging workup. This review presents the MR imaging patterns of these diseases and describes the benefit of the MR imaging in these indications compared with the other imaging modalities like plain radiographs or computed tomography scan. PMID:27417397

  8. Molecular mechanisms underlying the onset of degenerative aortic valve disease.

    PubMed

    Hakuno, Daihiko; Kimura, Naritaka; Yoshioka, Masatoyo; Fukuda, Keiichi

    2009-01-01

    Morbidity from degenerative aortic valve disease is increasing worldwide, concomitant with the ageing of the general population and the habitual consumption of diets high in calories and cholesterol. Immunohistologic studies have suggested that the molecular mechanism occurring in the degenerate aortic valve resembles that of atherosclerosis, prompting the testing of HMG CoA reductase inhibitors (statins) for the prevention of progression of native and bioprosthetic aortic valve degeneration. However, the effects of these therapies remain controversial. Although the molecular mechanisms underlying the onset of aortic valve degeneration are largely unknown, research in this area is advancing rapidly. The signaling components involved in embryonic valvulogenesis, such as Wnt, TGF-beta(1), BMP, and Notch, are also involved in the onset of aortic valve degeneration. Furthermore, investigations into extracellular matrix remodeling, angiogenesis, and osteogenesis in the aortic valve have been reported. Having noted avascularity of normal cardiac valves, we recently identified chondromodulin-I (chm-I) as a crucial anti-angiogenic factor. The expression of chm-I is restricted to cardiac valves from late embryogenesis to adulthood in the mouse, rat, and human. In human degenerate atherosclerotic valves, the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases and angiogenesis is observed in the area of chm-I downregulation. Gene targeting of chm-I resulted in VEGF expression, angiogenesis, and calcification in the aortic valves of aged mice, and aortic stenosis is detected by echocardiography, indicating that chm-I is a crucial factor for maintaining normal cardiac valvular function by preventing angiogenesis. The present review focuses on the animal models of aortic valve degeneration and recent studies on the molecular mechanisms underlying the onset of degenerative aortic valve disease. PMID:18766323

  9. Both expression of cytokines and posterior annulus fibrosus rupture are essential for pain behavior changes induced by degenerative intervertebral disc: An experimental study in rats.

    PubMed

    Li, Zemin; Liu, Hui; Yang, Hao; Wang, Jianru; Wang, Hua; Zhang, Kuibo; Ding, Wenbin; Zheng, Zhaomin

    2014-02-01

    The aim of this study was to analyze the relationship between intervertebral disc degeneration and low back pain (LBP). Rat L4/5 disc degeneration model was established by annular puncture using a 0.4 mm needle anteriorly or posteriorly. In both anterior and posterior puncture models, magnetic resonance imaging (MRI) and histological analyses revealed marked disc degeneration 2 weeks after puncture. Cytokine expression was up-regulated in different level in nucleus pulposus (NP) from 3 days after puncture. Pain behavioral tests indicated that the anterior disc puncture did not induce pain behavior changes, whereas the posterior disc puncture resulted in mechanical allodynia from 1 day to 21 days after injury. Besides, cytokine expression was significantly increased in dorsal root ganglion (DRG) at 1 and 2 weeks after posterior puncture, but not after the anterior puncture. These findings indicate the NP of the degenerative disc expresses different levels of inflammatory cytokines, and posterior disc puncture produced mechanical allodynia. The expression phase of cytokines in the NP was accordance with mechanical hyperalgesia in the posterior disc puncture model. Both expression of cytokines and posterior annulus fibrosus (AF) rupture in degenerative intervertebral disc are essential for pain behavior changes. PMID:24115280

  10. A Prospective Study of the Functional Outcome of Anterior Cervical Discectomy With Fusion in Single Level Degenerative Cervical Disc Prolapse

    PubMed Central

    Kamani, Mayur M; Shetty, Vikram; Rai, H. Ravindranath; Hegde, Deepak

    2016-01-01

    Introduction Cervical spondylotic myelo-radiculopathy is a form of spinal cord dysfunction syndrome and usually accompanies age related degeneration of the spine. Aim To determine the functional outcome of anterior cervical discectomy with fusion and plating in single level degenerative cervical disc prolapse. Materials and Methods A total of 20 patients diagnosed with degenerative single level cervical disc prolapse who presented to the Department of Orthopaedic Surgery, Justice KS Hegde Charitable Hospital, Mangalore from the period of November 2012 to May 2014 were enrolled in the study. Complete clinical and radiological evaluation of the patients was done. A trial of conservative management was tried in all these patients for a period of two months. They were taken up for surgery only when conservative management had failed. Scoring of neck function before the surgery was done as per the Modified Japanese Orthopaedic Association (MJOA) score. All patients underwent anterior cervical discectomy and fusion (ACDF) with tricortical iliac crest bone grafting. Fixation was performed with titanium locking cervical plates. All patients were reviewed at 6 weeks and 6 months postoperatively. Assessment of neck function was done as per the MJOA scoring during all the reviews. Radiographic assessment was also done during all the reviews. The complications noted were documented. The statistical analysis was done using percentages; the arithmetic mean was calculated using SPSS software (version 16.0). Results Amongst the 20 patients included in the study, 1 patient died postoperatively due to oesophageal rupture. of the remaining 19 patients reviewed and followed up, all of them had improvement of symptoms and were reported to be in the ‘mild category’ as per the MJOA score. One patient developed dysphonia, in the immediate postoperative period due to recurrent laryngeal nerve palsy which recovered in a period of three months postoperative. Conclusion Single level

  11. Hybrid Surgery Combined with Dynamic Stabilization System and Fusion for the Multilevel Degenerative Disease of the Lumbosacral Spine

    PubMed Central

    Lee, Soo Eon; Kim, Hyun Jib

    2015-01-01

    Background As motion-preserving technique has been developed, the concept of hybrid surgery involves simultaneous application of two different kinds of devices, dynamic stabilization system and fusion technique. In the present study, the application of hybrid surgery for lumbosacral degenerative disease involving two-segments and its long-term outcome were investigated. Methods Fifteen patients with hybrid surgery (Hybrid group) and 10 patients with two-segment fusion (Fusion group) were retrospectively compared. Results Preoperative grade for disc degeneration was not different between the two groups, and the most common operated segment had the most degenerated disc grade in both groups; L4-5 and L5-S1 in the Hybrid group, and L3-4 and L4-5 in Fusion group. Over 48 months of follow-up, lumbar lordosis and range of motion (ROM) at the T12-S1 global segment were preserved in the Hybrid group, and the segmental ROM at the dynamic stabilized segment maintained at final follow-up. The Fusion group had a significantly decreased global ROM and a decreased segmental ROM with larger angles compared to the Hybrid group. Defining a 2-mm decrease in posterior disc height (PDH) as radiologic adjacent segment pathology (ASP), these changes were observed in 6 and 7 patients in the Hybrid and Fusion group, respectively. However, the last PDH at the above adjacent segment had statistically higher value in Hybrid group. Pain score for back and legs was much reduced in both groups. Functional outcome measured by Oswestry disability index (ODI), however, had better improvement in Hybrid group. Conclusion Hybrid surgery, combined dynamic stabilization system and fusion, can be effective surgical treatment for multilevel degenerative lumbosacral spinal disease, maintaining lumbar motion and delaying disc degeneration. PMID:26484008

  12. Regenerative therapies for equine degenerative joint disease: a preliminary study.

    PubMed

    Broeckx, Sarah; Zimmerman, Marieke; Crocetti, Sara; Suls, Marc; Mariën, Tom; Ferguson, Stephen J; Chiers, Koen; Duchateau, Luc; Franco-Obregón, Alfredo; Wuertz, Karin; Spaas, Jan H

    2014-01-01

    Degenerative joint disease (DJD) is a major cause of reduced athletic function and retirement in equine performers. For this reason, regenerative therapies for DJD have gained increasing interest. Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) were isolated from a 6-year-old donor horse. MSCs were either used in their native state or after chondrogenic induction. In an initial study, 20 horses with naturally occurring DJD in the fetlock joint were divided in 4 groups and injected with the following: 1) PRP; 2) MSCs; 3) MSCs and PRP; or 4) chondrogenic induced MSCs and PRP. The horses were then evaluated by means of a clinical scoring system after 6 weeks (T1), 12 weeks (T2), 6 months (T3) and 12 months (T4) post injection. In a second study, 30 horses with the same medical background were randomly assigned to one of the two combination therapies and evaluated at T1. The protein expression profile of native MSCs was found to be negative for major histocompatibility (MHC) II and p63, low in MHC I and positive for Ki67, collagen type II (Col II) and Vimentin. Chondrogenic induction resulted in increased mRNA expression of aggrecan, Col II and cartilage oligomeric matrix protein (COMP) as well as in increased protein expression of p63 and glycosaminoglycan, but in decreased protein expression of Ki67. The combined use of PRP and MSCs significantly improved the functionality and sustainability of damaged joints from 6 weeks until 12 months after treatment, compared to PRP treatment alone. The highest short-term clinical evolution scores were obtained with chondrogenic induced MSCs and PRP. This study reports successful in vitro chondrogenic induction of equine MSCs. In vivo application of (induced) MSCs together with PRP in horses suffering from DJD in the fetlock joint resulted in a significant clinical improvement until 12 months after treatment. PMID:24465787

  13. Does degenerative disease of the lumbar spine cause arachnoiditis? A magnetic resonance study and review of the literature.

    PubMed

    Jackson, A; Isherwood, I

    1994-09-01

    The magnetic resonance appearances in 165 patients with symptoms suggestive of degenerative lumbar spine disease were reviewed. The aim of the study was to evaluate the relationship between abnormalities of nerve root distribution and degenerative disease of the lumbar spine in the absence of other known risk factors for arachnoiditis. Central clumping of nerve roots was present in 16 patients (9.7%) and was associated with spinal stenosis at one of the affected levels in all (p < 0.001). Spinal stenosis was present in 44 patients giving an incidence of abnormal nerve root distribution of 36% in this group. Nerve root clumping occurred in association with pure spinal stenosis (10 cases), stenosis secondary to disc prolapse (four cases) and degenerative spondylolisthesis (two cases). Nerve root clumping was confined to one vertebral level in nine cases and extended over two to four levels in seven. In five of the latter spinal stenosis was present at multiple levels. The appearance of nerve root clumping described here may result entirely from mechanical apposition of nerve roots but is indistinguishable from the central pattern of nerve root adhesions which occurs in adhesive lumbar arachnoiditis. No abnormalities of nerve root distribution were seen in association with any indicator of degenerative disk disease in the absence of stenosis. We have been unable to demonstrate the previously reported relationship between lumbar disk degeneration and arachnoiditis and discuss this with a critical review of the literature. Abnormal central clumping of nerve roots as described in arachnoiditis may occur in association with spinal stenosis in the absence of other risk factors although the cause for this appearance remains unexplained. Arachnoiditis-like changes extending over more than one vertebral level are rare (7%) except in the presence of spinal stenosis at multiple levels (29%). Awareness of this appearance may avoid a possibly incorrect diagnosis of arachnoiditis

  14. A Novel, Minimally-Invasive Approach to Repair Degenerative Disk Disease in an Ovine Model Using Injectable Polymethyl-Methacrylate and Bovine Collagen (PMMA/BC)

    PubMed Central

    Feldman, Erica; Narayan, Anisha; Taylor, William

    2016-01-01

    Background : The natural, inflammatory repair processes of an injured intervertebral degenerative disc can propagate further injury and destruction. While there are many different treatment modalities of the pain related to degenerative disc disease, none are actually reparative in nature. Treatment strategies to repair a degenerative disc without inducing a destructive inflammatory milieu have been elusive.  Purpose: The purpose of this experiment is to discover the feasibility of reconstructing an injured intervertebral disc using an injected, inert polymer as the foundation for endogenous collagen growth. Study Design: In this ovine model of six subjects in total, we introduce a modality where a large inert polymer, polymethyl methacrylate (PMMA), in conjunction bovine collagen (BC) is injected into the intervertebral disc. Following six months of observation, histologic specimens were evaluated macroscopically and microscopically for evidence of a benefit of the injectable PMMA/BC. Methods: We obtained six merino sheep for this study. Concentric injuries were made to four of their lumbar intervertebral discs. Two of those levels were treated with a percutaneous injection of 0.3 cc of PMMA/BC. The remaining lumbar levels were left untreated and were our controls. After six months, all subjects were sacrificed. Their four levels were extracted and were examined macroscopically and microscopically. Results: All subjects tolerated the lumbar injury and percutaneous injection of PMMA/BC well. After the six month interval, all subjects have demonstrated an intact architecture of their lumbar disc height at the macroscopic and microscopic level. Microscopically, there was no evidence of external migration of the PMMA/BC microspheres, nor was there any evidence of an inflammatory response by its presence. Notably, the PMMA/BC microspheres were well-incorporated into the concentric disc tears and had undergone endogenous collagen formation in its environment

  15. [Pathobiochemistry of joint destruction in inflammatory and degenerative joint diseases].

    PubMed

    Greiling, H; Kleesiek, K; Reinards, R

    1987-08-01

    While the biochemical mechanism which leads to the destruction of joints in the course of degenerative and inflammatory arthropathies has not been cleared up completely to this day, basic differences have been noted in the way the two types of arthropathy affect the articular cartilage. The differences are described from the viewpoint of pathobiochemistry as they are fundamental to causal therapy. PMID:3314203

  16. Bowman lecture on the role of inflammation in degenerative disease of the eye

    PubMed Central

    Forrester, J V

    2013-01-01

    Inflammation, in the pathogenesis of many diseases previously thought to be strictly genetic, degenerative, metabolic, or endocrinologic in aetiology, has gradually entered the framework of a general mechanism of disease. This is exemplified by conditions such as Parkinson's disease, Alzheimer's disease, atherosclerosis, diabetes, and the more recently described Metabolic Syndrome. Chronic inflammatory processes have a significant, if not primary role, in ophthalmic diseases, particularly in retinal degenerative diseases. However, inflammation itself is not easy to define, and some aspects of inflammation may be beneficial, in a process described as ‘para-inflammation' by Medhzitov. In contrast, the damaging effects of inflammation, mediated by pro-inflammatory macrophages through activation of the intracellular protein-signalling complexes, termed inflammasomes, are well recognised and are important therapeutic targets. In this review, the range of inflammatory processes in the eye is evaluated in the context of how these processes impact upon retinal degenerative disease, particularly diabetic retinopathy and age-related macular degeneration. PMID:23288138

  17. Detection of degenerative disease of the temporomandibular joint by bone scintigraphy: concise communication

    SciTech Connect

    Goldstein, H.A.; Bloom, C.Y.

    1980-10-01

    Nine patients with facial pain were evaluated with limited bone scans. The scintigrams correlated with microscopy in all patients, although radiographs correlated with microscopy in only five patients. The degenerative disease process in the temporomandibular joint was more extensive in the patients with radiographic and scintigraphic abnormalities than in those with scintigraphic abnormalities alone. The limited bone scan appears useful in detecting early degenerative changes in the temporomandibular joint.

  18. The degenerative cervical spine.

    PubMed

    Llopis, E; Belloch, E; León, J P; Higueras, V; Piquer, J

    2016-04-01

    Imaging techniques provide excellent anatomical images of the cervical spine. The choice to use one technique or another will depend on the clinical scenario and on the treatment options. Plain-film X-rays continue to be fundamental, because they make it possible to evaluate the alignment and bone changes; they are also useful for follow-up after treatment. The better contrast resolution provided by magnetic resonance imaging makes it possible to evaluate the soft tissues, including the intervertebral discs, ligaments, bone marrow, and spinal cord. The role of computed tomography in the study of degenerative disease has changed in recent years owing to its great spatial resolution and its capacity to depict osseous components. In this article, we will review the anatomy and biomechanical characteristics of the cervical spine, and then we provide a more detailed discussion of the degenerative diseases that can affect the cervical spine and their clinical management. PMID:26878769

  19. The ProDisc artificial disc: insertion technique.

    PubMed

    Aryan, Henry E; Acosta, Frank L; Ames, Christopher P

    2005-10-01

    The ProDisc artificial lumbar disc was designed for use in treatment of degenerative lumbar disease. The disc is implanted using an anterior approach to the lumbar spine with the assistance of intraoperative fluoroscopy. A variety of insertion instruments guide the surgeon through this process. The disc is implanted via an anterior approach, generally retroperitoneally but on occasion transperitoneally. The different approaches and insertion technique are described in this article. PMID:16326288

  20. Sagittal balance of the pelvis-spine complex and lumbar degenerative diseases. A comparative study about 85 cases

    PubMed Central

    Jund, Jérôme; Noseda, Olivier; Roussouly, Pierre

    2007-01-01

    Retrospective analysis of the spino-pelvic alignment in a population of 85 patients with a lumbar degenerative disease. Several previous publications reported the analysis of spino-pelvic alignment in the normal and low back pain population. Data suggested that patients with lumbar diseases have variations of sagittal alignment such as less distal lordosis, more proximal lumbar lordosis and a more vertical sacrum. Nevertheless most of these variations have been reported without reference to the pelvis shape which is well-known to strongly influence spino-pelvic alignment. The objective of this study was to analyse spino-pelvic parameters, including pelvis shape, in a population of 85 patients with a lumbar degenerative disease and compare these patients with a control group of normal volunteers. We analysed three different lumbar degenerative diseases: disc herniation (DH), n = 25; degenerative disc disease (DDD), n = 32; degenerative spondylolisthesis (DSPL), n = 28. Spino-pelvic alignment was analysed pre-operatively on full spine radiographs. Spino-pelvic parameters were measured as following: pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, thoracic kyphosis, spino-sacral angle and positioning of C7 plumb line. For each group of patients the sagittal profile was compared with a control population of 154 asymptomatic adults that was the subject of a previous study. In order to understand variations of spino-pelvic parameters in the patients’ population a stratification (matching) according to the pelvic incidence was done between the control group and each group of patients. Concerning first the pelvis shape, patients with DH and those with DDD demonstrated to have a mean pelvic incidence equal to 49.8° and 51.6°, respectively, versus 52° for the control group (no significant difference). Only young patients, less than 45 years old, with a disc disease (DH or DDD) demonstrated to have a pelvic incidence significantly lower (48.3°) than

  1. Surgical results of dynamic nonfusion stabilization with the Segmental Spinal Correction System for degenerative lumbar spinal diseases with instability: Minimum 2-year follow-up

    PubMed Central

    Ohta, Hideki; Matsumoto, Yoshiyuki; Morishita, Yuichirou; Sakai, Tsubasa; Huang, George; Kida, Hirotaka; Takemitsu, Yoshiharu

    2011-01-01

    Background When spinal fusion is applied to degenerative lumbar spinal disease with instability, adjacent segment disorder will be an issue in the future. However, decompression alone could cause recurrence of spinal canal stenosis because of increased instability on operated segments and lead to revision surgery. Covering the disadvantages of both procedures, we applied nonfusion stabilization with the Segmental Spinal Correction System (Ulrich Medical, Ulm, Germany) and decompression. Methods The surgical results of 52 patients (35 men and 17 women) with a minimum 2-year follow-up were analyzed: 10 patients with lumbar spinal canal stenosis, 15 with lumbar canal stenosis with disc herniation, 20 with degenerative spondylolisthesis, 6 with disc herniation, and 1 with lumbar discopathy. Results The Japanese Orthopaedic Association score was improved, from 14.4 ± 5.3 to 25.5 ± 2.8. The improvement rate was 76%. Range of motion of the operated segments was significantly decreased, from 9.6° ± 4.2° to 2.0° ± 1.8°. Only 1 patient had adjacent segment disease that required revision surgery. There was only 1 screw breakage, but the patient was asymptomatic. Conclusions Over a minimum 2-year follow-up, the results of nonfusion stabilization with the Segmental Spinal Correction System for unstable degenerative lumbar disease were good. It is necessary to follow up the cases with a focus on adjacent segment disorders in the future. PMID:25802671

  2. Histone Deacetylases Inhibitors in the Treatment of Retinal Degenerative Diseases: Overview and Perspectives

    PubMed Central

    Dai, Xufeng; Du, Wei; Pang, Ji-jing

    2015-01-01

    Retinal degenerative diseases are one of the important refractory ophthalmic diseases, featured with apoptosis of photoreceptor cells. Histone acetylation and deacetylation can regulate chromosome assembly, gene transcription, and posttranslational modification, which are regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. The histone deacetylase inhibitors (HDACis) have the ability to cause hyperacetylation of histone and nonhistone proteins, resulting in a variety of effects on cell proliferation, differentiation, anti-inflammation, and anti-apoptosis. Several HDACis have been approved for clinical trials to treat cancer. Studies have shown that HDACis have neuroprotective effects in nervous system damage. In this paper, we will summarize the neuroprotective effects of common HDACis in retinal degenerative diseases and make a prospect to the applications of HDACis in the treatment of retinal degenerative diseases in the future. PMID:26137316

  3. Short term outcome of posterior dynamic stabilization system in degenerative lumbar diseases

    PubMed Central

    Yang, Mingyuan; Li, Chao; Chen, Ziqiang; Bai, Yushu; Li, Ming

    2014-01-01

    .80 to 2.92 ± 0.18 and 6.99 ± 0.81 to 3.25 ± 0.37, (both P < 0.001) and for PLIF, VAS for back and leg pain also improved significantly (6.97 ± 0.84–3.19 ± 0.19 and 7.26 ± 0.76–3.56 ± 0.38, both P < 0.001). Significant improvement was found at final followup in both groups in Oswestry disability index (ODI) score (both P < 0.001). Besides, Dynesys group showed a greater improvement in ODI and VAS back and leg pain scores compared with the PLIF group (P < 0.001, P = 0.009 and P = 0.031, respectively). For radiological, height of the operated level was found increased in both groups (both P < 0.001), but there was no difference between two groups (P = 0.93). For range of motion (ROM) of operated level, significant decrease was found in both groups (P < 0.001), but Dynesys showed a higher preservation of motion at the operative levels (P < 0.001). However, no significant difference was found in the percentage change of ROM of adjacent levels between Dynesys and PLIF (0.74 ± 8.92% vs. 0.92 ± 4.52%, P = 0.91). Some patients suffered from degeneration of adjacent intervertebral disc at final followup, but there was no significant difference in adjacent intervertebral disc degeneration between two groups (P = 0.71). Moreover, there were no differences in complications between Dynesys and PLIF (P = 0.90), although the incidence of complication in Dynesys was lower than PLIF (16.67% vs. 17.78%). Conclusion: Dynamic stabilization system treating lumbar degenerative disease showed clinical benefits with motion preservation of the operated segments, but does not have the significant advantage on motion preservation at adjacent segments, to avoid the degeneration of adjacent intervertebral disk. PMID:25404769

  4. The degenerative spine: pattern recognition and guidelines to image interpretation.

    PubMed

    Parizel, P M; Van Hoyweghen, A J L; Bali, A; Van Goethem, J; Van Den Hauwe, L

    2016-01-01

    Degenerative disease of the spine, in the form of intervertebral disc degeneration and bony growth, causing osteophytes and impinging upon the spinal canal and neural foramina, is the most frequent disorder affecting the spine. In this chapter we first discuss briefly the indications for computed tomography or magnetic resonance imaging in suspected degenerative spine disease. We then describe changes of disc height, signal intensity, and disc contour with aging and repeated microtrauma, as well as the imaging techniques most appropriate to image them. A grading system for lumbar disc changes is provided. Stenosis of the canal and neural foramina is reviewed next, concluding with a description of degenerative changes affecting the vertebral endplates and bone marrow. PMID:27430442

  5. Motor training in degenerative spinocerebellar disease: ataxia-specific improvements by intensive physiotherapy and exergames.

    PubMed

    Synofzik, Matthis; Ilg, Winfried

    2014-01-01

    The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames ("exergames"). The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability). Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease. PMID:24877117

  6. Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

    PubMed Central

    2014-01-01

    The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”). The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability). Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease. PMID:24877117

  7. Insights into neurogenesis and aging: potential therapy for degenerative disease?

    PubMed Central

    Marr, Robert A; Thomas, Rosanne M; Peterson, Daniel A

    2010-01-01

    Neurogenesis is the process by which new neural cells are generated from a small population of multipotent stem cells in the adult CNS. This natural generation of new cells is limited in its regenerative capabilities and also declines with age. The use of stem cells in the treatment of neurodegenerative disease may hold great potential; however, the age-related incidence of many CNS diseases coincides with reduced neurogenesis. This review concisely summarizes current knowledge related to adult neurogenesis and its alteration with aging and examines the feasibility of using stem cell and gene therapies to combat diseases of the CNS with advancing age. PMID:20806052

  8. Restoration of synaptic function in sight for degenerative retinal disease.

    PubMed

    Schubert, Timm; Wissinger, Bernd

    2015-07-01

    Synaptic disorganization is a prominent feature of many neurological diseases of the CNS, including Parkinson's disease, intellectual development disorders, and autism. Although synaptic plasticity is critical for learning and memory, it is unclear whether this innate property helps restore synaptic function in disease once the primary cause of disease is abrogated. An answer to this question may come from a recent investigation in X-linked retinoschisis, a currently untreatable retinopathy. In this issue of the JCI, Ou, Vijayasarathy, and colleagues showed progressive disorganization of key functional elements of the synapse between photoreceptors and ON-bipolar cells in a retinoschisin-deficient mouse model. Moreover, they demonstrated that adeno-associated virus-mediated (AAV-mediated) delivery of the retinoschisin gene restores structure and function to the photoreceptor to ON-bipolar cell synapse in mouse models, even in adults at advanced stages of the disease. The results of this study hold promise that AAV-based supplemental gene therapy will benefit patients with X-linked retinoschisis in a forthcoming clinical trial. PMID:26098210

  9. [Childhood feeding, chronic-degenerative disease in adults, and nutrigenomics].

    PubMed

    Caramia, G

    2007-01-01

    Significant advances have been made in understanding the relation between dietary factors and disease prevention. However, the identification of those who will or will not benefit from dietary intervention strategies remains a major obstacle. The execution of the Human Genome Project has brought forth a wealth of information about the structure of the genome and the spectacular development of broad genomics technologies have catalyzed a new era in both medicine and nutrition. Each person is genetically unique and phenotypically distinct, and the genetic makeup that individuals inherit from their ancestors is responsible for variation in responses to food. Evidence continues to implicate dietary components and genetic susceptibilities as important determinants of chronic diseases, cancer risk and tumor behavior. Variation in incidence among and within populations with similar dietary patterns suggests that an individual's response may reflect interactions with genetic factors, which may modify gene, protein, and metabolite expression patterns. Nutrigenetics studies the genetic basis of the different individual responses to the same nutritional stimulus and Nutrigenomics is defined as the interaction between nutrition and an individual's genome. With the application of "omic" technologies, proteomic, metabolomic, transcriptomic, will increase our fundamental knowledge of the interaction between life processes and diet. The identification of diet-gene interactions will offers an opportunity to develop dietary interventions that will lead to evidence-based dietary strategies for restoring health and fitness, obviate the effects of genetic factors for preventing diet-related diseases and provide important clues about gene expression and gene modulation by environmental factors. PMID:18410060

  10. [Role of defective intracellular proteolysis in human degenerative diseases].

    PubMed

    Nezelof, Christian

    2012-11-01

    the nature of proteolysis. In this article, therefore, the following distinction should be made:--Lysosomal failures. They represent hereditary metabolic disorders involving all categories of cells. They are characterized by the accumulation of homogeneous material related to the underlying disease. Young people are predominantly affected--UPS failures. They represent sporadic conditions principally involving long-lived cells. The accumulated material is heterogeneous, composed of abnormal proteins and various "garbage-like" waste, including pigments. The elderly are predominatly affected, suggesting an epigenetic wear and tear process. Hypothetically, most the sporadic neurodegenerative diseases, from retinal macular degeneration and its associated drüsen to Alzheimer's disease, Parkinson's disease may represent fairly good examples of the UPS deficit. PMID:24313014

  11. [Whiplash injury of the cervical spine--on the role of pre-existing degenerative diseases].

    PubMed

    Meenen, N M; Katzer, A; Dihlmann, S W; Held, S; Fyfe, I; Jungbluth, K H

    1994-06-01

    Radiological investigations contribute little in differentiating the problems of patients with whiplash injuries. Nevertheless the more prolonged cases of whiplash injuries must not be attributed to preexisting degenerative disease, despite radiologically-proven medicolegal opinion. In this study, 60 patients who were seen for whiplash injuries in the Department for Trauma and Reconstructive Surgery at the University Hospital Hamburg-Eppendorf for clinical and radiological evaluation, an average of 5.7 years post injury, were divided into two groups (n = 30) depending on radiologically-proven preexisting degenerative changes of the cervical spine. On average the patients with degenerative changes were 11.2 years older than those with healthy vertebral columns and also demonstrated an increase in acute symptoms in the lower cervical spine (cervicobrachial syndrome). The chronicity of individual symptoms such as neck-pain, dizziness, nausea and psychological illness was also observed in both groups. Problems such as paresthesias as well as pain in the shoulder-arm-area appeared to increase in subsequent check-ups, irrespective of the earlier degenerative changes. Patients with typical posterior headaches recovered faster when they had radiologically normal spines. Presenting late, there was a significant accumulation of patients with pre-existing degenerative changes complaining merely of tinnitus. The earlier changes in any individual motion segment do not determine the clinical course of whiplash injuries, but merely represent an area of increased vulnerability to trauma. On the other hand, trauma has not been proven to influence the development or aggravation of degenerative changes in normal or diseased spines. We are not able to differentiate the posttraumatic course from the natural history of the degenerative process, either clinically or radiologically. Considering the involvement of sensitive neurological structures the classical objective organic diagnosis

  12. Vitamin A Derivatives as Treatment Options for Retinal Degenerative Diseases

    PubMed Central

    Perusek, Lindsay; Maeda, Tadao

    2013-01-01

    The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT) and retinal pigment epithelium-specific 65-kDa protein (RPE65) known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients. PMID:23857173

  13. [Theoretic basis on the same therapeutic program for different degenerative brain diseases in terms of the Governor Vessel: Alzheimer's disease and Parkinson's disease].

    PubMed

    Wu, Junyan; Wang, Jie; Zhang, Junlong

    2015-05-01

    Through the consultation of TCM ancient classical theory, the relationship of kidney essence, marrow and brain is analyzed. It is discovered that the degenerative brain diseases, represented by Alzheimer's disease (AD) and Parkinson's disease (PD) share the same etiological basis as "kidney essence deficiency and brain marrow emptiness" and have the mutual pathological outcomes as yang qi declining. The Governor Vessel gathers yang qi of the whole body and maintains the normal functional activity of zangfu organs in the human body through the storage, regulation and invigoration of yang qi. It is viewed that the theory of the Governor Vessel is applied to treat the different degenerative brain diseases, which provides the theoretic support and practice guide for the thought of TCM as the same therapeutic program for the different diseases. As a result, the degenerative brain diseases can be retarded and the approach is provided to the effective prevention and treatment of degenerative diseases in central nerve system: PMID:26255528

  14. Regeneration of the retina: toward stem cell therapy for degenerative retinal diseases.

    PubMed

    Jeon, Sohee; Oh, Il-Hoan

    2015-04-01

    Degenerative retinal diseases affect millions of people worldwide, which can lead to the loss of vision. However, therapeutic approaches that can reverse this process are limited. Recent efforts have allowed the possibility of the stem cell-based regeneration of retinal cells and repair of injured retinal tissues. Although the direct differentiation of pluripotent stem cells into terminally differentiated photoreceptor cells comprises one approach, a series of studies revealed the intrinsic regenerative potential of the retina using endogenous retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and retinal pigment epithelial cells are candidates for such retinal stem cells that can differentiate into multiple types of retinal cells and be integrated into injured or developing retina. In this review, we explore our current understanding of the cellular identity of these candidate retinal stem cells and their therapeutic potential for cell therapy against degenerative retinal diseases. PMID:25560700

  15. Neuroimaging and Genetic Risk for Alzheimer’s Disease and Addiction-Related Degenerative Brain Disorders

    PubMed Central

    Jahanshad, Neda; Leonardo, Cassandra D.; Thompson, Paul M.

    2014-01-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer’s disease (AD). Here we describe how multimodal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimaging studies of genetic polymorphisms associated with increased risk for late-onset Alzheimer’s disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear. PMID:24142306

  16. Disparities in Rates of Spine Surgery for Degenerative Spine Disease Between HIV Infected and Uninfected Veterans

    PubMed Central

    King, Joseph T.; Gordon, Adam J.; Perkal, Melissa F.; Crystal, Stephen; Rosenthal, Ronnie A.; Rodriguez-Barradas, Maria C.; Butt, Adeel A.; Gibert, Cynthia L.; Rimland, David; Simberkoff, Michael S.; Justice, Amy C.

    2011-01-01

    Study Design Retrospective analysis of nationwide Veterans Health Administration (VA) clinical and administrative data. Objective Examine the association between HIV infection and the rate of spine surgery for degenerative spine disease. Summary of Background Data Combination anti-retroviral therapy (cART) has prolonged survival in patients with HIV/AIDS, increasing the prevalence of chronic conditions such as degenerative spine disease that may require spine surgery. Methods We studied all HIV infected patients under care in the VA from 1996–2008 (n=40,038) and uninfected comparator patients (n=79,039) matched on age, gender, race, year, and geographic region. The primary outcome was spine surgery for degenerative spine disease defined by ICD-9 procedure and diagnosis codes. We used a multivariate Poisson regression to model spine surgery rates by HIV infection status, adjusting for factors that might affect suitability for surgery (demographics, year, comorbidities, body mass index, cART, and laboratory values). Results Two-hundred twenty eight HIV infected and 784 uninfected patients underwent spine surgery for degenerative spine disease during 700,731 patient-years of follow-up (1.44 surgeries per 1,000 patient-years). The most common procedures were spinal decompression (50%), and decompression and fusion (33%); the most common surgical sites were the lumbosacral (50%), and cervical (40%) spine. Adjusted rates of surgery were lower for HIV infected patients (0.86 per 1,000 patient-years of follow-up) than for uninfected patients (1.41 per 1,000 patient-years; IRR 0.61, 95% CI: 0.51, 0.74, P<0.001). Among HIV infected patients, there was a trend towards lower rates of spine surgery in patients with detectable viral loads levels (IRR 0.76, 95% CI: 0.55, 1.05, P=0.099). Conclusion In the VA, HIV infected patients experience significantly reduced rates of surgery for degenerative spine disease. Possible explanations include disease prevalence, emphasis on

  17. Delivering Mesenchymal Stem Cells in Collagen Microsphere Carriers to Rabbit Degenerative Disc: Reduced Risk of Osteophyte Formation

    PubMed Central

    Li, Yuk Yin; Diao, Hua Jia; Chik, Tze Kit; Chow, Cin Ting; An, Xiao Meng; Leung, Victor; Cheung, Kenneth Man Chi

    2014-01-01

    Mesenchymal stem cells (MSCs) have the potential to treat early intervertebral disc (IVD) degeneration. However, during intradiscal injection, the vast majority of cells leaked out even in the presence of hydrogel carrier. Recent evidence suggests that annulus puncture is associated with cell leakage and contributes to osteophyte formation, an undesirable side effect. This suggests the significance of developing appropriate carriers for intradiscal delivery of MSCs. We previously developed a collagen microencapsulation platform, which entraps MSCs in a solid microsphere consisting of collagen nanofiber meshwork. These solid yet porous microspheres support MSC attachment, survival, proliferation, migration, differentiation, and matrix remodeling. Here we hypothesize that intradiscal injection of MSCs in collagen microspheres will outperform that of MSCs in saline in terms of better functional outcomes and reduced side effects. Specifically, we induced disc degeneration in rabbits and then intradiscally injected autologous MSCs, either packaged within collagen microspheres or directly suspended in saline, into different disc levels. Functional outcomes including hydration index and disc height were monitored regularly until 6 months. Upon sacrifice, the involved discs were harvested for histological, biochemical, and biomechanical evaluations. MSCs in collagen microspheres showed advantage over MSCs in saline in better maintaining the dynamic mechanical behavior but similar performance in hydration and disc height maintenance and matrix composition. More importantly, upon examination of gross appearance, radiograph, and histology of IVD, delivering MSCs in collagen microspheres significantly reduced the risk of osteophyte formation as compared to that in saline. This work demonstrates the significance of using cell carriers during intradiscal injection of MSCs in treating disc degeneration. PMID:24372278

  18. Fusion versus Bryan Cervical Disc in two-level cervical disc disease: a prospective, randomised study

    PubMed Central

    Nie, Lin; Zhang, Li; Hou, Yong

    2008-01-01

    In this prospective study, our aim was to compare the functional results and radiographic outcomes of fusion and Bryan Cervical Disc replacement in the treatment of two-level cervical disc disease. A total of 65 patients with two-level cervical disc disease were randomly assigned to two groups, those operated on with Bryan Cervical Disc replacement (31) and those operated on with anterior cervical fusion with an iliac crest autograft and plate (34). Clinical evaluation was carried out using the visual analogue scale (VAS), the Short Form 36 (SF-36) and the neck disability index (NDI) during a two year follow-up. Radiological evaluation sought evidence of range of motion, stability and subsidence of the prosthesis. Substantial reduction in NDI scores occurred in both groups, with greater percent improvement in the Bryan group (P = 0.023). The arm pain VAS score improvement was substantial in both groups. Bryan artificial cervical disc replacement seems reliable and safe in the treatment of patients with two-level cervical disc disease. PMID:18956190

  19. Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Patel, Zarana; Huff, Janice; Saha, Janapriya; Wang, Minli; Blattnig, Steve; Wu, Honglu; Cucinotta, Francis

    2015-01-01

    Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray

  20. Novel Strategies for the Improvement of Stem Cells' Transplantation in Degenerative Retinal Diseases

    PubMed Central

    Nicoară, Simona Delia; Șușman, Sergiu; Tudoran, Oana; Bărbos, Otilia; Cherecheș, Gabriela; Aștilean, Simion; Potara, Monica; Sorițău, Olga

    2016-01-01

    Currently, there is no cure for the permanent vision loss caused by degenerative retinal diseases. One of the novel therapeutic strategies aims at the development of stem cells (SCs) based neuroprotective and regenerative medicine. The main sources of SCs for the treatment of retinal diseases are the embryo, the bone marrow, the region of neuronal genesis, and the eye. The success of transplantation depends on the origin of cells, the route of administration, the local microenvironment, and the proper combinative formula of growth factors. The feasibility of SCs based therapies for degenerative retinal diseases was proved in the preclinical setting. However, their translation into the clinical realm is limited by various factors: the immunogenicity of the cells, the stability of the cell phenotype, the predilection of SCs to form tumors in situ, the abnormality of the microenvironment, and the association of a synaptic rewiring. To improve SCs based therapies, nanotechnology offers a smart delivery system for biomolecules, such as growth factors for SCs implantation and differentiation into retinal progenitors. This review explores the main advances in the field of retinal transplantology and applications of nanotechnology in the treatment of retinal diseases, discusses the challenges, and suggests new therapeutic approaches in retinal transplantation. PMID:27293444

  1. Picking a bone with WISP1 (CCN4): new strategies against degenerative joint disease

    PubMed Central

    Maiese, Kenneth

    2016-01-01

    As the world’s population continues to age, it is estimated that degenerative joint disease disorders such as osteoarthritis will impact at least 130 million individuals throughout the globe by the year 2050. Advanced age, obesity, genetics, gender, bone density, trauma, and a poor level of physical activity can lead to the onset and progression of osteoarthritis. However, factors that lead to degenerative joint disease and involve gender, genetics, epigenetic mechanisms, and advanced age are not within the control of an individual. Furthermore, current therapies including pain management, improved nutrition, and regular programs for exercise do not lead to the resolution of osteoarthritis. As a result, new avenues for targeting the treatment of osteoarthritis are desperately needed. Wnt1 inducible signaling pathway protein 1 (WISP1), a matricellular protein and a downstream target of the wingless pathway Wnt1, is one such target to consider that governs cellular protection, stem cell proliferation, and tissue regeneration in a number of disorders including bone degeneration. However, increased WISP1 expression also has been associated with the progression of osteoarthritis. WISP1 has an intricate relationship with a number of proliferative and protective pathways that include phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin -6 (IL-6), transforming growth factor-β, matrix metalloproteinase, small non-coding ribonucleic acids (RNAs), sirtuin silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and the mechanistic target of rapamycin (mTOR). Taken together, this complex association WISP1 holds with these signaling pathways necessitates a fine biological regulation of WISP1 activity that can offset the progression of degenerative joint disease, but not limit the cellular protective capabilities of the WISP1 pathway. PMID:26893943

  2. Comparison of the Dynesys Dynamic Stabilization System and Posterior Lumbar Interbody Fusion for Lumbar Degenerative Disease

    PubMed Central

    Zhang, Yang; Shan, Jian-Lin; Liu, Xiu-Mei; Li, Fang; Guan, Kai; Sun, Tian-Sheng

    2016-01-01

    Background There have been few studies comparing the clinical and radiographic outcomes between the Dynesys dynamic stabilization system and posterior lumbar interbody fusion (PLIF). The objective of this study is to compare the clinical and radiographic outcomes of Dynesys and PLIF for lumbar degenerative disease. Methods Of 96 patients with lumbar degenerative disease included in this retrospectively analysis, 46 were treated with the Dynesys system and 50 underwent PLIF from July 2008 to March 2011. Clinical and radiographic outcomes were evaluated. We also evaluated the occurrence of radiographic and symptomatic adjacent segment degeneration (ASD). Results The mean follow-up time in the Dynesys group was 53.6 ± 5.3 months, while that in the PLIF group was 55.2 ± 6.8 months. At the final follow-up, the Oswestry disability index and visual analogue scale score were significantly improved in both groups. The range of motion (ROM) of stabilized segments in Dynesys group decreased from 7.1 ± 2.2° to 4.9 ± 2.2° (P < 0.05), while that of in PLIF group decreased from 7.3 ± 2.3° to 0° (P < 0.05). The ROM of the upper segments increased significantly in both groups at the final follow-up, the ROM was higher in the PLIF group. There were significantly more radiographic ASDs in the PLIF group than in the Dynesys group. The incidence of complications was comparable between groups. Conclusions Both Dynesys and PLIF can improve the clinical outcomes for lumbar degenerative disease. Compared to PLIF, Dynesys stabilization partially preserves the ROM of the stabilized segments, limits hypermobility in the upper adjacent segment, and may prevent the occurrence of ASD. PMID:26824851

  3. Preliminary results of automated removal of degenerative joint disease in bone scan lesion segmentation

    NASA Astrophysics Data System (ADS)

    Chu, Gregory H.; Lo, Pechin; Kim, Hyun J.; Auerbach, Martin; Goldin, Jonathan; Henkel, Keith; Banola, Ashley; Morris, Darren; Coy, Heidi; Brown, Matthew S.

    2013-03-01

    Whole-body bone scintigraphy (or bone scan) is a highly sensitive method for visualizing bone metastases and is the accepted standard imaging modality for detection of metastases and assessment of treatment outcomes. The development of a quantitative biomarker using computer-aided detection on bone scans for treatment response assessment may have a significant impact on the evaluation of novel oncologic drugs directed at bone metastases. One of the challenges to lesion segmentation on bone scans is the non-specificity of the radiotracer, manifesting as high activity related to non-malignant processes like degenerative joint disease, sinuses, kidneys, thyroid and bladder. In this paper, we developed an automated bone scan lesion segmentation method that implements intensity normalization, a two-threshold model, and automated detection and removal of areas consistent with non-malignant processes from the segmentation. The two-threshold model serves to account for outlier bone scans with elevated and diffuse intensity distributions. Parameters to remove degenerative joint disease were trained using a multi-start Nelder-Mead simplex optimization scheme. The segmentation reference standard was constructed manually by a panel of physicians. We compared the performance of the proposed method against a previously published method. The results of a two-fold cross validation show that the overlap ratio improved in 67.0% of scans, with an average improvement of 5.1% points.

  4. [Prediction of outcomes of surgical treatment of degenerative lumbar disk disease].

    PubMed

    Zhuravlev, Iu I; Nazarenko, G I; Cherkashov, A M; Riazanov, V V; Nazarenko, A G

    2009-01-01

    The paper focuses on algorithms of outcomes assessment of surgical treatment of the patients with degenerative lumbar disk disease. From 1997 to 2006 389 patients with discogenic lumbar pain were operated in the Medical Center of Central Bank of Russia. 185 patients underwent radiofrequency destruction of facet nerves, laser percutaneous lumbar discectomy was performed in 39 patients, microdiscectomy -- in 131, and decompression combined with lumbar spine stabilization -- in 31 cases. Clinical and radiological data of each patient were recorded in the database using 3-point scale according to intensity of the feature. Assessment of patients' condition was performed pre- and postoperatively (after discharge and after 6, 12 and 24 months interval). Postoperative outcome was recorded for the current period in compliance with modified criteria of Kawabata et al. Obtained data were mathematically and statistically processed. Developed algorithms allowed assessment of postoperative outcome in the patients with degenerative lumbar disk disease. Outcome data can be used for evaluation of feasibility of surgical treatment as well as for selection of surgical technique. PMID:19505029

  5. Compounded pimobendan for canine chronic degenerative mitral valve disease and pulmonary hypertension.

    PubMed

    Helms, Scott R; Fox, Samantha; Mixon, William; Vail, Jane

    2012-01-01

    Pimobendan (Vetmedin) is an effective treatment for canine chronic degenerative mitral valve disease and dilated cardiomyopathy. In an off-label use, it may also be of benefit for the treatment of pulmonary hypertension in dogs. In this report, we describe the effects of a palatable customized oral form of pimobendan used with both compounded and commercially manufactured conventional drug therapy to treat degenerative mitral valve disease and pulmonary hypertension in two small dogs. For those patients, who resisted many types of oral medication, the standard manufactured dose of pimobendan was inappropriate. Formulations of the preparations used to treat the patients described in this report are provided for easy reference. It should be noted that at the time of this writing, Boehringer Ingelheim GmbH (Ingelheim am Rhein, Germany), the manufacturer of pimobendan, has expressed concern about the stability of that agent in aqueous compounded form. To our knowledge, no current data confirming the stability or bioequivalence of compounded pimobendan exist. PMID:23050309

  6. Radiological and Radionuclide Imaging of Degenerative Disease of the Facet Joints.

    PubMed

    Shur, Natalie; Corrigan, Alexis; Agrawal, Kanhaiyalal; Desai, Amidevi; Gnanasegaran, Gopinath

    2015-01-01

    The facet joint has been increasingly implicated as a potential source of lower back pain. Diagnosis can be challenging as there is not a direct correlation between facet joint disease and clinical or radiological features. The purpose of this article is to review the diagnosis, treatment, and current imaging modality options in the context of degenerative facet joint disease. We describe each modality in turn with a pictorial review using current evidence. Newer hybrid imaging techniques such as single photon emission computed tomography/computed tomography (SPECT/CT) provide additional information relative to the historic gold standard magnetic resonance imaging. The diagnostic benefits of SPECT/CT include precise localization and characterization of spinal lesions and improved diagnosis for lower back pain. It may have a role in selecting patients for local therapeutic injections, as well as guiding their location with increased precision. PMID:26170560

  7. Radiological and Radionuclide Imaging of Degenerative Disease of the Facet Joints

    PubMed Central

    Shur, Natalie; Corrigan, Alexis; Agrawal, Kanhaiyalal; Desai, Amidevi; Gnanasegaran, Gopinath

    2015-01-01

    The facet joint has been increasingly implicated as a potential source of lower back pain. Diagnosis can be challenging as there is not a direct correlation between facet joint disease and clinical or radiological features. The purpose of this article is to review the diagnosis, treatment, and current imaging modality options in the context of degenerative facet joint disease. We describe each modality in turn with a pictorial review using current evidence. Newer hybrid imaging techniques such as single photon emission computed tomography/computed tomography (SPECT/CT) provide additional information relative to the historic gold standard magnetic resonance imaging. The diagnostic benefits of SPECT/CT include precise localization and characterization of spinal lesions and improved diagnosis for lower back pain. It may have a role in selecting patients for local therapeutic injections, as well as guiding their location with increased precision. PMID:26170560

  8. Redox Signaling as a Therapeutic Target to Inhibit Myofibroblast Activation in Degenerative Fibrotic Disease

    PubMed Central

    Berger, Peter; Zenzmaier, Christoph

    2014-01-01

    Degenerative fibrotic diseases encompass numerous systemic and organ-specific disorders. Despite their associated significant morbidity and mortality, there is currently no effective antifibrotic treatment. Fibrosis is characterized by the development and persistence of myofibroblasts, whose unregulated deposition of extracellular matrix components disrupts signaling cascades and normal tissue architecture leading to organ failure and death. The profibrotic cytokine transforming growth factor beta (TGFβ) is considered the foremost inducer of fibrosis, driving myofibroblast differentiation in diverse tissues. This review summarizes recent in vitro and in vivo data demonstrating that TGFβ-induced myofibroblast differentiation is driven by a prooxidant shift in redox homeostasis. Elevated NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H2O2) supported by concomitant decreases in nitric oxide (NO) signaling and reactive oxygen species scavengers are central factors in the molecular pathogenesis of fibrosis in numerous tissues and organs. Moreover, complex interplay between NOX4-derived H2O2 and NO signaling regulates myofibroblast differentiation. Restoring redox homeostasis via antioxidants or NOX4 inactivation as well as by enhancing NO signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases can inhibit and reverse myofibroblast differentiation. Thus, dysregulated redox signaling represents a potential therapeutic target for the treatment of wide variety of different degenerative fibrotic disorders. PMID:24701562

  9. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    PubMed Central

    Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand

    2015-01-01

    Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases. PMID:25650393

  10. Changes in rates of arthroscopy due to degenerative knee disease and traumatic meniscal tears in Finland and Sweden

    PubMed Central

    Mattila, Ville M; Sihvonen, Raine; Paloneva, Juha; Felländer-Tsai, Li

    2016-01-01

    Background and purpose Knee arthroscopy is commonly performed to treat degenerative knee disease symptoms and traumatic meniscal tears. We evaluated whether the recent high-quality randomized control trials not favoring arthroscopic surgery for degenerative knee disease affected the procedure incidence and trends in Finland and Sweden. Patients and methods We conducted a bi-national registry-based study including all adult (aged ≥18 years) inpatient and outpatient arthroscopic surgeries performed for degenerative knee disease (osteoarthritis (OA) and degenerative meniscal tears) and traumatic meniscal tears in Finland between 1997 and 2012, and in Sweden between 2001 and 2012. Results In Finland, the annual number of operations was 16,389 in 1997, reached 20,432 in 2007, and declined to 15,018 in 2012. In Sweden, the number of operations was 9,944 in 2001, reached 11,711 in 2008, and declined to 8,114 in 2012. The knee arthroscopy incidence for OA was 124 per 105 person-years in 2012 in Finland and it was 51 in Sweden. The incidence of knee arthroscopies for meniscal tears coded as traumatic steadily increased in Finland from 64 per 105 person-years in 1997 to 97 per 105 person-years in 2012, but not in Sweden. Interpretation The incidence of arthroscopies for degenerative knee disease declined after 2008 in both countries. Remarkably, the incidence of arthroscopy for degenerative knee disease and traumatic meniscal tears is 2 to 4 times higher in Finland than in Sweden. Efficient implementation of new high-quality evidence in clinical practice could reduce the number of ineffective surgeries. PMID:26122621

  11. Chronic sole ulcerations associated with degenerative bone disease in two Asian elephants (Elephas maximus).

    PubMed

    Luikart, Kimberly A; Stover, Susan M

    2005-12-01

    Chronic foot lesions and degenerative joint disease are common causes of morbidity in elephants. Lesions may become intractable and progressive despite intensive treatment regimens. The forelimbs of two Asian elephants (Elephas maximus) with chronic nonhealing sole ulcerations were examined using manual dissection and computed tomography. Both elephants had abnormal limb conformation that preceded the development of sole ulcerations. In both cases, sole ulcers were associated with remodeling and degeneration of underlying bones of the digits. Conformational abnormalities and altered weight distribution in these individuals may have induced compensatory bony degeneration and secondary ulcer formation. Sole ulcerations associated with digital abnormalities may have a guarded prognosis for resolution, even with aggressive treatment. Because limb conformational abnormalities could predispose to or result from chronic digital lesions, elephants with conformational abnormalities may have increased likelihood of having chronic sole ulcerations. PMID:17312727

  12. Symptoms and signs of degenerative back disease in concrete reinforcement workers.

    PubMed

    Wickström, G

    1978-01-01

    Concrete reinforcement work causes great static loads on the back from the prolonged adoption of bent-double work postures during the tying of steel rods and from substantial dynamic loads during the lifting and pulling of rods from the stack. Subjective manifestations and objective signs of "degenerative back disease" are common in active reinforcement workers. An age- and sex-adjusted comparison of the findings was, however, possible only with one other occupational group, computer technicians, who also often work in awkward positions. A history of sciatica and pain during forward bending in a clinical examination were significantly more common in reinforcement workers than in computer technicians. This finding suggests an effect of reinforcement work on the back, but definite conclusions require further study. PMID:149368

  13. Chemical pathology of homocysteine. V. Thioretinamide, thioretinaco, and cystathionine synthase function in degenerative diseases.

    PubMed

    McCully, Kilmer S

    2011-01-01

    Hyperhomocysteinemia was first associated with degenerative disease by observation of accelerated arteriosclerosis in children with inherited disorders of cystathionine synthase, methionine synthase, and methylene tetrohydrofolate reductase. The metabolic blockade of sulfate synthesis from homocysteine thiolactone in malignant cells is ascribed to a deficiency of a chemopreventive derivative of homocysteine thiolactone that occurs in normal cells. Its chemical structure was elucidated by the organic synthesis of thioretinamide from retinoic acid and homocysteine thiolactone. Oxidation of the sulfur atom of homocysteine is inhibited in scorbutic guinea pigs, demonstrating ascorbate function in sulfate synthesis from homocysteine. Studies of homocysteine metabolism in protein energy malnutrition led to the conclusion that the biosynthesis of thioretinamide from the retinol of transthyretin is catalyzed by dehydroascorbate and superoxide generated from the heme oxygenase group of cystathionine synthase. Newly synthesized thioretinamide is complexed with cobalamin to form thioretinaco, which is activated by ozone and oxygen to function as the active site of oxidative phosphorylation. In accordance with the trophoblastic theory of cancer, pancreatic enzymes are believed to be oncolytic because they hydrolyze the homocysteinylated proteins, nucleic acids and glycosaminoglycans of malignant tissues. The clonal selection of malignant cells that are deficient in the heme oxygenase function of cystathionine synthase produces cells dependent upon glycolysis for ATP synthesis, since they are deficient in synthesis of thioretinamide, thioretinaco and thioretinaco ozonide. The vulnerable plaque of arteriosclerosis originates from complexes of microbes with homocysteinylated lipoproteins, obstructing vasa vasorum narrowed by endothelial dysfunction, causing arterial ischemia, and intimal micro-abscesses. Degenerative diseases may be ameliorated by a proposed therapeutic protocol

  14. The Impact of Obesity on Perioperative Resource Utilization after Elective Spine Surgery for Degenerative Disease

    PubMed Central

    Planchard, Ryan F.; Higgins, Dominique M.; Mallory, Grant W.; Puffer, Ross C.; Jacob, Jeffrey T.; Curry, Timothy B.; Kor, Daryl J.; Clarke, Michelle J.

    2015-01-01

    Study Design Retrospective case series. Objective To determine the effect of obesity on the resource utilization and cost in 3270 consecutive patients undergoing elective noninstrumented decompressive surgeries for degenerative spine disease at Mayo Clinic Rochester between 2005 and 2012. Methods Groups were assessed for baseline differences (age, gender, and American Society of Anesthesiologists [ASA] classification, procedure type, and number of operative levels). Outcome variables included the transfusion requirements during surgery, the total anesthesia and surgical times, intensive care unit (ICU) admissions, standardized costs, as well as the ICU and hospital length of stay (LOS). Regression analysis was used to evaluate for strength of association between obesity and outcome variables. Results Baseline differences between the groups (nonobese: n = 1,853; obese: n = 1,417) were found with respect to age, ASA class, gender, procedure type, and number of operative levels. After correcting for differences, we found significant associations between obesity and surgical (p < 0.0001) and anesthesia times (p < 0.0001) and hospital LOS (p < 0.0001). Additionally, ICU admission rates (p = 0.02) and requirement for postoperative ventilation (p = 0.048) were significantly higher in obese patients. Finally, mean difference in total cost ($1,632, p < 0.0001) was significantly higher for the obese cohort. Conclusion Obesity is associated with increased resource utilization and cost in patients undergoing a noninstrumented decompressive surgery for degenerative spine disease. PMID:26225277

  15. Laser technologies in treatment of degenerative-dystrophic bone diseases in children

    NASA Astrophysics Data System (ADS)

    Abushkin, Ivan A.; Privalov, Valery A.; Lappa, Alexander V.; Noskov, Nikolay V.; Neizvestnykh, Elena A.; Kotlyarov, Alexander N.; Shekunova, Yulia G.

    2014-03-01

    Two low invasive laser technologies for treatment of degenerative-dystrophic bone diseases in children are presented. The first is the transcutaneous laser osteoperforation developed by us and initially applied for treatment of different inflammatory and traumatic diseases (osteomyelitides, osteal and osteoarticular panaritiums, delayed unions, false joints, and others). Now the technology was applied to treatment of aseptic osteonecrosis of different localizations in 134 children aged from 1 to 16 years, including 56 cases with necrosis of femoral head (Legg-Calve-Perthes disease), 42 with necrosis of 2nd metatarsal bone head (Kohler II disease), and 36 with necrosis of tibial tuberosity (Osgood-Schlatter disease). The second technology is the laser intracystic thermotherapy for treatment of bone cysts. The method was applied to 108 children aged from 3 to 16 years with aneurismal and solitary cysts of different localizations. In both technologies a 970 nm diode laser was used. The suggested technologies increase the efficiency of treatment, reduce its duration, can be performed on outpatient basis, which resulted in great economical effect.

  16. Reprint of "Ethical issues with artificial nutrition of children with degenerative brain diseases".

    PubMed

    Kohlschütter, Alfried; Riga, Carolina; Crespo, Dolores; Torres, José Manuel; Penchaszadeh, Victor; Schulz, Angela

    2015-10-01

    This report highlights viewpoints of the authors and comments from the auditory at a workshop, held during the 14th international Congress on neuronal ceroid lipofuscinoses (NCL) in Córdoba, Argentina, on ethical aspects of artificial nutrition in children with degenerative brain diseases. The discussion centers on what constitutes the best interest of a patient whose personality was immature before the onset of the disease, who has become demented during its course and is unable to communicate his/her own positions and desires. There is wide consensus that in a child with advanced disease who cannot be fed naturally, decisions to withhold nutrition or to institute or stop artificial nutrition, should only be made by parents (or their representatives) who are adequately prepared on an intellectual and emotional level. We try to show that such decisions are highly individual but can be made in a rationally and emotionally acceptable way after a careful and prolonged dialogue between families and professionals. A checklist summarizes important considerations. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)". PMID:26071856

  17. Ethical issues with artificial nutrition of children with degenerative brain diseases.

    PubMed

    Kohlschütter, Alfried; Riga, Carolina; Crespo, Dolores; Torres, José Manuel; Penchaszadeh, Victor; Schulz, Angela

    2015-07-01

    This report highlights viewpoints of the authors and comments from the auditory at a workshop, held during the 14th international Congress on neuronal ceroid lipofuscinoses (NCL) in Córdoba, Argentina, on ethical aspects of artificial nutrition in children with degenerative brain diseases. The discussion centers on what constitutes the best interest of a patient whose personality was immature before the onset of the disease, who has become demented during its course and is unable to communicate his/her own positions and desires. There is wide consensus that in a child with advanced disease who cannot be fed naturally, decisions to withhold nutrition or to institute or stop artificial nutrition, should only be made by parents (or their representatives) who are adequately prepared on an intellectual and emotional level. We try to show that such decisions are highly individual but can be made in a rationally and emotionally acceptable way after a careful and prolonged dialogue between families and professionals. A checklist summarizes important considerations. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)". PMID:25795594

  18. Spontaneous degenerative polioencephalomyelopathy in feeder pigs--a new motor neuron disease?

    PubMed

    Wohlsein, Peter; Brügmann, Michael; Pfeiffer, Ina; Ammer, Hermann; Wolf, Petra; Baumgartner, Wolfgang; Peters, Martin

    2012-01-01

    A central nervous disorder occurred spontaneously in a herd of feeder pigs characterized by muscle fasciculations, convulsions, squealing, and acute death in numerous animals. Histopathology revealed a degenerative poliomyeloencephalopathy of brain stem and spinal cord consisting of neuronal hypertrophy, chromatolysis, neuronophagia, and satellitosis associated with Wallerian degeneration of ventral rootlets and neurogenic muscle atrophy of limb musculature. The sudden onset of clinical signs and the pattern of morphological findings were suggestive of intoxication. Though parathion was found in two animals, serum acetylcholine esterase activity and morphological findings were not compatible with an organophosphate poisoning. A hereditary disorder was excluded by genetic analysis. Summarized findings in the present cases are reminiscent of changes observed in ruminants suffering from patulin poisoning, a neuromycotoxicosis caused by Aspergillus clavatus. However, toxicological and microbiological investigations failed to identify the cause of this unusual and so far not described disease in pigs. Morphologically, lesion distribution and alterations of motor neurons resemble changes observed in equine motor neuron disease, spinal muscular atrophy of certain canine breeds, and amyotrophic lateral sclerosis (Lou Gehrig's disease) in man. Therefore, the term spontaneous porcine motor neuron disease (SPMND) is proposed for this new and unique entitiy. PMID:23227771

  19. New Classification for Clinically Symptomatic Adjacent Segment Pathology in Cervical Disc Disease

    PubMed Central

    2015-01-01

    Study Design Clinical adjacent segment pathology (CASP) is common after cervical disc surgery. A critical examination of 320 patients operated for cervical disc prolapse revealed that CASP can also occur in patients with congenital and degenerative fusion of cervical spine. This has not been studied in depth and there is a need for a practically applicable classification of CASP. Purpose To develop a new classification scheme of CASP. Overview of Literature A review of the literature did not reveal a practically applicable classification incorporating the occurrence of CASP in congenital and degenerative fusion cases. Methods This was a retrospective analysis of 320 patients operated (509 disc spaces) on for cervical disc prolapse. Cases (n=316) were followed-up for 3-11 years. Random sampling of 220 patients with postoperative magnetic resonance imaging (MRI) in 165 cases was analyzed. Results Six symptomatic CASP cases required resurgery (1.9%), eight cases involved MRI proven CASP with axial neck pain only and 13 patients were asymptomatic with radiological adjacent segment pathology (RASP). The frequency rate was 8.5% (27/316). Four cases of congenital or degenerative fusion of vertebra developed CASP requiring surgery. CASP is classified as primary or secondary follows. Primary A1 was congenital fusion of vertebra and primary A2 was degenerative fusion of the vertebra. Secondary, which was after cervical disc surgery, comprised B1 (RASP in asymptomatic patients), B2 (CASP in patients with axial neck pain), and B3 (CASP with myeloradiculopathy). B3 was subdivided into single-level CASP (B3a) and multiple-level CASP (B3b). Conclusions Symptomatic CASP requiring resurgery is infrequent. CASP can occur in patients with congenital and degenerative fusion of the cervical spine. A new classification for CASP along with treatment strategy is proposed. Patients in Primary CASP and B3 CASP require resurgery while others require only observation. PMID:26712514

  20. Characterization of Intercostal Muscle Pathology in Canine Degenerative Myelopathy: A Disease Model for Amyotrophic Lateral Sclerosis

    PubMed Central

    Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Bujnak, Alyssa C.; Katz, Martin L.

    2014-01-01

    Dogs homozygous for missense mutations in the SOD1 gene develop a late-onset neuromuscular disorder called degenerative myelopathy (DM) that has many similarities to amyotrophic lateral sclerosis (ALS). Both disorders are characterized by widespread progressive declines in motor functions accompanied by atrophic changes in the descending spinal cord tracts , and some forms of ALS are also associated with SOD1 mutations. In end-stage ALS, death usually occurs as a result of respiratory failure due to severe functional impairment of respiratory muscles. The mechanisms that lead to this loss of function are not known. Dogs with DM are euthanized at all stages of disease progression providing an opportunity to characterize the onset and progression of any pathological changes in the respiratory muscles that may precede respiratory failure. To characterize such potential disease-related pathology we evaluated intercostal muscles from Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM disease progression. DM was found to result in intercostal muscle atrophy, fibrosis, increased variability in muscle fiber size and shape, and an alteration in muscle fiber type composition. This pathology was not accompanied by retraction of the motor neuron terminals from the muscle acetylcholine receptor complexes, suggesting that the muscle atrophy did not result from physical denervation. These findings provide a better understanding of the mechanisms that likely lead to respiratory failure in at least some forms of ALS and will be useful in the development and evaluation of potential therapeutic interventions using the DM model. PMID:24043596

  1. Predictive diagnostics and personalized medicine for the prevention of chronic degenerative diseases

    PubMed Central

    2010-01-01

    Progressive increase of mean age and life expectancy in both industrialized and emerging societies parallels an increment of chronic degenerative diseases (CDD) such as cancer, cardiovascular, autoimmune or neurodegenerative diseases among the elderly. CDD are of complex diagnosis, difficult to treat and absorbing an increasing proportion in the health care budgets worldwide. However, recent development in modern medicine especially in genetics, proteomics, and informatics is leading to the discovery of biomarkers associated with different CDD that can be used as indicator of disease’s risk in healthy subjects. Therefore, predictive medicine is merging and medical doctors may for the first time anticipate the deleterious effect of CDD and use markers to identify persons with high risk of developing a given CDD before the clinical manifestation of the diseases. This innovative approach may offer substantial advantages, since the promise of personalized medicine is to preserve individual health in people with high risk by starting early treatment or prevention protocols. The pathway is now open, however the road to an effective personalized medicine is still long, several (diagnostic) predictive instruments for different CDD are under development, some ethical issues have to be solved. Operative proposals for the heath care systems are now needed to verify potential benefits of predictive medicine in the clinical practice. In fact, predictive diagnostics, personalized medicine and personalized therapy have the potential of changing classical approaches of modern medicine to CDD. PMID:21172060

  2. Characterization of intercostal muscle pathology in canine degenerative myelopathy: a disease model for amyotrophic lateral sclerosis.

    PubMed

    Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Bujnak, Alyssa C; Katz, Martin L

    2013-12-01

    Dogs homozygous for missense mutations in the SOD1 gene develop a late-onset neuromuscular disorder called degenerative myelopathy (DM) that has many similarities to amyotrophic lateral sclerosis (ALS). Both disorders are characterized by widespread progressive declines in motor functions, accompanied by atrophic changes in the descending spinal cord tracts. Some forms of ALS are also associated with SOD1 mutations. In end-stage ALS, death usually occurs as a result of respiratory failure from severe functional impairment of respiratory muscles. The mechanisms that lead to this loss of function are not known. Dogs with DM are euthanized at all stages of disease progression, providing an opportunity to characterize the onset and progression of any pathological changes in the respiratory muscles that may precede respiratory failure. To characterize such potential disease-related pathology, we evaluated intercostal muscles from Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM disease progression. DM was found to result in intercostal muscle atrophy, fibrosis, increased variability in muscle fiber size and shape, and alteration in muscle fiber type composition. This pathology was not accompanied by retraction of the motor neuron terminals from the muscle acetylcholine receptor complexes, suggesting that the muscle atrophy did not result from physical denervation. These findings provide a better understanding of the mechanisms that likely lead to respiratory failure in at least some forms of ALS and will be useful in the development and evaluation of potential therapeutic interventions using the DM model. PMID:24043596

  3. Clinical Outcomes of Percutaneous Plasma Disc Coagulation Therapy for Lumbar Herniated Disc Diseases

    PubMed Central

    Kim, Sung Chul; Cho, Ki Hong

    2012-01-01

    Objective This is prospective study of clinical outcomes of percutaneous plasma disc coagulation Therapy (PDCT) in patients with herniated lumbar disc disease (HLD) to evaluate the safety and efficacy in its clinical application and usefulness as a reliable alternative to microscopic discectomy. Methods Forty-six patients were enrolled in this study from April 2006 to June 2010. All patients had one-level HLD. Disc degeneration was graded on routine T2-weighted magnetic resonance Image (MRI) using the Pfirrmann's grading system and all index levels were grade 3 and grade 4. Indications for surgery were radiculopathy caused by disc protrusion with soft consistency. MRI was done at one month after the procedure in all patients to check post-PDCT change. The clinical outcomes were evaluated using Visual Analog Scales (VAS) score and MacNab's criteria. Results This study was approved by the Institutional Review Board of our institution. The age of the study population ranged from 16 to 59 years with a mean age of 37.2 years. There were 29 males and 17 females in this study. The mean period of clinical follow-up was 21 months. The average preoperative VAS score for radiculopathy was 7.4±1.4, while the final follow-up VAS score was 1.4±0.7 (p<0.001). In MacNab's criteria, 41 patients (89.1%) had achieved favorable improvement (excellent and good) until later follow-up. There were one patient from infection and two patients who needed to convert to open discectomy. Conclusion PDCT is a safe and efficient treatment modality in a selective patient with HLD. PMID:22396836

  4. Mechanotransduction in intervertebral discs

    PubMed Central

    Tsai, Tsung-Ting; Cheng, Chao-Min; Chen, Chien-Fu; Lai, Po-Liang

    2014-01-01

    Mechanotransduction plays a critical role in intracellular functioning—it allows cells to translate external physical forces into internal biochemical activities, thereby affecting processes ranging from proliferation and apoptosis to gene expression and protein synthesis in a complex web of interactions and reactions. Accordingly, aberrant mechanotransduction can either lead to, or be a result of, a variety of diseases or degenerative states. In this review, we provide an overview of mechanotransduction in the context of intervertebral discs, with a focus on the latest methods of investigating mechanotransduction and the most recent findings regarding the means and effects of mechanotransduction in healthy and degenerative discs. We also provide some discussion of potential directions for future research and treatments. PMID:25267492

  5. Generating mouse models of degenerative diseases using Cre/lox-mediated in vivo mosaic cell ablation

    PubMed Central

    Fujioka, Masato; Tokano, Hisashi; Fujioka, Keiko Shiina; Okano, Hideyuki; Edge, Albert S.B.

    2011-01-01

    Most degenerative diseases begin with a gradual loss of specific cell types before reaching a threshold for symptomatic onset. However, the endogenous regenerative capacities of different tissues are difficult to study, because of the limitations of models for early stages of cell loss. Therefore, we generated a transgenic mouse line (Mos-iCsp3) in which a lox-mismatched Cre/lox cassette can be activated to produce a drug-regulated dimerizable caspase-3. Tissue-restricted Cre expression yielded stochastic Casp3 expression, randomly ablating a subset of specific cell types in a defined domain. The limited and mosaic cell loss led to distinct responses in 3 different tissues targeted using respective Cre mice: reversible, impaired glucose tolerance with normoglycemia in pancreatic β cells; wound healing and irreversible hair loss in the skin; and permanent moderate deafness due to the loss of auditory hair cells in the inner ear. These mice will be important for assessing the repair capacities of tissues and the potential effectiveness of new regenerative therapies. PMID:21576819

  6. Amyloid β accumulation and inner retinal degenerative changes in Alzheimer's disease transgenic mouse.

    PubMed

    Gupta, Vivek K; Chitranshi, Nitin; Gupta, Veer B; Golzan, Mojtaba; Dheer, Yogita; Wall, Roshana Vander; Georgevsky, Dana; King, Anna E; Vickers, James C; Chung, Roger; Graham, Stuart

    2016-06-01

    The APP-PS1ΔE9 mouse model of Alzheimer's disease (AD) exhibits age dependent amyloid β (Aβ) plaque formation in their central nervous system due to high expression of mutated human APP and PSEN1 transgenes. Here we evaluated Aβ deposition and changes in soluble Aβ accumulation in the retinas of aged APP-PS1 mice using a combination of immunofluorescence, retinal flat mounts and western blotting techniques. Aβ accumulation in the retina has previously been shown to be associated with retinal ganglion cell apoptosis in animal models of glaucoma. This study investigated changes in the inner retinal function and structure in APP-PS1 mice using electrophysiology and histological approaches respectively. We report for the first time a significant decline in scotopic threshold response (STR) amplitudes which represents inner retinal function in transgenic animals compared to the wild type counterparts (p<0.0001). Thinning of the retina particularly involving inner retinal layers and reduction in axonal density in the optic nerve was also observed. TUNEL staining was performed to examine neuronal apoptosis in the inner retina. Intraocular pressure (IOP) measurements showed that APP-PS1ΔE9 mice had a slightly elevated IOP, but the significance of this finding is not yet known. Together, these results substantiate previous observations and highlight that APP-PS1ΔE9 mice show evidence of molecular, functional and morphological degenerative changes in the inner retina. PMID:27133194

  7. Criterion Validation Testing of Clinical Metrology Instruments for Measuring Degenerative Joint Disease Associated Mobility Impairment in Cats

    PubMed Central

    Gruen, Margaret E.; Griffith, Emily H.; Thomson, Andrea E.; Simpson, Wendy; Lascelles, B. Duncan X.

    2015-01-01

    Introduction Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-dose daily meloxicam for the treatment of pain associated with degenerative joint disease in cats, and further validate two clinical metrology instruments, the Feline Musculoskeletal Pain Index (FMPI) and the Client Specific Outcome Measures (CSOM). Methods Sixty-six client owned cats with degenerative joint disease and owner-reported impairments in mobility were screened and enrolled into a double-masked, placebo-controlled, randomized clinical trial. Following a run-in baseline period, cats were given either placebo or meloxicam for 21 days, then in a masked washout, cats were all given placebo for 21 days. Subsequently, cats were given the opposite treatment, placebo or meloxicam, for 21 days. Cats wore activity monitors throughout the study, owners completed clinical metrology instruments following each period. Results Activity counts were increased in cats during treatment with daily meloxicam (p<0.0001) compared to baseline. The FMPI results and activity count data offer concurrent validation for the FMPI, though the relationship between baseline activity counts and FMPI scores at baseline was poor (R2=0.034). The CSOM did not show responsiveness for improvement in this study, and the relationship between baseline activity counts and CSOM scores at baseline was similarly poor (R2=0.042). Conclusions Refinements to the FMPI, including abbreviation of the instrument and scoring as percent of possible score are recommended. This study offered further validation of the FMPI as a clinical metrology instrument for use in detecting therapeutic efficacy in cats with degenerative joint disease. PMID:26162101

  8. Evaluation of risk factors for degenerative joint disease associated with hip dysplasia in dogs.

    PubMed

    Smith, G K; Popovitch, C A; Gregor, T P; Shofer, F S

    1995-03-01

    Passive coxofemoral joint laxity of dogs, as quantitated by a distraction-stress radiographic method, may have important prognostic value in determining susceptibility to hip dysplasia. Data from 151 dogs, representing 13 breeds, were included in a logistic regression model to evaluate the contribution of factors such as age, breed, weight, sex, distraction index, and Norberg angle to the risk of developing degenerative joint disease (DJD) of the coxofemoral joint. Of the factors studied, the amount of passive hip laxity, as quantitated by the distraction index, was the most significant (P < 0.0001) determinant of the risk to develop DJD of the coxofemoral joint. In the longitudinal and cross-sectional components of the study, distraction index was a significant (P < 0.001) risk factor for DJD, irrespective of age at evaluation (4, 12, or 24 months). The strength of the hip laxity:DJD correlation increased with the age of dog. In contrast, the Norberg angle, a measure of hip laxity on the standard hip-extended radiograph, was not found to be a significant risk factor for DJD, either in the longitudinal or cross-sectional analyses. Breed-specific probability curves of DJD susceptibility indicated that German Shepherd Dogs had a significantly (P < 0.05) greater risk of developing DJD than did the pool of non-German Shepherd Dogs. The information derived from this statistical model will help to scientifically characterize the role of passive hip laxity as a component in the pathogenesis of DJD of the coxofemoral joint. PMID:7744684

  9. Relationship of orthopedic examination, goniometric measurements, and radiographic signs of degenerative joint disease in cats

    PubMed Central

    2012-01-01

    Background Available information suggests a mismatch between radiographic and orthopedic examination findings in cats with DJD. However, the extent of the discrepancy between clinical and radiographic signs of OA in companion animals has not been described in detail. This study aimed to evaluate the relationship between orthopedic examination findings, joint goniometry, and radiographic signs of DJD in 100 cats, in a prospective observational design. Cat temperament, pain response to palpation, joint crepitus, effusion and thickening were graded. Radiographs of appendicular joints and the axial skeleton were made under sedation. Joint motion was measured by use of a plastic goniometer before and after sedation. Associations between radiographic degenerative joint disease (DJD) and examination findings were assessed to determine sensitivity, specificity and likelihood estimations. Results Pain response to palpation was elicited in 0-67% of the joints with DJD, with a specificity ranging from 62-99%; crepitus was detected in 0-56% of the joints and its specificity varied between 87 and 99%; for effusion, values ranged between 6 and 38% (specificity, 82-100%), and thickening, 0-59% (specificity, 74-99%). Joints with DJD tended to have a decreased range of motion. The presence of pain increased the odds of having DJD in the elbow (right: 5.5; left: 4.5); the presence of pain in the lower back increased the odds of spinal DJD being present (2.97 for lumbar; 4.67 for lumbo-sacral). Conclusions Radiographic DJD cannot be diagnosed with certainty using palpation or goniometry. However, negative findings tend to predict radiographically normal joints. Palpation and goniometry may be used as a tool to help to screen cats, mostly to rule out DJD. PMID:22281125

  10. The SNAP trial: a double blind multi-center randomized controlled trial of a silicon nitride versus a PEEK cage in transforaminal lumbar interbody fusion in patients with symptomatic degenerative lumbar disc disorders: study protocol

    PubMed Central

    2014-01-01

    Background Polyetheretherketone (PEEK) cages have been widely used in the treatment of lumbar degenerative disc disorders, and show good clinical results. Still, complications such as subsidence and migration of the cage are frequently seen. A lack of osteointegration and fibrous tissues surrounding PEEK cages are held responsible. Ceramic implants made of silicon nitride show better biocompatible and osteoconductive qualities, and therefore are expected to lower complication rates and allow for better fusion. Purpose of this study is to show that fusion with the silicon nitride cage produces non-inferior results in outcome of the Roland Morris Disability Questionnaire at all follow-up time points as compared to the same procedure with PEEK cages. Methods/Design This study is designed as a double blind multi-center randomized controlled trial with repeated measures analysis. 100 patients (18–75 years) presenting with symptomatic lumbar degenerative disorders unresponsive to at least 6 months of conservative treatment are included. Patients will be randomly assigned to a PEEK cage or a silicon nitride cage, and will undergo a transforaminal lumbar interbody fusion with pedicle screw fixation. Primary outcome measure is the functional improvement measured by the Roland Morris Disability Questionnaire. Secondary outcome parameters are the VAS leg, VAS back, SF-36, Likert scale, neurological outcome and radiographic assessment of fusion. After 1 year the fusion rate will be measured by radiograms and CT. Follow-up will be continued for 2 years. Patients and clinical observers who will perform the follow-up visits will be blinded for type of cage used during follow-up. Analyses of radiograms and CT will be performed independently by two experienced radiologists. Discussion In this study a PEEK cage will be compared with a silicon nitride cage in the treatment of symptomatic degenerative lumbar disc disorders. To our knowledge, this is the first randomized controlled

  11. Long-term Follow-up (Minimum 5 Years) Study of Single-level Posterior Dynamic Stabilization in Lumbar Degenerative Disease; 'Interspinous U' & 'DIAM'

    PubMed Central

    Kim, Yeon Joon; Park, Chan Woo; Son, Seong; Kim, Woo Kyung

    2012-01-01

    Objectives Recently posterior dynamic stabilizations (PDS) are increased in degenerative lumbar disease. But, some previous studies had doubts its long term prognosis. Long term clinical and radiological results of PDS using interspinous device (Interspinous U, DIAM) were analyzed. Methods We have used the 'interspinous U' and 'DIAM' for patients with lumbar spinal stenosis. We included single level lumbar spinal stenosis patients who completed minimum 60 months follow-up evaluation. All patients checked plain lateral and flexion-extension views at immediately after the surgery and each follow-up. The clinical outcome was measured by Odom's criteria. Complications including post operative infection, bony erosion, device fracture, device malformations, and instabilities were surveyed. Results We included 18 for 'Interspinous U' and 7 patients 'DIAM' groups. Mean follow-up durations for 'Interspinous U' and 'DIAM' were 74.6 and 62.6 months, respectively. Satisfactory groups were 50.0% and 42.9 % for 'Interspinous U' and 'DIAM' groups. In 'Interspinous U' group disc height ratio increased transiently in immediate postoperative period (from 0.18 to 0.21) and then, decreased significantly in last follow-up (0.18). In 'DIAM' group, disc height ratio increased transiently in immediate postoperative period (from 0.18 to 0.19), and then decreased significantly in the last follow-up (0.16). Three (16.7%) and two (28.6%) patients undergo on a re-operation due to severe back pain in 'Interspinous U' and 'DIAM' groups. Conclusion Long term follow up 'Interspinous U' and 'DIAM' group showed low patient satisfaction and poor radiological outcomes. To ascertain the benefit of PDS compare with posterior screw fixation, prospective analysis with larger population and multi-center study will be needed. PMID:25983797

  12. Deuk Laser Disc Repair® is a safe and effective treatment for symptomatic cervical disc disease

    PubMed Central

    Deukmedjian, Ara J.; Jason Cutright, S. T.; Augusto Cianciabella, PA-C; Deukmedjian, Arias

    2013-01-01

    Background: Deuk Laser Disc Repair® is a new full-endoscopic surgical procedure to repair symptomatic cervical disc disease. Methods: A prospective cohort of 66 consecutive patients underwent cervical Deuk Laser Disc Repair® for one (n = 21) or two adjacent (n = 45) symptomatic levels of cervical disc disease and were evaluated postoperatively for resolution of headache, neck pain, arm pain, and radicular symptoms. All patients were candidates for anterior cervical discectomy and fusion (ACDF) or arthroplasty. The Mann–Whitney Wilcoxon test was used to calculate P values. Results: All patients (n = 66) had significant improvement in preoperative symptoms with an average symptom resolution of 94.6%. Fifty percent (n = 33) had 100% resolution of all preoperative cervicogenic symptoms. Only 4.5% (n = 3) had less than 80% resolution of preoperative symptoms. Visual analog scale (VAS) significantly improved from 8.7 preoperatively to 0.5 postoperatively (P < 0.001) for the cohort. Average operative and recovery times were 57 and 52 minutes, respectively. There were no perioperative complications. Recurrent disc herniation occurred in one patient (1.5%). Average postoperative follow-up was 94 days and no significant intergroup difference in outcomes was observed (P = 0.111) in patients with <90 days (n = 52) or >90 days (n = 14, mean 319 days) follow-up. No significant difference in outcomes was observed (P = 0.774) for patients undergoing one or two level Deuk Laser Disc Repair®. Patients diagnosed with postoperative cervical facet syndrome did significantly worse (P < 0.001). Conclusion: Deuk Laser Disc Repair® is a safe and effective alternative to ACDF or arthroplasty for the treatment of one or two adjacent symptomatic cervical disc herniations with an overall success rate of 94.6%. PMID:23776754

  13. Cervical Deuk Laser Disc Repair®: A novel, full-endoscopic surgical technique for the treatment of symptomatic cervical disc disease

    PubMed Central

    Deukmedjian, Ara J.; Cianciabella, Augusto; Cutright, Jason; Deukmedjian, Arias

    2012-01-01

    Background: Cervical Deuk Laser Disc Repair® is a novel full-endoscopic, anterior cervical, trans-discal, motion preserving, laser assisted, nonfusion, outpatient surgical procedure to safely treat symptomatic cervical disc diseases including herniation, spondylosis, stenosis, and annular tears. Here we describe a new endoscopic approach to cervical disc disease that allows direct visualization of the posterior longitudinal ligament, posterior vertebral endplates, annulus, neuroforamina, and herniated disc fragments. All patients treated with Deuk Laser Disc Repair were also candidates for anterior cervical discectomy and fusion (ACDF). Methods: A total of 142 consecutive adult patients with symptomatic cervical disc disease underwent Deuk Laser Disc Repair during a 4-year period. This novel procedure incorporates a full-endoscopic selective partial decompressive discectomy, foraminoplasty, and posterior annular debridement. Postoperative complications and average volume of herniated disc fragments removed are reported. Results: All patients were successfully treated with cervical Deuk Laser Disc Repair. There were no postoperative complications. Average volume of herniated disc material removed was 0.09 ml. Conclusions: Potential benefits of Deuk Laser Disc Repair for symptomatic cervical disc disease include lower cost, smaller incision, nonfusion, preservation of segmental motion, outpatient, faster recovery, less postoperative analgesic use, fewer complications, no hardware failure, no pseudoarthrosis, no postoperative dysphagia, and no increased risk of adjacent segment disease as seen with fusion. PMID:23230523

  14. Litanium expandable pedicle screw for the treatment of degenerative and traumatic spinal diseases in osteoporotic patients: preliminary experience.

    PubMed

    Gazzeri, Roberto; Roperto, Raffaelino; Fiore, Claudio

    2012-12-01

    Osteoporosis is a major global health problem, with over 10 million people currently diagnosed with the disease. Although 80% of osteoporotic patients are women, a considerable number of men are also affected. Also, due to increasing life expectancy, the number of elderly patients with osteoporosis affected by degenerative and traumatic spinal diseases will increase further. Osteoporosis reduces bone quality through negative bone remodelling. Low bone quality can reduce the pull-out strength of pedicle screw, and negative bone remodelling can cause delayed bone fusion. However, pedicle screw instrumentation of the osteoporotic spine carries an increased risk of screw loosening, pull-out, and fixation failure. Our preliminary study aims to investigate the efficiency of expandable pedicle screws (OsseoScrew-Spinal Fixation System, Alphatec Spine Inc., Carlsbad, CA) in osteoporotic spinal patients. All osteoporotic patients with degenerative and traumatic spinal diseases admitted in our department underwent a pre-operative spinal x-Ray and MRI or CT. Pre-operative clinical assesment of patients was based on the visual analog scale (VAS) and Owestry Disability (ODI) questionnaire-a disease-specific outcome measure. Ten osteoporotic patients were treated with expandable pedicle screws (OsseoScrew). Post-operative clinical assessment of patients was based on the VAS and ODI questionnaire at 3 months and 1 year of follow-up. Post-operative radiologic follow-up was performed after 3 days (CT, x-ray); 3 months (x-ray); 6 months (spinal CT); and 1 year (spinal CT). Expandable pedicle screws improved pull-out strength as compared to standard pedicle screws in osteoporotic patients with degenerative and traumatic spinal diseases. PMID:23023577

  15. Percutaneous laser disc decompression for thoracic disc disease: report of 10 cases

    PubMed Central

    Haufe, Scott M.W.; Mork, Anthony R.; Pyne, Morgan; Baker, Ryan A.

    2010-01-01

    Background: Discogenic pain or herniation causing neural impingement of the thoracic vertebrae is less common than that in the cervical or lumbar regions. Treatment of thoracic discogenic pain usually involves conservative measures. If this fails, conventional fusion or discectomy can be considered, but these procedures carry significant risk. Objectives: To assess the efficacy and safety of percutaneous laser disc decompression (PLDD) for the treatment of thoracic disc disease. Methods: Ten patients with thoracic discogenic pain who were unresponsive to conservative intervention underwent the PLDD procedure. Thoracic pain was assessed using the Visual Analog Scale (VAS) scores preoperatively and at 6-month intervals with a minimum of 18-months follow-up. Patients were diagnosed and chosen for enrollment based on abnormal MRI findings and positive provocative discograms. Patients with gross herniations were not included. Results: Length of follow-up ranged from 18 to 31 months (mean: 24.2 mo). Median pretreatment thoracic VAS score was 8.5 (range: 5-10) and median VAS score at final follow-up was 3.8 (range: 0-9). Postoperative improvement was significant with a 99% confidence interval. Of interest, patients generally fell into two groups, those with significant pain reduction and those with little to no improvement. Although complications such as pneumothorax, discitis, or nerve damage were possible, no adverse events occurred during the procedures. Limitations: The study is limited by its small size and lack of a sham group. Larger controlled studies are warranted. Conclusions: With further clinical evidence, PLDD could be considered a viable option with a low risk of complication for the treatment of thoracic discogenic pain that does not resolve with conservative treatment. PMID:20567616

  16. Outcome of posterior lumbar interbody fusion versus posterolateral fusion in lumbar degenerative disease.

    PubMed

    Wu, Yungang; Tang, Hao; Li, Zhonghai; Zhang, Qiulin; Shi, Zhicai

    2011-06-01

    Between March 2003 and September 2007, 170 consecutive patients with lumbar degenerative disease were studied retrospectively. Eighty patients underwent posterior lumbar interbody fusion (PLIF group) with pedicle screw (PS) fixation, and 82 patients underwent posterolateral fusion (PLF group) with PS fixation. Eight patients were lost to follow-up. The minimum follow-up period in each group was 2.0years. The mean follow-up period for the PLIF group was 3.6years, and for the PLF group, the mean follow-up was 3.4years: there was no significant difference between the two groups for length of follow-up. The Pain Index (PI) improved from 66 to 27 in the PLF group (p<0.001) and from 69 to 29 in the PLIF group (p<0.001), but there was no significant difference between the two groups (p>0.05). In the PLF group, the preoperative mean Oswestry Disability Index (ODI) score was 34.5, which reduced to 14.2 at the final follow-up. In the PLIF group, the mean preoperative ODI was 36.4, which reduced to 16.2 at the final follow-up. There was no significant statistical difference between the two groups for ODI (p>0.05). Eighty-eight percent (n=72) of patients in the PLF group and 91% (n=73) in the PLIF group had radiologically confirmed union, with no significant difference in fusion percentage between the two groups (p>0.05). Twenty-two of 162 patients (14%) underwent a second operation: 18 (22%) in the PLF group and four (5%) patients in the PLIF group (p<0.001). The clinical and functional outcomes in both groups were similar, and no significant difference was found in the parameters tested. Both surgical procedures were effective, but patients in the PLF group showed more complications related to hardware biomechanics than patients in the PLIF group (p<0.001). PMID:21507656

  17. Decellularized allogeneic intervertebral disc: natural biomaterials for regenerating disc degeneration

    PubMed Central

    Hu, Zhijun; Chen, Kai; Shan, Zhi; Chen, Shuai; Wang, Jiying; Mo, Jian; Ma, Jianjun; Xu, Wenbing; Qin, An; Fan, Shunwu

    2016-01-01

    Intervertebral disc degeneration is associated with back pain and disc herniation. This study established a modified protocol for intervertebral disc (IVD) decellularization and prepared its extracellular matrix (ECM). By culturing mesenchymal stem cells (MSCs)(3, 7, 14 and 21 days) and human degenerative IVD cells (7 days) in the ECM, implanting it subcutaneously in rabbit and injecting ECM microparticles into degenerative disc, the biological safety and efficacy of decellularized IVD was evaluated both in vitro and in vivo. Here, we demonstrated that cellular components can be removed completely after decellularization and maximally retain the structure and biomechanics of native IVD. We revealed that allogeneic ECM did not evoke any apparent inflammatory reaction in vivo and no cytotoxicity was found in vitro. Moreover, IVD ECM can induce differentiation of MSCs into IVD-like cells in vitro. Furthermore, allogeneic ECM microparticles are effective on the treatment of rabbit disc degeneration in vivo. In conclusion, our study developed an optimized method for IVD decellularization and we proved decellularized IVD is safe and effective for the treatment of degenerated disc diseases. PMID:26933821

  18. Intervertebral disc extrusion in six cats.

    PubMed

    Knipe, M F; Vernau, K M; Hornof, W J; LeCouteur, R A

    2001-09-01

    Existing reports concerning intervertebral disc disease (IVDD) have focused almost exclusively on dogs, although a small number of individual case reports of IVDD of cats has been published. The medical records of six cats with IVDD were reviewed. Radiographic studies confirmed narrowed intervertebral disc spaces, mineralised intervertebral discs, and one or more extradural compressive lesions of the spinal cord in each cat. All disc extrusions were located in the thoracolumbar region. Surgical decompression of the spinal cord was achieved in all cats by means of hemilaminectomy and removal of compressive extradural material confirmed to be degenerative disc material. Good to excellent neurological recovery was noted in five of the six cats included in this report. Based on this review, it appears that IVDD of cats has many similarities to IVDD of dogs, and that healthy cats with acute intervertebral disc extrusion(s) respond favourably to surgical decompression of the spinal cord. PMID:11876633

  19. Degenerative Spinal Deformity.

    PubMed

    Ailon, Tamir; Smith, Justin S; Shaffrey, Christopher I; Lenke, Lawrence G; Brodke, Darrel; Harrop, James S; Fehlings, Michael; Ames, Christopher P

    2015-10-01

    Degenerative spinal deformity afflicts a significant portion of the elderly and is increasing in prevalence. Recent evidence has revealed sagittal plane malalignment to be a key driver of pain and disability in this population and has led to a significant shift toward a more evidence-based management paradigm. In this narrative review, we review the recent literature on the epidemiology, evaluation, management, and outcomes of degenerative adult spinal deformity (ASD). ASD is increasing in prevalence in North America due to an aging population and demographic shifts. It results from cumulative degenerative changes focused in the intervertebral discs and facet joints that occur asymmetrically to produce deformity. Deformity correction focuses on restoration of global alignment, especially in the sagittal plane, and decompression of the neural elements. General realignment goals have been established, including sagittal vertical axis <50 mm, pelvic tilt <22°, and lumbopelvic mismatch <±9°; however, these should be tailored to the patient. Operative management, in carefully selected patients, yields satisfactory outcomes that appear to be superior to nonoperative strategies. ASD is characterized by malalignment in the sagittal and/or coronal plane and, in adults, presents with pain and disability. Nonoperative management is recommended for patients with mild, nonprogressive symptoms; however, evidence of its efficacy is limited. Surgery aims to restore global spinal alignment, decompress neural elements, and achieve fusion with minimal complications. The surgical approach should balance the desired correction with the increased risk of more aggressive maneuvers. In well-selected patients, surgery yields excellent outcomes. PMID:26378361

  20. Mid-range outcomes in 64 consecutive cases of multilevel fusion for degenerative diseases of the lumbar spine

    PubMed Central

    Röllinghoff, Marc; Schlüter-Brust, Klaus; Groos, Daniel; Sobottke, Rolf; Michael, Joern William-Patrick; Eysel, Peer; Delank, Karl Stefan

    2010-01-01

    In the treatment of multilevel degenerative disorders of the lumbar spine, spondylodesis plays a controversial role. Most patients can be treated conservatively with success. Multilevel lumbar fusion with instrumentation is associated with severe complications like failed back surgery syndrome, implant failure, and adjacent segment disease (ASD). This retrospective study examines the records of 70 elderly patients with degenerative changes or instability of the lumbar spine treated between 2002 and 2007 with spondylodesis of more than two segments. Sixty-four patients were included; 5 patients had died and one patient was lost to follow-up. We evaluated complications, clinical/radiological outcomes, and success of fusion. Flexion-extension and standing X-rays in two planes, MRI, and/or CT scans were obtained pre-operatively. Patients were assessed clinically using the Oswestry disability index (ODI) and a Visual Analogue Scale (VAS). Surgery performed was dorsolateral fusion (46.9%) or dorsal fusion with anterior lumbar interbody fusion (ALIF; 53.1%). Additional decompression was carried out in 37.5% of patients. Mean follow-up was 29.4±5.4 months. Average patient age was 64.7±4.3 years. Clinical outcomes were not satisfactory for all patients. VAS scores improved from 8.6±1.3 to 5.6±3.0 pre- to post-operatively, without statistical significance. ODI was also not significantly improved (56.1±22.3 pre- and 45.1±26.4 post-operatively). Successful fusion, defined as adequate bone mass with trabeculation at the facets and transverse processes or in the intervertebral segments, did not correlate with good clinical outcomes. Thirty-five of 64 patients (54%) showed signs of pedicle screw loosening, especially of the screws at S1. However, only 7 of these 35 (20%) complained of corresponding back pain. Revision surgery was required in 24 of 64 patients (38%). Of these, indications were adjacent segment disease (16 cases), pedicle screw loosening (7 cases), and

  1. Pedicle-Screw-Based Dynamic Systems and Degenerative Lumbar Diseases: Biomechanical and Clinical Experiences of Dynamic Fusion with Isobar TTL

    PubMed Central

    Barrey, Cédric; Perrin, Gilles; Champain, Sabina

    2013-01-01

    Dynamic systems in the lumbar spine are believed to reduce main fusion drawbacks such as pseudarthrosis, bone rarefaction, and mechanical failure. Compared to fusion achieved with rigid constructs, biomechanical studies underlined some advantages of dynamic instrumentation including increased load sharing between the instrumentation and interbody bone graft and stresses reduction at bone-to-screw interface. These advantages may result in increased fusion rates, limitation of bone rarefaction, and reduction of mechanical complications with the ultimate objective to reduce reoperations rates. However published clinical evidence for dynamic systems remains limited. In addition to providing biomechanical evaluation of a pedicle-screw-based dynamic system, the present study offers a long-term (average 10.2 years) insight view of the clinical outcomes of 18 patients treated by fusion with dynamic systems for degenerative lumbar spine diseases. The findings outline significant and stable symptoms relief, absence of implant-related complications, no revision surgery, and few adjacent segment degenerative changes. In spite of sample limitations, this is the first long-term report of outcomes of dynamic fusion that opens an interesting perspective for clinical outcomes of dynamic systems that need to be explored at larger scale. PMID:25031874

  2. Echocardiographic assessment of mitral valve morphology and performance after triangular resection of the prolapsing posterior leaflet for degenerative myxomatous disease.

    PubMed

    Chiappini, Bruno; Gregorini, Renato; De Remigis, Franco; Petrella, Licia; Villani, Carmine; Di Pietrantonio, Fabrizio; Pavicevic, Srdan; Mazzola, Alessandro

    2009-08-01

    The gold standard for the surgical treatment of prolapse of the posterior leaflet of the mitral valve (MV) for degenerative myxomatous disease has been represented by the quadrangular resection of the leaflet, according to the Carpentier technique. Since 2006 we performed a triangular resection of the prolapsing leaflet in 20 patients with myxomatous mitral regurgitation (MR). Seventeen patients (85%) underwent the triangular resection of P2; one patient (5%) had a triple scallops triangular resection (P1, P2, P3) and two (10%) a double scallops (P2, P3) resection. In this study, we report the immediate and mid-term clinical and echocardiographic results of a cohort of 20 patients, who underwent this technique. Thirty-day mortality was 0. Acute renal failure occurred in three patients (15%) and they resolved with conservative management. One patient (5%) required re-exploration for bleeding. At the mean follow-up of 13.1+/-4.2 months survival was 95%; one patient died of lymphoma during the follow-up time. All the cases were in New York Heart Association (NYHA) class I. Nineteen survivors underwent transthoracic echocardiography (TTE) (5), or transesophageal echocardiography (TEE) (13), performed by two skilled cardiologists. All patients showed no or trivial MV regurgitation. We believe that triangular resection of posterior MV leaflet (PMVL) provides excellent mid-term results providing the surgeon with a reliable and reproducible surgical option for myxomatous degenerative MV regurgitation. PMID:19414490

  3. Arteriovenous fistula of the filum terminale misdiagnosed and previously operated as lower lumbar degenerative disease.

    PubMed

    Sharma, Pankaj; Ranjan, Alok; Lath, Rahul

    2014-06-01

    Filum terminale arteriovenous fistula (FTAVF) presenting as a cause of failed back surgery syndrome is a rare entity. We report a 48-year-old male patient who presented with clinical features of a conus medullaris/cauda equina lesion. He had upper and lower motor neuron signs in both the lower limbs with autonomic dysfunction. The patient was misdiagnosed and was operated twice earlier for lumbar canal stenosis and disc prolapse. After reviewing his clinical and radiological findings a diagnosis of FTAVF was made. He underwent surgery and there was a significant improvement in his neurological functions. We discuss the case and review the literature on FTAVF's. PMID:24967053

  4. Arteriovenous Fistula of the Filum Terminale Misdiagnosed and Previously Operated as Lower Lumbar Degenerative Disease

    PubMed Central

    Ranjan, Alok; Lath, Rahul

    2014-01-01

    Filum terminale arteriovenous fistula (FTAVF) presenting as a cause of failed back surgery syndrome is a rare entity. We report a 48-year-old male patient who presented with clinical features of a conus medullaris/cauda equina lesion. He had upper and lower motor neuron signs in both the lower limbs with autonomic dysfunction. The patient was misdiagnosed and was operated twice earlier for lumbar canal stenosis and disc prolapse. After reviewing his clinical and radiological findings a diagnosis of FTAVF was made. He underwent surgery and there was a significant improvement in his neurological functions. We discuss the case and review the literature on FTAVF's. PMID:24967053

  5. Posterior Interspinous Fusion Device for One-Level Fusion in Degenerative Lumbar Spine Disease : Comparison with Pedicle Screw Fixation - Preliminary Report of at Least One Year Follow Up

    PubMed Central

    Kim, Ho Jung; Chun, Hyoung Joon; Oh, Suck Jun; Kang, Tae Hoon; Yang, Moon Sool

    2012-01-01

    Objective Transpedicular screw fixation has some disadvantages such as postoperative back pain through wide muscle dissection, long operative time, and cephalad adjacent segmental degeneration (ASD). The purposes of this study are investigation and comparison of radiological and clinical results between interspinous fusion device (IFD) and pedicle screw. Methods From Jan. 2008 to Aug. 2009, 40 patients underwent spinal fusion with IFD combined with posterior lumbar interbody fusion (PLIF). In same study period, 36 patients underwent spinal fusion with pedicle screw fixation as control group. Dynamic lateral radiographs, visual analogue scale (VAS), and Korean version of the Oswestry disability index (K-ODI) scores were evaluated in both groups. Results The lumbar spine diseases in the IFD group were as followings; spinal stenosis in 26, degenerative spondylolisthesis in 12, and intervertebral disc herniation in 2. The mean follow up period was 14.24 months (range; 12 to 22 months) in the IFD group and 18.3 months (range; 12 to 28 months) in pedicle screw group. The mean VAS scores was preoperatively 7.16±2.1 and 8.03±2.3 in the IFD and pedicle screw groups, respectively, and improved postoperatively to 1.3±2.9 and 1.2±3.2 in 1-year follow ups (p<0.05). The K-ODI was decreased significantly in an equal amount in both groups one year postoperatively (p<0.05). The statistics revealed a higher incidence of ASD in pedicle screw group than the IFD group (p=0.029). Conclusion Posterior IFD has several advantages over the pedicle screw fixation in terms of skin incision, muscle dissection and short operative time and less intraoperative estimated blood loss. The IFD with PLIF may be a favorable technique to replace the pedicle screw fixation in selective case. PMID:23133725

  6. Increasing Incidence of Degenerative Spinal Diseases in Japan during 25 Years: The Registration System of Spinal Surgery in Tohoku University Spine Society.

    PubMed

    Aizawa, Toshimi; Kokubun, Shoichi; Ozawa, Hiroshi; Kusakabe, Takashi; Tanaka, Yasuhisa; Hoshikawa, Takeshi; Hashimoto, Ko; Kanno, Haruo; Morozumi, Naoki; Koizumi, Yutaka; Sato, Tetsuro; Hyodo, Hironori; Kasama, Fumio; Ogawa, Shinji; Murakami, Eiichi; Kawahara, Chikashi; Yahata, Jun-Ichiro; Ishii, Yushin; Itoi, Eiji

    2016-01-01

    Spinal disorders affect mainly older people and cause pain, paralysis and/or deformities of the trunk and/or extremities, which could eventually disturb locomotive functions. For ensuring safe and high-quality treatment of spinal disorders, in 1987, the Tohoku University Spine Society (TUSS) was established by orthopedic departments in Tohoku University School of Medicine and its affiliated hospitals in and around Miyagi Prefecture. All spine surgeries have been enrolled in the TUSS Spine Registry since 1988. Using the data from this registration system between 1988 and 2012, we demonstrate here the longitudinal changes in surgical trends for spinal disorders in Japan that has rushed into the most advanced "aging society" in the world. In total, data on 56,744 surgeries were retrieved. The number of spinal surgeries has annually increased approximately 4-fold. There was a particular increase among patients aged ≥ 70 years and those aged ≥ 80 years, with a 20- to 90-fold increase. Nearly 90% of the spinal operations were performed for degenerative disorders, with their number increasing approximately 5-fold from 705 to 3,448. The most common disease for surgery was lumbar spinal stenosis (LSS) (35.9%), followed by lumbar disc herniation (27.7%) and cervical myelopathy (19.8%). In 2012, approximately half of the patients with LSS and cervical myelopathy were ≥ 70 years of age. In conclusion, the number of spinal operations markedly increased during the 25-year period, particularly among older patients. As Japan has a notably aged population, the present study could provide a near-future model for countries with aging population. PMID:26876801

  7. A clinical study of auriculotherapy in canine thoracolumbar disc disease.

    PubMed

    Still, J

    1990-09-01

    Auriculotherapy (ear-point acupuncture) was used in dogs (n = 30) suffering from thoracolumbar disc disease, Types I-IV, with a duration of 1 to (47 means = 8) d. During auriculotherapy treatment, no analgaesics or antiinflammatory medications were used. Pressure-sensitive and electrically detectable points on the concave aspect of the external auricle were stimulated by insertion of stainless steel acupuncture needles for 20 min. One to 6 needles were used on each occasion in a maximum of 3 treatments. Fifty per cent of dogs recovered completely and 23% improved. Dogs with backpain only (Type I) and dogs with paresis (Type II) responded best with mean recovery times of 1.7 and 3.2 d respectively. The analgaesic effects were especially impressive. Auriculotherapy failed in 3 (50%) paralysed dogs (Types III and IV) in which post-mortem examinations confirmed focal myelitis and myelomalacia. Four of 12 dogs (33%) recorded relapsed in 1.4 to 26 weeks after successful treatment. PMID:2286993

  8. HLA analysis in patients with degenerative diseases of the temporomandibular joint.

    PubMed

    Learreta, Jorge A; Bono, Andrea E; Durst, Andreas C

    2011-01-01

    The aim of this study was to determine the presence of HLA alleles, specifically HLA-DR alleles, and to correlate them with clinical and radiological features of patients with degenerative processes (DP) of the temporomandibular joint (TMJ). The final goal was to determine which allele can be used to identify patients having more aggressive forms of the articular pathologies. Thirty-two (32) Caucasian patients with DP of the TMJ were included in the study. The SSOP (Luminex Corp., Austin, TX) method was used to determine class II HLA alleles. The presence of HLA-II DR in patients with DP of the TMJ was 98%. The presence of HLA was significantly higher in patients with DP of the TMJ than in healthy subjects (66%) (p=0.003). HLA DR52 was significantly more frequent in patients than in healthy individuals (40.62% vs. 13.79%, p = 0.041). While the percentage of DR11 positive individuals was also higher among patients than among healthy control subjects, the association with DP of the TMJ was not significant (p=0.220). Patients having the DR52 allele had higher deformation or DP. It was concluded that HLA-DR54 and DR11 alleles are associated with a higher susceptibility to DP of the TMJ, and HLA-DR54 and DR52 are associated with a higher severity of DP. PMID:21370767

  9. Neuroanatomic and pathophysiologic aspects of intervertebral disc disease in the dog.

    PubMed

    Thacher, C

    1989-01-01

    A sound understanding of anatomy and the pathophysiology of disease is important in all branches of medicine, but nowhere is it more critical to success than in the medical and surgical management of intervertebral disc disease. Due to the remote location and unforgiving nature of the spinal cord, the veterinary surgeon must possess an intimate working knowledge of the surgical anatomy of the vertebrae, ligaments and joints of the spine, intervertebral discs, spinal cord, and spinal nerves. In addition, proper localization of spinal cord lesions during the neurological evaluation requires awareness of the functional neuroanatomy of the upper and lower motor motor neurons, the sensory systems and tracts, and the reflex arcs. Knowledge of the pathophysiology the intervertebral disc degeneration and the response of the spinal cord to disc extrusions are also important in the overall understanding of the disease and enhances proper decision making for its management. This chapter reviews the portions of the gross and functional neuroanatomy and the pathophysiology of the intervertebral disc and the spinal cord that are pertinent to the dog with intervertebral disc disease. Emphasis is placed on concepts that are critical for the veterinary surgeon who is involved in the surgical management of the disc patient. PMID:2520119

  10. Double-level cervical total disc replacement for adjacent segment disease: is it a useful treatment? Description of late onset heterotopic ossification and review of the literature.

    PubMed

    Barbagallo, G M V; Certo, F; Visocchi, M; Sciacca, G; Albanese, V

    2014-01-01

    We report a rare case of double-level adjacent segment disease (ASD), occurring ten years later an anterior cervical discectomy (ACD) without fusion, treated by cervical arthroplasty, highlighting the outcome at long-term follow-up and focusing on heterotopic ossification. In 1995 a 25-year-old man satisfactorily underwent ACD at C4/C5. At that time MRI also showed signs of degenerative disc disease (DDD) at C3/C4 and C5/C6. Ten years later, a new MRI scan showed a large C3/C4 and a smaller C5/C6 soft disc hernia together with spondylotic changes at the level above and below the site of the first surgery. At C4/C5 imaging revealed a kyphotic stable "pseudoarthrosis" with anterior bridging osteophyte. The patient underwent double-level arthroplasty with ProDisc-C. Clinical and radiological outcome was satisfactory. 3 and 5 years after surgery, X-rays and CT scan documented the progressive development of heterotopic ossification, with gradual reduction of range of motion. A late onset heterotopic ossification can neutralize the theoretical advantages of cervical arthroplasty, which should be considered an effective surgical option only in selected cases. ACDF and restoration of normal lordosis can be a viable alternative in cervical revision surgery, as motion preservation can not be always mantained for a long time. PMID:24825036

  11. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

    Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju

    2015-01-01

    Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PMID:25777988

  12. Fast localization of optic disc and fovea in retinal images for eye disease screening

    NASA Astrophysics Data System (ADS)

    Yu, H.; Barriga, S.; Agurto, C.; Echegaray, S.; Pattichis, M.; Zamora, G.; Bauman, W.; Soliz, P.

    2011-03-01

    Optic disc (OD) and fovea locations are two important anatomical landmarks in automated analysis of retinal disease in color fundus photographs. This paper presents a new, fast, fully automatic optic disc and fovea localization algorithm developed for diabetic retinopathy (DR) screening. The optic disc localization methodology comprises of two steps. First, the OD location is identified using template matching and directional matched filter. To reduce false positives due to bright areas of pathology, we exploit vessel characteristics inside the optic disc. The location of the fovea is estimated as the point of lowest matched filter response within a search area determined by the optic disc location. Second, optic disc segmentation is performed. Based on the detected optic disc location, a fast hybrid level-set algorithm which combines the region information and edge gradient to drive the curve evolution is used to segment the optic disc boundary. Extensive evaluation was performed on 1200 images (Messidor) composed of 540 images of healthy retinas, 431 images with DR but no risk of macular edema (ME), and 229 images with DR and risk of ME. The OD location methodology obtained 98.3% success rate, while fovea location achieved 95% success rate. The average mean absolute distance (MAD) between the OD segmentation algorithm and "gold standard" is 10.5% of estimated OD radius. Qualitatively, 97% of the images achieved Excellent to Fair performance for OD segmentation. The segmentation algorithm performs well even on blurred images.

  13. Construction Strategy and Progress of Whole Intervertebral Disc Tissue Engineering.

    PubMed

    Yang, Qiang; Xu, Hai-Wei; Hurday, Sookesh; Xu, Bao-Shan

    2016-02-01

    Degenerative disc disease (DDD) is the major cause of low back pain, which usually leads to work absenteeism, medical visits and hospitalization. Because the current conservative procedures and surgical approaches to treatment of DDD only aim to relieve the symptoms of disease but not to regenerate the diseased disc, their long-term efficiency is limited. With the rapid developments in medical science, tissue engineering techniques have progressed markedly in recent years, providing a novel regenerative strategy for managing intervertebral disc disease. However, there are as yet no ideal methods for constructing tissue-engineered intervertebral discs. This paper reviews published reports pertaining to intervertebral disc tissue engineering and summarizes data concerning the seed cells and scaffold materials for tissue-engineered intervertebral discs, construction of tissue-engineered whole intervertebral discs, relevant animal experiments and effects of mechanics on the construction of tissue-engineered intervertebral disc and outlines the existing problems and future directions. Although the perfect regenerative strategy for treating DDD has not yet been developed, great progress has been achieved in the construction of tissue-engineered intervertebral discs. It is believed that ongoing research on intervertebral disc tissue engineering will result in revolutionary progress in the treatment of DDD. PMID:27028376

  14. Annulo-nucleoplasty using Disc-FX in the management of lumbar disc pathology: Early results

    PubMed Central

    Kumar, Aravind; Siddharth M, Shah; Sambhav P, Shah; Tan, Justin

    2014-01-01

    Background Back pain due to Lumbar Disc Disease is a major clinical problem. The treatment options range from physiotherapy to fusion surgery. A number of minimally invasive procedures have also been developed in the recent past for its management. Disc-FX is a new minimally invasive technique that combines percutaneous discectomy, nuclear ablation and annular modification. Literature on its role in the management of lumbar disc pathology is scarce. Methods We included 24 consecutive patients who underwent the Disc-FX for back pain due to lumbar disc pathology non-responsive to non-operative treatment for a period of at least 6 months. Based on Magnetic Resonance Imaging (MRI) these patients fell into 2 groups – those with degenerative disc disease (DDD) (n = 12) and those with a contained lumbar disc herniation (CLDH)(n = 12). They were evaluated using the Visual analogue scale (VAS), Oswestry Disability Index (ODI) and Short Form-36 (SF-36) scores preoperatively and postoperatively. Results The mean age was 37.9 years (21-53 years). There were 17 males and 7 females. One patient in each subgroup was excluded from the final evaluation. Significant improvement was seen in all outcome measures. The overall rate of reintervention for persistent symptoms was 18.18% (4/22); in the CLDH subgroup, it was 36.36% (4/11). Conclusions and level of evidence Early results after the Disc-FX procedure suggest that it s a reasonable treatment option for patients with back pain due to lumbar disc disease, especially for those with DDD who fail conservative treatment. It could be an alternative to procedures like fusion or disc replacement. This study presents Level IV evidence. Clinical relevance We feel that our study establishes Disc-FX as a modality of treating symptomatic lumbar disc disease due to DDD. However, longer term prospective studies are needed to prove this and to evaluate its role in the treatment of patients with CLDH. PMID:25694914

  15. Idiopathic REM sleep behavior disorder in the transition to degenerative disease.

    PubMed

    Postuma, Ronald B; Gagnon, Jean-Francois; Vendette, Melanie; Montplaisir, Jacques Y

    2009-11-15

    Idiopathic REM sleep behavior disorder (RBD) predicts Parkinson's disease (PD) and dementia. However, the nature of the disease that emerges from RBD has not been fully characterized. Since 2004, we have been conducting a prospective study of idiopathic RBD patients, providing an opportunity to directly observe patients as they transitioned to a defined neurodegenerative syndrome. Patients with idiopathic RBD underwent an extensive annual evaluation of motor function, olfaction, color vision, autonomic function, cognition and psychiatric symptoms. Neurodegenerative disease was defined according to standard criteria. We compared these measures in patients who had developed PD to those with dementia, all within the first year of developing disease. Of 67 patients, 6 developed PD and eleven developed dementia. Except for cognitive functioning, all tests of olfaction, color vision, autonomic function, depression, and quantitative measures of motor speed were similar in patients with PD and dementia. Of dementia patients, seven met criteria for probable Lewy body dementia (LBD) and four for Alzheimer's disease (or, possible LBD). In all probable LBD cases, the diagnosis was made because of parkinsonism, with no patient experiencing hallucinations or fluctuations. Patients with "Alzheimer's disease" seemed to have LBD, as they demonstrated typical LBD cognitive profiles on neuropsychological testing and were indistinguishable from LBD patients in ancillary measures. Therefore, among RBD patients with new-onset LBD, hallucinations or fluctuations are absent, suggesting that RBD is a reliable early sign of LBD. The indistinguishability of dementia and PD in all ancillary measures suggests a single unitary "RBD-then-neurodegeneration" process, the clinical presentation of which depends upon selective neuronal vulnerability. PMID:19768814

  16. In Vivo Mouse Intervertebral Disc Degeneration Model Based on a New Histological Classification

    PubMed Central

    Ohnishi, Takashi; Sudo, Hideki; Iwasaki, Koji; Tsujimoto, Takeru; Ito, Yoichi M.; Iwasaki, Norimasa

    2016-01-01

    Although human intervertebral disc degeneration can lead to several spinal diseases, its pathogenesis remains unclear. This study aimed to create a new histological classification applicable to an in vivo mouse intervertebral disc degeneration model induced by needle puncture. One hundred six mice were operated and the L4/5 intervertebral disc was punctured with a 35- or 33-gauge needle. Micro-computed tomography scanning was performed, and the punctured region was confirmed. Evaluation was performed by using magnetic resonance imaging and histology by employing our classification scoring system. Our histological classification scores correlated well with the findings of magnetic resonance imaging and could detect degenerative progression, irrespective of the punctured region. However, the magnetic resonance imaging analysis revealed that there was no significant degenerative intervertebral disc change between the ventrally punctured and non-punctured control groups. To induce significant degeneration in the lumbar intervertebral discs, the central or dorsal region should be punctured instead of the ventral region. PMID:27482708

  17. Canine degenerative myxomatous mitral valve disease: natural history, clinical presentation and therapy.

    PubMed

    Borgarelli, Michele; Haggstrom, Jens

    2010-07-01

    Myxomatous mitral valve disease is a common condition in geriatric dogs. Most dogs affected are clinically asymptomatic for a long time. However, about 30% of these animals present a progression to heart failure and eventually die as a consequence of the disease. Left atrial enlargement, and particularly a change in left atrial size, seems to be the most reliable predictor of progression in some studies, however further studies are needed to clarify how to recognize asymptomatic patients at higher risk of developing heart failure. According to the published data on the natural history of the disease and the results of published studies evaluating the effect of early therapy on delaying the progression of the disease, it seems that no currently available treatment delays the onset of clinical signs of congestive heart failure (CHF). Although the ideal treatment of more severely affected dogs is probably surgical mitral valve repair or mitral valve replacement, this is not a currently available option. The results of several clinical trials together with clinical experience suggest that dogs with overt CHF can be managed with acceptable quality of life for a relatively long time period with medical treatment including furosemide, an angiotensin-converting enzyme inhibitor, pimobendan, and spironolactone. PMID:20610017

  18. Huntington disease: a single-gene degenerative disorder of the striatum

    PubMed Central

    Nopoulos, Peggy C.

    2016-01-01

    Huntington disease (HD) is an autosomal dominant, neurodegenerative disorder with a primary etiology of striatal pathology. The Huntingtin gene (HTT) has a unique feature of a DNA trinucleotide (triplet) repeat, with repeat length ranging from 10 to 35 in the normal population. Repeat lengths between 36 and 39 cause HD at reduced penetrance (some will get the disease, others won't) and when expanded to 40 or more repeats (mHTT), causes HD at full penetrance (every person with this length or beyond will definitely develop the disease). The symptoms of HD may be motor, cognitive, and psychiatric, and are consistent with the pathophysiology of frontostriatal circuitry malfunction. Expressed ubiquitously and throughout the entire life cycle (development through adulthood), mHTT causes initial dysfunction and eventual death of a specific cell population within the striatum. Although all areas of the brain are eventually affected, the primary pathology of the disease is regionally specific. As a single-gene disorder, HD has the distinction of having the potential of treatment that is aimed directly at the known pathogenic mechanism by gene silencing, providing hope for neuroprotection and ultimately, prevention. PMID:27069383

  19. Repackaging FDA-approved drugs for degenerative diseases: promises and challenges.

    PubMed

    Cummings, Jeffrey L; Zhong, Kate

    2014-03-01

    Repurposing refers to the therapeutic use of a drug or drug candidate for a disease other than that for which it was originally intended. Repurposing is attractive as a drug development strategy since much is known about approved agents including their drug-likeness and pharmacokinetic features, dosing, safety, tolerability, formulation and manufacturing. Time savings are also robust accounting for several years of the drug development cycle. Tissue and cell-based assays, epidemiologic information and human studies identify approved drugs that might be repurposed from use in Alzheimer's disease and other neurodegenerative disorders. The total number of compounds available for repurposing that are brain-penetrant is relatively small. Intellectual property and patent protection issues for repurposed drugs are hurdles for this approach to drug development. Repurposing may contribute importantly to development of new therapies for neurodegenerative disorders. PMID:24502586

  20. Long-Term Follow-Up of the Cheilectomy for Degenerative Joint Disease of the First Metatarsophalangeal Joint.

    PubMed

    Nicolosi, Nicole; Hehemann, Chris; Connors, James; Boike, Allan

    2015-01-01

    Cheilectomy is the surgical resection of 20% to 30% of the dorsal metatarsal head and proximal phalanx. The present retrospective study evaluated the long-term efficacy of aggressive cheilectomy to address degenerative joint disease of the first metatarsophalangeal joint. To our knowledge, this is the second longest duration study to date to evaluate the long-term efficacy of the cheilectomy procedure, with a mean follow-up period of 7.14 years (range 39 weeks to 14.87 years). The mean patient age was 55.71 ± 9.51 years, and 37 (65%) of the patients were female. Age, sex, foot type, and preoperative radiographic parameters of hallux rigidus were also evaluated and correlated. The mean percentage of success with this operation was 87.69%. Of the 58 patients, 51 (87.93%) experienced no limitations in their daily activities. Only 2 patients (3.33%) subsequently required subsequent arthrodesis. The results of the present study suggest that cheilectomy offers long-term satisfaction for patients with hallux rigidus and is an acceptable alternative to the joint destructive procedure of first metatarsophalangeal arthrodesis. PMID:25981441

  1. Thoracolumbar spinal cord compression due to vertebral process degenerative joint disease in a family of Shiloh Shepherd dogs.

    PubMed

    McDonnell, John J; Knowles, Kim E; deLahunta, Alexander; Bell, Jerold S; Lowrie, Charles T; Todhunter, Rory J

    2003-01-01

    Five young Shiloh Shepherd Dogs (4 males and 1 female) related by a common sire were studied because of progressive pelvic limb weakness and incoordination. All dogs had a spastic paraparesis and pelvic limb ataxia consistent with an upper motor neuron and general proprioceptive lesion between spinal cord segments T3 and L3. Proliferative lesions involving one or more of the articular processes from the 11th thoracic vertebrae to the 2nd lumbar vertebra were observed on radiographs of the thoracolumbar vertebrae. Dorsal compression of the spinal cord was identified during imaging studies at these sites. Abnormalities of the synovial joints and bony proliferation of the involved articular processes were identified at postmortem examination in 2 dogs. The articular processes and associated vertebral arches protruded into the vertebral canal, indenting the dorsal surface of the spinalcord. Degenerative joint disease (DJD) was identified histologically. A compressive myelopathy was diagnosed in the spinal cord. These dogs were affected by a compressive myelopathy as a consequence of vertebral process DJD that likely has a geneticcomponent. The DJD could have been caused by a primary vertebral malformation or an injury to the processes at a young age causing malarticulation. PMID:12892304

  2. Regenerative Injection Therapy with Whole Bone Marrow Aspirate for Degenerative Joint Disease: A Case Series

    PubMed Central

    Hauser, Ross A.; Orlofsky, Amos

    2013-01-01

    Regenerative therapeutic strategies for joint diseases usually employ either enriched concentrates of bone marrow-derived stem cells, chondrogenic preparations such as platelet-rich plasma, or irritant solutions such as hyperosmotic dextrose. In this case series, we describe our experience with a simple, cost-effective regenerative treatment using direct injection of unfractionated whole bone marrow (WBM) into osteoarthritic joints in combination with hyperosmotic dextrose. Seven patients with hip, knee or ankle osteoarthritis (OA) received two to seven treatments over a period of two to twelve months. Patient-reported assessments were collected in interviews and by questionnaire. All patients reported improvements with respect to pain, as well as gains in functionality and quality of life. Three patients, including two whose progress under other therapy had plateaued or reversed, achieved complete or near-complete symptomatic relief, and two additional patients achieved resumption of vigorous exercise. These preliminary findings suggest that OA treatment with WBM injection merits further investigation. PMID:24046512

  3. Common pathways in health benefit properties of RSV in cardiovascular diseases, cancers and degenerative pathologies.

    PubMed

    Aires, Virginie; Delmas, Dominique

    2015-01-01

    Lots of epidemiological studies have put forward the beneficial effects of dietary polyphenols consumption in the prevention of diseases related to aging i.e vascular pathologies, neurodegeneration, cancers and associated inflammatory processes. Among polyphenols, resveratrol (trans-3,4',5- trihydroxystilbene, RSV), a naturally occurring stilbene widely distributed in foodstuffs such as grapes and wine, has been the most studied. Researches performed since the last decades in vitro, in animal models and in (pre)clinical studies have pointed out its pleiotropic health benefits by acting on multiple signaling pathways which go beyond its originally described direct antioxidant activity. However, its low bioavailability upon oral ingestion and lack of specificity may hamper the translation of the encouraging experimental data into human health benefits. Herein we provide an overview on the capacity of RSV to regulate oxidative stress-induced signaling and to modulate key components of signal transduction pathways which are commonly altered in cardiovascular, neurodegenerative and cancer pathologies. We also have attempted to provide a comprehensive outlook on RSV metabolism and biological activity of its main metabolites and discussed about the new strategies developed to circumvent its poor bioavailability and to improve its therapeutic efficacy, including synthesis of new derivatives and new formulations for its cell delivery. PMID:25601605

  4. BEST1-related autosomal dominant vitreoretinochoroidopathy: a degenerative disease with a range of developmental ocular anomalies

    PubMed Central

    Vincent, A; McAlister, C; VandenHoven, C; Héon, E

    2011-01-01

    Purpose To describe the spectrum of phenotypic characteristics of BEST1-related autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a family with p.V86M mutation. Methods A retrospective review of the clinical, psychophysical, and electrophysiological phenotypes of six subjects with ADVIRC. Five family members were sequenced for mutations in the BEST1gene. Results A heterozygous change, p.V86M (c.256G>A), was identified in the BEST1gene in the three affected subjects tested, and was shown to segregate with the disease phenotype. The distance visual acuity ranged from ⩾20/25 to absent perception of light. Clinical features observed included angle closure glaucoma (n=2), microcornea with shallow anterior chamber (n=1), iris dysgenesis (n=2), cataracts (n=4), classical peripheral concentric band of retinal hyperpigmentation (n=5), and optic nerve dysplasia (n=1). Full-field electroretinogram response amplitudes ranged from low normal (two cases; 27 and 32 years) to non-recordable (two cases; 42 and 63 years). Goldmann fields were normal in two (27 and 28 years) but were abnormal in two older subjects. Optical coherence tomography showed macular thinning in the proband, whereas his affected daughter had normal macular thickness. Electro-oculography showed borderline Arden's ratio (1.50) in the lone case tested (27 years). Conclusion ADVIRC is a slowly progressive vitreoretinal degeneration that demonstrates marked intra-familial phenotypic variability. Optic nerve dysplasia and iris dysgenesis are novel observations that extend the ocular phenotype of ADVIRC. PMID:21072067

  5. Deciphering Structural Intermediates and Genotoxic Fibrillar Aggregates of Albumins: A Molecular Mechanism Underlying for Degenerative Diseases

    PubMed Central

    Naeem, Aabgeena; Amani, Samreen

    2013-01-01

    The misfolding and aggregation of proteins is involved in some of the most prevalent neurodegenerative disorders. The importance of human serum albumin (HSA) stems from the fact that it is involved in bio-regulatory and transport phenomena. Here the effect of acetonitrile (ACN) on the conformational stability of HSA and by comparison, ovalbumin (OVA) has been evaluated in the presence and absence of NaCl. The results show the presence of significant amount of secondary structure in HSA at 70% ACN and in OVA at 50% ACN, as evident from far-UV Circular Dichroism (CD) and Attenuated Total Reflection Fourier transformed infra red spectroscopy (ATR-FTIR). Tryptophan and 8-Anilino-1-Naphthalene-Sulphonic acid (ANS) fluorescence indicate altered tryptophan environment and high ANS binding suggesting a compact “molten globule”-like conformation with enhanced exposure of hydrophobic surface area. However, in presence of NaCl no intermediate state was observed. Detection of aggregates in HSA and OVA was possible at 90% ACN. Aggregates possess extensive β-sheet structure as revealed by far-UV CD and ATR-FTIR. These aggregates exhibit increase Thioflavin T (Th T) fluorescence with a red shift of Congo red (CR) absorption spectrum. X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM) analysis confirmed the presence of fibrillar aggregates. Single cell gel electrophoresis (SCGE) assay of these fibrillar aggregates showed the DNA damage resulting in cell necrosis confirming their genotoxic nature. Some proteins not related to any human disease form fibrils in vitro. In the present study ACN gives access to a model system to study the process of aggregation. PMID:23342075

  6. MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine.

    PubMed

    Stolworthy, Dean K; Bowden, Anton E; Roeder, Beverly L; Robinson, Todd F; Holland, Jacob G; Christensen, S Loyd; Beatty, Amanda M; Bridgewater, Laura C; Eggett, Dennis L; Wendel, John D; Stieger-Vanegas, Susanne M; Taylor, Meredith D

    2015-12-01

    Animal models have historically provided an appropriate benchmark for understanding human pathology, treatment, and healing, but few animals are known to naturally develop intervertebral disc degeneration. The study of degenerative disc disease and its treatment would greatly benefit from a more comprehensive, and comparable animal model. Alpacas have recently been presented as a potential large animal model of intervertebral disc degeneration due to similarities in spinal posture, disc size, biomechanical flexibility, and natural disc pathology. This research further investigated alpacas by determining the prevalence of intervertebral disc degeneration among an aging alpaca population. Twenty healthy female alpacas comprised two age subgroups (5 young: 2-6 years; and 15 older: 10+ years) and were rated according to the Pfirrmann-grade for degeneration of the cervical intervertebral discs. Incidence rates of degeneration showed strong correlations with age and spinal level: younger alpacas were nearly immune to developing disc degeneration, and in older animals, disc degeneration had an increased incidence rate and severity at lower cervical levels. Advanced disc degeneration was present in at least one of the cervical intervertebral discs of 47% of the older alpacas, and it was most common at the two lowest cervical intervertebral discs. The prevalence of intervertebral disc degeneration encourages further investigation and application of the lower cervical spine of alpacas and similar camelids as a large animal model of intervertebral disc degeneration. PMID:26135031

  7. Chronic pain coping styles in patients with herniated lumbar discs and coexisting spondylotic changes treated surgically: Considering clinical pain characteristics, degenerative changes, disability, mood disturbances, and beliefs about pain control

    PubMed Central

    Misterska, Ewa; Jankowski, Roman; Głowacki, Maciej

    2013-01-01

    Background Pain catastrophizing, appraisals of pain control, styles of coping, and social support have been suggested to affect functioning in patients with low back pain. We investigated the relation of chronic pain coping strategies to psychological variables and clinical data, in patients treated surgically due to lumbar disc herniation and coexisting spondylotic changes. Material/Methods The average age of study participants (n=90) was 43.47 years (SD 10.21). Patients completed the Polish versions of the Chronic Pain Coping Inventory-42 (PL-CPCI-42), Beck Depression Inventory (BDI-PL), Coping Strategies Questionnaire (CSQ-PL), Beliefs about Pain Control Questionnaire (BPCQ-PL), and Roland-Morris Disability Questionnaire (RMQ-PL). Results In the PL-CPCI-42 results, resting, guarding and coping self-statements were frequently used as coping strategies (3.96 SD 1.97; 3.72 SD 1.72; 3.47 SD 2.02, respectively). In the CSQ-PL domains, catastrophizing and praying/hoping were frequently used as coping strategies (3.62 SD 1.19). The mean score obtained from the BDI-PL was 11.86 SD 7.23, and 12.70 SD 5.49 from the RMDQ-PL. BPCQ-PL results indicate that the highest score was in the subscale measuring beliefs that powerful others can control pain (4.36 SD 0.97). Exercise correlated significantly with beliefs about internal control of pain (rs=0.22). We identified associations between radiating pain and guarding (p=0.038) and between sports recreation and guarding (p=0.013) and task persistence (p=0.041). Conclusions Back pain characteristics, depressive mood, disability, and beliefs about personal control of pain are related to chronic LBP coping styles. Most of the variables related to advancement of degenerative changes were not associated with coping efforts. PMID:24370564

  8. Biological Treatment Approaches for Degenerative Disk Disease: A Literature Review of In Vivo Animal and Clinical Data

    PubMed Central

    Moriguchi, Yu; Alimi, Marjan; Khair, Thamina; Manolarakis, George; Berlin, Connor; Bonassar, Lawrence J.; Härtl, Roger

    2016-01-01

    Study Design  Literature review. Objective  Degenerative disk disease (DDD) has a negative impact on quality of life and is a major cause of morbidity worldwide. There has been a growing interest in the biological repair of DDD by both researchers and clinicians alike. To generate an overview of the recent progress in reparative strategies for the treatment of DDD highlighting their promises and limitations, a comprehensive review of the current literature was performed elucidating data from in vivo animal and clinical studies. Methods  Articles and abstracts available in electronic databases of PubMed, Web of Science, and Google Scholar as of December 2014 were reviewed. Additionally, data from unpublished, ongoing clinical trials was retrieved from clinicaltrials.gov and available abstracts from research forums. Data was extracted from the most recent in vivo animal or clinical studies involving any of the following: (1) treatment with biomolecules, cells, or tissue-engineered constructs and (2) annulus fibrosus repair. Results  Seventy-five articles met the inclusion criteria for review. Among these, 17 studies involved humans; 37, small quadrupeds; and 21, large quadrupeds. Findings from all treatments employed demonstrated improvement either in regenerative capacity or in pain attenuation, with the exception of one clinical study. Conclusion  Published clinical studies on cell therapy have reported encouraging results in the treatment of DDD and resultant back pain. We expect new data to emerge in the near future as treatments for DDD continue to evolve in parallel to our greater understanding of disk health and pathology. PMID:27433434

  9. Quantitative MRI as a diagnostic tool of intervertebral disc matrix composition and integrity

    PubMed Central

    Mwale, Fackson; Iatridis, James C.

    2008-01-01

    Degenerative disc disease has been implicated as a major component of spine pathology. The current major clinical procedures for treating disc degeneration have been disappointing, because of altered spinal mechanics leading to subsequent degeneration at adjacent disc levels. Disc pathology treatment is shifting toward prevention and treatment of underlying etiologic processes at the level of the disc matrix composition and integrity and the biomechanics of the disc. The ability to perform such treatment relies on one’s ability to accurately and objectively assess the state of the matrix and the effectiveness of treatment by a non-invasive technique. In this review, we will summarize our advances in efforts to develop an objective, accurate, non-invasive diagnostic tool (quantitative MRI) in the detection and quantification of matrix composition and integrity and of biomechanical changes in early intervertebral disc degeneration. PMID:19005703

  10. Canine degenerative myelopathy.

    PubMed

    Coates, Joan R; Wininger, Fred A

    2010-09-01

    Canine degenerative myelopathy (DM) is an adult-onset fatal neurodegenerative disease that occurs in many breeds. The initial upper motor neuron spastic paraparesis and general proprioceptive ataxia in the pelvic limbs progress to a flaccid lower motor neuron tetraparesis. Recently, a missense mutation in the superoxide dismutase 1 (SOD1) gene was found to be a risk factor for DM, suggesting that DM is similar to some forms of human amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). This article reviews the current knowledge of canine DM with regard to its signalment, clinical spectrum, diagnostic approach, and treatment. The implications of the SOD1 mutation on both diseases are discussed, comparing pathogenic mechanisms while conveying perspectives to translational medicine. PMID:20732599

  11. Structural Studies on Acetylcholinesterase and Paraoxonase Directed Towards Development of Therapeutic Biomolecules for the Treatment of Degenerative Diseases and Protection Against Chemical Threat Agents

    NASA Astrophysics Data System (ADS)

    Sussman, Joel L.; Silman, Israel

    Acetylcholinesterase and paraoxonase are important targets for treatment of degenerative diseases, Alzheimer's disease and atherosclerosis, respectively, both of which impose major burdens on the health care systems in Western society. Acetylcholinesterase is the target of lethal nerve agents, and paraoxonase is under consideration as a bioscavenger for their detoxification. Both are thus the subject of research and development in the context of nerve agent toxicology. The crystal structures of the two enzymes are described, and structure/function relationships are discussed in the context of drug development and of development of means of protection against chemical threats.

  12. Notochord Cells in Intervertebral Disc Development and Degeneration

    PubMed Central

    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

    The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

  13. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins.

    PubMed

    Capossela, S; Schläfli, P; Bertolo, A; Janner, T; Stadler, B M; Pötzel, T; Baur, M; Stoyanov, J V

    2014-01-01

    Degeneration of intervertebral discs (IVDs) is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP) to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases. PMID:24706108

  14. The role of polymorphisms of genes encoding collagen IX and XI in lumbar disc disease.

    PubMed

    Janeczko, Łukasz; Janeczko, Magdalena; Chrzanowski, Robert; Zieliński, Grzegorz

    2014-01-01

    The intervertebral disc disease (IDD) is one of the most common musculoskeletal disorders. A number of environment and anthropometric risk factors may contribute to it. The recent reports have suggested the importance of genetic factors, especially these which encode collagen types IX and XI. The allelic variants in the collagen IX genes - COL9A2 (Trp2) and COL9A3 (Trp3) have been identified as genetic risk factors for IDD, because they interfere the cross-linking between collagen types II, IX and XI and result in decreased stability of intervertebral discs. Type XI collagen is a minor component of cartilage collagen fibrils, but it is present in the annulus fibrosus and nucleus pulposus of intervertebral discs. Some studies have shown the association between gene COL11A1 polymorphism c.4603C>T and IDD. The frequency of 4603T allele was significantly higher in the patients with IDD than in the healthy controls. PMID:24636772

  15. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 7: lumbar fusion for intractable low-back pain without stenosis or spondylolisthesis.

    PubMed

    Eck, Jason C; Sharan, Alok; Ghogawala, Zoher; Resnick, Daniel K; Watters, William C; Mummaneni, Praveen V; Dailey, Andrew T; Choudhri, Tanvir F; Groff, Michael W; Wang, Jeffrey C; Dhall, Sanjay S; Kaiser, Michael G

    2014-07-01

    Establishing an appropriate treatment strategy for patients presenting with low-back pain, in the absence of stenosis or spondylolisthesis, remains a controversial subject. Inherent to this situation is often an inability to adequately identify the source of low-back pain to justify various treatment recommendations, such as lumbar fusion. The current evidence does not identify a single best treatment alternative for these patients. Based on a number of prospective, randomized trials, comparable outcomes, for patients presenting with 1- or 2-level degenerative disc disease, have been demonstrated following either lumbar fusion or a comprehensive rehabilitation program with a cognitive element. Limited access to such comprehensive rehabilitative programs may prove problematic when pursuing this alternative. For patients whose pain is refractory to conservative care, lumbar fusion is recommended. Limitations of these studies preclude the ability to present the most robust recommendation in support of lumbar fusion. A number of lesser-quality studies, primarily case series, also support the use of lumbar fusion in this patient population. PMID:24980584

  16. Outcome of physiotherapy after surgery for cervical disc disease: a prospective randomised multi-centre trial

    PubMed Central

    2014-01-01

    Background Many patients with cervical disc disease require leave from work, due to long-lasting, complex symptoms, including chronic pain and reduced levels of physical and psychological function. Surgery on a few segmental levels might be expected to resolve disc-specific pain and reduce neurological deficits, but not the non-specific neck pain and the frequent illness. No study has investigated whether post-surgery physiotherapy might improve the outcome of surgery. The main purpose of this study was to evaluate whether a well-structured rehabilitation programme might add benefit to the customary post-surgical treatment for cervical disc disease, with respect to function, disability, work capability, and cost effectiveness. Methods/Design This study was designed as a prospective, randomised, controlled, multi-centre study. An independent, blinded investigator will compare two alternatives of rehabilitation. We will include 200 patients of working age, with cervical disc disease confirmed by clinical findings and symptoms of cervical nerve root compression. After providing informed consent, study participants will be randomised to one of two alternative physiotherapy regimes; (A) customary treatment (information and advice on a specialist clinic); or (B) customary treatment plus active physiotherapy. Physiotherapy will follow a standardised, structured programme of neck-specific exercises combined with a behavioural approach. All patients will be evaluated both clinically and subjectively (with questionnaires) before surgery and at 6 weeks, 3 months, 6 months, 12 months, and 24 months after surgery. The main outcome variable will be neck-specific disability. Cost-effectiveness will also be calculated. Discussion We anticipate that the results of this study will provide evidence to support physiotherapeutic rehabilitation applied after surgery for cervical radiculopathy due to cervical disc disease. Trial registration ClinicalTrials.gov identifier: NCT01547611

  17. Percutaneous Transforaminal Lumbar Interbody Fusion (pTLIF) with a Posterolateral Approach for the Treatment of Degenerative Disk Disease: Feasibility and Preliminary Results

    PubMed Central

    Morgenstern, Christian

    2015-01-01

    Background Interbody fusion by open discectomy is the usual treatment for degenerative disk disease but requires a relatively long recovery period. The transforaminal posterolateral approach is a well-known standard in endoscopic spine surgery that allows direct access to the disk with progressive tissue dilation. The aim of this study was to assess the feasibility of percutaneous transforaminal interbody fusion (pTLIF) with insertion of an expandable or a standard rigid interbody implant for patients with degenerative disk disease with or without spondylolisthesis and for revision surgery. Methods Between 2009 and 2014, the pTLIF procedure was performed in 30 patients. Ten patients underwent insertion of a rigid implant (group A) and the remaining 20 underwent insertion of an expandable titanium interbody implant as the initial procedure (n = 10) (group B) or after failed back surgery (n = 10) (group C). Patient outcomes were scored with visual analogic scale (VAS), Oswestry disability index (ODI) and modified Macnab criteria. Results The mean follow-up period was 38 (17) (range 11 to 67) months. The outcome was excellent in 18, good in 10 and fair in 2. No poor results and no major complications were reported. No differences in VAS and ODI scores according to the study group were found. Median postoperative time until hospital discharge was 26 hours (20 to 68 hours). Postoperative values for VAS and ODI scores improved significantly (p<0.05) compared to preoperative data in all study groups. Conclusions These preliminary results have shown the feasibility and efficacy of the pTLIF procedure using a posterolateral approach for the treatment of degenerative disk disease with or without spondylolisthesis up to grade 2 and in revision surgery. No significant differences in outcome were observed between an expandable and a rigid cage. Median postoperative time until hospital discharge was faster compared to standard TLIF (26 hours vs. 9.3 days). PMID:26484004

  18. Two-level total lumbar disc replacement

    PubMed Central

    Bakaloudis, Georgios; Lolli, Francesco; Vommaro, Francesco; Parisini, Patrizio

    2009-01-01

    Total lumbar disc replacement (TDR) has been widely used as a treatment option for 2-level symptomatic degenerative disc disease. However, recent studies have presented conflicting results and some authors concluded that outcome deteriorated when disc replacement was performed bisegmentally, with an increase of complications for bisegmental replacements in comparison with monosegmental disc arthroplasty. The goal of the present retrospective study is to investigate results in a group of patients who have received bisegmental TDR with SB Charitè III artificial disc for degenerative disc disease with a minimum follow-up of 3 years, and to compare the results of 2-level disc replacement versus 1-level patients treated with the same prosthesis. A total of 32 patients had at least 3-years follow-up and were reviewed. The average age of the patients was 38.5 years. There were 11 males and 21 females. About 16 patients received 2-level TDR (SB Charitè III) and 16 received 1-level TDR (SB Charitè III). Both radiographic and functional outcome analysis, including patient’s satisfaction, was performed. There were no signs of degenerative changes of the adjacent segments in any case of the 2- or 1-level TDR. There was no statistically significant difference between 2- and 1-level TDR both at 12 months and at 3-years follow-up on functional outcome scores. There was a statistically insignificant difference concerning the patients satisfaction between 1- and 2-level surgeries at the last follow-up (P = 0.46). In the 2-level TDR patients, there were 5 minor complications (31.25%), whereas major complications occurred in 4 more patients (25%) and required a new surgery in 2 cases (12.5%). In the 1-level cases there were 2 minor complications (12.5%) and 2 major complications (12.5%) and a new revision surgery was required in 1 patient (6.25%). In conclusion, the use of 2-level disc replacement at last follow-up presented a higher incidence of complications than in cases

  19. Gene expression profile analysis of human intervertebral disc degeneration

    PubMed Central

    Chen, Kai; Wu, Dajiang; Zhu, Xiaodong; Ni, Haijian; Wei, Xianzhao; Mao, Ningfang; Xie, Yang; Niu, Yunfei; Li, Ming

    2013-01-01

    In this study, we used microarray analysis to investigate the biogenesis and progression of intervertebral disc degeneration. The gene expression profiles of 37 disc tissue samples obtained from patients with herniated discs and degenerative disc disease collected by the National Cancer Institute Cooperative Tissue Network were analyzed. Differentially expressed genes between more and less degenerated discs were identified by significant analysis of microarray. A total of 555 genes were significantly overexpressed in more degenerated discs with a false discovery rate of < 3%. Functional annotation showed that these genes were significantly associated with membrane-bound vesicles, calcium ion binding and extracellular matrix. Protein-protein interaction analysis showed that these genes, including previously reported genes such as fibronectin, COL2A1 and β-catenin, may play key roles in disc degeneration. Unsupervised clustering indicated that the widely used morphology-based Thompson grading system was only marginally associated with the molecular classification of intervertebral disc degeneration. These findings indicate that detailed, systematic gene analysis may be a useful way of studying the biology of intervertebral disc degeneration. PMID:24130454

  20. Biomechanics of Degenerative Spinal Disorders

    PubMed Central

    Iorio, Justin A.; Jakoi, Andre M.

    2016-01-01

    The spine has several important functions including load transmission, permission of limited motion, and protection of the spinal cord. The vertebrae form functional spinal units, which represent the smallest segment that has characteristics of the entire spinal column. Discs and paired facet joints within each functional unit form a three-joint complex between which loads are transmitted. Surrounding the spinal motion segment are ligaments, composed of elastin and collagen, and joint capsules which restrict motion to within normal limits. Ligaments have variable strengths and act via different lever arm lengths to contribute to spinal stability. As a consequence of the longer moment arm from the spinous process to the instantaneous axis of rotation, inherently weaker ligaments (interspinous and supraspinous) are able to provide resistance to excessive flexion. Degenerative processes of the spine are a normal result of aging and occur on a spectrum. During the second decade of life, the intervertebral disc demonstrates histologic evidence of nucleus pulposus degradation caused by reduced end plate blood supply. As disc height decreases, the functional unit is capable of an increased range of axial rotation which subjects the posterior facet capsules to greater mechanical loads. A concurrent change in load transmission across the end plates and translation of the instantaneous axis of rotation further increase the degenerative processes at adjacent structures. The behavior of the functional unit is impacted by these processes and is reflected by changes in the stress-strain relationship. Back pain and other clinical symptoms may occur as a result of the biomechanical alterations of degeneration. PMID:27114783

  1. Biomechanics of Degenerative Spinal Disorders.

    PubMed

    Iorio, Justin A; Jakoi, Andre M; Singla, Anuj

    2016-04-01

    The spine has several important functions including load transmission, permission of limited motion, and protection of the spinal cord. The vertebrae form functional spinal units, which represent the smallest segment that has characteristics of the entire spinal column. Discs and paired facet joints within each functional unit form a three-joint complex between which loads are transmitted. Surrounding the spinal motion segment are ligaments, composed of elastin and collagen, and joint capsules which restrict motion to within normal limits. Ligaments have variable strengths and act via different lever arm lengths to contribute to spinal stability. As a consequence of the longer moment arm from the spinous process to the instantaneous axis of rotation, inherently weaker ligaments (interspinous and supraspinous) are able to provide resistance to excessive flexion. Degenerative processes of the spine are a normal result of aging and occur on a spectrum. During the second decade of life, the intervertebral disc demonstrates histologic evidence of nucleus pulposus degradation caused by reduced end plate blood supply. As disc height decreases, the functional unit is capable of an increased range of axial rotation which subjects the posterior facet capsules to greater mechanical loads. A concurrent change in load transmission across the end plates and translation of the instantaneous axis of rotation further increase the degenerative processes at adjacent structures. The behavior of the functional unit is impacted by these processes and is reflected by changes in the stress-strain relationship. Back pain and other clinical symptoms may occur as a result of the biomechanical alterations of degeneration. PMID:27114783

  2. Characterization of Thoracic Motor and Sensory Neurons and Spinal Nerve Roots in Canine Degenerative Myelopathy, a Potential Disease Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Shelton, G. Diane; Katz, Martin L.

    2014-01-01

    Canine Degenerative Myelopathy (DM) is a progressive adult-onset multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced stage DM. To determine if other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MN) and dorsal root ganglia (DRG), and in motor and sensory nerve root axons from DM-affected Boxers and Pembroke Welsh Corgis (PWCs). No alterations in MNs, or motor root axons were observed in either breed. However, advanced stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, or of their axons. Axonal loss in thoracic sensory roots and sensory nerve death suggest sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS. PMID:24375814

  3. Characterization of thoracic motor and sensory neurons and spinal nerve roots in canine degenerative myelopathy, a potential disease model of amyotrophic lateral sclerosis.

    PubMed

    Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Shelton, G Diane; Katz, Martin L

    2014-04-01

    Canine degenerative myelopathy (DM) is a progressive, adult-onset, multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced-stage DM. To determine whether other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MNs) and dorsal root ganglia (DRG) and in motor and sensory nerve root axons from DM-affected boxers and Pembroke Welsh corgis (PWCs). No alterations in MNs or motor root axons were observed in either breed. However, advanced-stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, nor of their axons. Axonal loss in thoracic sensory roots and sensory neuron death suggest that sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS. PMID:24375814

  4. Lumbar disc replacement: preliminary results with ProDisc II after a minimum follow-up period of 1 year.

    PubMed

    Tropiano, Patrick; Huang, Russel C; Girardi, Federico P; Marnay, Thierry

    2003-08-01

    Total disc replacement has the potential to replace fusion as the gold standard surgical treatment of degenerative disc disease. Potential advantages of disc replacement over fusion include avoidance of pseudarthrosis, postoperative orthoses, and junctional degeneration. After observing satisfactory clinical results at 7-11 years' follow-up with the ProDisc first-generation implant, a second-generation prosthesis was designed. This study is a prospective analysis of the early results of total disc replacement with the ProDisc II total disc prosthesis. Fifty-three patients had single-level or multilevel disc replacement and were evaluated clinically and radiographically preoperatively and at mean 1.4-year follow-up. There were clinically and statistically significant improvements in back and leg pain Visual Analog Scale and Oswestry disability scores that were maintained at final follow-up. The clinical results of patients with single- and multilevel surgery were equivalent. Satisfactory results were achieved in 90% of patients who had previous lumbar surgery. Complications occurred in 9% of patients and included vertebral body fracture, transient radicular pain, implant malposition, and transient retrograde ejaculation. Three patients (6%) required reoperation to address complications. No mechanical failure of the implants or loosening was observed, and the prostheses retained motion. Randomized, prospective, long-term studies will be necessary to compare the effectiveness of arthrodesis with total disc replacement. PMID:12902952

  5. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases.

    PubMed

    Calabriso, Nadia; Massaro, Marika; Scoditti, Egeria; Pellegrino, Mariangela; Ingrosso, Ilaria; Giovinazzo, Giovanna; Carluccio, Maria Annunziata

    2016-01-01

    Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases. PMID:27589705

  6. Hybrid Surgery Versus Anterior Cervical Discectomy and Fusion in Multilevel Cervical Disc Diseases

    PubMed Central

    Zhang, Jianfeng; Meng, Fanxin; Ding, Yan; Li, Jie; Han, Jian; Zhang, Xintao; Dong, Wei

    2016-01-01

    Abstract To investigate the outcomes and reliability of hybrid surgery (HS) versus anterior cervical discectomy and fusion (ACDF) for the treatment of multilevel cervical spondylosis and disc diseases. Hybrid surgery, combining cervical disc arthroplasty (CDA) with fusion, is a novel treatment to multilevel cervical degenerated disc disease in recent years. However, the effect and reliability of HS are still unclear compared with ACDF. To investigate the studies of HS versus ACDF in patients with multilevel cervical disease, electronic databases (Medline, Embase, Pubmed, Cochrane library, and Cochrane Central Register of Controlled Trials) were searched. Studies were included when they compared HS with ACDF and reported at least one of the following outcomes: functionality, neck pain, arm pain, cervical range of motion (ROM), quality of life, and incidence of complications. No language restrictions were used. Two authors independently assessed the methodological quality of included studies and extracted the relevant data. Seven clinical controlled trials were included in this study. Two trials were prospective and the other 5 were retrospective. The results of the meta-analysis indicated that HS achieved better recovery of NDI score (P = 0.038) and similar recovery of VAS score (P = 0.058) compared with ACDF at 2 years follow-up. Moreover, the total cervical ROM (C2–C7) after HS was preserved significantly more than the cervical ROM after ACDF (P = 0.000) at 2 years follow-up. Notably, the compensatory increase of the ROM of superior and inferior adjacent segments was significant in ACDF groups at 2-year follow-up (P < 0.01), compared with HS. The results demonstrate that HS provides equivalent outcomes and functional recovery for cervical disc diseases, and significantly better preservation of cervical ROM compared with ACDF in 2-year follow-up. This suggests the HS is an effective alternative invention for the treatment of multilevel cervical

  7. Flexible Stabilisation of the Degenerative Lumbar Spine Using PEEK Rods

    PubMed Central

    Benezech, Jacques; Garlenq, Bruno; Larroque, Gilles

    2016-01-01

    Posterior lumbar interbody fusion using cages, titanium rods, and pedicle screws is considered today as the gold standard of surgical treatment of lumbar degenerative disease and has produced satisfying long-term fusion rates. However this rigid material could change the physiological distribution of load at the instrumental and adjacent segments, a main cause of implant failure and adjacent segment disease, responsible for a high rate of further surgery in the following years. More recently, semirigid instrumentation systems using rods made of polyetheretherketone (PEEK) have been introduced. This clinical study of 21 patients focuses on the clinical and radiological outcomes of patients with lumbar degenerative disease treated with Initial VEOS PEEK®-Optima system (Innov'Spine, France) composed of rods made from PEEK-OPTIMA® polymer (Invibio Biomaterial Solutions, UK) without arthrodesis. With an average follow-up of 2 years and half, the chances of reoperation were significantly reduced (4.8%), quality of life was improved (ODI = 16%), and the adjacent disc was preserved in more than 70% of cases. Based on these results, combined with the biomechanical and clinical data already published, PEEK rods systems can be considered as a safe and effective alternative solution to rigid ones. PMID:26981285

  8. Signaling Networks of Retinal Ganglion Cell Formation and the Potential Application of Stem Cell-Based Therapy in Retinal Degenerative Diseases.

    PubMed

    Wu, Nan; Wang, Yi; Yang, Lanbo; Cho, Kin-Sang

    2016-08-01

    Retinal degenerative diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma result in permanent loss of retinal neurons and vision. Stem cell therapy could be a novel treatment strategy to restore visual function. In an ideal situation, a homogenous population of stem cell-derived retinal neurons with high purity is used for replacement therapy. Thus, it is crucial to elucidate the molecular mechanisms that regulate the development of retinal progenitor cells and subsequent generation of specific retinal neurons. Here, recent findings concerning the intrinsic and extrinsic factors that regulate retinal progenitor cell maintenance and differentiation are summarized, especially transcriptional factors and extrinsic signals. Understanding these mechanisms is indispensable because they have potential clinical applications, chiefly the generation of specific retinal cells such as retinal ganglion cells to treat glaucoma and other optic neuropathy diseases. PMID:27466076

  9. Solid-state temporomandibular joint imaging: accuracy in detecting osseous changes of degenerative joint disease and determining condylar spatial relations.

    PubMed

    Scarfe, William C; Farman, Allan G; Silveira, Anibal; Fairbanks, Brandon W; Kelly, Paul J

    2003-10-01

    The purpose of this study was to evaluate the off-label use of an intraoral charge-coupled device (CCD) for extraoral transcranial radiography of the temporomandibular joint. Corrected linear tomograms and transcranial images made with conventional screen-film combinations and a CCD detector were compared with sectioned cadaver specimens. Radiation dosage, qualitative assessment of condylar degenerative features, and condylar position within the glenoid fossa of the 3 modalities were assessed and compared. The CCD method required special adjustments to achieve adequate quality, and it involved greater exposure than the other methods. This use of this intraoral system for extraoral imaging cannot now be recommended, but future refinements might make it more viable. PMID:14560277

  10. Inflammation in intervertebral disc degeneration and regeneration

    PubMed Central

    Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.

    2015-01-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

  11. Global Transcriptome Analysis of the Tentacle of the Jellyfish Cyanea capillata Using Deep Sequencing and Expressed Sequence Tags: Insight into the Toxin- and Degenerative Disease-Related Transcripts

    PubMed Central

    Liu, Dan; Wang, Qianqian; Ruan, Zengliang; He, Qian; Zhang, Liming

    2015-01-01

    Background Jellyfish contain diverse toxins and other bioactive components. However, large-scale identification of novel toxins and bioactive components from jellyfish has been hampered by the low efficiency of traditional isolation and purification methods. Results We performed de novo transcriptome sequencing of the tentacle tissue of the jellyfish Cyanea capillata. A total of 51,304,108 reads were obtained and assembled into 50,536 unigenes. Of these, 21,357 unigenes had homologues in public databases, but the remaining unigenes had no significant matches due to the limited sequence information available and species-specific novel sequences. Functional annotation of the unigenes also revealed general gene expression profile characteristics in the tentacle of C. capillata. A primary goal of this study was to identify putative toxin transcripts. As expected, we screened many transcripts encoding proteins similar to several well-known toxin families including phospholipases, metalloproteases, serine proteases and serine protease inhibitors. In addition, some transcripts also resembled molecules with potential toxic activities, including cnidarian CfTX-like toxins with hemolytic activity, plancitoxin-1, venom toxin-like peptide-6, histamine-releasing factor, neprilysin, dipeptidyl peptidase 4, vascular endothelial growth factor A, angiotensin-converting enzyme-like and endothelin-converting enzyme 1-like proteins. Most of these molecules have not been previously reported in jellyfish. Interestingly, we also characterized a number of transcripts with similarities to proteins relevant to several degenerative diseases, including Huntington’s, Alzheimer’s and Parkinson’s diseases. This is the first description of degenerative disease-associated genes in jellyfish. Conclusion We obtained a well-categorized and annotated transcriptome of C. capillata tentacle that will be an important and valuable resource for further understanding of jellyfish at the molecular

  12. Repair and Regenerative Therapies of the Annulus Fibrosus of the Intervertebral Disc.

    PubMed

    Li, Xiaolong; Dou, Qingyu; Kong, Qingquan

    2016-02-01

    Degeneration of the intervertebral disc is implicated as the main cause of low back pain. Current treatment strategies for degenerative disc disease, such as conservative treatments and surgeries, only relieve the symptoms of low back pain without treating the causes of underlying degeneration. Surgical treatments cannot reverse the degeneration of the intervertebral disc degeneration, and may even accelerate the degeneration. The development of tissue engineering and regenerative therapeutic strategies have brought new hope for repair and regeneration of the degenerated intervertebral disc. These strategies have been developed mainly targeting to the repair and regeneration of the nucleus pulposus of the degenerated but intervertebral disc. Although many studies that focused on the nucleus pulposus repair have achieved successes in laboratory settings but disc repair without giving much regard to annulus fibrosus could not recover the normal mechanical environment, which might make the disc degenerative change continuously exacerbate. Lately, the strategy to simultaneously repair the damaged annulus fibrosus and nucleus pulposus has attracted more attention, which could be considered to slow the disc degenerative rate and obtain better repair effect. An extensive literature search up to March 2015 for annulus fibrosus repair and regeneration in vitro or in vivo studies and clinical trials with the key words of "annulus fibrosus, repair, regeneration, tissue engineering, intervertebral disc and scaffold" were performed through PubMed, China National Knowledge Infrastructure and China Biology Medicine. The goal of this paper was to review the current research progress of annulus fibrosus repair and regeneration, and also suggest directions for future research. PMID:26876403

  13. The history of spinal surgery for disc disease: an illustrated timeline.

    PubMed

    Castro, Igor de; Santos, Daniel Paes dos; Christoph, Daniel de Holanda; Landeiro, José Alberto

    2005-09-01

    This article presents the evolution in medical history which leads to the surgical treatment for ruptured discs. Only at the last century the precise diagnosis of a ruptured lumbar disc could be made after tremendous efforts of the many medical pioneers in the study of the spine. The experience gained with the lumbar spine was rapidly transferred to the cervical spine. We describe the evolution of the clinical and surgical aspects about ruptured discs in the lumbar and cervical spine. An illustrative timeline of the major events regarding the surgical treatment for ruptured disks is outlined in a straight forward manner. Our understandings of the relation between symptoms and signs and of that between anatomy and pathophysiology have led to more successful surgical treatment for this disease. Nowadays lumbar and cervical discectomies are the most frequent operations carried out by neurosurgeons. Our current care of patients with this kind of spinal disorders is based on the work of our ancient medical heroes. PMID:16172729

  14. Role of Cytokines in Intervertebral Disc Degeneration: Pain and Disc-content

    PubMed Central

    Risbud, Makarand V.; Shapiro, Irving. M

    2014-01-01

    Degeneration of the intervertebral disc is the major contributor to back/neck and radicular pain. It is characterized by an elevation in levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1 α/β, IL-6 and IL-17 secreted by the disc cells themselves; these cytokines promote matrix degradation, chemokine production and changes in cell phenotype. The resulting imbalance between catabolic and anabolic responses leads to degeneration, as well as herniation and radicular pain. Release of chemokines from degenerating discs promote infiltration and activation of T and B cells, macrophages, neutrophils, and mast cells further amplifying the inflammatory cascade. Immunocyte migration into the disc is accompanied by the appearance of microvasculature and nerve fibers arising from the dorsal root ganglion (DRG). In this inflammatory milieu, neurogenic factors in particular nerve growth factor (NGF) and brain-derive neurotrophic factor (BDNF) generated by disc and immune cells induce expression of pain associated cation channels in DRGs. Depolarization of these channels is likely to promote discogenic and radicular pain and reinforce the cytokine-mediated degenerative cascade. Taken together, the enhanced understanding of the contribution of cytokines and immune cells to catabolic and nociceptive processes provide new targets for treating symptomatic disc disease. PMID:24166242

  15. Cervical arthroplasty using ProDisc-C case report.

    PubMed

    Nica, D A; Copaciu, R

    2013-03-15

    Cervical disc replacement is an emerging motion-preserving technology in the surgical treatment of the cervical degenerative disc disorders used as an alternative to the classic interbody fusion. We present a case report of a patient diagnosed with C6-7 right disc herniation who underwent anterior discectomy and received a total disc replacement using ProDisc C artificial disc prosthesis. PMID:23599830

  16. Percutaneous Disc Coagulation Therapy (PDCT) comparing with Automated Percutaneous Lumbar Discectomy (APLD) in Patients of Herniated Lumbar Disc Disease: Preliminary Report

    PubMed Central

    Park, Cheon Wook; Lee, Joo Yong; Choi, Woo Jin

    2012-01-01

    Objective Percutaneous techniques are rapidly replacing traditional open surgery. This is a randomized controlled trial study of clinical outcomes of Percutaneous Plasma Disc Coagulation Therapy (PDCT) in patients with HLD(herniated lumbar disc) as a new percutaneous access in comparison with Automated Percutaneous Lumbar Discectomy (APLD) in its clinical application and usefulness as a reliable alternative method. Methods The authors analyzed 25 patients who underwent PDCT randomized 1:1 to 25 who underwent APLD between June, 2010 and October, 2011. All patients had herniated lumbar disc diseases. The clinical outcomes were evaluated using Visual Analog Scales (VAS) score and MacNab's criteria. Results The age of the patients who underwent PDCT ranged from 29 to 88 years with a mean age of 51.8 years. The age of the APLD undergone patients' population ranged from 30 to 66 with a mean age of 46.0 years. The average preoperative VAS score in PDCT was 7.60 and 1.94 at 7months post-operatively, and in APLD was 7.32, and 3.53 at 7 months post-operatively (p<0.001). In Macnab's criteria, 20 patients (80%) had achieved favorable improvement (excellent and good) in PDCT group. In Macnab's criteria, 16 patients (64%) had achieved favorable improvement in APLD group (p<0.001). Conclusion PDCT can be considered a viable option as a new percutaneous access to herniated lumbar disc. PDCT showed to be more effective than APLD in this study, allowing stable decompression and safe minimally invasive operation to an area desired by the operator in lumbar disc herniation patients, although further long term clinical evaluations are still necessary. PMID:25983808

  17. Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc.

    PubMed

    Meisel, Hans Jörg; Siodla, Vilma; Ganey, Timothy; Minkus, Yvonne; Hutton, William C; Alasevic, Olivera J

    2007-02-01

    Disc herniation treated by discectomy results in a significant loss of nucleus material and disc height. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. Chondrocytes that have been removed from damaged cartilaginous tissues maintain a capacity to proliferate, produce and secrete matrix components and respond to physical stimuli such as dynamic loading. Nucleus regeneration using autologous cultured disc-derived chondrocytes (ADCT) has been demonstrated in a canine model and in clinical pilot studies. In 2002 a prospective, controlled, randomised, multi-center study, EuroDISC, comparing safety and efficacy of autologous disc chondrocyte transplant, chondrotransplant DISC, plus discectomy (ADCT), with discectomy alone was initiated. A dog model was used to investigate the hypothesis that autologous disc chondrocytes can be used to repair damaged intervertebral disc. Disc chondrocytes were harvested and expanded in culture under controlled and defined conditions, returned to the same animals from which they had been sampled (autologous transplantation) via percutaneous delivery. The animals were analyzed at specific times after transplantation by several methods to examine whether disc chondrocytes integrated with the surrounding tissue, produced the appropriate intervertebral disc extracellular matrix, and might provide a formative solution to disc repair. The clinical goals of the EuroDISC study, were to provide long-term pain relief, maintain disc height and prevent adjacent segment disease. Interim analysis was performed after 2 years; Oswestry (low back pain/disability), Quebec Back-Pain Disability Scale, as well as Prolo and VAS score were used for the evaluation. Disc height was assessed by MRI. In the context of degenerative changes in an injury model: () autologous disc chondrocytes were expended in culture and returned to the disc by a

  18. Footprint mismatch in lumbar total disc arthroplasty.

    PubMed

    Gstoettner, Michaela; Michaela, Gstoettner; Heider, Denise; Denise, Heider; Liebensteiner, Michael; Bach, Christian Michael; Michael, Bach Christian

    2008-11-01

    Lumbar disc arthroplasty has become a popular modality for the treatment of degenerative disc disease. The dimensions of the implants are based on early published geometrical measurements of vertebrae; the majority of these were cadaver studies. The fit of the prosthesis in the intervertebral space is of utmost importance. An undersized implant may lead to subsidence, loosening and biomechanical failure due to an incorrect center of rotation. The aim of the present study was to measure the dimensions of lumbar vertebrae based on CT scans and assess the accuracy of match in currently available lumbar disc prostheses. A total of 240 endplates of 120 vertebrae were included in the study. The sagittal and mediolateral diameter of the upper and lower endplates were measured using a digital measuring system. For the levels L4/L5 and L5/S1, an inappropriate size match was noted in 98.8% (Prodisc L) and 97.6% (Charite) with regard to the anteroposterior diameter. Mismatch in the anterior mediolateral diameter was noted in 79.3% (Prodisc L) and 51.2% (Charite) while mismatch in the posterior mediolateral diameter was observed in 91.5% (Prodisc L) and 78% (Charite) of the endplates. Surgeons and manufacturers should be aware of the size mismatch of currently available lumbar disc prostheses, which may endanger the safety and efficacy of the procedure. Larger footprints of currently available total disc arthroplasties are required. PMID:18791748

  19. Footprint mismatch in lumbar total disc arthroplasty

    PubMed Central

    Michaela, Gstoettner; Denise, Heider; Liebensteiner, Michael

    2008-01-01

    Lumbar disc arthroplasty has become a popular modality for the treatment of degenerative disc disease. The dimensions of the implants are based on early published geometrical measurements of vertebrae; the majority of these were cadaver studies. The fit of the prosthesis in the intervertebral space is of utmost importance. An undersized implant may lead to subsidence, loosening and biomechanical failure due to an incorrect center of rotation. The aim of the present study was to measure the dimensions of lumbar vertebrae based on CT scans and assess the accuracy of match in currently available lumbar disc prostheses. A total of 240 endplates of 120 vertebrae were included in the study. The sagittal and mediolateral diameter of the upper and lower endplates were measured using a digital measuring system. For the levels L4/L5 and L5/S1, an inappropriate size match was noted in 98.8% (Prodisc L) and 97.6% (Charite) with regard to the anteroposterior diameter. Mismatch in the anterior mediolateral diameter was noted in 79.3% (Prodisc L) and 51.2% (Charite) while mismatch in the posterior mediolateral diameter was observed in 91.5% (Prodisc L) and 78% (Charite) of the endplates. Surgeons and manufacturers should be aware of the size mismatch of currently available lumbar disc prostheses, which may endanger the safety and efficacy of the procedure. Larger footprints of currently available total disc arthroplasties are required. PMID:18791748

  20. Preclinical and clinical experience with a viscoelastic total disc replacement

    PubMed Central

    Rischke, Burkhard; Ross, Raymond S.; Jollenbeck, Boris A.; Zimmers, Kari B.; Defibaugh, Neal D.

    2011-01-01

    Background The purpose of this study is to describe the mechanical durability and the clinical and radiographic outcomes of a viscoelastic total disc replacement (VTDR). The human intervertebral disc is a complex, viscoelastic structure, permitting and constraining motion in 3 axes, thus providing stability. The ideal disc replacement should be viscoelastic and deformable in all directions, and it should restore disc height and angle. Methods Mechanical testing was conducted to validate the durability of the VTDR, and a clinical study was conducted to evaluate safety and performance. Fifty patients with single-level, symptomatic lumbar degenerative disc disease at L4-5 or L5-S1 were enrolled in a clinical trial at 3 European sites. Patients were assessed clinically and radiographically for 2 years by the Oswestry Disability Index (ODI), a visual analog scale (VAS), and independent radiographic analyses. Results The VTDR showed a fatigue life in excess of 50 million cycles (50-year equivalent) and a physiologically appropriate level of stiffness, motion, geometry, and viscoelasticity. We enrolled 28 men and 22 women in the clinical study, with a mean age of 40 years. Independent quantitative radiographic assessment indicated that the VTDR restored and maintained disc height and lordosis while providing physiologic motion. Mean ODI scores decreased from 48% preoperatively to 23% at 2 years’ follow-up. Mean VAS low-back pain scores decreased from 7.1 cm to 2.9 cm. Median scores indicated that half of the patient population had ODI scores below 10% and VAS low-back pain scores below 0.95 cm at 2 years. Conclusions The VTDR has excellent durability and performs clinically and radiographically as intended for the treatment of symptomatic lumbar degenerative disc disease. Clinical Relevance The VTDR is intended to restore healthy anatomic properties and stability characteristics to the spinal segment. This study is the first to evaluate a VTDR in a 50-patient

  1. Efficacy of Percutaneous Epidural Neuroplasty Does Not Correlate with Dural Sac Cross-Sectional Area in Single Level Disc Disease

    PubMed Central

    Ji, Gyu Yeul; Oh, Chang Hyun; Moon, Bongju; Choi, Seung Hyun; Yoon, Young Sul; Kim, Keung Nyun

    2015-01-01

    Purpose Percutaneous epidural neuroplasty (PEN) is a minimally invasive treatment. The efficacy of PEN has been relatively well investigated; however, the relationship between the clinical effectiveness of PEN and the severity of spinal canal stenosis by disc material has not yet been established. The purpose of this study was to compare clinical outcomes of PEN according to the dural sac cross-sectional area in single level disc disease. Materials and Methods This study included 363 patients with back pain from single level disc disease with and without radiculopathy. Patients were categorized into groups according to spinal canal compromise by disc material: Category 1, less or more than 50%; and Category 2, three subgroups with lesser than a third, between a third and two thirds, and more than two thirds. Clinical outcomes were assessed according to the Visual Analog Scale (VAS) score for back pain and leg pain and Odom's criteria at 1, 3, 6, 12, and 24 months after treatment. Results The demographic data showed no difference between groups according to spinal canal compromise by disc material except age (older age correlated with more spinal canal compromise). The dural sac cross-sectional area did not correlate with the VAS scores for back and leg pain after PEN in single level disc disease in Groups 1 and 2. Odom's criteria after PEN were also not different according to dural sac cross-sectional area by disc material. Conclusion PEN is an effective procedure in treating single level lumbar disc herniation without affecting dural sac cross-sectional area. PMID:25837174

  2. Soft tissue ossification and condylar cartilage degeneration following TMJ disc perforation in a rabbit pilot study

    PubMed Central

    Embree, Mildred C.; Iwaoka, George M.; Kong, Danielle; Martin, Brittany N.; Patel, Ryan K.; Lee, Andrew; Nathan, John M.; Eisig, Sidney B.; Safarov, Aram; Koslovsky, David A; Koch, Alia; Romanov, Alex; Mao, Jeremy J

    2015-01-01

    Objective There are limited clinical treatments for temporomandibular joint pathologies, including degenerative disease, disc perforation and heterotopic ossification. One barrier hindering the development of new therapies is that animal models recapitulating TMJ diseases are poorly established. The objective of this study was to develop an animal model for TMJ cartilage degeneration and disc pathology, including disc perforation and soft tissue heterotopic ossification. Methods New Zealand white rabbits (n=9 rabbits) underwent unilateral TMJ disc perforation surgery and sham surgery on the contralateral side. A 2.5 mm defect was created using a punch biopsy in rabbit TMJ disc. The TMJ condyles and discs were evaluated macroscopically and histologically after 4, 8 and 12 weeks. Condyles were blindly scored by 4 independent observers using OARSI recommendations for macroscopic and histopathological scoring of osteoarthritis in rabbit tissues. Results Histological evidence of TMJ condylar cartilage degeneration was apparent in experimental condyles following disc perforation relative to sham controls after 4 and 8 weeks, including surface fissures and loss of Safranin O staining. At 12 weeks, OARSI scores indicated experimental condylar cartilage erosion into the subchondral bone. Most strikingly, heterotopic ossification occurred within the TMJ disc upon perforation injury in 6 rabbits after 8 and 12 weeks. Conclusion We report for the first time a rabbit TMJ injury model that demonstrates condylar cartilage degeneration and disc ossification, which is indispensible for testing the efficacy of potential TMJ therapies. PMID:25573797

  3. Systematic Review of Thigh Symptoms after Lateral Transpsoas Interbody Fusion for Adult Patients with Degenerative Lumbar Spine Disease

    PubMed Central

    Gammal, Isaac D.; Bendo, John A.

    2015-01-01

    Background Lateral transpsoas interbody fusion (LTIF) is a minimally invasive technique for achieving lumbar spinal fusion. While it has many advantages over open techniques it carries with it a distinct set of risks, most commonly post-operative ipsilateral thigh pain, weakness and sensory disturbances. It is vital for both the surgeon and patient to understand the risks for and outcomes of injury associated with this procedure. We conducted a systematic review of the literature to evaluate the incidence, risks, and long-term clinical outcomes of post-operative thigh symptoms in patients treated with LTIF. Methods We conducted a search of MEDLINE, EMBASE, CINAHL, Scopus, Web of Science and the Cochrane Collaboration Library, using keywords and MeSH terms, for English-language literature published through September 2014, as well as reference lists from key articles. Studies were then manually filtered to retrieve articles that met inclusion criteria. We were interested in studies that reported postoperative lower extremity symptoms after LTIF, such as pain, weakness and changes in sensation. The strength of evidence was determined based on precepts outlined by the Grades of Recommendation Assessment, Development and Evaluation Working Group (GRADE). Results A total of 392 articles were initially retrieved, with 24 ultimately meeting criteria for inclusion. The incidence of any post-operative thigh symptom varied, ranging as high as 60.7%, with 9.3% of patients experiencing a motor deficit related to direct nerve injury. Several studies reported cases of persistent symptoms at 6 months follow up. Additionally, inclusion of the L4-5 disc space and a longer duration of surgery were both identified as risks for developing postoperative thigh symptoms. Conclusion The risk of postoperative thigh symptoms after LTIF is high. Thigh pain, paresthesias and weakness were the most commonly reported symptoms. While most patients’ symptoms resolved by 6 months follow up

  4. My Retina Tracker™: An On-line International Registry for People Affected with Inherited Orphan Retinal Degenerative Diseases and their Genetic Relatives - A New Resource.

    PubMed

    Fisher, Joan K; Bromley, Russell L; Mansfield, Brian C

    2016-01-01

    My Retina Tracker™ is a new on-line registry for people affected with inherited orphan retinal degenerative diseases, and their unaffected, genetic relatives. Created and supported by the Foundation Fighting Blindness, it is an international resource designed to capture the disease from the perspective of the registry participant and their retinal health care providers. The registry operates under an Institutional Review Board (IRB)-approved protocol and allows sharing of de-identified data with participants, researchers and clinicians. All participants sign an informed consent that includes selecting which data they wish to share. There is no minimum age of participation. Guardians must sign on behalf of minors, and children between the ages of 12 to 17 also sign an informed assent. Participants may compare their disease to others in the registry using graphical interpretations of the aggregate registry data. Researchers and clinicians have two levels of access. The first provides an interface to interrogate all data fields registrants have agreed to share based on their answers in the IRB informed consent. The second provides a route to contact people in the registry who may be eligible for studies or trials, through the Foundation. PMID:26427418

  5. Intervertebral disc degeneration in the dog. Part 1: Anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration.

    PubMed

    Bergknut, Niklas; Smolders, Lucas A; Grinwis, Guy C M; Hagman, Ragnvi; Lagerstedt, Anne-Sofie; Hazewinkel, Herman A W; Tryfonidou, Marianna A; Meij, Björn P

    2013-03-01

    Intervertebral disc (IVD) degeneration is common in dogs and can give rise to a number of diseases, such as IVD herniation, cervical spondylomyelopathy, and degenerative lumbosacral stenosis. Although there have been many reports and reviews on the clinical aspects of canine IVD disease, few reports have discussed and reviewed the process of IVD degeneration. In this first part of a two-part review, the anatomy, physiology, histopathology, and biochemical and biomechanical characteristics of the healthy and degenerated IVD are described. In Part 2, the aspects of IVD degeneration in chondrodystrophic and non-chondrodystrophic dog breeds are discussed in depth. PMID:23177522

  6. [Musculoskeletal pathology in occupational risks and common degenerative disease: reflections on the intensity and duration of the risk].

    PubMed

    Bergamini, Roberta; Astengo, Rossana

    2014-01-01

    Nowadays, in Italy the reports of mnusculoskeletal diseases increase as confirmed in the last INAIL (national insurance for occupational diseases and injuries) annual report. The Emilia-Ronmagna is one of the region with the highest number of reports: 15.9% of the total in 2012. The decree no. 81/08 has partially simplified the medico-legal activities related to musculoskeletal diseases; however, the medico-legal physicians have still to deal with some issues such as risk assessment quality, economic crisis, and specific work environments (e.g. agriculture and many handicraft activities). Tire risk factors of musculoskeletal diseases and their assessments are quite well studied. The latency period of these diseases needs to be investigated, since it could be a relevant aspect for legal medical judgment, insurance protection and prevention. Based on literature data and INAIL experience, authors propose some considerations useful for a scientific debate. PMID:25558730

  7. MicroRNAs: New players in intervertebral disc degeneration.

    PubMed

    Wang, Cheng; Wang, Wen-Jun; Yan, Yi-Guo; Xiang, Yong-Xiao; Zhang, Jian; Tang, Zhi-Han; Jiang, Zhi-Sheng

    2015-10-23

    Chronic low back pain is generally attributed to intervertebral disc (IVD) degeneration (IDD), which is closely associated with apoptosis, extracellular matrix (ECM) disruption, cell proliferation and inflammatory response. Currently, there is no clinical therapy targeting the pathophysiology of disc degeneration. microRNAs (miRNAs) are a class of small noncoding RNA molecules that negatively regulate gene expression at the post-transcriptional levels. miRNAs not only regulate many normal physiological processes, but also play an important role in the development of most disorders, including degenerative disc disease. A variety of miRNAs are differentially expressed in degenerative human IVD tissues and cells. Among these, some of the miRNAs have been shown to be involved in multiple pathological processes during disc degeneration, including apoptosis, ECM degradation, cell proliferation and inflammatory response. This review will mainly focus on the expression profiles, roles, and therapeutic implications of miRNAs in IDD. With continued efforts, restoration of dysregulated miRNA expression may represent a promising biological treatment approach for mitigating or reversing IVD degeneration. PMID:26368266

  8. High mechanical strain of primary intervertebral disc cells promotes secretion of inflammatory factors associated with disc degeneration and pain

    PubMed Central

    2014-01-01

    Introduction Excessive mechanical loading of intervertebral discs (IVDs) is thought to alter matrix properties and influence disc cell metabolism, contributing to degenerative disc disease and development of discogenic pain. However, little is known about how mechanical strain induces these changes. This study investigated the cellular and molecular changes as well as which inflammatory receptors and cytokines were upregulated in human intervertebral disc cells exposed to high mechanical strain (HMS) at low frequency. The impact of these metabolic changes on neuronal differentiation was also explored to determine a role in the development of disc degeneration and discogenic pain. Methods Isolated human annulus fibrosus (AF) and nucleus pulposus (NP) cells were exposed to HMS (20% cyclical stretch at 0.001 Hz) on high-extension silicone rubber dishes coupled to a mechanical stretching apparatus and compared to static control cultures. Gene expression of Toll-like receptors (TLRs), neuronal growth factor (NGF) and tumour necrosis factor α (TNFα) was assessed. Collected conditioned media were analysed for cytokine content and applied to rat pheocromocytoma PC12 cells for neuronal differentiation assessment. Results HMS caused upregulation of TLR2, TLR4, NGF and TNFα gene expression in IVD cells. Medium from HMS cultures contained elevated levels of growth-related oncogene, interleukin 6 (IL-6), IL-8, IL-15, monocyte chemoattractant protein 1 (MCP-1), MCP-3, monokine induced by γ interferon, transforming growth factor β1, TNFα and NGF. Exposure of PC12 cells to HMS-conditioned media resulted in both increased neurite sprouting and cell death. Conclusions HMS culture of IVD cells in vitro drives cytokine and inflammatory responses associated with degenerative disc disease and low-back pain. This study provides evidence for a direct link between cellular strain, secretory factors, neoinnervation and potential degeneration and discogenic pain in vivo. PMID:24457003

  9. Complex Regional Pain Syndrome Caused by Lumbar Herniated Intervertebral Disc Disease.

    PubMed

    Kim, Se Hee; Choi, Sang Sik; Lee, Mi Kyung; Kin, Jung Eun

    2016-07-01

    Most cases of complex regional pain syndrome (CRPS) occur after some inciting injury. There are a few cases of CRPS after an operation for disc disease. CRPS from a mild herniated intervertebral disc (HIVD) without surgical intervention is even rarer than CRPS after an operation for disc disease.A 22-year-old man was transferred to a pain clinic. He had continuously complained about back and right leg pain. He presented with a skin color change in the right lower leg, intermittent resting tremor, stiffness, and swelling in the right leg. He complained of a pulling sensation and numbness in his right buttock, posterior thigh, lateral calf, and ankle. This symptom was in accordance with L4/5 radiculopathy. Magnetic resonance imaging (MRI) also showed L4/5 HIVD that was central to the bilateral subarticular protrusion.He was diagnosed as having CRPS, which fits the revised International Association for the Study of Pain (IASP) criteria. He fulfilled 4 symptom categories (allodynia, temperature asymmetry and skin color change, sweating changes, decreased range of motion and motor dysfunction) and 3 of 4 sign categories (allodynia, temperature asymmetry and skin color changes, decreased range of motion and motor dysfunction). The bone scan and thermography also revealed CRPS.For the past 2 months, we have performed intensive treatments. But, he never became pain-free and walking for 5 minutes led to persistent leg pain. We decided to perform percutaneous nucleoplasty, which can directly decompress a HIVD. On the next day, he achieved dramatic symptom relief. The visual analog scale (VAS) score improved to 3, compared to the VAS score of 9 at the first visit. The skin color change, allodynia, and tremor in the right leg disappeared, and the temperature asymmetry normalized. Motor weakness of the right leg also recovered.We report an unusual case of CRPS that was caused by L4/5 HIVD without a history of trauma or surgery. It has a clear causal relationship between HIVD

  10. Non-enzymatic glycation of α-crystallin as an in vitro model for aging, diabetes and degenerative diseases.

    PubMed

    Karumanchi, Devi Kalyan; Karunaratne, Nuwan; Lurio, Laurence; Dillon, James P; Gaillard, Elizabeth R

    2015-12-01

    Alpha crystallin, a small heat-shock protein, has been studied extensively for its chaperone function. Alpha crystallin subunits are expressed in stress conditions and have been found to prevent apoptosis by inhibiting the activation of caspase pathway. Non-enzymatic glycation of protein leads to the formation of advanced glycation end-products (AGEs). These AGEs bind to receptors and lead to blocking the signaling pathways or cause protein precipitation as observed in aggregation-related diseases. Methylglyoxal (MGO) is one of the major glycating agents expressed in pathological conditions due to defective glycolysis pathway. MGO reacts rapidly with proteins, forms AGEs and finally leads to aggregation. The goal of this study was to understand the non-enzymatic glycation-induced structural damage in alpha crystallin using biophysical and spectroscopic characterization. This will help to develop better disease models for understanding the biochemical pathways and also in drug discovery. PMID:26215735

  11. An unusual degenerative disorder of neurons associated with a novel intranuclear hyaline inclusion (neuronal intranuclear hyaline inclusion disease). A clinicopathological study of a case.

    PubMed

    Sung, J H; Ramirez-Lassepas, M; Mastri, A R; Larkin, S M

    1980-03-01

    A 21-year-old woman with an unusual, progressive, degenerative neurological disorder is described. The disorder is characterized clinically by behavioral abnormality, peculiar involuntary movements, and ataxia starting in early childhood and subsequent development of dementia, choreoathetosis, rectal and bladder incontinence, bulbar and spinal muscular weakness, pes cavus, kyphoscoliosis, and generalized seizures. The clinical manifestations are correlated, with widespread pathological changes affecting almost all neuronal systems. The pathological changes are discussed in relation to the wide spectrum of "multisystem atrophies." Particular attention is directed to the ubiquitous occurrence of a novel intranuclear, eosinophilic, hyaline inclusion in almost all types of central, peripheral, and autonomic neurons. The ubiquitous neuronal involvement seems to explain the diffuse multiple system degeneration. The pathogenesis of the neuronal inclusions is unknown, but it is speculated that the disorder may represent a metabolic abnormality affecting the nuclear protein of neurons, rather than a viral infection. The pathological features, consisting of the neuronal intranuclear hyaline inclusions associated with multiple system atrophy, have not hitherto been described, and "neuronal intranuclear hyaline inclusion disease" is proposed as a name for the disorder. Rectal biopsy demonstrating the intranuclear hyaline inclusions in ganglion cells of the hyenteric plexuses may serve as a diagnostic procedure for the disorder. PMID:6154779

  12. Cucurbitacin E, An Experimental Lead Triterpenoid with Anticancer, Immunomodulatory and Novel Effects Against Degenerative Diseases. A Mini-Review.

    PubMed

    Attard, Everaldo; Martinoli, Maria-Grazia

    2015-01-01

    A growing number of studies have revealed that natural molecules own interesting antioxidant and anti-apoptotic properties in cell culture as well as in animal models of human diseases such as cancer, inflammatory and neurodegenerative diseases. During the past sixty years, several cucurbitacins have been isolated from a number of cucurbitaceous species, amongst others. Cucurbitacins are triterpenoid compounds originally identify as the bitter components of the Cucurbit family that demonstrated several pro-survival activities in various model of cellular decay. Specifically, Cucurbitacin E (CuE), an oxygenated tetracyclic triterpenoid, has been investigated in a wider array of bioactivities, mainly immunomodulatory. Recently, CuE has been reported to possess anti-inflammatory and anti-tumorigenic properties mediated by its action on the cellular cytoskeleton, on mitotic pathways as well as on cellular autophagy. Few studies also pinpoint the role of CuE in the nervous system as cytostatic for gliomas and neuroprotective in a model of Parkinson's diseases. This review deals with the use of CuE in various experimental models as one of the most promising therapeutic natural molecules against cancer proliferation, as an immunomudulator and for the prevention of neurodegeneration. PMID:25915611

  13. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage.

    PubMed

    Ames, Bruce N

    2006-11-21

    Inadequate dietary intakes of vitamins and minerals are widespread, most likely due to excessive consumption of energy-rich, micronutrient-poor, refined food. Inadequate intakes may result in chronic metabolic disruption, including mitochondrial decay. Deficiencies in many micronutrients cause DNA damage, such as chromosome breaks, in cultured human cells or in vivo. Some of these deficiencies also cause mitochondrial decay with oxidant leakage and cellular aging and are associated with late onset diseases such as cancer. I propose DNA damage and late onset disease are consequences of a triage allocation response to micronutrient scarcity. Episodic shortages of micronutrients were common during evolution. Natural selection favors short-term survival at the expense of long-term health. I hypothesize that short-term survival was achieved by allocating scarce micronutrients by triage, in part through an adjustment of the binding affinity of proteins for required micronutrients. If this hypothesis is correct, micronutrient deficiencies that trigger the triage response would accelerate cancer, aging, and neural decay but would leave critical metabolic functions, such as ATP production, intact. Evidence that micronutrient malnutrition increases late onset diseases, such as cancer, is discussed. A multivitamin-mineral supplement is one low-cost way to ensure intake of the Recommended Dietary Allowance of micronutrients throughout life. PMID:17101959

  14. A pilot study of the prevalence of lumbar disc degeneration in elite athletes with lower back pain at the Sydney 2000 Olympic Games

    PubMed Central

    Ong, A; Anderson, J; Roche, J

    2003-01-01

    Objectives: To observe the prevalence of lumbar intervertebral disc degeneration in elite athletes as compared with published literature of changes seen in non-athletes—that is, normal population. Methods: The lumbar spines of 31 Olympic athletes who presented to the Olympic Polyclinic with low back pain and/or sciatica were examined using magnetic resonance imaging. Three criteria were looked at: (a) the loss of disc signal intensity; (b) the loss of disc height; (c) the presence of disc displacement. The results were then recorded and correlated with the lumbar levels. Results: The disc signal intensity was progressively reduced the more caudal the disc space. It was most common at the L5/S1 level, and, of the abnormal group, 36% (n = 11) showed the most degenerative change. Disc height reduction was also found to be most common at the L5/S1 level. However, the most common height reduction was only mild. A similar trend of increased prevalence of disc herniation was noted with more caudal levels. At the L5/S1 level, 58% were found to have an element of disc displacement, most of which were disc bulges. Compared with changes seen in the normal population (non-athletes) as described in the literature, disc degeneration defined by the above criteria was found to be significantly more severe in these Olympic athletes. Conclusions: Although the study was limited, the results suggest that elite athletes have a greater prevalence and greater degree of lumbar disc degeneration than the normal population. A more detailed follow up study should be considered to investigate which particular training activities have the most impact on the lumbar spine, and how to modify training methods so as to avoid the long term sequelae of degenerative disc disease of the lumbar spine. PMID:12782554

  15. Outcomes observed during a 1-year clinical and radiographic follow-up of patients treated for 1- or 2-level cervical degenerative disease using a biodegradable anterior cervical plate.

    PubMed

    Chen, Mengcun; Yang, Shuhua; Yang, Cao; Xu, Weihua; Ye, Shunan; Wang, Jing; Feng, Yong; Yang, Wen; Liu, Xianzhe

    2016-08-01

    OBJECTIVE The purpose of this study was to present an initial surgical experience in the management of 1- or 2-level degenerative disc disease of the cervical spine using biodegradable anterior cervical plates (bACPs) in anterior cervical discectomy and fusion (ACDF). The authors also aimed to provide insight into this critical and controversial clinical issue by clarifying outcomes for patients receiving bACPs and by comparing their outcomes with those achieved using a traditional metallic anterior cervical plate (mACP) implant. METHODS A retrospective review was conducted for 2 series of patients who had undergone ACDF using either bACP (31 patients, 38 segments) or mACP (47 patients, 57 segments) instrumentation. The patients were followed up for a mean 13.5 ± 0.9 months (range 12-18 months) in the bACP group and 14.8 ± 1.5 months (range 14-22 months) in the mACP group. Clinical outcomes were determined according to scores on the visual analog scale (VAS), the modified Japanese Orthopaedic Association (mJOA) scoring system, and Odom's criteria. Radiological images were used to assess fusion rates, intervertebral height, Cobb's angle, and the width of prevertebral soft tissue. RESULTS Both VAS and mJOA scores were significantly improved at each follow-up in both groups. Excellent or good results according to Odom's criteria were achieved in 93.5% (29/31) of patients in the bACP group and 93.6% (44/47) of patients in the mACP group. At 6 months postoperatively, the fusion rate was 94.7% (36/38) in the bACP group and 96.5% (55/57) in the mACP group, but subsidence of the intervertebral space at the surgical level was more evident in the bACP group. Angulation, as measured by Cobb's angle, demonstrated obvious healing in both groups, while better maintenance was observed in the mACP group. The local inflammatory reaction was uneventful during follow-up. Dysphonia and dysphagia were observed in both groups during the follow-up. CONCLUSIONS The relatively comparable

  16. Associative learning in degenerative neostriatal disorders: contrasts in explicit and implicit remembering between Parkinson's and Huntington's diseases.

    PubMed

    Sprengelmeyer, R; Canavan, A G; Lange, H W; Hömberg, V

    1995-01-01

    The performances of 12 patients with Parkinson's disease (PD), 16 with Huntington's disease (HD), and young and old healthy controls were assessed on a number of tests of verbal and nonverbal declarative memory, on a test of nonmotor conditional associative learning (words and colors), and on a number of reaction time (RT) tasks. The RT tasks consisted of cued simple and choice reactions. The relationship between the precue and the imperative stimulus in the S1-S2 paradigm was nonarbitrary in the first series and arbitrary in the second series. The series with arbitrary S1-S2 associations was repeated across two successive blocks of trials. The rationale of the study was to investigate the function of the basal ganglia "complex loop," and it was postulated that HD patients would show greater deficits because of greater involvement of the caudate nucleus. The patients with HD had the slowest RTs. Across the two blocks with arbitrary S1-S2 associations, the patients with HD but not PD nevertheless showed evidence of learning in their precued RTs. In contrast, the patients with PD were better able to remember the associations in free recall than were the HD patients. It is concluded that patients with PD have relatively greater deficits in procedural learning, whereas those with HD have relatively more impairments in declarative memory, and the greater level of cognitive impairment in HD overall is interpreted as being due to more serious damage to the caudate loop. PMID:7885356

  17. A Chaplain-led Spiritual Life Review Pilot Study for Patients with Brain Cancers and Other Degenerative Neurologic Diseases

    PubMed Central

    Piderman, Katherine M.; Breitkopf, Carmen Radecki; Jenkins, Sarah M.; Euerle, Terin T.; Lovejoy, Laura A.; Kwete, Gracia M.; Jatoi, Aminah

    2015-01-01

    Objective: This pilot study was designed to describe changes in spiritual well-being (SWB), spiritual coping, and quality of life (QOL) in patients with brain cancer or other neurodegenerative diseases participating in a chaplain-led spiritual life review interview and development of a spiritual legacy document (SLD). Methods: Eligible participants were enrolled and completed baseline questionnaires. They were interviewed by a board-certified chaplain about spiritual influences, beliefs, practices, values, and spiritual struggles. An SLD was prepared for each participant, and one month follow-up questionnaires were completed. Two cases are summarized, and spiritual development themes are illustrated within a spiritual development framework. Results: A total of 27 patients completed baseline questionnaires and the interview; 24 completed the SLD, and 15 completed the follow-up questionnaire. Increases in SWB, religious coping, and QOL were detected. The majority maintained the highest (best) scores of negative religious coping, demonstrating minimal spiritual struggle. Conclusions: Despite the challenges of brain cancers and other neurodegenerative diseases, participants demonstrated improvements in SWB, positive religious coping, and QOL. Patient comments indicate that benefit is related to the opportunity to reflect on and integrate spiritual experiences and to preserve them for others. Research with a larger, more diverse sample is needed, as well as clinical applications for those too vulnerable to participate in longitudinal follow-up. PMID:25973267

  18. Anterior Lumbar Interbody Fusion for Degenerative Discogenic Low Back Pain: Evaluation of L4-S1 Fusion.

    PubMed

    Ni, Jianqiang; Fang, Xiutong; Zhong, Weiye; Liu, Ning; Wood, Kirkham B

    2015-10-01

    The treatment of degenerative discogenic pain is controversial, and anterior lumbar fusion for the treatment of degenerative discogenic low back pain has also been a controversial topic for over a generation.The aim of this systematic review was to evaluate the outcome of different anterior lumbar fusion levels for degenerative discogenic low back pain.In this study, we performed a clinical outcome subgroup analysis. The outcomes of 84 consecutive patients who underwent anterior lumbar interbody fusion from 2004 to 2009 were reviewed. The operative time, intraoperative blood loss, hospital stay, Oswestry Disability Index (ODI), visual analog scale (VAS) results, and complication rate were recorded separately.Medical indications were degenerative disc disease (73.8%), postdiscectomy disc disease (16.1%), and disc herniation (9.5%). Patients with severe spondylolysis or disc degeneration, with more than 3 or multilevel lesions, were excluded.The mean operative time was 124.5 ± 10.9 min (range 51-248 min), the mean intraoperative blood loss was 242.1 ± 27.7 mL (range 50-2700 mL), the mean hospital stay was 3.9 ± 1.1 days (range 3-6 days), the mean preoperative VAS score was 7.5 ± 1.4, and the mean preoperative ODI score was 60.0 ± 5.7. At the 1-year follow-up, the mean postoperative VAS score was 3.3 ± 1.3 and the mean postoperative ODI score was 13.6 ± 3.4 (P < 0.05). L4-L5 disc fusion led to better clinical results than 2-level L4-L5/L5-S1 disc fusion. Additionally, the 2-level fusion of L4-L5/L5-S1 had better clinical results than the L5-S1 disc fusion at both the 1 and 2-year postoperative follow-ups regarding the VAS score and the ODI score. The rate of complications was more frequent in the 2-level L4-L5/L5-S1 group (27.3%) (group C) than in the L4-L5 group (9.1%) (group A) and the L5-S1 group (12.5%) (group B). There was no difference between the L4-L5 group (9.1%) and the L5-S1 group (12.5%). A venous tear

  19. Evidence from Raman Spectroscopy of a Putative Link Between Inherent Bone Matrix Chemistry and Degenerative Joint Disease

    PubMed Central

    Kerns, Jemma G; Gikas, Panagiotis D; Buckley, Kevin; Shepperd, Adam; Birch, Helen L; McCarthy, Ian; Miles, Jonathan; Briggs, Timothy W R; Keen, Richard; Parker, Anthony W; Matousek, Pavel; Goodship, Allen E

    2014-01-01

    Objective Osteoarthritis (OA) is a common debilitating disease that results in degeneration of cartilage and bone in the synovial joints. Subtle changes in the molecular structure of the subchondral bone matrix occur and may be associated with cartilage changes. The aim of this study was to explore whether the abnormal molecular changes observed in the matrix of OA subchondral bone can be identified with Raman spectroscopy. Methods Tibial plateaus from patients undergoing total knee replacement for OA (n = 10) were compared with healthy joints from patients undergoing leg amputation (n = 5; sex- and laterality-matched) and with non-OA cadaveric knee specimens (n = 5; age-matched). The samples were analyzed with Raman spectroscopy, peripheral quantitative computed tomography, and chemical analysis to compare changes in defined load-bearing sites in both the medial and lateral compartments. Results OA subchondral bone matrix changes were detected by Raman spectroscopy. Within each cohort, there was no spectral difference in bone matrix chemistry between the medial and lateral compartments, whereas a significant spectral difference (P < 0.001) was observed between the non-OA and OA specimens. Type I collagen chain ratios were normal in the non-OA specimens but were significantly elevated in the OA specimens. Conclusion In comparing the results of Raman spectroscopy with those obtained by other standard techniques, these findings show, for the first time, that subchondral bone changes, or inherent differences, exist in both the medial and lateral (beneath intact cartilage) compartments of OA knees. The development of Raman spectroscopy as a screening tool, based on molecular-specific modifications in bone, would facilitate the identification of clinical disease, including early molecular changes. PMID:24470432

  20. Disc replacement using Pro-Disc C versus fusion: a prospective randomised and controlled radiographic and clinical study

    PubMed Central

    Ahlhelm, F.; Pitzen, T.; Steudel, W. I.; Jung, J.; Shariat, K.; Steimer, O.; Bachelier, F.; Pape, D.

    2006-01-01

    Anterior cervical discectomy and fusion (ACDF) may be considered to be the gold standard for treatment of symptomatic degenerative disc disease within the cervical spine. However, fusion of the segment may result in progressive degeneration of the adjacent segments. Therefore, dynamic stabilization procedures have been introduced. Among these, artificial disc replacement by disc prosthesis seems to be promising. However, to be so, segmental motion must be preserved. This, again, is very difficult to judge and has not yet been proven. The aim of the current study was to first analyse the segmental motion following artificial disc replacement using a disc prosthesis. A second aim was to compare both segmental motion as well as clinical result to the current gold standard (ACDF). This is a prospective controlled study. Twenty-five patients with cervical disc herniation were enrolled and assigned to either study group (receiving a disc prosthesis) or control group (receiving ACDF, using a cage with bone graft and an anterior plate.) Radiostereometric analysis was used to quantify intervertebral motion immediately as well as 3, 6, 12 and 24 weeks postoperatively. Further, clinical results were judged using visual analogue scale and neuro-examination. Cervical spine segmental motion decreased over time in the presence of disc prosthesis or ACDF. However, the loss of segmental motion is significantly higher in the ACDF group, when looked at 3, 6, 12 and 24 weeks after surgery. We observed significant pain reduction in neck and arm postoperatively, without significant difference between both groups (P > 0.05). Cervical spine disc prosthesis preserves cervical spine segmental motion within the first 6 months after surgery. The clinical results are the same when compared to the early results following ACDF. PMID:17106665

  1. Peripheral disc margin shape and internal disc derangement: imaging correlation in significantly painful discs identified at provocation lumbar discography.

    PubMed

    Bartynski, W S; Rothfus, W E

    2012-06-01

    Annular margin shape is used to characterize lumbar disc abnormality on CT/MR imaging studies. Abnormal discs also have internal derangement including annular degeneration and radial defects. The purpose of this study was to evaluate potential correlation between disc-margin shape and annular internal derangement on post-discogram CT in significantly painful discs encountered at provocation lumbar discography (PLD). Significantly painful discs were encountered at 126 levels in 86 patients (47 male, 39 female) studied by PLD where no prior surgery had been performed and response to intradiscal lidocaine after provocation resulted in either substantial/total relief or no improvement after lidocaine administration. Post-discogram CT and discogram imaging was evaluated for disc-margin characteristics (bulge/protrusion), features of disc internal derangement (radial annular defect [RD: radial tear/fissure/annular gap], annular degeneration) and presence/absence of discographic contrast leakage. In discs with focal protrusion, 50 of 63 (79%) demonstrated Grade 3 RD with 13 (21%) demonstrating severe degenerative change only. In discs with generalized-bulge-only, 48 of 63 (76%) demonstrated degenerative change only (primarily Dallas Grade 3) with 15 of 63 (24%) demonstrating a RD (Dallas Grade 3). Differences were highly statistically significant (p<0.001). Pain elimination with intra-discal lidocaine correlated with discographic contrast leakage (p<0.001). Disc-margin shape correlates with features of internal derangement in significantly painful discs encountered at PLD. Discs with focal protrusion typically demonstrate RD while generalized bulging discs typically demonstrated degenerative changes only (p<0.001). Disc-margin shape may provide an important imaging clue to the cause of chronic discogenic low back pain. PMID:22681741

  2. Peripheral Disc Margin Shape and Internal Disc Derangement: Imaging Correlation in Significantly Painful Discs Identified at Provocation Lumbar Discography

    PubMed Central

    Bartynski, W.S.; Rothfus, W.E.

    2012-01-01

    Summary Annular margin shape is used to characterize lumbar disc abnormality on CT/MR imaging studies. Abnormal discs also have internal derangement including annular degeneration and radial defects. The purpose of this study was to evaluate potential correlation between disc-margin shape and annular internal derangement on post-discogram CT in significantly painful discs encountered at provocation lumbar discography (PLD). Significantly painful discs were encountered at 126 levels in 86 patients (47 male, 39 female) studied by PLD where no prior surgery had been performed and response to intradiscal lidocaine after provocation resulted in either substantial/total relief or no improvement after lidocaine administration. Post-discogram CT and discogram imaging was evaluated for disc-margin characteristics (bulge/protrusion), features of disc internal derangement (radial annular defect [RD: radial tear/fissure/annular gap], annular degeneration) and presence/absence of discographic contrast leakage. In discs with focal protrusion, 50 of 63 (79%) demonstrated Grade 3 RD with 13 (21%) demonstrating severe degenerative change only. In discs with generalized-bulge-only, 48 of 63 (76%) demonstrated degenerative change only (primarily Dallas Grade 3) with 15 of 63 (24%) demonstrating a RD (Dallas Grade 3). Differences were highly statistically significant (p<0.001). Pain elimination with intra-discal lidocaine correlated with discographic contrast leakage (p<0.001). Disc-margin shape correlates with features of internal derangement in significantly painful discs encountered at PLD. Discs with focal protrusion typically demonstrate RD while generalized bulging discs typically demonstrated degenerative changes only (p<0.001). Disc-margin shape may provide an important imaging clue to the cause of chronic discogenic low back pain. PMID:22681741

  3. REM Sleep Behavior Disorder and REM Sleep Without Atonia as an Early Manifestation of Degenerative Neurological Disease

    PubMed Central

    McCarter, Stuart J.; St Louis, Erik K.

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by repeated episodes of dream enactment behavior and REM sleep without atonia (RSWA) during polysomnography recording. RSWA is characterized by increased phasic or tonic muscle activity seen on polysomnographic electromyogram channels. RSWA is a requisite diagnostic feature of RBD, but may also be seen in patients without clinical symptoms or signs of dream enactment as an incidental finding in neurologically normal individuals, especially in patients receiving antidepressant therapy. RBD may be idiopathic or symptomatic. Patients with idiopathic RBD often later develop other neurological features including parkinsonism, orthostatic hypotension, anosmia, or cognitive impairment. RSWA without clinical symptoms as well as clinically overt RBD also often occurs concomitantly with the α-synucleinopathy family of neurodegenerative disorders, which includes idiopathic Parkinson disease, Lewy body dementia, and multiple system atrophy. This review article considers the epidemiology of RBD, clinical and polysomnographic diagnostic standards for both RBD and RSWA, previously reported associations of RSWA and RBD with neurodegenerative disorders and other potential causes, the pathophysiology of which brain structures and networks mediate dysregulation of REM sleep muscle atonia, and considerations for the effective and safe management of RBD. PMID:22328094

  4. Diagnostic dilemma of degenerative joint disease, chronic avascular necrosis or metastasis in planar Tc-99m-methylene diphosphonate planar skeletal scintigraphy excluded by single positron emission computed tomography/computed tomography

    PubMed Central

    Jain, Tarun Kumar; Phulsunga, Rohit Kumar; Basher, Rajender Kumar; Kumar, Narendra; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2015-01-01

    We present a 71-year-old male patient subjected to skeletal scintigraphy for metastasis work up of prostate cancer. Whole body planar images revealed a solitary focal tracer uptake in left femoral head mimicking as solitary metastatic focus. Single positron emission computed tomography/computed tomography images localized this increased tracer uptake to the subchondral cysts with minimal sclerosis in left femur head with no decrease in size of femur head and was reported as (degenerative joint disease). PMID:26170582

  5. Indications for full prosthetic disc arthroplasty: a correlation of clinical outcome against a variety of indications.

    PubMed

    Bertagnoli, Rudolf; Kumar, Selva

    2002-10-01

    In this prospective study, a total of 134 prosthetic discs were replaced in 108 patients undergoing total disc replacement surgeries for degenerative disc disease. It was the aim of this study to correlate the clinical findings and the outcome of our patients treated with Prodisc II prostheses for various indications and to formulate indication criteria for disc replacement surgeries. The discs were implanted at L5/S1 in 61 patients, L5/L6 in 3 patients, L4/L5 in 31 patients, L3/L4 in 7 patients, and L2/L3 in 3 patients. There were 12 patients with two-level implants: from L4 to S1 in 11 of them and from L2 to L5 in the remaining one. Two patients also had three-level implants, from L3 to S1. Follow-up evaluation included plain radiographs, physical evaluation, and subjective evaluation by the patient using the Oswestry scale, the visual analog pain scale, and the SF-36V2 well-being questionnaire. The evaluation exercise showed that 90.8% of patients had excellent results, 7.4% had good results and 1.8% had fair results, with no poor results seen. Postoperatively, the average vertebral motion was increased in all patients at the operated level. Progression of disc degeneration at the adjacent levels was noted in ten patients. The average time to resuming activities of daily living unaided was 2.3 weeks. No implant failures or complications due to surgery were encountered in this study. Total prosthesis disc replacement for degenerative disc disease was found to be a good treatment modality, provided proper patient selection and criteria are adhered to. We were able to formulate indication criteria based on this. PMID:12384734

  6. Degenerative cervical myelopathy.

    PubMed

    Kato, So; Fehlings, Michael

    2016-09-01

    Cervical myelopathy is the most common cause of acquired spinal cord compromise. The concept of degenerative cervical myelopathy (DCM), defined as symptomatic myelopathy associated with degenerative arthropathic changes in the spine axis, is being introduced. Given its progressive nature, treatment options have to be chosen in a timely manner. Surgical options include anterior discectomy and fusion (ACDF), anterior corpectomy and fusion (ACCF), arthroplasty (in highly select cases), posterior laminectomy with/without fusion, and laminoplasty. Indications for each should be carefully considered in individual patients. Riluzole, a sodium-glutamate antagonist, is a promising option to optimize neurologic outcomes post-surgery and is being examined in the CSM-Protect Randomized Controlled Trial. Preoperative risk assessment is mandatory for prognostication. Sagittal alignment is known to play an important role to optimize surgical outcome. Guidelines for optimal management of DCM are in process. In principle, all but the mildest cases of DCM should be offered surgery for optimal outcome. PMID:27250040

  7. Current concepts on spinal arthrodesis in degenerative disorders of the lumbar spine

    PubMed Central

    Lykissas, Marios G; Aichmair, Alexander

    2013-01-01

    Back pain is a common chronic disorder that represents a large burden for the health care system. There is a broad spectrum of available treatment options for patients suffering from chronic lower back pain in the setting of degenerative disorders of the lumbar spine, including both conservative and operative approaches. Lumbar arthrodesis techniques can be divided into sub-categories based on the part of the vertebral column that is addressed (anterior vs posterior). Furthermore, one has to differentiate between approaches aiming at a solid fusion in contrast to motion-sparing techniques with the proposed advantage of a reduced risk of developing adjacent disc disease. However, the field of application and long-term outcomes of these novel motion-preserving surgical techniques, including facet arthroplasty, nucleus replacement, and lumbar disc arthroplasty, need to be more precisely evaluated in long-term prospective studies. Innovative surgical treatment strategies involving minimally invasive techniques, such as lateral lumbar interbody fusion or transforaminal lumbar interbody fusion, as well as percutaneous implantation of transpedicular or transfacet screws, have been established with the reported advantages of reduced tissue invasiveness, decreased collateral damage, reduced blood loss, and decreased risk of infection. The aim of this study was to review well-established procedures for lumbar spinal fusion with the main focus on current concepts on spinal arthrodesis and motion-sparing techniques in degenerative disorders of the lumbar spine. PMID:24303453

  8. D-penicillamine Induced Degenerative Dermopathy

    PubMed Central

    Khandpur, Sujay; Jain, Naresh; Singla, Shweta; Chatterjee, Priti; Behari, Madhuri

    2015-01-01

    D-penicillamine interferes with elastin and collagen metabolism and produces several cutaneous and multi-systemic side-effects. We present two cases of Wilson's disease who on long-term penicillamine therapy developed drug-induced degenerative dermopathy manifesting as skin fragility over pressure sites and cutis laxa-like changes. PMID:26288416

  9. Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis

    PubMed Central

    Noponen-Hietala, N; Kyllonen, E; Mannikko, M; Ilkko, E; Karppinen, J; Ott, J; Ala-Kokko, L

    2003-01-01

    Background: Degenerative lumbar spinal stenosis (LSS) is usually caused by disc herniation or degeneration. Several genetic factors have been implicated in disc disease. Tryptophan alleles in COL9A2 and COL9A3 have been shown to be associated with lumbar disc disease in the Finnish population, and polymorphisms in the vitamin D receptor gene (VDR) (FokI and TaqI), the matrix metalloproteinase-3 gene (MMP-3) and an aggrecan gene (AGC1) VNTR have been reported to be associated with disc degeneration. In addition, an IVS6-4 a>t polymorphism in COL11A2 has been found in connection with stenosis caused by ossification of the posterior longitudinal ligament in the Japanese population. Objective: To study the role of genetic factors in LSS. Methods: 29 Finnish probands were analysed for mutations in the genes coding for intervertebral disc matrix proteins, COL1A1, COL1A2, COL2A1, COL9A1, COL9A2, COL9A3, COL11A1, COL11A2, and AGC1. VDR and MMP-3 polymorphisms were also analysed. Sequence variations were tested in 56 Finnish controls. Results: Several disease associated alleles were identified. A splice site mutation in COL9A2 leading to a premature translation termination codon and the generation of a truncated protein was identified in one proband, another had the Trp2 allele, and four others the Trp3 allele. The frequency of the COL11A2 IVS6-4 t allele was 93.1% in the probands and 72.3% in controls (p = 0.0016). The differences in genotype frequencies for this site were less significant (p = 0.0043). Conclusions: Genetic factors have an important role in the pathogenesis of LSS. PMID:14644861

  10. Biosynthesis, Characterization, and Efficacy in Retinal Degenerative Diseases of Lens Epithelium-derived Growth Factor Fragment (LEDGF1–326), a Novel Therapeutic Protein*

    PubMed Central

    Baid, Rinku; Upadhyay, Arun K.; Shinohara, Toshimichi; Kompella, Uday B.

    2013-01-01

    For vision-threatening retinitis pigmentosa and dry age-related macular degeneration, there are no United States Food and Drug Administration (FDA)-approved treatments. We identified, biosynthesized, purified, and characterized lens epithelium-derived growth factor fragment (LEDGF1–326) as a novel protein therapeutic. LEDGF1–326 was produced at about 20 mg/liter of culture when expressed in the Escherichia coli system, with about 95% purity and aggregate-free homogeneous population with a mean hydrodynamic diameter of 9 ± 1 nm. The free energy of unfolding of LEDGF1–326 was 3.3 ± 0.5 kcal mol−1, and melting temperature was 44.8 ± 0.2 °C. LEDGF1–326 increased human retinal pigment epithelial cell viability from 48.3 ± 5.6 to 119.3 ± 21.1% in the presence of P23H mutant rhodopsin-mediated aggregation stress. LEDGF1–326 also increased retinal pigment epithelial cell FluoSphere uptake to 140 ± 10%. Eight weeks after single intravitreal injection in Royal College of Surgeons (RCS) rats, LEDGF1–326 increased the b-wave amplitude significantly from 9.4 ± 4.6 to 57.6 ± 8.8 μV for scotopic electroretinogram and from 10.9 ± 5.6 to 45.8 ± 15.2 μV for photopic electroretinogram. LEDGF1–326 significantly increased the retinal outer nuclear layer thickness from 6.34 ± 1.6 to 11.7 ± 0.7 μm. LEDGF1–326 is a potential new therapeutic agent for treating retinal degenerative diseases. PMID:23640891

  11. Surgical Outcome Predictor in Degenerative Lumbar Spinal Disease Based on Health Related Quality of Life Using Euro-Quality 5 Dimensions Analysis

    PubMed Central

    Lee, Byung Ho; Yang, Jae-Ho; Lee, Hwan-Mo; Park, Jun-Young; Park, Sang-Eun

    2016-01-01

    Purpose We aim to introduce the predictive value of a quantitatively described formula model in a multicenter prospective analysis using the EuroQol-5 dimensions (EQ-5D) health scale to anticipate postoperative improvement in patients with degenerative lumbar spine disease (DLSD). Materials and Methods Quality of life was evaluated in 376 patients from 17 tertiary hospitals before and after spinal decompression and fusion surgery. The five items of the EQ-5D, mobility (M), self-care (S), usual activities (A), pain/discomfort (P), and anxiety/depression (D), were checked as level 1, 2, or 3, with 3 being the worst. A minimal significant change in the calculated EQ-5D (cEQ-5D) was set as 0.05. Logistic regression analysis was performed to predict the highest successful outcome (cEQ-5D improvement after operation >0.05) with the given sets of 5 items of the EQ-5D. Results In the cEQ-5D analysis, among patients with a formula score of S+A+2×P+D≤8, 18/68 (27%) showed significant improvement in the cEQ-5D at 1 year postoperatively (p<0.05). However, in patients with a formula score of ≥9, 265/308 (86%) demonstrated significant improvements in the cEQ-5D at 1 year postoperatively (p<0.05). Conclusion We suggest that S+A+2×P+D≥9 in the EQ-5D can quantitatively describe the better surgical outcome predictors for DLSD. With a definite DLSD lesion confirmed by an imaging study, patients who meet the formula scores of 9 or over and have refractory symptoms to non-operative treatment could be better surgical candidates resulting in satisfactory surgical outcomes of over 86%, than those who scored 8 or lower. PMID:27401654

  12. Effect of complications within 90 days on patient-reported outcomes 3 months and 12 months following elective surgery for lumbar degenerative disease.

    PubMed

    Chotai, Silky; Parker, Scott L; Sivaganesan, Ahilan; Sielatycki, J Alex; Asher, Anthony L; McGirt, Matthew J; Devin, Clinton J

    2015-12-01

    OBJECT There is a paradigm shift toward rewarding providers for quality rather than volume. Complications appear to occur at a fairly consistent frequency in large aggregate data sets. Understanding how complications affect long-term patient-reported outcomes (PROs) following degenerative lumbar surgery is vital. The authors hypothesized that 90-day complications would adversely affect long-term PROs. METHODS Nine hundred six consecutive patients undergoing elective surgery for degenerative lumbar disease over a period of 4 years were enrolled into a prospective longitudinal registry. The following PROs were recorded at baseline and 12-month follow-up: Oswestry Disability Index (ODI) score, numeric rating scales for back and leg pain, quality of life (EQ-5D scores), general physical and mental health (SF-12 Physical Component Summary [PCS] and Mental Component Summary [MCS] scores) and responses to the North American Spine Society (NASS) satisfaction questionnaire. Previously published minimum clinically important difference (MCID) threshold were used to define meaningful improvement. Complications were divided into major (surgicalsite infection, hardware failure, new neurological deficit, pulmonary embolism, hematoma and myocardial infarction) and minor (urinary tract infection, pneumonia, and deep venous thrombosis). RESULTS Complications developed within 90 days of surgery in 13% (118) of the patients (major in 12% [108] and minor in 8% [68]). The mean improvement in ODI scores, EQ-5D scores, SF-12 PCS scores, and satisfaction at 3 months after surgery was significantly less in the patients with complications than in those who did not have major complications (ODI: 13.5 ± 21.2 vs 21.7 ± 19, < 0.0001; EQ-5D: 0.17 ± 0.25 vs 0.23 ± 0.23, p = 0.04; SF-12 PCS: 8.6 ± 13.3 vs 13.0 ± 11.9, 0.001; and satisfaction: 76% vs 90%, p = 0.002). At 12 months after surgery, the patients with major complications had higher ODI scores than those without complications (29.1

  13. Calcification in the ovine intervertebral disc: a model of hydroxyapatite deposition disease

    PubMed Central

    Burkhardt, D.; Taylor, T. K. F.; Dillon, C. T.; Read, R.; Cake, M.; Little, C. B.

    2009-01-01

    The study design included a multidisciplinary examination of the mineral phase of ovine intervertebral disc calcifications. The objective of the study was to investigate the mineral phase and its mechanisms of formation/association with degeneration in a naturally occurring animal model of disc calcification. The aetiology of dystrophic disc calcification in adult humans is unknown, but occurs as a well-described clinical disorder with hydroxyapatite as the single mineral phase. Comparable but age-related pathology in the sheep could serve as a model for the human disorder. Lumbar intervertebral discs (n = 134) of adult sheep of age 6 years (n = 4), 8 years (n = 12) and 11 years (n = 2) were evaluated using radiography, morphology, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray powder diffraction, histology, immunohistology and proteoglycan analysis. Half of the 6-year, 84% of the 8-year and 86% of the 11-year-old discs had calcific deposits. These were not well delineated by plain radiography. They were either: (a) punctate deposits in the outer annulus, (b) diffuse deposits in the transitional zone or inner annulus fibrosus with occasional deposits in the nucleus, or (c) large deposits in the transitional zone extending variably into the nucleus. Their maximal incidence was in the lower lumbar discs (L4/5–L6/7) with no calcification seen in the lumbosacral or lower thoracic discs. All deposits were hydroxyapatite with large crystallite sizes (800–1,300 Å) compared to cortical bone (300–600 Å). No type X-collagen, osteopontin or osteonectin were detected in calcific deposits, although positive staining for bone sialoprotein was evident. Calcified discs had less proteoglycan of smaller hydrodynamic size than non-calcified discs. Disc calcification in ageing sheep is due to hydroxyapatite deposition. The variable, but large, crystal size and lack of protein markers indicate that this does not occur by

  14. Foraminoplastic transfacet epidural endoscopic approach for removal of intraforaminal disc herniation at the L5-S1 level

    PubMed Central

    Kaczmarczyk, Jacek; Nowakowski, Andrzej; Sulewski, Adam

    2014-01-01

    Transforaminal endoscopic disc removal in the L5-S1 motion segment of the lumbar spine creates a technical challenge due to anatomical reasons and individual variability. The majority of surgeons prefer a posterior classical or minimally invasive approach. There is only one foraminoplastic modification of the technique in the literature so far. In this paper we present a new technique with a foraminoplastic transfacet approach that may be suitable in older patients with advanced degenerative disease of the spine. PMID:24729817

  15. Lumbar percutaneous KTP532 wavelength laser disc decompression and disc ablation in the management of discogenic pain.

    PubMed

    Knight, Martin; Goswami, Ankul

    2002-02-01

    The objective of this research was to determine the outcome of laser disc decompression and laser disc ablation in the management of painful degenerative disc disease with or without associated disc prolapse. Nonendoscopic percutaneous laser disc decompression was performed under x-ray control via the posterolateral approach with side-firing probes. All patients with chronic back pain who had reproduced pain during discography of a nature, pattern, and distribution similar to what they experienced normally were included in the study. Magnetic resonance which confirmed stenosis and sequestrated discs, and patients with acute neurological findings were excluded from the study. Laser disc decompression or ablation was done using the KTP532 wavelength. The functional outcome was assessed prospectively using the Oswestry Disability Index. Clinical benefit was considered significant in those patients with a percentage change in the index of > or =50% at review 3-9 years (mean, 5.33 years) following surgery. A total of 52% of patients demonstrated a sustained significant clinical benefit, with an additional 21% in whom functional improvement was noted. Cohort integrity was 67%. Long-term benefit of the laser disc ablation and decompression for discogenic pain suggests a mechanism other than principally mechanical as a cause of chronic back and sciatic pain. It may suggest that efficacy occurs by reduction in the intradiscal production of irritative products and by an effect upon discal and annular neoneuralization. The sustained nature of the benefit after long-term preoperative symptoms (mean, 4.7 years) rules out any placebo effect. Selection should be restricted to patients without significant lateral recess stenosis, retrolisthesis or olisthesis of > or =3 mm, significant dorsal or foraminal osteophytosis, extrusion, or sequestration. PMID:11902355

  16. SDF-1/CXCR4 axis induces apoptosis of human degenerative nucleus pulposus cells via the NF-κB pathway

    PubMed Central

    LIU, ZONGCHAO; MA, CHUAN; SHEN, JIELIANG; WANG, DAWU; HAO, JIE; HU, ZHENMING

    2016-01-01

    Intervertebral disc degeneration (IVDD) is a major cause of lower back pain, and increased cell apoptosis is a key characteristic of IVDD. The present study aimed to investigate the effects and mechanism of the stromal cell-derived factor-1 (SDF-1)/C-X-C motif chemokine receptor 4 (CXCR4) axis on apoptosis in human degenerative nucleus pulposus cells (NPCs). The expression levels of SDF-1 and CXCR4 in human intervertebral discs (IVD) were determined using immunohistochemistry and western blot analysis. Apoptosis of primary cultured NPCs was quantified by Annexin V/propidium iodide staining following stimulation with SDF-1 and knockdown of CXCR4 using small interfering RNA (siRNA). The association with the nuclear factor-κB (NF-κB) signaling pathway was investigated using CXCR4-siRNA and NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), treatment. The results demonstrated that SDF-1 and its receptor, CXCR4, were upregulated in degenerative IVD samples compared with normal samples. Stimulation with SDF-1 increased the level of apoptosis in cultured NPCs, and conversely, the apoptosis level was suppressed post-transfection with CXCR4 siRNA compared with SDF-1 stimulation alone. Furthermore, SDF-1 treatment increased the level of phosphorylated NF-κB subunit P65, which was downregulated following CXCR4 siRNA and PDTC treatment. In addition, CXCR4 siRNA and PDTC inhibited the nuclear translocation of P65, which was induced by SDF-1. Taken together, SDF-1-mediated apoptosis was suppressed by NF-κB inhibition using PDTC. In conclusion, the SDF-1/CXCR4 axis promoted cell apoptosis in human degenerative NPCs via the NF-κB pathway, thus suggesting that SDF-1/CXCR signaling may be a therapeutic target for the treatment of degenerative IVD diseases. PMID:27220474

  17. SDF‑1/CXCR4 axis induces apoptosis of human degenerative nucleus pulposus cells via the NF‑κB pathway.

    PubMed

    Liu, Zongchao; Ma, Chuan; Shen, Jieliang; Wang, Dawu; Hao, Jie; Hu, Zhenming

    2016-07-01

    Intervertebral disc degeneration (IVDD) is a major cause of lower back pain, and increased cell apoptosis is a key characteristic of IVDD. The present study aimed to investigate the effects and mechanism of the stromal cell‑derived factor‑1 (SDF‑1)/C‑X‑C motif chemokine receptor 4 (CXCR4) axis on apoptosis in human degenerative nucleus pulposus cells (NPCs). The expression levels of SDF‑1 and CXCR4 in human intervertebral discs (IVD) were determined using immunohistochemistry and western blot analysis. Apoptosis of primary cultured NPCs was quantified by Annexin V/propidium iodide staining following stimulation with SDF‑1 and knockdown of CXCR4 using small interfering RNA (siRNA). The association with the nuclear factor‑κB (NF‑κB) signaling pathway was investigated using CXCR4‑siRNA and NF‑κB inhibitor, pyrrolidine dithiocarbamate (PDTC), treatment. The results demonstrated that SDF‑1 and its receptor, CXCR4, were upregulated in degenerative IVD samples compared with normal samples. Stimulation with SDF‑1 increased the level of apoptosis in cultured NPCs, and conversely, the apoptosis level was suppressed post‑transfection with CXCR4 siRNA compared with SDF‑1 stimulation alone. Furthermore, SDF‑1 treatment increased the level of phosphorylated NF‑κB subunit P65, which was downregulated following CXCR4 siRNA and PDTC treatment. In addition, CXCR4 siRNA and PDTC inhibited the nuclear translocation of P65, which was induced by SDF‑1. Taken together, SDF‑1‑mediated apoptosis was suppressed by NF‑κB inhibition using PDTC. In conclusion, the SDF‑1/CXCR4 axis promoted cell apoptosis in human degenerative NPCs via the NF‑κB pathway, thus suggesting that SDF‑1/CXCR signaling may be a therapeutic target for the treatment of degenerative IVD diseases. PMID:27220474

  18. Syndecan-4 in intervertebral disc and cartilage: Saint or synner?

    PubMed

    Binch, Abbie L A; Shapiro, Irving M; Risbud, Makarand V

    2016-01-01

    The ECM of the intervertebral disc and articular cartilage contains a highly organised network of collagens and proteoglycans which resist compressive forces applied to these tissues. A pathological hallmark of the intervertebral disc is the imbalance between production of anabolic and catabolic factors by the resident cells. This process is thought to be mediated by pro-inflammatory cytokines, predominantly TNF-α and IL-1β, which upregulate expression of matrix degrading enzymes such as MMPs and ADAMTSs. This imbalance ultimately results in tissue degeneration causing failure of the biomechanical function of the tissues. A similar cascade of events is thought to occur in articular cartilage during development of osteoarthritis. Within these skeletal tissues a small, cell surface heparan sulphate proteoglycan; syndecan-4 (SDC4) has been implicated in maintaining physiological functions. However in the degenerating niche of the intervertebral disc and cartilage, dysregulated activities of this molecule may exacerbate pathological changes. Studies in recent years have elucidated a role for SDC4 in mediating matrix degradation in both intervertebral discs and cartilage by controlling ADAMTS-5 function and MMP3 expression. Discourse presented in this review highlights the potential of SDC4 as a possible therapeutic target in slowing the progression of ECM degradation in both degenerative disc disease and osteoarthritis. PMID:26796346

  19. High Glucose Accelerates Autophagy in Adult Rat Intervertebral Disc Cells

    PubMed Central

    Kong, Chae-Gwan; Kim, Man Soo; Park, Eun-Young

    2014-01-01

    Study Design In vitro cell culture. Purpose The purpose of this study was to investigate the effect of high glucose on autophagy in adult rat intervertebral disc cells. Overview of Literature Diabetes mellitus is considered to be an important etiologic factor for intervertebral disc degeneration, resulting in degenerative disc diseases. A glucose-mediated increase of autophagy is a major causative factor for the development of diseases associated with diabetes mellitus. However, no information is available for the effect of high glucose on autophagy in adult intervertebral disc cells. Methods Nucleus pulposus and annulus fibrosus cells were isolated from 24-week-old adult rats, cultured and placed in either 10% fetal bovine serum (normal control) or 10% fetal bovine serum plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days, respectively. The expressions of autophagy markers, such as beclin-1, light chain 3-I (LC3-I) and LC3-II, autophagy-related gene (Atg) 3, 5, 7 and 12, were identified and quantified. Results Two high glucoses significantly increased the expressions of beclin-1, LC3-II, Atg3, 5, 7, and 12 in adult rat nucleus pulposus and annulus fibrosus cells in a dose- and time-dependent manner. The ratio of LC3-II/LC3-I expression was also increased in a dose-respectively time-dependent manner. Conclusions The results suggest that autophagy of adult nucleus pulposus and annulus fibrosus cells might be a potential mechanism for the intervertebral disc degeneration in adult patients with diabetes mellitus. Thus, the prevention of autophagy in adult intervertebral disc cells might be considered as a novel therapeutic target to prevent or to delay the intervertebral disc degeneration in adult patients with diabetes mellitus. PMID:25346805

  20. Wnt Signaling Activates Shh Signaling in Early Postnatal Intervertebral Discs, and Re-Activates Shh Signaling in Old Discs in the Mouse

    PubMed Central

    Sinner, Debora; Wylie, Christopher C.; Dahia, Chitra Lekha

    2014-01-01

    Intervertebral discs (IVDs) are strong fibrocartilaginous joints that connect adjacent vertebrae of the spine. As discs age they become prone to failure, with neurological consequences that are often severe. Surgical repair of discs treats the result of the disease, which affects as many as one in seven people, rather than its cause. An ideal solution would be to repair degenerating discs using the mechanisms of their normal differentiation. However, these mechanisms are poorly understood. Using the mouse as a model, we previously showed that Shh signaling produced by nucleus pulposus cells activates the expression of differentiation markers, and cell proliferation, in the postnatal IVD. In the present study, we show that canonical Wnt signaling is required for the expression of Shh signaling targets in the IVD. We also show that Shh and canonical Wnt signaling pathways are down-regulated in adult IVDs. Furthermore, this down-regulation is reversible, since re-activation of the Wnt or Shh pathways in older discs can re-activate molecular markers of the IVD that are lost with age. These data suggest that biological treatments targeting Wnt and Shh signaling pathways may be feasible as a therapeutic for degenerative disc disease. PMID:24892825

  1. Hybrid Surgery Versus Anterior Cervical Discectomy and Fusion in Multilevel Cervical Disc Diseases: A Meta-Analysis.

    PubMed

    Zhang, Jianfeng; Meng, Fanxin; Ding, Yan; Li, Jie; Han, Jian; Zhang, Xintao; Dong, Wei

    2016-05-01

    To investigate the outcomes and reliability of hybrid surgery (HS) versus anterior cervical discectomy and fusion (ACDF) for the treatment of multilevel cervical spondylosis and disc diseases.Hybrid surgery, combining cervical disc arthroplasty (CDA) with fusion, is a novel treatment to multilevel cervical degenerated disc disease in recent years. However, the effect and reliability of HS are still unclear compared with ACDF.To investigate the studies of HS versus ACDF in patients with multilevel cervical disease, electronic databases (Medline, Embase, Pubmed, Cochrane library, and Cochrane Central Register of Controlled Trials) were searched. Studies were included when they compared HS with ACDF and reported at least one of the following outcomes: functionality, neck pain, arm pain, cervical range of motion (ROM), quality of life, and incidence of complications. No language restrictions were used. Two authors independently assessed the methodological quality of included studies and extracted the relevant data.Seven clinical controlled trials were included in this study. Two trials were prospective and the other 5 were retrospective. The results of the meta-analysis indicated that HS achieved better recovery of NDI score (P = 0.038) and similar recovery of VAS score (P = 0.058) compared with ACDF at 2 years follow-up. Moreover, the total cervical ROM (C2-C7) after HS was preserved significantly more than the cervical ROM after ACDF (P = 0.000) at 2 years follow-up. Notably, the compensatory increase of the ROM of superior and inferior adjacent segments was significant in ACDF groups at 2-year follow-up (P < 0.01), compared with HS.The results demonstrate that HS provides equivalent outcomes and functional recovery for cervical disc diseases, and significantly better preservation of cervical ROM compared with ACDF in 2-year follow-up. This suggests the HS is an effective alternative invention for the treatment of multilevel cervical spondylosis to

  2. Effect of autologous platelet leukocyte rich plasma injections on atrophied lumbar multifidus muscle in low back pain patients with monosegmental degenerative disc disease

    PubMed Central

    Hussein, Mohamed; Hussein, Tamer

    2016-01-01

    Background: Lumbar multifidus muscle dysfunction and chronic low back pain are strongly correlated. There is no consensus regarding treatment of chronic LBP. The effect of platelet leukocyte rich plasma (PLRP) injections on atrophied lumbar multifidus (LMF) muscle and chronic low back pain has never been studied before. Patients and methods: One hundred fifteen patients with chronic non-specific LBP fulfilled the inclusion criteria. Patients were treated with weekly PLRP injections for six weeks and followed up for 24 months. Primary outcome measures included Numerical Rating Scale (NRS) and Oswestry Disability Index (ODI). Secondary outcome measures included Patient Satisfaction Index (PSI), modified MacNab criteria, and lumbar MRI at 12 months follow-up. Results: One hundred and four patients completed the trial. There were no serious complications. NRS significantly improved gradually from a mean of 8.8 ± 8 pre-injection to 3.45 ± 2.9 by 12 months and ODI significantly improved gradually from a mean of 36.7 ± 3.9 to 14.6 ± 12.8 by 12 months (P < 0.005). After reaching maximum improvement between 12 and 18 months, all outcome measures remained stable till the end of the 24 months follow-up period with statistically insignificant changes (P > 0.05). 87.8% (65/74) of the satisfied patients showed increased cross-sectional area and decreased fatty degeneration of LMF muscle on MRI at 12 months follow-up. Conclusion: PLRP injections into atrophied lumbar multifidus muscle represent a safe, effective method for relieving chronic low back pain and disability with long-term patient satisfaction and success rate of 71.2%. We recommend the use of the lumbar PLRP injections of LMF muscle to refine the inclusion criteria of lumbar fusion to avoid failed back syndrome. PMID:27163101

  3. Inflammatory Cytokines Associated with Degenerative Disc Disease Control Aggrecanase-1 (ADAMTS-4) Expression in Nucleus Pulposus Cells through MAPK and NF-κB

    PubMed Central

    Tian, Ye; Yuan, Wen; Fujita, Nobuyuki; Wang, Jianru; Wang, Hua; Shapiro, Irving M.; Risbud, Makarand V.

    2014-01-01

    We investigated TNF-α and IL-1β regulation of ADAMTS-4 expression in nucleus pulposus (NP) cells and its role in aggrecan degradation. Real-time quantitative RT-PCR, Western blotting, and transient transfections with rat NP cells and lentiviral silencing with human NP cells were performed to determine the roles of MAPK and NF-κB in cytokine-mediated ADAMTS-4 expression and function. ADAMTS4 expression and promoter activity increased in NP cells after TNF-α and IL-1β treatment. Treatment of cells with MAPK and NF-κB inhibitors abolished the inductive effect of the cytokines on ADAMTS4 mRNA and protein expression. Although ERK1, p38α, p38β2, and p38γ were involved in induction, ERK2 and p38δ played no role in TNF-α–dependent promoter activity. The inductive effect of p65 on ADAMTS4 promoter was confirmed through gain and loss-of-function studies. Cotransfection of p50 completely blocked p65-mediated induction. Lentiviral transduction with shRNA plasmids shp65, shp52, shIKK-α, and shIKK-β significantly decreased TNF-α–dependent increase in ADAMTS-4 and -5 levels and aggrecan degradation. Silencing of either ADAMTS-4 or -5 resulted in reduction in TNF-α–dependent aggrecan degradation in NP cells. By controlling activation of MAPK and NF-κB signaling, TNF-α and IL-1β modulate expression of ADAMTS-4 in NP cells. To our knowledge, this is the first study to show nonredundant contribution of both ADAMTS-4 and ADAMTS-5 to aggrecan degradation in human NP cells in vitro. PMID:23602832

  4. TU-C-12A-12: Differentiating Bone Lesions and Degenerative Joint Disease in NaF PET/CT Scans Using Machine Learning

    SciTech Connect

    Perk, T; Bradshaw, T; Muzahir, S; Jeraj, R; Meyer, E

    2014-06-15

    Purpose: [F-18]NaF PET can be used to image bone metastases; however, tracer uptake in degenerative joint disease (DJD) often appears similar to metastases. This study aims to develop and compare different machine learning algorithms to automatically identify regions of [F-18]NaF scans that correspond to DJD. Methods: 10 metastatic prostate cancer patients received whole body [F-18]NaF PET/CT scans prior to treatment. Image segmentation resulted in 852 ROIs, 69 of which were identified by a nuclear medicine physician as DJD. For all ROIs, various PET and CT textural features were computed. ROIs were divided into training and testing sets used to train eight different machine learning classifiers. Classifiers were evaluated based on receiver operating characteristics area under the curve (AUC), sensitivity, specificity, and positive predictive value (PPV). We also assessed the added value of including CT features in addition to PET features for training classifiers. Results: The training set consisted of 37 DJD ROIs with 475 non-DJD ROIs, and the testing set consisted of 32 DJD ROIs with 308 non-DJD ROIs. Of all classifiers, generalized linear models (GLM), decision forests (DF), and support vector machines (SVM) had the best performance. AUCs of GLM (0.929), DF (0.921), and SVM (0.889) were significantly higher than the other models (p<0.001). GLM and DF, overall, had the best sensitivity, specificity, and PPV, and gave a significantly better performance (p<0.01) than all other models. PET/CT GLM classifiers had higher AUC than just PET or just CT. GLMs built using PET/CT information had superior or comparable sensitivities, specificities and PPVs to just PET or just CT. Conclusion: Machine learning algorithms trained with PET/CT features were able to identify some cases of DJD. GLM outperformed the other classification algorithms. Using PET and CT information together was shown to be superior to using PET or CT features alone. Research supported by the Prostate

  5. Disc cell senescence in intervertebral disc degeneration: Causes and molecular pathways

    PubMed Central

    Feng, Chencheng; Liu, Huan; Yang, Minghui; Zhang, Yang; Huang, Bo; Zhou, Yue

    2016-01-01

    ABSTRACT The accumulation of senescent disc cells in degenerative intervertebral disc (IVD) suggests the detrimental roles of cell senescence in the pathogenesis of intervertebral disc degeneration (IDD). Disc cell senescence decreased the number of functional cells in IVD. Moreover, the senescent disc cells were supposed to accelerate the process of IDD via their aberrant paracrine effects by which senescent cells cause the senescence of neighboring cells and enhance the matrix catabolism and inflammation in IVD. Thus, anti-senescence has been proposed as a novel therapeutic target for IDD. However, the development of anti-senescence therapy is based on our understanding of the molecular mechanism of disc cell senescence. In this review, we focused on the molecular mechanism of disc cell senescence, including the causes and various molecular pathways. We found that, during the process of IDD, age-related damages together with degenerative external stimuli activated both p53-p21-Rb and p16-Rb pathways to induce disc cell senescence. Meanwhile, disc cell senescence was regulated by multiple signaling pathways, suggesting the complex regulating network of disc cell senescence. To understand the mechanism of disc cell senescence better contributes to developing the anti-senescence-based therapies for IDD. PMID:27192096

  6. LUMBAR DISC HERNIATION

    PubMed Central

    Vialle, Luis Roberto; Vialle, Emiliano Neves; Suárez Henao, Juan Esteban; Giraldo, Gustavo

    2015-01-01

    Lumbar disc herniation is the most common diagnosis among the degenerative abnormalities of the lumbar spine (affecting 2 to 3% of the population), and is the principal cause of spinal surgery among the adult population. The typical clinical picture includes initial lumbalgia, followed by progressive sciatica. The natural history of disc herniation is one of rapid resolution of the symptoms (four to six weeks). The initial treatment should be conservative, managed through medication and physiotherapy, sometimes associated with percutaneous nerve root block. Surgical treatment is indicated if pain control is unsuccessful, if there is a motor deficit greater than grade 3, if there is radicular pain associated with foraminal stenosis, or if cauda equina syndrome is present. The latter represents a medical emergency. A refined surgical technique, with removal of the extruded fragment and preservation of the ligamentum flavum, resolves the sciatic symptoms and reduces the risk of recurrence over the long term. PMID:27019834

  7. Vertebral body split fracture after a single-level cervical total disc replacement.

    PubMed

    Tu, Tsung-Hsi; Wu, Jau-Ching; Fay, Li-Yu; Ko, Chin-Chu; Huang, Wen-Cheng; Cheng, Henrich

    2012-03-01

    Cervical total disc replacement (TDR) is a viable option for the surgical treatment of degenerative disc disease. This 67-year-old nonsmoking male patient underwent single-level ProDisc-C cervical TDR at C5-6 without any intraoperative problem. His radicular pain improved and he had no neck pain immediately after the operation. However, on postoperative Day 3, a radiograph demonstrated a vertical split fracture of the C-5 vertebra. This fracture was managed conservatively, and 2 years postoperatively a follow-up CT scan demonstrated stable device position and fusion of the fracture. Although the linear fracture caused no neurological symptoms or device migration, the authors advocate prudence in selection and installation of keel-design prostheses, even in a single-level cervical TDR scenario. PMID:22176434

  8. Transforaminal Percutaneous Endoscopic Discectomy for Lumbar Disc Herniation in Parkinson's Disease: A Case-Control Study

    PubMed Central

    Giovannopoulou, Eirini; Charitoudis, George; Kazakos, Konstantinos

    2016-01-01

    Study Design A case-control study. Purpose To investigate the effectiveness of transforaminal percutaneous endoscopic discectomy (TPED) in Parkinson's disease (PD). Overview of Literature Patients with PD frequently suffer from radiculopathy and low back pain. Additionally, they demonstrate higher complication rates after open spine surgery. However, the clinical outcome of minimally invasive techniques for lumbar discectomy, such as TPED, have not been established for this population. Methods Patients diagnosed with lumbar disc hernia were divided into Group A (11 patients diagnosed with PD), and Group B (10 patients as the control, non-PD group). All patients underwent TPED. Indexes of visual analogue scale (VAS) for leg pain and Oswestry disability index (ODI) were assessed right before surgery and at six weeks, three months, six months and one year post-surgery. Results At the baseline visit, groups did not differ significantly with age (p=0.724), gender (p=0.835), level of operation (p=0.407), ODI (p=0.497) and VAS (p=0.772). Parkinson's patients had higher scores in ODI at every visit, but the outcome was statistically significant only at 3 months (p=0.004) and one year (p=0.007). Similarly, VAS measurements were higher at each time point, with the difference being significant at 3 (p<0.001), 6 (0.021), and 12 (p<0.001) months after surgery. At the end of a year of follow up, ODI was reduced by 49.6% (±16.7) in Group A and 59.2% (±8.0) in Group B (p=0.111), translating to a 79.5% (±13.0) and 91.5% (±4.1) average improvement in daily functionality (p=0.024). VAS was reduced by 59.1 mm (±11.8) in Group A and 62.2 mm (±7.4) in Group B (p=0.485), leading to an 85.3 % (±4.0) and 91.9% (±2.6) general improvement in leg pain (p<0.001). Conclusions Our data indicate that TPED led to satisfactory improvement in leg pain and daily living in PD patients a year after surgery. PMID:27559446

  9. Gene Expression Profiling Identifies Interferon Signalling Molecules and IGFBP3 in Human Degenerative Annulus Fibrosus.

    PubMed

    Kazezian, Zepur; Gawri, Rahul; Haglund, Lisbet; Ouellet, Jean; Mwale, Fackson; Tarrant, Finbarr; O'Gaora, Peadar; Pandit, Abhay; Alini, Mauro; Grad, Sibylle

    2015-01-01

    Low back pain is a major cause of disability especially for people between 20 and 50 years of age. As a costly healthcare problem, it imposes a serious socio-economic burden. Current surgical therapies fail to replace the normal disc in facilitating spinal movements and absorbing load. The focus of regenerative medicine is on identifying biomarkers and signalling pathways to improve our understanding about cascades of disc degeneration and allow for the design of specific therapies. We hypothesized that comparing microarray profiles from degenerative and non-degenerative discs will lead to the identification of dysregulated signalling and pathophysiological targets. Microarray data sets were generated from human annulus fibrosus cells and analysed using IPA ingenuity pathway analysis. Gene expression values were validated by qRT-PCR, and respective proteins were identified by immunohistochemistry. Microarray analysis revealed 238 differentially expressed genes in the degenerative annulus fibrosus. Seventeen of the dysregulated molecular markers showed log2-fold changes greater than ±1.5. Various dysregulated cellular functions, including cell proliferation and inflammatory response, were identified. The most significant canonical pathway induced in degenerative annulus fibrosus was found to be the interferon pathway. This study indicates interferon-alpha signalling pathway activation with IFIT3 and IGFBP3 up-regulation, which may affect cellular function in human degenerative disc. PMID:26489762

  10. Gene Expression Profiling Identifies Interferon Signalling Molecules and IGFBP3 in Human Degenerative Annulus Fibrosus

    PubMed Central

    Kazezian, Zepur; Gawri, Rahul; Haglund, Lisbet; Ouellet, Jean; Mwale, Fackson; Tarrant, Finbarr; O’Gaora, Peadar; Pandit, Abhay; Alini, Mauro; Grad, Sibylle

    2015-01-01

    Low back pain is a major cause of disability especially for people between 20 and 50 years of age. As a costly healthcare problem, it imposes a serious socio-economic burden. Current surgical therapies fail to replace the normal disc in facilitating spinal movements and absorbing load. The focus of regenerative medicine is on identifying biomarkers and signalling pathways to improve our understanding about cascades of disc degeneration and allow for the design of specific therapies. We hypothesized that comparing microarray profiles from degenerative and non-degenerative discs will lead to the identification of dysregulated signalling and pathophysiological targets. Microarray data sets were generated from human annulus fibrosus cells and analysed using IPA ingenuity pathway analysis. Gene expression values were validated by qRT-PCR, and respective proteins were identified by immunohistochemistry. Microarray analysis revealed 238 differentially expressed genes in the degenerative annulus fibrosus. Seventeen of the dysregulated molecular markers showed log2-fold changes greater than ±1.5. Various dysregulated cellular functions, including cell proliferation and inflammatory response, were identified. The most significant canonical pathway induced in degenerative annulus fibrosus was found to be the interferon pathway. This study indicates interferon-alpha signalling pathway activation with IFIT3 and IGFBP3 up-regulation, which may affect cellular function in human degenerative disc. PMID:26489762

  11. Transplantation of adipose derived mesenchymal stem cells for acute thoracolumbar disc disease with no deep pain perception in dogs

    PubMed Central

    Kim, Yongsun; Lee, Seung Hoon; Kim, Wan Hee

    2016-01-01

    Thirty-four dogs with no deep pain perception due to acute thoracolumbar intervertebral disc disease underwent decompression surgery within 1 week of diagnosis. All dogs underwent hemilaminectomy. Adipose derived mesenchymal stem cells (AD-MSCs) were transplanted into the injured spinal cord parenchyma for the AD-MSCs transplant dogs. Long-term outcome was evaluated at the end of the follow-up period (> 6 months). AD-MSCs combination treatment showed better recovery outcomes compared to decompression surgery alone. These results indicate that this stem cell therapy is a potential therapeutic strategy to overcome the limitations of treatment for spinal cord injury in clinical medicine. PMID:27051350

  12. Biological repair of the degenerated intervertebral disc by the injection of growth factors

    PubMed Central

    2008-01-01

    The homeostasis of intervertebral disc (IVD) tissues is accomplished through a complex and precise coordination of a variety of substances, including cytokines, growth factors, enzymes and enzyme inhibitors. Recent biological therapeutic strategies for disc degeneration have included attempts to up-regulate the production of key matrix proteins or to down-regulate the catabolic events induced by pro-inflammatory cytokines. Several approaches to deliver these therapeutic biologic agents have been proposed and tested in a preclinical setting. One of the most advanced biological therapeutic approaches to regenerate or repair a degenerated disc is the injection of a recombinant growth factor. Abundant evidence for the efficacy of growth factor injection therapy for the treatment of IVD degeneration can be found in preclinical animal studies. Recent data obtained from animal studies on changes in cytokine expression following growth factor injection illustrate the great potential for patients with chronic discogenic low back pain. The first clinical trial for growth factor injection has been initiated and the results of that study may prove the usefulness of growth factor injection for treating the symptoms of patients with degenerative disc diseases. The focus of this review article is the effects of an in vivo injection of growth factors on the biological repair of the degenerated intervertebral disc in animal models. The effects of growth factor injection on the symptoms of patients with low back pain, the therapeutic target of growth factor injection and the limitations of the efficacy of growth factor therapy are also reviewed. Further quantitative studies on the effect of growth factor injection on pain generation and the long term effects on the endplate and cell survival after an injection using large animals are needed. An international academic-industrial consortium addressing these aims, such as was achieved for osteoarthritis (The Osteoarthritis Initiative

  13. Structured bilaminar co-culture outperforms stem cells and disc cells in a simulated degenerate disc environment

    PubMed Central

    Allon, Aliza A.; Butcher, Kristin; Schneider, Richard A.; Lotz, Jeffrey C.

    2011-01-01

    Study Design This study explores the use of bilaminar coculture pellets of mesenchymal stem cells (MSC) and Nucleus Pulposus cells (NPC) as a cell-based therapy for intervertebral disc regeneration. The pellets were tested under conditions that mimic the degenerative disc. Objective Our goal is to optimize our cell-based therapy in vitro under conditions representative of the eventual diseased tissue. Summary of Background Data Harnessing the potential of stem cells is an important strategy for regenerative medicine. Our approach seeks to direct the behavior of stem cells by mimicking embryonic processes underlying cartilage and intervertebral disc development. Prior experiments have shown that bilaminar co-culture can help differentiate MSC and substantially improve new matrix deposition. Methods We have designed a novel spherical bilaminar cell pellet (BCP) where MSC are enclosed in a shell of NPC. There were three groups: MSC, NPC, and BCP. The pellets were tested under three different culture conditions: in a bioreactor that provides pressure & hypoxia (mimicking normal disc conditions), with inflammatory cytokines (IL-1b and TNF-a), and a bioreactor with inflammation (mimicking painful disc conditions). Results When cultured in the bioreactor, the NPC pellets produced significantly more glycosaminoglycan (GAG)/cell than the other groups: 70-80% more than the BCP and MSC alone. When cultured in an inflammatory environment, the MSC and BCP groups produced 30-34% more GAG/cell than NPC (p<0.05). When the pellets were cultured in a bioreactor with inflammation, the BCP made 25% more GAG/cell than MSC and 57% more than NPC (p<0.05). Conclusion This study shows that BCP outperform controls in a simulated degenerated disc environment. Adapting inductive mechanisms from development to trigger differentiation and restore diseased tissue has many advantages. As opposed to strategies that require growth factor supplements or genetic manipulations, our method is self

  14. Coexistence of expanding abdominal aortic aneurysm and aggravated intervertebral disc extrusion -a case report-.

    PubMed

    Kim, Nan Seol; Kang, Sung Hyun; Park, Sun Young

    2013-10-01

    Abdominal aortic aneurysm is included in the differential diagnosis of lower back pain. Although rare, this important disease can cause potentially lethal complications. In this case, expanding abdominal aortic aneurysm coexisted with intervertebral disc extrusion. The diagnosis of abdominal aortic aneurysm was delayed, putting the patient at risk of aneurysmal rupture. In the management of patients with degenerative spinal diseases, we should not overlook the possibility of comorbidities such as an abdominal aortic aneurysm. We also suggest the importance of interpreting images more carefully, especially for elderly male patients. PMID:24228150

  15. Varus deformity of the left lower extremity causing degenerative lesion of the posterior horn of the left medial meniscus in a patient with Paget’s disease of bone

    PubMed Central

    Al Kaissi, Ali; Ganger, Rudolf; Mindler, Gabriel; Klaushofer, Klaus; Grill, Franz

    2014-01-01

    We report on a 42-year-old woman who presented with persistent pain in her left knee with no history of trauma. Sagittal T1-weighted MRI of the left knee showed discontinuity between the anterior and posterior horns of the left medial meniscus, causing effectively the development of degenerative lesion of the posterior horn. The latter was correlated to varus deformity of the left lower extremity associated with subsequent narrowing of the medial knee joint. The unusual craniofacial contour of the patient, the skeletal survey and the elevated serum alkaline phosphatase were compatible with the diagnosis of Paget’s disease of the bone. To alleviate the adverse effect of the mal-alignment of the left femur onto the left knee, corrective osteotomy of the left femoral diaphysis by means of fixators was performed. To the best of our knowledge this is the first clinical report describing the management and the pathological correlation of a unilateral varus deformity of the femoral shaft and degenerative lesions of the left knee in a patient with Paget’s disease of the bone. PMID:25276115

  16. Continuous lumbar hemilaminectomy for intervertebral disc disease in an Amur tiger (Panthera tigris altaica).

    PubMed

    Flegel, Thomas; Böttcher, Peter; Alef, Michaele; Kiefer, Ingmar; Ludewig, Eberhard; Thielebein, Jens; Grevel, Vera

    2008-09-01

    A 13-yr-old Amur tiger (Panthera tigris altaica) was presented for an acute onset of paraplegia. Spinal imaging that included plain radiographs, myelography, and computed tomography performed under general anesthesia revealed lateralized spinal cord compression at the intervertebral disc space L4-5 caused by intervertebral disc extrusion. This extrusion was accompanied by an extensive epidural hemorrhage from L3 to L6. Therefore, a continuous hemilaminectomy from L3 to L6 was performed, resulting in complete decompression of the spinal cord. The tiger was ambulatory again 10 days after the surgery. This case suggests that the potential benefit of complete spinal cord decompression may outweigh the risk of causing clinically significant spinal instability after extensive decompression. PMID:18817014

  17. Degenerative myelopathy in two Boxer dogs.

    PubMed

    Miller, A D; Barber, R; Porter, B F; Peters, R M; Kent, M; Platt, S R; Schatzberg, S J

    2009-07-01

    Degenerative myelopathy (DM) is a common, slowly progressive, debilitating disease reported in several dog breeds, including the German Shepherd Dog and Pembroke Welsh Corgi. Boxer dogs present occasionally for a thoracolumbar myelopathy for which no cause is identified on MRI or cerebrospinal fluid analysis. Despite a lack of a histologic description of DM in the Boxer in the veterinary literature, such dogs are presumed to have DM. Here we report 2 histologically confirmed cases of DM in the Boxer breed in which histologic studies disclosed marked degenerative changes in the spinal cord that were most prominent in the thoracic and cranial lumbar segments. Lesions consisted of myelin vacuolation and degeneration, myelophagocytosis, reactive astrocytosis, and ellipsoid formation most prominent in the lateral and ventral funiculi. We present a detailed histologic description of DM in the Boxer dog and compare it to DM in other purebred dogs. PMID:19276068

  18. Spondylosis deformans and diffuse idiopathic skeletal hyperostosis (dish) resulting in adjacent segment disease.

    PubMed

    Ortega, Maria; Gonçalves, Rita; Haley, Allison; Wessmann, Annette; Penderis, Jacques

    2012-01-01

    Spondylosis deformans and diffuse idiopathic skeletal hyperostosis (DISH) are usually incidental findings and in most dogs are either asymptomatic or associated with mild clinical signs. Severe spondylosis deformans and DISH can result in complete bony fusion of consecutive vertebral segments. One of the recognised complications following vertebral fusion in human patients is the development of adjacent segment disease, which is defined as degenerative changes, most commonly degenerative intervertebral disc disease, in the mobile vertebral segment neighboring a region of complete vertebral fusion. A similar syndrome following cervical fusion in dogs has been termed the domino effect. The purpose of this retrospective study was to investigate the hypothesis that vertebral fusion occurring secondary to spondylosis deformans or DISH in dogs would protect fused intervertebral disc spaces from undergoing degeneration, but result in adjacent segment disease at neighbouring unfused intervertebral disc spaces. Eight dogs with clinical signs of thoracolumbar myelopathy, magnetic resonance imaging of the thoracolumbar vertebral column, and spondylosis deformans or DISH producing fusion of > or = 2 consecutive intervertebral disc spaces were evaluated. Vertebral fusion of > or = 2 consecutive intervertebral disc spaces was correlated (P = 0.0017) with adjacent segment disease at the neighbouring unfused intervertebral disc space. Vertebral fusion appeared to protect fused intervertebral disc spaces from undergoing degeneration (P < 0.0001). Adjacent segment disease should be considered in dogs with severe spondylosis deformans or DISH occurring in conjunction with a thoracolumbar myelopathy. PMID:22734148

  19. Lumbar Facet Joint Motion in Patients with Degenerative Spondylolisthesis

    PubMed Central

    Yao, Qi; Wang, Shaobai; Shin, Jae-Hyuk; Li, Guoan; Wood, Kirkham B.

    2012-01-01

    Study Design Controlled laboratory study. Objective To investigate the in vivo biomechanical effect of degenerative lumbar spondylolisthesis (DLS) on the motion of the facet joint during various functional weight-bearing activities. Summary of Background Data Although the morphological changes of the facet joints in patients with DLS have been reported in a few studies, no data has been reported on the kinematics of these facet joints. Methods Ten patients with DLS at L4–L5 were studied. Each patient underwent a magnetic resonance imaging (MRI) scan to obtain three-dimensional (3D) models of the lumbar vertebrae from L2–L5 as well as a dual fluoroscopic imaging scan in different postures: flexion-extension, left-right bending and left-right torsion. The positions of the vertebrae were reproduced by matching the MRI-based vertebral models to the fluoroscopic images. The kinematics of the facet joint and the ranges of motion (ROMs) were compared with those of healthy subjects and those of patients with degenerative disc diseases (DDD) previously published. Results In DLS patients, the range of rotation of the facet joints was significantly less at the DLS level (L4–L5) than that at the adjacent levels (L2–L3 and L3–L4), while the range of translation was similar at all levels. The range of rotation at the facet joints of the DLS level decreased compared to those of both the DDD patients and healthy subjects at the corresponding vertebral level (L4–L5), while no significant difference was found in the range of translation. The ROM of facet joints in DLS and in DDD patients was similar at the adjacent levels (L2–L3 and L3–L4). Conclusion The range of rotation decreased at the facet joints at the DLS level (L4–L5) in patients compared to those in healthy subjects and DDD patients. This decrease in range of rotation implies that the DLS disease may cause restabilization of the joint. The data may help the selection of conservative treatment or different

  20. Consensus Paper: Management of Degenerative Cerebellar Disorders

    PubMed Central

    Ilg, W.; Bastian, A. J.; Boesch, S.; Burciu, R. G.; Celnik, P.; Claaßen, J.; Feil, K.; Kalla, R.; Miyai, I.; Nachbauer, W.; Schöls, L.; Strupp, M.; Synofzik, M.; Teufel, J.

    2015-01-01

    Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation. PMID:24222635

  1. Low expression of microRNA-143 is related to degenerative scoliosis possibly by regulation of cyclooxygenase-2 expression

    PubMed Central

    Zheng, Jie; Yang, Yonghong; Zhao, Kefeng; Wang, Ran

    2015-01-01

    Aims: This study is to determine if expression level of microRNA-143 (miR-143) and cyclooxygenase-2 (COX-2) are related to the occurrence and development of degenerative scoliosis. Methods: A total of 30 patients with degenerative scoliosis, 30 patients with adolescent idiopathic scoliosis were enrolled in this study. For control, 30 patients with spinal burst fractures were also enrolled in this study. Real-time PCR and western blotting was performed to measure the expression levels of COX-2 in intervertebral disc tissues, peripheral blood and cerebrospinal. Expression levels of miR-143 in intervertebral disc tissues, peripheral blood and cerebrospinal were detected by real-time PCR. Results: The expression levels of COX-2 were increased in intervertebral disc tissues, peripheral blood and cerebrospinal of patients with degenerative scoliosis when compared with those of patients with adolescent idiopathic scoliosis and spinal burst fractures (P < 0.05). However, the expression levels of miR-143 were decreased in intervertebral disc tissues, peripheral blood and cerebrospinal of patients with degenerative scoliosis when compared with those of patients with adolescent idiopathic scoliosis and spinal burst fractures (P < 0.05). Conclusions: COX-2 is highly expressed whereas miR-143 is lowly expressed in patients with degenerative scoliosis. Decreased expression of miR-143 may be related to the aggravation of degenerative scoliosis by regulation of COX-2. PMID:26064322

  2. Magnetic resonance imaging diagnosis of intervertebral disc disease and myelomalacia in an American black bear (Ursus americanus).

    PubMed

    Knafo, S Emmanuelle; Divers, Stephen J; Rech, Raquel; Platt, Simon R

    2012-06-01

    A 23-yr-old black bear (Ursus americanus) was examined because of paralysis of unknown duration. The precise onset of clinical signs was unknown as a result of seasonal torpor. The bear was immobilized and transported to a university veterinary teaching hospital for further evaluation and treatment. Radiography revealed increased mineral opacity and ventral bridging across vertebral segments T8-11. Magnetic resonance imaging demonstrated dorsal and ventral compression of the spinal cord at T8-9. Given the bear's advanced age, the unknown duration of spinal cord compression, unknown presence of deep pain perception, and thus an unknown prognosis for surgical success, euthanasia was elected. Postmortem examination revealed severe spondylosis deformans from T7 to L3 and dorsal extradural extruded disc material in the area of T8-9. Histopathology demonstrated the dorsal horns of the spinal cord at T9 were replaced by foamy macrophages extending into the dorsal and lateral funiculi of the white matter compatible with focal, severe, chronic myelomalacia. This is the first report of intervertebral disc disease and myelomalacia diagnosed using MRI in a large carnivore. PMID:22779249

  3. Comparison of Operating Time between Stand-alone Cage and a Standard Method for a Single Level Cervical Disc Disease

    PubMed Central

    Kim, Chang Hyoun; Chung, Chun Kee; Jahng, Tae-Ahn

    2012-01-01

    Objective Autologous bone graft with anterior plating had been a standard method for anterior cervical discectomy and fusion (ACDF). Drawbacks of a standard method were donor site problem and problem associated with anterior plate. The stand-alone cage was introduced to reduce such problems. However, problems associated with subsidence and local kyphosis at the index level (segmental kyphosis) still persist with stand-alone cage and a standard method would be required in some cases. It seems that harvest of autologous bone and anterior plating procedure is time consuming, but this has not been verified. The aim of this study was to compare the operating time between patients operated on with stand-alone cage versus a standard method for single-level cervical disc disease. Methods Consecutive 29 patients (M:F=18:11; mean age, 58.4±12.4 years), who had undergone ACDF for single-level disc disease by a single surgeon from incision to closure during 2009-2011, were selected for this retrospective study. Seventeen patients were operated with stand-alone cage (Group I), and twelve patients were with a standard method (Group II). Operating time (from incision to closure), estimated blood loss, clinical and radiological outcomes were compared. Follow-up period was 11.4±6.3 months. Results Operating time was not different between groups longer; Group I (96.1±28.7 minutes) and Group II (112.4±31.7 minutes) (p=0.13). There was no surgery related complication. Excellent or good outcome was achieved in 11 and 10 patients of group I and II, respectively. Bony fusion was achieved in 15 and 10 patients of group I and II respectively, while one subsidence occurred in each group. Postoperative segmental angle at the index level and cervical curvature was not different between groups. No patient complained donor site pain at the last follow-up. Conclusions ACDF with a standard method for single-level cervical disc disease was not a time-consuming procedure comparing stand

  4. The Effect of Gamma Irradiation on the Biological Properties of Intervertebral Disc Allografts: In Vitro and In Vivo Studies in a Beagle Model

    PubMed Central

    Ding, Yu; Ruan, Dike; Luk, Keith D. K.; He, Qing; Wang, Chaofeng

    2014-01-01

    Study Design An animal experiment about intervertebral disc allograft. Objective To explore the feasibility to decellularize disc allografts treated by 6°Co Gamma Irradiation, and simultaneously, to assess the possibility to make use of the decellularized natural disc scaffold for disc degeneration biotherapy. Summary of Background Data Studies of both animal and human disc allograft transplantation indicated that the disc allograft may serve as a scaffold to undertake the physiological responsibility of the segment. Methods Experiment in vitro: 48 discs of beagles were harvested and divided randomly into four groups including a control group and three irradiated groups. Immediate cell viability and biomechanical properties of the discs were checked and comparisons were made among these groups. Experiment in vivo: 24 beagles accepted single-level allografted disc treated with different doses of gamma irradiation. Plain X-rays and MRIs were taken before and after surgery. Then, the spinal columns were harvested en bloc from the sacrificed beagles and were examined morphologically. Results There were significant differences of both the annulus fibrosus and nucleus pulposus immediate cell viabilities among the various groups. There were no obvious differences of the biomechanical properties among the four groups. The disc height and range of motion decreased significantly in all groups as time went on. The observed indexes in irradiated groups were much smaller than those in the control group, but the indexes in 18-kGy group were larger than those in 25-kGy and 50-kGy groups. Both MRI and macroscopic findings showed that the segmental degeneration in the control and 18-kGy group was less severe than that in 25-kGy and 50-kGy groups. Conclusion Gamma Irradiation can decellularize disc allograft successfully to provide natural scaffold for the study of degenerative disc disease therapy, and also can be used as an effective method to produce adjustable animal models

  5. Understanding nucleus pulposus cell phenotype: A prerequisite for stem cell based therapies to treat intervertebral disc degeneration

    PubMed Central

    Choi, Hyowon; Johnson, Zariel I.; Risbud, Makarand V.

    2015-01-01

    Intervertebral disc (IVD) degeneration and associated low back pain (LBP) remains a major burden to our society without a significant improvement in treatment strategies or patient’s quality of life. While the recent cell-transplantation studies for treatment of degenerative disc disease showed promising results, to better gauge the success and functional outcomes of these therapies, it is crucial to understand if transplanted cells give rise to healthy nucleus pulposus (NP) tissue. NP cell phenotype is unique and is defined by expression of a characteristic set of markers that reflect their specialized physiology and function. This review summarizes phenotypic markers that mirror unique physiology and function of NP cells and their progenitors and should be considered to measure outcomes of cell-based therapies to treat disc degeneration. PMID:25584906

  6. Stem cell treatment of degenerative eye disease☆

    PubMed Central

    Mead, Ben; Berry, Martin; Logan, Ann; Scott, Robert A.H.; Leadbeater, Wendy; Scheven, Ben A.

    2015-01-01

    Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment. PMID:25752437

  7. Cervical Arthroplasty for Moderate to Severe Disc Degeneration: Clinical and Radiological Assessments after a Minimum Follow-Up of 18 Months: Pfirrmann Grade and Cervical Arthroplasty

    PubMed Central

    Oh, Chang Hyun; Kim, Do Yeon; Ji, Gyu Yeul; Kim, Yeo Ju; Hyun, Dongkeun; Kim, Eun Young; Park, Hyeonseon; Park, Hyeong-Chun

    2014-01-01

    Purpose Clinical outcomes and radiologic results after cervical arthroplasty have been reported in many articles, yet relatively few studies after cervical arthroplasty have been conducted in severe degenerative cervical disc disease. Materials and Methods Sixty patients who underwent cervical arthroplasty (Mobi-C®) between April 2006 and November 2011 with a minimum follow-up of 18 months were enrolled in this study. Patients were divided into two groups according to Pfirrmann classification on preoperative cervical MR images: group A (Pfirrmann disc grade III, n=38) and group B (Pfirrmann disc grades IV or V, n=22). Visual analogue scale (VAS) scores of neck and arm pain, modified Oswestry Disability Index (mODI) score, and radiological results including cervical range of motion (ROM) were assessed before and after surgery. Results VAS and mean mODI scores decreased after surgery from 5.1 and 57.6 to 2.7 and 31.5 in group A and from 6.1 and 59.9 to 3.7 and 38.4 in group B, respectively. In both groups, VAS and mODI scores significantly improved postoperatively (p<0.001), although no significant intergroup differences were found. Also, cervical dynamic ROM was preserved or gradually improved up to 18 months after cervical arthroplasty in both groups. Global, segmental and adjacent ROM was similar for both groups during follow-up. No cases of device subsidence or extrusion were recorded. Conclusion Clinical and radiological results following cervical arthroplasty in patients with severe degenerative cervical disc disease were no different from those in patients with mild degenerative cervical disc disease after 18 months of follow-up. PMID:24954339

  8. Detection of degenerative change in lateral projection cervical spine x-ray images

    NASA Astrophysics Data System (ADS)

    Jebri, Beyrem; Phillips, Michael; Knapp, Karen; Appelboam, Andy; Reuben, Adam; Slabaugh, Greg

    2015-03-01

    Degenerative changes to the cervical spine can be accompanied by neck pain, which can result from narrowing of the intervertebral disc space and growth of osteophytes. In a lateral x-ray image of the cervical spine, degenerative changes are characterized by vertebral bodies that have indistinct boundaries and limited spacing between vertebrae. In this paper, we present a machine learning approach to detect and localize degenerative changes in lateral x-ray images of the cervical spine. Starting from a user-supplied set of points in the center of each vertebral body, we fit a central spline, from which a region of interest is extracted and image features are computed. A Random Forest classifier labels regions as degenerative change or normal. Leave-one-out cross-validation studies performed on a dataset of 103 patients demonstrates performance of above 95% accuracy.

  9. Relative Contribution of Upper and Lower Lumbar Spinal Segments to Flexion/Extension: Comparison between Normal Spines and Spines with Disc Disease in Asian Patients

    PubMed Central

    Kumar, Malhar N.

    2015-01-01

    Study Design Prospective cohort study. Purpose To evaluate the contribution of upper and lower lumbar segments to flexion and extension of the lumbar spine in normal and diseased spines. Overview of Literature The specific contributions of upper and lower lumbar segments during flexion/extension have rarely been reported. Furthermore, no comparisons between the flexion/extension behaviors of normal and diseased spines have been reported until now. Methods Flexion and extension lateral radiographs of 52 adult, asymptomatic volunteers, and 67 adult patients with lumbar spine disc disease were measured using software for total lumbar lordosis, upper lumbar lordosis and lower lumbar lordosis and the intervertebral angles of all segments. Results In asymptomatic volunteers, the range of movement between flexion and extension was a mean of only 4.2° in the lower lumbar spine and a mean of 19.4° in the upper lumbar spine. In patients with disc degeneration, the range of movement between flexion and extension was an average 6.5° for lower lumbar spine and 15.6° for the upper lumbar spine. Conclusions The results showed that upper lumbar spine contributes more to the range of motion in flexion and extension than the lower lumbar spine in asymptomatic individuals without lumbar disc disease, as well as in patients with disc degeneration. PMID:26435797

  10. Mid- to Long-Term Outcomes of Cervical Disc Arthroplasty versus Anterior Cervical Discectomy and Fusion for Treatment of Symptomatic Cervical Disc Disease: A Systematic Review and Meta-Analysis of Eight Prospective Randomized Controlled Trials

    PubMed Central

    Hu, Yan; Lv, Guohua; Ren, Siying; Johansen, Daniel

    2016-01-01

    Purpose This study aimed to investigate the mid- to long-term outcomes of cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF) for the treatment of 1-level or 2-level symptomatic cervical disc disease. Methods Medline, Embase, and the Cochrane Central Register of Controlled Trials databases were searched to identify relevant randomized controlled trials that reported mid- to long-term outcomes (at least 48 months) of CDA versus ACDF. All data were analyzed by Review Manager 5.3 software. The relative risk (RR) and 95% confidence intervals (CIs) were calculated for dichotomous variables. The weighted mean difference (WMD) and 95%CIs were calculated for continuous variables. A random effect model was used for heterogeneous data; otherwise, a fixed effect model was used. Results Eight prospective randomized controlled trials (RCTs) were retrieved in this meta-analysis, including 1317 and 1051 patients in CDA and ACDF groups, respectively. Patients after an ACDF had a significantly lower rate of follow-up than that after CDA. Pooled analysis showed patients in CDA group achieved significantly higher rates of overall success, Neck Disability Index (NDI) success, neurological success and significantly lower rates of implant/surgery-related serious adverse events and secondary procedure compared with that in ACDF group. The long-term functional outcomes (NDI, Visual Analog Scale (VAS) neck and arm pain scores, the Short Form 36 Health Survey physical component score (SF-36 PCS)), patient satisfaction and recommendation, and the incidence of superior adjacent segment degeneration also favored patients in CDA group with statistical difference. Regarding inferior adjacent segment degeneration, patients in CDA group had a lower rate without statistical significance. Conclusions This meta-analysis showed that cervical disc arthroplasty was superior over anterior discectomy and fusion for the treatment of symptomatic cervical disc disease in

  11. Percutaneous laser disc decompression.

    PubMed

    Choy, D S

    1995-06-01

    Herniated disc disease has an incidence of 1.7% in the U.S. Heretofore, open operative procedures were the rule for this condition when conservative measures were ineffective. Choy and Ascher introduced this new technique in February 1986 using a Nd:YAG laser introduced into the disc through an optical fiber in a needle. Percutaneous laser disc decompression is based on the principle that in an enclosed hydraulic space, such as an intact disc, a small reduction in volume is associated with a disproportionate fall in pressure. In the disc, this partial vacuum causes the herniated portion to move away from the nerve root back toward the center of the disc. This technique has been taught worldwide and is being performed in most of Europe, Japan, the United States, and Korea. In this special issue devoted to percutaneous laser disc decompression (PLDD), we will set forth the basic science of PLDD, patient selection, use of the holmium:YAG, and the Nd:YAG lasers, operative technique, and results. PMID:10150634

  12. Dose-Dependent Response of Tissue-Engineered Intervertebral Discs to Dynamic Unconfined Compressive Loading

    PubMed Central

    Hudson, Katherine D.; Mozia, Robert I.

    2015-01-01

    Because of the limitations of current surgical methods in the treatment of degenerative disc disease, tissue-engineered intervertebral discs (TE-IVDs) have become an important target. This study investigated the biochemical and mechanical responses of composite TE-IVDs to dynamic unconfined compression. TE-IVDs were manufactured by floating an injection molded alginate nucleus pulposus (NP) in a type I collagen annulus fibrosus (AF) that was allowed to contract for 2 weeks before loading. The discs were mechanically stimulated at a range of strain amplitude (1–10%) for 2 weeks with a duty cycle of 1 h on–1 h off–1 h on before being evaluated for their biochemical and mechanical properties. Mechanical loading increased all properties in a dose-dependent manner. Glycosaminoglycans (GAGs) increased between 2.8 and 2.2 fold in the AF and NP regions, respectively, whereas the hydroxyproline content increased between 1.2 and 1.8 fold. The discs also experienced a 2-fold increase in the equilibrium modulus and a 4.3-fold increase in the instantaneous modulus. Full effects for all properties were seen by 5% strain amplitude. These data suggest that dynamic loading increases the functionality of our TE-IVDs with region-dependent responses using a method that may be scaled up to larger disc models to expedite maturation for implantation. PMID:25277703

  13. On total disc replacement.

    PubMed

    Berg, Svante

    2011-02-01

    Low back pain consumes a large part of the community's resources dedicated to health care and sick leave. Back disorders also negatively affect the individual leading to pain suffering, decreased quality-of-life and disability. Chronic low back pain (CLBP) due to degenerative disc disease (DDD) is today often treated with fusion when conservative treatment has failed and symptoms are severe. This treatment is as successful as arthroplasty is for hip arthritis in restoring the patient's quality of life and reducing disability. Even so, there are some problems with this treatment, one of these being recurrent CLBP from an adjacent segment (ASD) after primarily successful surgery. This has led to the development of alternative surgical treatments and devices that maintain or restore mobility, in order to reduce the risk for ASD. Of these new devices, the most frequently used are the disc prostheses used in Total Disc Replacement (TDR). This thesis is based on four studies comparing total disc replacement with posterior fusion. The studies are all based on a material of 152 patients with DDD in one or two segments, aged 20-55 years that were randomly treated with either posterior fusion or TDR. The first study concerned clinical outcome and complications. Follow-up was 100% at both one and two years. It revealed that both treatment groups had a clear benefit from treatment and that patients with TDR were better in almost all outcome scores at one-year follow-up. Fusion patients continued to improve during the second year. At two-year follow-up there was a remaining difference in favour of TDR for back pain. 73% in the TDR group and 63% in the fusion group were much better or totally pain-free (n.s.), while twice as many patients in the TDR group were totally pain free (30%) compared to the fusion group (15%). Time of surgery and total time in hospital were shorter in the TDR group. There was no difference in complications and reoperations, except that seventeen of the

  14. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.

    PubMed

    Kaminsky, Natalie; Bihari, Ofer; Kanner, Sivan; Barzilai, Ari

    2016-06-01

    The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit. PMID:27245308

  15. Atomic Absorption Spectrometry Analysis of Trace Elements in Degenerated Intervertebral Disc Tissue

    PubMed Central

    Kubaszewski, Łukasz; Zioła-Frankowska, Anetta; Frankowski, Marcin; Nowakowski, Andrzej; Czabak-Garbacz, Róża; Kaczmarczyk, Jacek; Gasik, Robert

    2014-01-01

    Background Few studies have investigated trace elements (TE) in human intervertebral disc (IVD) tissue. Trace element presence can have diverse meanings: essential TE show the metabolic modalities of the tissue, while environmentally-related TE indicate pollution and tissue-specific absorption and accumulation. IVD is a highly specific compartment with impaired communication with adjacent bone. Analysis of TE in IVD provides new insights regarding tissue metabolism and IVD communication with other tissues. Material/Methods Thirty intervertebral discs were acquired from 22 patients during surgical treatment for degenerative disease. Atomic absorption spectrometry was used to evaluate the concentrations of Al, Cd, Pb, Cu, Ni, Mo, Mg, and Zn. Results Al, Pb, Cu, Mg, and Zn were detected in all samples. Pb was significantly positively correlated with age, and Ni concentration was weakly correlated with population count in the patient’s place of residence. Only Cu was observed in higher concentrations in IVD compared to in other tissues. Significant positive correlations were observed between the following pairs: Mg/Zn, Mg/Al, Mg/Pb, Zn/Al, Zn/Pb, and Al/Pb. Negative correlations were observed between Mg/Cd, Zn/Cd, Mg/Mo, and Mo/Pb. Conclusions This study is one of few to profile the elements in intervertebral discs in patients with degenerative changes. We report significant differences between trace element concentrations in intervertebral discs compared to in other tissues. Knowledge of the TE accumulation pattern is vital for better understanding intervertebral disc nutrition and metabolism. PMID:25366266

  16. [Neuropathologic markers in degenerative dementias].

    PubMed

    Hauw, J J; Seilhean, D; Colle, M A; Hogenhuys, J; Duyckaerts, C

    1998-01-01

    The number of neuropathological markers used for the diagnosis of degenerative dementias is rapidly increasing, and this is somewhat confusing: some lesions described a long time ago, such as ballooned cells, proved to be less specific than they were supposed to be; this is also the case for Lewy bodies, that have been recognised in a larger spectrum of disorders than thought a few years ago. On the contrary, for an increasing number of neuropathologists, Pick bodies are now mandatory for the diagnosis of Pick disease, and this contrasts with the prevalent opinions of the late sixties or seventies. There are a number of reasons for the changing significance of neuropathological markers. Three of them can be easily identified: 1) the burst of immunohistochemistry into neuropathology allowed an easier recognition, a better delineation and new pathophysiological approaches to old lesions, and a dramatic increase in the description of new markers, especially in glial cells; 2) in some conditions characterized by the number and distribution of some lesions rather than by their mere presence, such as aging and Alzheimer disease, a better neuroanatomical point of view permitted new insights into the concept of disease versus age-related changes; 3) more accurate clinicopathologic correlations showed clearly the need of grouping or lumping together some entities: for example, obvious relationship aroused between progressive supranuclear palsy and corticobasal degeneration; in contrast, distinguishing different disorders in the frontal lobe dementias grouped together into "Pick disease" was felt necessary. This review summarizes the main criteria for identification, and the presumed meaning of the chief markers indicating the presence of abnormally phosphorylated tau proteins, A beta peptides, and PrP proteins. Abnormally phosphorylated tau proteins can be stored in the neurons, and participate in the constitution of many lesions (neurofibrillary tangles, neuropil threads

  17. Lumbar total disc replacement using ProDisc II: a prospective study with a 2-year minimum follow-up.

    PubMed

    Chung, Sung Soo; Lee, Chong Suh; Kang, Chang Seok

    2006-08-01

    A lumbar total disc replacement (TDR) is believed to be a promising substitute in the surgical treatment for lumbar degenerative disc disease. The purpose of this study is to report the clinical and radiographic outcomes of 36 consecutive patients who underwent lumbar TDR using ProDisc II, and the factors associated with a better clinical outcome after a 2-year minimum follow-up. At the time of the latest follow-up, the success rate was 94% of 36 patients according to the criteria of the US Food and Drug Administration. Of the 10 patients unable to work preoperatively, 7 patients returned to work. Moreover, mean score on the visual analog scale for low back and leg pain improved significantly from 7.5 and 4.7 to 3.0 and 1.2, respectively (P<0.001). In addition, mean Oswestry disability index scores improved significantly from 69.2 to 21.0 (P<0.001). Mean disc height at the operative level increased significantly from 9.0 to 17.6 mm, and mean range of motion increased significantly from 9.7 to 12.7 degrees (P<0.01). Statistical analysis showed that the factors associated with a better clinical outcome were single level, and a higher postoperative segmental ROM at the operative level. At a minimum follow-up of 2 years, the lumbar TDR using ProDisc II showed excellent clinical and radiographic outcomes without any significant complication. However, future efforts need to be directed toward the evaluation of a larger number of patients with longer follow-up. PMID:16891976

  18. Analysis of magnetic resonance imaging characteristics and pain in temporomandibular joints with and without degenerative changes of the condyle.

    PubMed

    Campos, M I G; Campos, P S F; Cangussu, M C T; Guimarães, R C; Line, S R P

    2008-06-01

    The aim of this study was to investigate temporomandibular joint (TMJ) pain and magnetic resonance imaging characteristics in 104 TMJs with and 58 without degenerative changes of the condyle, such as osteophytes, erosion, avascular necrosis, subcondral cyst and intra-articular loose bodies. TMJ images were also assessed for flattening, retropositioning and hypomobility of condyle and disc displacement. Comparison of the TMJ side-related data showed a significant relationship between disc displacement without reduction (DDwoR) and the presence of degenerative bony changes (p=0.00). Flattening, retropositioning and hypomobility of condyle showed no significant difference in relation to the presence or absence of degenerative bony changes. Retropositioning of the condyle was significantly associated to disc displacement with reduction (DDwR) (p=0.00), while condylar hypomobility was significantly more frequent in TMJ with DDwoR (p<0.05). Independent of the presence or type of DD, TMJ pain was more frequent in the presence of degenerative bony changes. When considering only DDwR, TMJ pain was significantly associated to a degenerative condition (p=0.03). When there were no degenerative bony changes, TMJ pain was significantly more frequent in DDwoR (p=0.04). Despite the present findings, the absence of symptoms in some patients with condylar bony changes suggests that the diagnosis of osteoarthritis should be established by evaluation of magnetic resonance images in association with clinical examination. PMID:18440778

  19. Early clinical and radiographical results of keel-less and shallow keel cervical disc replacement

    PubMed Central

    Ling, Ji Min; Tiruchelvarayan, Rajendra

    2015-01-01

    good, and we await further long-term outcome results. The authors felt that cervical disc replacement will have an important role in the treatment of cervical degenerative disc disease in the future. PMID:25767568

  20. Copper deficiency myelopathy in the setting of advanced degenerative cervical spondylosis.

    PubMed

    Page, Paul S; Nazar, Ryan G; Park, Michael C; James, Robert F

    2016-08-01

    When presenting conjointly, degenerative cervical spondylosis and copper deficiency myelopathy may be difficult to differentiate providing the potential for mismanagement and unnecessary surgery. We present a case of a 69-year-old female with copper deficiency myelopathy secondary to previous bowel resection in the setting of advanced degenerative cervical spondylotic disease. PMID:26337459

  1. MMP-2 mediates local degradation and remodeling of collagen by annulus fibrosus cells of the intervertebral disc

    PubMed Central

    2013-01-01

    Introduction Degeneration of the intervertebral disc (IVD) is characterized by marked degradation and restructuring of the annulus fibrosus (AF). Although several matrix metalloproteinases (MMPs) have been found to be more prevalent in degenerate discs, their coordination and function within the context of the disease process are still not well understood. In this study, we sought to determine whether MMP-2 is associated with degenerative changes in the AF and to identify the manner by which AF cells use MMP-2. Methods Two established animal models of disc degeneration, static compression and transannular needle puncture of rodent caudal discs, were examined for MMP-2 immunopositivity. With lentiviral transduction of an shRNA expression cassette, we screened and identified an effective shRNA sequence for generating stable RNA interference to silence MMP-2 expression in primary rat AF cells. Gelatin films were used to compare gelatinase activity and spatial patterns of degradation between transduced cells, and both noninfected and nonsense shRNA controls. The functional significance of MMP-2 was determined by assessing the ability for cells to remodel collagen gels. Results Both static compression and 18-g annular puncture of rodent caudal discs stimulated an increase in MMP-2 activity with concurrent lamellar disorganization in the AF, whereas 22-g and 26-g needle injuries did not. To investigate the functional role of MMP-2, we established lentivirus-mediated RNAi to induce stable knockdown of transcript levels by as much as 88%, and protein levels by as much as 95% over a 10-day period. Culturing transduced cells on gelatin films confirmed that MMP-2 is the primary functional gelatinase in AF cells, and that MMP-2 is used locally in regions immediately around AF cells. In collagen gels, transduced cells demonstrated an inability to remodel collagen matrices. Conclusions Our study indicates that increases in MMP-2 observed in human degenerate discs are mirrored in

  2. Lumbar disk replacement with the ProDisc prosthesis.

    PubMed

    Mirovsky, Yigal; Shalmon, Ehud; Halpern, Zvi; Halperin, Nahum; Blankstein, Alexander; Peer, Amir

    2008-02-01

    Twenty-two ProDisc II prostheses (Spine Solutions, New York, New York) were implanted in 21 patients with degenerative disk disease at L5-S1 (19 disks) and L4-L5 (3 disks). After mean follow-up of 3.1 years (range, 17-49 months), pain intensity in all but 3 patients had improved from an average of 7.7 preoperatively to 4.6 postoperatively (P< .001) on a visual analog scale. Average Oswestry Disability Index score improved from 61 to 35 (P< .001). Radiographic reconstruction of the disk space height was achieved in all cases. Previous diskectomy at the implanted level and disk degeneration adjacent to previous fusion negatively influenced the results. PMID:19292209

  3. Optical methods for diagnostics and feedback control in laser-induced regeneration of spine disc and joint cartilages

    NASA Astrophysics Data System (ADS)

    Sobol, Emil; Sviridov, Alexander; Omeltchenko, Alexander; Baum, Olga; Baskov, Andrey; Borchshenko, Igor; Golubev, Vladimir; Baskov, Vladimir

    2011-03-01

    In 1999 we have introduced a new approach for treatment of spine diseases based on the mechanical effect of nondestructive laser radiation on the nucleus pulposus of the intervertebral disc. Laser reconstruction of spine discs (LRD) involves puncture of the disc and non-destructive laser irradiation of the nucleus pulposus to activate reparative processes in the disc tissues. In vivo animal study has shown that LRD allows activate the growth of hyaline type cartilage in laser affected zone. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reparation in cartilages of spine and joints. The results of laser reconstruction of intervertebral discs for 510 patients have shown substantial relief of back pain for 90% of patients. Laser technology has been experimentally tested for reparation of traumatic and degenerative diseases in joint cartilage of 20 minipigs. It is shown that laser regeneration of cartilage allows feeling large (more than 5 mm) defects which usually never repair on one's own. Optical techniques have been used to promote safety and efficacy of the laser procedures.

  4. Comparison of Single-Level and Multiple-Level Outcomes of Total Disc Arthroplasty: 24-Month Results

    PubMed Central

    Ritter-Lang, Karsten; Gössel, Lutz; Dreßler, Nadine

    2015-01-01

    Background Low back pain is one of the most prevalent problems in industrialized countries, affecting as many as 80% of all adults at some time in their lives. Among the significant contributors to low back pain is degenerative disc disease (DDD). Although fusion has been well accepted for treatment of DDD, high rates of complications and stress to adjacent segments remain a concern. Lumbar total disc replacement (TDR) was developed with a goal of preserving motion and avoiding various fusion-related complications, but the relative merits of single vs. multiple level arthroplasty remain unclear. Methods This is a multi-center, single arm, prospective post-market registry of the M6-L, consisting of consecutive patients presenting with lumbar DDD who agreed to participate. This paper reports on those patients who have completed at least 24 months of followup to date. Clinical outcome measures include the Oswestry Disability Index (ODI) and back and leg Visual Analogue Scales (VAS). Radiographic analysis of disc angle and range of motion (ROM) was also performed. Results Results for 83 patients comprising 121 implants in two cohorts (49 single level (SL), 34 multiple levels (ML)) are reported. Both cohorts experienced significant improvement at 24 months including significant decreases in ODI and VAS. Relative to SL procedures, ML procedures demonstrated either comparable results, or results that trended favorably towards the ML procedures. Index and global ROM at 24 months were not significantly different between the two cohorts, while the disc angles were larger in the SL cohort regardless of index level. Conclusions This is the first study to report clinical and radiographic outcomes of TDR with the M6-L in SL vs ML procedures with two years of followup. The results suggest initial device safety and effectiveness when used for the treatment of lumbar degenerative disc disease at one or more levels. PMID:26056629

  5. [MicroRNAs: a type of novel regulative factor for intervertebral disc degeneration].

    PubMed

    Cheng, Wang; Wenjun, Wang; Wei, Yang; Xiaohua, Y U; Yiguo, Yan; Jian, Zhang; Zhisheng, Jiang

    2016-03-25

    Intervertebral disc degeneration (IDD) is one of major causes for intervertebral disc degenerative diseases, and patients with IDD usually suffer from serious low back pain. The current treatments for patients with IDD only relieve the clinical symptom rather than restore biological balance of IDD, leading to inadequate and unsatisfactory results. MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNA molecules, which regulate the gene expression at the post-transcription levels. Research evidences support the involvement of miRNAs in many biological processes, such as lipid metabolism, apoptosis, differentiation and organ development. Accumulating evidences indicate that the expressions of miRNAs change significantly in degenerative tissues. In addition, dysregulated miRNAs contribute to multiple pathological process of IDD, including proliferation and apoptosis of nucleus pulposus and extracellular matrix components, inflammatory response and cartilage endplates degeneration. In this review article, we summarize the expression profiles and roles of miRNAs in IDD, which may provide a novel strategy of biological therapy for the disease. PMID:27273991

  6. Decompression without Fusion for Low-Grade Degenerative Spondylolisthesis

    PubMed Central

    Cheung, Jason Pui Yin; Cheung, Prudence Wing Hang; Cheung, Kenneth Man Chee

    2016-01-01

    Study Design Retrospective series. Purpose Assess results of decompression-only surgery for low-grade degenerative spondylolisthesis with consideration of instability. Overview of Literature There is no consensus on whether fusion or decompression-only surgery leads to better outcomes for patients with low-grade degenerative spondylolisthesis. Current trends support fusion but many studies are flawed due to over-generalization without consideration of radiological instability and their variable presentations and natural history. Methods Patients with surgically treated degenerative spondylolisthesis from 1990–2013 were included. Clinical and radiological instability measures were included. Any residual or recurrence of symptoms, revision surgery performed and functional outcome scores including the numerical global rate of change scale, visual analogue scale, and modified Barthel index were measured. Follow-up periods for patients were divided into short-term (<5 years), mid-term (5–10 years) and long-term (>10 years). Results A total of 64 patients were recruited. Mechanical low back pain was noted in 48 patients and most (85.4%) had relief of back pain postoperatively. Radiological instability was noted in 4 subjects by flexion-extension radiographs and 12 subjects with prone traction radiographs by increased disc height and reduction of olisthesis and slip angle. From the results of the short-term, mid-term and long-term follow-up, reoperation only occurred within the first 5-year follow-up period. All functional scores improved from preoperative to postoperative 1-year follow-up. Conclusions Decompression-only for low-grade degenerative spondylolisthesis has good long-term results despite instability. Further higher-level studies should be performed on this patient group with radiological instability to suggest the superior surgical option. PMID:26949462

  7. [Diagnostics and therapy of spinal disc herniation].

    PubMed

    Zimmer, A; Reith, W

    2014-11-01

    Degenerative processes in a movement segment of the vertebral column, which can potentially give rise to herniation of elements of the nucleus pulposus, are complex and of variable clinical and radiological dimensions; however the mere assumption that degenerative changes precede disc herniation remains a matter of debate. By definition, spinal disc herniation (SDH) refers to components of the gelatinous nucleus pulposus protruding beyond the dorsal level of the vertebral body margin through tears in the annulus fibrosus. Clinical presentation may include pain, paresis and sensory disturbances. Magnetic resonance imaging (MRI) is considered the gold standard in the diagnosis of SDH. In the majority of patients a conservative approach with physical therapy exercises and adequate analgesic and antiphlogistic medical treatment results in a substantial improvement of symptoms. PMID:25398570

  8. Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association For European Cardiovascular Pathology: II. Noninflammatory degenerative diseases - nomenclature and diagnostic criteria.

    PubMed

    Halushka, Marc K; Angelini, Annalisa; Bartoloni, Giovanni; Basso, Cristina; Batoroeva, Lubov; Bruneval, Patrick; Buja, L Maximilian; Butany, Jagdish; d'Amati, Giulia; Fallon, John T; Gallagher, Patrick J; Gittenberger-de Groot, Adriana C; Gouveia, Rosa H; Kholova, Ivana; Kelly, Karen L; Leone, Ornella; Litovsky, Silvio H; Maleszewski, Joseph J; Miller, Dylan V; Mitchell, Richard N; Preston, Stephen D; Pucci, Angela; Radio, Stanley J; Rodriguez, E Rene; Sheppard, Mary N; Stone, James R; Suvarna, S Kim; Tan, Carmela D; Thiene, Gaetano; Veinot, John P; van der Wal, Allard C

    2016-01-01

    Surgical aortic specimens are usually examined in Pathology Departments as a result of treatment of aneurysms or dissections. A number of diseases, genetic syndromes (Marfan syndrome, Loeys-Dietz syndrome, etc.), and vasculopathic aging processes involved in vascular injury can cause both distinct and nonspecific histopathologic changes with degeneration of the media as a common denominator. Terminology for these changes has varied over time leading to confusion and inconsistencies. This consensus document has established a revised, unified nomenclature for the variety of noninflammatory degenerative aortic histopathologies seen in such specimens. Older terms such as cystic medial necrosis and medionecrosis are replaced by more technically accurate terms such as mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, and smooth muscle cell nuclei loss. A straightforward system of grading is presented to gauge the extent of medial degeneration and synoptic reporting tables are provided. Herein we present a standardized nomenclature that is accessible to general pathologists and useful for future publications describing these entities. PMID:27031798

  9. Clinical outcomes of two types of cages used in transforaminal lumbar interbody fusion for the treatment of degenerative lumbar diseases: n-HA/PA66 cages versus PEEK cages.

    PubMed

    Deng, Qian-xing; Ou, Yun-sheng; Zhu, Yong; Zhao, Zeng-hui; Liu, Bo; Huang, Qiu; Du, Xing; Jiang, Dian-ming

    2016-06-01

    This study reports the clinical effects of nano-hydroxyapatite/polyamide66 cages (n-HA/PA66 cages) and compares the clinical outcomes between n-HA/PA66 and polyetheretherketone cages (PEEK cages) for application in transforaminal lumbar interbody fusion (TLIF). A retrospective and case-control study involving 124 patients using n-HA/PA66 cages and 142 patients using PEEK cages was conducted. All patients underwent TLIF and had an average of 2-years of follow-up. The Oswestry Disability Index and Visual Analog Scale were selected to assess the pain of low back and leg, as well as neurological status. The intervertebral space height and segmental angle were also measured to estimate the radiological changes. At the 1-year and final follow-ups, the fusion and subsidence rates were evaluated. There was no significant difference between the two groups regarding clinical and radiological results. At the final follow-up, the bony fusion rate was 92.45 and 91.57 % for the n-HA/PA66 and PEEK groups, respectively, and the subsidence rate was 7.55 and 8.99 %, respectively. The study indicated that both n-HA/PA66 and PEEK cages could promote effective clinical and radiographic outcomes when used to treat degenerative lumbar diseases. The high fusion and low subsidence rates revealed that n-HA/PA66 cages could be an alternative ideal choice as the same to PEEK cages for lumbar reconstruction after TLIF. PMID:27091044

  10. Failing as doorman and disc jockey at the same time: Amygdalar dysfunction in Parkinson's disease.

    PubMed

    Diederich, Nico J; Goldman, Jennifer G; Stebbins, Glenn T; Goetz, Christopher G

    2016-01-01

    In Braak's model of ascending degeneration in Parkinson's disease (PD), involvement of the amygdala occurs simultaneously with substantia nigra degeneration. However, the clinical manifestations of amygdalar involvement in PD have not been fully delineated. Considered a multitask manager, the amygdala is a densely connected "hub," coordinating and integrating tasks ranging from prompt, multisensorial emotion recognition to adequate emotional responses and emotional tuning of memories. Although phylogenetically predisposed to handle fear, the amygdala handles both aversive and positive emotional inputs. In PD, neuropathological and in vivo studies suggest primarily amygdalar hypofunction. However, as dopamine acts as an inverted U-shaped amygdalar modulator, medication-induced hyperactivity of the amygdala can occur. We propose that amygdalar (network) dysfunction contributes to reduced recognition of negative emotional face expressions, impaired theory of mind, reactive hypomimia, and impaired decision making. Similarly, impulse control disorders in predisposed individuals, hallucinations, anxiety, and panic attacks may be related to amygdalar dysfunction. When available, we discuss amygdala-independent trigger mechanisms of these symptoms. Although dopaminergic agents have mostly an activation effect on amygdalar function, adaptive and compensatory network changes may occur as well, but these have not been sufficiently explored. In conclusion, our model of amygdalar involvement brings together several elements of Parkinson's disease phenomenology heretofore left unexplained and provides a framework for testable hypotheses in patients during life and in autopsy analyses. PMID:26650182

  11. Prevalence of Age-Related Changes in Ovine Lumbar Intervertebral Discs during Computed Tomography and Magnetic Resonance Imaging.

    PubMed

    Nisolle, Jean-François; Bihin, Benoît; Kirschvink, Nathalie; Neveu, Fabienne; Clegg, Peter; Dugdale, Alexandra; Wang, Xiaoqing; Vandeweerd, Jean-Michel

    2016-01-01

    Ovine models are used to study intervertebral disc (IVD) degeneration. The objective of the current study was to assess the naturally occurring age-related changes of the IVD that can be diagnosed by CT and MRI in the lumbar spine of sheep. We used CT and T2-weighted MR images to score the IVD (L6S1 to L1L2) in 41 sheep (age, 6 mo to 11 y) that were euthanized for reasons not related to musculoskeletal disease. T2 mapping and measurement of T2 time of L6S1 to L2L3 were performed in 22 of the sheep. Degenerative changes manifested as early as 2 y of age and occurred at every IVD level. Discs were more severely damaged in older sheep. The age effect of the L6S1 IVD was larger than the average age effect for the other IVD. The current study provides evidence that lesions similar to those encountered in humans can be identified by CT and MRI in lumbar spine of sheep. Ideally, research animals should be assessed at the initiation of preclinical trials to determine the extent of prevalent degenerative changes. The ovine lumbosacral disc seems particularly prone to degeneration and might be a favorable anatomic site for studying IVD degeneration. PMID:27538861

  12. Neuropeptides in experimental and degenerative arthritis.

    PubMed

    Niissalo, S; Hukkanen, M; Imai, S; Törnwall, J; Konttinen, Y T

    2002-06-01

    Classical symptoms of both inflammatory and degenerative arthritides may contribute to neurogenic responses like wheal, flare, edema, and pain. Rheumatoid arthritis (RA) is an autoimmune disease with an immunogenetic background. Neurogenic inflammation has been considered to play an essential role in RA, in part because of the symmetrical involvement (cross-spinal reflexes) and the predominant involvement of the most heavily innervated small joints of the hands and the feet (highly represented in the hominiculus). In contrast, osteoarthritis (OA) is considered to arise as a result of degeneration of the hyaline articular cartilage, which secondarily results in local inflammation and pain. However, it is possible that the age-related and predominant (compared to nociceptive nerves) degeneration of the proprioceptive, kinesthetic and vasoregulatory nerves can represent the primary pathogenic events. This leads to progressive damage of tissue with extremely poor capacity for self-regeneration. Inflammation, be it primary/autoimmune or secondary/degenerative, leads to peripheral sensitization and stimulation, which may further lead to central sensitization, neurogenic amplification of the inflammatory responses and activation of the neuro-endocrine axis. Neuropeptides serve as messengers, which modulate and mediate the actions in these cascades. Accordingly, many neuropeptides have been used successfully as experimental treatments, most recently VIP, which effectively controlled collagen-induced arthritis in mice. Therefore, it can safely be concluded that better treatment/control of disease activity and pain can be achieved by blocking the cascade leading to initiation and/or amplification of inflammatory process combined with effects on central nociceptive and neuroendocrine responses. PMID:12114296

  13. MSC response to pH levels found in degenerating intervertebral discs

    SciTech Connect

    Wuertz, Karin Godburn, Karolyn; Iatridis, James C.

    2009-02-20

    Painful degenerative disc disease is a major health problem and for successful tissue regeneration, MSCs must endure and thrive in a harsh disc microenvironment that includes matrix acidity as a critical factor. MSCs were isolated from bone marrow of Sprague-Dawley rats from two different age groups (<1 month, n = 6 and 4-5 months, n = 6) and cultured under four different pH conditions representative of the healthy, mildly or severely degenerated intervertebral disc (pH 7.4, 7.1, 6.8, and 6.5) for 5 days. Acidity caused an inhibition of aggrecan, collagen-1, and TIMP-3 expression, as well as a decrease in proliferation and viability and was associated with a change in cell morphology. Ageing had generally minor effects but young MSCs maintained greater mRNA expression levels. As acidic pH levels are typical of increasingly degenerated discs, our findings demonstrate the importance of early interventions and predifferentiation when planning to use MSCs for reparative treatments.

  14. ISSLS PRIZE WINNER: INHIBITION OF NF-κB ACTIVITY AMELIORATES AGE-ASSOCIATED DISC DEGENERATION IN A MOUSE MODEL OF ACCELERATED AGING

    PubMed Central

    Nasto, Luigi A.; Seo, Hyoung-Yeon; Robinson, Andria R.; Tilstra, Jeremy S.; Clauson, Cheryl L.; Sowa, Gwendolyn A.; Ngo, Kevin; Dong, Qing; Pola, Enrico; Lee, Joon Y.; Niedernhofer, Laura J.; Kang, James D.; Robbins, Paul D.; Vo, Nam V.

    2012-01-01

    Study Design NF-κB activity was pharmacologically and genetically blocked in an accelerated aging mouse model to mitigate age-related disc degenerative changes. Objective To study the mediatory role of NF-κB signaling pathway in age-dependent intervertebral disc degeneration. Summary of Background Data Aging is a major contributor to intervertebral disc degeneration (IDD), but the molecular mechanism behind this process is poorly understood. NF-κB is a family of transcription factors which play a central role in mediating cellular response to damage, stress, and inflammation. Growing evidence implicates chronic NF-κB activation as a culprit in many aging-related diseases, but its role in aging-related IDD has not been adequately explored. We studied the effects of NF-κB inhibition on IDD using a DNA repair-deficient mouse model of accelerated aging (Ercc1-/Δ mice) previously been reported to exhibit age-related IDD. Methods Systemic inhibition of NF-κB activation was achieved either genetically by deletion of one allele of the NF-κB subunit p65 (Ercc1-/Δp65+/- mice) or pharmacologically by chronic intra-peritoneal administration of the Nemo Binding Domain (8K-NBD) peptide to block the formation of the upstream activator of NF-κB, IκB Inducible Kinase (IKK), in Ercc1-/Δ mice. Disc cellularity, total proteoglycan content and proteoglycan synthesis of treated mice and untreated controls were assessed. Results Decreased disc matrix proteoglycan content, a hallmark feature of IDD, and elevated disc NF-κB activity were observed in discs of progeroid Ercc1-/Δ mice and naturally aged wild-type compared to young WT mice. Systemic inhibition of NF-κB by the 8K-NBD peptide in Ercc1-/Δ mice increased disc proteoglycan synthesis and ameriolated loss disc cellularity and matrix proteoglycan. These results were confirmed genetically by using the p65 haploinsufficient Ercc1-/Δp65+/- mice. Conclusion These findings demonstrate that the IKK/NF-κB signaling pathway

  15. Cordycepin inhibits LPS-induced inflammatory and matrix degradation in the intervertebral disc.

    PubMed

    Li, Yan; Li, Kang; Mao, Lu; Han, Xiuguo; Zhang, Kai; Zhao, Changqing; Zhao, Jie

    2016-01-01

    Cordycepin is a component of the extract obtained from Cordyceps militaris and has many biological activities, including anti-cancer, anti-metastatic and anti-inflammatory effects. Intervertebral disc degeneration (IDD) is a degenerative disease that is closely related to the inflammation of nucleus pulposus (NP) cells. The effect of cordycepin on NP cells in relation to inflammation and degeneration has not yet been studied. In our study, we used a rat NP cell culture and an intervertebral disc (IVD) organ culture model to examine the inhibitory effects of cordycepin on lipopolysaccharide (LPS)-induced gene expression and the production of matrix degradation enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5) and oxidative stress-associated factors (nitric oxide and PGE2). We found a protective effect of cordycepin on NP cells and IVDs against LPS-induced matrix degradation and macrophage infiltration. In addition, western blot and luciferase assay results demonstrated that pretreatment with cordycepin significantly suppressed the LPS-induced activation of the NF-κB pathway. Taken together, the results of our research suggest that cordycepin could exert anti-inflammatory and anti-degenerative effects on NP cells and IVDs by inhibiting the activation of the NF-κB pathway. Therefore, cordycepin may be a potential treatment for IDD in the future. PMID:27190710

  16. Cordycepin inhibits LPS-induced inflammatory and matrix degradation in the intervertebral disc

    PubMed Central

    Mao, Lu; Han, Xiuguo; Zhang, Kai; Zhao, Changqing

    2016-01-01

    Cordycepin is a component of the extract obtained from Cordyceps militaris and has many biological activities, including anti-cancer, anti-metastatic and anti-inflammatory effects. Intervertebral disc degeneration (IDD) is a degenerative disease that is closely related to the inflammation of nucleus pulposus (NP) cells. The effect of cordycepin on NP cells in relation to inflammation and degeneration has not yet been studied. In our study, we used a rat NP cell culture and an intervertebral disc (IVD) organ culture model to examine the inhibitory effects of cordycepin on lipopolysaccharide (LPS)-induced gene expression and the production of matrix degradation enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5) and oxidative stress-associated factors (nitric oxide and PGE2). We found a protective effect of cordycepin on NP cells and IVDs against LPS-induced matrix degradation and macrophage infiltration. In addition, western blot and luciferase assay results demonstrated that pretreatment with cordycepin significantly suppressed the LPS-induced activation of the NF-κB pathway. Taken together, the results of our research suggest that cordycepin could exert anti-inflammatory and anti-degenerative effects on NP cells and IVDs by inhibiting the activation of the NF-κB pathway. Therefore, cordycepin may be a potential treatment for IDD in the future. PMID:27190710

  17. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

    PubMed Central

    Kell, Douglas B

    2009-01-01

    Background The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular 'reactive oxygen species' (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. Review We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, since in some circumstances (especially the presence of poorly liganded iron) molecules that are nominally antioxidants can actually act as pro-oxidants. The reduction of redox

  18. Novel BAC mouse model of Huntington’s disease with 225 CAG repeats exhibits an early widespread and stable degenerative phenotype

    PubMed Central

    Wegrzynowicz, Michal; Bichell, Terry Jo; Soares, Barbara D.; Loth, Meredith K.; McGlothan, Jennifer L.; Alikhan, Fatima S.; Hua, Kegang; Coughlin, Jennifer M.; Holt, Hunter K.; Jetter, Christopher S.; Mori, Susumu; Pomper, Martin G.; Osmand, Alexander P.; Guilarte, Tomás R.; Bowman, Aaron B.

    2015-01-01

    BACKGROUND Unusually large CAG repeat expansions (>60) in exon one of Huntingtin (HTT) are invariably associated with a juvenile-onset form of Huntington’s disease (HD), characterized by a more extensive and rapidly progressing neuropathology than the more prevalent adult-onset form. However, existing mouse models of HD that express the full-length Htt gene with CAG repeat lengths associated with juvenile HD (ranging between ~75 to ~150 repeats in published models) exhibit selective neurodegenerative phenotypes more consistent with adult-onset HD. OBJECTIVE To determine if a very large CAG repeat (>200) in full-length Htt elicits neurodegenerative phenotypes consistent with juvenile HD. METHODS Using a bacterial artificial chromosome (BAC) system, we generated mice expressing full-length mouse Htt with ~225 CAG repeats under control of the mouse Htt promoter. Mice were characterized using behavioral, neuropathological, biochemical and brain imaging methods. RESULTS BAC-225Q mice exhibit phenotypes consistent with a subset of features seen in juvenile-onset HD: very early motor behavior abnormalities, reduced body weight, widespread and progressive increase in Htt aggregates, gliosis, and neurodegeneration. Early striatal pathology was observed, including reactive gliosis and loss of dopamine receptors, prior to detectable volume loss. HD-related blood markers of impaired energy metabolism and systemic inflammation were also increased. Aside from an age-dependent progression of diffuse nuclear aggregates at 6 months of age to abundant neuropil aggregates at 12 months of age, other pathological and motor phenotypes showed little to no progression. CONCLUSIONS The HD phenotypes present in animals 3 to 12 months of age make the BAC-225Q mice a unique and stable model of full-length mutant Htt associated phenotypes, including body weight loss, behavioral impairment and HD-like neurodegenerative phenotypes characteristic of juvenile-onset HD and/or late-stage adult

  19. Treatment of symptomatic lumbar spinal degenerative pathologies by means of combined conservative biochemical treatments.

    PubMed

    Alexandre, A; Corò, L; Paradiso, R; Dall'aglio, R; Alexandre, A M; Fraschini, F; Spaggiari, P G

    2011-01-01

    Research in spine surgery has proposed new soft and less invasive techniques. These are the results of our experience with oxygen-ozone therapy, which we could experiment within the Italian National Health System over 3 years. A total of 1,920 patients were admitted on the basis of unselected enrolment because of lumbosciatic pain. Patients were divided into three groups: (A) Patients with degenerative disc disease and arthropathy: 509 (26.5%), (B) Patients with failed back surgery syndrome (FBSS): 1,027 (53.489%), and (C) Patients with pure herniated lumbar disc: 384 (20%). The rationale of the treatment for all these different pathologies we have taken into consideration is the biochemical mechanism by which they can engender pain and dysfunction. Treatment for group A: paravertebral injection and phleboclysis (two cycles of 6 sessions, one each 3 days) +endoscopic neurolysis. Treatment for group B: paravertebral injection and phleboclysis (two cycles of 6 sessions, one each 3 days) + endoscopic neurolysis with intradiscal procedure (named percutaneous peridurodiscolysis). Treatment for group C: paravertebral injection (two cycles of 6 sessions, one each 3 days) + percutaneous discolysis.The perceived quality of result for this minimally invasive procedure makes oxygen-ozone therapy an interesting weapon in the hands of doctors. Furthermore, if the technique loses its clinical effectiveness, it can be repeated without harm for the patient, and costs for the health organization are notably very low, above all if compared to surgical procedures.We underline the need that this treatment should be performed in protected structures, in operative rooms, under anesthesiologic control, and in the hands of specialists. PMID:21107949

  20. A Comparison of Magnetic Resonance Imaging Muscle Fat Content in the Lumbar Paraspinal Muscles with Patient-Reported Outcome Measures in Patients with Lumbar Degenerative Disk Disease and Focal Disk Prolapse.

    PubMed

    Bhadresha, Ashwin; Lawrence, Owen John; McCarthy, Michael J H

    2016-06-01

    Study Design Retrospective study. Objectives To assess the fatty atrophy of the lumbar paraspinal muscles (LPMs) as determined using magnetic resonance imaging in patients with lumbar degenerative disk disease (DDD) and focal disk herniation and to determine if fatty atrophy is associated with patient-reported outcome measures (PROMS). Methods One hundred sixty-five patients with lumbar DDD were identified from a PROMS database of >1,500 patients. These patients were divided into two study groups: DDD alone (n = 58) and DDD with disk herniation (n = 107). A grid was randomly applied to the axial scans at the L3-L4, L4-L5, and L5-S1 levels. The muscle-to-fat ratio of the LPMs was recorded and compared with PROMS data. Subcutaneous fat thickness at each level was also measured. Results This study found no difference in the muscle-to-fat ratio between the DDD and disk herniation groups. There was no association between the muscle-to-fat ratio and PROMS data in either group. There was significantly more subcutaneous fat at all levels in the DDD group as compared with the disk prolapse group. In DDD and disk prolapses, subcutaneous fat was thicker in women (p = 0.013 and 0.001). In patients with DDD, more subcutaneous fat was associated with disability (p < 0.001). Muscle content of erector spinae and multifidus negatively correlated with increasing age in both groups at the L3-L4 level. Conclusions Muscle fat content in the LPM does not appear to relate to PROMS. Muscle content decreases with age. Those with low back pain (DDD) have greater subcutaneous fat thickness. PMID:27190744

  1. A Comparison of Magnetic Resonance Imaging Muscle Fat Content in the Lumbar Paraspinal Muscles with Patient-Reported Outcome Measures in Patients with Lumbar Degenerative Disk Disease and Focal Disk Prolapse

    PubMed Central

    Bhadresha, Ashwin; Lawrence, Owen John; McCarthy, Michael J. H.

    2016-01-01

    Study Design Retrospective study. Objectives To assess the fatty atrophy of the lumbar paraspinal muscles (LPMs) as determined using magnetic resonance imaging in patients with lumbar degenerative disk disease (DDD) and focal disk herniation and to determine if fatty atrophy is associated with patient-reported outcome measures (PROMS). Methods One hundred sixty-five patients with lumbar DDD were identified from a PROMS database of >1,500 patients. These patients were divided into two study groups: DDD alone (n = 58) and DDD with disk herniation (n = 107). A grid was randomly applied to the axial scans at the L3–L4, L4–L5, and L5–S1 levels. The muscle-to-fat ratio of the LPMs was recorded and compared with PROMS data. Subcutaneous fat thickness at each level was also measured. Results This study found no difference in the muscle-to-fat ratio between the DDD and disk herniation groups. There was no association between the muscle-to-fat ratio and PROMS data in either group. There was significantly more subcutaneous fat at all levels in the DDD group as compared with the disk prolapse group. In DDD and disk prolapses, subcutaneous fat was thicker in women (p = 0.013 and 0.001). In patients with DDD, more subcutaneous fat was associated with disability (p < 0.001). Muscle content of erector spinae and multifidus negatively correlated with increasing age in both groups at the L3–L4 level. Conclusions Muscle fat content in the LPM does not appear to relate to PROMS. Muscle content decreases with age. Those with low back pain (DDD) have greater subcutaneous fat thickness. PMID:27190744

  2. Seven-year cost-effectiveness of ProDisc-C total disc replacement: results from investigational device exemption and post-approval studies.

    PubMed

    Radcliff, Kris; Lerner, Jason; Yang, Chao; Bernard, Thierry; Zigler, Jack E

    2016-05-01

    OBJECTIVE The purpose of this study was to evaluate the 7-year cost-effectiveness of cervical total disc replacement (CTDR) versus anterior cervical discectomy and fusion (ACDF) for the treatment of patients with single-level symptomatic degenerative disc disease. A change in the spending trajectory for spine care is to be achieved, in part, through the selection of interventions that have been proven effective yet cost less than other options. This analysis complements and builds upon findings from other cost-effectiveness evaluations of CTDR through the use of long-term, patient-level data from a randomized study. METHODS This was a 7-year health economic evaluation comparing CTDR versus ACDF from the US commercial payer perspective. Prospectively collected health care resource utilization and treatment effects (quality-adjusted life years [QALYs]) were obtained from individual patient-level adverse event reports and SF-36 data, respectively, from the randomized, multicenter ProDisc-C total disc replacement investigational device exemption (IDE) study and post-approval study. Statistical distributions for unit costs were derived from a commercial claims database and applied using Monte Carlo simulation. Patient-level costs and effects were modeled via multivariate probabilistic analysis. Confidence intervals for 7-year costs, effects, and net monetary benefit (NMB) were obtained using the nonparametric percentile method from results of 10,000 bootstrap simulations. The robustness of results was assessed through scenario analysis and within a parametric regression model controlling for baseline variables. RESULTS Seven-year follow-up data were available for more than 70% of the 209 randomized patients. In the base-case analysis, CTDR resulted in mean per-patient cost savings of $12,789 (95% CI $5362-$20,856) and per-patient QALY gains of 0.16 (95% CI -0.073 to 0.39) compared with ACDF over 7 years. CTDR was more effective and less costly in 90.8% of probabilistic

  3. Long term preservation of motion with artificial cervical disc implants: A comparison between cervical disc replacement and rigid fusion with cage

    PubMed Central

    Cincu, Rafael; Lorente, Francisco de Asis; Gomez, Joaquin; Eiras, Jose; Agrawal, Amit

    2014-01-01

    Background: With the advancement of technologies there is more interest in the maintenance of the spine's biomechanical properties focusing on the preservation of the functional motion segment. In present article we describe our experience with 25 cases managed with artificial cervical discs with 28 Solis cage following cervical discectomy with a mean follow-up period of 7.5 year. Materials and Methods: All surgeries were performed by single surgeon from March 2004 to June 2005 with a follow-up till date. Patients with symptomatic single or multiple level diseases that had no prior cervical surgery were candidates for the study. Cohort demographics were comparable. Standardized clinical outcome measures and radiographic examinations were used at prescribed post-operative intervals to compare the treatment groups. Relief in radicular pain, cervical spine motion, and degenerative changes at follow-up were noted. Results: In a total 53 cases, the mean age in prosthesis group was 47 years (age range: 30-63 years) and mean age in cage group was 44 years (32-62 years). Mean hospital stay was 2.7 days in both the groups. At 4 weeks complete cervical movements could be achieved in 19 cases in artificial disc group. Maintenance of movement after 7.5 years was in 76% of these patients. Lordosis was maintained in all cases till date. There was no mortality or wound infection in our series. Conclusions: We conclude that artificial cervical disc could be an alternative to fixed spinal fusion as it represents the most physiological substitute of disc. However, there is need for further studies to support the use of artificial cervical disc prosthesis. PMID:25685218

  4. Using Nutrition Against Aging and Degenerative Disease.

    ERIC Educational Resources Information Center

    Rokosz, Francis M.

    A review of historical and research literature presents various perspectives on the growing controversy surrounding the use of vitamin and mineral supplements to maintain good health and for preventive health care. Several points are made in opposition to many health professionals' opinions that most nutritional supplements are unnecessary.…

  5. Cartilage tissue engineering for degenerative joint disease.

    PubMed

    Nesic, Dobrila; Whiteside, Robert; Brittberg, Mats; Wendt, David; Martin, Ivan; Mainil-Varlet, Pierre

    2006-05-20

    Pain in the joint is often due to cartilage degeneration and represents a serious medical problem affecting people of all ages. Although many, mostly surgical techniques, are currently employed to treat cartilage lesions, none has given satisfactory results in the long term. Recent advances in biology and material science have brought tissue engineering to the forefront of new cartilage repair techniques. The combination of autologous cells, specifically designed scaffolds, bioreactors, mechanical stimulations and growth factors together with the knowledge that underlies the principles of cell biology offers promising avenues for cartilage tissue regeneration. The present review explores basic biology mechanisms for cartilage reconstruction and summarizes the advances in the tissue engineering approaches. Furthermore, the limits of the new methods and their potential application in the osteoarthritic conditions are discussed. PMID:16574268

  6. A Double-Blind, Placebo-Controlled, Parallel-Group Pilot Study of Milnacipran for Chronic Radicular Pain (Sciatica) Associated With Lumbosacral Disc Disease

    PubMed Central

    Pae, Chi-Un; Patkar, Ashwin A.

    2014-01-01

    Objective: The current study investigates whether milnacipran, an equipotent serotonin-norepinephrine reuptake inhibitor, is effective in reducing chronic radicular pain in patients (N = 11) with lumbosacral disc disease. Method: This study is a 10-week randomized, parallel-group, double-blind, placebo-controlled trial of milnacipran (100–200 mg/d, dosed twice a day). Subjects (enrolled from October 2010 to September 2011 through the Duke University Pain and Palliative Care Clinic, Durham, North Carolina) included patients with radiologically confirmed disc disease with nerve root compression. The primary outcome measure was radicular pain measured by visual analog scale score (VAS-Rad); patients were asked to specifically rate radicular pain (“shooting or electrical or prickly pain in 1 or both legs”). Secondary outcome measures included nociceptive low back pain by visual analog scale (VAS-Noc), Oswestry Low Back Pain Disability Questionnaire, Neuropathic Pain Questionnaire, Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey, Beck Depression Inventory, and State-Trait Anxiety Inventory. Between-group changes in outcome measures between baseline and endpoint were analyzed using Mann-Whitney U nonparametric measure of central tendency. Results: Milnacipran treatment yielded statistically significant reduction in radicular pain (VAS-Rad, P = .01) and nociceptive low back pain (VAS-Noc, P = .04) compared to placebo. No statistically significant between-group differences were observed in the other secondary outcome measures. Conclusions: In this small pilot study, milnacipran treatment was associated with reduction in radicular and nociceptive low back pain in patients with lumbosacral disc disease. Larger studies of milnacipran in this population are warranted. Trial Registration: ClinicalTrials.gov identifier: NCT01777581. PMID:25664215

  7. Comparison of Posterior Lumbar Interbody Fusion and Posterolateral Lumbar Fusion in Monosegmental Vacuum Phenomenon within an Intervertebral Disc

    PubMed Central

    An, Ki-Chan; Kong, Gyu-Min; Park, Dae-Hyun; Youn, Ji-Hong; Lee, Woon-Seong

    2016-01-01

    Study Design Retrospective. Purpose To compare the clinical and radiological outcomes of posterolateral lumbar interbody fusion (PLIF) and posterolateral lumbar fusion (PLF) in monosegmental vacuum phenomenon within an intervertebral disc. Overview of Literature The vacuum phenomenon within an intervertebral disc is a serious form of degenerative disease that destabilizes the intervertebral body. Outcomes of PLIF and PLF in monosegmental vacuum phenomenon are unclear. Methods Monosegmental instrumented PLIF and PLF was performed on 84 degenerative lumbar disease patients with monosegmental vacuum phenomenon (PLIF, n=38; PLF, n=46). Minimum follow-up was 24 months. Clinical outcomes of leg and back pain were assessed using visual analogue scales for leg pain (LVAS) and back pain (BVAS), and the Oswestry disability index (ODI). The radiographic outcome was the estimated bony union rate. Results LVAS, BVAS, and ODI improved in both groups. There was no significant difference in the degree of these improvements between PLIF and PLF patients (p>0.05). Radiological union rate was 91.1% in PLIF group and 89.4% in PLF group at postoperative 24 months (p>0.05). Conclusions No significant differences in clinical results and union rates were found between PLIF and PLF patients. Selection of the operation technique will reflect the surgeon's preferences and patient condition. PMID:26949464

  8. Janus discs.

    PubMed

    Walther, Andreas; André, Xavier; Drechsler, Markus; Abetz, Volker; Müller, Axel H E

    2007-05-16

    We describe the synthesis and the solution properties of sheet- and disclike Janus particles, containing an inner crosslinked polybutadiene (PB) layer and two different outer sides of polystyrene (PS) and poly(tert-butyl methacrylate) (PtBMA). The structures formed upon adsorption of the flat Janus particles onto solid substrates as well as in THF solution are investigated. The Janus discs are obtained in a template-assisted synthetic pathway followed by sonication. Selectively crosslinking the lamellar PB domains in a well-ordered lamellar microphase-separated bulk morphology of PS-block-PB-block-PtBMA (SBT) block terpolymers leads to the conservation of the compartmentalization of the two outer blocks. Sonication of the crosslinked block terpolymer templates renders soluble sheet- and disclike Janus particles, the size of which can be tuned from the micrometer range down to the nanometer scale. Small-angle X-ray scattering, transmission electron microscopy, dynamic light scattering, scanning force microscopy, and scanning electron microscopy are used to characterize the template-assisted synthetic process and the solution properties. Cryogenic transmission electron microscopy in THF and TEM of particles, embedded into a photo-crosslinkable silicon oil, indicate a supramolecular aggregation behavior of the Janus discs in concentrated solutions. Pendant drop tensiometry demonstrates that Janus sheets and discs can be used to stabilize liquid-liquid interfaces, rendering these materials interesting for future applications. PMID:17441717

  9. Assessment of Magnetic Resonance Imaging Artifact Following Cervical Total Disc Arthroplasty

    PubMed Central

    Fayyazi, Amir H.; Taormina, Jennifer; Svach, David; Stein, Jeff

    2015-01-01

    Background Cervical disc arthroplasty has become a technique for the treatment of cervical degenerative disc disease. Clinically, the need to accurately assess the neural elements at the operative and adjacent levels is critical postoperatively. The purpose of this study was to quantitatively and qualitatively measure the amount of MRI artifact produced by various cervical total disc replacements. Methods T1 and T2-weighted turbo spin-echo MRI sequences were collected on the cervical spine (C2-T1) of a 68 year-old unembalmed male cadaver. A discectomy was performed at C5-6, followed by successive implantation of six different total disc replacements. The scans were quantitatively evaluated by three of the authors. The volume of artifact was measured using image analysis software. Qualitative analysis of the adjacent and index neural elements was performed. Results The artifact in the T2 weighted images was noted to be 58.6±7.3 cm3 for Prestige ST, 14.2±1.3 cm3 for ProDisc-C, 7.5±0.8 cm3 for Discover, 8.0±0.3 cm3 for Prestige LP, 6.6±0.7 cm3 for Bryan, and 7.3±0.6 cm3 for ProDisc-C titanium prototype. Acceptable intraobserver and excellent interobsever correlation was demonstrated using Pearson Correlation and Concordance Correlation Coefficient analysis. The adjacent and implanted level neural elements (spinal cord and neuroforamina) were easily visualized on the T2 weighted images after the implantation of titanium devices (ProDisc-C titanium prototype, Discover, Prestige LP and Bryan). After implantation of a cobalt chrome implant (ProDisc-C), the adjacent level neural elements were easily visualized but the implanted level could not be fully visualized due to distortion of the images. The quality of the distortion was least favorable after the implantation of the stainless steel implant (Prestige ST), where neither the adjacent nor the index level could be fully visualized. Conclusion The volume of the artifact seen following cervical total disc

  10. Effect of intervertebral disc degeneration on disc cell viability: a numerical investigation.

    PubMed

    Galbusera, Fabio; Mietsch, Antje; Schmidt, Hendrik; Wilke, Hans-Joachim; Neidlinger-Wilke, Cornelia

    2013-01-01

    Degeneration of the intervertebral disc may be initiated and supported by impairment of the nutrition processes of the disc cells. The effects of degenerative changes on cell nutrition are, however, only partially understood. In this work, a finite volume model was used to investigate the effect of endplate calcification, water loss, reduction of disc height and cyclic mechanical loading on the sustainability of the disc cell population. Oxygen, lactate and glucose diffusion, production and consumption were modelled with non-linear coupled partial differential equations. Oxygen and glucose consumption and lactate production were expressed as a function of local oxygen concentration, pH and cell density. The cell viability criteria were based on local glucose concentration and pH. Considering a disc with normal water content, cell death was initiated in the centre of the nucleus for oxygen, glucose, and lactate diffusivities in the cartilaginous endplate below 20% of the physiological values. The initial cell population could not be sustained even in the non-calcified endplates when a reduction of diffusion inside the disc due to water loss was modelled. Alterations in the disc shape such as height loss, which shortens the transport route between the nutrient sources and the cells, and cyclic mechanical loads, could enhance cell nutrition processes. PMID:21970697

  11. A combinatorial relative mass value evaluation of endogenous bioactive proteins in three-dimensional cultured nucleus pulposus cells of herniated intervertebral discs: identification of potential target proteins for gene therapeutic approaches.

    PubMed

    Mern, Demissew S; Fontana, Johann; Beierfuß, Anja; Thomé, Claudius; Hegewald, Aldemar A

    2013-01-01

    Painful degenerative disc diseases have been targeted by different biological treatment approaches. Nucleus pulposus (NP) cells play a central role in intervertebral disc (IVD) maintenance by orchestrating catabolic, anabolic and inflammatory factors that affect the extracellular matrix. IVD degeneration is associated with imbalances of these factors, resulting in a catabolic inflammatory metabolism. Therefore, accurate knowledge about their quantity and quality with regard to matrix synthesis is vital for a rational gene therapeutic approach. NP cells were isolated from 63 patients operated due to lumbar disc herniation (mean age 56 / range 29 - 84 years). Then, three-dimensional culture with low-glucose was completed in a collagen type I scaffold for four weeks. Subsequently cell proliferation evaluation was performed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and intracellular concentration of 28 endogenously expressed anabolic, catabolic, inflammatory factors and relevant matrix proteins was determined by enzyme-linked immunosorbent assay. Specimen-related grades of degeneration were confirmed by preoperative magnetic resonance imaging. Independent from gender, age and grade of degeneration proliferation rates remained similar in all groups of NP cells. Progressive grades of degeneration, however, showed a significant influence on accumulation of selective groups of factors such as disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix metalloproteinase 3, metalloproteinase inhibitor 1 and 2, interleukin-1β and interleukin-1 receptor. Along with these changes, the key NP matrix proteins aggrecan and collagen II decreased significantly. The concentration of anabolic factors bone morphogenetic proteins 2, 4, 6 and 7, insulin-like growth factor 1, transforming growth factor beta 1 and 3, however, remained below the minimal detectable quantities. These findings indicate that progressive degenerative changes in NP may

  12. A Combinatorial Relative Mass Value Evaluation of Endogenous Bioactive Proteins in Three-Dimensional Cultured Nucleus Pulposus Cells of Herniated Intervertebral Discs: Identification of Potential Target Proteins for Gene Therapeutic Approaches

    PubMed Central

    Mern, Demissew S.; Fontana, Johann; Beierfuß, Anja; Thomé, Claudius; Hegewald, Aldemar A.

    2013-01-01

    Painful degenerative disc diseases have been targeted by different biological treatment approaches. Nucleus pulposus (NP) cells play a central role in intervertebral disc (IVD) maintenance by orchestrating catabolic, anabolic and inflammatory factors that affect the extracellular matrix. IVD degeneration is associated with imbalances of these factors, resulting in a catabolic inflammatory metabolism. Therefore, accurate knowledge about their quantity and quality with regard to matrix synthesis is vital for a rational gene therapeutic approach. NP cells were isolated from 63 patients operated due to lumbar disc herniation (mean age 56 / range 29 - 84 years). Then, three-dimensional culture with low-glucose was completed in a collagen type I scaffold for four weeks. Subsequently cell proliferation evaluation was performed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and intracellular concentration of 28 endogenously expressed anabolic, catabolic, inflammatory factors and relevant matrix proteins was determined by enzyme-linked immunosorbent assay. Specimen-related grades of degeneration were confirmed by preoperative magnetic resonance imaging. Independent from gender, age and grade of degeneration proliferation rates remained similar in all groups of NP cells. Progressive grades of degeneration, however, showed a significant influence on accumulation of selective groups of factors such as disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix metalloproteinase 3, metalloproteinase inhibitor 1 and 2, interleukin-1β and interleukin-1 receptor. Along with these changes, the key NP matrix proteins aggrecan and collagen II decreased significantly. The concentration of anabolic factors bone morphogenetic proteins 2, 4, 6 and 7, insulin-like growth factor 1, transforming growth factor beta 1 and 3, however, remained below the minimal detectable quantities. These findings indicate that progressive degenerative changes in NP may

  13. Coxofemoral joint laxity from distraction radiography and its contemporaneous and prospective correlation with laxity, subjective score, and evidence of degenerative joint disease from conventional hip-extended radiography in dogs.

    PubMed

    Smith, G K; Gregor, T P; Rhodes, W H; Biery, D N

    1993-07-01

    A 3-year prospective study of large-breed dogs (4 months to 3 years of age) was conducted to evaluate the influence of radiographic positioning and age on coxofemoral joint (hip) laxity, subjective hip score, and development of degenerative joint disease (DJD). The dogs (n = 142) were breeder- or client-owned and represented 14 breeds. With dogs under heavy sedation, hips were radiographed in the standard hip-extended position and in the new compression/distraction position at 4, 6, 12, 24, and 36 months of age. The standard hip-extended radiographic view was evaluated by 3 methods: subjective evaluation by a board-certified veterinary radiologist (WHR), according to the standard 7-point Orthopedic Foundation for Animals (OFA) scoring scheme (OFA/WHR); joint laxity quantitation, using the Norberg angle (NA) method; and subjective scoring by a veterinary orthopedic surgeon for radiographic evidence of DJD. The hips in the distraction radiographic view were evaluated for passive hip laxity, as measured by use of a unitless distraction index (DI). Results of the study indicated that at a specific age (4, 6, 12, 24, or 36 months), all methods of hip evaluation correlated with each other at a moderate level (P < 0.05). The strength of contemporaneous correlation tended to increase with age of evaluation. Longitudinally, the between-method correlations were usually significant (P < 0.05), but not at a sufficiently high level to permit reliable between-method prediction. Prospective intraclass (within-method) statistical analysis of the various hip-scoring methods indicated that DI was superior to NA and OFA/WHR in comparability of score over time. The intraclass correlation coefficient ranged from 0.55 to 0.91 for DI in contrast to 0.40 to 0.78 for NA, and 0.06 to 0.39 for OFA/WHR over the age intervals of the study. For reference, the highest Kappa of 0.39 for the subjective OFA/WHR scoring reflected a maximal level of agreement between time intervals, only slightly

  14. TGFβ and BMP Dependent Cell Fate Changes Due to Loss of Filamin B Produces Disc Degeneration and Progressive Vertebral Fusions.

    PubMed

    Zieba, Jennifer; Forlenza, Kimberly Nicole; Khatra, Jagteshwar Singh; Sarukhanov, Anna; Duran, Ivan; Rigueur, Diana; Lyons, Karen M; Cohn, Daniel H; Merrill, Amy E; Krakow, Deborah

    2016-03-01

    Spondylocarpotarsal synostosis (SCT) is an autosomal recessive disorder characterized by progressive vertebral fusions and caused by loss of function mutations in Filamin B (FLNB). FLNB acts as a signaling scaffold by linking the actin cytoskleteon to signal transduction systems, yet the disease mechanisms for SCT remain unclear. Employing a Flnb knockout mouse, we found morphologic and molecular evidence that the intervertebral discs (IVDs) of Flnb-/-mice undergo rapid and progressive degeneration during postnatal development as a result of abnormal cell fate changes in the IVD, particularly the annulus fibrosus (AF). In Flnb-/-mice, the AF cells lose their typical fibroblast-like characteristics and acquire the molecular and phenotypic signature of hypertrophic chondrocytes. This change is characterized by hallmarks of endochondral-like ossification including alterations in collagen matrix, expression of Collagen X, increased apoptosis, and inappropriate ossification of the disc tissue. We show that conversion of the AF cells into chondrocytes is coincident with upregulated TGFβ signaling via Smad2/3 and BMP induced p38 signaling as well as sustained activation of canonical and noncanonical target genes p21 and Ctgf. These findings indicate that FLNB is involved in attenuation of TGFβ/BMP signaling and influences AF cell fate. Furthermore, we demonstrate that the IVD disruptions in Flnb-/-mice resemble aging degenerative discs and reveal new insights into the molecular causes of vertebral fusions and disc degeneration. PMID:27019229

  15. BMP7 enhances the effect of BMSCs on extracellular matrix remodeling in a rabbit model of intervertebral disc degeneration.

    PubMed

    Xu, Jun; E, Xiao-Qiang; Wang, Nan-Xiang; Wang, Mo-Nan; Xie, Huan-Xin; Cao, Yan-Hui; Sun, Li-Hua; Tian, Jun; Chen, Hua-Jiang; Yan, Jing-Long

    2016-05-01

    Intervertebral discs (IVDs) provide stability and flexibility to the spinal column; however, IVDs, and in particular the nucleus pulposus (NP), undergo a degenerative process characterized by changes in the disc extracellular matrix (ECM), decreased cell viability, and reduced synthesis of proteoglycan and type II collagen. Here, we investigated the efficacy and feasibility of stem cell therapy using bone marrow mesenchymal stem cells (BMSCs) over-expressing bone morphogenetic protein 7 (BMP7) to promote ECM remodeling of degenerated IVDs. Lentivirus-mediated BMP7 over-expression induced differentiation of BMSCs into an NP phenotype, as indicated by expression of the NP markers collagen type II, aggrecan, SOX9 and keratins 8 and 19, increased the content of glycosaminoglycan, and up-regulated β-1,3-glucuronosyl transferase 1, a regulator of chondroitin sulfate synthesis in NP cells. These effects were suppressed by Smad1 silencing, indicating that the effect of BMP7 on ECM remodeling was mediated by the Smad pathway. In vivo analysis in a rabbit model of disc degeneration showed that implantation of BMSCs over-expressing BMP7 promoted cell differentiation and proliferation in the NP, as well as their own survival, and these effects were mediated by the Smad pathway. The results of the present study indicate the beneficial effects of BMP7 on restoring ECM homeostasis in NP cells, and suggest potential strategies for improving cell therapy for the treatment of disc diseases. PMID:26929154

  16. TGFβ and BMP Dependent Cell Fate Changes Due to Loss of Filamin B Produces Disc Degeneration and Progressive Vertebral Fusions

    PubMed Central

    Zieba, Jennifer; Forlenza, Kimberly Nicole; Khatra, Jagteshwar Singh; Sarukhanov, Anna; Duran, Ivan; Rigueur, Diana; Lyons, Karen M.; Cohn, Daniel H.; Merrill, Amy E.; Krakow, Deborah

    2016-01-01

    Spondylocarpotarsal synostosis (SCT) is an autosomal recessive disorder characterized by progressive vertebral fusions and caused by loss of function mutations in Filamin B (FLNB). FLNB acts as a signaling scaffold by linking the actin cytoskleteon to signal transduction systems, yet the disease mechanisms for SCT remain unclear. Employing a Flnb knockout mouse, we found morphologic and molecular evidence that the intervertebral discs (IVDs) of Flnb–/–mice undergo rapid and progressive degeneration during postnatal development as a result of abnormal cell fate changes in the IVD, particularly the annulus fibrosus (AF). In Flnb–/–mice, the AF cells lose their typical fibroblast-like characteristics and acquire the molecular and phenotypic signature of hypertrophic chondrocytes. This change is characterized by hallmarks of endochondral-like ossification including alterations in collagen matrix, expression of Collagen X, increased apoptosis, and inappropriate ossification of the disc tissue. We show that conversion of the AF cells into chondrocytes is coincident with upregulated TGFβ signaling via Smad2/3 and BMP induced p38 signaling as well as sustained activation of canonical and noncanonical target genes p21 and Ctgf. These findings indicate that FLNB is involved in attenuation of TGFβ/BMP signaling and influences AF cell fate. Furthermore, we demonstrate that the IVD disruptions in Flnb–/–mice resemble aging degenerative discs and reveal new insights into the molecular causes of vertebral fusions and disc degeneration. PMID:27019229

  17. Copeptin constitutes a novel biomarker of degenerative aortic stenosis.

    PubMed

    Mizia-Stec, Katarzyna; Lasota, Bartosz; Mizia, Magdalena; Chmiel, Artur; Adamczyk, Tomasz; Chudek, Jerzy; Gasior, Zbigniew

    2013-09-01

    Copeptin is a new biomarker of cardiovascular diseases. Its diagnostic value in degenerative aortic valve stenosis (AS) with preserved left ventricle systolic function is unknown. We aimed to assess the association of serum copeptin levels with AS severity and coexistence of coronary artery disease (CAD). Sixty-four patients with AS and preserved left ventricle systolic function including 40 with severe degenerative AS (group sAS, effective orifice area EOA = 0.67 cm(2)) and 24 with moderate degenerative AS (group mAS, EOA = 1.40 cm(2)) were enrolled into the study. Twenty-three patients without AS and heart failure, matched for age, sex, and CAD occurrence served as the control group (group C). Serum levels of copeptin and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured using enzyme-linked immunosorbent assay. The mean serum copeptin concentrations were significantly higher in patients with AS: sAS (405 pg/ml) and mAS (351 pg/ml; sAS vs mAS P < 0.05), compared with group C (302 pg/ml, P < 0.05). Serum copeptin levels correlated inversely with EOA (r = -0.55; P < 0.001) in AS patients. There was no correlation between copeptin and NT-proBNP or association with the coexisting CAD. Receiver-operating characteristics analysis showed that copeptin was a good marker of severe/moderate AS (sensitivity 71 %; specificity 87 %), with the optimized cut-off value of 354 pg/ml. Serum copeptin concentration constitutes a novel biomarker of degenerative AS. Coexisting CAD does not interfere with copeptin level. PMID:23142954

  18. MRI analysis of the ISOBAR TTL internal fixation system for the dynamic fixation of intervertebral discs: a comparison with rigid internal fixation

    PubMed Central

    2014-01-01

    Objectives Using magnetic resonance imaging (MRI), we analyzed the efficacy of the posterior approach lumbar ISOBAR TTL internal fixation system for the dynamic fixation of intervertebral discs, with particular emphasis on its effects on degenerative intervertebral disc disease. Methods We retrospectively compared the MRIs of 54 patients who had previously undergone either rigid internal fixation of the lumbar spine or ISOBAR TTL dynamic fixation for the treatment of lumbar spondylolisthesis. All patients had received preoperative and 6-, 12-, and 24-month postoperative MRI scans of the lumbar spine with acquisition of both routine and diffusion-weighted images (DWI). The upper-segment discs of the fusion were subjected to Pfirrmann grading, and the lumbar intervertebral discs in the DWI sagittal plane were manually drawn; the apparent diffusion coefficient (ADC) value was measured. Results ADC values in the ISOBAR TTL dynamic fixation group measured at the 6-, 12-, and 24-month postoperative MRI studies were increased compared to the preoperative ADC values. The ADC values in the ISOBAR TTL dynamic fixation group at 24 months postoperatively were significantly different from the preoperative values (P < 0.05). At 24 months, the postoperative ADC values were significantly different between the rigid fixation group and the ISOBAR TTL dynamic fixation group (P < 0.05). Conclusion MRI imaging findings indicated that the posterior approach lumbar ISOBAR TTL internal fixation system can prevent or delay the degeneration of intervertebral discs. PMID:24898377

  19. Epigallocatechin 3-gallate suppresses interleukin-1β-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats.

    PubMed

    Krupkova, O; Sekiguchi, M; Klasen, J; Hausmann, O; Konno, S; Ferguson, S J; Wuertz-Kozak, K

    2014-01-01

    Intervertebral disc (IVD) disease, which is characterised by age-related changes in the adult disc, is the most common cause of disc failure and low back pain. The purpose of this study was to analyse the potential of the biologically active polyphenol epigallocatechin 3-gallate (EGCG) for the treatment of painful IVD disease by identifying and explaining its anti-inflammatory and anti-catabolic activity. Human IVD cells were isolated from patients undergoing surgery due to degenerative disc disease (n = 34) and cultured in 2D or 3D. An inflammatory response was activated by IL-1β, EGCG was added, and the expression/activity of inflammatory mediators and pathways was measured by qRT-PCR, western blotting, ELISA, immunofluorescence and transcription factor assay. The small molecule inhibitor SB203580 was used to investigate the involvement of the p38 pathway in the observed effects. The analgesic properties of EGCG were analysed by the von Frey filament test in Sprague-Dawley rats (n = 60). EGCG significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB. PMID:25422948

  20. Artificial Disc Replacement

    MedlinePlus

    ... treat this condition, alternatives to disc replacement include fusion, nonoperative care or no treatment. Typically, surgery is ... operative treatment for disc pain has been spinal fusion. This is a surgical procedure in which disc ...

  1. Intervertebral disc creep behavior assessment through an open source finite element solver.

    PubMed

    Castro, A P G; Wilson, W; Huyghe, J M; Ito, K; Alves, J L

    2014-01-01

    Degenerative Disc Disease (DDD) is one of the largest health problems faced worldwide, based on lost working time and associated costs. By means of this motivation, this work aims to evaluate a biomimetic Finite Element (FE) model of the Intervertebral Disc (IVD). Recent studies have emphasized the importance of an accurate biomechanical modeling of the IVD, as it is a highly complex multiphasic medium. Poroelastic models of the disc are mostly implemented in commercial finite element packages with limited access to the algorithms. Therefore, a novel poroelastic formulation implemented on a home-developed open source FE solver is briefly addressed throughout this paper. The combination of this formulation with biphasic osmotic swelling behavior is also taken into account. Numerical simulations were devoted to the analysis of the non-degenerated human lumbar IVD time-dependent behavior. The results of the tests performed for creep assessment were inside the scope of the experimental data, with a remarkable improvement of the numerical accuracy when compared with previously published results obtained with ABAQUS(®). In brief, this in-development open-source FE solver was validated with literature experimental data and aims to be a valuable tool to study the IVD biomechanics and DDD mechanisms. PMID:24210477

  2. Molecular and genetic advances in the regeneration of the intervertebral disc

    PubMed Central

    Maerz, Tristan; Herkowitz, Harry; Baker, Kevin

    2013-01-01

    Background: Owing to the debilitating nature of degenerative disc disease (DDD) and other spine pathologies, significant research has been performed with the goal of healing or regenerating the intervertebral disc (IVD). Structural complexity, coupled with low vascularity and cellularity, make IVD regeneration an extremely challenging task. Methods: Tissue engineering-based strategies utilize three components to enhance tissue regeneration; scaffold materials to guide cell growth, biomolecules to enhance cell migration and differentiation, and cells (autologous, or allogeneic) to initiate the process of tissue formation. Significant advances in IVD regeneration have been made utilizing these tissue engineering strategies. Results: The current literature demonstrates that members of the transforming growth factor beta (TGF-β) superfamily are efficacious in the regeneration of an anabolic response in the IVD and to facilitate chondrogenic differentiation. Gene therapy, though thwarted by safety concerns and the risk of ectopic transfection, has significant potential for a targeted and sustained regenerative response. Stem cells in combination with injectable, biocompatible, and biodegradable scaffolds in the form of hydrogels can differentiate into de novo IVD tissue and facilitate regeneration of the existing matrix. Therapies that address both anabolism and the inherent catabolic state of the IVD using either direct inhibitors or broad-spectrum inhibitors show extensive promise. Conclusion: This review article summarizes the genetic and molecular advances that promise to play an integral role in the development of new strategies to combat DDD and promote healing of injured discs. PMID:23646279

  3. Artificial disc and vertebra system: a novel motion preservation device for cervical spinal disease after vertebral corpectomy

    PubMed Central

    Dong, Jun; Lu, Meng; Lu, Teng; Liang, Baobao; Xu, Junkui; Qin, Jie; Cai, Xuan; Huang, Sihua; Wang, Dong; Li, Haopeng; He, Xijing

    2015-01-01

    OBJECTIVE: To determine the range of motion and stability of the human cadaveric cervical spine after the implantation of a novel artificial disc and vertebra system by comparing an intact group and a fusion group. METHODS: Biomechanical tests were conducted on 18 human cadaveric cervical specimens. The range of motion and the stability index range of motion were measured to study the function and stability of the artificial disc and vertebra system of the intact group compared with the fusion group. RESULTS: In all cases, the artificial disc and vertebra system maintained intervertebral motion and reestablished vertebral height at the operative level. After its implantation, there was no significant difference in the range of motion (ROM) of C3–7 in all directions in the non-fusion group compared with the intact group (p>0.05), but significant differences were detected in flexion, extension and axial rotation compared with the fusion group (p<0.05). The ROM of adjacent segments (C3−4, C6−7) of the non-fusion group decreased significantly in some directions compared with the fusion group (p<0.05). Significant differences in the C4-6 ROM in some directions were detected between the non-fusion group and the intact group. In the fusion group, the C4−6 ROM in all directions decreased significantly compared with the intact and non-fusion groups (p<0.01). The stability index ROM (SI-ROM) of some directions was negative in the non-fusion group, and a significant difference in SI-ROM was only found in the C4−6 segment of the non-fusion group compared with the fusion group. CONCLUSION: An artificial disc and vertebra system could restore vertebral height and preserve the dynamic function of the surgical area and could theoretically reduce the risk of adjacent segment degeneration compared with the anterior fusion procedure. However, our results should be considered with caution because of the low power of the study. The use of a larger sample should be considered

  4. [INFLUENCE OF AUTOLOGOUS CHONDROCYTES TRANSPLANTATION ON THE INTERVERTEBRAL DISC STATE IN EXPERIMENTAL MODEL OF OSTEOCHONDROSIS].

    PubMed

    Khyzhnyak, M V

    2015-07-01

    The degenerative changes in the nucleus pulposus and fibrous ring of the intervertebral discs are the basis of spinal osteochondrosis. A large number of models, including biological, where some mechanisms of their development were worked out and studied, was used to study the morphogenesis and pathogenesis of degenerative spinal changes. The deserved place in the comparative experiments and especially the different methods of therapeutic effects on the tissues of the intervertebral discs in degenerative spinal changes is taken by the experimental methods. The biochemical changes of the intervertebral disc structures were analyzed under the administration of cultured autologous cell of nucleus pulposus suspension against a background of experimental model of rat osteochondrosis. PMID:26591226

  5. Degenerative myelopathy in 18 Pembroke Welsh Corgi dogs.

    PubMed

    March, P A; Coates, J R; Abyad, R J; Williams, D A; O'Brien, D P; Olby, N J; Keating, J H; Oglesbee, M

    2009-03-01

    Postmortem examination was performed on 18 Pembroke Welsh Corgi dogs (mean age 12.7 years) with clinical signs and antemortem diagnostic tests compatible with a diagnosis of degenerative myelopathy. Tissue sections from specific spinal cord and brain regions were systematically evaluated in all dogs. Axonal degeneration and loss were graded according to severity and subsequently compared across different spinal cord segments and funiculi. White matter lesions were identified in defined regions of the dorsal, lateral, and ventral funiculi. The dorsolateral portion of the lateral funiculus was the most severely affected region in all cord segments. Spinal cord segment T12 exhibited the most severe axonal loss. Spinal nerve roots, peripheral nerves, and brain sections were within normal limits, with the exception of areas of mild astrogliosis in gray matter of the caudal medulla. Dogs with more severe lesions showed significant progression of axonal degeneration and loss at T12 and at cord segments cranial and caudal to T12. Severity of axonal loss in individual dogs positively correlated with the duration of clinical signs. The distribution of axonal degeneration resembled that reported in German Shepherd Dog degenerative myelopathy but differed with respect to the transverse and longitudinal extent of the lesions within more clearly defined funicular areas. Although these lesion differences might reflect disease longevity, they could also indicate a form of degenerative myelopathy unique to the Pembroke Welsh Corgi dog. PMID:19261635

  6. The FasFADD death domain complex structure reveals the basis of DISC assembly and disease mutations

    SciTech Connect

    Wang, Liwei; Yang, Jin Kuk; Kabaleeswaran, Venkataraman; Rice, Amanda J.; Cruz, Anthony C.; Park, Ah Young; Yin, Qian; Damko, Ermelinda; Jang, Se Bok; Raunser, Stefan; Robinson, Carol V.; Siegel, Richard M.; Walz, Thomas; Wu, Hao

    2010-10-10

    The death-inducing signaling complex (DISC) formed by the death receptor Fas, the adaptor protein FADD and caspase-8 mediates the extrinsic apoptotic program. Mutations in Fas that disrupt the DISC cause autoimmune lymphoproliferative syndrome (ALPS). Here we show that the Fas-FADD death domain (DD) complex forms an asymmetric oligomeric structure composed of 5-7 Fas DD and 5 FADD DD, whose interfaces harbor ALPS-associated mutations. Structure-based mutations disrupt the Fas-FADD interaction in vitro and in living cells; the severity of a mutation correlates with the number of occurrences of a particular interaction in the structure. The highly oligomeric structure explains the requirement for hexameric or membrane-bound FasL in Fas signaling. It also predicts strong dominant negative effects from Fas mutations, which are confirmed by signaling assays. The structure optimally positions the FADD death effector domain (DED) to interact with the caspase-8 DED for caspase recruitment and higher-order aggregation.

  7. Quantitative Pfirrmann Disc Degeneration Grading System to Overcome the Limitation of Pfirrmann Disc Degeneration Grade

    PubMed Central

    2016-01-01

    Objective Pfirrmann disc degeneration grade is one of morphologic disc degeneration grading system and it was reliable on routine T2-weighted magnetic resonance (MR) images. The purpose of this study was to evaluate the agreement of Pfirrmann disc degeneration grade, and check the alternative technique of disc degeneration grading system. Methods Fifteen volunteers (4 medical doctors related to spinal disease, 2 medical doctors not related to spinal disease, 6 nurses in spinal hospital, and 3 para-medicines) were included in this study. Three different digitalized MR images were provided all volunteers, and they checked Pfirrmann disc degeneration grade of each disc levels after careful listening to explanation. Indeed, all volunteers checked the signal intensity of disc degeneration at the points of nucleus pulposus (NP), disc membrane, ligaments, fat, and air to modify the quantitative Pfirrmann disc degeneration grade. Results Total 225 grade results of Pfirrmann disc degeneration grade and 405 signal intensity results of quantitative Pfirrmann disc degeneration grade were analyzed. Average interobserver agreement was "moderate (mean±standard deviation, 0.575±0.251)" from poor to excellent. Completely agreed levels of Pfirrmann disc degeneration grade were only 4 levels (26.67%), and the disagreement levels were observed in 11 levels; two different grades in 8 levels (53.33%) and three different grades in 3 levels (20%). Quantitative Pfirrmann disc degeneration showed relatively cluster distribution with the interobserver deviations of 0.41-1.56 at the ratio of NP and disc membrane, and it showed relatively good cluster and distribution indicating that the proposed grading system has good discrimination ability. Conclusion Pfirrmann disc degeneration grade showed the limitation of different interobserver results, but this limitation could be overcome by using quantitative techniques of MR signal intensity. Further evaluation is needed to access its advantage

  8. Redundant disc

    NASA Technical Reports Server (NTRS)

    Barack, W. N.; Domas, P. A.; Beekman, S. W. (Inventor)

    1978-01-01

    A rotatable disc is described that consists of parallel plates tightly joined together for rotation about a hub. Each plate is provided with several angularly projecting spaced lands. The lands of each plate are interposed in alternating relationship between the lands of the next adjacent plate. In this manner, circumferential displacement of adjacent sectors in any one plate is prevented in the event that a crack develops. Each plate is redundantly sized so that, in event of structural failure of one plate, the remaining plates support a proportionate share of the load of the failed plate. The plates are prevented from separating laterally through the inclusion of generally radially extending splines which are inserted to interlock cooperating, circumferentially adjacent lands.

  9. Subsequent surgery rates after cervical total disc replacement using a Mobi-C Cervical Disc Prosthesis versus anterior cervical discectomy and fusion: a prospective randomized clinical trial with 5-year follow-up.

    PubMed

    Jackson, Robert J; Davis, Reginald J; Hoffman, Gregory A; Bae, Hyun W; Hisey, Michael S; Kim, Kee D; Gaede, Steven E; Nunley, Pierce Dalton

    2016-05-01

    OBJECTIVE Cervical total disc replacement (TDR) has been shown in a number of prospective clinical studies to be a viable treatment alternative to anterior cervical discectomy and fusion (ACDF) for the treatment of symptomatic degenerative disc disease. In addition to preserving motion, evidence suggests that cervical TDR may result in a lower incidence of subsequent surgical intervention than treatment with fusion. The goal of this study was to evaluate subsequent surgery rates up to 5 years in patients treated with TDR or ACDF at 1 or 2 contiguous levels between C-3 and C-7. METHODS This was a prospective, multicenter, randomized, unblinded clinical trial. Patients with symptomatic degenerative disc disease were enrolled to receive 1- or 2-level treatment with either TDR as the investigational device or ACDF as the control treatment. There were 260 patients in the 1-level study (179 TDR and 81 ACDF patients) and 339 patients in the 2-level study (234 TDR and 105 ACDF patients). RESULTS At 5 years, the occurrence of subsequent surgical intervention was significantly higher among ACDF patients for 1-level (TDR, 4.5% [8/179]; ACDF, 17.3% [14/81]; p = 0.0012) and 2-level (TDR, 7.3% [17/234]; ACDF, 21.0% [22/105], p = 0.0007) treatment. The TDR group demonstrated significantly fewer index- and adjacent-level subsequent surgeries in both the 1- and 2-level cohorts. CONCLUSIONS Five-year results showed treatment with cervical TDR to result in a significantly lower rate of subsequent surgical intervention than treatment with ACDF for both 1 and 2 levels of treatment. Clinical trial registration no.: NCT00389597 ( clinicaltrials.gov ). PMID:26799118

  10. Percutaneous diode laser disc nucleoplasty

    NASA Astrophysics Data System (ADS)

    Menchetti, P. P.; Longo, Leonardo

    2004-09-01

    The treatment of herniated disc disease (HNP) over the years involved different miniinvasive surgical options. The classical microsurgical approach has been substituted over the years both by endoscopic approach in which is possible to practice via endoscopy a laser thermo-discoplasty, both by percutaneous laser disc nucleoplasty. In the last ten years, the percutaneous laser disc nucleoplasty have been done worldwide in more than 40000 cases of HNP. Because water is the major component of the intervertebral disc, and in HNP pain is caused by the disc protrusion pressing against the nerve root, a 980 nm Diode laser introduced via a 22G needle under X-ray guidance and local anesthesia, vaporizes a small amount of nucleous polposus with a disc shrinkage and a relief of pressure on nerve root. Most patients get off the table pain free and are back to work in 5 to 7 days. Material and method: to date, 130 patients (155 cases) suffering for relevant symptoms therapy-resistant 6 months on average before consulting our department, have been treated. Eightyfour (72%) males and 46 (28%) females had a percutaneous laser disc nucleoplasty. The average age of patients operated was 48 years (22 - 69). The level of disc removal was L3/L4 in 12 cases, L4/L5 in 87 cases and L5/S1 in 56 cases. Two different levels were treated at the same time in 25 patients. Results: the success rate at a minimum follow-up of 6 months was 88% with a complication rate of 0.5%.

  11. [Endovascular repair of iliocaval arteriovenous fistula complicating lumbar disc surgery].

    PubMed

    Ben Jemaa, H; Maalej, A; Lazzez, K; Jemal, H; Karray, S; Ben Mahfoudh, K

    2016-05-01

    Vascular complications of lumbar disc surgery are rare. Few cases have been reported. Arteriovenous fistulas are the most common. They are due to anatomical relationships between the last lumbar vertebrae, the corresponding discs, and the iliac vessels; degenerative lesions of the intervertebral discs facilitate instrumental vessel perforation, and operative difficulty. Computed tomography is particularly accurate for making the diagnosis. Treatment strategies consist in surgery or endovascular management. Percutaneous endovascular treatment using a stent-graft is a reasonable option for treating arteriovenous fistula. We describe the case of a 50-year-old patient who developed an iliocaval arteriovenous fistula following lumbar disc hernia surgery. The lesion was excluded by a stent-graft. The postoperative period was uneventful. PMID:26920402

  12. Angiogenesis in the degeneration of the lumbar intervertebral disc

    PubMed Central

    David, Gh; Iencean, SM; Mohan, A

    2010-01-01

    The goal of the study is to show the histological and biochemical changes that indicate the angiogenesis of the intervertebral disc in lumbar intervertebral disc hernia and the existence of epidemiological correlations between these changes and the risk factors of lumbar intervertebral disc hernia, as well as the patient's quality of life (QOL). We have studied 50 patients aged between 18 and 73 years old, who have undergone lumbar intervertebral disc hernia surgery, making fibroblast growth factor and vascular endothelial growth factor level measurements, as elements in the process of appreciating the disc angiogenesis. Also, pre–surgery and post–surgery QOL has been measured, as well as the intensity of the pain syndrome. We have identified factors capable of stimulating vascular endothelial growth (VEGF, FGF–2) for the examined disc material, but histological examination did not show angiogenesis. The process of angiogenesis at the degenerated intervertebral disc level affects the patient's quality of life both pre and postoperatively, and may be a predictive factor for the post–operative results. Patients can prevent the appearance of angiogenesis type degenerative processes of the intervertebral disc by avoiding angiogenesis correlated factors (weight control, physical effort, and smoking). PMID:20968201

  13. Broken discs: warp propagation in accretion discs

    NASA Astrophysics Data System (ADS)

    Nixon, Christopher J.; King, Andrew R.

    2012-04-01

    We simulate the viscous evolution of an accretion disc around a spinning black hole. In general, any such disc is misaligned, and warped by the Lense-Thirring effect. Unlike previous studies, we use effective viscosities constrained to be consistent with the internal fluid dynamics of the disc. We find that non-linear fluid effects, which reduce the effective viscosities in warped regions, can promote breaking of the disc into two distinct planes. This occurs when the Shakura & Sunyaev dimensionless viscosity parameter α is ≲0.3 and the initial angle of misalignment between the disc and hole is ≳45°. The break can be a long-lived feature, propagating outwards in the disc on the usual alignment time-scale, after which the disc is fully co-aligned or counter-aligned with the hole. Such a break in the disc may be significant in systems where we know the inclination of the outer accretion disc to the line of sight, such as some X-ray binaries: the inner disc, and so any jets, may be noticeably misaligned with respect to the orbital plane.

  14. Disc-planet interactions in subkeplerian discs

    NASA Astrophysics Data System (ADS)

    Paardekooper, S.-J.

    2009-11-01

    Context: One class of protoplanetary disc models, the X-wind model, predicts strongly subkeplerian orbital gas velocities, a configuration that can be sustained by magnetic tension. Aims: We investigate disc-planet interactions in these subkeplerian discs, focusing on orbital migration for low-mass planets and gap formation for high-mass planets. Methods: We use linear calculations and nonlinear hydrodynamical simulations to measure the torque and look at gap formation. In both cases, the subkeplerian nature of the disc is treated as a fixed external constraint. Results: We show that, depending on the degree to which the disc is subkeplerian, the torque on low-mass planets varies between the usual type I torque and the one-sided outer Lindblad torque, which is also negative but an order of magnitude stronger. In strongly subkeplerian discs, corotation effects can be ignored, making migration fast and inward. Gap formation near the planet's orbit is more difficult in such discs, since there are no resonances close to the planet accommodating angular momentum transport. The location of the gap is shifted inwards with respect to the planet, leaving the planet on the outside of a surface density depression. Conclusions: Depending on the degree to which a protoplanetary disc is subkeplerian, disc-planet interactions can be very different from the usual Keplerian picture, making these discs in general more hazardous for young planets.

  15. [Controversies about instrumented surgery and pain relief in degenerative lumbar spine pain. Results of scientific evidence].

    PubMed

    Robaina-Padrón, F J

    2007-10-01

    Investigation and development of new techniques for intrumented surgery of the spine is not free of conflicts of interest. The influence of financial forces in the development of new technologies an its immediately application to spine surgery, shows the relationship between the published results and the industry support. Even authors who have defend eagerly fusion techniques, it have been demonstrated that them are very much involved in the revision of new articles to be published and in the approval process of new spinal technologies. When we analyze the published results of spine surgery, we must bear in mind what have been call in the "American Stock and Exchange" as "the bubble of spine surgery". The scientific literature doesn't show clear evidence in the cost-benefit studies of most instrumented surgical interventions of the spine compare with the conservative treatments. It has not been yet demonstrated that fusion surgery and disc replacement are better options than the conservative treatment. It's necessary to point out that at present "there are relationships between the industry and back pain, and there is also an industry of the back pain". Nonetheless, the "market of the spine surgery" is growing up because patients are demanding solutions for their back problems. The tide of scientific evidence seams to go against the spinal fusions in the degenerative disc disease, discogenic pain and inespecific back pain. After decades of advances in this field, the results of spinal fusions are mediocre. New epidemiological studies show that "spinal fusion must be accepted as a non proved or experimental method for the treatment of back pain". The surgical literature on spinal fusion published in the last 20 years following the Cochrane's method establish that: 1- this is at least incomplete, not reliable and careless; 2- the instrumentation seems to slightly increase the fusion rate; 3- the instrumentation doesn't improve the clinical results in general, lacking

  16. Viscoelastic Disc Arthroplasty Provides Superior Back and Leg Pain Relief in Patients with Lumbar Disc Degeneration Compared to Anterior Lumbar Interbody Fusion

    PubMed Central

    Rischke, Burkhard; Smith, Eric

    2015-01-01

    .93 additional points; 95% CI 0.10 to 1.77; p = 0.029) and higher leg pain at baseline (0.83 points additional pain relief per level of preoperative leg pain; 95% CI 0.70 to 0.96). In both models the L3/4 segment showed 2.36 points (95% CI -4.27 to -0.45; p = 0.016) and 3.69 points (95% CI -5.66 to -1.71; p < 0.001) less pain relief than L5/S1. Discussion Significantly higher back and leg pain relief were observed after viscoelastic total disc replacement in comparison with anterior lumbar interbody fusion. The new less rigid materials used in the second generation total disc replacements (TDRs) may make artificial disc replacement an increasingly attractive option for patients with degenerative lumbar disc disease. Further controlled and long-term follow-up studies are required for more detailed comparisons of the outcomes of these types of disc implants. The Freedom Lumbar Disc is limited by U.S. federal law to investigational use only. PMID:26196033

  17. Comparison of vertebral and intervertebral disc lesions in aging humans and rhesus monkeys

    PubMed Central

    Bailey, Jeannie F.; Fields, Aaron J.; Liebenberg, Ellen; Mattison, Julie A.; Lotz, Jeffrey C.; Kramer, Patricia A.

    2014-01-01

    Objective To compare gross and histologic patterns of age-related degeneration within the intervertebral disc and adjacent vertebra between rhesus monkeys and humans. Materials and methods We examined age-related patterns of disc degeneration from mid-sagittal sections of the intervertebral disc and adjacent vertebral bodies among six rhesus monkey thoracolumbar and seven human lumbar spines. Gross morphology and histopathology were assessed via the Thompson grading scheme and other degenerative features of the disc and adjacent bone. Results Thompson grades ranged from 3 through 5 for rhesus monkey discs (T9-L1) and 2 through 5 for the human discs (T12-S1). In both rhesus monkey and human discs, presence of distinct lesions were positively associated with Thompson grade of the overall segment. Degenerative patterns differed for radial tears, which were more prevalent with advanced disc degeneration in humans only. Additionally, compared to the more uniform anteroposterior disc degeneration patterns of humans, rhesus monkeys showed more severe osteophytosis and degeneration on the anterior border of the vertebral column. Conclusions Rhesus monkey spines evaluated in the present study appear to develop age-related patterns of disc degeneration similar to humans. One exception is the absence of an association between radial tears and disc degeneration, which could reflect species-specific differences in posture and spinal curvature. Considering rhesus monkeys demonstrate similar patterns of disc degeneration, and age at a faster rate than humans, these findings suggest longitudinal studies of rhesus monkeys may be a valuable model for better understanding the progression of human age-related spinal osteoarthritis and disc degeneration. PMID:24821664

  18. Minimally-invasive posterior lumbar stabilization for degenerative low back pain and sciatica. A review.

    PubMed

    Bonaldi, G; Brembilla, C; Cianfoni, A

    2015-05-01

    The most diffused surgical techniques for stabilization of the painful degenerated and instable lumbar spine, represented by transpedicular screws and rods instrumentation with or without interbody cages or disk replacements, require widely open and/or difficult and poorly anatomical accesses. However, such surgical techniques and approaches, although still considered "standard of care", are burdened by high costs, long recovery times and several potential complications. Hence the effort to open new minimally-invasive surgical approaches to eliminate painful abnormal motion. The surgical and radiological communities are exploring, since more than a decade, alternative, minimally-invasive or even percutaneous techniques to fuse and lock an instable lumbar segment. Another promising line of research is represented by the so-called dynamic stabilization (non-fusion or motion preservation back surgery), which aims to provide stabilization to the lumbar spinal units (SUs), while maintaining their mobility and function. Risk of potential complications of traditional fusion methods (infection, CSF leaks, harvest site pain, instrumentation failure) are reduced, particularly transitional disease (i.e., the biomechanical stresses imposed on the adjacent segments, resulting in delayed degenerative changes in adjacent facet joints and discs). Dynamic stabilization modifies the distribution of loads within the SU, moving them away from sensitive (painful) areas of the SU. Basic biomechanics of the SU will be discussed, to clarify the mode of action of the different posterior stabilization devices. Most devices are minimally invasive or percutaneous, thus accessible to radiologists' interventional practice. Devices will be described, together with indications for patient selection, surgical approaches and possible complications. PMID:24906245

  19. Fuchs' Uveitis: Failure to Associate Vitritis and Disc Hyperfluorescence with the Disease is the Major Factor for Misdiagnosis and Diagnostic Delay

    PubMed Central

    Bouchenaki, Nadia; Herbort, Carl P

    2009-01-01

    Purpose: Fuchs' uveitis is often diagnosed with substantial delay at the origin of deleterious consequences such as unnecessary treatment. The aim of the study was to analyse the type and frequency of posterior inflammatory and fluorescein angiographic signs in Fuchs' uveitis in conjunction with the other clinical signs and evaluate their respective importance in the diagnosis of the disease. In particular, diagnostic delay and erroneous diagnoses were investigated. Patients and Methods: Patients seen in our centers between 1995 and 2008 with the diagnosis of Fuchs' uveitis were analysed. The data collected included age, initial and final visual acuities, clinical findings at presentation, mean diagnostic delay, erroneous diagnoses, laser flare photometry values, fundus and fluorescein angiography manifestations and ocular complications. Results: One hundred and five patients were included. The mean age at diagnosis was 34 years. Twelve patients (11.4%) had bilateral involvement. The mean diagnostic delay was 3.04 ± 4.30 years. The most frequent clinical signs were vitreous infiltration (97.40%), typical Fuchs' keratic precipitates (94.90%), crystalline lens opacities or cataract (47%), heterochromia (42.60%), ocular hypertension or glaucoma (12.80%). The mean laser flare photometry value at presentation was 9.85 ± 6.28 ph/ms. Thirty-nine patients (37.14%) had undergone fluorescein angiography showing disc hyperfluorescence in 97.7% and peripheral retinal vascular leakage in 13.6%. Conclusions: Fuchs' uveitis is significantly underdiagnosed likely because vitreous involvement was previously described but not commonly recognized as an association with Fuchs' uveitis in the clinician's mind and therefore has often been given a different diagnostic label. Moreover, the very frequent inflammatory signs on fluorescein angiography such as disc hyperfluorescence and more rarely peripheral retinal vascular leakage, which has not been typically associated with Fuchs

  20. In-vivo endoscopic visualization of patho-anatomy in painful degenerative conditions of the lumbar spine.

    PubMed

    Yeung, Anthony T; Yeung, Christopher A

    2006-01-01

    The degenerative processes in an aging spine have been defined traditionally only by our knowledge of the biology of disc and facet degeneration, as well as interpretation of post-mortem cryosections by forensic anatomist Wolfgang Rauschning, M.D. In this chapter, visualization of in-vivo patho-anatomy in a degenerating disc and spinal segment is demonstrated at surgery using the Yeung Endoscopic Spine System (Y.E.S.S.), (Richard Wolf Surgical Instrument Company, Vernon Hills, IL, USA). An Institutional Review Board (IRB)-approved study of endoscopic treatment for degenerative conditions of the lumbar spine incorporated intraoperative probing under local anesthesia and endoscopic treatment of the visualized patho-anatomy. An intraoperative evocative chromo-discogram, using indigocarmine, was used to elicit discogenic pain and label the fissured and degenerative nucleus pulposus for surgical removal and thermal modulation. Painful patho-anatomy was probed in a conscious patient. The most common endoscopic finding was Inflammatory tissue in the disc and annulus. Inflammation was correlated with the presence of annular tears. Patho-physiologic changes that affect the exiting nerve, which contains the Dorsal Root Ganglion (DRG), was associated with stenotic and chemical irritation. Unavoidable postoperative dysesthesia was associated with the presence of an inflammatory membrane, and removal or thermal coagulation of "anomalous" furcal nerves in the foramen that branched off of the exiting spinal nerve. Neo-angiogenesis and neurogenesis in the inflammatory membrane present in the foraminal triangle was a new finding not reported in traditional clinical studies. Visualization and treatment of pathologic findings inside (annular tears) and outside the disc in Herniated Nucleus Pulposus (HNP), synovial cysts, foraminal stenosis, central stenosis, spondylolisthesis, is demonstrated. The endoscopic foraminal approach to the spine and disc is a technique that provides access

  1. Stimulation of Synaptic Vesicle Exocytosis by the Mental Disease Gene DISC1 is Mediated by N-Type Voltage-Gated Calcium Channels

    PubMed Central

    Tang, Willcyn; Thevathasan, Jervis Vermal; Lin, Qingshu; Lim, Kim Buay; Kuroda, Keisuke; Kaibuchi, Kozo; Bilger, Marcel; Soong, Tuck Wah; Fivaz, Marc

    2016-01-01

    Lesions and mutations of the DISC1 (Disrupted-in-schizophrenia-1) gene have been linked to major depression, schizophrenia, bipolar disorder and autism, but the influence of DISC1 on synaptic transmission remains poorly understood. Using two independent genetic approaches—RNAi and a DISC1 KO mouse—we examined the impact of DISC1 on the synaptic vesicle (SV) cycle by population imaging of the synaptic tracer vGpH in hippocampal neurons. DISC1 loss-of-function resulted in a marked decrease in SV exocytic rates during neuronal stimulation and was associated with reduced Ca2+ transients at nerve terminals. Impaired SV release was efficiently rescued by elevation of extracellular Ca2+, hinting at a link between DISC1 and voltage-gated Ca2+ channels. Accordingly, blockade of N-type Cav2.2 channels mimics and occludes the effect of DISC1 inactivation on SV exocytosis, and overexpression of DISC1 in a heterologous system increases Cav2.2 currents. Collectively, these results show that DISC1-dependent enhancement of SV exocytosis is mediated by Cav2.2 and point to aberrant glutamate release as a probable endophenotype of major psychiatric disorders. PMID:27378904

  2. A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic

    PubMed Central

    Ghosh, Peter

    2016-01-01

    Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored. PMID:27314030

  3. A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic.

    PubMed

    Daly, Chris; Ghosh, Peter; Jenkin, Graham; Oehme, David; Goldschlager, Tony

    2016-01-01

    Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored. PMID:27314030

  4. MicroRNA Expression Signature in Degenerative Aortic Stenosis

    PubMed Central

    2016-01-01

    Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n = 4) and patients with degenerative AS (n = 4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease. PMID:27579316

  5. MicroRNA Expression Signature in Degenerative Aortic Stenosis.

    PubMed

    Shi, Jing; Liu, Hui; Wang, Hui; Kong, Xiangqing

    2016-01-01

    Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n = 4) and patients with degenerative AS (n = 4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease. PMID:27579316

  6. Simulating the sensitivity of cell nutritive environment to composition changes within the intervertebral disc

    NASA Astrophysics Data System (ADS)

    Wills, C. Ruiz; Malandrino, A.; van Rijsbergen, MM.; Lacroix, D.; Ito, K.; Noailly, J.

    2016-05-01

    Altered nutrition in the intervertebral disc affects cell viability and can generate catabolic cascades contributing to extracellular matrix (ECM) degradation. Such degradation is expected to affect couplings between disc mechanics and nutrition, contributing to accelerate degenerative processes. However, the relation of ECM changes to major biophysical events within the loaded disc remains unclear. A L4-L5 disc finite element model including the nucleus (NP), annulus (AF) and endplates was used and coupled to a transport-cell viability model. Solute concentrations and cell viability were evaluated along the mid-sagittal plane path. A design of experiment (DOE) was performed. DOE parameters corresponded to AF and NP biochemical tissue measurements in discs with different degeneration grades. Cell viability was not affected by any parameter combinations defined. Nonetheless, the initial water content was the parameter that affected the most the solute contents, especially glucose. Calculations showed that altered NP composition could negatively affect AF cell nutrition. Results suggested that AF and NP tissue degeneration are not critical to nutrition-related cell viability at early-stage of disc degeneration. However, small ECM degenerative changes may alter significantly disc nutrition under mechanical loads. Coupling disc mechano-transport simulations and enzyme expression studies could allow identifying spatiotemporal sequences related to tissue catabolism.

  7. Mesenchymal stem cells: potential application in intervertebral disc regeneration

    PubMed Central

    Shen, Bojiang; Williams, Lisa; Diwan, Ashish

    2014-01-01

    Chronic low back pain is one of the leading public health problems in developed countries. Degeneration of the intervertebral disc (IVD) is a major pathological process implicated in low back pain, which is characterized by cellular apoptosis and senescence with reduced synthesis of extracellular matrix (ECM). Currently, there is no clinical therapy targeting the reversal of disc degeneration. Recent advances in cellular and molecular biology have provided an exciting approach to disc regeneration that focuses on the delivery of viable cells to the degenerative disc. Adult mesenchymal stem cells (MSCs) are multipotent stem cells with self-renewal capacities and are able to differentiate into diverse specialized cell types, including chondrocyte lineages. The potential of stem cell therapy in disc degeneration is to repopulate the disc with viable cells capable of producing the ECM and restoring damaged tissue. The present literature review summarizes recent advances in basic research and clinical trials of MSCs to provide an outline of the key roles of MSCs therapies in disc repair. The review also discusses the controversies, challenges and therapeutic concepts for the future. PMID:26835326

  8. The Use of Percutaneous Lumbar Fixation Screws for Bilateral Pedicle Fractures with an Associated Dislocation of a Lumbar Disc Prosthesis

    PubMed Central

    Harrison, William D.; Harrison, David J.

    2013-01-01

    Study Design. Case report. Objective. To identify a safe technique for salvage surgery following complications of total disc replacement. Summary of Background Data. Lumbar total disc replacement (TDR) is considered by some as the gold standard for discogenic back pain. Revision techniques for TDR and their complications are in their infancy. This case describes a successful method of fixation for this complex presentation. Methods and Results. A 48-year-old male with lumbar degenerative disc disease and no comorbidities. Approximately two weeks postoperatively for a TDR, the patient represented with acute severe back pain and the TDR polyethylene inlay was identified as dislocated anteriorly. Subsequent revision surgery failed immediately as the polyethylene inlay redislocated intraoperatively. Further radiology identified bilateral pedicle fractures, previously unseen on the plain films. The salvage fusion of L5/S1 reutilized the anterior approach with an interbody fusion cage and bone graft. The patient was then turned intraoperatively and redraped. The percutaneous pedicle screws were used to fix L5 to the sacral body via the paracoccygeal corridor. Conclusion. The robust locking screw in the percutaneous screw allowed a complete fixation of the pedicle fractures. At 3-year followup, the patient has an excellent result and has returned to playing golf. PMID:24294533

  9. The Mobi-C cervical disc for one-level and two-level cervical disc replacement: a review of the literature

    PubMed Central

    Alvin, Matthew D; Mroz, Thomas E

    2014-01-01

    Background Cervical disc arthroplasty (CDA) is a novel motion-preserving procedure that is an alternative to fusion. The Mobi-C disc prosthesis, one of many Food and Drug Administration (FDA)-approved devices for CDA, is the only FDA-approved prosthesis for two-level CDA. Hence, it may allow for improved outcomes compared with multilevel fusion procedures. Purpose To critically assess the available literature on CDA with the Mobi-C prosthesis, with a focus on two-level CDA. Methods All clinical articles involving the Mobi-C disc prosthesis for CDA through September 1, 2014 were identified on Medline. Any paper that presented Mobi-C CDA clinical results was included. Study design, sample size, length of follow-up, use of statistical analysis, quality of life outcome scores, conflict of interest, and complications were recorded. Results Fifteen studies were included that investigated Mobi-C CDA, only one of which was a level Ib randomized control trial. All studies included showed non-inferiority of one-level Mobi-C CDA to one-level anterior cervical discectomy and fusion (ACDF). Only one study analyzed outcomes of one-level versus two-level Mobi-C CDA, and only one study analyzed two-level Mobi-C CDA versus two-level ACDF. In comparison with other cervical disc prostheses, the Mobi-C prosthesis is associated with higher rates of heterotopic ossification (HO). Studies with conflicts of interest reported lower rates of HO. Adjacent segment degeneration or disease, along with other complications, were not assessed in most studies. Conclusion One-level Mobi-C CDA is non-inferior, but not superior, to one-level ACDF for patients with cervical degenerative disc disease. The Mobi-C CDA procedure is associated with high rates of HO. Two-level Mobi-C CDA may be superior to two-level ACDF. However, insufficient evidence exists, thereby mandating a need for unbiased, well-designed prospective studies with well-defined outcomes in the future. PMID:25473319

  10. Discs Large Homolog 5 (DLG5) Gene Polymorphism and Crohn's Disease: A Meta-Analysis of the Published Studies.

    PubMed

    Shafieyoun, Arezoo; Moraveji, Sharareh; Bashashati, Mohammad; Rezaei, Nima

    2016-05-01

    The real pathophysiology of Crohn's disease is unknown. The higher prevalence of Crohn's disease in Caucasian and Jewish ethnicities, as well as its familial aggregation and higher concordance among monozygotic twins, suggest some roles for genes in its development, clinical progression, and outcome. Recent original studies have indicated DLG5113G/A gene polymorphism as a risk factor for Crohn's disease. Meanwhile, the results of these studies are not consistent. We performed the current meta-analysis to understand whether there is any association between DLG5 gene polymorphism and the risk of Crohn's disease. PubMed was searched to find the case-control studies on DLG5 gene polymorphisms and Crohn's disease. This search compiled 65 articles and based on our criteria. 11 articles were included in this meta-analysis. The association between the DLG5 113G/A polymorphism and the risk of disease was assessed using odds ratio (OR) and 95% confidence interval (95% CI). Heterogeneity was evaluated based on I2 values.  Random and fixed-effect models were used when I2>50% and I2≤50%, respectively. Eleven studies with a total of 4648 cases and 5677 controls were pooled. Based on our meta-analysis, DLG5113G/A gene polymorphism both at genotypic and allelic levels were not associated with the risk of Crohn's disease. Pooled data indicated no significant association between DLG5113G/A gene polymorphism and the development of Crohn's disease. In order to achieve a superior conclusion, multicenter studies on larger number of patients are recommended. PMID:27309475

  11. CT myelography of the thoraco-lumbar spine in 8 dogs with degenerative myelopathy.

    PubMed

    Jones, Jeryl C; Inzana, Karen D; Rossmeisl, John H; Bergman, Robert L; Wells, Tana; Butler, Katherine

    2005-12-01

    CT myelography of the T11-L2 region was performed in 8 large-breed dogs with a clinical diagnosis of degenerative myelopathy (DM) and 3 large-breed dogs that were clinically normal. CT myelographic characteristics were recorded for each dog, at each disc level. Area measurements of the spinal cord, dural sac, vertebral canal, and vertebral body were recorded at 4 slice locations for each disc level. Mean area ratios were calculated and graphically compared, by slice location and group. In all dogs, CT myelography identified morphologic abnormalities that were not suspected from conventional myelograms. Characteristics observed with higher frequency in DM versus normal dogs were: spinal stenosis, disc protrusion, focal attenuation of the subarachnoid space, spinal cord deformity, small spinal cord, and paraspinal muscle atrophy. Mean spinal cord:dural sac, spinal cord:vertebral canal, dural sac: vertebral canal, and vertebral canal:vertebral body ratios were smaller in DM versus normal dogs at more than one disc level. Some CT myelographic characteristics in DM dogs were similar to those previously reported in humans, dogs and horses with stenotic myelopathy. PMID:16293999

  12. Molecular neuroimaging in degenerative dementias.

    PubMed

    Jiménez Bonilla, J F; Carril Carril, J M

    2013-01-01

    In the context of the limitations of structural imaging, brain perfusion and metabolism using SPECT and PET have provided relevant information for the study of cognitive decline. The introduction of the radiotracers for cerebral amyloid imaging has changed the diagnostic strategy regarding Alzheimer's disease, which is currently considered to be a "continuum." According to this new paradigm, the increasing amyloid load would be associated to the preclinical phase and mild cognitive impairment. It has been possible to observe "in vivo" images using 11C-PIB and PET scans. The characteristics of the 11C-PIB image include specific high brain cortical area retention in the positive cases with typical distribution pattern and no retention in the negative cases. This, in combination with 18F-FDG PET, is the basis of molecular neuroimaging as a biomarker. At present, its prognostic value is being evaluated in longitudinal studies. 11C-PIB-PET has become the reference radiotracer to evaluate the presence of cerebral amyloid. However, its availability is limited due to the need for a nearby cyclotron. Therefore, 18F labeled radiotracers are being introduced. Our experience in the last two years with 11C-PIB, first in the research phase and then as being clinically applied, has shown the utility of the technique in the clinical field, either alone or in combination with FDG. Thus, amyloid image is a useful tool for the differential diagnosis of dementia and it is a potentially useful method for early diagnosis and evaluation of future treatments. PMID:23933381

  13. Video Discs in Education.

    ERIC Educational Resources Information Center

    Barker, Philip

    1986-01-01

    This discussion of the use of images in learning processes focuses on recent developments in optical storage disc technology, particularly compact disc read-only (CD-ROM) and optical video discs. Interactive video systems and user interfaces are described, and applications in education and industry in the United Kingdom are reviewed. (Author/LRW)

  14. Turbine disc sealing assembly

    DOEpatents

    Diakunchak, Ihor S.

    2013-03-05

    A disc seal assembly for use in a turbine engine. The disc seal assembly includes a plurality of outwardly extending sealing flange members that define a plurality of fluid pockets. The sealing flange members define a labyrinth flow path therebetween to limit leakage between a hot gas path and a disc cavity in the turbine engine.

  15. Pineal gland calcification, lumbar intervertebral disc degeneration and abdominal aorta calcifying atherosclerosis correlate in low back pain subjects: A cross-sectional observational CT study.

    PubMed

    Turgut, Ahmet Tuncay; Sönmez, Iclal; Cakıt, Burcu Duyur; Koşar, Pınar; Koşar, Uğur

    2008-06-01

    The goal of this cross-sectional observational study was to assess the possible impact of pineal gland calcification upon the intervertebral disc degeneration and abdominal aorta atherosclerosis in subjects with low back pain, and to investigate the course of these processes with aging. The study was carried out on 81 (66 women and 15 men) subjects: younger than 45 years (group X, n=22), 45-65 years of age (group Y, n=45), and older than 65 years (group Z, n=14). In addition to clinical data, computed tomography (CT) scan of the brain as well as X-ray and CT examination of the lumbar spine were recorded in this study. The degree of disc degeneration and calcification rates of aortic wall and pineal gland were independently determined by two radiologists. Both ratio of calcified pineal gland and density of pineal calcification increased progressively with aging. Also, both the degree of aortic wall calcification and disc degeneration score increased with advancing age. On CT scan, a positive correlation between degree of aortic wall calcification and disc degeneration score was found (r=0.306, p<0.01). Importantly, there was a positive association between calcification of the pineal gland and degenerative disc disease in X-ray or CT study (r=0.378 and r=0.295, p<0.005 and p<0.01, respectively), as well as between abdominal aorta atherosclerosis and pineal calcification (r=0.634, p<0.001). Our findings suggest that there is a significant interaction between pineal gland calcification and lumbar intervertebral disc degeneration and also abdominal aorta atherosclerosis. However, further studies with a larger subject cohorts are needed. PMID:18215511

  16. Link Protein N-terminal Peptide Binds to Bone Morphogenetic Protein (BMP) Type II Receptor and Drives Matrix Protein Expression in Rabbit Intervertebral Disc Cells*

    PubMed Central

    Wang, Zili; Weitzmann, M. Neale; Sangadala, Sreedhara; Hutton, William C.; Yoon, S. Tim

    2013-01-01

    Intervertebral disc (IVD) degeneration and associated spinal disorders are leading sources of morbidity, and they can be responsible for chronic low back pain. Treatments for degenerative disc diseases continue to be a challenge. Intensive research is now focusing on promoting regeneration of degenerated discs by stimulating production of the disc matrix. Link protein N-terminal peptide (LPP) is a proteolytic fragment of link protein, an important cross-linker and stabilizer of the major structural components of cartilage, aggrecan and hyaluronan. In this study we investigated LPP action in rabbit primary intervertebral disc cells cultured ex vivo in a three-dimensional alginate matrix. Our data reveal that LPP promotes disc matrix production, which was evidenced by increased expression of the chondrocyte-specific transcription factor SOX9 and the extracellular matrix macromolecules aggrecan and collagen II. Using colocalization and pulldown studies we further document a noggin-insensitive direct peptide-protein association between LPP and BMP-RII. This association mediated Smad signaling that converges on BMP genes leading to expression of BMP-4 and BMP-7. Furthermore, through a cell-autonomous loop BMP-4 and BMP-7 intensified Smad1/5 signaling though a feedforward circuit involving BMP-RI, ultimately promoting expression of SOX9 and downstream aggrecan and collagen II genes. Our data define a complex regulatory signaling cascade initiated by LPP and suggest that LPP may be a useful therapeutic substitute for direct BMP administration to treat IVD degeneration and to ameliorate IVD-associated chronic low back pain. PMID:23940040

  17. Systems Pharmacology Links GPCRs with Retinal Degenerative Disorders

    PubMed Central

    Chen, Yu; Palczewski, Krzysztof

    2015-01-01

    In most biological systems, second messengers and their key regulatory and effector proteins form links between multiple cellular signaling pathways. Such signaling nodes can integrate the deleterious effects of genetic aberrations, environmental stressors, or both in complex diseases, leading to cell death by various mechanisms. Here we present a systems (network) pharmacology approach that, together with transcriptomics analyses, was used to identify different G protein–coupled receptors that experimentally protected against cellular stress and death caused by linked signaling mechanisms. We describe the application of this concept to degenerative and diabetic retinopathies in appropriate mouse models as an example. Systems pharmacology also provides an attractive framework for devising strategies to combat complex diseases by using (repurposing) US Food and Drug Administration–approved pharmacological agents. PMID:25839098

  18. Retrolisthesis as a Compensatory Mechanism in Degenerative Lumbar Spine

    PubMed Central

    Jeon, Ikchan

    2015-01-01

    Objective Posterior vertebral translation as a type of spondylolisthesis, retrolisthesis is observed commonly in patients with degenerative spinal problems. Nevertheless, there is insufficient literature on retrolisthesis compared to anterolisthesis. The purpose of this study is to clarify the clinical features of retrolisthesis, and its developmental mechanism associated with a compensatory role in sagittal imbalance of the lumbar spine. Methods From 2003 to 2012, 230 Korean patients who underwent spinal surgery in our department under the impression of degenerative lumbar spinal disease were enrolled. All participants were divided into four groups : 35 patients with retrolisthesis (group R), 32 patients with simultaneous retrolisthesis and anterolisthesis (group R+A), 76 patients with anterolisthesis (group A), and 87 patients with non-translation (group N). The clinical features and the sagittal parameters related to retrolisthesis were retrospectively analyzed based on the patients' medical records. Results There were different clinical features and developmental mechanisms between retrolisthesis and anterolisthesis. The location of retrolisthesis was affected by the presence of simultaneous anterolisthesis, even though it predominantly manifest in L3. The relative lower pelvic incidence, pelvic tilt, and lumbar lordosis compared to anterolisthesis were related to the generation of retrolisthesis, with the opposite observations of patients with anterolisthesis. Conclusion Retrolisthesis acts as a compensatory mechanism for moving the gravity axis posteriorly for sagittal imbalance in the lumbar spine under low pelvic incidence and insufficient intra-spinal compensation. PMID:25810857

  19. Cervical Total Disc Arthroplasty

    PubMed Central

    Basho, Rahul; Hood, Kenneth A.

    2012-01-01

    Symptomatic adjacent segment degeneration of the cervical spine remains problematic for patients and surgeons alike. Despite advances in surgical techniques and instrumentation, the solution remains elusive. Spurred by the success of total joint arthroplasty in hips and knees, surgeons and industry have turned to motion preservation devices in the cervical spine. By preserving motion at the diseased level, the hope is that adjacent segment degeneration can be prevented. Multiple cervical disc arthroplasty devices have come onto the market and completed Food and Drug Administration Investigational Device Exemption trials. Though some of the early results demonstrate equivalency of arthroplasty to fusion, compelling evidence of benefits in terms of symptomatic adjacent segment degeneration are lacking. In addition, non-industry-sponsored studies indicate that these devices are equivalent to fusion in terms of adjacent segment degeneration. Longer-term studies will eventually provide the definitive answer. PMID:24353955

  20. Structure and evolutionary history of DISC1.

    PubMed

    Sanchez-Pulido, Luis; Ponting, Chris P

    2011-10-15

    Evolutionary and protein structural analyses can provide functional insights into genes implicated in human psychiatric diseases. Even eukaryotic organisms lacking nervous systems contain homologues of many key signalling molecules of animal neurons implying that human cognition derives, in part, from modifications of ancestral molecules and complexes. One protein whose evolutionary origin is obscure is DISC1 (disrupted in schizophrenia 1) whose gene locus has been associated with many psychiatric conditions including schizophrenia, clinical depression and bipolar disorder. This protein's rapid evolution and its unusual amino acid and α-helix composition have hindered searches for DISC1 homologues in species other than vertebrates. Here, we review the evolution and structure of the DISC1 protein in the light of in-depth sequence analyses. These predict DISC1 orthologues in diverse eukaryotic organisms, including early-branching animals such as amphioxus, sea anemone, amoebas and Trichoplax, and in plants and algae. DISC1 thus is widespread among eukaryotes, although it remains absent from fungi, nematodes and Diptera, including fruit flies. These observations now permit studies of DISC1 function in simple non-vertebrate model organisms. Surprisingly, these analyses also identify between two and four sequence repeats in DISC1 orthologues. The first two of these repeats show significant sequence similarity to the UVR family of globular domains. These UVR-like repeats are predicted to contain, not coiled coil structures, but rather two closely associated antiparallel α-helices. One common missense variant in DISC1 (L607F) lies within the second DISC1 UVR-like domain. These observations should assist in delineating the functional regions of the DISC1 protein. PMID:21852244

  1. Assessment of Functional and Behavioral Changes Sensitive to Painful Disc Degeneration

    PubMed Central

    Lai, Alon; Moon, Andrew; Purmessur, Devina; Skovrlj, Branko; Winkelstein, Beth A.; Cho, Samuel K.; Hecht, Andrew C.; Iatridis, James C.

    2015-01-01

    The development of an in vivo rodent discogenic pain model can provide insight into mechanisms for painful disc degeneration. Painful disc degeneration in rodents can be inferred by examining responses to external stimuli, observing pain-related behaviors, and measuring functional performance. This study compared the sensitivity of multiple pain and functional assessment methods to disc disruption for identifying the parameters sensitive to painful disc degeneration in rats. Disc degeneration was induced in rats by annular injury with saline injection. The severity of disc degeneration, pain sensitivity, and functional performance were compared to sham and näve control rats. Saline injection induced disc degeneration with decreased disc height and MRI signal intensity as well as more fibrous nucleus pulposus, disorganized annular lamellae and decreased proteoglycan. Rats also demonstrated increased painful behaviors including decreased hindpaw mechanical and thermal sensitivities, increased grooming, and altered gait patterns with hindpaw mechanical hyperalgesia and duration of grooming tests being most sensitive. This is the first study to compare sensitivities of different pain assessment methods in an in vivo rat model of disc degeneration. Hindpaw mechanical sensitivity and duration of grooming were the most sensitive parameters to surgically induced degenerative changes and overall results were suggestive of disc degeneration associated pain. PMID:25731955

  2. Prevalence of Propionibacterium acnes in Intervertebral Discs of Patients Undergoing Lumbar Microdiscectomy: A Prospective Cross-Sectional Study

    PubMed Central

    Capoor, Manu N.; Ruzicka, Filip; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Schmitz, Jonathan E.; Hermanova, Marketa; Sana, Jiri; Michu, Elleni; Baird, John C.; Ahmed, Fahad S.; Maca, Karel; Lipina, Radim; Alamin, Todd F.; Coscia, Michael F.; Stonemetz, Jerry L.; Witham, Timothy; Ehrlich, Garth D.; Gokaslan, Ziya L.; Mavrommatis, Konstantinos; Birkenmaier, Christof; Fischetti, Vincent A.; Slaby, Ondrej

    2016-01-01

    findings are due to contamination and supports the hypothesis P. acnes acts as a pathogen in these cases of degenerative disc disease. PMID:27536784

  3. Fracture of the articular disc in the temporomandibular joint: two case reports

    PubMed Central

    An, S-Y

    2015-01-01

    Disc fracture of the temporomandibular joint (TMJ) is a little-known pathological condition owing to its extreme rarity. We report two cases of elderly patients who were diagnosed with disc fracture of the TMJ based on MRI, and we review related reports. On physical examination, an incomplete bite and mild joint pain were observed on the affected side in both patients. An MRI showed a complete fracture in the intermediate zone of the articular disc in the TMJ; the posterior fragment was displaced posteriorly, causing occlusal change in the closed position of the condyle and an incomplete bite. Conservative treatment including manual manipulation, physical therapy and oral appliance had no effect on the occlusal abnormality. Although the inciting cause of the disc fracture remained unclear, the degenerative changes in the joint may have been a factor by increasing the brittleness and reducing the elasticity of the disc. PMID:25308829

  4. DEGENERATIVE STENOSIS OF THE LUMBAR SPINE

    PubMed Central

    Zylbersztejn, Sérgio; Spinelli, Leandro de Freitas; Rodrigues, Nilson Rodinei; Werlang, Pablo Mariotti; Kisaki, Yorito; Rios, Aldemar Roberto Mieres; Bello, Cesar Dall

    2015-01-01

    This paper presents an update on degenerative stenosis of the lumbar spine, which is a common pathological condition among patients over the age of 65 years. The anamnesis and physical examination need to be precise, since radiography often only provides indirect signs. Magnetic resonance imaging is necessary if the symptoms persist. The treatment for lumbar stenosis is a matter of controversy. However, there seems to be some benefit from surgical treatment rather than conservative treatment, such that surgery brings improvements in symptoms and functions for a period of up to two years. PMID:27042635

  5. Little-known Swiss contributions to the description, diagnosis, and surgery of lumbar disc disease before the Mixter and Barr era.

    PubMed

    Stienen, Martin Nikolaus; Surbeck, Werner; Tröhler, Ulrich; Hildebrandt, Gerhard

    2013-12-01

    The understanding of lumbar spine pathologies made substantial progress at the turn of the twentieth century. The authors review the original publication of Otto Veraguth in 1929 reporting on the successful resection of a herniated lumbar disc, published exclusively in the German language. His early report is put into the historical context, and its impact on the understanding of pathologies of the intervertebral disc (IVD) is estimated. The Swiss surgeon and Nobel Prize laureate Emil Theodor Kocher was among the first physicians to describe the traumatic rupture of the IVD in 1896. As early as 1909 Oppenheim and Krause published 2 case reports on surgery for a herniated lumbar disc. Goldthwait was the first physician to delineate the etiopathogenes is between annulus rupture, symptoms of sciatica, and neurological signs in his publication of 1911. Further publications by Middleton and Teacher in 1911 and Schmorl in 1929 added to the understanding of lumbar spinal pathologies. In 1929, the Swiss neurologist Veraguth (surgery performed by Hans Brun) and the American neurosurgeon Walter Edward Dandy both published their early experiences with the surgical therapy of a herniated lumbar disc. Veraguth's contribution, however, has not been appreciated internationally to date. The causal relationship between lumbar disc pathology and sciatica remained uncertain for some years to come. The causal relationship was not confirmed until Mixter and Barr's landmark paper in 1934 describing the association of sciatica and lumbar disc herniation, after which the surgical treatment became increasingly popular. Veraguth was among the first physicians to report on the clinical course of a patient with successful resection of a herniated lumbar disc. His observations should be acknowledged in view of the limited experience and literature on this ailment at that time. PMID:24074509

  6. Stem Cell Therapies for Intervertebral Disc Degeneration: Immune Privilege Reinforcement by Fas/FasL Regulating Machinery.

    PubMed

    Ma, Chi-Jiao; Liu, Xu; Che, Lu; Liu, Zhi-Heng; Samartzis, Dino; Wang, Hai-Qiang

    2015-01-01

    As a main contributing factor to low back pain, intervertebral disc degeneration (IDD) is the fundamental basis for various debilitating spinal diseases. The pros and cons of current treatment modalities necessitate biological treatment strategies targeting for reversing or altering the degeneration process in terms of molecules or genes. The advances in stem cell research facilitate the studies aiming for possible clinical application of stem cell therapies for IDD. Human NP cells are versatile with cell morphology full of variety, capable of synthesizing extracellular matrix components, engulfing substances by autophagy and phagocytosis, mitochondrial vacuolization indicating dysfunction, expressing Fas and FasL as significant omens of immune privileged sites. Human discs belong to immune privilege organs with functional FasL expression, which can interact with invasive immune cells by Fas-FasL regulatory machinery. IDD is characterized by decreased expression level of FasL with dysfunctional FasL, which in turn unbalances the interaction between NP cells and immune cells. Certain modulation factors might play a role in the process, such as miR-155. Accumulating evidence indicates that Fas-FasL network expresses in a variety of stem cells. Given the expression of functional FasL and insensitive Fas in stem cells (we term as FasL privilege), transplantation of stem cells into the disc may regenerate the degenerative disc by not only differentiating into NP-like cells, increasing extracellular matrix, but also reinforce immune privilege via interaction with immune cells by Fas-FasL network. PMID:25381758

  7. Primary Bovine Intervertebral Disc Cells Transduced with Adenovirus Overexpressing 12 BMPs and Sox9 Maintain Appropriate Phenotype

    PubMed Central

    Zhang, Yejia; Markova, Dessislava; Im, Hee-Jeong; Hu, Wenyang; Thonar, Eugene J.-M.A.; He, Tong-Chuan; An, Howard S.; Phillips, Frank M.; Anderson, D. Greg

    2010-01-01

    Objective To confirm that primary intervertebral disc cells cultured in monolayer transduced with adenovirus maintained their phenotype, hence is an appropriate system to test gene therapy agents. Design Adult bovine nucleus pulposus and anulus fibrosus cells cultured in monolayer were transduced with adenoviruses expressing human bone morphogenetic proteins (AdBMPs) or Sox9 (AdSox9), or green fluorescence protein (AdGFP, as control). Chondrocyte phenotypic markers (e.g., type II collagen and aggrecan) and the chondrocyte hypertrophy marker (type X collagen) were measured 6 days after viral transduction by reverse-transcription polymerase chain reaction. Results Primary nucleus pulposus and anulus fibrosus cells transduced with AdBMPs, AdSox9, or adenovirus-expressing green fluorescence protein only (AdGFP, as control) continue to express healthy chondrocyte phenotypic markers and showed no evidence of the expression of the chondrocyte hypertrophy marker (type X collagen gene). Thus, we have shown that bovine nucleus pulposus and anulus fibrosus cells transduced with adenovirus overexpressing 12 different bone morphogenetic proteins or Sox9 maintain their phenotype in short-term culture. Conclusions In this study, primary bovine intervertebral disc cells transduced with adenovirus overexpressing 12 bone morphogenetic proteins or Sox9 preserved their phenotype in short-term culture. These cells did not express the type X collagen gene, an undesirable chondrocyte hypertrophic gene that could lead to ossification. Therefore, low-passage intervertebral disc cells cultured in monolayer is an appropriate culture system to test therapeutic genes. We further suggest that these cells may also be appropriate for engineering tissues or for cell therapy for degenerative disc diseases. PMID:19454853

  8. Gender difference in genetic association between IL1A variant and early lumbar disc degeneration: a three-year follow-up

    PubMed Central

    Eskola, Pasi J; Kjaer, Per; Sorensen, Joan S; Okuloff, Annaleena; Wedderkopp, Niels; Daavittila, Iita; Ala-Kokko, Leena; Männikkö, Minna; Karppinen, Jaro

    2012-01-01

    Objective The purpose of the present study was to analyze the associations between specific genetic markers and early disc degeneration (DD) or early disc degeneration progression (DDP) defined by magnetic resonance imaging (MRI). Methods We selected eleven of the most promising single nucleotide polymorphisms (SNP) and compared the distributions of these genetic markers between groups defined by MRI in a Danish adolescent population (N=166) over a three-year follow-up period. Results We observed a ten-fold higher annual incidence of endplate changes than previously reported in adults. The gender difference in IL1A rs1800587 association with DD remained significant and another association with DDP emerged in follow-up assessment. Among girls, the rs1800587 T-allele was associated both with DD (OR 2.82 [95% CI 1.29-6.16]) and with DDP (OR 2.45 [95% CI 1.03-5.82]). Among boys, the IL6 rs1800795 genotype G/C was protective in both DD (OR 0.26 [95% CI 0.09-0.72]) and DDP (OR 0.32 [95% CI 0.12-0.88]) with the IL6 rs1800797 genotype G/A was associated with a decreased likelihood of DD (OR 0.27 [95% CI 0.10-0.77]). Gender-genotype interactions were significant for polymorphisms in both IL1A and IL6. Correction for multiple testing weakened the associations for IL6 polymorphisms. Conclusion We conclude that gender specific effects in lumbar disc degeneration and its progression are possible. However, further evaluations in larger populations are needed. Our results provide some support to the hypothesis that early disc degeneration is an especially important phase in the cascade of degenerative disc disease. PMID:23050050

  9. Wake-up stroke in a young woman with rotational vertebral artery occlusion due to far-lateral cervical disc herniation.

    PubMed

    Okawa, Masakazu; Amamoto, Takaaki; Abe, Hiroshi; Yoshimura, Sohei; Higashi, Toshio; Inoue, Tooru

    2015-08-01

    Wake-up stroke is most likely to be caused by small-vessel disease, and is related to snoring. The authors present a rare case of far-lateral cervical disc herniation with neck rotation, resulting in wake-up stroke in a young woman. The patient, a 31-year-old woman, was admitted to the hospital because of dysarthria and confusion when she awoke in the morning. Brain MRI showed acute infarction in the posterior fossa. Cerebral angiography showed thrombus in the distal top of the basilar artery and the bilateral posterior cerebral arteries. During angiography, the thrombus size decreased with heparinization. There was severe stenosis of the right vertebral artery (VA) at C5-6, and head rotation to the right resulted in complete occlusion of the right VA. Neck MRI showed far-lateral intervertebral disc herniation. Surgical decompression of the VA was performed via the anterior cervical approach. Histological examination showed a degenerative intervertebral disc. Postoperative angiography confirmed successful decompression of the VA. PMID:25932602

  10. Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells.

    PubMed

    Johnson, Zariel I; Gogate, Shilpa S; Day, Rebecca; Binch, Abbie; Markova, Dessislava Z; Chiverton, Neil; Cole, Ashley; Conner, Matt; Shapiro, Irving M; Le Maitre, Christine L; Risbud, Makarand V

    2015-05-20

    Objectives of this study were to investigate whether AQP1 and AQP5 expression is altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate their expression in NP cells. AQP expression was measured in human tissues from different degenerative grades; regulation by hypoxia and HIF-1 was studied using promoter analysis and gain- and loss-of-function experiments. We show that both AQPs are expressed in the disc and that mRNA and protein levels decline with human disease severity. Bioinformatic analyses of AQP promoters showed multiple evolutionarily conserved HREs. Surprisingly, hypoxia failed to induce promoter activity or expression of either AQP. While genomic chromatin immunoprecipitation showed limited binding of HIF-1α to conserved HREs, their mutation did not suppress promoter activities. Stable HIF-1α suppression significantly decreased mRNA and protein levels of both AQPs, but HIF-1α failed to induce AQP levels following accumulation. Together, our results demonstrate that AQP1 and AQP5 expression is sensitive to human disc degeneration and that HIF-1α uniquely maintains basal expression of both AQPs in NP cells, independent of oxemic tension and HIF-1 binding to promoter HREs. Diminished HIF-1 activity during degeneration may suppress AQP levels in NP cells, compromising their ability to respond to extracellular osmolarity changes. PMID:25844601

  11. Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: novel HIF-1-mediated regulation of aquaporins in NP cells

    PubMed Central

    Day, Rebecca; Binch, Abbie; Markova, Dessislava Z.; Chiverton, Neil; Cole, Ashley; Conner, Matt; Shapiro, Irving M.; Le Maitre, Christine L.; Risbud, Makarand V.

    2015-01-01

    Objectives of this study were to investigate whether AQP1 and AQP5 expression is altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate their expression in NP cells. AQP expression was measured in human tissues from different degenerative grades; regulation by hypoxia and HIF-1 was studied using promoter analysis and gain- and loss-of-function experiments. We show that both AQPs are expressed in the disc and that mRNA and protein levels decline with human disease severity. Bioinformatic analyses of AQP promoters showed multiple evolutionarily conserved HREs. Surprisingly, hypoxia failed to induce promoter activity or expression of either AQP. While genomic chromatin immunoprecipitation showed limited binding of HIF-1α to conserved HREs, their mutation did not suppress promoter activities. Stable HIF-1α suppression significantly decreased mRNA and protein levels of both AQPs, but HIF-1α failed to induce AQP levels following accumulation. Together, our results demonstrate that AQP1 and AQP5 expression is sensitive to human disc degeneration and that HIF-1α uniquely maintains basal expression of both AQPs in NP cells, independent of oxemic tension and HIF-1 binding to promoter HREs. Diminished HIF-1 activity during degeneration may suppress AQP levels in NP cells, compromising their ability to respond to extracellular osmolarity changes. PMID:25844601

  12. Degenerative meniscus: Pathogenesis, diagnosis, and treatment options

    PubMed Central

    Howell, Richard; Kumar, Neil S; Patel, Nimit; Tom, James

    2014-01-01

    The symptomatic degenerative meniscus continues to be a source of discomfort for a significant number of patients. With vascular penetration of less than one-third of the adult meniscus, healing potential in the setting of chronic degeneration remains low. Continued hoop and shear stresses upon the degenerative meniscus results in gross failure, often in the form of complex tears in the posterior horn and midbody. Patient history and physical examination are critical to determine the true source of pain, particularly with the significant incidence of simultaneous articular pathology. Joint line tenderness, a positive McMurray test, and mechanical catching or locking can be highly suggestive of a meniscal source of knee pain and dysfunction. Radiographs and magnetic resonance imaging are frequently utilized to examine for osteoarthritis and to verify the presence of meniscal tears, in addition to ruling out other sources of pain. Non-operative therapy focused on non-steroidal anti-inflammatory drugs and physical therapy may be able to provide pain relief as well as improve mechanical function of the knee joint. For patients refractory to conservative therapy, arthroscopic partial meniscectomy can provide short-term gains regarding pain relief, especially when combined with an effective, regular physiotherapy program. Patients with clear mechanical symptoms and meniscal pathology may benefit from arthroscopic partial meniscectomy, but surgery is not a guaranteed success, especially with concomitant articular pathology. Ultimately, the long-term outcomes of either treatment arm provide similar results for most patients. Further study is needed regarding the short and long-term outcomes regarding conservative and surgical therapy, with a particular focus on the economic impact of treatment as well. PMID:25405088

  13. Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study.

    PubMed

    Fusellier, Marion; Colombier, Pauline; Lesoeur, Julie; Youl, Samy; Madec, Stéphane; Gauthier, Olivier; Hamel, Olivier; Guicheux, Jérôme; Clouet, Johann

    2016-01-01

    Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD) degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP) is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi)), radiography (IVD height index), and histology (NP area and Boos' scoring). The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos' scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration. PMID:27247937

  14. Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study

    PubMed Central

    Colombier, Pauline; Lesoeur, Julie; Youl, Samy; Madec, Stéphane; Gauthier, Olivier; Hamel, Olivier; Guicheux, Jérôme; Clouet, Johann

    2016-01-01

    Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD) degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP) is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi)), radiography (IVD height index), and histology (NP area and Boos' scoring). The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos' scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration. PMID:27247937

  15. Precision diagnostic disc injections.

    PubMed

    Fortin, J D

    2000-07-01

    Spinal pain is an important public health problem affecting the population indiscriminately. The structures responsible for pain in the spine include the vertebrae, intervertebral discs, spinal cord, nerve roots, facet joints, ligaments, muscles, atlanto-occipital joints, atlanto-axial joints, and sacroiliac joints. Even though disc herniation, facet joints, strained muscles, and torn ligaments have been attributed to be the cause of most spinal pain, either in the neck and upper extremities, upper and mid back, or low back and lower extremities, disorders of the disc other than disc herniation have been implicated more frequently than any other disorders. Once stifled by misinformation, discography now has applications in a number of clinical settings. While cervical and lumbar discography is well studied and well known, thoracic discography is in its nascent stages of clinical application. The value of discography lies in its ability to produce pain and thereby identify a "pain generator." This allows treatment to be based on the specific cause of pain. The three primary components of diagnostic disc injection are: provocation/analgesia, discometry, and nucleography. Despite the recent exponential growth of noninvasive spinal technology, diagnostic disc injection remains the sole direct method for definitively determining whether a disc is a physiological pain generator. It is clear that discography is a safe and powerful complement to the overall clinical context. PMID:16906185

  16. Proteomic Signature of the Murine Intervertebral Disc

    PubMed Central

    McCann, Matthew R.; Patel, Priya; Frimpong, Agya; Xiao, Yizhi; Siqueira, Walter L.; Séguin, Cheryle A.

    2015-01-01

    Low back pain is the most common musculoskeletal problem and the single most common cause of disability, often attributed to degeneration of the intervertebral disc. Lack of effective treatment is directly related to our limited understanding of the pathways responsible for maintaining disc health. While transcriptional analysis has permitted initial insights into the biology of the intervertebral disc, complete proteomic characterization is required. We therefore employed liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) protein/peptide separation and mass spectrometric analyses to characterize the protein content of intervertebral discs from skeletally mature wild-type mice. A total of 1360 proteins were identified and categorized using PANTHER. Identified proteins were primarily intracellular/plasma membrane (35%), organelle (30%), macromolecular complex (10%), extracellular region (9%). Molecular function categorization resulted in three distinct categories: catalytic activity (33%), binding (molecule interactions) (29%), and structural activity (13%). To validate our list, we confirmed the presence of 14 of 20 previously identified IVD-associated markers, including matrix proteins, transcriptional regulators, and secreted proteins. Immunohistochemical analysis confirmed distinct localization patterns of select protein with the intervertebral disc. Characterization of the protein composition of healthy intervertebral disc tissue is an important first step in identifying cellular processes and pathways disrupted during aging or disease progression. PMID:25689066

  17. Lentivirus-mediated TGF-β3, CTGF and TIMP1 gene transduction as a gene therapy for intervertebral disc degeneration in an in vivo rabbit model

    PubMed Central

    LIU, YONG; YU, TAO; MA, XUE-XIAO; XIANG, HONG-FEI; HU, YOU-GU; CHEN, BO-HUA

    2016-01-01

    The present study examined the effects of transforming growth factor (TGF)-β3, connective tissue growth factor (CTGF) and tissue inhibitor of metalloproteinase 1 (TIMP1) gene transduction, using a lentiviral vector, on rabbit intervertebral disc degeneration in vivo, with the intention of investigating their potential use in gene therapy. A model of lumbar intervertebral disc degeneration was created by needle puncture into the annulus fibrosus of 15 New Zealand white rabbits. Empty lentivirus or recombinant lentiviral plasmid lenti-TGFβ3-P2A-CTGF-T2A-TIMP1 was injected into degenerative lumbar intervertebral discs (representing the control and experimental groups, respectively), whilst untreated degenerative lumbar intervertebral discs served as the puncture group. After 16 and 20 weeks, magnetic resonance imaging (MRI) was conducted and the changes in intensity on micrographs of degenerative intervertebral discs were measured. The mRNA levels of aggrecan and type II collagen in nucleus pulposus tissue were determined by reverse transcription-polymerase chain reaction, and protein expression levels of type II collagen and aggrecan were determined by western blot analysis. MRI results indicated that intervertebral disc degeneration was ameliorated in the experimental group when compared with the control and the puncture group. Furthermore, the expression levels of type II collagen and aggrecan in the puncture and control groups were significantly lower than in the experimental group (P<0.05). In conclusion, lenti-TGFβ3-P2A-CTGF-T2A-TIMP1 co-transduction can promote synthesis of aggrecan and type II collagen in degenerative intervertebral discs, thereby delaying intervertebral disc degeneration. These results indicate the potential of gene therapy in treatment of intervertebral disc degeneration. PMID:27073456

  18. Clinical outcomes of single-level lumbar artificial disc replacement compared with transforaminal lumbar interbody fusion in an Asian population

    PubMed Central

    Lee, Wei Ting; Liu, Gabriel; Thambiah, Joseph; Wong, Hee Kit

    2015-01-01

    INTRODUCTION The objective of this study was to examine the clinical outcome of single-level lumbar artificial disc replacement (ADR) compared to that of transforaminal lumbar interbody fusion (TLIF) for the treatment of symptomatic degenerative disc disease (DDD) in an Asian population. METHODS This was a retrospective review of 74 patients who had surgery performed for discogenic lower backs that involved only the L4/5 and L5/S1 levels. All the patients had lumbar DDD without radiculopathy or spondylolithesis, and concordant pain with discogram at the pathological level. The patients were divided into two groups – those who underwent ADR and those who underwent TLIF. RESULTS A trend suggesting that the ADR group had better perioperative outcomes (less blood loss, shorter operating time, shorter hospital stay and shorter time to ambulation) than the TLIF group was observed. However, a trend indicating that surgical-approach-related complications occurred more frequently in the ADR group than the TLIF group was also observed. The rate of revision surgery was comparable between the two groups. CONCLUSION Our findings suggest that for the treatment of discogenic lower back pain, lumbar ADR has better perioperative outcomes and a similar revision rate when compared with TLIF. However, the use of ADR was associated with a higher incidence of surgical-approach-related complications. More studies with bigger cohort sizes and longer follow-up periods are needed to determine the long-term efficacy and safety of ADR in lumbar DDD. PMID:25917472

  19. Clinical outcomes after treatment with disc prostheses in three lumbar segments compared to one- or two segments

    PubMed Central

    Gillberg-Aronsson, Nina

    2015-01-01

    Background Fusion surgery in the rare patients suffering from symptomatic degenerative disc disease (DDD) at three segments has been reported to produce poor results and a high frequency of complications, why patients suffering from DDD at three segments are seldom offered surgical treatment. Purpose To compare clinical outcome after one- and two years, between patients that have undergone disc replacement surgery (TDR) at three segments and patients that have been treated at less segments. Methods The present study is based on data recorded in the Swedish Spine Registry (SweSpine). The study group consisted of 30 patients who underwent three-segment TDR, the comparative group of 700 patients treated in one or two segments. Analyses included comparisons of preoperative data, postoperative results and improvement from baseline. Results Our results showed no differences in outcome between groups at one- and two years postoperatively. Improvements achieved after surgery in both groups well exceeded established values for minimally clinically important difference (MCID). Conclusions The results of this study show that patients with a diagnosis of therapy-resistant chronic low back pain (CLBP) due to DDD in one, two or even three lumbar segments achieve similar and good results after TDR surgery. Clinical relevance The rare patients with severe and convincing DDD from three segments might in carefully selected cases be offered surgery, with a reasonable chance of a beneficial outcome. PMID:26512343

  20. Spinal Deformity in Aged Zebrafish Is Accompanied by Degenerative Changes to Their Vertebrae that Resemble Osteoarthritis

    PubMed Central

    Hayes, Anthony J.; Reynolds, Scott; Nowell, Mari A.; Meakin, Lee B.; Habicher, Judith; Ledin, Johan; Bashford, Andrew; Caterson, Bruce; Hammond, Chrissy L.

    2013-01-01

    Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding of these changes through the development of experimental models may lead to improvements in existing clinical treatment options. The zebrafish is a well-established model for the study of skeletogenesis with significant potential in gerontological research. With advancing age, zebrafish frequently develop gross deformities of their vertebral column, previously ascribed to reduced trunk muscle tone. In this study, we assess degenerative changes specifically within the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years of age. We show increased frequency and severity of spinal deformities/curvatures with age. Underlying the most severe phenotypes are partial or complete vertebral dislocations and focal thickening of the vertebral bone at the joint margins. MicroCT examination demonstrates small defects, fractures and morphological evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the vertebrae during aging, but no significant change in bone density. Light and electron microscopic examination reveal striking age-related changes in cell morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral cartilage, particularly within the pericellular micro-environment. Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a consistent, age-related increase in the yield of total chondroitin sulfate disaccharide, but no change in sulfation pattern, supported by immunohistochemical analysis. Immunohistochemistry strongly identifies all three chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the vertebral cartilage, particularly within the pericellular micro-environment. In contrast, keratan sulfate immunolocalises specifically with the notochordal tissue of the intervertebral disc, and its

  1. Extreme lateral interbody fusion for the treatment of adult degenerative scoliosis.

    PubMed

    Caputo, Adam M; Michael, Keith W; Chapman, Todd M; Jennings, Jason M; Hubbard, Elizabeth W; Isaacs, Robert E; Brown, Christopher R

    2013-11-01

    Extreme lateral interbody fusion (XLIF; NuVasive Inc., San Diego, CA, USA) is a minimally invasive lateral transpsoas approach to the thoracolumbar spine. Though the procedure is rapidly increasing in popularity, limited data is available regarding its use in deformity surgery. We aimed to evaluate radiographic correction using XLIF in adults with degenerative lumbar scoliosis. Thirty consecutive patients were followed for an average of 14.3 months. Interbody fusion was completed using the XLIF technique with supplemental posterior instrumentation. Plain radiographs were obtained on all patients preoperatively, postoperatively, and at most recent follow-up. Plain radiographic measurements of coronal Cobb angle, apical vertebral translation, segmental lordosis, global lordosis, disc height, neuroforaminal height and neuroforaminal width were made at each time point. CT scans were obtained for all patients 1 year after surgery to evaluate for fusion. There was significant improvement in multiple radiographic parameters from preoperative to postoperative. Cobb angle corrected 72.3%, apical vertebral translation corrected 59.7%, neuroforaminal height increased 80.3%, neuroforaminal width increased 7.4%, and disc height increased 116.7%. Segmental lordosis at L4-L5 increased 14.1% and global lordosis increased 11.5%. There was no significant loss of correction from postoperative to most recent follow-up. There was an 11.8% pseudoarthrosis rate at levels treated with XLIF. Complications included lateral incisional hernia (n=1), rupture of anterior longitudinal ligament (n=2), wound breakdown (n=2), cardiac instability (n=1), pedicle fracture (n=1), and nonunion requiring revision (n=1). XLIF significantly improves coronal plane deformity in patients with adult degenerative scoliosis. XLIF has the ability to correct sagittal plane deformity, although it is most effective at lower lumbar levels. PMID:23906522

  2. Magnetic resonance imaging assessment of degenerative cervical myelopathy: a review of structural changes and measurement techniques.

    PubMed

    Nouri, Aria; Martin, Allan R; Mikulis, David; Fehlings, Michael G

    2016-06-01

    Degenerative cervical myelopathy encompasses a spectrum of age-related structural changes of the cervical spine that result in static and dynamic injury to the spinal cord and collectively represent the most common cause of myelopathy in adults. Although cervical myelopathy is determined clinically, the diagnosis requires confirmation via imaging, and MRI is the preferred modality. Because of the heterogeneity of the condition and evolution of MRI technology, multiple techniques have been developed over the years in an attempt to quantify the degree of baseline severity and potential for neurological recovery. In this review, these techniques are categorized anatomically into those that focus on bone, ligaments, discs, and the spinal cord. In addition, measurements for the cervical spine canal size and sagittal alignment are also described briefly. These tools have resulted collectively in the identification of numerous useful parameters. However, the development of multiple techniques for assessing the same feature, such as cord compression, has also resulted in a number of challenges, including introducing ambiguity in terms of which methods to use and hindering effective comparisons of analysis in the literature. In addition, newer techniques that use advanced MRI are emerging and providing exciting new tools for assessing the spinal cord in patients with degenerative cervical myelopathy. PMID:27246488

  3. The Application of Fiber-Reinforced Materials in Disc Repair

    PubMed Central

    Pei, Bao-Qing; Li, Hui; Zhu, Gang; Li, De-Yu; Fan, Yu-Bo; Wu, Shu-Qin

    2013-01-01

    The intervertebral disc degeneration and injury are the most common spinal diseases with tremendous financial and social implications. Regenerative therapies for disc repair are promising treatments. Fiber-reinforced materials (FRMs) are a kind of composites by embedding the fibers into the matrix materials. FRMs can maintain the original properties of the matrix and enhance the mechanical properties. By now, there are still some problems for disc repair such as the unsatisfied static strength and dynamic properties for disc implants. The application of FRMs may resolve these problems to some extent. In this review, six parts such as background of FRMs in tissue repair, the comparison of mechanical properties between natural disc and some typical FRMs, the repair standard and FRMs applications in disc repair, and the possible research directions for FRMs' in the future are stated. PMID:24383057

  4. The Incidence of Potential Candidates for Total Disc Replacement among Lumbar and Cervical Fusion Patient Populations

    PubMed Central

    Goldstein, Jeffrey A.; Bendo, John A.; Kim, Yong; Spivak, Jeffrey M.

    2011-01-01

    Study Design Retrospective chart review. Purpose To evaluate the incidence of potential total disc replacement (TDR) candidates among cervical and lumbar fusion patient populations using strict Food and Drug Administration (FDA) criteria and with relative exclusion criteria removed. Overview of Literature Recent studies suggest that the potential percentage of patients that are candidates for TDR ranges from 0-5% in lumbar fusions and 43% in cervical fusions. Methods We performed a retrospective chart review of 280 consecutive patients who had lumbar (n = 174) and cervical (n = 106) fusion or TDR performed by one of four independent adult orthopaedic spine surgeons. Charts were screened for investigational device exemption (IDE) inclusion/exclusion criteria and later reanalyzed excluding relative exclusion criteria, such as history of chronic medical illness, twolevel disease (cervical cases), and history of prior fusion surgery in the anatomic region. Results Of the 174 lumbar surgeries, 10 were TDR with Prodisc-L and 164 were lumbar fusions. The most common TDR exclusion criteria were lytic spondylolisthesis or spinal stenosis (47.7% of patients) and more than 2 level degenerative disc disease (37.9%). 14.9% had no IDE exclusion criteria and would be considered candidates for TDR. After excluding the relative lumbar exclusion criteria, this percentage increased to 25.8%. Of the 106 cervical cases, 3 had a TDR with Prodisc-C and 103 had a cervical fusion. Twenty eight percent had no IDE exclusion criteria and would be considered candidates for cervical TDR. Conclusions A larger percentage of cervical fusion candidates are potential candidates for TDR (28%) than lumbar fusion candidates (14.9%) based on the strict IDE criteria. PMID:22164315

  5. Disc in Flames: Roles of TNF-α and IL-1β in Intervertebral Disc Degeneration

    PubMed Central

    Johnson, Zariel I.; Schoepflin, Zachary R.; Choi, Hyowon; Shapiro, Irving M.; Risbud, Makarand V.

    2016-01-01

    The intervertebral disc is an important mechanical structure that allows range of motion of the spinal column. Degeneration of the intervertebral disc, incited by aging, traumatic insult, genetic predisposition, or other factors, is often defined by functional and structural changes in the tissue, including excessive breakdown of the extracellular matrix, increased disc cell senescence and death, and compromised biomechanical function of the tissue. Intervertebral disc degeneration is strongly correlated with low back pain, which is a highly prevalent and costly condition, significantly contributing to loss in productivity and health care costs. Disc degeneration is a chronic, progressive condition, and current therapies are limited and often focused on symptomatic pain relief rather than curtailing the progression of the disease. Inflammatory processes, exacerbated by cytokines TNF-α and IL-1β are believed to be key mediators of disc degeneration and low back pain. In this review, we describe the contributions of TNF-α and IL-1β to changes seen during disc degeneration at the cellular and tissue level, new evidence suggesting a link between infection of the spine and low back pain, and the emerging therapeutic modalities aimed at combating these processes. PMID:26388614

  6. Herniated Lumbar Disc

    MedlinePlus

    ... 50. A herniated lumbar disc may also cause back pain, although back pain alone (without leg pain) can have many causes ... 90% success); surgery is less effective in relieving back pain. Nonsurgical treatment Your doctor may prescribe nonsurgical treatments ...

  7. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype.

    PubMed

    Hirata, Hiroaki; Yurube, Takashi; Kakutani, Kenichiro; Maeno, Koichiro; Takada, Toru; Yamamoto, Junya; Kurakawa, Takuto; Akisue, Toshihiro; Kuroda, Ryosuke; Kurosaka, Masahiro; Nishida, Kotaro

    2014-03-01

    The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2α-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration. PMID:24285589

  8. Spinal Cord Diseases

    MedlinePlus

    ... this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such as meningitis and polio Inflammatory diseases Autoimmune diseases Degenerative diseases such as amyotrophic lateral ...

  9. Degenerative Changes in the Cervical Spine Are More Common in Middle-Aged Individuals with Thalidomide Embryopathy than in Healthy Controls

    PubMed Central

    Ghassemi Jahani, Shadi A.; Danielsson, Aina; Ab-Fawaz, Rana; Hebelka, Hanna; Danielson, Barbro; Brisby, Helena

    2016-01-01

    Background Thalidomide was used as a sedative drug for pregnant women in the 1950–60:s and resulted in children born with thalidomide embryopathy (TE), including upper limb malformations. These may alter the motion pattern of the cervical spine by the use of head/shoulder and mouth grip. Aims To compare degenerative changes in the cervical spine in TE individuals with healthy controls (CTR). Methods and Procedures Twenty-seven middle-aged TE individuals and 27 age- and gender-matched CTR were examined by cervical spine MRI. The presence of malformations, disc herniation(s), osteophytes, nerve and medullary compression and the degree of disc degeneration (DD) were evaluated. Outcomes and Results Significantly higher degree of DD was seen in the TE group compared with the controls (p<0.001). Similar frequencies of disc herniation and disc space narrowing were observed in the two groups, but more foraminal narrowing was seen in the TE group (p = 0.002). DD was observed relatively frequently at all cervical levels in the TE group, however, mainly at the two lower levels in the CTR. Conclusions and Implications Middle-aged individuals with TE have a higher frequency of degenerative changes in the cervical spine than controls, possibly caused by an altered load on the cervical spine. PMID:27175919

  10. Herniated lumbar disc

    PubMed Central

    2011-01-01

    Introduction Herniated lumbar disc is a displacement of disc material (nucleus pulposus or annulus fibrosis) beyond the intervertebral disc space. The highest prevalence is among people aged 30 to 50 years, with a male to female ratio of 2:1. There is little evidence to suggest that drug treatments are effective in treating herniated disc. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, non-drug treatments, and surgery for herniated lumbar disc? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 37 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acupuncture, advice to stay active, analgesics, antidepressants, bed rest, corticosteroids (epidural injections), cytokine inhibitors (infliximab), discectomy (automated percutaneous, laser, microdiscectomy, standard), exercise therapy, heat, ice, massage, muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), percutaneous disc decompression, spinal manipulation, and traction. PMID:21711958

  11. Prospective, Randomized Comparison of One-level Mobi-C Cervical Total Disc Replacement vs. Anterior Cervical Discectomy and Fusion: Results at 5-year Follow-up

    PubMed Central

    Zigler, Jack E.; Jackson, Robert; Nunley, Pierce D.; Bae, Hyun W.; Kim, Kee D.; Ohnmeiss, Donna D.

    2016-01-01

    Introduction There is increasing interest in the role of cervical total disc replacement (TDR) as an alternative to anterior cervical discectomy and fusion (ACDF). Multiple prospective randomized studies with minimum 2 year follow-up have shown TDR to be at least as safe and effective as ACDF in treating symptomatic degenerative disc disease at a single level. The purpose of this study was to compare outcomes of cervical TDR using the Mobi-C® with ACDF at 5-year follow-up. Methods This prospective, randomized, controlled trial was conducted as a Food and Drug Administration regulated Investigational Device Exemption trial across 23 centers with 245 patients randomized (2:1) to receive TDR with Mobi-C® Cervical Disc Prosthesis or ACDF with anterior plate and allograft. Outcome assessments included a composite overall success score, Neck Disability Index (NDI), visual analog scales (VAS) assessing neck and arm pain, Short Form-12 (SF-12) health survey, patient satisfaction, major complications, subsequent surgery, segmental range of motion, and adjacent segment degeneration. Results The 60-month follow-up rate was 85.5% for the TDR group and 78.9% for the ACDF group. The composite overall success was 61.9% with TDR vs. 52.2% with ACDF, demonstrating statistical non-inferiority. Improvements in NDI, VAS neck and arm pain, and SF-12 scores were similar between groups and were maintained from earlier follow-up through 60 months. There was no significant difference between TDR and ACDF in adverse events or major complications. Range of motion was maintained with TDR through 60 months. Device-related subsequent surgeries (TDR: 3.0%, ACDF: 11.1%, p<0.02) and adjacent segment degeneration at the superior level (TDR: 37.1%, ACDF: 54.7%, p<0.03) were significantly lower for TDR patients. Conclusions Five-year results demonstrate the safety and efficacy of TDR with the Mobi-C as a viable alternative to ACDF with the potential advantage of lower rates of reoperation and

  12. STUDIES OF MOLECULAR CHANGES IN INTERVERTEBRAL DISC DEGENERATION IN ANIMAL MODEL

    PubMed Central

    de Campos, Marcelo Ferraz; de Oliveira, Cintia Pereira; Neff, Charles Benjamin; Correa, Olga Maria de Toledo; Pinhal, Maria Aparecida Silva; Rodrigues, Luciano Miller Reis

    2016-01-01

    ABSTRACT Objective: To evaluate the structural and molecular changes in the extracellular matrix (ECM) during the process of intervertebral disc degeneration, using animal model. Methods: Wistar rats underwent intervertebral disc degeneration through 20-gauge needle puncture, and 360° rotation applied for 30 sec, representing the degenerated group, while control group was not submitted to this procedure. Histological parameters and expression of extracellular matrix molecules were evaluated in the 15th and 28th days after degenerative induction. Results: Fifteen days after the induction of intervertebral disc degeneration, significant changes were observed, such as reduction in the expression metalloprotease-9 (MMP9) and interleukins (IL-6 and IL-10). There was a significant increase in the expression of vascular endothelial growth factor (VEGF) and caspase-3. However, different alterations in the ECM were observed at 28 days, the level of collagen I, metalloprotease-2 (MMP2) and caspase-3 were enhanced. Furthermore, expression of heparanase isoforms (HPSE1 and HPSE2) mRNA were increased in the degenerative intervertebral disc. Conclusion: The different profiles of ECM molecules observed during the intervertebral disc degeneration suggest that molecular processes such as ECM remodeling, neovascularization, apoptosis and inflammation occur. Experimental Study. PMID:26997908

  13. Footprint Mismatch of Cervical Disc Prostheses with Chinese Cervical Anatomic Dimensions

    PubMed Central

    Dong, Liang; Tan, Ming-Sheng; Yan, Qin-Hua; Yi, Ping; Yang, Feng; Tang, Xiang-Sheng; Hao, Qing-Ying

    2015-01-01

    Background: The footprint of most prostheses is designed according to Caucasian data. Total disc replacement (TDR) has been performed widely for cervical degenerative diseases in China. It is essential to analyze the match sizes of prostheses footprints and Chinese cervical anatomic dimensions in our study. Methods: The anatomic dimensions of the C4–C7 segments of 138 patients (age range 16–77 years) in a Chinese population were measured by computed tomography scans. We compared the footprints of the most commonly used cervical disc prostheses (Bryan: Medtronic, Minneapolis, MN, USA; Prestige LP: Medtronic, Fridley, Minnesota, USA; Discover: DePuy, Raynham, MA, USA; Prodisc-C: Synthes, West Chester, PA, USA) in China with Chinese cervical anatomic dimensions and assessed the match of their size. Results: The mismatch of available dimensions of prostheses and anatomic data of cervical endplates ranged from 17.03% (C4/C5, Prestige LP, Prodisc-C) to 57.61% (C6/C7, Discover) in the anterior-posterior (AP) diameter, and 35.51% (C4/C5, Prodisc-C, Prestige LP) to 94.93% (C6/C7, Bryan) in the center mediolateral (CML) diameter. About 21.01% of endplates were larger than the largest prostheses in the AP diameter and 57.25% in the CML diameter. All available footprints of prostheses expect the Bryan with an unfixed height, can accommodate the disc height (DH), however, 36.23% of the middle DH was less than the smallest height of the prostheses. The average disc sagittal angles (DSAs) of C4–C7 junctions were 5.04°, 5.15°, and 4.13° respectively. Only the Discover brand had a built-in 7° lordotic angle, roughly matching with the DSA. Conclusions: There is a large discrepancy between footprints of prostheses and Chinese cervical anatomic data. In recent years, possible complications of TDR related with mismatch sizes are increasing, such as subsidence, displacement, and heterotopic ossification. Manufacturers of prostheses should introduce or produce additional

  14. Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation.

    PubMed

    Liao, Zhenhua; Fogel, Guy R; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

    2015-01-01

    BACKGROUND The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. MATERIAL AND METHODS Eighteen human cadaveric spines (C2-T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3-4 ACDR+C4-6 ACDF+C6-7ACDR; hybrid C3-5ACDF+C5-6ACDR+C6-7ACDR; hybrid C3-4ACDR+C4-5ACDR+C5-7ACDF); and 4-level fusion. RESULTS Four-level fusion resulted in significant decrease in the C3-C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. CONCLUSIONS Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835

  15. Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation

    PubMed Central

    Liao, Zhenhua; Fogel, Guy R.; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

    2015-01-01

    Background The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. Material/Methods Eighteen human cadaveric spines (C2–T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3–4 ACDR+C4–6 ACDF+C6–7ACDR; hybrid C3–5ACDF+C5–6ACDR+C6–7ACDR; hybrid C3–4ACDR+C4–5ACDR+C5–7ACDF); and 4-level fusion. Results Four-level fusion resulted in significant decrease in the C3–C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. Conclusions Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835

  16. Does lumbar facet arthrosis precede disc degeneration? A postmortem study.

    PubMed

    Eubanks, Jason David; Lee, Michael J; Cassinelli, Ezequiel; Ahn, Nicholas U

    2007-11-01

    It is believed lumbar degeneration begins in the disc, where desiccation and collapse lead to instability and compensatory facet arthrosis. We explored the contrary contention that facet degeneration precedes disc degeneration by examining 647 skeletal lumbar spines. Using facet osteophytosis as a measure of facet degeneration and vertebral rim osteophytosis as a measure of disc degeneration, we assumed bone degeneration in both locations equally reflected the progression of those in the soft tissues. We graded arthrosis Grade 0 to 4 on a continuum from no arthritis to ankylosis. The data were analyzed for different age groups to examine patterns of degeneration with age. Specimens younger than 30 years of age had a higher prevalence of facet osteophytosis compared with vertebral rim osteophotosis at L1-L2 and L2-L3. Specimens aged 30 to 39 years showed more facet osteophytosis than vertebral rim osteophytosis at L4-L5. Specimens older than 40 years, however, showed more vertebral rim osteophytosis compared with facet osteophytosis at all levels except L4-L5 and L5-S1. This skeletal study suggests facet osteophytosis appears early in the degenerative process, preceding vertebral rim osteophytosis of degenerating intervertebral discs. However, once facets begin deteriorating with age, vertebral rim osteophytosis overtakes continued facet osteophytosis. These data challenge the belief that facet osteophytosis follows vertebral rim osteophytosis; rather, it appears vertebral rim osteophytosis progresses more rapidly in later years, but facet osteophotosis occurs early, predominating in younger individuals. PMID:17767079

  17. A Comparative Study of Lateral Lumbar Interbody Fusion and Posterior Lumbar Interbody Fusion in Degenerative Lumbar Spondylolisthesis

    PubMed Central

    Hughes, Alexander P.; Sama, Andrew A.; Girardi, Federico P.; Lebl, Darren R.; Cammisa, Frank P.

    2015-01-01

    Study Design Level 4 retrospective review. Purpose To compare the radiographic and clinical outcomes between posterior lumbar interbody fusion (PLIF) and lateral lumbar interbody fusion (LLIF) with posterior segmental spinal instrumentation (SSI) for degenerative lumbar spondylolisthesis. Overview of Literature Both PLIF and LLIF have been performed for degenerative spondylolisthesis with good results, but no study has directly compared these two techniques so far. Methods The electronic medical and radiographic records of 78 matched patients were analyzed. In one group, 39 patients underwent PLIF with SSI at 41 levels (L3-4/L4-5), while in the other group, 39 patients underwent the LLIF procedure at 48 levels (L3-4/L4-5). Radiological outcomes such as restoration of disc height and neuroforaminal height, segmental lumbar lordosis, total lumbar lordosis, incidence of endplate fracture, and subsidence were measured. Perioperative parameters were also recorded in each group. Clinical outcome in both groups was assessed by the short form-12, Oswestry disability index and visual analogue scale scores. The average follow-up period was 16.1 months in the LLIF group and 21 months in the PLIF group. Results The restoration of disc height, foraminal height, and segmental lumbar lordosis was significantly better in the LLIF group (p<0.001). The duration of the operation was similar in both groups, but the average blood loss was significantly lower in the LLIF group (p<0.001). However, clinical outcome scores were similar in both groups. Conclusions Safe, effective interbody fusion can be achieved at multiple levels with neuromonitoring by the lateral approach. LLIF is a viable treatment option in patients with new onset symptoms due to degenerative spondylolisthesis who have had previous lumbar spine surgery, and it results in improved sagittal alignment and indirect foraminal decompression. PMID:26435782

  18. MRI findings in Hirayama's disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease?

    PubMed

    Schröder, R; Keller, E; Flacke, S; Schmidt, S; Pohl, C; Klockgether, T; Schlegel, U

    1999-11-01

    Hirayama's disease is a benign juvenile form of focal amyotrophy affecting the upper limbs. Previous studies have suggested that the disorder is a neck flexion induced cervical myelopathy. We report clinical and magnetic resonance imaging findings in nine patients with Hirayama's disease. Cervical imaging of seven patients revealed spinal cord changes consisting of focal atrophy and foci of signal alterations. On neck flexion a forward movement and mild reduction in the anteroposterior diameter of the lower cervical cord against the vertebral bodies was noted in affected individuals as well as in five normal controls. In contrast to earlier reports, none of our patients showed complete obliteration of the posterior subarachnoid space. Measurement of the anteroposterior spinal cord diameter in each vertebral segment (C4-C7) revealed no significant differences in the degree of spinal cord flattening between the two groups. Furthermore, two of our patients had significant degenerative changes in the cervical spine (disc herniation, retrospondylosis) contralateral to the clinically affected side. These degenerative changes resulted in a marked cord compression on neck flexion but were not associated with ipsilateral clinical abnormalities or spinal cord alterations. Our results argue against a flexion-induced cervical myelopathy and support the view that Hirayama's disease is an intrinsic motor neuron disease. PMID:10631640

  19. Reported Outcome Measures in Degenerative Cervical Myelopathy: A Systematic Review

    PubMed Central

    McHugh, Maire; Elgheriani, Ali; Kolias, Angelos G.; Tetreault, Lindsay A.; Hutchinson, Peter J. A.; Fehlings, Michael G.; Kotter, Mark R. N.

    2016-01-01

    Objective Degenerative cervical myelopathy [DCM] is a disabling and increasingly prevalent group of diseases. Heterogeneous reporting of trial outcomes limits effective inter-study comparison and optimisation of treatment. This is recognised in many fields of healthcare research. The present study aims to assess the heterogeneity of outcome reporting in DCM as the premise for the development of a standardised reporting set. Methods A systematic review of MEDLINE and EMBASE databases, registered with PROSPERO (CRD42015025497) was conducted in accordance with PRISMA guidelines. Full text articles in English, with >50 patients (prospective) or >200 patients (retrospective), reporting outcomes of DCM were eligible. Results 108 studies, assessing 23,876 patients, conducted world-wide, were identified. Reported outcome themes included function (reported by 97, 90% of studies), complications (reported by 56, 52% of studies), quality of life (reported by 31, 29% of studies), pain (reported by 29, 27% of studies) and imaging (reported by 59, 55% of studies). Only 7 (6%) studies considered all of domains in a single publication. All domains showed variability in reporting. Conclusions Significant heterogeneity exists in the reporting of outcomes in DCM. The development of a consensus minimum dataset will facilitate future research synthesis. PMID:27482710

  20. Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Taylor, Alexandra C; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2016-02-01

    Canine degenerative myelopathy (CDM) represents a unique naturally occurring animal model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs, neuropathologic findings, and involvement of the superoxide dismutase 1 (SOD1) mutation. A definitive diagnosis can only be made postmortem through microscopic detection of axonal degeneration, demyelination and astroglial proliferation, which is more severe in the dorsal columns of the thoracic spinal cord and in the dorsal portion of the lateral funiculus. Interestingly, the muscle acetylcholine receptor complexes are intact in CDM prior to functional impairment, thus suggesting that muscle atrophy in CDM does not result from physical denervation. Moreover, since sensory involvement seems to play an important role in CDM progression, a more careful investigation of the sensory pathology in ALS is also warranted. The importance of SOD1 expression remains unclear, while oxidative stress and denatured ubiquinated proteins appear to play a crucial role in the pathogenesis of CDM. In this updated narrative review we performed a systematic search of the published studies on CDM that may shed light on the pathophysiological mechanisms of human ALS. A better understanding of the factors that determine the disease progression in CDM may be beneficial for the development of effective treatments for ALS. PMID:26432396

  1. Degenerative lumbar spinal stenosis and its imposters: three case studies

    PubMed Central

    Ammendolia, Carlo

    2014-01-01

    Degenerative lumbar spinal stenosis causing neurogenic claudicaton is a common condition impacting walking ability in older adults. There are other highly prevalent conditions in this patient population that have similar signs and symptoms and cause limited walking ability. The purpose of this study is to highlight the diagnostic challenges using three case studies of older adults who present with limited walking ability who have imaging evidence of degenerative lumbar spinal stenosis. PMID:25202160

  2. The Relationship between Increased Intervertebral Disc Height and Development of Postoperative Axial Neck Pain after Anterior Cervical Fusion

    PubMed Central

    Chang, Han; Baek, Dong-Hoon

    2014-01-01

    Objective To evaluate the relationship between postoperative increase in intervertebral disc space height (IVH) and posterior axial neck in cases of degenerative cervical disease treated with anterior cervical discectomy and fusion (ACDF). Methods A total of 155 patients who underwent ACDF with more than 1 year follow up were included. Radiologically, IVH and interfacet distance (IFD) of the operated segment were measured preoperatively and postoperatively. We clinically evaluated neck and arm pains according to visual analogue scale (VAS) scores and assessed neck disability index (NDI) scores preoperatively, postoperatively, at 3 months, 6 months, and 1 year postoperatively. The relationship between radiological parameters, and clinical scores were analyzed using a regression analysis. Results The mean increase in IVH was 2.62 mm, and the mean increase in IFD was 0.67 mm. The VAS scores for neck pain preoperatively, postoperatively, and at 3 months, 6 months, 1 year postoperatively were 4.46, 2.11, 2.07, 1.95, and 1.29; those for arm pain were 5.89, 3.24, 3.20, 3.03, and 2.18. The NDI scores were improved from 18.52 to 7.47. No significant relationship was observed between the radiological evaluation results regarding the increase in intervertebral height or interfacet distance and clinical changes in VAS or NDI scores. Conclusion The increase in intervertebral space or interfacet distance by the insertion of a large graft material while performing ACDF for the treatment of degenerative cervical disease was not related with the change in VAS scores for neck and arm pains and NDI scores postoperatively and during the follow-up period. PMID:25237430

  3. Who should have surgery for degenerative spondylolisthesis?

    PubMed Central

    Pearson, Adam M.; Lurie, Jon D.; Tosteson, Tor D.; Zhao, Wenyan; Abdu, William A.; Weinstein, James N.

    2013-01-01

    Study Design Combined prospective randomized controlled trial and observational cohort study of degenerative spondylolisthesis (DS) with an as-treated analysis. Objective To determine modifiers of the treatment effect (TE) of surgery (the difference between surgical and nonoperative outcomes) for DS using subgroup analysis. Summary of Background Data SPORT demonstrated a positive surgical TE for DS at the group level. However, individual characteristics may affect TE. Methods DS patients were treated with either surgery (n=395) or nonoperative care (n=206) and were analyzed according to treatment received. Fifty-five baseline variables were used to define subgroups for calculating the time-weighted average TE for the Oswestry Disability Index (ODI) over 4 years (TE=ΔODIsurgery-ΔODInonoperative). Variables with significant subgroup-by-treatment interactions (p<0.05) were simultaneously entered into a multivariate model to select independent TE predictors. Results All analyzed subgroups that included at least 50 patients improved significantly more with surgery than with nonoperative treatment (p<0.05). Multivariate analyses demonstrated that age ≤ 67 (TE −15.7 vs. −11.8 for age>67, p=0.014); female gender (TE −15.6 vs. −11.2 for males, p=0.01); the absence of stomach problems (TE −15.2 vs. −11.3 for those with stomach problems, p=0.035); neurogenic claudication (TE −15.3 vs. −9.0 for those without claudication, p=0.004); reflex asymmetry (TE −17.3 vs. −13.0 for those without asymmetry, p=0.016); opioid use (TE −18.4 vs. −11.7 for those not using opioids, p<0.001); not taking antidepressants (TE −14.5 vs. −5.4 for those on antidepressants, p=0.014); dissatisfaction with symptoms (TE −14.5 vs. −8.3 for those satisfied or neutral, p=0.039); and anticipating a high likelihood of improvement with surgery (TE −14.8 vs. −5.1 for anticipating a low likelihood of improvement with surgery, p=0.019) were independently associated with

  4. The Chemistry of Optical Discs.

    ERIC Educational Resources Information Center

    Birkett, David

    2002-01-01

    Explains the chemistry used in compact discs (CD), digital versatile discs (DVD), and magneto-optical (MO) discs focusing on the steps of initial creation of the mold, the molding of the polycarbonate, the deposition of the reflective layers, the lacquering of the CDs, and the bonding of DVDs. (Contains 15 references.) (YDS)

  5. How do accretion discs break?

    NASA Astrophysics Data System (ADS)

    Dogan, Suzan

    2016-07-01

    Accretion discs are common in binary systems, and they are often found to be misaligned with respect to the binary orbit. The gravitational torque from a companion induces nodal precession in misaligned disc orbits. In this study, we first calculate whether this precession is strong enough to overcome the internal disc torques communicating angular momentum. We compare the disc precession torque with the disc viscous torque to determine whether the disc should warp or break. For typical parameters precession wins: the disc breaks into distinct planes that precess effectively independently. To check our analytical findings, we perform 3D hydrodynamical numerical simulations using the PHANTOM smoothed particle hydrodynamics code, and confirm that disc breaking is widespread and enhances accretion on to the central object. For some inclinations, the disc goes through strong Kozai cycles. Disc breaking promotes markedly enhanced and variable accretion and potentially produces high-energy particles or radiation through shocks. This would have significant implications for all binary systems: e.g. accretion outbursts in X-ray binaries and fuelling supermassive black hole (SMBH) binaries. The behaviour we have discussed in this work is relevant to a variety of astrophysical systems, for example X-ray binaries, where the disc plane may be tilted by radiation warping, SMBH binaries, where accretion of misaligned gas can create effectively random inclinations and protostellar binaries, where a disc may be misaligned by a variety of effects such as binary capture/exchange, accretion after binary formation.

  6. Revival of the Jumping Disc

    ERIC Educational Resources Information Center

    Ucke, C.; Schlichting, H-J.

    2009-01-01

    Snap discs made of bimetal have many technical applications as thermostats. Jumping discs are a toy version of such snap discs. Besides giving technical information, we describe physical investigations. We show especially how, through simple measurements and calculations, you can determine the initial speed ([approximately equal to]3.5 m…

  7. Learning Language on Disc.

    ERIC Educational Resources Information Center

    Desmarais, Norman

    1995-01-01

    Presents a comparison of two types of compact disc (CD-ROM) foreign language tutorials: (1) those made by publishers who favor an immersion approach; and (2) those made by publishers who use grammar-based approaches. Both types of CD-ROMs address various age groups, skill levels, and learning styles. (JMV)

  8. The DISC Quotient

    NASA Astrophysics Data System (ADS)

    Elliott, John R.; Baxter, Stephen

    2012-09-01

    D.I.S.C: Decipherment Impact of a Signal's Content. The authors present a numerical method to characterise the significance of the receipt of a complex and potentially decipherable signal from extraterrestrial intelligence (ETI). The purpose of the scale is to facilitate the public communication of work on any such claimed signal, as such work proceeds, and to assist in its discussion and interpretation. Building on a "position" paper rationale, this paper looks at the DISC quotient proposed and develops the algorithmic steps and comprising measures that form this post detection strategy for information dissemination, based on prior work on message detection, decipherment. As argued, we require a robust and incremental strategy, to disseminate timely, accurate and meaningful information, to the scientific community and the general public, in the event we receive an "alien" signal that displays decipherable information. This post-detection strategy is to serve as a stepwise algorithm for a logical approach to information extraction and a vehicle for sequential information dissemination, to manage societal impact. The "DISC Quotient", which is based on signal analysis processing stages, includes factors based on the signal's data quantity, structure, affinity to known human languages, and likely decipherment times. Comparisons with human and other phenomena are included as a guide to assessing likely societal impact. It is submitted that the development, refinement and implementation of DISC as an integral strategy, during the complex processes involved in post detection and decipherment, is essential if we wish to minimize disruption and optimize dissemination.

  9. The Teddy Bears' Disc.

    ERIC Educational Resources Information Center

    Laurillard, Diana

    1985-01-01

    Reports an evaluation of the Teddy Bear disc, an interactive videodisc developed at the Open University for a second-level course in metallurgy and materials technology. Findings from observation of students utilizing the videodisc are reviewed; successful design features and design problems are considered; and development costs are outlined. (MBR)

  10. Creutzfeldt-Jakob Disease

    MedlinePlus

    Creutzfeldt-Jakob disease (CJD) is a rare, degenerative brain disorder. Symptoms usually start around age 60. Memory problems, behavior changes, vision ... during a medical procedure Cattle can get a disease related to CJD called bovine spongiform encephalopathy (BSE) ...

  11. Correlations between severity of clinical signs and histopathological changes in 60 dogs with spinal cord injury associated with acute thoracolumbar intervertebral disc disease.

    PubMed

    Henke, D; Vandevelde, M; Doherr, M G; Stöckli, M; Forterre, F

    2013-10-01

    The outcome of spinal surgery in dogs with absent voluntary motor function and nociception following intervertebral disc (IVD) herniation is highly variable, which likely attests to differences in the severity of spinal cord damage. This retrospective study evaluated the extent to which neurological signs correlated with histologically detected spinal cord damage in 60 dogs that were euthanased because of thoracolumbar IVD herniation. Clinical neurological grades correlated significantly with the extent of white matter damage (P<0.001). However, loss of nociception also occurred in 6/31 (19%) dogs with relatively mild histological changes. The duration of clinical signs, Schiff-Sherrington posture, loss of reflexes and pain on spinal palpation were not significantly associated with the severity of spinal cord damage. Although clinical-pathological correlation was generally good, some clinical signs frequently thought to indicate severe cord injury did not always correlate with the degree of cord damage, suggesting functional rather than structural impairment in some cases. PMID:23702280

  12. Tissue Engineering a Biological Repair Strategy for Lumbar Disc Herniation

    PubMed Central

    O'Connell, Grace D.; Leach, J. Kent; Klineberg, Eric O.

    2015-01-01

    Abstract The intervertebral disc is a critical part of the intersegmental soft tissue of the spinal column, providing flexibility and mobility, while absorbing large complex loads. Spinal disease, including disc herniation and degeneration, may be a significant contributor to low back pain. Clinically, disc herniations are treated with both nonoperative and operative methods. Operative treatment for disc herniation includes removal of the herniated material when neural compression occurs. While this strategy may have short-term advantages over nonoperative methods, the remaining disc material is not addressed and surgery for mild degeneration may have limited long-term advantage over nonoperative methods. Furthermore, disc herniation and surgery significantly alter the mechanical function of the disc joint, which may contribute to progression of degeneration in surrounding tissues. We reviewed recent advances in tissue engineering and regenerative medicine strategies that may have a significant impact on disc herniation repair. Our review on tissue engineering strategies focuses on cell-based and inductive methods, each commonly combined with material-based approaches. An ideal clinically relevant biological repair strategy will significantly reduce pain and repair and restore flexibility and motion of the spine. PMID:26634189

  13. Histological analysis of surgical samples and a proposed scoring system for infections in intervertebral discs.

    PubMed

    Rao, Prashanth J; Phan, Kevin; Maharaj, Monish M; Scherman, Daniel B; Lambie, Neil; Salisbury, Elizabeth; Mobbs, Ralph J

    2016-08-01

    Back pain remains one the most prevalent types of pain and disability worldwide. Infection is estimated to be the underlying cause in approximately 0.01% of patients. Despite recent evidence demonstrating prominent infection rates, a standardised algorithm for diagnosis of disc infection is lacking. Histopathological evaluation can aid in confirming inflammatory changes and also in identifying degenerative changes. Hence, standardising practice through a clear scoring system with regards to inflammation and degeneration may have some utility in the clinical setting. To our knowledge no such systems exist specifically for intervertebral disc infection. A literature review of current methods of scoring inflammation and degeneration in spine surgery and orthopaedic surgery was performed. Based on the current evidence, a scoring system for disc inflammatory and degenerative changes was proposed. We propose four domains for consideration: (1) granulation tissue, (2) dense fibrosis, (3) chronic inflammatory cells, and (4) neutrophil count. The non-standardised nature of diagnosing infections and degeneration in the spinal surgery literature means that this scoring system is currently of particular value. Based on a literature review, our proposed method for diagnosis incorporates a combination of histopathological criteria expected to increase diagnostic sensitivity in the setting of disc infection. Overall, scoring can be applied to surgically obtained material and integrated directly into routine pathological practice. PMID:27050918

  14. TNF-α and IL-1β Promote a Disintegrin-like and Metalloprotease with Thrombospondin Type I Motif-5-mediated Aggrecan Degradation through Syndecan-4 in Intervertebral Disc*

    PubMed Central

    Wang, Jianru; Markova, Dessislava; Anderson, D. Greg; Zheng, Zhaomin; Shapiro, Irving M.; Risbud, Makarand V.

    2011-01-01

    Elevated levels of TNF-α, IL-1β and a resultant increase in ADAMTS (a disintegrin-like and metalloprotease with thrombospondin type I motifs) expression is seen during disc degeneration. However, if these pro-inflammatory cytokines control ADAMTS activity is not definitively known. The goal of the investigation was to study if TNF-α and IL-1β regulate syndecan-4 (SDC4) expression, and if SDC4 was responsible for promoting aggrecan degradation through controlling ADAMTS activity in nucleus pulposus cells of the intervertebral disc. Cytokine treatment increased SDC4 expression and promoter activity. Use of inhibitor, SM7368 and co-transfections with IκBα, RelA/p50 showed that NF-κΒ regulated both basal and cytokine-dependent SDC4 transcription. SDC4 promoter harboring RelA binding site mutation was unresponsive to the cytokines. Moreover, cytokines failed to increase SDC4 promoter activity in RelA-null cells. Cytokines increased ADAMTS-4/5 expression and aggrecan degradation and promoted SDC4 interaction with ADAMTS-5. Treatment with heparinase-III and p-nitrophenyl-β-d-xylopyranoside (PNPX), an inhibitor of heparan sulfate synthesis and transfection with SDC4-shRNA partially blocked cytokine mediated aggrecan degradation. Analysis of human tissues showed increased aggrecan degradation with a concomitant increase in SDC4 and ADAMTS-5 protein expression with severity of disc disease. Likewise, SDC4, TNF-α, IL-1β, ADAMTS-4, and ADAMTS-5 mRNA expression increased in degenerate tissues. We conclude that in nucleus pulposus, TNF-α and IL-1β regulate SDC4 expression, which plays a key role in pathogenesis of degenerative disc disease by promoting aggrecan degradation by ADAMTS-5. PMID:21949132

  15. Spontaneous regression of herniated lumbar discs: Report of one illustrative case and review of the literature.

    PubMed

    Yang, Xiaohui; Zhang, Qin; Hao, Xiaoning; Guo, Xinghua; Wang, Liping

    2016-04-01

    Lumbar disc herniation (LDH) is a common disease that induces back pain and radicular pain. The most efficient method for the treatment of lumbar disc herniation is still controversial. Spontaneous regression of LDH has been recognized with the advancement of radiological diagnostic tools and can explain the reason of spontaneous relief of symptoms without treatment. The proposed hypotheses are; dehydration, retraction of the disc to the hernia in the annulus fibrosis, enzymatic catabolism and phagocytosis. In this study, the case of a patient with huge lumbar disc hernia regressing by itself has been presented and the potential mechanisms of disc regression have been discussed. PMID:26907997

  16. Biomechanics of Disc Degeneration

    PubMed Central

    Palepu, V.; Kodigudla, M.; Goel, V. K.

    2012-01-01

    Disc degeneration and associated disorders are among the most debated topics in the orthopedic literature over the past few decades. These may be attributed to interrelated mechanical, biochemical, and environmental factors. The treatment options vary from conservative approaches to surgery, depending on the severity of degeneration and response to conservative therapies. Spinal fusion is considered to be the “gold standard” in surgical methods till date. However, the association of adjacent level degeneration has led to the evolution of motion preservation technologies like spinal arthroplasty and posterior dynamic stabilization systems. These new technologies are aimed to address pain and preserve motion while maintaining a proper load sharing among various spinal elements. This paper provides an elaborative biomechanical review of the technologies aimed to address the disc degeneration and reiterates the point that biomechanical efficacy followed by long-term clinical success will allow these nonfusion technologies as alternatives to fusion, at least in certain patient population. PMID:22745914

  17. [Cervical disc herniation].

    PubMed

    Schnake, K J; Hoffmann, C-H; Kandziora, F

    2012-12-01

    The cervical disc herniation is characterized by prolapsed nucleus pulposus material through the annulus into the spinal canal. The local mechanical or chemical irritation of neural structures typically leads to symptoms of radiculopathy, cervicocephalgia or myelopathy. Pronounced sensorimotor deficits or intractable pain constitute surgical treatment. In all other cases conservative treatment is indicated, including pain medication, active and passive physiotherapy, and local injections, respectively. Anterior cervical discectomy and interbody fusion (ACDF) is still the surgical treatment of choice. Predominantly, cages with or without plates are in use to obtain solid fusion. The implantation of a total disc replacement is a viable alternative, if no contraindications exist. Other surgical techniques may be performed in proper selected cases. The overall clinical and radiological results of both surgical and conservative treatment are good. PMID:23296562

  18. Total disc replacement.

    PubMed

    Vital, J-M; Boissière, L

    2014-02-01

    Total disc replacement (TDR) (partial disc replacement will not be described) has been used in the lumbar spine since the 1980s, and more recently in the cervical spine. Although the biomechanical concepts are the same and both are inserted through an anterior approach, lumbar TDR is conventionally indicated for chronic low back pain, whereas cervical TDR is used for soft discal hernia resulting in cervicobrachial neuralgia. The insertion technique must be rigorous, with precise centering in the disc space, taking account of vascular anatomy, which is more complex in the lumbar region, particularly proximally to L5-S1. All of the numerous studies, including prospective randomized comparative trials, have demonstrated non-inferiority to fusion, or even short-term superiority regarding speed of improvement. The main implant-related complication is bridging heterotopic ossification with resulting loss of range of motion and increased rates of adjacent segment degeneration, although with an incidence lower than after arthrodesis. A sufficiently long follow-up, which has not yet been reached, will be necessary to establish definitively an advantage for TDR, particularly in the cervical spine. PMID:24412045

  19. Counter-rotating accretion discs

    NASA Astrophysics Data System (ADS)

    Dyda, S.; Lovelace, R. V. E.; Ustyugova, G. V.; Romanova, M. M.; Koldoba, A. V.

    2015-01-01

    Counter-rotating discs can arise from the accretion of a counter-rotating gas cloud on to the surface of an existing corotating disc or from the counter-rotating gas moving radially inwards to the outer edge of an existing disc. At the interface, the two components mix to produce gas or plasma with zero net angular momentum which tends to free-fall towards the disc centre. We discuss high-resolution axisymmetric hydrodynamic simulations of viscous counter-rotating discs for the cases where the two components are vertically separated and radially separated. The viscosity is described by an isotropic α-viscosity including all terms in the viscous stress tensor. For the vertically separated components, a shear layer forms between them and the middle part of this layer free-falls to the disc centre. The accretion rates are increased by factors of ˜102-104 over that for a conventional disc rotating in one direction with the same viscosity. The vertical width of the shear layer and the accretion rate are strongly dependent on the viscosity and the mass fraction of the counter-rotating gas. In the case of radially separated components where the inner disc corotates and the outer disc rotates in the opposite direction, a gap between the two components opens and closes quasi-periodically. The accretion rates are ≳25 times larger than those for a disc rotating in one direction with the same viscosity.

  20. Have protoplanetary discs formed planets?

    NASA Astrophysics Data System (ADS)

    Greaves, J. S.; Rice, W. K. M.

    2010-09-01

    It has recently been noted that many discs around T Tauri stars appear to comprise only a few Jupiter masses of gas and dust. Using millimetre surveys of discs within six local star formation regions, we confirm this result, and find that only a few per cent of young stars have enough circumstellar material to build gas giant planets, in standard core accretion models. Since the frequency of observed exoplanets is greater than this, there is a `missing-mass' problem. As alternatives to simply adjusting the conversion of dust flux to disc mass, we investigate three other classes of solution. Migration of planets could hypothetically sweep up the disc mass reservoir more efficiently, but trends in multiplanet systems do not support such a model, and theoretical models suggest that the gas accretion time-scale is too short for migration to sweep the disc. Enhanced inner-disc mass reservoirs are possible, agreeing with predictions of disc evolution through self-gravity, but not adding to millimetre dust flux as the inner disc is optically thick. Finally, the incidence of massive discs is shown to be higher at the protostellar stages, Classes 0 and I, where discs substantial enough to form planets via core accretion are abundant enough to match the frequency of exoplanets. Gravitational instability may also operate in the Class 0 epoch, where half the objects have potentially unstable discs of >~30 per cent of the stellar mass. However, recent calculations indicate that forming gas giants inside 50 au by instability is unlikely, even in such massive discs. Overall, the results presented suggest that the canonically `protoplanetary' discs of Class II T Tauri stars have globally low masses in dust observable at millimetre wavelengths, and conversion to larger bodies (anywhere from small rocks up to planetary cores) must already have occurred.

  1. Disc edge veins of Kraupa associated with optic disc drusen

    PubMed Central

    Díaz, Andrea; Almela, Miguel Angel

    2014-01-01

    Objective: Disc edge veins of Kraupa are a rare anomaly of the retinal venous system in which the main trunk of the retinal vein disappeared into the margin of the optic disc instead of its centre. Methods: A 40-year-old woman was detected to have an anomaly in her left optic disc in a routine eye examination. The eyes had an anomaly of the retinal venous system in which all branches of the retinal vein joined in a common trunk that entered the disc margin inferonasally. The central retinal artery issued from the centre of the disc separately of the venous system. B-scan ultrasonografhy revealed the presence of hyperechoic imaging at the optic nerve head in both eyes. Results: We describe the association of disc edge veins of Kraupa with optic disc drusen. Conclusion: Vascular complications of optic disc drusen hav been described. We don’t know the implication of disc edge veins in the pathogenesis of these complications.

  2. Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated discs : Results from in-vivo serial post-contrast MRI studies in 365 human lumbar discs.

    PubMed

    Rajasekaran, S; Venkatadass, K; Naresh Babu, J; Ganesh, K; Shetty, Ajoy P

    2008-05-01

    Degenerative disc disease (DDD) is still a poorly understood phenomenon because of the lack of availability of precise definition of healthy, ageing and degenerated discs. Decreased nutrition is the final common pathway for DDD and the status of the endplate (EP) plays a crucial role in controlling the extent of diffusion, which is the only source of nutrition. The vascular channels in the subchondral plate have muscarinic receptors but the possibility of enhancing diffusion pharmacologically by dilation of these vessels has not been probed. Although it is well accepted that EP damage will affect diffusion and thereby nutrition, there is no described method to quantify the extent of EP damage. Precise definitions with an objective method of differentiating healthy, ageing and degenerated discs on the basis of anatomical integrity of the disc and physiological basis of altered nutrition will be useful. This information is an urgent necessity for better understanding of DDD and also strategizing prevention and treatment. Seven hundred and thirty endplates of 365 lumbar discs from 73 individuals (26 healthy volunteers and 47 patients) with age ranging from 10-64 years were evaluated by pre-contrast and 10 min, 2, 4, 6 and 12 h post contrast MRI after IV injection of 0.3 mmol/kg of Gadodiamide. End plates were classified according to the extent of damage into six grades and an incremental score was given for each category. A total endplate score (TEPS) was derived by adding the EP score of the two endplates for each concerned disc. The base line value (SI(base)) and the signal intensity at particular time periods were used to derive the enhancement percentage for each time period (Enhancement (%) = SI(tp) - SI(base)/SI(base) x 100). The enhancement percentage for each time period, the time for peak enhancement (T-max) and the time intensity curve (TIC) over 12 h were used to study and compare the diffusion characteristics. The differences in pattern of diffusion were

  3. Progressive Agraphia Can Be a Harbinger of Degenerative Dementia

    ERIC Educational Resources Information Center

    Fukui, Toshiya; Lee, Eiyai

    2008-01-01

    By investigating three patients with progressive agraphia, we explored the possibility that this entity is an early sign of degenerative dementia. Initially, these patients complained primarily of difficulties writing Kanji (Japanese morphograms) while other language and cognitive impairments were relatively milder. Impairments in writing Kana…

  4. Enclosed rotary disc air pulser

    DOEpatents

    Olson, A. L.; Batcheller, Tom A.; Rindfleisch, J. A.; Morgan, John M.

    1989-01-01

    An enclosed rotary disc air pulser for use with a solvent extraction pulse olumn includes a housing having inlet, exhaust and pulse leg ports, a shaft mounted in the housing and adapted for axial rotation therein, first and second disc members secured to the shaft within the housing in spaced relation to each other to define a chamber therebetween, the chamber being in communication with the pulse leg port, the first disc member located adjacent the inlet port, the second disc member being located adjacent the exhaust port, each disc member having a milled out portion, the disc members positioned on the shaft so that as the shaft rotates, the milled out portions permit alternative cyclical communication between the inlet port and the chamber and the exhaust port and the chamber.

  5. Edge-on thick discs

    NASA Astrophysics Data System (ADS)

    Kasparova, A.; Katkov, I.; Chilingarian, I.; Silchenko, O.; Moiseev, A.; Borisov, S.

    2016-06-01

    Although thick stellar discs are detected in nearly all edge-on disc galaxies, their formation scenarios still remain a matter of debate. Due to observational difficulties, there is a lack of information about their stellar populations. Using the Russian 6-m telescope BTA we collected deep spectra of thick discs in three edge-on early-type disc galaxies located in different environments: NGC4111 in a dense group, NGC4710 in the Virgo cluster, and NGC5422 in a sparse group. We see intermediate age (4 ‑ 5 Gyr) metal rich ([Fe/H] ~ ‑0.2 ‑ 0.0 dex) stellar populations in NGC4111 and NGC4710. On the other hand, NGC5422 does not harbour young stars, its only disc is thick and old (10 Gyr) and its α-element abundance suggests a long formation epoch implying its formation at high redshift. Our results prove the diversity of thick disc formation scenarios.

  6. Selection of a Suitable Disc Bioassay for the Screening of Anti-Tumor Molecules

    PubMed Central

    Trigui, Fatma; Pigeon, Pascal; Jalleli, Karim; Top, Siden; Aifa, Sami; El Arbi, Mehdi

    2013-01-01

    The crown gall induced in potato discs by Agrobacterium tumefaciens is becoming largely utilised in screening anti-tumor agents. The present work is showing that beet discs are more adequate for the anti-tumor screening test. In fact, maximal tumor induction was observed on beet discs (87.5%), followed by carrot discs (75%) and potato discs (68.5%). Beet discs present the most sensibility to crown gall disease with a fast expression of symptoms and more visible galls without any staining need. The beet discs bioassay was carried out by using some synthesized organometallics known for their antitumor activity in mammalian cells. We found significant crown gall inhibition (20.7% to 40.55%) of the tested compounds. Overall results supported that beet bioassay might be a potential prescreen system of anti-tumor molecules in mammalian cells. PMID:24711759

  7. Biomechanical comparison between lumbar disc arthroplasty and fusion.

    PubMed

    Chen, Shih-Hao; Zhong, Zheng-Cheng; Chen, Chen-Sheng; Chen, Wen-Jer; Hung, Chinghua

    2009-03-01

    The artificial disc is a mobile implant for degenerative disc replacement that attempts to lessen the degeneration of the adjacent elements. However, inconsistent biomechanical results for the neighboring elements have been reported in a number of studies. The present study used finite element (FE) analysis to explore the biomechanical differences at the surgical and both adjacent levels following artificial disc replacement and interbody fusion procedures. First, a three-dimensional FE model of a five-level lumbar spine was established by the commercially available medical imaging software Amira 3.1.1, and FE software ANSYS 9.0. After validating the five-level intact (INT) model with previous in vitro studies, the L3/L4 level of the INT model was modified to either insert an artificial disc (ProDisc II; ADR) or incorporate bilateral posterior lumbar interbody fusion (PLIF) cages with a pedicle screw fixation system. All models were constrained at the bottom of the L5 vertebra and subjected to 150N preload and 10Nm moments under four physiological motions. The ADR model demonstrated higher range of motion (ROM), annulus stress, and facet contact pressure at the surgical level compared to the non-modified INT model. At both adjacent levels, ROM and annulus stress were similar to that of the INT model and varied less than 7%. In addition, the greatest displacement of posterior annulus occurred at the superior-lateral region. Conversely, the PLIF model showed less ROM, less annulus stress, and no facet contact pressure at the surgical level compared to the INT model. The adjacent levels had obviously high ROM, annulus stress, and facet contact pressure, especially at the adjacent L2/3 level. In conclusion, the artificial disc replacement revealed no adjacent-level instability. However, instability was found at the surgical level, which might accelerate degeneration at the highly stressed annulus and facet joint. In contrast to disc replacement results, the posterior

  8. Intervertebral disc regeneration using platelet-rich plasma-containing bone marrow-derived mesenchymal stem cells: A preliminary investigation

    PubMed Central

    WANG, SHAN-ZHENG; JIN, JI-YANG; GUO, YU-DONG; MA, LIANG-YU; CHANG, QING; PENG, XIN-GUI; GUO, FANG-FANG; ZHANG, HAI-XIANG; HU, XIN-FENG; WANG, CHEN

    2016-01-01

    Platelet-rich plasma (PRP) is a promising strategy for intervertebral disc degeneration (IDD). However, the short half-life of growth factors released from PRP cannot continuously stimulate the degenerated discs. Thus, the present study hypothesized that the combined use of PRP and bone marrow-derived mesenchymal stem cells (BMSCs) may repair the early degenerated discs in the long term for their synergistic reparative effect. In the present study, following the induction of early IDD by annular puncture in rabbits, PRP was prepared and mixed with BMSCs (PRP-BMSC group) for injection into the early degenerated discs. As controls, phosphate-buffered saline (PBS; PBS group) and PRP (PRP group) were similarly injected. Rabbits without any intervention served as a control group. At 8 weeks following treatment, histological changes of the injected discs were assessed. Magnetic resonance imaging (MRI) was used to detect the T2-weighted signal intensity of the targeted discs at weeks 1, 2 and 8 following treatment. Annular puncture resulted in disc narrowing and decreased T2-weighted signal intensity. At weeks 1 and 3, MRI examinations showed regenerative changes in the PRP-BMSC group and PRP group, whereas the PBS group exhibited a continuous degenerative process of the discs. At 8 weeks post-injection, the PRP-BMSCs induced a statistically significant restoration of discs, as shown by MRI (PRP-BMSCs, vs.PRP and PBS; P<0.05), which was also confirmed by histological evaluations. Thus, compared with PRP, the administration of PRP-containing BMSCs resulted in a superior regenerative effect on the early degenerated discs, which may be a promising therapeutic strategy for the restoration of early degenerated discs. PMID:26956080

  9. [The results of decompression and anterior lumbar interbody fusion with the use of interbody cages for the treatment of degenerative lumbar spondylolisthesis].

    PubMed

    Luczkiewicz, Piotr; Smoczyński, Andrzej; Smoczyński, Maciej; Pankowski, Rafał; Piotrowski, Maciej

    2006-01-01

    In this paper we reviewed 28 patients who had been treated surgically for lumbar degenerative spondylolisthesis. They were operated between 1998-2003. The decompression and anterior lumbar interbody fusion with the use of interbody cages, was performed in all of them. The outcome was assessed using rating system of Prolo and VAPS. The disc height, degree of slippage and segmental lordosis were measured, on the radiographs, before surgery, after 6 weeks and at the time of final follow-up. In all cases spinal fusion was achieved. The disc height, degree of slipage and segmental lordosis were improved and these results were stable in time. A significant decrease in radicular pain and low back pain were seen but the relation between clinical and radiological autcomes was not observed. PMID:17131721

  10. Numbered nasal discs for waterfowl

    USGS Publications Warehouse

    Bartonek, J.C.; Dane, C.W.

    1964-01-01

    Numbered nasal discs were successfully used in studies requiring large numbers of individually marked waterfowl. The procedure for constructing these discs is outlined. Blue-winged teal (Anas discors) with 5/8-inch discs, and canvasback (Aythya valisineria) and redhead (A. americana) with 3/4-inch discs can be individually identified up to 50 and 80 yards, respectively, with a gunstock-mounted, 20-power spotting scope. The particular value of these markers is their durability, the number of combinations possible, and the apparent absence of behavioral or mortality influence among such species as the blue-winged teal.

  11. Degenerative Grade Affects the Responses of Human Nucleus Pulposus Cells to Link-N, CTGF, and TGFβ3

    PubMed Central

    Abbott, Rosalyn D.; Purmessur, Devina; Monsey, Robert D.; Brigstock, David R.; Laudier, Damien M.; Iatridis, James C.

    2012-01-01

    Study Design Cells isolated from moderately and severely degenerated human intervertebral discs (IVDs) cultured in an alginate scaffold. Objective To compare the regenerative potential of moderately vs. severely degenerated cells using three pro-anabolic stimulants. Summary of Background Data Injection of soluble cell signaling factors has potential to slow the progression of IVD degeneration. While degenerative grade is thought to be an important factor in targeting therapeutic interventions it remains unknown whether cells in severely degenerated IVDs have impaired metabolic functions compared to lesser degenerative levels or if they are primarily influenced by the altered microenvironment. Methods NP cells were cultured in alginate for 21 days and treated with three different pro-anabolic stimulants: a growth factor/anti-inflammatory combination of TGFβ3+Dex, or matricellular proteins CTGF or Link-N. They were assayed for metabolic activity, DNA content, glycosaminoglycan (GAG), and qRT-PCR gene profiling. Results Moderately degenerated cells responded to stimulation with increased proliferation, decreased IL-1β, MMP9 and COL1A1 expression, and upregulated HAS1 as compared to severely degenerated cells. TGFβR1 (ALK5) receptors were expressed at greater levels in moderately than severely degenerated cells. TGFβ3+Dex had a notable stimulatory effect on moderately degenerated NP cells with increased anabolic gene expression, and decreased COL1A1 and ADAMTS5 gene expression. Link-N and CTGF had similar responses in all assays, and both treatments up-regulated IL-1β expression and had a more catabolic response than TGFβ3+Dex, particularly in the more severely degenerated group. All groups, including different degenerative grades, produced similar amounts of GAG. Conclusion Pro-anabolic stimulants alone had limited capacity to overcome the catabolic and pro-inflammatory cytokine expression of severely degenerated NP cells and likely require additional anti

  12. 78 FR 36305 - Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-17

    ... AFFAIRS Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune, Crystalline and Infectious Arthritis) and Dysbaric Osteonecrosis Disability Benefits Questionnaire) Activity... disability benefits related to a claimant's diagnosis of a non-degenerative arthritis or...