Lee, Yu Chao; Zotti, Mario Giuseppe Tedesco; Osti, Orso Lorenzo
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.
Lee, Yu Chao; Osti, Orso Lorenzo
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
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
Saleem, Shafaq; Rehmani, Muhammad Asim Khan; Raees, Aisha; Alvi, Arsalan Ahmad; Ashraf, Junaid
Study Design Cross sectional and observational. Purpose To evaluate the different aspects of lumbar disc degenerative disc disease and relate them with magnetic resonance image (MRI) findings and symptoms. Overview of Literature Lumbar disc degenerative disease has now been proven as the most common cause of low back pain throughout the world. It may present as disc herniation, lumbar spinal stenosis, facet joint arthropathy or any combination. Presenting symptoms of lumbar disc degeneration are lower back pain and sciatica which may be aggravated by standing, walking, bending, straining and coughing. Methods This study was conducted from January 2012 to June 2012. Study was conducted on the diagnosed patients of lumbar disc degeneration. Diagnostic criteria were based upon abnormal findings in MRI. Patients with prior back surgery, spine fractures, sacroiliac arthritis, metabolic bone disease, spinal infection, rheumatoid arthritis, active malignancy, and pregnancy were excluded. Results During the targeted months, 163 patients of lumbar disc degeneration with mean age of 43.92±11.76 years, came into Neurosurgery department. Disc degeneration was most commonly present at the level of L4/L5 105 (64.4%).Commonest types of disc degeneration were disc herniation 109 (66.9%) and lumbar spinal stenosis 37 (22.7%). Spondylolisthesis was commonly present at L5/S1 10 (6.1%) and associated mostly with lumbar spinal stenosis 7 (18.9%). Conclusions Results reported the frequent occurrence of lumbar disc degenerative disease in advance age. Research efforts should endeavor to reduce risk factors and improve the quality of life. PMID:24353850
Munoz, Hector E.; Yao, Jianhua; Burns, Joseph E.; Pham, Yasuyuki; Stieger, James; Summers, Ronald M.
Degenerative disc disease (DDD) develops in the spine as vertebral discs degenerate and osseous excrescences or outgrowths naturally form to restabilize unstable segments of the spine. These osseous excrescences, or osteophytes, may progress or stabilize in size as the spine reaches a new equilibrium point. We have previously created a CAD system that detects DDD. This paper presents a new system to determine the severity of DDD of individual vertebral levels. This will be useful to monitor the progress of developing DDD, as rapid growth may indicate that there is a greater stabilization problem that should be addressed. The existing DDD CAD system extracts the spine from CT images and segments the cortical shell of individual levels with a dual-surface model. The cortical shell is unwrapped, and is analyzed to detect the hyperdense regions of DDD. Three radiologists scored the severity of DDD of each disc space of 46 CT scans. Radiologists' scores and features generated from CAD detections were used to train a random forest classifier. The classifier then assessed the severity of DDD at each vertebral disc level. The agreement between the computer severity score and the average radiologist's score had a quadratic weighted Cohen's kappa of 0.64.
Li, S.; Lin, A.; Tay, K.; Romano, W.; Osman, Said
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.
Wang, Shaobai; Xia, Qun; Passias, Peter; Li, Weishi; Wood, Kirkham; Li, Guoan
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
Stuber, Kent; Sajko, Sandy; Kristmanson, Kevyn
Background: Nutritional supplements are commonly used for a variety of musculoskeletal conditions, including knee and hip degenerative joint disease. Although these supplements are occasionally recommended for patients with degenerative disc disease and spinal degenerative joint disease, the evidence supporting this use is unknown. Objective: To systematically search and assess the quality of the literature on the use of glucosamine, chondroitin sulfate, and methylsulfonylmethane for the treatment of spinal osteoarthritis / degenerative joint disease, and degenerative disc disease. Data Sources: The Index of Chiropractic Literature, AMED, Medline, and CINAHL were searched for randomized controlled trials in English from 1984 to July 2009. Data Extraction and Synthesis: Data from studies meeting the inclusion criteria was extracted and reviewed by three reviewers. The Jadad scale was used to assess study quality. No attempts were made at meta-analysis due to variation in study design. Results: Two articles met the inclusion criteria. One study was found to have good quality but reported negative results for the supplemented group compared with placebo, the other study had low quality but reported significant positive results for the supplemented group when compared with a no intervention control group. Conclusion: There was little literature found to support the use of common nutritional supplements for spinal degeneration, making it difficult to determine whether clinicians should recommend them. PMID:21403782
van den Eerenbeemt, Karin D.; van Royen, Barend J.; Peul, Wilco C.; van Tulder, Maurits W.
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
Xu, Bao-Shan; Liu, Yue; Xu, Hai-Wei; Yang, Qiang; Ma, Xin-Long; Hu, Yong-Cheng
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. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.
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
To assess the safety and efficacy of artificial disc replacement (ADR) technology for degenerative disc disease (DDD). 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. 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) compared with spinal fusion?What is the rate of major
Arneja, Amarjit S; Kotowich, Alan; Staley, Doug; Summers, Randy; Tappia, Paramjit S
Aim: To examine the effects of low-amplitude, low frequency electromagnetic field therapy (EMF) therapy in patients with persistent chronic lower back pain associated with degenerative disc disease. Design: Double-blind, randomized and placebo controlled. Intervention: EMF using a medical device resonator; control group underwent same procedures, except the device was turned off. Outcome measures: Pain reduction and mobility. Results: Improvements in overall physical health, social functioning and reduction in bodily pain were observed in the EMF group. The pain relief rating scale showed a higher level of pain relief at the target area in the EMF group. An increase in left lateral mobility was seen only in the EMF group. Conclusion: EMF treatment may be of benefit to patients with chronic nonresponsive lower back pain associated with degenerative disc disease. PMID:28031951
Poureisa, Masoud; Daghighi, Mohammad Hossein; Mesbahi, Sepideh; Hagigi, Amir
Study Design Case-control. Purpose To determine whether a disproportion between two neighboring vertebral end plates is associated with degenerative disc disease. Overview of Literature Recently, it has been suggested that disproportion of the end plates of two adjacent vertebrae may increase the risk of disc herniation. Methods Magnetic resonance (MR) images (n=160) with evidence of grades I-II lumbar degenerative disc disease (modified Pfirrmann's classification) and normal MR images of the lumbar region (n=160) were reviewed. On midsagittal sections, the difference of anteroposterior diameter of upper and lower end plates neighboring a degenerated (in the case group) or normal (in the control group) intervertebral disc was calculated (difference of end plates [DEP]). Results Mean DEP was significantly higher in the case group at the L5-S1 level (2.73±0.23 mm vs. 2.21±0.12 mm, p=0.03). Differences were not statistically significant at L1-L2 (1.31±0.13 mm in the cases vs. 1.28±0.08 mm in the controls, p=0.78), L2-L3 (1.45±0.12 mm in the cases vs. 1.37±0.08 mm in the controls, p=0.58), L3-L4 (1.52±0.13 mm in the cases vs. 1.49±0.10 mm in the controls, p=0.88), and L4-L5 (2.15±0.21 mm in the cases vs. 2.04±0.20 mm in the controls, p=0.31) levels. The difference at the L5-S1 level did not remain significant after adjusting for body mass index (BMI), which was significantly higher in the patients. Conclusions End plate disproportion may be a significant, BMI-dependent risk factor for lumbar degenerative disc disease. PMID:25187856
Kelly, Michael P.; Mitchell, M. David; Hacker, Robert J.; Riew, K. Daniel; Sasso, Rick C.
Study Design Post hoc analysis of prospective, randomized trial. Objective To investigate the disability associated with driving and single-level degenerative, cervical disc disease and to investigate the effect of surgery on driving disability. Methods Post hoc analysis of data obtained from three sites participating in a multicenter, randomized, controlled trial comparing cervical disc arthroplasty (TDA) with anterior cervical discectomy and fusion (ACDF). The driving subscale of the Neck Disability Index (NDI) was analyzed for all patients. A dichotomous severity score was created from the NDI. Statistical comparisons were made within and between groups. Results Two-year follow-up was available for 118/135 (87%) patients. One half of the study population (49.6%) reported moderate or severe preoperative driving difficulty. This disability associated with driving was similar among the two groups (ACDF: 2.5 ± 1.1, TDA: 2.6 ± 1.0, p = 0.646). The majority of patients showed improvement, with no or little driving disability, at the sixth postoperative week (ACDF: 75%, TDA: 90%, p = 0.073). At no follow-up point did a difference exist between groups according to the severity index. Conclusions Many patients suffering from radiculopathy or myelopathy from cervical disc disease are limited in their ability to operate an automobile. Following anterior cervical spine surgery, most patients are able to return to comfortable driving at 6 weeks. PMID:24436875
Imbalanced Protein Expression Patterns of Anabolic, Catabolic, Anti-Catabolic and Inflammatory Cytokines in Degenerative Cervical Disc Cells: New Indications for Gene Therapeutic Treatments of Cervical Disc Diseases
Mern, Demissew S.; Beierfuß, Anja; Fontana, Johann; Thomé, Claudius; Hegewald, Aldemar A.
Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix
Imbalanced protein expression patterns of anabolic, catabolic, anti-catabolic and inflammatory cytokines in degenerative cervical disc cells: new indications for gene therapeutic treatments of cervical disc diseases.
Mern, Demissew S; Beierfuβ, Anja; Fontana, Johann; Thomé, Claudius; Hegewald, Aldemar A
Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix
Moriguchi, Yu; Hussain, Ibrahim; Bonssar, Lawrence; Härtl, Roger
Biologic-based treatment strategies for musculoskeletal diseases have gained traction over the past 20 years as alternatives to invasive, costly, and complicated surgical interventions. Spinal degenerative disc disease (DDD) is among the anatomic areas being investigated among this group, notably due to its high incidence and functional debilitation. In this review, we report the literature encompassing the use of biologic-based therapies for DDD. Articles published between January 1995 and November 2015 were reviewed, with a subset meeting the primary and secondary inclusion criteria of clinical trial results that could be sub-classified into bimolecular, cell-based, or gene therapies, as well as studies investigating the utility of allogeneic and tissue-engineered intervertebral discs. Ongoing clinical trials that have not yet published results are also mentioned to present the current state of the field. This exciting area has demonstrated positive and encouraging results across multiple strategies; thus, future bimolecular and regenerative techniques and understanding will likely lead to an increase in the number of human clinical trials assessing these therapies. PMID:28018762
A 66-year-old female client with cervical degenerative disc disease at lateral left facet joint C6/C7 was experiencing symptoms of chronic neck pain accompanied by limited cervical range of motion, as well as radicular left shoulder and arm pain. The objective of this case report was to describe the effect of therapeutic massage on the client's symptoms and impairments of cervical DDD. Therapeutic massage interventions included soft-tissue manipulation using petrissage and neuromuscular techniques, fascial work, facilitated stretching, joint play, hydrotherapy, education on self-stretching, and positive guidance about condition management. Assessment included pain-free cervical ROM and a subjective verbal pain scale. After several treatment sessions, client's symptoms had decreased and cervical ROM had improved moderately. There was also a decrease in reported pain and an increase in functional daily activities. Client showed a greater understanding of the physiologic barriers which degenerative changes may present. This client responded favorably to massage therapy as a treatment intervention for cervical DDD symptoms.
Background: A 66-year-old female client with cervical degenerative disc disease at lateral left facet joint C6/C7 was experiencing symptoms of chronic neck pain accompanied by limited cervical range of motion, as well as radicular left shoulder and arm pain. The objective of this case report was to describe the effect of therapeutic massage on the client’s symptoms and impairments of cervical DDD. Methods: Therapeutic massage interventions included soft-tissue manipulation using petrissage and neuromuscular techniques, fascial work, facilitated stretching, joint play, hydrotherapy, education on self-stretching, and positive guidance about condition management. Assessment included pain-free cervical ROM and a subjective verbal pain scale. Results: After several treatment sessions, client’s symptoms had decreased and cervical ROM had improved moderately. There was also a decrease in reported pain and an increase in functional daily activities. Client showed a greater understanding of the physiologic barriers which degenerative changes may present. Conclusions: This client responded favorably to massage therapy as a treatment intervention for cervical DDD symptoms. PMID:23087777
Lee, Sang-Bok; Cho, Kyoung-Suok; Kim, Jong-Youn; Yoo, Do-Sung; Lee, Tae-Gyu; Huh, Pil-Woo
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). 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. 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. Hybrid surgery is a safe and effective alternative to fusion for the management of multilevel cervical spondylosis.
Jia, Zhiwei; Mo, Zhongjun; Ding, Fan; He, Qing; Fan, Yubo; Ruan, Dike
The optimal surgical technique for multilevel cervical degenerative disc diseases (DDD) remains controversial. Hybrid surgery (HS) incorporating anterior cervical discectomy and fusion (ACDF) and cervical disc replacement (CDR) is increasingly performed for cervical DDD. This study aims to evaluate the biomechanical and clinical evidence available for HS and to provide a systematic review of current understanding of HS. This systematic review was undertaken by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Multiple databases and online registers of clinical trials were searched up to February 2014. The biomechanical and clinical studies on HS for cervical DDD written in English were included. Two authors independently assessed methodological quality and extracted data. Fifteen studies including eight biomechanical studies and seven clinical studies were indentified. The biomechanical studies showed that HS was benefit to motion preservation of the operative levels and revealed less adverse effect on adjacent segments. All clinical studies demonstrated improvement in validated functional scores after HS. Segment motion and immobilization were achieved at the arthroplasty level and arthrodesis level, respectively. Postoperative assessments and complication rate were similar or in favor of HS when comparing with ACDF or CDR. However, the overall quality of evidence for HS was low to very low. There is a paucity of high quality evidence for HS. HS may be a safe and efficacious technique to benefit a select group of multilevel cervical DDD, which is needed to be confirmed by further prospective, randomized controlled trials.
Lee, Sang-Bok; Kim, Jong-Youn; Yoo, Do-Sung; Lee, Tae-Gyu; Huh, Pil-Woo
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
Matta, Ajay; Karim, M. Zia; Isenman, David E.; Erwin, W. Mark
Degenerative disc disease (DDD) is associated with spinal pain often leading to long-term disability. However, the non-chondrodystrophic canine intervertebral disc is protected from the development of DDD, ostensibly due to its retention of notochordal cells (NC) in the nucleus pulposus (NP). In this study, we hypothesized that secretome analysis of the NC-rich NP will lead to the identification of key proteins that delay the onset of DDD. Using mass-spectrometry, we identified 303 proteins including components of TGFβ- and Wnt-signaling, anti-angiogeneic factors and proteins that inhibit axonal ingrowth in the bioactive fractions of serum free, notochordal cell derived conditioned medium (NCCM). Ingenuity Pathway Analysis revealed TGFβ1 and CTGF as major hubs in protein interaction networks. In vitro treatment with TGFβ1 and CTGF promoted the synthesis of healthy extra-cellular matrix proteins, increased cell proliferation and reduced cell death in human degenerative disc NP cells. A single intra-discal injection of recombinant TGFβ1 and CTGF proteins in a pre-clinical rat-tail disc injury model restored the NC and stem cell rich NP. In conclusion, we demonstrate the potential of TGFβ1 and CTGF to mitigate the progression of disc degeneration and the potential use of these molecules in a molecular therapy to treat the degenerative disc. PMID:28358123
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
[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.
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
[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
Jabłońska, Renata; Ślusarz, Robert; Królikowska, Agnieszka; Haor, Beata; Antczak, Anna; Szewczyk, Maria
Objectives The purpose of this study was to evaluate the effects of psychosocial factors on pain levels and depression, before and after surgical treatment, in patients with degenerative lumbar and cervical vertebral disc disease. Patients and methods The study included 188 patients (98 women, 90 men) who were confirmed to have cervical or lumbar degenerative disc disease on magnetic resonance imaging, and who underwent a single microdiscectomy procedure, with no postoperative surgical complications. All patients completed two questionnaires before and after surgery – the Beck Depression Inventory scale (I–IV) and the Visual Analog Scale for pain (0–10). On hospital admission, all patients completed a social and demographic questionnaire. The first pain and depression questionnaire evaluations were performed on the day of hospital admission (n=188); the second on the day of hospital discharge, 7 days after surgery (n=188); and the third was 6 months after surgery (n=140). Results Patient ages ranged from 22 to 72 years, and 140 patients had lumbar disc disease (mean age, 42.7±10.99 years) and 44 had cervical disc disease (mean age, 48.9±7.85 years). Before surgery, symptoms of depression were present in 47.3% of the patients (11.7% cervical; 35.6% lumbar), at first postoperative evaluation in 25.1% of patients (7% cervical; 18.1% lumbar), and 6 months following surgery in 31.1% of patients (7.5% cervical; 23.6% lumbar). Patients with cervical disc disease who were unemployed had the highest incidence of depression before and after surgery (p=0.037). Patients with lumbar disc disease who had a primary level of education or work involving standing had the highest incidence of depression before and after surgery (p=0.368). Conclusion This study highlighted the association between social and demographic factors, pain perception, and depression that may persist despite surgical treatment for degenerative vertebral disc disease. PMID:28115868
MacDowall, Anna; Robinson, Yohan; Skeppholm, Martin; Olerud, Claes
Introduction Pain drawings have been frequently used in the preoperative evaluation of spine patients. Until now most investigations have focused on low back pain patients, even though pain drawings are used in neck pain patients as well. The aims of this study were to investigate the pain drawing and its association to preoperative demographics, psychological impairment, and pain intensity. Methods We carried out a post hoc analysis of a randomized controlled trial, comparing cervical disc replacement to fusion for radiculopathy related to degenerative disc disease. Preoperatively the patients completed a pain drawing, the Hospital Anxiety and Depression Scale (HADS), and a visual analogue scale (VAS). The pain drawing was evaluated according to four established methods, now modified for cervical conditions. Comparisons were made between the pain drawing and age, sex, smoking, and employment status as well as HADS and VAS. Results Included were 151 patients, mean age of 47 years, female/male: 78/73. Pain drawing results were not affected by age, sex, smoking, and employment status. Patients with non-neurogenic pain drawings according to the modified method by Ransford had higher points on HADS-anxiety, HADS-depression, and HADS-total. Patients with markings in the head region had higher score on HADS-depression. Markings in the neck and lower arm region were associated with high values of VAS-neck and VAS-arm. Conclusions Pain drawings were affected by both pain intensity and anxiety/depression in cervical spine patients. Therefore, the pain drawing can be a useful tool when interpreting the patients’ pain in correlation to psychological impairment and pain location. PMID:28503982
Ding, Fan; Jia, Zhiwei; Zhao, Zhigang; Xie, Lin; Gao, Xinfeng; Ma, Dezhang; Liu, Ming
Although many meta-analyses have been performed to compare total disc replacement (TDR) and fusion for treating lumbar degenerative disc disease (LDDD), their findings are inconsistent. This study aimed to conduct a systematic review of overlapping meta-analyses comparing TDR with fusion for treating LDDD, to assist decision makers in selection among conflicting meta-analyses, and to provide treatment recommendations based on the best available evidence. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Multiple databases were comprehensively searched for meta-analyses comparing TDR with fusion for treating LDDD. Meta-analyses only comprising randomised controlled trials (RCTs) were included. Two authors independently assessed meta-analysis quality and extracted data. The Jadad decision algorithm was used to ascertain which meta-analyses represented the best evidence. A total of five meta-analyses were included. All these studies only included RCTs were determined as Level-II evidence. The scores of Assessment of Multiple Systematic Reviews (AMSTAR) ranged from 6 to 9 (median 7). A high-quality Cochrane review was chosen according to the Jadad algorithm. This best available evidence found that statistical significances were observed between TDR and fusion for LDDD regarding disability, pain relief, and pain in the short term, but it was not over clinically important differences. The prevent effects on adjacent segment and facet joint degeneration, as the primary goal of adopting TDR stated by the manufacturers, were not appropriately evaluated. There is discord in results from meta-analyses that assessed TDR and fusion for LDDD. According to this systematic review of overlapping meta-analyses comparing TDR and fusion for LDDD, the current best available evidence suggests that TDR may be an effective technique for the treatment of selected patients with LDDD, and is at least equal to lumbar
Park, Chun-Kun; Ryu, Kyeong-Sik; Lee, Ki-Yeol; Lee, Hong-Jae
A retrospective clinical data analysis. To determine the therapeutic effectiveness of lumbar total disc replacement (TDR) using ProDisc-L (Synthes Spine, West Chester, PA) in the patients with degenerative disc diseases (DDD) with a minimum follow-up of 5 years. Early successful clinical results of lumbar TDR have been reported. However, few reports have published its therapeutic effectiveness in the long term. The patients were examined preoperatively and at 3 months, 1 year, 2 years, and more than 5 years postoperatively, and assessed using visual analog scale (VAS), Oswestry disability index (ODI), physical health component summary (PCS) of the 36-Item Short Form Health Survey questionnaire, and sporting activity scale scores. At last follow-up visits, two additional questions were asked: satisfaction with surgery and willingness to undergo the same treatment. Finally, clinical success was assessed using the Food and Drug Administration definition. Thirty-five patients were included in the study. The mean follow-up period was 72 months (6 years). Postoperatively, all outcome measure scores (VAS, mean ODI, PCS, and sports activity scores) immediately improved and these improvements were maintained at last follow-up visits with statistical significance. However, outcome score improvements were observed to be slightly, though significantly, lower at last follow-up visits than at 1 or 2 years postoperatively. Eighty-eight percent of patients were "satisfied" or "somewhat satisfied" with treatment and 60% were prepared to undergo the same treatment again. Twenty-five patients (71.4%) achieved clinical success. This study reveals that lumbar TDR using ProDisc-L is a safe and effective treatment for chronic back pain caused by lumbar DDD as assessed at more than 5 years postoperatively. Nevertheless, outcome scores were slightly, though significantly lower at last follow-up visits than at 1 and 2 years postoperatively. A longer-term follow-up study is warranted.
Tonosu, Juichi; Inanami, Hirohiko; Oka, Hiroyuki; Katsuhira, Junji; Takano, Yuichi; Koga, Hisashi; Yuzawa, Yohei; Shiboi, Ryutaro; Oshima, Yasushi; Baba, Satoshi; Tanaka, Sakae; Matsudaira, Ko
To evaluate the usefulness of our original five questions in a medical interview for diagnosing discogenic low back pain (LBP), and to establish a support tool for diagnosing discogenic LBP. The degenerative disc disease (DDD) group (n = 42) comprised patients diagnosed with discogenic LBP associated with DDD, on the basis of magnetic resonance imaging findings and response to analgesic discography (discoblock). The control group (n = 30) comprised patients with LBP due to a reason other than DDD. We selected patients from those who had been diagnosed with lumbar spinal stenosis and had undergone decompression surgery without fusion. Of them, those whose postoperative LBP was significantly decreased were included in the control group. We asked patients in both groups whether they experienced LBP after sitting too long, while standing after sitting too long, squirming in a chair after sitting too long, while washing one's face, and in the standing position with flexion. We analyzed the usefulness of our five questions for diagnosing discogenic LBP, and performed receiver operating characteristic (ROC) curve analysis to develop a diagnostic support tool. There were no significant differences in baseline characteristics, except age, between the groups. There were significant differences between the groups for all five questions. In the age-adjusted analyses, the odds ratios of LBP after sitting too long, while standing after sitting too long, squirming in a chair after sitting too long, while washing one's face, and in standing position with flexion were 10.5, 8.5, 4.0, 10.8, and 11.8, respectively. The integer scores were 11, 9, 4, 11, and 12, respectively, and the sum of the points of the five scores ranged from 0 to 47. Results of the ROC analysis were as follows: cut-off value, 31 points; area under the curve, 0.92302; sensitivity, 100%; and specificity, 71.4%. All five questions were useful for diagnosing discogenic LBP. We established the scoring system as a
Li, Weishi; Wang, Shaobai; Xia, Qun; Passias, Peter; Kozanek, Michal; Wood, Kirkham; Li, Guoan
Study Design Controlled laboratory study. Objective To evaluate the effect of lumbar degenerative disc diseases (DDDs) on motion of the facet joints during functional weight-bearing activities. Summary of Background Data It has been suggested that DDD adversely affects the biomechanical behavior of the facet joints. Altered facet joint motion, in turn, has been thought to associate with various types of lumbar spine pathology including facet degeneration, neural impingement, and DDD progression. However, to date, no data have been reported on the motion patterns of the lumbar facet joint in DDD patients. Methods Ten symptomatic patients of DDD at L4–S1 were studied. Each participant underwent magnetic resonance images to obtain three-dimensional models of the lumbar vertebrae (L2–S1) and dual fluoroscopic imaging during three characteristic trunk motions: left-right torsion, left-right bending, and flexion-extension. In vivo positions of the vertebrae were reproduced by matching the three-dimensional models of the vertebrae to their outlines on the fluoroscopic images. The kinematics of the facet joints and the ranges of motion (ROMs) were compared with a group of healthy participants reported in a previous study. Results In facet joints of the DDD patients, there was no predominant axis of rotation and no difference in ROMs was found between the different levels. During left-right torsion, the ROMs were similar between the DDD patients and the healthy participants. During left-right bending, the rotation around mediolateral axis at L4–L5, in the DDD patients, was significantly larger than that of the healthy participants. During flexion-extension, the rotations around anterioposterior axis at L4–L5 and around craniocaudal axis at the adjacent level (L3–L4), in the DDD patients, were also significantly larger, whereas the rotation around mediolateral axis at both L2–L3 and L3–L4 levels in the DDD patients were significantly smaller than those of the
Gautschi, Oliver P; Corniola, Marco V; Joswig, Holger; Smoll, Nicolas R; Chau, Ivan; Jucker, Dario; Stienen, Martin N
We report on the use and performance of an objective measure of functional impairment, the timed up and go (TUG) test, in clinical practice for patients with lumbar degenerative disc disease (DDD). We illustrate nine representative patients with lumbar DDD, who were selected from an ongoing prospective study, to report our clinical experience with the TUG test. In addition, a preliminary sample of 30 non-selected consecutive patients is presented. The following parameters were assessed preoperatively, and 3 days and 6 weeks postoperatively: back and leg pain using the visual analogue scale (VAS); functional impairment using the Oswestry disability index (ODI) and Roland-Morris disability index (RMDI); health-related quality of life using the EuroQol 5D (EQ5D) and Short-Form 12 (SF-12). The TUG test results improved by 2.6 and 5.4s after 3 days and 6 weeks compared to the baseline assessment. The mean VAS for back and leg pain decreased by 2.3 and 5.3, respectively, after 3 days, and by 2.7 and 4.6 after 6 weeks. The mean RMDI and ODI decreased by 3.4 and 23.3, respectively, after 3 days, and by 7.0 and 28.0 after 6 weeks. The mean EQ5D increased by 0.38 after 3 days and 0.358 after 6 weeks. The mean SF-12 mental component scale decreased by 0.2 after 3 days and increased by 5.6 after 6 weeks, whereas the mean SF-12 physical component scale increased by 6.4 after 3 days and by 9.8 after 6 weeks. The TUG test proved to be a useful, easy to use tool that could add a new, objective dimension to the armamentarium of clinical tests for the diagnosis and management of DDD. From our preliminary experience, we conclude that the TUG test accurately reflects a patient's objective functional impairment before and after surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.
Stienen, Martin N; Smoll, Nicolas R; Joswig, Holger; Corniola, Marco V; Schaller, Karl; Hildebrandt, Gerhard; Gautschi, Oliver P
OBJECTIVE The Timed Up and Go (TUG) test is a simple, objective, and standardized method to measure objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD). The objective of the current work was to validate the OFI baseline severity stratification (BSS; with levels of "none," "mild," "moderate," and "severe"). METHODS Data were collected in a prospective IRB-approved 2-center study. Patients were assessed with a comprehensive panel of scales for measuring pain (visual analog scale [VAS] for back and leg pain), functional impairment (Roland-Morris Disability Index [RMDI] and Oswestry Disability Index [ODI]), and health-related quality of life (HRQOL; EQ-5D and SF-12). OFI BSS was determined using age- and sex-adjusted cutoff values. RESULTS A total of 375 consecutive patients scheduled for lumbar spine surgery were included. Each 1-step increase on the OFI BSS corresponded to an increase of 0.53 in the back pain VAS score, 0.69 in the leg pain VAS score, 1.81 points in the RMDI, and 5.93 points in the ODI, as well as to a decrease in HRQOL of -0.073 in the EQ-5D, -1.99 in the SF-12 physical component summary (PCS), and -1.62 in the SF-12 mental component summary (MCS; all p < 0.001). Patients with mild, moderate, and severe OFI had increased leg pain by 0.90 (p = 0.044), 1.54 (p < 0.001), and 1.94 (p < 0.001); increased ODI by 7.99 (p = 0.004), 12.64 (p < 0.001), and 17.13 (p < 0.001); and decreased SF-12 PCS by -2.57 (p = 0.049), -3.63 (p = 0.003), and -6.23 (p < 0.001), respectively. CONCLUSIONS The OFI BSS is a valid measure of functional impairment for use in daily clinical practice. The presence of OFI indicates the presence of significant functional impairment on subjective outcome measures.
Tonosu, Juichi; Inanami, Hirohiko; Oka, Hiroyuki; Katsuhira, Junji; Takano, Yuichi; Koga, Hisashi; Yuzawa, Yohei; Shiboi, Ryutaro; Oshima, Yasushi; Baba, Satoshi; Tanaka, Sakae; Matsudaira, Ko
Purposes To evaluate the usefulness of our original five questions in a medical interview for diagnosing discogenic low back pain (LBP), and to establish a support tool for diagnosing discogenic LBP. Materials and Methods The degenerative disc disease (DDD) group (n = 42) comprised patients diagnosed with discogenic LBP associated with DDD, on the basis of magnetic resonance imaging findings and response to analgesic discography (discoblock). The control group (n = 30) comprised patients with LBP due to a reason other than DDD. We selected patients from those who had been diagnosed with lumbar spinal stenosis and had undergone decompression surgery without fusion. Of them, those whose postoperative LBP was significantly decreased were included in the control group. We asked patients in both groups whether they experienced LBP after sitting too long, while standing after sitting too long, squirming in a chair after sitting too long, while washing one’s face, and in the standing position with flexion. We analyzed the usefulness of our five questions for diagnosing discogenic LBP, and performed receiver operating characteristic (ROC) curve analysis to develop a diagnostic support tool. Results There were no significant differences in baseline characteristics, except age, between the groups. There were significant differences between the groups for all five questions. In the age-adjusted analyses, the odds ratios of LBP after sitting too long, while standing after sitting too long, squirming in a chair after sitting too long, while washing one’s face, and in standing position with flexion were 10.5, 8.5, 4.0, 10.8, and 11.8, respectively. The integer scores were 11, 9, 4, 11, and 12, respectively, and the sum of the points of the five scores ranged from 0 to 47. Results of the ROC analysis were as follows: cut-off value, 31 points; area under the curve, 0.92302; sensitivity, 100%; and specificity, 71.4%. Conclusions All five questions were useful for diagnosing
Lisiński, Przemysław; Huber, Juliusz
Comparative clinical and neurophysiological study in three groups of patients with general diagnosis of neck pain. To determine symptoms of muscles dysfunction in patients with myofascial pain syndrome, disc-root conflict, and degenerative changes at cervical spine. The explanation for cervical pain origin should be based on results from chosen clinical and neurophysiological studies in correlation with neuroimaging findings. Three subgroups of patients (N = 60 each) with certain symptoms were examined. Clinical evaluation included examination of pain intensity in VAS scale, muscle strength in Lovett scale, evaluation of reflexes, Spurling test, assessment of active trigger points (TRPs), and superficial sensory perception. Neurophysiological testing included surface electromyography at rest (rEMG) and during maximal contraction (mcEMG) as well as electroneurography (ENG). The greatest pain intensity with its decentralization phenomenon occurred in patients with disc-root conflict. Significant decrease of muscle strength was detected in trapezius muscle in myofascial pain syndrome subgroup. Weakness of abductor pollicis brevis muscle in patients with disc-root conflict differed them from patients with myofascial pain syndrome (P = 0.05). Patients with disc-root conflict and degenerative spine disease showed differences (P = 0.03) in reflexes evoked from triceps brachii. Positive Spurling symptom was most common (56.7%) in disc-root conflict subgroup. TRPs in trapezius muscle were found in all patients with myofascial pain syndrome. Results of rEMG amplitude measurements differed patients at P = 0.05. Only mcEMG recording from abductor pollicis brevis muscle allows for their clear cut differentiation. ENG studies showed abnormalities in patients with disc-root conflict and degenerative spine disease (P from 0.05 to 0.02). Positive correlation of VAS, TRPs, and rEMG as well as Lovett scores, mcEMG, and ENG results was found. Only applying several
Zhou, Jian; Xia, Qing; Dong, Jian; Li, Xilei; Zhou, Xiaogang; Fang, Taolin; Lin, Hong
Anterior cervical decompression and fusion (ACDF) is a widely accepted surgical procedure for the treatment of cervical degenerative disc diseases. This retrospective study was designed to analyze and compare the efficacy and outcomes of anterior cervical fusion using stand-alone polyetheretherketone (PEEK) cages and autogenous iliac crest grafts with the anterior cervical plating system. A total of 72 consecutive patients suffering from cervical degenerative disc diseases treated with ACDF from June 2005 to Dec 2008 were enrolled in the study. Patients in group A (40 patients, 64 segments) had anterior interbody fusion with stand-alone PEEK cages and patients in group B (32 patients, 51 segments) with autogenous iliac crest graft combined with anterior plate fixation. The operative time and intraoperative blood loss were recorded. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scoring system; cervical lordosis, intervertebral height, and cervical fusion status were assessed on X-ray and computed tomography. The mean follow-up period was 17.3 months in the stand-alone cage group and 23.2 months in the autologous iliac crest graft group. The operative time and intraoperative blood loss in group A were much less than those in group B (p < 0.05). All the patients in both groups got complete interbody fusion. Postoperative JOA scores in both group A and group B were more than the preoperative ones with significant differences, and the improvement rate of JOA scores had no statistical differences between group A and group B. Postoperative cervical physiological curvature and intervertebral height in both groups were better than the preoperative ones with statistical significances. The stand-alone PEEK cage is a good substitute for fusion in patients with cervical disc disease; it can effectively restore the cervical physiological curvature and the intervertebral height, facilitate radiological follow-up, cause few complications, and
Yang, Zhuo; Nunley, Pierce; Stone, Marcus B.; Lee, Darrin; Kim, Kee D.
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
Lackey, Alan; Phan, Kevin; Mobbs, Ralph
A systematic review and meta-analysis was performed to assess the effect of hybrid constructs which involve a total disc arthroplasty (TDA) with stand-alone anterior lumbar interbody fusion (ALIF) versus non-hybrid constructs including multi-level TDA, multi-level transforaminal lumbar interbody fusion (TLIF) with posterior transpedicular fixation or multi-level stand-alone ALIF as a surgical intervention for degenerative disc disease (DDD) in the lumbar spine. Primary outcomes analysed included the Oswestry Disability Index (ODI) and the Visual Analogue Scale (VAS) for back pain. A systematic search of Medline, Embase, Pubmed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Google Scholar was undertaken by two separate reviewers and a meta-analysis of the outcomes was performed. Three studies met our search criteria. When comparing hybrid constructs to multi-level TDA or lumbar fusion (LF) improvements in back pain were found with a VAS back pain score reduction of 1.38 (P<0.00001) postoperatively and a VAS back pain score reduction of 0.99 points (P=0.0006) at 2-years follow-up. Results so far slightly favour clinically significant improved VAS back pain score outcomes postoperatively and at 2-years follow-up for hybrid constructs in multi-level lumbar DDD of the spine when compared with non-hybrid multi-level LF or TDA. It cannot however be concluded that a hybrid construct is superior to multi-level LF or TDA based on this meta-analysis. The results highlight the need for further prospective studies to delineate best practice in the management of degenerative disc disease of the lumbar spine.
Cincu, Rafael; Lorente, Francisco de Asis; Gomez, Joaquin; Eiras, Jose; Agrawal, Amit
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
Pappou, Ioannis P; Cammisa, Frank P; Girardi, Federico P
The sagittal profile of the lumbar end plates on magnetic resonance imaging (MRI) has not been investigated in patients with degenerative disc disease (DDD) or herniated nucleus pulposus (HNP). To examine the shape of the end plates in patients treated surgically for a) low back pain or b) radiculopathy with HNP. Furthermore, to investigate the correlation between end plate shape and disc degeneration on the one, and end plate shape and symptoms on the other. Retrospective review of charts and radiographs. The charts, operative reports, preoperative lateral plain radiographs, and MRI scans of 178 patients (85 with low back pain and 93 with HNP) were reviewed. End plate shape was determined on midsagittal MRI cuts, disc degeneration was graded on T2 sequences, and disc height was measured on lateral plain radiographs from L1 to S1 in all patients. Student t-test and chi(2) test were used to detect significant differences and associations. Flat and irregular levels were most common in the lower lumbar spine. The L5/S1 segment was flat in most cases, due to a flat sacral end plate. In DDD patients, disc degeneration on MRI and plain radiographs worsened from concave to flat, to irregular levels. In HNP patients, MRI demonstrated concave levels to be less degenerated, whereas no difference was detected between flat and irregular levels. Disc height of irregular levels was well preserved in HNP patients. Comparing the two groups, flat levels were more degenerated on MRI in HNP patients. Despite similar degrees of degeneration on MRI, concave and irregular levels in DDD patients had lower disc heights. A higher frequency of symptoms was found in flat and irregular levels for both patient groups. The sagittal profile of end plates in the lumbar spine was described for patients with DDD on the one and HNP on the other. A higher association with symptoms was observed for flat and irregular levels in both patient groups. In DDD patients, disck degeneration on both MRI and
Qureshi, Sheeraz; Goz, Vadim; McAnany, Steven; Cho, Samuel K; Hecht, Andrew C; Delamarter, Rick B; Fehlings, Michael G
Cost-effectiveness analysis (CEA) of medical interventions has become increasingly relevant to the discussion of optimization of care. The use of utility scales in CEA permits a quantitative assessment of effectiveness of a given intervention. There are no published utility values for degenerative disc disease (DDD) of the cervical spine, anterior cervical discectomy and fusion (ACDF), or cervical disc replacement (CDR). The purpose of this study was to define health utility values for those health states. The 36-Item Short Form Health Survey data from the ProDisc-C investigational device exemption study were obtained for single-level DDD at baseline and 24 months postoperatively after ACDF or CDR procedures. Patients in the original study were randomized to either ACDF or CDR. Utilizing a commercially available Short Form-6 dimensions program, utility scores were calculated for each health state using a set of parametric preference weights obtained from a sample of the general population using the recognized valuation technique of standard gamble. The baseline health state utility (HSU) value for a patient with single-level DDD was 0.54 in both the ACDF and CDR groups. Postoperative changes in HSU values were seen in both intervention groups at 24 months. Cervical disc replacement had a HSU value of 0.72. Anterior cervical discectomy and fusion was found to have a postoperative utility state of 0.71. No statistically significant difference was found in the HSU for ACDF and CDR at 24 months of follow-up. This study represents the first calculated HSU value for a patient with single-level cervical DDD. Additionally, 2 common treatment interventions for this disease state were assessed. Both treatments were found to have significant impact on the HSU values. These values are integral to future CEA of ACDF and CDR.
Ahsan, M K; Hossain, M A; Sakeb, N; Khan, S I; Zaman, N
This prospective interventional study carried out at Bangabandhu Sheikh Mujib Medical University and a private hospital in Dhaka, Bangladesh during the period from October 2003 to September 2011. Surgical treatment of degenerative disc disease (DDD) should aim to re-expand the interbody space and stabilize until fusion is complete. The present study conducted to find out the efficacy of using interbody fusion device (Cage) to achieve interbody space re-expansion and fusion in surgical management of DDD. We have performed the interventional study on 53 patients, 42 female and 11 male, with age between 40 to 67 years. All the patients were followed up for 36 to 60 months (average 48 months). Forty seven patients were with spondylolisthesis and 06 with desiccated disc. All subjects were evaluated with regard to immediate and long term complications, radiological fusion and interbody space re-expansion and maintenance. The clinical outcome (pain and disability) was scored by standard pre and postoperative questionnaires. Intrusion, extrusion and migration of the interbody fusion cage were also assessed. Forty seven patients were considered to have satisfactory outcome in at least 36 months follow up. Pseudoarthrosis developed in 04 cases and 06 patients developed complications. In this series posterior lumbar interbody fusion (PLIF) with interbody cage and instrumentation in DDD showed significant fusion rate and maintenance of interbody space. Satisfactory outcome observed in 88.68% cases.
Dai, Feng; Belfer, Inna; Schwartz, Carolyn E; Banco, Robert; Martha, Julia F; Tighioughart, Hocine; Tromanhauser, Scott G; Jenis, Louis G; Kim, David H
Surgical treatment for lumbar degenerative disc disease (DDD) has been associated with highly variable results in terms of postoperative pain relief and functional improvement. Many experts believe that DDD should be considered a chronic pain disorder as opposed to a degenerative disease. Genetic variation of the catechol-O-methyltransferase (COMT) gene has been associated with variation in human pain sensitivity and response to analgesics in previous studies. To determine whether genetic variation of COMT is associated with clinical outcome after surgical treatment for DDD. Prospective genetic association study. Sixty-nine patients undergoing surgical treatment for lumbar DDD. Diagnosis was based on documentation of chronic disabling low back pain (LBP) present for a minimum of 6 months and unresponsive to supervised nonoperative treatment, including activity modification, medication, physical therapy, and/or injection therapy. Plain radiographs and magnetic resonance imaging revealed intervertebral disc desiccation, tears, and/or collapse without focal herniation, nerve root compression, stenosis, spondylolisthesis, spondylolysis, or alternative diagnoses. Oswestry Disability Index (ODI) and visual analog score (VAS) for LBP. Surgical treatment included 65 instrumented fusions and four disc arthroplasty procedures. All patients completed preoperative and 1-year postoperative ODI questionnaires. DNA was extracted from a sample of venous blood, and genotype analysis was performed for five common COMT single nucleotide polymorphisms (SNPs). Potential genetic association between these COMT SNPs and the primary outcome variable, 1-year change in ODI, was investigated using both single-marker and haplotype association analyses. Association with VAS scores for LBP was analyzed as a secondary outcome variable. Single-marker analysis revealed that the COMT SNP rs4633 was significantly associated with greater improvement in ODI score 1 year after surgery (p=.03), with
Oh, Hyeong-Seok; Shim, Chan Shik; Lee, Sang-Ho
Objective This consecutive retrospective study was designed to analyze and to compare the efficacy and outcomes of anterior cervical discectomy and fusion (ACDF) using a fibular and femur allograft with anterior cervical plating. Methods A total of 88 consecutive patients suffering from cervical degenerative disc disease (DDD) who were treated with ACDF from September 2007 to August 2010 were enrolled in this study. Thirty-seven patients (58 segments) underwent anterior interbody fusion with a femur allograft, and 51 patients (64 segments) were treated with a fibular allograft. The mean follow-up period was 16.0 (range, 12-25) months in the femur group and 19.5 (range, 14-39) months in the fibular group. Cage fracture and breakage, subsidence rate, fusion rate, segmental angle and height and disc height were assessed by using radiography. Clinical outcomes were assessed using a visual analog scale and neck disability index. Results At 12 months postoperatively, cage fracture and breakage had occurred in 3.4% (2/58) and 7.4% (4/58) of the patients in the femur group, respectively, and 21.9% (14/64) and 31.3% (20/64) of the patients in the fibular group, respectively (p<0.05). Subsidence was noted in 43.1% (25/58) of the femur group and in 50.5% (32/64) of the fibular group. No difference in improvements in the clinical outcome between the two groups was observed. Conclusion The femur allograft showed good results in subsidence and radiologic parameters, and sustained the original cage shape more effectively than the fibular allograft. The present study suggests that the femur allograft may be a good choice as a fusion substitute for the treatment of cervical DDD. PMID:23439721
Oh, Hyeong-Seok; Shim, Chan Shik; Kim, Jin-Sung; Lee, Sang-Ho
This consecutive retrospective study was designed to analyze and to compare the efficacy and outcomes of anterior cervical discectomy and fusion (ACDF) using a fibular and femur allograft with anterior cervical plating. A total of 88 consecutive patients suffering from cervical degenerative disc disease (DDD) who were treated with ACDF from September 2007 to August 2010 were enrolled in this study. Thirty-seven patients (58 segments) underwent anterior interbody fusion with a femur allograft, and 51 patients (64 segments) were treated with a fibular allograft. The mean follow-up period was 16.0 (range, 12-25) months in the femur group and 19.5 (range, 14-39) months in the fibular group. Cage fracture and breakage, subsidence rate, fusion rate, segmental angle and height and disc height were assessed by using radiography. Clinical outcomes were assessed using a visual analog scale and neck disability index. At 12 months postoperatively, cage fracture and breakage had occurred in 3.4% (2/58) and 7.4% (4/58) of the patients in the femur group, respectively, and 21.9% (14/64) and 31.3% (20/64) of the patients in the fibular group, respectively (p<0.05). Subsidence was noted in 43.1% (25/58) of the femur group and in 50.5% (32/64) of the fibular group. No difference in improvements in the clinical outcome between the two groups was observed. The femur allograft showed good results in subsidence and radiologic parameters, and sustained the original cage shape more effectively than the fibular allograft. The present study suggests that the femur allograft may be a good choice as a fusion substitute for the treatment of cervical DDD.
Kuciel-Lewandowska, Jadwiga; Paprocka-Borowicz, Małgorzata
Degenerative joints and disc disease is accompanied by chronic pain which is the main symptom of the disease. Medical spa therapy has the task of providing comprehensive treatment embracing diseases of limbs as well as other systems and the essential role of medical treatment, in particular spa therapy, is pain relief. The aim of the study was to evaluate the effect of the spa treatment on the level of pain perception in patients with degenerative joints and disc disease. The observation embraced 120 people with degenerative joints and disc disease treated in the spa. The study included a comprehensive therapy conducted over a 21-day stays at the spa Przerzeczyn-Zdrój with the application of selected physical treatments, physiotherapy and the use of therapeutic natural resources: peloid mud and healing radon-sulphide water. Moreover, there was psychological counseling and health education conducted. The study also included observation of 21 persons from the control group. However, the patients in the control group did not benefit from balneotherapy, psychological care and education. There was a standard VAS scale for pain and non-standard questionnaire of pain assessment constructed for the study purposes. The assessment of pain using the VAS scale and questionnaire of pain assessment both in the study group and the control group were performed before and after the treatment. The results were analyzed statistically, there was Statistica program in Polish version used. In the analysis of the obtained results there were two tests scheduled: the sign test, the Wilcoxon test and descriptive statistics. As a result of the spa therapy and treatments administered on an outpatient basis there was reduction of pain intensity observed. 1. Spa therapy and outpatient treatment reduce the level of pain in patients with degenerative joints and disc disease. 2. The reduction of pain level was more effective in case of therapy conducted in the spa.
Tian, Peng; Fu, Xin; Li, Zhi-Jun; Sun, Xiao-Lei; Ma, Xin-Long
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.
Iampreechakul, Prasert; Srisawat, Chaichan; Tirakotai, Wuttipong
To study clinical and radiographic outcome of patients who underwent the Cervios cage-assisted anterior cervical discectomy and fusion (ACDF) without plate fixation in single to two-level degenerative disc disease (DDD). Sixty-seven patients suffering from cervical DDD with various symptoms such as radiculopathy, myelopathy, or both were retrospectively evaluated. The cervical DDD was confirmed by plain radiographs and MR imaging The patients underwent radiographic evaluation to assess cervical lordosis, intervertebral height (IH), fusion, and subsidence. Clinical assessment was graded using a visual analog scale (VAS), Modified JOA (Japanese Orthopedic Association) score, Neck Disability Index (NDI). There were ninety two ACFD in two levels of operation. Single-level ACDF was performed in 42 patients and two-level in 25. The outcomes revealed the significant improvement of clinical outcome and restoration of cervical lordosis. The fusion rate was 97%, whereas subsidence occurred 7.61% but produced no symptom. There was no anterior or posterior migration of the cage. Complications included transient dysphagia in three patients and superficial wound infection in two patients. The present study indicates that one- to two-level stand alone Cervios cage-assisted interbody fusion without plate fixation provides improvement of clinical outcomes, restoration of lordosis and high fusion rate. However subsidence occurred in 7.61% but did not cause clinical symptoms and the patients had to use the cervical collar postoperatively.
Zong, Qiang; Ni, Dongkui; Li, Lijun; Shi, Yubo
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
Zong, Qiang; Ni, Dongkui; Li, Lijun; Shi, Yubo
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.
Shichang, Liu; Yueming, Song; Limin, Liu; Lei, Wang; Zhongjie, Zhou; Chunguang, Zhou; Xi, Yang
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.
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 ...
Li, Zhonghai; Yu, Shunzhi; Zhao, Yantao; Hou, Shuxun; Fu, Qiang; Li, Fengning; Hou, Tiesheng; Zhong, Hongbin
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.
Tian, Peng; Fu, Xin; Li, Zhi-Jun; Sun, Xiao-Lei; Ma, Xin-Long
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
McGregor, Alison H
Objectives Despite lumbar degenerative disc disease (LDDD) being significantly associated with non-specific low back pain and effective treatment remaining elusive, specialist multidisciplinary clinical stakeholder opinion remains unexplored. The present study examines the views of such experts. Design A reliable and valid electronic survey was designed to establish trends using theoretical constructs relating to current assessment and management practices. Clinicians from the Society of Back Pain Research (SBPR) UK were invited to take part. Quantitative data were collated and coded using Bristol Online Surveys (BOS) software, and content analysis was used to systematically code and categorise qualitative data. Setting Specialist multidisciplinary spinal interest group in the UK. Participants 38/141 clinically active, multidisciplinary SBPR members with specialist spinal interest participated. Among them, 84% had >9 years postgraduate clinical experience. Interventions None. Outcome measures Frequency distributions were used to establish general trends in quantitative data. Qualitative responses were coded and categorised in relation to each theme and percentage responses were calculated. Results LDDD symptom recurrence, in the absence of psychosocial influence, was associated with physical signs of joint stiffness (26%), weakness (17%) and joint hypermobility (6%), while physical factors (21%) and the ability to adapt (11%) were postulated as reasons why some experience pain and others do not. No one management strategy was supported exclusively or with consensus. Regarding effective modalities, there was no significant difference between allied health professional and medic responses (p=0.1–0.8). The future of LDDD care was expressed in terms of improvements in patient communication (35%), patient education (38%) and treatment stratification (24%). Conclusions Results suggest that multidisciplinary expert spinal clinicians appear to follow UK
related ICD-9-CM codes 723.0 Spinal stenosis , cervical 724.00, 724.01, 724.02, 724.09 Spinal stenosis ,other 723.1 Cervicalgia 724.2 Lumbago 724.3...that 87 percent of all those evacuated for musculoskeletal disease/injury – and 86 percent of those evacuated for “ spinal pain” – did not return to
Gautschi, Oliver P; Smoll, Nicolas R; Corniola, Marco V; Joswig, Holger; Chau, Ivan; Hildebrandt, Gerhard; Schaller, Karl; Stienen, Martin N
There are few objective measures of functional impairment to support clinical decision making in lumbar degenerative disc disease (DDD). We present the validation (and reliability measures) of the Timed Up and Go (TUG) test. In a prospective, 2-center study, 253 consecutive patients were assessed using the TUG test. A representative cohort of 110 volunteers served as control subjects. The TUG test values were assessed for validity and reliability. The TUG test had excellent intra- (intraclass correlation coefficient: 0.97) and interrater reliability (intraclass correlation coefficient: 0.99), with a standard error of measurement of 0.21 and 0.23 seconds, respectively. The validity of the TUG test was demonstrated by a good correlation with the Visual Analog Scale (VAS) back (Pearson's correlation coefficient [PCC]: 0.25) and VAS (PCC: 0.29) leg pain, functional impairment (Roland-Morris Disability Index [PCC: 0.38] and Oswestry Disability Index [PCC: 0.34]), as well as with health-related quality of life (Short Form-12 Mental Component Summary score [PCC: -0.25], Short Form-12 Physical Component Summary score [PCC: -0.32], and EQ-5D [PCC: -0.28]). The upper limit of "normal" was 11.52 seconds. Mild (lower than the 33rd percentile), moderate (33rd to 66th percentiles), and severe objective functional impairment (higher than the 66th percentile) as determined by the TUG test was <13.4 seconds, 13.4 to 18.4 seconds, and >18.4 seconds, respectively. The TUG test is a quick, easy-to-use, valid, and reliable tool to evaluate objective functional impairment in patients with lumbar degenerative disc disease. In the clinical setting, patients scoring a TUG test time of over 12 seconds can be considered to have functional impairment. BMI, body mass indexDDD, degenerative disc diseaseHRQOL, health-related quality of lifeICC, intraclass correlationLDH, lumbar disc herniationLSS, lumbar spinal stenosisODI, Oswestry Disability IndexOFI, objective functional impairment
Chang, Ting-Kuo; Hsu, Ching-Chi; Chen, Kuan-Ting
Anterior cervical discectomy and fusion is a common surgical procedure performed to remove a degenerative or herniated disc in cervical spine. Unfortunately, clinical complications of anterior cervical plate (ACP) systems still occur, such as weak fixation stability and implant loosening. Previous researchers have attempted to ameliorate these complications by varying screw orientations, but the screw orientations are mainly determined according to the investigator's experiences. Thus, the aim of this study was to discover the optimal screw orientations of ACP systems to achieve acceptable fixation stability using finite element simulations and engineering algorithms. Three-dimensional finite element models of C3-T2 multi-level segments with an ACP system were first developed to analyze the fixation stability using ANSYS Workbench 14.5. Then, artificial neural networks were applied to create one objective function, and the optimal screw orientations of an ACP system were discovered by genetic algorithms. Finally, the numerical models and the optimization study were validated using biomechanical tests. The results showed that the optimal design of the ACP system had highest fixation stability compared with other ACP designs. The neuro-genetic algorithm has effectively reduced the time and effort required for discovering for the optimal screw orientations of an ACP system. The optimum screw orientation of the ACP system could be successfully discovered, and it revealed excellent fixation stability for the treatment of cervical degenerative disc disease. This study could directly provide the biomechanical rationale and surgical suggestion to orthopedic surgeons.
Wenger, Markus; Markwalder, Thomas-Marc
Total disc arthroplasty is a new option in the treatment of cervical degenerative disc disease. Several types of cervical disc prostheses currently challenge the gold-standard discectomy and fusion procedures. This review describes the Bryan Cervical Disc System and presents the Bryan prosthesis, its indications, surgical technique, complications, and outcomes, as given in the literature. PMID:22915917
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?
Assietti, Roberto; Corbino, Leonardo; Olindo, Giuseppe; Foti, Pietro V.; Russo, Vittorio; Albanese, Vincenzo
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
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?
Barbagallo, Giuseppe M V; Assietti, Roberto; Corbino, Leonardo; Olindo, Giuseppe; Foti, Pietro V; Russo, Vittorio; Albanese, Vincenzo
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 degrees ) 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.
Cervical total disc replacement with the Mobi-C cervical artificial disc compared with anterior discectomy and fusion for treatment of 2-level symptomatic degenerative disc disease: a prospective, randomized, controlled multicenter clinical trial: clinical article.
Davis, Reginald J; Kim, Kee D; Hisey, Michael S; Hoffman, Gregory A; Bae, Hyun W; Gaede, Steven E; Rashbaum, Ralph F; Nunley, Pierce Dalton; Peterson, Daniel L; Stokes, John K
Cervical total disc replacement (TDR) is intended to treat neurological symptoms and neck pain associated with degeneration of intervertebral discs in the cervical spine. Anterior cervical discectomy and fusion (ACDF) has been the standard treatment for these indications since the procedure was first developed in the 1950s. While TDR has been shown to be a safe and effective alternative to ACDF for treatment of patients with degenerative disc disease (DDD) at a single level of the cervical spine, few studies have focused on the safety and efficacy of TDR for treatment of 2 levels of the cervical spine. The primary objective of this study was to rigorously compare the Mobi-C cervical artificial disc to ACDF for treatment of cervical DDD at 2 contiguous levels of the cervical spine. This study was a prospective, randomized, US FDA investigational device exemption pivotal trial of the Mobi-C cervical artificial disc conducted at 24 centers in the US. The primary clinical outcome was a composite measure of study success at 24 months. The comparative control treatment was ACDF using allograft bone and an anterior plate. A total of 330 patients were enrolled, randomized, and received study surgery. All patients were diagnosed with intractable symptomatic cervical DDD at 2 contiguous levels of the cervical spine between C-3 and C-7. Patients were randomized in a 2:1 ratio (TDR patients to ACDF patients). A total of 225 patients received the Mobi-C TDR device and 105 patients received ACDF. At 24 months only 3.0% of patients were lost to follow-up. On average, patients in both groups showed significant improvements in Neck Disability Index (NDI) score, visual analog scale (VAS) neck pain score, and VAS arm pain score from preoperative baseline to each time point. However, the TDR patients experienced significantly greater improvement than ACDF patients in NDI score at all time points and significantly greater improvement in VAS neck pain score at 6 weeks, and at 3, 6, and
Gautschi, Oliver P; Corniola, Marco V; Smoll, Nicolas R; Joswig, Holger; Schaller, Karl; Hildebrandt, Gerhard; Stienen, Martin N
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.
Segura-Trepichio, M; Ferrández-Sempere, D; López-Prats, F; Segura-Ibáñez, J; Maciá-Soler, L
The Dynesys(®) system is a non-fusion pedicular dynamic stabilization system. The aim of our study is to evaluate the clinical outcomes in patients with degenerative disc disease and/or stenosis, and to measure the prevalence of screw loosening and breakage after 4 years of follow up. All patients who underwent surgery with Dynesys(®) system in 2008 were reviewed. The surgery was performed in cases of low back pain of more than 6 months duration and a positive MRI for degenerative disc disease and/or stenosis. A total of 22 patients (11 females, 11 males) with a mean age of 44.40 ± 11 years were included, 20 patients (91%) underwent Dynesys(®) without any associated decompression maneuver. The evaluation of back and leg pain (0-10mm) showed a mean decrease of 2.4 ± 2.06 mm (P=.0001). The preoperative value of the Oswestry disability index was 52.36 ± 16.56% (severe functional limitation). After surgery, this value was 34.27 ± 17.87% (moderate functional limitation) (P=.001) with a decrease of 18.09 ± 16.03% (P=.001). A total of 4 (18%) patients showed signs of loosening screws. One patient (4.5%) had a screw breakage. Surgery with Dynesys(®) shows favorable long term clinical results, however the range of improvement in our series is lower than those reported in other studies. Comparative studies between Dynesys(®) and decompression need to be performed in order to isolate the benefit of the dynamic stabilization system. Implant-related complications are not uncommon. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.
Singh, Pritish; Shekhawat, Vishal
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
Armbrecht, Gabriele; Felsenberg, Dieter; Ganswindt, Melanie; Lunt, Mark; Kaptoge, Stephen K; Abendroth, Klaus; Aroso Dias, Antonio; Bhalla, Ashok K; Cannata Andia, Jorge; Dequeker, Jan; Eastell, Richard; Hoszowski, Krysztoff; Lyritis, George; Masaryk, Pavol; van Meurs, Joyce; Miazgowski, Tomasz; Nuti, Ranuccio; Poór, Gyula; Redlund-Johnell, Inga; Reid, David M; Schatz, Helmut; Todd, Christopher J; Woolf, Anthony D; Rivadeneira, Fernando; Javaid, Muhammad K; Cooper, Cyrus; Silman, Alan J; O’Neill, Terence W; Reeve, Jonathan
Objectives To assess the prevalence across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal bone mineral density (aBMD) and change in aBMD with time. Methods In the population-based European Prospective Osteoporosis Study 27 age-stratified samples of men and women from across the continent aged 50+ had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature. Results Images from 10,132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD. Discussion KL Grades 3 and 4 are often used clinically to categorise radiological DDD. Highly variable European prevalences of radiologically-defined DDD Grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes. PMID:28398504
Wu, Ting-Kui; Wang, Bei-Yu; Cheng, Ding; Rong, Xin; Lou, Ji-Gang; Hong, Ying; Liu, Hao
We describe the radiographic changes of IS and investigate the safety and feasibility of hybrid surgery (HS) coupling cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) for the treatment of skip-level cervical degenerative disc disease (CDDD). Twenty-seven patients who received HS were retrospectively reviewed. Clinical evaluation based on the Japanese Orthopedic Association (JOA) and Neck Disability Index (NDI) and Visual Analog Scale (VAS) scores. Radiographic parameters included cervical alignment (CA), functional spine unite (FSU) angle of intermediated segment (IS), range of motion (ROM) and intervertebral disc height (IDH). Data regarding radiographic changes at IS were collected. The mean follow-up duration of 30.10months. Compared with preoperative value, JOA, NDI and VAS scores significantly improved after surgery (p<0.05). The CA was recovered significantly after surgery (p<0.05). There was no significant difference in the FSU angle and the IDH of IS between before and at 24months postoperatively (p>0.05). The ROM of IS significantly decreased at the first week after surgery (p<0.05), was similar to preoperative value at 3months postoperatively and significantly increased after 6months (p<0.05). Radiographic changes at IS were observed in 2 patients and Class II Heterotopic ossification (HO) was detected in 2 patients. HS is a safe and feasible alternative procedure for the treatment of skip-level CDDD. It preserved the IS intact and achieved satisfactory clinical and radiographic outcomes over a 24-month follow-up.
Kolmstetter, C; Munson, L; Ramsay, E C
Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions.
Centeno, Christopher; Markle, Jason; Dodson, Ehren; Stemper, Ian; Williams, Christopher J; Hyzy, Matthew; Ichim, Thomas; Freeman, Michael
Degenerative disc disease (DDD) is a common cause of lower back pain with radicular symptoms and has a significant socioeconomic impact given the associated disability. Limited effective conservative therapeutic options result in many turning to surgical alternatives for management, which vary in the rate of success and also carry an increased risk of morbidity and mortality associated with the procedures. Several animal based studies and a few human pilot studies have demonstrated safety and suggest efficacy in the treatment of DDD with mesenchymal stem cells (MSCs). The use of bone marrow-derived MSCs for the treatment of DDD is promising and in the present study we report on the safety and efficacy findings from a registry based proof of concept study using a percutaneous intradiscal injection of cultured MSCs for the management of DDD with associated radicular symptoms. Thirty-three patients with lower back pain and disc degeneration with a posterior disc bulge diagnosed on magnetic resonance imaging (MRI) met the inclusion criteria and were treated with culture-expanded, autologous, bone marrow-derived MSCs. Prospective registry data was obtained at multiple time intervals up to 6 years post-treatment. Collected outcomes included numeric pain score (NPS), a modified single assessment numeric evaluation (SANE) rating, functional rating index (FRI), measurement of the intervertebral disc posterior dimension, and adverse events. Three patients reported pain related to procedure that resolved. There were no serious adverse events (i.e. death, infection, or tumor) associated with the procedure. NPS change scores relative to baseline were significant at 3, 36, 48, 60, and 72 months post-treatment. The average modified SANE ratings showed a mean improvement of 60% at 3 years post-treatment. FRI post-treatment change score averages exceeded the minimal clinically important difference at all time points except 12 months. Twenty of the patients treated underwent
Chen, Shuai; Fang, Xiang-Qian; Wang, Qiang; Wang, Shao-Wei; Hu, Zhi-Jun; Zhou, Zhi-Jie; Xu, Wen-Bing; Wang, Ji-Ying; Qin, An; Fan, Shun-Wu
Intervertebral disc degeneration is a major cause of low back pain. The nucleus pulposus (NP) is an important intervertebral disc component. Recent studies have shown that carbonic anhydrase 12 (CA12) is a novel NP marker. However, the mechanism by which CA12 is regulated and its physiological function are unclear. In our study, CA12, hypoxia-inducible factor 1α (HIF-1α) and HIF-2α expression levels were examined in 81 human degenerated NP samples using real-time RT-PCR, immunohistochemistry and western blot. Rat NP cells were cultured in a hypoxic environment, and hypoxia-induced CA12 expression was examined. Rat NP cells were treated with HIF-1α siRNA or the prolyl hydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG) to evaluate the role of PHD/HIF-1 in regulating CA12 expression. Rat NP cells were treated with CA12 siRNA to determine the function of CA12. A rat ex vivo model was established to confirm that PHD, HIF-1, and CA12 have important roles in disc degeneration. We found that CA12 was significantly downregulated in degenerated human NP samples at the mRNA and protein levels. CA12 expression sharply increased by ~30-fold in response to hypoxia. The expression of HIF-1α, but not HIF-2α, also decreased in degenerated human NP samples and was positively correlated with CA12 expression. HIF-1α knockdown under hypoxia reduced the CA12 mRNA and protein expression levels. DMOG treatment increased HIF-1α and CA12 expression. CA12 knockdown significantly inhibited anabolic protein expression, whereas catabolic enzymes remained unchanged. The ex vivo experiments supported our in vitro studies of the role of PHD/HIF-1/CA12. In conclusion, CA12 is downregulated in degenerated NPs, and its expression may be regulated by the PHD/HIF-1 axis. Decreased CA12 expression may lead to decreased extracellular matrix synthesis, which contributes to degenerative disc disease progression.
Kim, Suhyeong; Yi, Hyeon-Joong; Bak, Koang Hum; Kim, Dong Won; Lee, Yoon Kyoung
Objective Various procedures have been introduced for anterior interbody fusion in degenerative cervical disc disease including plate systems with autologous iliac bone, carbon cages, and cylindrical cages. However, except for plate systems, the long-term results of other methods have not been established. In the present study, we evaluated radiologic findings for cylindrical cervical cages over long-term follow up periods. Methods During 4 year period, radiologic findings of 138 patients who underwent anterior cervical fusion with cylindrical cage were evaluated at 6, 12, 24, and 36 postoperative months using plain radiographs. We investigated subsidence, osteophyte formation (anterior and posterior margin), cage direction change, kyphotic angle, and bone fusion on each radiograph. Results Among the 138 patients, a minimum of 36 month follow-up was achieved in 99 patients (mean follow-up : 38.61 months) with 115 levels. Mean disc height was 7.32 mm for preoperative evaluations, 9.00 for immediate postoperative evaluations, and 4.87 more than 36 months after surgery. Osteophytes were observed in 107 levels (93%) of the anterior portion and 48 levels (41%) of the posterior margin. The mean kyphotic angle was 9.87° in 35 levels showing cage directional change. There were several significant findings : 1) related subsidence [T-score (p=0.039) and anterior osteophyte (p=0.009)], 2) accompanying posterior osteophyte and outcome (p=0.05). Conclusion Cage subsidence and osteophyte formation were radiologically observed in most cases. Low T-scores may have led to subsidence and kyphosis during bone fusion although severe neurologic aggravation was not found, and therefore cylindrical cages should be used in selected cases. PMID:23091668
Gautschi, Oliver P; Stienen, Martin N; Corniola, Marco V; Joswig, Holger; Schaller, Karl; Hildebrandt, Gerhard; Smoll, Nicolas R
The Timed Up and Go Test (TUG Test) has previously been described as a reliable tool to evaluate objective functional impairment in patients with degenerative disc disease. The aim of this study was to assess the minimum clinically important difference (MCID) of the TUG Test. The TUG Test (measured in seconds) was correlated with validated patient-reported outcome measures (PROs) of pain intensity (Visual Analog Scale for back and leg pain), functional impairment (Oswestry Disability Index, Roland Morris Disability Index), and health-related quality of life measures (Short Form-12 and EuroQol 5D). Three established methods were used to establish anchor-based MCID values using responders of the following PROs (Visual Analog Scale back and leg pain, Oswestry Disability Index, Roland Morris Disability Index, EuroQol 5D index, and Short Form-12 Physical Component Summary) as anchors: (1) average change, (2) minimum detectable change, and (3) change difference approach. One hundred patients with a mean ± SD age of 56.2 ± 16.1 years, 57 (57%) male, 45 patients undergoing microdiscectomy, 35 undergoing lumbar decompression, and 20 undergoing fusion surgery were studied. The 3 MCID computation methods revealed a range of MCID values according to the PRO used from 0.9 s (Oswestry Disability Index based on the change difference approach) to 6.0 s (EuroQol 5D index based on the minimum detectable change approach), with a mean MCID of 3.4 s for all measured PROs. The MCID for the TUG Test time is highly variable depending on the computation technique used. The average TUG Test MCID was 3.4 s using all 3 methods and all anchors.
Faour, Mhamad; Anderson, Joshua T; Haas, Arnold R; Percy, Rick; Woods, Stephen T; Ahn, Uri M; Ahn, Nicholas U
Retrospective cohort comparative study. To evaluate presurgical and surgical factors that affect return to work (RTW) status after multilevel cervical fusion, and to compare outcomes after multilevel cervical fusion for degenerative disc disease (DDD) versus radiculopathy. Cervical fusion provides more than 90% of symptomatic relief for radiculopathy and myelopathy. However, cervical fusion for DDD without radiculopathy is considered controversial. In addition, multilevel fusion is associated with poorer surgical outcomes with increased levels fused. Data of cervical comorbidities was collected from Ohio Bureau of Workers' Compensation for subjects with work-related injuries. The study population included subjects who underwent multilevel cervical fusion. Patients with radiculopathy or DDD were identified. Multivariate logistic regression was performed to identify factors that affect RTW status. Surgical and functional outcomes were compared between groups. Stable RTW status within 3 years after multilevel cervical fusion was negatively affected by: fusion for DDD, age > 55 years, preoperative opioid use, initial psychological evaluation before surgery, injury-to-surgery > 2 years and instrumentation.DDD group had lower rate of achieving stable RTW status (P= 0.0001) and RTW within 1 year of surgery (P= 0.0003) compared with radiculopathy group. DDD patients were less likely to have a stable RTW status [odds ratio, OR = 0.63 (0.50-0.79)] or RTW within 1 year after surgery [OR = 0.65 (0.52-0.82)].DDD group had higher rate of opioid use (P= 0.001), and higher rate of disability after surgery (P= 0.002). Multiple detriments affect stable RTW status after multilevel cervical fusion including DDD. DDD without radiculopathy was associated with lower RTW rates, less likelihood to return to work, higher disability, and higher opioid use after surgery. Multilevel cervical fusion for DDD may be counterproductive. Future studies should investigate further
Gautschi, Oliver P; Joswig, Holger; Corniola, Marco V; Smoll, Nicolas R; Schaller, Karl; Hildebrandt, Gerhard; Stienen, Martin N
The Timed Up and Go (TUG) test is a reliable tool for evaluating objective functional impairment (OFI) in patients with degenerative disc disease before a surgical intervention. The aim of this study is to assess the validity of the TUG test to measure change in function postoperatively. In a prospective two-center study, OFI was assessed by the TUG test in patients scheduled for lumbar spine surgery, as well as 3 days (D3) and 6 weeks (W6) postoperatively. At each time point, the TUG test results were correlated with established subjective measures of pain intensity (visual analogue scale (VAS) for back and leg pain), functional impairment (Oswestry Disability Index (ODI)) and health-related quality of life (HRQoL; Short Form-12 (SF12)). The patient cohort comprised 136 patients with a mean age of 57.7 years; 76 were males, 54 had a microdiscectomy for lumbar disc herniation, 58 a decompression for a lumbar spinal stenosis, 24 had a surgical fusion procedure. The mean OFI t-score was 125.1 before surgery, and as patients improved on the subjective measures in the postoperative interval, the OFI t-score likewise decreased to 118.8 (D3) and 103.4 (W6). The Pearson correlation coefficient (PCC) between the OFI t-score and VAS leg pain was 0.187 preoperatively (p = 0.029) and 0.252 at W6 (p = 0.003). The PCC between OFI t-score and the ODI was 0.324 preoperatively (p < 0.001) and 0.413 at W6 (p < 0.001). The PCC between OFI t-score and physical HRQoL (SF12) was -0.091 preoperatively (p = 0.293) and -0.330 at W6 (p < 0.001). The TUG test is sensitive to change, and reflects the postoperative functional outcome even more exact than preoperatively, as indicated by better correlation coefficients of the OFI t-score with subjective measures of pain intensity, functional impairment and HRQoL.
Faour, Mhamad; Anderson, Joshua T; Haas, Arnold R; Percy, Rick; Woods, Stephen T; Ahn, Uri M; Ahn, Nicholas U
A retrospective comparative cohort study. To compare return to work (RTW) rates for patients who underwent single-level cervical fusion for radiculopathy compared with fusion for degenerative disc disease (DDD) as an indication for surgery. Studies have shown that workers' compensation subjects have less favorable surgical and functional outcomes compared with the general population. Cervical decompression and fusion have provided great results with relieving radicular symptoms. Fusion for DDD, however, remains controversial. We retrospectively collected data of 21 169 subjects with cervical comorbidities who filed their claims for work-related injuries with Ohio Bureau of Workers' Compensation (BWC) between 1993 and 2011. The primary outcome was whether subjects met RTW criteria within 3-year follow-up after fusion. The secondary outcome measures and data on presurgical characteristics and secondary outcomes of each cohort were also collected. Successful RTW status was affected by a number of presurgical risk factors: DDD as an indication for surgery, age of more than 50 years, out of work for more than 6 months, psychological evaluation, opioid use, legal litigation, and permanent disability. The DDD group had lower rate of successful RTW status (50.9%) and was less likely to have a sustained RTW status (odds ratio = 0.61, 95% confidence interval: 0.48-0.79, P = 0.0001) compared with the radiculopathy group (successful RTW rate 62.9%). RTW rate within 1 year after surgery was lower in the DDD group (39.9%) compared with the radiculopathy group (53.1%; P = 0.0001). DDD patients were absent 112 days more on average after surgery compared with radiculopathy patients (P = 0.0003). Cervical fusion for DDD is associated with lower rate of successful RTW status when compared with fusion for radiculopathy in a worker's compensation setting. The decision to include surgical intervention in the management plan of cervical DDD should be approached with
Pillon, B; Czernecki, V; Dubois, B
A dysexecutive syndrome is observed not only in frontotemporal lobar degeneration, but also in subcortical degenerative diseases, and even in Alzheimer's disease whose lesions predominate in temporoparietal associative areas. The association between a dysexecutive syndrome and various cerebral localisations may be explained by the fact that cognitive and behavioral organisation recruits anatomofunctional frontostriatal and frontoparietal circuits. Both animal experimentation and human clinical observation argue in favour of a functional continuity and complementarity among these loops. The prefrontal cortex would be particularly needed in new situations, to inhibit old programs of action not adapted to the present context and to elaborate new ones; the basal ganglia would be rather required by the repetition of the situation to progressively transform the new program in routine. If we refer to Shallice model, we can hypothesize that optimal executive functions require the preservation not only of the Supervisory Attentional System, mainly dependent on the prefrontal cortex, but also of the Contention Scheduling, recruiting the basal ganglia, and of the Schemas of Action, represented in parietal and premotor areas. Therefore, the neuropsychological assessment of patients with degenerative diseases contributes to the understanding of the anatomofunctional architecture of executive functions.
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.
Zigler, Jack E; Delamarter, Rick B
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. 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. 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 conservative care. The percentage
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.
Radcliff, Kris; Coric, Domagoj; Albert, Todd
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
Fusco, Mariella; Skaper, Stephen D; Coaccioli, Stefano; Varrassi, Giustino; Paladini, Antonella
Rheumatic and joint diseases, as exemplified by osteoarthritis and rheumatoid arthritis, are among the most widespread painful and disabling pathologies across the globe. Given the continuing rise in life expectancy, their prevalence is destined to grow. Osteoarthritis, a degenerative joint disease, is, in particular, on its way to becoming the fourth leading cause of disability worldwide by 2020, with the rising incidence of obesity in addition to age being important factors. It is estimated that 25% of osteoarthritic individuals are unable to perform daily activities. Accompanying osteoarthritis is rheumatoid arthritis, which is a chronic systemic disease that often causes pain and deformity. At least 50% of those affected are unable to remain gainfully employed within 10 years of disease onset. A growing body of evidence now points to inflammation, locally and more systemically, as a promoter of damage to joints and bones, as well as joint-related functional deficits. The pathogenesis underlying joint diseases remains unclear; however, it is currently believed that cross-talk between cartilage and subchondral bone-and loss of balance between these two structures in joint diseases-is a critical element. This view is amplified by the presence of mast cells, whose dysregulation is associated with alterations of junction structures (cartilage, bone, synovia, matrix, nerve endings, and blood vessels). In addition, persistent activation of mast cells facilitates the development of spinal neuroinflammation mediated through their interaction with microglia. Unfortunately, current treatment strategies for rheumatic and articular disease are symptomatic and do little to limit disease progression. Research now should be directed at therapeutic modalities that target osteoarticular structural elements and thereby delaying disease progression and joint replacement.
Illien-Jünger, Svenja; Pattappa, Girish; Peroglio, Marianna; Benneker, Lorin M; Stoddart, Martin J; Sakai, Daisuke; Mochida, Joji; Grad, Sibylle; Alini, Mauro
Homing of human bone marrow-derived mesenchymal stem cells (BMSCs) was studied using ex vivo cultured bovine caudal intervertebral discs (IVDs). To investigate in a whole organ culture whether metabolic and mechanical challenges can induce BMSC recruitment into the IVD. Cells from injured tissues release cytokines and mediators that enable the recruitment of progenitor cells. BMSCs have the ability to survive within the IVD. Bovine IVDs with or without endplates were cultured for 1 week under simulated physiological or degenerative conditions; disc cells were analyzed for cell viability and gene expression, whereas media was analyzed for nitric oxide production and chemotaxis. Homing of BMSCs was investigated by supplying PKH-labeled human BMSCs onto cultured IVDs (1 × 10(6) cells/disc on d 8, 10, and 12 of culture); on day 14, the number of homed BMSCs was microscopically assessed. Moreover, a comparative study was performed between transduced BMSCs (transduced with an adenovirus encoding for insulin-like growth factor 1 [IGF-1]) and nontransduced BMSCs. Disc proteoglycan synthesis rate was quantified via (35)S incorporation. The secretion of IGF-1 was evaluated by enzyme-linked immunosorbent assay on both simulated physiological and degenerative discs. Discs cultured under degenerative conditions showed reduced cell viability, upregulation of matrix degrading enzymes, and increased nitric oxide production compared with simulated physiological discs. Greater homing occurred under degenerative compared with physiological conditions with or without endplate. Media of degenerative discs demonstrated a chemoattractive activity toward BMSCs. Finally, discs homed with IGF-1-transduced BMSCs showed increased IGF-1 secretion and significantly higher proteoglycan synthesis rate than discs supplied with nontransduced BMSCs. We have demonstrated for the first time that degenerative conditions induce the release of factors promoting BMSC recruitment in an ex vivo organ
Unglaub, Frank; Wolf, Maya B; Dragu, Adrian; Schwarz, Stephan; Kroeber, Markus W; Horch, Raymund E
Traumatic and degenerative disc lesions cause ulnar-sided wrist pain. To date, anatomical investigations of cadaver triangular fibrocartilage discs examining the innervation of the triangular fibrocartilage complex have found no evidence of nerve fibers in the healthy disc. In this study, we immunohistologically investigated biopsies from patients with either central traumatic or degenerative disc lesions, to determine the existence of nerve fibers. We hypothesized that an ingrowth of nerve fibers causes ulnar-sided wrist pain associated with traumatic and degenerative disc lesions. We included 32 patients with a traumatic Palmer 1A lesion and 17 patients with a degenerative Palmer 2C lesion in the study. We obtained a biopsy of each patient and stained the specimen with protein gene product 9.5 for nerve fiber detection. There were no nerve fibers in either traumatic or degenerative disc lesions. In addition, the marginal areas of the biopsies showed no evidence of nerve fibers. Traumatic and degenerative disc lesions show no ingrowth of nerve fibers. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.
Five-year results of the prospective, randomized, multicenter, Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement versus circumferential arthrodesis for the treatment of single-level degenerative disc disease.
Zigler, Jack E; Delamarter, Rick B
The purpose of this study was to evaluate the long-term safety and effectiveness of the ProDisc-L total disc replacement (TDR) as part of an FDA-mandated postmarket approval study. This report summarizes the clinical findings after 5 years of follow-up. Two hundred thirty-six patients were treated and followed up for 5 years; 161 TDRs and 75 fusions had been performed in these patients. The primary outcome was a 10-component success end point. Secondary outcome measures included neurological status, secondary surgery, Oswestry Disability Index (ODI), 36-Item Short Form Health Survey (SF-36), visual analog scale (VAS) assessing pain and satisfaction, radiographic data, narcotic use, activity, and recreation status. Patients were monitored through their 5-year postoperative visits under the FDA postmarket surveillance provisions in the original investigational device exemption approval. The overall follow-up rate at 5 years was 81.8%. Study success demonstrated that TDR was noninferior to fusion with a 12.5% margin (p = 0.0099). Both TDR and fusion treatment groups maintained significant improvement on the ODI at 5 years compared with baseline (p < 0.0001). Secondary surgeries at the index level were performed in 12% of fusion patients and 8% of TDR patients. Radiographically, none of the TDRs developed spontaneous fusion. The segmental range of motion following TDR remained within normal range, although it decreased by approximately 0.5° in years 3 to 5. The VAS pain scores decreased from preoperative values by 48% in both treatment groups at 5 years. Patient satisfaction remained high in both groups (77%), while the percentage of patients indicating that they would have the surgery again was higher in TDR patients (82.5%) than in fusion patients (68.0%). Patients in both groups maintained significant improvement during the 5-year follow-up. The TDR group had significantly better improvement on some scales. Although TDR patients avoid the stiffness of fusion and
Jiang, Wei; Zhang, Xuemei; Hao, Jie; Shen, Jieliang; Fang, Ji; Dong, Wen; Wang, Dawu; Zhang, Xiaojun; Shui, Wei; Luo, Yi; Lin, Liangbo; Qiu, Quanhe; Liu, Bin; Hu, Zhenming
SIRT1 could protect degenerative human NP cells against apoptosis, and there were extensive and intimate connection between apoptosis and autophagy. Up to now, the role of autophagy in the process of human IVD degeneration is unclear. We sought to explore the relationship between autophagy and human IVD degeneration and to understand whether autophagy is involved in the protective effect of SIRT1 against apoptosis in NP cells. Our results showed that the autophagosomes number, the mRNA level of LC3 and Beclin-1, the protein expression of LC3-II/I and Beclin-1, decreased in NP from DDD. Resveratrol could increase the protein expression of LC3-II/I and Beclin-1, and reduce apoptosis in degenerative NP cells. In contrast, the protein levels of LC3-II/I and Beclin-1 were down-regulated and apoptosis level was significantly up-regulated in treatment with nicotinamide or SIRT1-siRNA transfection. Further analysis identified that the expression of cleaved Caspase3 and apoptosis incidence significantly increased with the pretreatment of bafilomycin A, whether resveratrol was added or not. These suggested that autophagy may play an important role in IVD degeneration, and SIRT1 protected degenerative human NP cells against apoptosis via promoting autophagy. These findings would aid in the development of novel therapeutic approaches for degenerative disc disease treatment. PMID:25503852
Kim, Seong Joon
Objective Anterior cervical discectomy and fusion (ACDF) is often complicated by subsidence, pseudoarthrosis, kyphosis, and graft donor site morbidities. To decrease the occurrence of these complications, various types of cages have been developed. We designed this retrospective study to analyze and compare the efficacy and outcomes of ACDF using double cylindrical cages (DCC) (BK Medical, Seoul, Korea) versus an anterior cervical plating system with autogenous iliac crest grafts. Methods Forty-eight patients were treated with autograft and plating (plate group), and 48 with DCC group from October 2007 to October 2011. We analyzed construct length, cervical lordotic curvarture, the thickness of the prevertebral soft tissue, segmental instability, and clinical outcomes. Results There were no significant differences between the two groups with regard to the decrease in construct length or cervical lodortic curvature at the 3-, 6-, and 12-month follow-ups. The prevertebral soft tissue was thinner in the DCC group than the plate group immediately after surgery and at the 3-, 6-, and 12-month follow-ups. The difference in interspinous distance on flexion-extension was shorter in the plate group than the DCC group at the 3- and 6-month follow-ups. However, there was no significant difference in this distance between the two groups at the 12-month follow-up. Conclusion A double cylindrical cage is a good alternative for fusion in patients with cervical degenerative diseases; the surgical method is relatively simple, allows good synostosis, has less associated prevertebral soft tissue swelling, and complications associated with autografting can be avoided. PMID:24570812
Cage subsidence does not, but cervical lordosis improvement does affect the long-term results of anterior cervical fusion with stand-alone cage for degenerative cervical disc disease: a retrospective study.
Wu, Wen-Jian; Jiang, Lei-Sheng; Liang, Yu; Dai, Li-Yang
Clinical outcomes of the stand-alone cage have been encouraging when used in anterior cervical discectomy and fusion (ACDF), but concerns remain regarding its complications, especially cage subsidence. This retrospective study was undertaken to investigate the long-term radiological and clinical outcomes of the stand-alone titanium cage and to evaluate the incidence of cage subsidence in relation to the clinical outcome in the surgical treatment of degenerative cervical disc disease. A total of 57 consecutive patients (68 levels) who underwent ACDF using a titanium box cage for the treatment of cervical radiculopathy and/or myelopathy were reviewed for the radiological and clinical outcomes. They were followed for at least 5 years. Radiographs were obtained before and after surgery, 3 months postoperatively, and at the final follow-up to determine the presence of fusion and cage subsidence. The Cobb angle of C2-C7 and the vertebral bodies adjacent to the treated disc were measured to evaluate the cervical sagittal alignment and local lordosis. The disc height was measured as well. The clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score for cervical myelopathy, before and after surgery, and at the final follow-up. The recovery rate of JOA score was also calculated. The Visual Analogue Scale (VAS) score of neck and radicular pain were evaluated as well. The fusion rate was 95.6% (65/68) 3 months after surgery. Successful bone fusion was achieved in all patients at the final follow-up. Cage subsidence occurred in 13 cages (19.1%) at 3-month follow-up; however, there was no relation between fusion and cage subsidence. Cervical and local lordosis improved after surgery, with the improvement preserved at the final follow-up. The preoperative disc height of both subsidence and non-subsidence patients was similar; however, postoperative posterior disc height (PDH) of subsidence group was significantly greater than of non-subsidence group
Unglaub, F; Lorenz, H; Nerlich, A; Richter, W; Kroeber, M W
Degeneration of the intervertebral disc is a common disease in the adults, especially at advanced age. A causal therapy is not known, but the progress in new therapeutic strategies, for example in tissue engineering, shows new possibilities. The goal of our study was to develop a new animal model that stimulates a load induced degeneration of the disc. We used the New Zealand rabbit, because morphology is similar to the human intervertebral disc. The degeneration was induced by axial compression of the disc L4 - L5 with an external fixateur. After different loading intervals, the animals were sacrified and the discs examined by radiology, histology, apoptosis and biomechanical testing. Radiography showed a significant decrease of the disc thickness in all loaded groups. Morphologically the intervertebral discs of loaded rabbits showed degenerative changes which were comparable to those in humans. A significantly increased number of dead cells in the annulus occurred after 14 and 28 days loading compared to the controls. The bending stress measured as the load to failure was not significantly different between the unloaded discs and the 28 days loaded discs. The results show that our animal modell can create degeneration. Four weeks compression leads to significant degeneration. Degeneration of the discs persisted in animals that were allowed a recovery time of 28 days after 28 days of loading.
Pasku, Dritan; Katonis, Pavlos; Karantanas, Apostolos; Hadjipavlou, Alexander
A rare case of a wide congenital atlas defect is reported. A 25 year-old woman was admitted after complaints of radicular pain in the right arm. Radiographs incidentally revealed aplasia of the posterior arch of the atlas together with anterior rachischisis. A review of the literature is presented and a possible association with early disc degeneration is discussed.
The 'Lumbar Fusion Outcome Score' (LUFOS): a new practical and surgically oriented grading system for preoperative prediction of surgical outcomes after lumbar spinal fusion in patients with degenerative disc disease and refractory chronic axial low back pain.
Mattei, Tobias A; Rehman, Azeem A; Teles, Alisson R; Aldag, Jean C; Dinh, Dzung H; McCall, Todd D
In order to evaluate the predictive effect of non-invasive preoperative imaging methods on surgical outcomes of lumbar fusion for patients with degenerative disc disease (DDD) and refractory chronic axial low back pain (LBP), the authors conducted a retrospective review of 45 patients with DDD and refractory LBP submitted to anterior lumbar interbody fusion (ALIF) at a single center from 2007 to 2010. Surgical outcomes - as measured by Visual Analog Scale (VAS/back pain) and Oswestry Disability Index (ODI) - were evaluated pre-operatively and at 6 weeks, 3 months, 6 months, and 1 year post-operatively. Linear mixed-effects models were generated in order to identify possible preoperative imaging characteristics (including bone scan/99mTc scintigraphy increased endplate uptake, Modic endplate changes, and disc degeneration graded according to Pfirrmann classification) which may be predictive of long-term surgical outcomes . After controlling for confounders, a combined score, the Lumbar Fusion Outcome Score (LUFOS), was developed. The LUFOS grading system was able to stratify patients in two general groups (Non-surgical: LUFOS 0 and 1; Surgical: LUFOS 2 and 3) that presented significantly different surgical outcomes in terms of estimated marginal means of VAS/back pain (p = 0.001) and ODI (p = 0.006) beginning at 3 months and continuing up to 1 year of follow-up. In conclusion, LUFOS has been devised as a new practical and surgically oriented grading system based on simple key parameters from non-invasive preoperative imaging exams (magnetic resonance imaging/MRI and bone scan/99mTc scintigraphy) which has been shown to be highly predictive of surgical outcomes of patients undergoing lumbar fusion for treatment for refractory chronic axial LBP.
Li, Zhonghai; Wang, Huadong; Li, Li; Tang, Jiaguang; Ren, Dongfeng; Hou, Shuxun
To investigate the clinical and radiological results of the new zero-profile, stand-alone Fidji cervical cage to treat single- and multiple-level cervical DDD, and evaluate the safety and efficiency. Between October 2011 and July 2014, 72 consecutive patients (41 males and 31 females; mean age 50.9years [range, 33-68years]) with cervical DDD who underwent surgery and were followed for more than 2years were enrolled in this study (mean 31.1months, range 24-47months). The study compared clinical outcomes, radiologic parameters and complication rates. The SF-36, VAS, NDI, and JOA scores of all patients were improved significantly after surgery at any time point. (all p<0.05). The C2-C7 Cobb angle and the disc height index (DHI) of all patients were improved significantly after surgery at any time point (all p<0.05). From 3months after surgery to final follow-up the DHI showed a significant reduction comparing 1week after surgery (all p<0.05). The fusion rates were 91.7% (66/72) and the radiologic mean fusion time was 9.9months. Radiological evidence of adjacent segment degeneration (ASD) was observed in 4/41 patients (9.8%). Postoperative complications included epidural hematoma, hoarseness, dysphagia, axial neck pain, and subsidence. The zero-profile, stand-alone Fidji cervical cage for ACDF can be considered an effective, reliable and safe alternative procedure in the treatment of cervical DDD. Copyright © 2017 Elsevier Ltd. All rights reserved.
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
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
Shrot, S; Sayah, A; Berkowitz, F
To evaluate whether various patterns of bone marrow oedema could be used to discriminate between infection and degenerative change. Seventy patients with imaging features suspicious for discitis and available clinical follow-up were blindly reviewed for vertebral marrow oedema on sagittal short-tau inversion recovery (STIR) images according to the following patterns: I, vertebra oedema is adjacent to the intervertebral space and sharply-marginated; II, vertebral oedema is adjacent to the intervertebral space but not sharply marginated from normal marrow or involves the entire vertebral body; and III, vertebral oedema is distant from the endplate with intervening hypointense marrow signal. Of 45 patients with a clinical diagnosis of discitis, pattern II was the most common oedema pattern (64%). Approximately 20% and 9% of discitis patients showed patterns I and III, respectively. In patients with degenerative changes, 44% patients showed pattern I, 32% showed pattern II, and 24% showed pattern III. Pattern II had a sensitivity, specificity, and positive predictive value of 0.64, 0.68, and 0.78 for diagnosing spine infection, respectively. Although bone marrow oedema in infective discitis most often extends from the disc space and has indistinct margins, the oedema may also have sharp margins or be remote from the involved intervertebral space. Bone marrow oedema patterns of infective discitis overlap with those of degenerative disease and are not sufficiently reliable to exclude infection in cases with magnetic resonance imaging findings suggestive of discitis. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Long-term Changes in Sagittal Alignment and its Clinical Implications After Cervical Interbody Fusion Cage Subsidence for Degenerative Cervical Disc Disease. A Prospective Study with Standalone Lordotic Tantalum Cages.
Tomé-Bermejo, Félix; Morales-Valencia, Julián A; Moreno-Pérez, Javier; Marfil-Pérez, Juan; Díaz-Dominguez, Elena; Piñera, Angel R; Alvarez, Luis
A retrospective, observational study of prospectively collected outcomes. To investigate the long-term clinical course of anterior cervical discectomy and fusion with interbody fusion cages (ACDF-IFC) with lordotic tantalum implants and to correlate the radiological findings with the clinical outcomes, with special emphasis in the significance and influence of implant subsidence. Cage subsidence is the most frequently reported complication after ACDF-IFC. However, most reports fail to correlate cage subsidence with lower fusion rates, or with unsatisfactory clinical results. Forty-one consecutive patients with symptomatic degenerative cervical disc disease with failure of conservative treatment. All patients underwent one/two-level ACDF-IFC with lordotic tantalum implants. Mean follow-up of was 4.91 years. Final follow-up fusion rate was 96.96% (32/33). Interspace height (IH) at the affected levels was significantly incremented after implant insertion, and despite a gradual loss in the height occurred over time, final follow-up IH was significantly higher than preoperatively (P<0.0001). Anterior-IH and posterior-IH lost 55.8% and 76.2% of the initially incremented height respectively, with a final increase of 72% in the AIH-PIH height differential. Implant subsidence (>3 mm) occurred in 11 disc spaces (26.82%). Pre and postop-IH was significantly higher in the subsidence patients, however, there was no difference in final follow-up IH (P>0.05). Patients with ≥3 years of follow-up (n=29) did not demonstrate further significant subsidence beyond the second year. Regarding C1-C7 lordosis, segmental Cobb angle, cervical Visual Analogue Scale and Neck Disability Index questionnaires, no difference between patients with or without final follow-up endplate subsidence was encountered. Until fusion occurs, tantalum cage settlement into the vertebral body is to be expected. Further subsidence could be the result of segmental adaptative changes. Graft subsidence did not
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
Bae, Hyun W.; Davis, Reginald; Gaede, Steven; Hoffman, Greg; Kim, Kee; Nunley, Pierce D.; Peterson, Daniel; Rashbaum, Ralph; Stokes, John
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
Vadalà, Gianluca; Russo, Fabrizio; Di Martino, Alberto; Denaro, Vincenzo
Low back pain is one of the major health problems in industrialized countries, as a leading source of disability in the working population. Intervertebral disc degeneration has been identified as its main cause, being a progressive process mainly characterized by alteration of extracellular matrix composition and water content. Many factors are involved in the degenerative cascade, such as anabolism/catabolism imbalance, reduction of nutrition supply and progressive cell loss. Currently available treatments are symptomatic, and surgical procedures consisting of disc removal are often necessary. Recent advances in our understanding of intervertebral disc biology led to an increased interest in the development of novel biological treatments aimed at disc regeneration. Growth factors, gene therapy, stem cell transplantation and biomaterials-based tissue engineering might support intervertebral disc regeneration by overcoming the limitation of the self-renewal mechanism. The aim of this paper is to overview the literature discussing the current status of our knowledge from the degenerative cascade of the intervertebral disc to the latest molecular, cell-based therapies and tissue-engineering strategies for disc regeneration.
Du, Hong-Gen; Liao, Sheng-Hui; Jiang, Zhong; Huang, Huan-Ming; Ning, Xi-Tao; Jiang, Neng-Yi; Pei, Jian-Wei; Huang, Qin; Wei, Hui
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.
Dooley, D M
Fifty per cent of patients diagnosed as having multiple sclerosis, primary lateral sclerosis, or hereditary spinocerebellar disorders were observed to have enduring favorable changes in neurological function during the 15 to 27 months they have been followed. The patients who were the least severely disabled were benefitted the most by the stimulation and made the most rapid progress. For example, the patient having only an ataxic or a spastic gait typically was observed to improve faster than the patient having both an ataxic and a spastic gait. The long term effect of electrostimulation of the spinal cord on these patients is unknown. The purpose of the stimulation is to attempt to obtain an improvement in neurological function so that the patient may experience a better life style. It is not thought that the electrical current has any effect on the basic disease process. Electrostimulation over the posterior spinal roots and spinal cord, although not new, has not been used extensively for the treatment of patients with arterial disease. The patients who have responded the most dramatically to electrostimulation are those with vasospastic disorders. A larger percentage of patients showed a greater response to implanted stimulation than to transcutaneous stimulation. Electrostimulation of the nervous system is not designed to replace standard therapeutic measures of treatment of patients with vascular disease, but to supplement them.
Panush, R.S.; Schmidt, C.; Caldwell, J.R.; Edwards, N.L.; Longley, S.; Yonker, R.; Webster, E.; Nauman, J.; Stork, J.; Pettersson, H.
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.
Klee, S; Ungemach, F R
The pharmacological treatment of degenerative joint diseases is restricted essentially to the alleviation of acute symptoms of activated arthropathies. Suitable compounds are the non-steroidal and steroidal antiinflammatory drugs, which however do not allow long-term therapy due to their overall catabolic effects on cartilage metabolism. Since causally acting drugs are not available, the progressive course of the disease cannot be prevented so far. Natural components of the cartilage's matrix, being recommended as so-called chondroprotective drugs, do not fulfill the expectation of a remission of the degenerative process. Indeed, regarding the necessity of multiple local applications of these drugs, they are not superior to antiinflammatory drugs. Provided careful dosing and surveillance of untoward gastrointestinal effects, non-steroidal antiinflammatory agents still are the drugs of first choice.
the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited retinal degenerative diseases is estimated at...for autosomal dominant retinitis pigmentosa ). As new interventions become available for clinical evaluation, the creation of such a network will...dominant retinitis pigmentosa at six sites- the CTEC site at University of Utah and five recruitment sites- the Retina Foundation of the Southwest
Eadie, M J
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. Copyright © 1974 Australian Physiotherapy Association. Published by . All rights reserved.
Anderson, D Greg; Izzo, Marc W; Hall, David J; Vaccaro, Alexander R; Hilibrand, Alan; Arnold, William; Tuan, Rocky S; Albert, Todd J
A rabbit annular laceration model was used to investigate intervertebral disc gene expression in normal and lacerated discs. To determine and compare the pattern of expression of potentially important genes in normal and lacerated discs and to determine if the changes in gene expression were similar to human degenerative discs. Little is known regarding gene expression in normal or degenerating disc tissue. Eighteen rabbits were subjected to annular laceration of the L1-L2 and L2-L3 discs while two rabbits served as sham controls. Control and lacerated discs were harvested 1 week, 3 weeks, and 6 weeks following surgery and subjected to histologic examination and gene expression analysis using the reverse transcription-polymerase chain reaction (RT-PCR). The genes studied included collagen Type I (Col I), collagen Type II (Col II), decorin, fibronectin (FN), interleukin-1a (IL-1alpha), bone morphogenetic protein 2 (BMP-2), Fas, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 13 (MMP-13), and tumor necrosis factor (TNF). Expression levels of each gene were normalized to that of glyceraldehyde-3-phosphate dehydrogenase (GADPH), a constitutively expressed gene. Histology confirmed progressive degeneration of the discs over the 6-week study period. Different patterns of gene expression were observed in control and lesioned discs. Annular laceration caused a marked upregulation (two- to eightfold) of the expression of Col I, Col II, FN, MMP-1, MMP-9, MMP-13, and Fas genes, whereas that of BMP-2, IL-1alpha, and TNF genes was unaffected. Expression of the decorin gene was downregulated approximately sixfold after annular laceration. Annular laceration in this animal model resulted in marked changes in gene expression. Upregulation of gene expression was observed for some molecules found at high concentration in human degenerated discs, suggesting similarities to human disc degeneration at the molecular level. This supports
Kolmakova, Tatyana V.
The paper describes the model of the cervical spine segment (C3-C4) and the calculation results of the deformation behavior of the segment under degenerative changes of the intervertebral disc. The segment model was built based on the experimental literature data taking into account the presence of the cortical and cancellous bone tissue of vertebral bodies. The calculation results show that degenerative changes of the intervertebral disc cause the immobility of the C3 vertebra at flexion.
Bharti, Kapil; Rao, Mahendra; Hull, Sara Chandros; Stroncek, David; Brooks, Brian P.; Feigal, Ellen; van Meurs, Jan C.; Huang, Christene A.; Miller, Sheldon S.
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
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.
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
Liang, Qian-Qian; Zhou, Quan; Zhang, Min; Hou, Wei; Cui, Xue-Jun; Li, Chen-Guang; Li, Tian-Fang; Shi, Qi; Wang, Yong-Jun
Both forelimbs of rats were amputated, and these rats were kept in the custom-made cages that kept the rats in prolonged upright posture. Pathologic changes were observed in the lumbar spine at different time points after the surgery. To investigate the effect of upright posture on intervertebral discs of rat lumbar spine. Previous studies have shown that increased axial forces on the spine can decrease the height of the intervertebral disc, but there are no data to indicate whether or not long-term and repeated assumption of the upright posture could result in degenerative changes. The forelimbs of 30 rats were amputated when they were 1-month old. These rats were kept in the custom-made cages and were forced to stand upright on their hind-limbs and tails to obtain water and food. Normal rats of the same ages kept in regular cages were used as control. The rats were killed at 5, 7, and 9 months after the surgery, and the intervertebral discs samples of lumbar spine were harvested for histologic and immunohistochemical studies. Total RNA isolated from these samples was used for real-time PCR of type II collagen (Col2alpha1), type X collagen (Col10alpha1), matrix metalloproteinase-13 (MMP-13), aggrecan, and disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5). RESULTS.: Histologic analysis showed degenerative changes of the intervertebral discs after surgery such as disordered collagen structure of endplate cartilage, fragmentation of annulus fibrosus, and decreased height of disc. Immunostaining revealed decreased protein level of type II collagen and increased protein expression of type X collagen. Real-time PCR showed upregulated expression of MMP 13, ADAMTS-5, and Col10alpha1 mRNA and downregulated mRNA expression of Col2alpha1 and aggrecan. Long-term and repeated assumption of the upright stance accelerates disc degeneration in rats.
Madigan, Luke; Vaccaro, Alexander R; Spector, Leo R; Milam, R Alden
Symptomatic lumbar degenerative disk disease, or discogenic back pain, is difficult to treat. Patients often report transverse low back pain that radiates into the sacroiliac joints. Radicular or claudicatory symptoms are generally absent unless there is concomitant nerve compression. Physical examination findings are often unremarkable. Radiographic examination may reveal disk space narrowing, end-plate sclerosis, or vacuum phenomenon in the disk; magnetic resonance imaging is useful for revealing hydration of the disk, annular bulging, or lumbar spine end-plate (Modic) changes in the adjacent vertebral bodies. The use of diskography as a confirmatory study remains controversial. Recent prospective, randomized trials and meta-analyses of the literature have helped expand what is known about degenerative disk disease. In most patients with low back pain, symptoms resolve without surgical intervention; physical therapy and nonsteroidal anti-inflammatory drugs are the cornerstones of nonsurgical treatment. Intradiskal electrothermal treatment has not been shown to be effective, and arthrodesis remains controversial for the treatment of discogenic back pain. Nucleus replacement and motion-sparing technology are too new to have demonstrated long-term data regarding their efficacy.
Two-year comprehensive medical management of degenerative lumbar spine disease (lumbar spondylolisthesis, stenosis, or disc herniation): a value analysis of cost, pain, disability, and quality of life: clinical article.
Parker, Scott L; Godil, Saniya S; Mendenhall, Stephen K; Zuckerman, Scott L; Shau, David N; McGirt, Matthew J
important difference in any outcome measure. The mean 2-year total cost (direct plus indirect) of medical management was $6606 for spondylolisthesis, $7747 for stenosis, and $7097 for herniation. In an institution-wide, prospective, longitudinal quality of life registry that measures cost and effectiveness of all spine care provided, comprehensive medical management did not result in sustained improvement in pain, disability, or quality of life for patients with surgically eligible degenerative lumbar spondylolisthesis, stenosis, or disc herniation. From both the societal and payer perspective, continued medical management of patients with these lumbar pathologies in whom 6 weeks of conservative therapy failed was of minimal value given its lack of health utility and effectiveness and its health care costs. The findings from this real-world practice setting may more accurately reflect the true value and effectiveness of nonoperative care in surgically eligible patient populations.
Zhou, Ren-Peng; Wu, Xiao-Shan; Wang, Zhi-Sen; Xie, Ya-Ya; Ge, Jin-Fang; Chen, Fei-Hu
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
Kovacs, F M; Arana, E
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.
Bjerkeset, Tormod; Johnsen, Lars Gunnar; Kibsgaard, Leif; Fuglesang, Paul
The diagnosis and treatment of painful degenerative spinal diseases remains controversial in the literature, and surgical treatment differs greatly between centres and surgeons. We have evaluated our results over a nine-year period. 237 patients referred with chronic degenerative spinal diseases could be evaluated, 132 women and 105 men, median age 48 (17 - 85). Median symptom duration was 10 years (1.5 - 50 years). The patient files were retrospectively studied independently by two surgeons. Out of the patients, 83 (35 %) had previously had lumbar spine operations, mainly discectomies. All patients were controlled as outpatients with clinical examination and an X-ray taken of the lower spine columna at least once. The final evaluation of patient satisfaction with the operation, pain and walking and working capacity was based on a questionnaire. Out of these patients, 64 were treated with decompression only, 173 had additional posterolateral fusion with bone or instrument. Fusion rate was 90 %, with no significant difference between type of fusion (p = 0.07). After a median observation time of 5.2 years (0.5 - 10.5 years) 75 % of the patients were very satisfied or satisfied with the outcome; 48 % were back at work. Factors significantly related to poor results were little preoperative pain (p < 0.001), previous back operations (p = 0.003) and long preoperative sick leave (p = 0.015). Our results are comparable with most published studies. One should be restrictive with surgery on patients with little pain, long sick leave, preoperative inactivity, and previous multiple spinal operations.
Malandrino, Andrea; Noailly, Jérôme; Lacroix, Damien
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
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.
Di Nicola, Valerio; Di Nicola, Renato
This study presents a method for treating and structurally improving articulations affected by degenerative joint disease (DJD). The focus of this analysis is on two groups of patients: the first comprised patients over eighty years old, and the second comprised patients aged 45 to 55 years. The first group was a high surgical risk and both had been nonresponders to current conservative therapies. Scholars like Davis, Filatov, and Cerletti have been studying and using the regenerative properties of placenta, amnios and other nonvital tissues since the early 1900s. These pioneering studies have opened a new track for tissue renewal. More recently, the new biological knowledge about extracellular nucleic acids, growth factors (GF) (as by-products of trauma response), and heat shock proteins (Hsp) has helped research even further. Building on those experiences, we have developed a regenerative gel obtained with distressed, processed blood, polydeoxyribonucleotides (Pdrn), and a thickening substance. The objective was to stimulate the local innate stem cells with our gel in order induce tissue repair. From 2003 until 2009, we treated 948 patients. As mentioned, the first group comprided of 86 ultra-octogenarian patients with severe osteoarthritis (OA) of the hip and/or knee, and the second group comprised of 90 younger patients (around 50 years old) affected by the same disease. Treated patients have been clinically and radiologically evaluated with a follow-up of 6 to 48 months. Results show a statistically significant improvement in terms of pain and joint mobility, sometimes coupled with clear improvement in radiological imaging. Follow-up shows encouraging data in terms of clinical stability over time. During the study, we encountered virtually no side effects, adverse reactions, or toxicity. Currently the pharmacological treatment of DJD is palliative, though toxicity and side effects of the drugs remain problematic. Patients who can be operated on conclude their
Huang, Yiming; Enzmann, Volker; Ildstad, Suzanne T.
Retinal degenerative diseases that target photoreceptors or the adjacent retinal pigment epithelium (RPE) affect millions of people worldwide. Retinal degeneration (RD) is found in many different forms of retinal diseases including retinitis pigmentosa (RP), age-related macular degeneration (AMD), diabetic retinopathy, cataracts, and glaucoma. Effective treatment for retinal degeneration has been widely investigated. Gene-replacement therapy has been shown to improve visual function in inherited retinal disease. However, this treatment was less effective with advanced disease. Stem cell-based therapy is being pursued as a potential alternative approach in the treatment of retinal degenerative diseases. In this review, we will focus on stem cell-based therapies in the pipeline and summarize progress in treatment of retinal degenerative disease. PMID:20859770
Son, Colin; Tavakoli, Samon; Bartanusz, Viktor
Industry sponsorship of clinical research of degenerative diseases of the spine has been associated with excessive positive published results as compared to research carried out without industry funding. We sought the rates of publication of clinical trials of degenerative diseases of the spine based on funding source as a possible explanation for this phenomenon. We reviewed all clinical trials registered at clinicaltrials.gov relating to degenerative diseases of the spine as categorized under six medical subject heading terms (spinal stenosis, spondylolisthesis, spondylolysis, spondylosis, failed back surgery syndrome, intervertebral disc degeneration) and with statuses of completed or terminated. These collected studies were categorized as having, or not having, industry funding. Published results for these studies were then sought within the clinicaltrials.gov database itself, PubMed and Google Scholar. One hundred sixty-one clinical trials met these criteria. One hundred nineteen of these trials had industry funding and 42 did not. Of those with industry funding, 45 (37.8%) had identifiable results. Of those without industry funding, 17 (40.5%) had identifiable results. There was no difference in the rates of publication of results from clinical trials of degenerative diseases of the spine no matter the funding source.
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
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
Dias, Isabela Maddalena; Coelho, Patrícia Rocha; Picorelli Assis, Neuza Maria Souza; Pereira Leite, Fabiola Pessôa; Devito, Karina Lopes
The aim was to evaluate the correlation between disc displacements and degenerative bone changes in magnetic resonance images (MRI) of 112 patients of both genders, with signs and symptoms of temporomandibular disorder. For this purpose, a calibrated examiner evaluated 224 MRI by assigning scores for the displacement of the disc and degenerative bone changes. Disc displacement was found in 58.42% of the temporomandibular joints (TMJs) evaluated. Anterior displacement of the disc with reduction was the most common, occurring in 67.18% cases of joints with disc displacement. Degenerative bone changes were observed in 53.94% of the TMJs analysed. There was significant correlation between disc displacement with reduction and condylar flattening, disc displacement without reduction and condylar flattening, disc displacement without reduction, and associated degenerative bone changes (flattening and erosion, flattening, osteophyte and erosion; flattening and osteophytes, erosion and sclerosis, flattening and sclerosis, flattening, osteophytes and sclerosis). The correlation between advanced cases of disc displacement and the occurrence of degenerative bone changes emphasises the importance of MRI for an accurate diagnosis and development of an appropriate treatment plan and in cases in which clinical examination is not sufficient for these purposes. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Reyes-Sanchez, Alejandro; Miramontes, Victor; Olivarez, Luis M Rosales; Aquirre, Armando Alpizar; Quiroz, Alfredo Ortega; Zarate-Kalfopulos, Baron
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. 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. 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 that patients treated at
Reyes-Sanchez, Alejandro; Miramontes, Victor; Olivarez, Luis M. Rosales; Aquirre, Armando Alpizar; Quiroz, Alfredo Ortega; Zarate-Kalfopulos, Baron
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
Degenerative Cervical Disc Disease: Long-term Changes in Sagittal Alignment and Their Clinical Implications After Cervical Interbody Fusion Cage Subsidence: A Prospective Study With Standalone Lordotic Tantalum Cages.
Tomé-Bermejo, Félix; Morales-Valencia, Julián A; Moreno-Pérez, Javier; Marfil-Pérez, Juan; Díaz-Dominguez, Elena; Piñera, Angel R; Alvarez, Luis
A retrospective, observational study of prospectively collected outcomes. To investigate the long-term clinical course of anterior cervical discectomy and fusion with interbody fusion cages (ACDF-IFC) with lordotic tantalum implants and to correlate the radiologic findings with the clinical outcomes, with special emphasis on the significance and the influence of implant subsidence. Cage subsidence is the most frequently reported complication after ACDF-IFC. However, most reports fail to correlate cage subsidence with lower fusion rates or with unsatisfactory clinical results. Forty-one consecutive patients with symptomatic degenerative cervical disk disease with failure of conservative treatment were included. All patients underwent 1-/2-level ACDF-IFC with lordotic tantalum implants. The mean follow-up was 4.91 years. The final follow-up fusion rate was 96.96% (32/33). The interspace height (IH) at the affected levels was significantly incremented after implant insertion, and despite a gradual loss in the height over time, the final follow-up IH was significantly higher than that measured preoperatively (P<0.0001). Anterior IH and posterior IH lost 55.8% and 76.2% of the initially incremented height, respectively, with a final increase of 72% in the AIH-PIH height differential. Implant subsidence (>3 mm) occurred in 11 disk spaces (26.82%). Preoperative and postoperative IH were significantly higher in subsidence patients; however, there was no difference in the final follow-up IH (P>0.05). Patients with ≥3 years of follow-up (n=29) did not demonstrate further significant subsidence beyond the second year. Regarding C1-C7 lordosis, the segmental Cobb angle, the cervical Visual Analogue Scale, and Neck Disability Index questionnaires, no difference between patients with or without final follow-up endplate subsidence was encountered. Until fusion occurs, tantalum cage settlement into the vertebral body is to be expected. Further subsidence could be the result of
Alvin, Matthew D; Qureshi, Sheeraz; Klineberg, Eric; Riew, K Daniel; Fischer, Dena J; Norvell, Daniel C; Mroz, Thomas E
Systematic review. To perform an evidence-based synthesis of the literature assessing the cost-effectiveness of surgery for patients with symptomatic cervical degenerative disc disease (DDD). Cervical DDD is a common cause of clinical syndromes such as neck pain, cervical radiculopathy, and myelopathy. The appropriate surgical intervention(s) for a given problem is controversial, especially with regard to quality-of-life outcomes, complications, and costs. Although there have been many studies comparing outcomes and complications, relatively few have compared costs and, more importantly, cost-effectiveness of the interventions. We conducted a systematic search in PubMed/MEDLINE, EMBASE, the Cochrane Collaboration Library, the Cost-Effectiveness Analysis registry database, and the National Health Service Economic Evaluation Database for full economic evaluations published through January 16, 2014. Identification of full economic evaluations that were explicitly designed to evaluate and synthesize the costs and consequences of surgical procedures or surgical intervention with nonsurgical management in patients with cervical DDD were considered for inclusion, based on 4 key questions. Five studies were included, each specific to 1 or more of our focus questions. Two studies suggested that cervical disc replacement may be more cost-effective compared with anterior cervical discectomy and fusion. Two studies comparing anterior with posterior surgical procedures for cervical spondylotic myelopathy suggested that anterior surgery was more cost-effective than posterior surgery. One study suggested that posterior cervical foraminotomy had a greater net economic benefit than anterior cervical discectomy and fusion in a military population with unilateral cervical radiculopathy. No studies assessed the cost-effectiveness of surgical intervention compared with nonoperative treatment of cervical myelopathy or radiculopathy, although it is acknowledged that existing studies
Zioła-Frankowska, Anetta; Kubaszewski, Łukasz; Dąbrowski, Mikołaj; Frankowski, Marcin
There is a growing body of evidence concerning the significant role of silicon in development and composition of both connective and bone tissue. Bio-essential silicon shows strong chemical and biological affinity to aluminum, which is toxic and biologically inessential element. The presence of silicon was confirmed in a variety of tissues; however, it has never been examined in intervertebral disc tissue, neither in healthy nor in degenerated one. In this paper, for the first time in the literature, we present the content of silicon in the degenerated intervertebral disc tissue. We also compared the results of silicon analysis with aluminum values in degenerated intervertebral disc tissue in humans. We used chemometric methods to find correlations and similarities between silicon, aluminum, and elements associated with tissue metabolism (Mg) and degenerative processes (Zn and Cu). The presence of silicon was confirmed in all 30 samples harvested from 22 patients operated on due to degenerative changes. Its concentration was within the range of 5.37-12.8 μg g(-1) d.w., with the mean concentration of 7.82 μg g(-1) d.w. The analysis showed significant correlation between Si and both Al and Mg and weak or negative correlation with Zn and Cu, where the latter was probably the result of degenerative processes. Although silicon is considered essential in glycosaminoglycan and collagen synthesis in connective tissue, it did not show any correlation nor similarities with elements reflecting changes associated with the degenerative process of the intervertebral disc. Silicon showed significant correlation with aluminum, similar to those observed in other human tissues.
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
Markova, Dessislava Z; Kepler, Christopher K; Addya, Sankar; Murray, Hallie B; Vaccaro, Alexander R; Shapiro, Irving M; Anderson, D Greg; Albert, Todd J; Risbud, Makarand V
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. 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. 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. 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.
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
Bar-Dayan, Y; Weisbort, M; Bar-Dayan, Y; Velan, G J; Ravid, M; Hendel, D; Shemer, J
Parachuting, be it static line or skydiving, places enormous stresses on the human spine. It is, therefore, important to determine the prevalence and severity of degenerative changes in the lumbar spine of subjects who practice this sport activity. Seventy four parachuting instructors, mean age 33 years and with an average of 410 static line and skydiving jumps, were included in the study. Past radiographs were examined and compared to current anterolateral and lateral views of the lumbar spine, in order to determine the prevalence of degenerative changes and document possible progression. Doubtful radiographic changes in the lumbar spine were identified in 47.4 percent of the parachuting instructors, mild degeneration in 9.6 percent, moderate degenerative disease in 10.9 percent and severe radiographic changes in 5.5 percent. Schmorll nodes were found in 8.1 percent of the subjects. Traction spurs--osteophytes were identified in 6.8 percent. The degenerative changes correlated with age and the number of jumps. Spondylolysis of L5-S1 and L3-L4 segments were observed in 12.2 and 1.4 percent respectively. Progressive spondylolisthesis was found in 2 subjects. No correlation was found between the severity of radiographic changes and either the prevalence and the severity of low back pain. The present findings provide a rational for considering repeated sheer stress as an etiology of degenerative changes in the spinal cord, and as a possible contributing factor to the pathogenesis of spondylolysis. Further study has to be done comparing parachuting instructors to a non-parachuting group, or equivalent physically active individuals, in order to assess the effect of sport-background on the development of degenerative changes.
Eisele, Yvonne S.; Monteiro, Cecilia; Fearns, Colleen; Encalada, Sandra E.; Wiseman, R. Luke; Powers, Evan T.; Kelly, Jeffery W.
The aggregation of specific proteins is hypothesized to underlie several degenerative diseases, collectively called amyloid disorders. However, the mechanistic connection between the process of protein aggregation and tissue degeneration is not yet fully understood. Here, we review current and emerging strategies to ameliorate aggregation-associated degenerative disorders, with a focus on disease-modifying strategies that prevent the formation of and/or eliminate protein aggregates. Persuasive pharmacologic and genetic evidence now support protein aggregation as the cause of post-mitotic tissue dysfunction or loss. However, a more detailed understanding of the factors that trigger and sustain aggregate formation, as well as the structure-activity relationships underlying proteotoxicity are needed to develop future disease-modifying therapies. PMID:26338154
Perez, Victor L.; Caspi, Rachel R.
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
Radło, Paweł; Smetkowski, Andrzej; Tesiorowski, Maciej
Lumbar disc herniation is one of the most common damage of musculoskeletal system. The incidence of pain of lumbosacral spine is estimated approximately on 60-90% in general population, whereas the incidence of disc herniation in patients experiencing low back pain is about 91%. Despite the high incidence and uncomplicated pathogenesis of disc disease there is a problem with the nomenclature. In the vast majority of cases, the naming confusion stems from ignorance of the etiology of low back pain. Different terminologies: morphological, topographical, Radiological and Clinical are used interchangeably. In addition, diagnosis is presented in a variety of languages: Polish, English and Latin. Moreover, the medical and traditional language are used alternately. The authors found in Polish literature more, than 20 terms to describe lumbar disc herniation. All of these terms in the meaning of the authors are used to determine one pathology--mechanical damage to the intervertebral disc and moving the disc material beyond the anatomical area.
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
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
Peng, Ying-Qian; Tang, Luo-Sheng; Yoshida, Shigeo; Zhou, Ye-Di
Gene therapy is a potentially effective treatment for retinal degenerative diseases. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been developed as a new genome-editing tool in ophthalmic studies. Recent advances in researches showed that CRISPR/Cas9 has been applied in generating animal models as well as gene therapy in vivo of retinitis pigmentosa (RP) and leber congenital amaurosis (LCA). It has also been shown as a potential attempt for clinic by combining with other technologies such as adeno-associated virus (AAV) and induced pluripotent stem cells (iPSCs). In this review, we highlight the main points of further prospect of using CRISPR/Cas9 in targeting retinal degeneration. We also emphasize the potential applications of this technique in treating retinal degenerative diseases. PMID:28503441
Bellei, Barbara; Pitisci, Angela; Ottaviani, Monica; Ludovici, Matteo; Cota, Carlo; Luzi, Fabiola; Dell'Anna, Maria Lucia; Picardo, Mauro
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
Kuo, Ya-Wen; Hsu, Yu-Chun; Chuang, I-Ting; Chao, Pen-Hsiu Grace; Wang, Jaw-Lin
Biomechanical experiment using an in situ porcine model. To find the effect of traction treatment on annulus microstructure, molecular convection, and cell viability of degraded discs. Spinal traction is a conservative treatment for disc disorders. The recognized biomechanical benefits include disc height recovery, foramen enlargement, and intradiscal pressure reduction. However, the influence of traction treatment on annulus microstructure, molecular transportation, and cell viability of degraded discs has not been fully investigated. A total of 48 thoracic discs were dissected from 8 porcine spines (140 kg, 6-month old) within 4 hours after killing them and then divided into 3 groups: intact, degraded without traction, and degraded with traction. Each disc was incubated in a whole-organ culture system and subjected to diurnal loadings for 7 days. Except for the intact group, discs were degraded with 0.5 mL of trypsin on day 1 and a 5-hour fatigue loading on day 2. From day 4 to day 6, half of the degraded discs received a 30-minute traction treatment per day (traction force: 20 kg; loading: unloading = 30 s: 10 s). By the end of the incubation, the discs were inspected for disc height loss, annulus microstructure, molecular (fluorescein sodium) intensity, and cell viability. Collagen fibers were crimped and delaminated, whereas the pores were occluded in the annulus fibrosus of the degraded discs. Molecular transportation and cell viability of the discs decreased after matrix degradation. With traction treatment, straightened collagen fibers increased within the degraded annulus fibrosus, and the annulus pores were less occluded. Both molecular transportation and cell viability increased, but not to the intact level. Traction treatment is effective in enhancing nutrition supply and promoting disc cell proliferation of the degraded discs. N/A.
Gobelet, C; Luthi, F; Al-Khodairy, A T; Chamberlain, M A
This article focuses on work disability and sick leave and their cost; it also discusses the value of vocational rehabilitation programmes in rheumatic conditions such as rheumatoid arthritis, ankylosing spondylitis, hip and knee osteoarthritis. It acknowledges the importance of work not only for the worker who has one of these diseases but also for the public purse. Much can be done to improve the health of the persons and reduce their disability and its impact in the workplace which will have an important effect on their and their family's quality of life. It is important that neither rehabilitation nor vocational rehabilitation are regarded as bolt-on activities after drug treatment but are seen as an integral part of effective management. Publications dealing with return to work are relatively common in rheumatoid arthritis, less common in ankylosing spondylitis and relatively rare in osteoarthritis. Vocational rehabilitation programmes should aim to facilitate job retention or, failing that, to improve the ability to return to work. The process must be started with in the health arena and it has to be recognised that slow or poor practice in the health service can jeopardise the patient's work potential.
Stuart, B.O. )
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.
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.
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
... link) National Institute of Neurological Disorders and Stroke: Low Back Pain Fact Sheet Educational Resources (8 links) American Association ... MalaCards: intervertebral disc disease Merck Manual Consumer Version: Low Back Pain Merck Manual Consumer Version: Neck Pain The Children's ...
Grams, Astrid Ellen; Rehwald, Rafael; Bartsch, Alexander; Honold, Sarah; Freyschlag, Christian Franz; Knoflach, Michael; Gizewski, Elke Ruth; Glodny, Bernhard
Spondylosis leads to an overestimation of bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) but not with quantitative computed tomography (QCT). The correlation between degenerative changes of the spine and QCT-BMD was therefore investigated for the first time. One hundred thirty-four patients (66 female and 68 male) with a mean age of 49.0 ± 14.6 years (range: 19-88 years) who received a CT scan and QCT-BMD measurements of spine and hip were evaluated retrospectively. The occurrence and severity of spondylosis, osteochondrosis, and spondylarthrosis and the height of the vertebral bodies were assessed. A negative correlation was found between spinal BMD and number of spondylophytes (ρ = -0.35; p < 0.01), disc heights (r = -0.33; p < 0.01), number of discal air inclusions (ρ = -0.34; p < 0.01), the number of Schmorl nodules (ρ = -0.25; p < 0.01), the number (ρ = -0.219; p < 0.05) and the degree (ρ = -0.220; p < 0.05) of spondylarthrosis. Spinal and hip BMD correlated moderately, but the latter did not correlate with degenerative changes of the spine. In linear regression models age, osteochondrosis and spondylarthrosis were factors influencing spinal BMD. Degenerative spinal changes may be associated with reduced regional spinal mineralization. This knowledge could lead to a modification of treatment of degenerative spine disease with early treatment of osteopenia to prevent secondary fractures.
Daneshmand, Mani A; Milano, Carmelo A; Rankin, J Scott; Honeycutt, Emily F; Swaminathan, Madhav; Shaw, Linda K; Smith, Peter K; Glower, Donald D
Recent advances in surgical technique allow repair of most mitral valves with degenerative disease. However, few long-term data exist to support the superiority of repair versus prosthetic valve replacement, and repair could be limited by late durability or other problems. This study was designed to compare survival characteristics of mitral valve repair versus prosthetic replacement for degenerative disorders during a 20-year period. From 1986 to 2006, 2,580 patients underwent isolated mitral valve procedures (with or without coronary artery bypass grafting), with 989 classified as having degenerative origin. Of these, 705 received valve repair, and 284 had prosthetic valve replacement. Differences in baseline characteristics between groups were assessed, and unadjusted survival estimates were generated using Kaplan-Meier methods. Survival curves were examined after adjustment for differences in baseline profiles using a Cox model, and average adjusted survival differences were quantified by area under the curve methodology. Survival differences during 15 years of follow-up also were assessed with propensity matching. Baseline characteristics were similar, except for (variable: repair, replacement) age: 62 years, 68 years; concomitant coronary artery bypass grafting: 24%, 32%; ejection fraction: 0.51, 0.55; congestive heart failure: 68%, 43%; and preoperative arrhythmia: 11%, 7% (all p < 0.05). Long-term survival was significantly better in the repair group, both for unadjusted data (p < 0.001) and for risk-adjusted results (p = 0.040). Patient survival in the course of 15 years averaged 7.3% better with repair, and increased with time of follow-up: 0.7% better for 0 to 5 years, 4.9% better for 5 to 10 years, and 21.3% better for 10 to 15 years. Treatment interaction between repair or replacement and age was negative (p = 0.66). In the propensity analysis, survival advantages of repair versus replacement were similar in magnitude with a p value of 0.046. As
Kamani, Mayur M; Shetty, Vikram; Rai, H. Ravindranath; Hegde, Deepak
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
Choi, Keum Hwa; Buhl, Gail; Ponder, Julia
A permanently captive 21-year-old male bald eagle was diagnosed with chronic degenerative joint disease in the right stifle with severe lameness (Grade 5) based on radiography. Clinical signs included decreased movement, vocalization, non weight-bearing on the affected limb, inappetence, depression, and pododermatitis on the left foot (bumblefoot, Grade 3). The eagle was treated with anti-inflammatory or analgesic drugs including carprofen and celecoxib. As there was no observed clinical improvement with any of the treatments, acupuncture treatment was provided. The eagle was treated with dry needle acupuncture once per week for 2 months and biweekly for another 2 months. The Traditional Eastern Medicine diagnosis of this eagle was Bony Bi syndrome. The selected acupuncture points were ST 36, LI 4, BL 40, BL 60, GB 34, and Ba Feng (Table 3). The lameness score improved from Grade 5 to Grade 1 after 4 months of acupuncture treatment. The observed pododermatitis improved from Grade 3 to Grade 0. Symptoms including inappetence and vocalizations were significantly reduced over the 4 month period. There was no significant improvement in the radiographic signs. In conclusion, acupuncture may be a potential medical option for permanently captive raptors having musculoskeletal conditions, such as degenerative joint disease. Copyright © 2016. Published by Elsevier B.V.
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
Women do not fare worse than men after lumbar fusion surgery: Two-year follow-up results from 4,780 prospectively collected patients in the Swedish National Spine Register with lumbar degenerative disc disease and chronic low back pain.
Triebel, Jan; Snellman, Greta; Sandén, Bengt; Strömqvist, Fredrik; Robinson, Yohan
Proper patient selection is of utmost importance in the surgical treatment of degenerative disc disease (DDD) with chronic low back pain (CLBP). Among other factors, gender was previously found to influence lumbar fusion surgery outcome. This study investigates whether gender affects clinical outcome after lumbar fusion. This is a national registry cohort study. Between 2001 and 2011, 2,251 men and 2,521 women were followed prospectively within the Swedish National Spine Register (SWESPINE) after lumbar fusion surgery for DDD and CLBP. Patient-reported outcome measures (PROMs), visual analog scale (VAS) for leg and back pain, Oswestry Disability Index (ODI), quality of life (QoL) parameter EQ5D, and labor status and pain medication were collected preoperatively, 1 and 2 years after surgery. Gender differences of baseline data and PROM improvement from baseline were analyzed. The effect of gender on clinically important improvement of PROM was determined in a multivariate logistic regression model. Furthermore, gender-related differences in return-to-work were investigated. Preoperatively, women had worse leg pain (p<.001), back pain (p=.002), lower QoL (p<.001), and greater disability than men (p=.001). Postoperatively, women presented greater improvement 2 years from baseline for pain, function, and QoL (all p<.01). Women had better chances of a clinically important improvement than men for leg pain (odds ratio [OR]=1.39, 95% confidence interval [CI]: 1.19-1.61, p<.01) and back pain (OR=1.20,95% CI:1.03-1.40, p=.02) as well as ODI (OR=1.24, 95% CI:1.05-1.47, p=.01), but improved at a slower pace in leg pain (p<.001), back pain (p=.009), and disability (p=.008). No gender differences were found in QoL and return to work at 2 years postoperatively. Swedish women do not have worse results than men after spinal fusion surgery. Female patients present with worse pain and function preoperatively, but improve more than men do after surgery. Copyright © 2016 The Author
Sánchez Pérez, M; Gil Sierra, A; Sánchez Martín, A; Gallego Gómez, P; Pereira Boo, D
This article reviews the terminology used to describe morphological alterations in the intervertebral discs. Radiologists must be able to communicate information about the type, location, and severity of these alterations to medical and surgical clinicians. It is crucial to use simple, standard, and unified terminology to ensure comprehension not only among radiologists but also with professionals from the different specialties for whom the radiology reports are written (fundamentally traumatologists and neurosurgeons). This terminology will help ensure a more accurate diagnosis and better patient management.
Stupar, Maja; Peterson, Cynthia K
Background Cervical pillar hyperplasia (CPH) is a recently described phenomenon of unknown etiology and clinical significance. Global assessment of pillar hyperplasia of the cervical spine as a unit has not shown a relationship with degenerative joint disease, but a more sensible explanation of the architectural influence of CPH on cervical spine biomechanics may be segment-specific. Objective The objective of this study was to determine the level of association between degenerative joint disease (DJD) and cervical pillar hyperplasia (CPH) in an age- and gender-matched sample on a [cervical spine] by-level basis. Research Methods Two-hundred and forty radiographs were collected from subjects ranging in age between 40 and 69 years. The two primary outcome measures used in the study were the segmental presence/absence of cervical pillar hyperplasia from C3 to C6, and segment-specific presence/absence of degenerative joint disease from C1 to C7. Contingency Coefficients, at the 5% level of significance, at each level, were used to determine the strength of the association between CPH and DJD. Odds Ratios (OR) with their 95% Confidence Intervals (95% CI) were also calculated at each level to assess the strength of the association. Results Our study suggests that an approximately two-to-one odds, or a weak-to-moderate correlation, exists at C4 and C5 CPH and adjacent level degenerative disc disease (DDD); with the strongest (overall) associations demonstrated between C4 CPH and C4–5 DDD and between C5 CPH and C5–6 DDD. Age-stratified results demonstrated a similar pattern of association, even reaching the initially hypothesized OR ≥ 5.0 (95% CI > 1.0) or "moderately-strong correlation of C ≥ .4 (p ≤ .05)" in some age categories, including the 40–44, 50–59, and 60–64 years of age subgroups; these ORs were as follows: OR = 5.5 (95% CI 1.39–21.59); OR = 6.7 (95% CI 1.65–27.34); and OR = 5.3 (95% CI 1.35–21.14), respectively. Conclusion Our results
Stupar, Maja; Peterson, Cynthia K
Cervical pillar hyperplasia (CPH) is a recently described phenomenon of unknown etiology and clinical significance. Global assessment of pillar hyperplasia of the cervical spine as a unit has not shown a relationship with degenerative joint disease, but a more sensible explanation of the architectural influence of CPH on cervical spine biomechanics may be segment-specific. The objective of this study was to determine the level of association between degenerative joint disease (DJD) and cervical pillar hyperplasia (CPH) in an age- and gender-matched sample on a [cervical spine] by-level basis. Two-hundred and forty radiographs were collected from subjects ranging in age between 40 and 69 years. The two primary outcome measures used in the study were the segmental presence/absence of cervical pillar hyperplasia from C3 to C6, and segment-specific presence/absence of degenerative joint disease from C1 to C7. Contingency Coefficients, at the 5% level of significance, at each level, were used to determine the strength of the association between CPH and DJD. Odds Ratios (OR) with their 95% Confidence Intervals (95% CI) were also calculated at each level to assess the strength of the association. Our study suggests that an approximately two-to-one odds, or a weak-to-moderate correlation, exists at C4 and C5 CPH and adjacent level degenerative disc disease (DDD); with the strongest (overall) associations demonstrated between C4 CPH and C4-5 DDD and between C5 CPH and C5-6 DDD. Age-stratified results demonstrated a similar pattern of association, even reaching the initially hypothesized OR >or= 5.0 (95% CI > 1.0) or "moderately-strong correlation of C >or= .4 (p
Stem cell-derived retinal pigment epithelium (RPE) and photoreceptors (PRs) have restored vision in preclinical models of human retinal degenerative disease. This review discusses characteristics of stem cell therapy in the eye and the challenges to clinical implementation that are being confronted today. Based on encouraging results from Phase I/II trials, the first Phase II clinical trials of stem cell-derived RPE transplantation are underway. PR transplant experiments have demonstrated restoration of visual function in preclinical models of retinitis pigmentosa and macular degeneration, but also indicate that no single approach is likely to succeed in overcoming PR loss in all cases. A greater understanding of the mechanisms controlling synapse formation as well as the immunoreactivity of transplanted retinal cells is urgently needed.
Leone, A; Costantini, A M; Guglielmi, G; Tancioni, V; Moschini, M
Degeneration of the intervertebral disk complex begins early in life and is a consequence of a variety of environmental factors as well as of normal aging. Degeneration of bone and soft tissue spinal elements is the most common cause of spinal stenosis. The term "degeneration" as commonly applied to the spine covers such a wide variety of clinical, radiological and pathological manifestations that the word is really only a symbol of our ignorance. Computed tomography and myelography have long been used for diagnosing the effects of degenerative diseases' of the lumbar spine. Despite the continuous improvement in magnetic resonance scanning for this purpose, computed tomography can provide excellent screening for disk herniation and spinal stenosis.
Zarbin, Marco A; Montemagno, Carlo; Leary, James F; Ritch, Robert
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.
Cahlíková, Lucie; Macáková, Katerina; Chlebek, Jakub; Host'álková, Anna; Kulhánková, Andrea; Opletal, Lubomír
Beside ecdysone (1), ecdysterone (2) is one of the most common 5beta-cholest-7-en-6-one (ecdysteroid) derivatives, which, besides having a hormonal effect on invertebrates, possesses a number of favorable non-hormonal biological effects on mammals. The most interesting of these is that on degenerative diseases, one of which, up to now not clarified in detail, is the so-called adaptogenic effect (protection of the organism against adverse stress factors) associated with anabolic, gastroprotective, and antioxidant effects. A second group of favorable effects is the possibility of suppression of neurodegenerative processes and protection of the cardiovascular system (metabolic syndrome symptom suppression, antidiabetic activity, and protection of heart and blood vessels). Because of these properties, ecdysterone has the potential to be developed as a medicinal agent.
Dezawa, Mari; Ishikawa, Hiroto; Hoshino, Mikio; Itokazu, Yutaka; Nabeshima, Yo-ichi
Cell transplantation is a promising strategy for the treatment of neurodegenerative and muscle degenerative diseases. Many kinds of cells, including embryonic stem cells and tissue stem cells, have been considered as candidates for transplantation therapy. Bone marrow stromal cells (MSCs) have great potential as therapeutic agents since they are easy to isolate and can be expanded from patients without serious ethical or technical problems. We discovered a new method for the highly efficient and specific induction of functional Schwann cells, neurons and skeletal muscle lineage cells from both rat and human MSCs. These induced cells were transplanted into animal models of neurotraumatic injuries, Parkinson’s disease, stroke and muscle dystrophies, resulting in the successful integration of transplanted cells and an improvement in behavior of the transplanted animals. Here we focus on the respective potentials of MSC-derived cells and discuss the possibility of clinical application in degenerative diseases. PMID:18369401
In order to achieve a balanced approach to risk assessment between carcinogenic and non-carcinogenic health effects one must examine the risk of disease or death in the general population exposed to a particular air pollutant that can be related quantitatively to intensity and duration of exposures (National Academy of Sciences, 1983). Such risk assessment should be based upon careful evaluation of scientific findings of dose-response relationships in the chronically exposed population. Quantitative assessment of environmentally produced disease in man has proven to be complex and demanding. A variety of factors play important roles in this task. As an example, there are induction-latency periods for chronic diseases, including cancer, which may range from five to twenty-five years. The diseases themselves, whether proliferative or degenerative, may follow several stages of progression. There is only sparse epidemiological data on serious health effects that may be due to environmental as compared to occupational exposures. Exposures to chemical or radiological air contaminants do not occur singly but to a multiplicity of agents, and disease processes are frequently markedly affected by the interaction of a variety of factors, particularly that of cigarette smoking. There is growing recognition of potentially sensitive subpopulations, including the elderly and the very young, but adequate techniques for assessing the magnitude of increased risks to these groups have not yet been developed.
Stuart, B O
In order to achieve a balanced approach to risk assessment between carcinogenic and non-carcinogenic health effects one must examine the risk of disease or death in the general population exposed to a particular air pollutant that can be related quantitatively to intensity and duration of exposures (National Academy of Sciences, 1983). Such risk assessment should be based upon careful evaluation of scientific findings of dose-response relationships in the chronically exposed population. Quantitative assessment of environmentally produced disease in man has proven to be complex and demanding. A variety of factors play important roles in this task. As an example, there are induction-latency periods for chronic diseases, including cancer, which may range from five to twenty-five years. The diseases themselves, whether proliferative or degenerative, may follow several stages of progression. There is only sparse epidemiological data on serious health effects that may be due to environmental as compared to occupational exposures. Exposures to chemical or radiological air contaminants do not occur singly but to a multiplicity of agents, and disease processes are frequently markedly affected by the interaction of a variety of factors, particularly that of cigarette smoking. There is growing recognition of potentially sensitive subpopulations, including the elderly and the very young, but adequate techniques for assessing the magnitude of increased risks to these groups have not yet been developed.
Ciurea, AV; Mitrica, M; Mohan, A
The complexity of the clinical, biochemical, hystochemical and immunologic aspects of the intervertebral disk, along with its molecular biology, justifies the object of our study on the extracellular matrix modifications in lumbar disk hernias and their impact on patient quality of life. Material and method: the research lot was composed of 50 patients, aged between 18 and 73, who have undergone lumbar disk hernia surgery. MMP–9 (metalloproteinase–9) and TIMP–1 (tissue inhibitor of matrix metalloprotease 1) have been dosed in order to study the modifications on extracellular disk matrix, and quality of life assessment was carried out both in pre–operatory and post–operatory periods. Conclusions: patients may prevent the appearance of degenerative processes of the intervertebral disk with care and responsibility by controlling their weight, avoiding intense physical activities and ceasing to smoke. PMID:22567050
Liang, Qian-Qian; Cui, Xue-Jun; Xi, Zhi-Jie; Bian, Qin; Hou, Wei; Zhao, Yong-Jian; Shi, Qi; Wang, Yong-Jun
An in vivo study of the cervical intervertebral discs (IVDs) response to upright posture was performed using an amputated bipedal rat model. To investigate the effects of upright posture on IVDs of rat cervical spine. The distinct arrangement of human neck muscle from that of cat and rhesus indicated that in the evolution process, upright posture might have affected cervical spine of human ancestors. However, the effects of upright posture on cervical spine have not been assessed. Forty-one-month-old rats were randomly divided into 5-month-control, 5-month-surgery, 7-month-control, and 7-month surgery group (n = 10 per group). Both forelimbs of 2 surgery group rats were amputated, and those rats were then induced to be upright in the custom-made cages. Two control group rats were kept in regular cages. These rats were respectively killed at the fifth and seventh month after surgery and the IVD samples of lumbar spine were harvested for histologic and immunohistochemical studies. Total RNA isolated from these samples were used for real-time polymerase chain reaction of type II collagen (Col2a1), type X collagen, matrix metalloproteinase 13 (MMP-13), MMP-3, aggre-can, and aggrecanase-2 (ADAMTS-5). Upright posture affects histologic changes of the cervical IVDs such as fissures of anulus fibrosus and decreased height of disc, decreased protein level of Col2a1 at nucleus pulposus and anulus fibrosus, up-regulated MMP-13, MMP-3, ADAMTS-5, and type X collagen mRNA expression, and downregulated mRNA expression of Col2a1 and aggrecan. Upright stance accelerates cervical disc degeneration in rats.
Yasuda, Taketoshi; Hori, Takeshi; Suzuki, Kayo; Kawaguchi, Yoshiharu
Study Design Retrospective study. Purpose The aims of the current study are to evaluate the minimum 10-year follow-up clinical results of anterior lumbar interbody fusion (ALIF) for degenerative spondylolisthesis. Overview of Literature ALIF has been widely used as a treatment regimen in the management of lumbar spondylolisthesis. Still much controversy exists regarding the factors that affect the postoperative clinical outcomes. Methods The author performed a retrospective review of 20 patients with degenerative spondylolisthesis treated with ALIF (follow-up, 16.4 years). The clinical results were assessed by the Japanese Orthopaedic Association (JOA) score for low back pain, vertebral slip and disc height index on the radiographs. Results The mean preoperative JOA score was 7.1 ± 1.8 points (15-point-method). At 1 year, 5 years, and 10 years or more after surgery, the JOA scores were assessed as 12.4 ± 2.2 points, 12.7 ± 2.6 points, 12.0 ± 2.5 points, respectively (excluding the data of reoperated cases). The adjacent disc degeneration developed in all cases during the long-term follow-up. The progressive pattern of disc degeneration was divided into three types. Initially, disc degeneration occurred due to disc space narrowing. After that, the intervertebral discs showed segmental instability with translation at the upper level. But the lower discs showed osteophyte formation, and occasionally lead to the collapse or spontaneous union. Conclusions The clinical results of the long-term follow-up data after ALIF became worse due to the adjacent disc degeneration. The progressive pattern of disc degeneration was different according to the adjacent levels. PMID:22708014
Calore, Martina; Lorenzon, Alessandra; De Bortoli, Marzia; Poloni, Giulia; Rampazzo, Alessandra
Arrhythmogenic cardiomyopathy (ACM) is an acquired progressive disease having an age-related penetrance and showing clinical manifestations usually during adolescence and young adulthood. It is characterized clinically by a high incidence of severe ventricular tachyarrhythmias and sudden cardiac death and pathologically by degeneration of ventricular cardiomyocytes with replacement by fibro-fatty tissue. Whereas, in the past, the disease was considered to involve only the right ventricle, more recent clinical studies have established that the left ventricle is frequently involved. ACM is an inherited disease in up to 50% of cases, with predominantly an autosomal dominant pattern of transmission, although recessive inheritance has also been described. Since most of the pathogenic mutations have been identified in genes encoding desmosomal proteins, ACM is currently defined as a disease of desmosomes. However, on the basis of the most recent description of the intercalated disc organization and of the identification of a novel ACM gene encoding for an area composita protein, ACM can be considered as a disease of the intercalated disc, rather than only as a desmosomal disease. Despite increasing knowledge of the genetic basis of ACM, we are just beginning to understand early molecular events leading to cardiomyocyte degeneration, fibrosis and fibro-fatty substitution. This review summarizes recent advances in our comprehension of the link between the molecular genetics and pathogenesis of ACM and of the novel role of cardiac intercalated discs.
Wang, Yue; Nataraj, Andrew
Foot drop is a condition that can substantially add to the disability of patients with degenerative lumbar spinal disorders. The most common degenerative conditions associated with foot drop are lumbar disc herniation and lumbar spinal stenosis. The level most commonly affected is the L4/5 spinal level. Most patients are treated with surgery, although there is insufficient evidence to support that surgery is superior to conservative therapy. In most surgical patients, foot dorsiflexion will improve to some degree. The preoperative power of foot dorsiflexion is the key factor associated with prognosis. Copyright © 2013 Elsevier B.V. All rights reserved.
Feldman, Erica; Narayan, Anisha; Taylor, William
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
Joseph, Jacob R; Farooqui, Zishaan; Smith, Brandon W; Kahn, Elyne N; Liu, Xilin; La Marca, Frank; Park, Paul
OBJECTIVE Obesity and low-back pain associated with degenerative spondylosis or spondylolisthesis are common comorbid conditions. Many patients report that the pain and disability associated with degenerative lumbar disease are key factors in their inability to lose weight. The aim of this retrospective study was to determine if there is an association between improved functional status and weight loss following a successful transforaminal lumbar interbody fusion (TLIF) procedure. METHODS A retrospective cohort study of patients who underwent single-level TLIF was performed. Inclusion criteria were preoperative body mass index (BMI) greater than 30 kg/m(2), achievement of minimum clinically important difference in the Oswestry Disability Index (ODI, defined as improvement of 15 points), and minimum 1-year postoperative followup BMI. Preoperative and postoperative BMI, ODI, and visual analog scale (VAS) scores were compared. A subgroup analysis of patients who achieved substantial clinical benefit (SCB, defined as a net improvement of 18.8 points on the ODI) was also performed. RESULTS A total of 56 patients met the inclusion criteria. The mean age of the study population was 55.6 ± 13.7 years. The mean preoperative BMI was 34.8 ± 4.6 kg/m(2), the mean preoperative ODI was 66.2 ± 10.1, and the mean preoperative VAS score was 7.1 ± 1.7. The mean change in ODI was -33.1 ± 13.5 (p < 0.01) and the mean change in the VAS score was -4.1 ± 2.1 (p < 0.01). The mean change in BMI was +0.15 ± 2.1 kg/m(2) (range -4.2 to +6.5 kg/m(2); p = 0.6). SCB was achieved in 46 patients on the ODI. The mean preoperative BMI for patients with SCB was 34.8 ± 4.8 kg/m(2), and the mean postoperative BMI was 34.7 ± 5.0 kg/m(2). The mean change in BMI was -0.03 ± 1.9 kg/m(2) (p = 0.9). CONCLUSIONS Despite successful surgical intervention via TLIF with achievement of improved function and pain, obese patients did not have significant change in weight postoperatively.
Shangguan, Lei; Ning, Guang-Zhi; Tang, Yu; Wang, Zhe; Luo, Zhuo-Jing; Zhou, Yue
Objective Symptomatic cervical disc disease (SCDD) is a common degenerative disease, and Discover artificial cervical disc, a new-generation nonconstrained artificial disk, has been developed and performed gradually to treat it. We performed this meta-analysis to compare the efficacy and safety between Discover cervical disc arthroplasty (DCDA) and anterior cervical discectomy and fusion (ACDF) for SCDD. Methods An exhaustive literature search of PubMed, EMBASE, and the Cochrane Library was conducted to identify randomized controlled trials that compared DCDA with ACDF for patients suffering SCDD. A random-effect model was used. Results were reported as standardized mean difference or risk ratio with 95% confidence interval. Results Of 33 articles identified, six studies were included. Compared with ACDF, DCDA demonstrated shorter operation time (P < 0.0001), and better range of motion (ROM) at the operative level (P < 0.00001). But no significant differences were observed in blood loss, neck disability index (NDI) scores, neck and arm pain scores, Japanese orthopaedic association (JOA) scores, secondary surgery procedures and adverse events (P > 0.05). Subgroup analyses did not demonstrated significant differences. Conclusion In conclusion, DCDA presented shorter operation time, and better ROM at the operative level. However, no significant differences were observed in blood loss, NDI scores, neck and arm pain scores, JOA scores, secondary surgery procedures and adverse events between the two groups. Additionally, more studies of high quality with mid- to long-term follow-up are required in future. PMID:28358860
Lin, Tung-Yi; Liao, Jen-Chung; Tsai, Tsung-Ting; Lu, Meng-Ling; Niu, Chi-Chien; Chen, Wen-Jer; Chen, Lih-Hui
The vacuum phenomenon within the intervertebral disc usually represents disc degeneration. There are no reports in the English literature that focus on the effect of an anterior vacuum disc on surgical outcome of same-segment spondylolisthesis. Patients with degenerative spondylolisthesis (DS) or isthmic spondylolisthesis (IS) who underwent a spinal surgery between January 2005 and December 2006 were reviewed. Patients who met certain criteria, including (1) only mono-segment spondylolisthesis, (2) gas air within the disc space of the spondylolisthesis segment on preoperative radiographs, (3) having received posterior decompression, posterior pedicle screw fixation, and posterolateral fusion, and (4) at least 12 months of follow-up radiographs available to define the posterolateral fusion rate, were enrolled into the study. Four radiographic parameters (disc height, translation, intradiscal angle, segmental angle) were assessed. Two-year postoperative radiographs were used to determine whether the posterolateral segment was fused or not. Clinical outcome and complications during the follow-up period were documented. Incidence of the disc vacuum phenomenon was significantly higher in the IS group than in the DS group (p < 0.001). The IS group had more listhesis and a narrower disc height on preoperative static radiographs; however, the DS group had a more prominent angle and listhesis change in preoperative dynamic variables. The posterolateral fusion rate was significantly higher in the IS group (p = 0.019). The preoperative Oswestry Disability Index (ODI) score, the final ODI, and the ODI difference were similar between groups. More excellent and good results were seen in the IS group. Besides, better final ODI and results were seen in the bilateral fusion group than in the nonfusion group. The disc vacuum phenomenon is not equal to anterior instability absolutely. Determination of stability or instability in a vacuum disc should be considered by a
Saks, L A
The aim of the article is an evaluation of effectiveness of the complex outpatient care to patients with osteoarthrosis and degenerative-dystrophic diseases ofjuxtaarticular soft tissues. Recent researches showed that the key factors of the pathogenesis of diseases were degenerative-dystrophic and inflammatory changes in the synovio-entheseal complex ofparaarticular muscles' tendon. 411 patients with osteoarthrosis of 531 synovial joints and degenerative-dystrophic diseases of periarticular soft tissues underwent sequential corticosteroid therapy combined with hyaluronic acid injections. In 84% of cases positive results were observed.
Jackson, A; Isherwood, I
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
MA, XUEXIAO; LIN, YAZHOU; YANG, KUN; YUE, BIN; XIANG, HONGFEI; CHEN, BOHUA
Lower back pain is a common concern, and 40% of all cases involve the degeneration of the intervertebral disc (IVD). However, the excessive apoptosis of disc cells plays an important role in IVD degeneration, particularly in the nucleus pulposus (NP). Thus, anti-apoptotic gene therapy to attenuate or reverse the degenerative process within the NP is being developed. Survivin is a unique inhibitor of apoptosis (IAP) and has been extensively investigated in cancer cells. However, little is known of the effects of survivin transfection on NP cells derived from degenerative human disc. In this study, we aimed to investigate the effects of lentivirus (LV)-mediated survivin transfection on the morphology and apoptosis of NP cells derived from degenerative human disc in vitro. NP cells were transfected with LV-mediated survivin. Subsequently, cell morphology was observed and the survivin mRNA expression levels were measured by RT-qPCR. Apoptosis was analyzed by flow cytometry and by measuring caspase-3 activity. The results revealed that the morphology of the NP cells derived from degenerative human disc transfected with LV-mediated survivin was significantly altered as evidenced by cytomorphosis, the reduction of the cytoplasm and cell shrinkage. Following transfection, survivin gene expression significantly increased in the transfected cells and subsequent generation cells; however, no significant differences in the cell apoptotic rate and caspase-3 activity were observed. We found that transfection of the survivin gene into NP cells led to the stable expression of survivin and induced marked changes in cell morphology. Furthermore, no significant anti-apoptotic effects were observed following LV-mediated survivin transfection. Overall, our findings demonstrate that LV carrying surviving may be used to successfully enforce the expression of survivin in NP cells. However, cell morphology was evidently altered, whereas the apoptotic rate did not decrease. Comprehensive
Bolon, B; Grisanti, M; Villasenor, K; Morony, S; Feige, U; Simonet, W S
Bone structure is modulated by the interaction between receptor activator of nuclear factor-κB (RANK) and RANK ligand (RANKL). Osteoprotegerin (OPG), a decoy receptor for RANKL, modifies osteoclast-mediated bone resorption directly and spares articular cartilage indirectly in rodents with immune-mediated arthritis by preventing subchondral bone destruction. The OPG/RANKL balance also seems to be critical in maintaining joint integrity in osteoarthritis, a condition featuring articular bone and cartilage damage in the absence of profound inflammation. The current study explored the role of OPG in sparing articular cartilage by evaluating joint lesions in adult C57BL/6J mice lacking osteoprotegerin (Opg (-) (/-)). At 3, 5, 7, 9, and 12 months of age, both sexes of Opg (-) (/-) mice developed severe degenerative joint disease (DJD) characterized by progressive loss of cartilage matrix and eventually articular cartilage. Lesions developed earlier and more severely in Opg (-) (/-) mice relative to age-matched, wild-type (Opg (+) (/+)), or heterozygous (Opg (+) (/-)) littermates (P ≤ .05). The femorotibial joint was affected bilaterally at 3 months, while other key weight-bearing diarthrodial joints (eg, coxofemoral, scapulohumeral, humeroradioulnar) were affected later and unilaterally. Cortical bone in subchondral plates and long bone diaphyses of Opg (-) (/-) mice but not Opg (+/+) or Opg (+) (/-) animals was osteoporotic by 3 months of age (P ≤ .05); the extent of porosity was less than the degree of DJD. Closure of the physes in long bones (P ≤ .05) and cartilage retention in the femoral primary spongiosa (P ≤ .05) affected chiefly Opg (-) (/-) mice. These data suggest that OPG plays an essential direct role in maintaining cartilage integrity in the articular surfaces and physes. © The Author(s) 2015.
Broeckx, Sarah; Zimmerman, Marieke; Crocetti, Sara; Suls, Marc; Mariën, Tom; Ferguson, Stephen J.; Chiers, Koen; Duchateau, Luc; Franco-Obregón, Alfredo
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
Monarca, S; Zerbini, I; Simonati, C; Gelatti, U
Since the 1950s a causal relation between water hardness and cardiovascular diseases (CVD) in humans has been hypothesized. In order to evaluate the influence of calcium and magnesium, the minerals responsible for the hardness of drinking water, on human health, a review of all the articles published on the subject from 1980 up to today has been carried out. Many but not all geographic correlation studies showed an inverse association between water hardness and mortality for CVD. Most case-control and one cohort studies showed an inverse relation, statistically significant, between mortality from CVD and water levels of magnesium, but not calcium. Consumption of water containing high concentrations of magnesium seems to reduce of about 30-35% the mortality for CVD, but not the incidence. This inverse association is supported by clinical and experimental findings and is biologically plausible and in line with Hill's criteria for a cause-effect relationship.
Johnsen, Lars Gunnar; Storheim, Kjersti; Nygaard, Øystein P; Brox, Jens Ivar; Rossvoll, Ivar; Rø, Magne; Sandvik, Leiv; Grundnes, Oliver
Objective To compare the efficacy of surgery with disc prosthesis versus non-surgical treatment for patients with chronic low back pain. Design A prospective randomised multicentre study. Setting Five university hospitals in Norway. Participants 173 patients with a history of low back pain for at least one year, Oswestry disability index of at least 30 points, and degenerative changes in one or two lower lumbar spine levels (86 patients randomised to surgery). Patients were treated from April 2004 to September 2007. Interventions Surgery with disc prosthesis or outpatient multidisciplinary rehabilitation for 12-15 days. Main outcome measures The primary outcome measure was the score on the Oswestry disability index after two years. Secondary outcome measures were low back pain, satisfaction with life (SF-36 and EuroQol EQ-5D), Hopkins symptom check list (HSCL-25), fear avoidance beliefs (FABQ), self efficacy beliefs for pain, work status, and patients’ satisfaction and drug use. A blinded independent observer evaluated scores on the back performance scale and Prolo scale at two year follow-up. Results The study was powered to detect a difference of 10 points on the Oswestry disability index between the groups at two years. At two years there was a mean difference of −8.4 points (95% confidence interval −13.2 to −3.6) in favour of surgery. In the analysis of prespecified secondary outcomes, there were significant differences in favour of surgery for low back pain (mean difference −12.2, −21.3 to −3.1), patients’ satisfaction (63% (n=46) v 39% (n=26)), SF-36 physical component score (mean difference 5.8, 2.5 to 9.1), self efficacy for pain (mean difference 1.0, 0.2 to 1.9), and the Prolo scale (mean difference 0.9, 0.1 to 1.6). There were no significant differences in return to work, SF-36 mental component score, EQ-5D, fear avoidance beliefs, Hopkins symptom check list, drug use, and the back performance scale. One serious complication of leg
Ross, J S; Modic, M T
Radiography (plain roentgenography, myelography, computed tomography (CT), computed tomographic myelography) has been used to identify morphologic changes involving the various components of the diskovertebral unit. Added to this armamentarium of imaging techniques is magnetic resonance (MR) imaging, with its superior ability to define anatomy, its improved contrast sensitivity, and its potential to provide unique biochemical and physiologic information. The authors review the current use of MR imaging in defining degenerative changes in the spine including the various patterns of herniation, annular tears, canal stenosis, and the use of gadolinium-diethylenetriamine-pentaacetic acid for previously unoperated and operated patients. Prospective studies have compared surface-coil MR imaging, CT, and myelography in the evaluation of disk herniation and stenosis and found an 82.6% accuracy between MR imaging and surgical findings for the type and location of the disease. Recent experience with precontrast and postcontrast MR imaging in the postoperative lumbar spine indicated that it was 96% accurate in differentiating scar from disk in 44 patients at 50 reoperated levels. Three-dimensional imaging is, more and more, becoming an integral part of routine MR imaging. The theoretical and practical advantages of three-dimensional imaging are several and include a theoretical increase in the signal-to-noise ratio over two-dimensional imaging (by the square root of the number of partitions selected), the ability to obtain thin contiguous slices from the volume without the problem of cross-talk found in two-dimensional imaging, more accurate slice thickness than that achieved in two-dimensional imaging, and a reduction in susceptibility artifacts. Different three-dimensional techniques are capable of providing either high or low signal intensity cerebrospinal fluid (CSF), with excellent suppression of CSF pulsation artifacts. Certain sequences provide a high enough signal
Sollberger, Marc; Neuhaus, John; Ketelle, Robin; Stanley, Christine M.; Beckman, Victoria; Growdon, Matthew; Jung, Jang; Miller, Bruce L.; Rankin, Katherine P.
Background Different degenerative brain diseases result in distinct personality changes as a result of divergent patterns of brain damage, however, little is known about the natural history of these personality changes throughout the course of each disease. Objective To investigate how interpersonal traits change as a function of degenerative brain disease type and severity. Methods Using the Interpersonal Adjective Scales, informant ratings of retrospective premorbid and current scores for dominance, extraversion, warmth, and ingenuousness were collected annually for one to four years on 188 patients [67 behavioural variant frontotemporal dementia (bvFTD), 40 semantic dementia (SemD), 81 Alzheimer’s disease (AD)] and 65 older healthy controls. Using random coefficient models, interpersonal behaviour scores at very mild, mild, or moderate-to-severe disease stages were compared within and between patient groups. Results Group-level changes from premorbid personality occurred as a function of disease type and severity, and were apparent even at a very mild disease stage (Clinical Dementia Rating=0.5) for all three diseases. Decreases in interpersonal traits associated with emotional affiliation (i.e., extraversion, warmth, and ingenuousness) and more rigid interpersonal behaviour differentiated bvFTD and SemD patients from AD patients. Conclusions Specific changes in affiliative interpersonal traits differentiate degenerative brain diseases even at a very mild disease stage, and patterns of personality change differ across bvFTD, SemD, and AD with advancing disease. This study describes the typical progression of change of interpersonal traits in each disease, improving the ability of clinicians and caregivers to predict and plan for symptom progression. PMID:21172858
Forrester, J V
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
Jund, Jérôme; Noseda, Olivier; Roussouly, Pierre
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
Barrey, Cédric; Jund, Jérôme; Noseda, Olivier; Roussouly, Pierre
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 degrees and 51.6 degrees, respectively, versus 52 degrees 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
Stewart, G J; Williams, E A
Nine cases of locking of the metacarpo-phalangeal joint are described. The previously asymptomatic middle finger joint in an elderly person was most likely to be affected. Radiology of the joint has shown degenerative changes in all cases. In two patients, spontaneous unlocking of the joint occurred and in a further six operative release was undertaken. The important anatomical features of the condition are discussed in relation to the mechanism of locking and the surgical treatment.
Gruen, Margaret E; Messenger, Kristen M; Thomson, Andrea E; Griffith, Emily H; Aldrich, Lauren A; Vaden, Shelly; Lascelles, B Duncan X
Degenerative joint disease is common in cats, with signs of pain frequently found on orthopedic examination and radiographs often showing evidence of disease. However, understanding of the pathophysiology of degenerative joint disease and associated pain remains limited. Several cytokines have been identified as having a role in pain in humans, but this has not been investigated in cats. The present study was performed to use a multiplex platform to evaluate the concentration of 19 cytokines and chemokines in serum samples obtained from cats with and without degenerative joint disease and associated pain. Samples from a total of 186 cats were analyzed, with cats representing a range of severity on radiographic and orthopedic evaluations and categorized by degenerative joint disease scores and pain scores. Results showed that cats with higher radiographic degenerative joint disease scores have higher serum concentrations of IL-4 and IL-8, while cats with higher orthopedic exam pain scores have higher concentrations of IL-8, IL-2, and TNF-α; increased concentration of IL-8 in degenerative joint disease and pain may be confounded by the association with age. Discriminant analysis was unable to identify one or more cytokines that distinguish between groups of cats classified based on degenerative joint disease score category or pain score category. Finally, cluster analysis driven by analyte concentrations shows separation of groups of cats, but features defining the groups remain unknown. Further studies are warranted to investigate any changes in cytokine concentrations in response to analgesic therapies, and further evaluate the elevations in cytokine concentrations found here, particularly focused on studies of local cytokines present in synovial fluid. Copyright © 2016 Elsevier B.V. All rights reserved.
Goldstein, H.A.; Bloom, C.Y.
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.
Skytte, Ditte; Schmökel, Hugo
Three dogs were presented with lumbosacral hyperesthesia. Computerized tomography scans were performed in all the cases, and magnetic resonance imaging was also performed in cases 1 and 3. There was intervertebral disc (IVD) protrusion causing nerve root compression and epidural gas accumulation in all the three cases. The gas-filled cystic structures in cases 1 and 3 were within the spinal canal; in case 2, the gas was within the disc protrusion. The IVD vacuum phenomenon is relatively common in dogs, but the formation of an epidural gas accumulation in cases of a lumbar disc protrusion is rare. The clinical significance of these epidural gas accumulations is unknown. Two of the dogs were treated surgically, improved after surgery, and showed no signs of pain in the follow-up examinations.
Yi, Zhou; Guanjun, Tu; Lin, Cong; Zifeng, Pei
Study Design. Prospective, randomized controlled animal study.Objective. To observe ECM changes in degenerative IVD after transplantation of bone marrow mesenchymal stem cells (BMSCs) virally transfected with a construct expressing human tissue inhibitor of metalloproteinase 1 (hTIMP-1), and to discuss the feasibility of using this approach to treat intervertebral disc degeneration (IDD).Summary of Background Data. Intervertebral disc (IVD) degeneration is characterized by decreased cell numbers, bioactivity of the nucleus pulposus (NP), and remodeled extracellular matrix (ECM). Exogenous genes can be targeted into cells to produce inhibition of ECM degradation and increase ECM content in IVDs, and thereby potentially stop or reverse degenerative processes and modify disc structure.Methods. BMSCs were isolated from a pure New-Zealand rabbit and identified by flow cytometry. Transgenic BMSCs were acquired by transfection with a recombinant adenovirus vector carrying the hTIMP-1 gene. Animal models of IDD were established by annulus puncture and then given intra-NP injections according to their random assignment into three groups: (1) a transgenic BMSC transplantation (TgBT) group that received BMSCs transfected with an hTIMP-1-expressing adenovirus vector; (2) a BMSC transplantation (BT) group that received unaltered BMSCs; and (3) a control (PCon) group that received cell-free phosphate-buffered saline. Degree of degeneration was evaluated 12 wks after modeling. ECM content was quantified using immunohistochemistry (IHC) and spectrophotography. Expression of hTIMP-1 was observed via quantitative PCR, western blot, and IHC.Results. Significantly fewer degenerative changes and increased ECM content were observed in the TBT and BT groups compared to PCon animals (P < .05). The TBT group had greater ECM content than did the BT group (P < .05), as well as higher levels of hTIMP-1 mRNA and protein.Conclusions. Transplantation of BMSCs transfected with hTIMP-1 can
Chowdhury, Anindita; Kunjiappan, Selvaraj; Panneerselvam, Theivendren; Somasundaram, Balasubramanian; Bhattacharjee, Chiranjib
Degenerative diseases are results of deterioration of cells and tissues with aging either by unhealthy lifestyle or normal senescence. The degenerative disease likely affects central nervous system and cardiovascular system to a great extent. Certain medications and therapies have emerged for the treatment of degenerative diseases, but in most cases bearing with poor solubility, lower bioavailability, drug resistance, and incapability to cross the blood-brain barrier (BBB). Hence, it has to be overcome with conventional treatment system; in this connection, nanotechnology has gained a great deal of interest in recent years. Moreover, nanotechnology and nanocarrier-based approach drug delivery system could revolutionize the treatment of degenerative diseases by faster absorption of drug, targeted interaction at specific site, and its release in a controlled manner into human body with minimal side effects. The core objective of this review is to customize and formulate therapeutically active molecules with specific site of action and without affecting other organs and tissues to obtain effective result in the improvement of quality of health. In addition, the review provides a concise insight into the recent developments and applications of nanotech and nanocarrier-based drug delivery for the treatment of various degenerative diseases.
Wang, Hui-Wang; Hu, Yong-Cheng; Wu, Zhan-Yong; Wu, Hua-Rong; Wu, Chun-Fu; Zhang, Lian-Suo; Xu, Wei-Kun; Fan, Hui-Long; Cai, Jin-Sheng; Ma, Jian-Qing
To evaluate the clinical effect of the minimally invasive transforaminal lumbar interbody fusion combined with posterolateral fusion and unilateral fixation using a tubular retractor in the management of degenerative lumbar disease. A retrospective analysis was conducted to analyze the clinical outcome of 58 degenerative lumbar disease patients who were treated with minimally invasive transforaminal lumbar interbody fusion combined with posterolateral fusion and unilateral fixation during December 2012 to January 2015. The spine was unilaterally approached through a 3.0-cm skin incision centered on the disc space, located 2.5 cm lateral to the midline, and the multifidus muscles and longissimus dorsi were stripped off. After transforaminal lumbar interbody fusion and posterolateral fusion the unilateral pedicle screw fixation was performed. The visual analogue scale (VAS) for back and leg pain, the Oswestry disability index (ODI), and the MacNab score were applied to evaluate clinical effects. The operation time, peri-operative bleeding, postoperative time in bed, hospitalization costs, and the change in the intervertebral height were analyzed. Radiological fusion based on the Bridwell grading system was also assessed at the last follow-up. The quality of life of the patients before and after the operation was assessed using the short form-36 scale (SF-36). Fifty-eight operations were successfully performed, and no nerve root injury or dural tear occurred. The average operation time was 138 ± 33 min, intraoperative blood loss was 126 ± 50 mL, the duration from surgery to getting out of bed was 46 ± 8 h, and hospitalization cost was 1.6 ± 0.2 ten thousand yuan. All of the 58 patients were followed up for 7-31 months, with an average of 14.6 months. The postoperative VAS scores and ODI score were significantly improved compared with preoperative data (P < 0.05). The evaluation of the MacNab score was excellent in 41 patients, good
Ibrahim, Michael; Rao, Christopher; Athanasiou, Thanos
The surgical repair of degenerative mitral valve disease involves a number of technical points of importance. The use of artificial chordae for the repair of degenerative disease has increased as a part of the move from mitral valve replacement to repair of the mitral valve. The use of artificial chordae provides an alternative to the techniques pioneered by Carpentier (including the quadrangular resection, transfer of native chordae and papillary muscle shortening/plasty), which can be more technically difficult. Despite a growth in their uptake and the indications for their use, a number of challenges remain for the use of artificial chordae in mitral valve repair, particularly in the determination of the correct length to ensure optimal leaflet coaptation. Here, we analyse over 40 techniques described for artificial chordae mitral valve repair in the setting of degenerative disease. PMID:22962321
Keener, Jay D; Skelley, Nathan W; Stobbs-Cucchi, Georgia; Steger-May, Karen; Chamberlain, Aaron M; Aleem, Alex W; Brophy, Robert H
This study prospectively examined the relationship of direct and indirect measures of shoulder activity with the risks of tear progression and pain development in subjects with an asymptomatic degenerative rotator cuff tear. A cohort of asymptomatic degenerative rotator cuff tears was prospectively monitored annually, documenting tear size progression with ultrasound imaging and potential shoulder pain development. Shoulder activity level, self-reported occupational and physical demand level, and hand dominance were compared with risks of tear enlargement and future pain development. The study monitored 346 individuals with a mean age of 62.1 years for a median duration of 4.1 years (interquartile range [IQR], 2.4-7.9 years). Tear enlargement was seen in 177 shoulders (51.2%), and pain developed in 161 shoulders (46.5%) over time. Tear presence in the dominant shoulder was associated with a greater risk of tear enlargement (hazard ratio, 1.40; P = .03) and pain development (hazard ratio, 1.63; P = .002). Shoulder activity level (P = .37) and occupational demand level (P = .62) were not predictive of tear enlargement. Occupational demand categories of manual labor (P = .047) and "in between" (P = .045) had greater risks of pain development than sedentary demands. The median shoulder activity score for shoulders that became painful was lower than for shoulders that remained asymptomatic (10.0 [IQR, 7.0-13.0] vs. 11.0 [IQR, 8.0-14.0], P = .02). Tear enlargement and pain development in asymptomatic tears are more common with involvement of the dominant shoulder. Shoulder activity level is not related to tear progression risks. Pain development is associated with a lower shoulder activity level even though patients with higher occupational demands are more likely to develop pain. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.
Islam, Md Asiful; Alam, Fahmida; Solayman, Md; Khalil, Md Ibrahim; Kamal, Mohammad Amjad; Gan, Siew Hua
Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.
Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described. PMID:27721914
David, Tirone E
Degenerative diseases of the mitral valve (MV) are the most common cause of mitral regurgitation in the Western world and the most suitable pathology for MV repair. Several studies have shown excellent long-term durability of MV repair for degenerative diseases. The best follow-up results are obtained with isolated prolapse of the posterior leaflet, however even with isolated prolapse of the anterior leaflet or prolapse of both leaflets the results are gratifying, particularly in young patients. The freedom from reoperation on the MV at 15 years exceeds 90% for isolated prolapse of the posterior leaflet and it is around 70-85% for prolapse of the anterior leaflet or both leaflets. The degree of degenerative change in the MV also plays a role in durability of MV repair. Most studies have used freedom from reoperation to assess durability of the repair but some studies that examined valve function late after surgery suggest that recurrent mitral regurgitation is higher than estimated by freedom from reoperation. We can conclude that MV repair for degenerative mitral regurgitation is associated with low probability of reoperation for up to two decades after surgery. However, almost one-third of the patients develop recurrent moderate or severe mitral regurgitation suggesting that surgery does not arrest the degenerative process.
Degenerative diseases of the mitral valve (MV) are the most common cause of mitral regurgitation in the Western world and the most suitable pathology for MV repair. Several studies have shown excellent long-term durability of MV repair for degenerative diseases. The best follow-up results are obtained with isolated prolapse of the posterior leaflet, however even with isolated prolapse of the anterior leaflet or prolapse of both leaflets the results are gratifying, particularly in young patients. The freedom from reoperation on the MV at 15 years exceeds 90% for isolated prolapse of the posterior leaflet and it is around 70-85% for prolapse of the anterior leaflet or both leaflets. The degree of degenerative change in the MV also plays a role in durability of MV repair. Most studies have used freedom from reoperation to assess durability of the repair but some studies that examined valve function late after surgery suggest that recurrent mitral regurgitation is higher than estimated by freedom from reoperation. We can conclude that MV repair for degenerative mitral regurgitation is associated with low probability of reoperation for up to two decades after surgery. However, almost one-third of the patients develop recurrent moderate or severe mitral regurgitation suggesting that surgery does not arrest the degenerative process. PMID:26539345
Nie, Lin; Zhang, Li; Hou, Yong
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
Kaĭsarov, G A; Bagirova, V V
To evaluate prevalence of osteoarthrosis (OA) in metallurgists in conditions of high tension of the locomotor system and exposure to industrial pollutants depending on the age, sex and duration of service. Epidemiological survey covered 713 workers (284 females and 429 males) of the Orsko-Khalilovsky Metallurgical Company. OA detection was made basing on screening questionnaire N 1, record N 2 and OA diagnostic criteria designed and tested in the RAMS Rheumatism Institute. Prevalence of OA among workers of the metallurgic company reached 71.6%. 83.5 and 63.8% females and males had degenerative changes in the joints and spine, respectively. This rate got higher with age and duration of service. Combination of OA with osteochondrosis (OC) was registered in 61.7%, isolated OC and OA--in 25.0 and 13.3%, respectively. OC developed most frequently in the lumbar, cervical-lumbar, cervical-thoracic spine while OA was found in the knee, shoulder and hand joints. Workers engaged in metallurgic industry work in conditions of high static-dynamic tension of the osteomuscular system and exposure to industrial chemical and physical hazards. The above risk factors contribute to high OA incidence. With age and longer exposure, both men and women fall ill with OA more frequently and have combined lesions of the spine and peripheral joints: 64.5 and 59.1% for women and men, respectively.
Maleki, Farid; Meybodi, Ali Tayebi; Mahdavi, Ali; Saberi, Hooshang
Study Design A cross-sectional case-control study was designed to compare the sagittal alignment of lumbosacral regions in two groups of patients suffering from low back pain, one with intervertebral disc pathologies and one without. Purpose To evaluate the correlation between lumbosacral sagittal alignment and disc degeneration. Overview of Literature Changes in lumbar lordosis and pelvic parameters in degenerative disc lesions have been assessed in few studies. Overall, patients with discopathy were shown to have lower lumbar lordosis and more vertical sacral profiles. Methods From patients with intractable low back pain undergoing lumbosacral magnetic resonance imaging, 50 subjects with disc degeneration and 50 controls with normal scans were consecutively enrolled. A method was defined with anterior tangent-lines going through anterior bodies of L1 and S1 to measure global lumbosacral angle, incorporating both lumbar lordosis and sacral slope. Global lumbosacral angle using the proposed method and lumbar lordosis using Cobb's method were measured in both groups. Results Lumbar lordosis based on Cobb's method was lower in group with discopathy (20°-67°; mean, 40.48°±9.89°) than control group (30°-62°; mean, 44.96°±7.68°), although it was not statistically significant. The proposed global lumbosacral angle in subject group (53°-103°; mean, 76.5°±11.018°) was less than control group (52°-101°; mean, 80.18°±9.95°), with the difference being statistically significant (p=0.002). Conclusions Patients with intervertebral disc lesions seem to have more straightened lumbosacral profiles, but it has not been proven which comes first: disc degeneration or changes in sagittal alignment. Finding an answer to this dilemma demands more comprehensive long-term prospective studies. PMID:25558325
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
Kreutziger, K L; Mahan, P E
The anatomy and function of the temporomandibular joint (TMJ) are described in the detail needed to evaluate and treat temporomandibular degenerative joint disease (TDJD). Innervation of the joint and the mechanism of arthralgia are described and related to TDJD. The clinical course of TDJD, radiographic evaluation of it, histopathologic description, and etiology are presented.
Li, Yuk Yin; Diao, Hua Jia; Chik, Tze Kit; Chow, Cin Ting; An, Xiao Meng; Leung, Victor; Cheung, Kenneth Man Chi
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
Li, Yuk Yin; Diao, Hua Jia; Chik, Tze Kit; Chow, Cin Ting; An, Xiao Meng; Leung, Victor; Cheung, Kenneth Man Chi; Chan, Barbara Pui
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.
Wang, Hui; Ma, Lei; Yang, Dalong; Wang, Tao; Liu, Sen; Yang, Sidong; Ding, Wenyuan
Abstract The purpose of this study was to explore incidence and risk factors of adjacent segment disease (ASD) following posterior decompression and instrumented fusion for degenerative lumbar disorders, and hope to provide references in decision making and surgical planning for both spinal surgeon and surgically treated patients. By retrieving the medical records from January 2011 to December 2013 in our hospital, 237 patients were retrospectively reviewed. According to the occurrence of ASD at follow up, patients were divided into 2 groups: ASD and N-ASD group. To investigate risk values for the occurrence of ASD, 3 categorized factors were analyzed statistically: Patient characteristics: age, sex, body mass index (BMI), bone mineral density (BMD), duration. Surgical variables: surgical strategy, number of fusion level, surgery segment, surgery time, blood loss, intraoperative superior facet joint violation. Radiographic parameters: preoperative lumbar lordosis, preoperative angular motion at adjacent segment, preoperative adjacent segment disc degeneration, preoperative paraspinal muscle degeneration. Postoperative ASD was developed in 15 of 237 patients (6.3%) at final follow up. There was no statistically significant difference between the 2 groups in patient characteristics of age, sex composition, BMD, duration, while the BMI was higher in ASD group than that in N-ASD group. There was no difference in surgical variables of surgical strategy, number of fusion level, surgery segment, surgery time, blood loss, while intraoperative superior facet joint violation was more common in ASD group than that in N-ASD group. There was no difference in radiographic parameters of preoperative lumbar lordosis, preoperative paraspinal muscle degeneration, while preoperative adjacent segment disc degeneration were more severe in ASD group than that in N-ASD group. The Logistic regression analysis revealed that, BMI >25 kg/m2, preoperative disc degeneration, and superior
Wang, Hui; Ma, Lei; Yang, Dalong; Wang, Tao; Liu, Sen; Yang, Sidong; Ding, Wenyuan
The purpose of this study was to explore incidence and risk factors of adjacent segment disease (ASD) following posterior decompression and instrumented fusion for degenerative lumbar disorders, and hope to provide references in decision making and surgical planning for both spinal surgeon and surgically treated patients.By retrieving the medical records from January 2011 to December 2013 in our hospital, 237 patients were retrospectively reviewed. According to the occurrence of ASD at follow up, patients were divided into 2 groups: ASD and N-ASD group. To investigate risk values for the occurrence of ASD, 3 categorized factors were analyzed statistically: Patient characteristics: age, sex, body mass index (BMI), bone mineral density (BMD), duration. Surgical variables: surgical strategy, number of fusion level, surgery segment, surgery time, blood loss, intraoperative superior facet joint violation. Radiographic parameters: preoperative lumbar lordosis, preoperative angular motion at adjacent segment, preoperative adjacent segment disc degeneration, preoperative paraspinal muscle degeneration.Postoperative ASD was developed in 15 of 237 patients (6.3%) at final follow up. There was no statistically significant difference between the 2 groups in patient characteristics of age, sex composition, BMD, duration, while the BMI was higher in ASD group than that in N-ASD group. There was no difference in surgical variables of surgical strategy, number of fusion level, surgery segment, surgery time, blood loss, while intraoperative superior facet joint violation was more common in ASD group than that in N-ASD group. There was no difference in radiographic parameters of preoperative lumbar lordosis, preoperative paraspinal muscle degeneration, while preoperative adjacent segment disc degeneration were more severe in ASD group than that in N-ASD group. The Logistic regression analysis revealed that, BMI >25 kg/m, preoperative disc degeneration, and superior facet joint
Uruha, Akinori; Nishino, Ichizo
While the pathogenesis of inclusion body myositis (IBM) remains undetermined, there are two major hypotheses: the autoimmune hypothesis and the degeneration hypothesis. Herein, we review these hypotheses as well as potential therapeutic approaches. Evidence in favor of a primary autoimmune etiology includes the frequent complication of other autoimmune diseases in patients with IBM and the presence of autoantibodies against cytosolic 5'-nucleotidase 1A. Interleukin (IL)-1β reportedly leads to accumulation of amyloid β via nitric oxide stress in vitro. The degeneration hypothesis addresses the following aspects of IBM: accumulation of amyloid β and other abnormal proteins that are observed in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease; relation to aging; and poor response to immunotherapy. Overexpression of IL-1β in skeletal muscles of patients with IBM and its secretion from skeletal muscle cells suggests an important role for IL-1β in the pathogenesis of IBM. Thus, IL-1β is a potential treatment target.
Herrmann, Wolfgang; Knapp, Jean-Pierre
Hyperhomocysteinemia (HHCY) is a consequence of disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological and clinical studies have proven HHCY to be an independent risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Trials in progress may clarify the "causality" of high homocysteine (HCY) concentrations and will assess the value of HCY lowering therapy. HHCY is also seen as a risk factor for neurodegenerative diseases such as cognitive impairment, dementia, Alzheimer's disease, and also for depression. There is a high prevalence of HHCY as a syndrome of vitamin shortage in elderly subjects, which strongly increases with advancing age. Elderly people have a high frequency of vitamin B12 deficiency which is more reliably diagnosed by measurement of serum methylmalonic acid and holotranscobalamin II, the metabolically active B12 fraction, than by total serum vitamin B12. Subjects who follow a strict vegetarian diet also have a high prevalence of HHCY caused by vitamin B12 deficiency. For prevention of neurological damages an early diagnosis of vitamin B12 deficiency is important. Furthermore, HHCY is a factor in the pathogenesis of neural tube defects and preeclampsia. HCY should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in adipose subjects, in elderly people, in vegetarians, in postmenopausal women, and in early pregnancy.
Brander, V A; Kaelin, D L; Oh, T H; Lim, P A
This self-directed learning module highlights assessment and therapeutic options in the rehabilitation of patients with osteoarthritis. It is part of the chapter on rehabilitation of orthopedic and rheumatologic disorders in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. New advances covered in this article include updates on conservative and operative treatment of lumbar spinal stenosis and pediatric hip diseases, prophylactic therapy for thromboembolic disease after lower limb joint replacement, new therapies for osteoarthritis, and the impact of exercise on outcome following hip replacement in active persons.
Comparative long-term results of mitral valve repair in adults with chronic rheumatic disease and degenerative disease: is repair for "burnt-out" rheumatic disease still inferior to repair for degenerative disease in the current era?
Dillon, Jeswant; Yakub, Mohd Azhari; Kong, Pau Kiew; Ramli, Mohd Faizal; Jaffar, Norfazlina; Gaffar, Intan Fariza
Mitral valve repair is perceived to be of limited durability for advanced rheumatic disease in adults. We aim to examine the long-term outcomes of repair for rheumatic disease, identify predictors of durability, and compare with repair for degenerative disease. Rheumatic and degenerative mitral valve repairs in patients aged 40 years or more were prospectively analyzed. The primary outcomes investigated were mortality, freedom from reoperation, and valve failure. Logistic regression analysis was performed to define predictors of poor outcome. Between 1997 and 2011, 253 rheumatic and 148 degenerative mitral valves were repaired. The age of patients in both groups was similar, with a mean of 54.1 ± 8.4 years versus 55.6 ± 7.3 years (P = .49). Freedom from reoperation for rheumatic valves at 5 and 10 years was 98.4%, comparable to 95.3% (P = .12) for degenerative valves. Freedom from valve failure at 5 and 10 years was 91.4% and 81.5% for rheumatic repairs and 82.5% and 75.4% for degenerative repairs, respectively (P = .15). The presence of residual mitral regurgitation greater than 2+ before discharge was the only significant independent predictor of reoperation, whereas residual mitral regurgitation greater than 2+ and leaflet procedures were significant risk factors for valve failure. The durability of rheumatic mitral valve repair in the current era has improved and is comparable to the outstanding durability of repairs for degenerative disease, even in the adult rheumatic population. Modifications of standard repair techniques, adherence to the importance of good leaflet coaptation, and strict quality control with stringent use of intraoperative transesophageal echocardiography have all contributed to the improved long-term results. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Tochitsky, Ivan; Kramer, Richard H
Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are progressive retinal diseases that result from the death of rod and cone photoreceptors, ultimately leading to blindness. The only currently approved vision restoration treatment employs an implanted retinal ‘chip’ as a prosthetic device to electrically stimulate retinal neurons that survive after the photoreceptors are gone, thereby restoring light-driven neural signaling to the brain. An alternative strategy has been proposed, which would utilize optogenetic or opto-pharmacological tools to enable direct optical stimulation of surviving retinal neurons. Here, we review the latest studies evaluating the feasibility of these molecular tools as potential therapeutics for restoring visual function in human blinding disease. PMID:25706312
Canver, C C; Chanda, J; DeBellis, D M; Kelley, J M
We report an unusual clinical presentation of Lyme carditis in a previously healthy 20-year-old black woman without any epidemiologic history of Lyme disease, fulminant in nature, involving a heart valve necessitating emergent mitral valve replacement, and requiring further surgical intervention because of the development of pericardial effusion and tamponade. A dilated right ventricle with normal contractility and severe tricuspid regurgitation with increase in the right atrial size diagnosed later remains under close surveillance.
Dorenbeck, U; Schreyer, A G; Schlaier, J; Held, P; Feuerbach, S; Seitz, J
Assessing degenerative disease in the cervical spine remains a challenge. There is much controversy about imaging the cervical spine using MRI. Our aim in this prospective study was to compare a T2*-weighted 2D spoiled gradient-echo multiecho sequence (MEDIC) with a magnetisation transfer saturation pulse with cervical myelography and postmyelographic CT. Using an assessment scale we looked at the vertebral bodies, intervertebral discs, neural foramina, anterior and posterior nerve roots, grey matter, ligamentaflava, oedema in the spinal cord and stenosis of the spinal canal. We also evaluated postmyelography CT and the MEDIC sequence for assessing narrowing of the neural foramina in a cadaver cervical spine. We examined 67 disc levels in 18 patients, showing 18 disc prolapses and 21 osteophytes narrowing the spinal canal or the neural foramina. All MRI studies showed these abnormalities findings equally well. Postmyelography CT was significantly better for showing the bony structures and the anterior and posterior nerve roots. The MEDIC sequence provided excellent demonstration of soft-tissue structures such as the intervertebral disc and ligamentum flavum. No statistical differences between the imaging modalities were found in the assessment of narrowing of the neural foramina or the extent of spinal stenosis. The cadaver measurements showed no overestimation of abnormalities using the MEDIC sequence.
Kim, Sang-Bum; Jeon, Taek-Soo; Heo, Youn-Moo; Lee, Woo-Suk; Yi, Jin-Woong; Kim, Tae-Kyun; Hwang, Cheol-Mog
To assess the radiographic results in patients who underwent transforaminal lumbar interbody fusion (TLIF), particularly the changes in segmental lordosis in the fusion segment, whole lumbar lordosis and disc height. Twenty six cases of single-level TLIF in degenerative lumbar diseases were analyzed. The changes in segmental lordosis, whole lumbar lordosis, and disc height were evaluated before surgery, after surgery and at the final follow-up. The segmental lordosis increased significantly after surgery but decreased at the final follow-up. Compared to the preoperative values, the segmental lordosis did not change significantly at the final follow-up. Whole lumbar lordosis at the final follow-up was significantly higher than the preoperative values. The disc height was significantly higher in after surgery than before surgery (p = 0.000) and the disc height alter surgery and at the final follow-up was similar. When performing TLIF, careful surgical techniques and attention are needed to restore and maintain the segmental lordosis at the fusion level.
Wu, Junyan; Wang, Jie; Zhang, Junlong
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:
Marti, B.; Knobloch, M.; Tschopp, A.; Jucker, A.; Howald, H.
OBJECTIVE--To determine the effects of regular long distance running on the state of the hips in later life. DESIGN--Retrospective study of a cohort of elite athletes and a group of normal, healthy, untrained controls examined 15 years after initial testing. SETTING--Research project at school for physical education and sports. SUBJECTS--27 Former long distance runners (mean age 42), nine former bobsleigh riders (mean age 42), and 23 normal, healthy, untrained men (mean age 35) who had been examined in 1973 and who agreed to re-examination in 1988. MAIN OUTCOME MEASURE--Radiological evidence of degenerative hip disease in 1988. RESULTS--Physiological and exercise characteristics of all subjects had been recorded in 1973, and in 1988 these measurements were repeated together with radiological examination of the hips. An additive radiological index of hip disease based on grades of subchondral sclerosis, osteophyte formation, and joint space narrowing was significantly increased among runners as compared with bobsleigh riders and untrained controls. After adjustment for age the significant effect of type of sports activity remained (p = 0.032). In multivariate analyses age and milage run in 1973 (97 km/week) emerged as independent, significant, and positive predictors of radiological signs of degenerative hip disease in 1988 (p = 0.017 and p = 0.024 respectively). Among runners alone running pace in 1973 rather than milage run was the stronger predictor of subsequent degenerative hip disease. The milage run in 1988 was not particularly predictive of the radiological index, but endurance in 1988 was inversely related to degenerative hip disease seen radiologically. CONCLUSION--Long term, high intensity, high milage running should not be dismissed as a potential risk factor for premature osteoarthritis of the hip. PMID:2504343
von Engelhardt, L V; Schmitz, A; Burian, B; Pennekamp, P H; Schild, H H; Kraft, C N; von Falkenhausen, M
The literature contains only a few studies investigating the magnetic resonance imaging (MRI) diagnostics of degenerative cartilage diseases. Studies on MRI diagnostics of the cartilage using field strengths of 3-Tesla demonstrate promising results. To assess the value of 3-Tesla MRI for decision making regarding conservative or operative treatment possibilities, this study focused on patients with degenerative cartilage diseases. Thirty-two patients with chronic knee pain, a minimum age of 40 years, a negative history of trauma, and at least grade II degenerative cartilage disease were included. Cartilage abnormalities detected at preoperative 3-Tesla MRI (axial/koronar/sagittal PD-TSE-SPAIR, axial/sagittal 3D-T1-FFE, axial T2-FFE; Intera 3.0T, Philips Medical Systems) were classified (grades I-IV) and compared with arthroscopic findings. Thirty-six percent (70/192) of the examined cartilage surfaces demonstrated no agreement between MRI and arthroscopic grading. In most of these cases, grades II and III cartilage lesions were confounded with each other. Regarding the positive predictive values, the probability that a positive finding in MRI would be exactly confirmed by arthroscopy was 39-72%. In contrast, specificities and negative predictive values of different grades of cartilage diseases were 85-95%. Regarding the high specificities and negative predictive values, 3-Tesla MRI is a reliable method for excluding even slight cartilage degeneration. In summary, in degenerative cartilage diseases, 3-Tesla MRI is a supportive, noninvasive method for clinical decision making regarding conservative or operative treatment possibilities. However, the value of diagnostic arthroscopy for a definitive assessment of the articular surfaces and for therapeutic planning currently cannot be replaced by 3-Tesla MRI. This applies especially to treatment options in which a differentiation between grade II and III cartilage lesions is of interest.
Perusek, Lindsay; Maeda, Tadao
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
Perusek, Lindsay; Maeda, Tadao
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.
Jeon, Sohee; Oh, Il-Hoan
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.
Roussotte, Florence F; Daianu, Madelaine; Jahanshad, Neda; Leonardo, Cassandra D; Thompson, Paul M
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 multi-modal 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.
Zolfaghari, Farid; Faridmoayer, Alireza; Soleymani, Bahram; Mahabadi, Maryam
Study Design Descriptive cross-sectional study. Purpose To determine the prevalence of vitamin D deficiency in patients with degenerative diseases of the spine about to undergo spinal surgery and the relations between such deficiency and potential risk factors. Overview of Literature Vitamin D has a major role in musculoskeletal system health maintenance. Recently, studies on degenerative diseases of the spine have shown a high prevalence of vitamin D deficiency in patients undergoing spine surgery. Methods Serum levels of 25(OH)D were determined by an electrochemiluminescence detection assay. The other variables were determined through relevant questionnaires, and the data was analyzed through analysis of variance, t-test, chi-square and multivariate logistic regression analysis. Results A total of 110 patients were enrolled in the study. The mean serum level of 25(OH)D was 27.45±18.75 ng/mL, and 44.5% of patients showed vitamin D deficiency (25(OH)D<20 ng/mL), with an additional 17.3% of patients having a serum level of 25(OH)D that was insufficient (20≤25(OH)D<30 ng/mL). The prevalence of vitamin D deficiency was significantly higher in the younger age group compared to the older age group (p<0.001) and the ones without a history of taking vitamin D supplements (p=0.013). Compared to men, women showed significantly higher levels of vitamin D (p=0.029). Conclusions A high prevalence of vitamin D deficiency is seen in patients with degenerative diseases of the spine. On the other hand, the conventional risk factors such as old age or female sex alone did not seem to be sufficient in determining the likelihood of deficiency. Thus, it is recommended that vitamin D deficiency prevention strategies comprise a broader spectrum of the population through which such degenerative diseases and their consequences may be prevented or delayed. PMID:27790310
Loperfido, Mariana; Steele-Stallard, Heather B; Tedesco, Francesco Saverio; VandenDriessche, Thierry
Human pluripotent stem cells represent a unique source for cell-based therapies and regenerative medicine. The intrinsic features of these cells such as their easy accessibility and their capacity to be expanded indefinitely overcome some limitations of conventional adult stem cells. Furthermore, the possibility to derive patient-specific induced pluripotent stem (iPS) cells in combination with the current development of gene modification methods could be used for autologous cell therapies of some genetic diseases. In particular, muscular dystrophies are considered to be a good candidate due to the lack of efficacious therapeutic treatments for patients to date, and in view of the encouraging results arising from recent preclinical studies. Some hurdles, including possible genetic instability and their efficient differentiation into muscle progenitors through vector/transgene-free methods have still to be overcome or need further optimization. Additionally, engraftment and functional contribution to muscle regeneration in pre-clinical models need to be carefully assessed before clinical translation. This review offers a summary of the advanced methods recently developed to derive muscle progenitors from pluripotent stem cells, as well as gene therapy by gene addition and gene editing methods using ZFNs, TALENs or CRISPR/Cas9. We have also discussed the main issues that need to be addressed for successful clinical translation of genetically corrected patient-specific pluripotent stem cells in autologous transplantation trials for skeletal muscle disorders.
Buckle, Kelly N; Alley, Maurice R
A juvenile, male, yellow-eyed penguin (Megadyptes antipodes) with abnormal stance and decreased mobility was captured, held in captivity for approximately 6 weeks, and euthanized due to continued clinical signs. Radiographically, there was bilateral degenerative joint disease with coxofemoral periarticular osteophyte formation. Grossly, the bird had bilaterally distended, thickened coxofemoral joints with increased laxity, and small, roughened and angular femoral heads. Histologically, the left femoral articular cartilage and subchondral bone were absent, and the remaining femoral head consisted of trabecular bone overlain by fibrin and granulation tissue. There was no gross or histological evidence of infection. The historic, gross, radiographic, and histopathologic findings were most consistent with bilateral aseptic femoral head degeneration resulting in degenerative joint disease. Although the chronicity of the lesions masked the initiating cause, the probable underlying causes of aseptic bilateral femoral head degeneration in a young animal are osteonecrosis and osteochondrosis of the femoral head. To our knowledge, this is the first reported case of bilateral coxofemoral degenerative joint disease in a penguin.
Yu, Fei; Ma, Junxuan
Low back pain (LBP) is the leading cause of disability in the elderly. Intervertebral disc degeneration (IDD) was considered as the main cause for LBP. Degeneration of cartilaginous endplate was a crucial harmful factor during the initiation and development of IDD. Oxidative stress was implicated in IDD. However, the underlying molecular mechanism for the degeneration of cartilaginous endplate remains elusive. Herein, we found that oxidative stress could induce apoptosis and autophagy in endplate chondrocytes evidenced by western blot analysis, flow cytometry, immunofluorescence staining, GFP-LC3B transfection, and MDC staining. In addition, we also found that the apoptosis of endplate chondrocytes was significantly increased after the inhibition of autophagy by bafilomycin A1 shown by flow cytometry. Furthermore, mTOR pathway upstream autophagy was greatly suppressed suggested by western blot assay. In conclusion, our study strongly revealed that oxidative stress could increase autophagy and apoptosis of endplate chondrocytes in intervertebral disc. The increase of autophagy activity could prevent endplate chondrocytes from apoptosis. The autophagy in endplate chondrocytes induced by oxidative stress was mTOR dependent. These findings might shed some new lights on the mechanism for IDD and provide new strategies for the treatments of IDD. PMID:28321270
Degenerative instability affecting the functional spinal unit is discussed as a cause of symptoms. The value of imaging signs for assessing the resulting functional impairment is still unclear. To determine the relationship between slight degrees of degeneration and function, we performed a biomechanical study with 18 multisegmental (L2-S2) human lumbar cadaveric specimens. The multidirectional spinal deformation was measured during the continuous application of pure moments of flexion/extension, bilateral bending and rotation in a spine tester. The three flexibility parameters neutral zone, range of motion and neutral zone ratio were evaluated. Different grading systems were used: (1) antero-posterior and lateral radiographs (degenerative disk disease) (2) oblique radiographs (facet joint degeneration) (3) macroscopic and (4) microscopic evaluation. The most reliable correlation was between the grading of microscopic findings and the flexibility parameters; the imaging evaluation was not as informative. PMID:18839226
Llopis, E; Belloch, E; León, J P; Higueras, V; Piquer, J
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. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.
Seaman, David R
It is the rare physician who includes diet therapy and nutritional supplements in patient care. Perhaps this is because chiropractic and medical schools devote very few classroom hours to nutrition. It is also possible that physicians are under the misconception that a detailed biochemical understanding of each individual disease is required before nutritional interventions can be used. The purpose of this article is two-fold: (1) to demonstrate that chronic pain and other degenerative conditions encountered in clinical practice have similar biochemical etiologies, such as a diet-induced proinflammatory state, and (2) to outline a basic nutritional program that can be used by all practitioners. The data were accumulated over a period of years by reviewing contemporary articles and books and subsequently by retrieving relevant articles. Articles were also selected through MEDLINE and manual library searches. The typical American diet is deficient in fruits and vegetables and contains excessive amounts of meat, refined grain products, and dessert foods. Such a diet can have numerous adverse biochemical effects, all of which create a proinflammatory state and predispose the body to degenerative diseases. It appears that an inadequate intake of fruits and vegetables can result in a suboptimal intake of antioxidants and phytochemicals and an imbalanced intake of essential fatty acids. Through different mechanisms, each nutritional alteration can promote inflammation and disease. We can no longer view different diseases as distinct biochemical entities. Nearly all degenerative diseases have the same underlying biochemical etiology, that is, a diet-induced proinflammatory state. Although specific diseases may require specific treatments, such as adjustments for hypomobile joints, beta-blockers for hypertension, and chemotherapy for cancer, the treatment program must also include nutritional protocols to reduce the proinflammatory state.
Patel, Zarana; Huff, Janice; Saha, Janapriya; Wang, Minli; Blattnig, Steve; Wu, Honglu; Cucinotta, Francis
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
Gómez, Rossana; Monteiro, Henrique; Cossio-Bolaños, Marco Antonio; Fama-Cortez, Domingo; Zanesco, Angelina
Chronic degenerative diseases constitute one of the main causes of death at a global level, and their significant increase has alerted many countries, which are taking measures to reduce risk factors, some of which are modifiable; being the regular exercise a means of prevention and rehabilitation of these diseases. The objective of this revision is to analyze the necessary parameters to take into account for the prescription of an exercise program in patients with obesity, high blood pressure dyslipidemia and diabetes mellitus type 2.
Bydder, G M
Objective: This study compared T1 fluid attenuation inversion recovery (FLAIR) and T1 turbo spin echo (TSE) sequences for evaluation of cervical spine degenerative disease at 3 T. Methods: 72 patients (44 males and 28 females; mean age of 39 years; age range, 27–75 years) with suspected cervical spine degenerative disease were prospectively evaluated. Sagittal images of the spine were obtained using T1 FLAIR and T1 TSE sequences. Two experienced neuroradiologists compared the sequences qualitatively and quantitatively. Results: On qualitative evaluation, cerebrospinal fluid (CSF) nulling and contrast at cord–CSF, disc–CSF and disc–cord interfaces were significantly higher on fast T1 FLAIR images than on T1 TSE images (p < 0.001). No significant difference was seen between the sequences in evaluation of neural foramina and bone–disc interface. On quantitative evaluation, the signal-to-noise ratios of cord and CSF on fast T1 FLAIR images were significantly higher than those on T1 TSE images (p < 0.05). Contrast-to-noise ratios (CNRs) of cord to CSF on T1 FLAIR images were significantly higher than those of T1 TSE images (p < 0.05). CNRs of bone to disc for T1 weighted TSE images were significantly higher than those of T1 FLAIR images (p < 0.05). Conclusion: At 3 T, T1 FLAIR imaging is superior to T1 TSE for evaluating cervical spine degenerative disease, owing to higher cord–CSF, disc–cord and disc–CSF contrast. However, intrinsic cord contrast is low on T1 FLAIR images. Advances in knowledge: T1 FLAIR is more promising and sensitive than T1 TSE for evaluation of degenerative spondyloarthropathy and may provide a foundation for development of MR protocols for early detection of degenerative and neoplastic diseases. PMID:25010068
Holan, Vladimir; Hermankova, Barbora; Kossl, Jan
Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy and glaucoma, mostly affect the elderly population, and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell-based therapy which could replace diseased or missing retinal cells, and support regeneration. In this respect, mesenchymal stem cells (MSCs) which can be obtained from the particular patient, and used as autologous cells, have turned out to be a promising stem cell type for treatment. Here we show that MSCs can differentiate into cells expressing markers of retinal cells, inhibit production of proinflammatory cytokines by retinal tissue and produce a number of growth and neuroprotective factors for retinal regeneration. All of these properties make MSCs a prospective cell type for cell-based therapy of age-related retinal degenerative diseases.
Nicoară, Simona Delia; Șușman, Sergiu; Tudoran, Oana; Bărbos, Otilia; Cherecheș, Gabriela; Aștilean, Simion; Potara, Monica; Sorițău, Olga
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
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.
Zook, Jason; Djurasovic, Mladen; Crawford, Charles; Bratcher, Kelly; Glassman, Steven; Carreon, Leah
Clinicians use descriptive classification systems when treating patients with low back pain as an adjunct to surgical decision making. Magnetic resonance imaging (MRI) changes, including Modic changes, the presence of a high-intensity zone, and internal disk desiccation, are commonly used descriptors. The question remains whether different clinicians interpret these terms similarly. This study evaluated the inter- and intraobserver reliability of commonly used MRI classifications in patients presenting with low back pain.Sixty-six patients who underwent lumbar spine fusion surgery at a single multiphysician spine specialty practice for degenerative disk disease were identified. For each surgical level, the following MRI variables were determined independently by 3 fellowship-trained spine surgeons: presence or absence of high-intensity zone and/or internal disk desiccation, presence and classification of disk herniation, Modic grade, and disk height. Each surgeon reviewed the same set of MRI studies a second time at least 2 weeks from the first reading. Inter- and intraobserver reliability was determined using multiobserver Kappa coefficients. Intraobserver reliability ranged from 0.563 to 0.988, with greatest agreement in determining disk height. The greatest interobserver agreement was for determining Modic changes (0.819).Controversy remains on the criteria for diagnosing degenerative disk disease. In patients presenting with low back pain diagnosed with degenerative disk disease, the inter- and intraobserver reliability with use of several common MRI diagnostic tools was substantial. These data imply that clinicians interpret these findings in a reproducible fashion and interpret these terms similarly. Copyright 2011, SLACK Incorporated.
Zhang, Yang; Shan, Jian-Lin; Liu, Xiu-Mei; Li, Fang; Guan, Kai; Sun, Tian-Sheng
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
Shchedrenok, V V; Zakhmatova, T V; Zuev, I V; Moguchaia, O V; Topol'skova, N V; Sebelev, K I; Malova, A M
The article presents the results of examination and surgery of 185 patients with degenerative diseases as well as with a cervical spine trauma. The circulatory disturbance of the vertebral artery took place in all patients. A different degree of changes was observed in color duplex scanning. There were minor circulatory disturbances, course deformations (angular, C, S, V-shaped twists) and dissection of the vertebral artery. Color duplex scanning allowed estimating of local and system hemodynamic significance of extravasal influences. The strategy of treatment and volume of surgical interference were defined by the degree of circulatory disturbance in the vertebral artery.
Japan became a superaging society. We have been putting a new focus on locomotive syndrome and frailty. The prevention and treatment of locomotive syndromes, such as osteoarthritis, degenerative spondylosis, lumbar canal stenosis, osteoporosis, upper extremity diseases, rheumatoid arthritis, and many other disorders of the locomotive organs are important. Because, the locomotive syndrome results in deterioration of the exercise function and loss of mental and physical health. The aim of locomotive syndrome exercises are: to reduce pain, to restore and improve joint function. We need to take a comprehensive approach to locomotive syndrome, including lifestyle modification, muscle exercise, stretching and therapeutic exercise.
Baldi, D; Izzotti, A; Bonica, P; Pera, P; Pulliero, A
Chronic-degenerative dentistry diseases, including periodontal diseases and oral osteonecrosis, are widespread in human populations and represent a significant problem for public health. These diseases result from pathogenic mechanisms created by the interaction between environmental genotoxic risk-factors and genetic assets conferring individual susceptibility. Osteonecrosis occurs in subjects undergoing exposure to high doses of DNA-damaging agents for chemo- and radiotherapy of neoplastic diseases. In susceptible patients, ionizing radiation and biphosphonate-chemotherapy induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular necrosis of the jaw. This may also occur in patients receiving biphosphonate for osteoporosis therapy. Periodontal diseases include chronic, aggressive, and necrotizing periodontitis, often resulting in severe alteration of periodontal tissues and tooth loss. Cigarette smoking and chronic inflammation caused by specific bacteria are the main risk factors for periodontitis. Oxidative damage plays a fundamental pathogenic role, as established by detection of mitochondrial DNA damage in the gingival tissue of patients with periodontitis. Endogenous risk factors in dental diseases include polymorphisms for metabolic enzymes such as glutathione transferases M1 and T1, N-acetyl transferase 2, and CYP 1A1. Other genetic polymorphisms that confer susceptibility to dentistry diseases affect genes encoding metalloproteases (involved in periodontal tissue remodeling and degradation), cytokines (involved in inflammation), prothrombin, and DNA repair activities. These findings provide evidence that dentistry diseases are related to risk factors associated with environmental mutagenesis. This issue warrants future investigations aimed at improving oral health and preventing oral degenerative diseases using molecular and experimental approaches currently utilized in mutagenicity studies.
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
Uddanapalli, Srinivasan Sreeramulu
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. To develop a new classification scheme of CASP. A review of the literature did not reveal a practically applicable classification incorporating the occurrence of CASP in congenital and degenerative fusion cases. 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. 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). 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.
Ignatieva, Natalia; Zakharkina, Olga; Andreeva, Irina; Sobol, Emil; Kamensky, Vladislav; Lunin, Valery
The number of in vitro experimental studies was carried out with the use of intact tissues to establish a mechanism of laser-tissue interaction. However, in the process of degeneration, both biochemical composition and behavior of the disc were altered drastically. The objective of this study was to evaluate the role of the main matrix components in laser modification of annulus fibrosus (AF) under IR laser irradiation. The samples of AF in a motion segment after hyaluronidase treatment, trypsin digestion and glycation by glyceraldehyde were heated in hydrothermal bath (95 degrees C, 2 min) or irradiated by laser at 1.56 microm. Specimens were imaged by cross-polarization optical coherence tomography (CP-OCT), and then analyzed by differential scanning calorimery (DSC). According to CP-OCT and DSC data non-significant alteration was revealed in AF after hyaluronidase treatment, glycation led to stabilization of annulus collagen and trypsin digestion resulted in a noticeable impairment of collagen fibrils. Laser treatment induced subsequent damages of AF matrix but these damages cannot be explained by laser heating only. The specificity of chemical modification of AF matrix has an influence on a character of collagen network alteration due to IR laser effect. Minimal and maximal alterations are observed for hyaluronidase and trypsin treated samples respectively. Glyceraldehyde fixed samples showed failure of the collagen structure after moderate laser treatment; at the same time thermal denaturation of collagen macromolecules was negligible. We assume that a mechanical effect of laser irradiation plays an important role in laser-induced annulus collagen modification and propose the scheme of physico-chemical process occurring under non-uniform IR laser treatment in AF tissue. CP-OCT and DSC techniques allow us to record the alteration of collagen network organization as a result of chemical modification. There were detected significant and specific effects of the
Martocchia, Antonio; Stefanelli, Manuela; Falaschi, Giulia Maria; Toussan, Lavinia; Ferri, Claudio; Falaschi, Paolo
The metabolic syndrome (MetS) presents an increasing prevalence in elderly people. A significant role in MetS is played by the stress response and cortisol. The hypothalamic-pituitary-adrenal (HPA) axis activity is increased by central (loss of hippocampal glucocorticoid receptors) and peripheral (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1, hyperactivity) mechanisms. The HPA hyperactivity has been found in chronic diseases affecting the endocrine (abdominal obesity with MetS, type 2 diabetes), cardiovascular (atherosclerosis, essential hypertension), and nervous systems (dementia, depression), in aging. A novel therapeutic approach (11β-HSD1 inhibition) is promising in treating the HPA axis hyperactivity in chronic diseases with MetS. A large-scale national clinical trial (AGICO, AGIng, and COrtisol study) has been proposed by our group to evaluate the role of cortisol and MetS in the main pathologies of aging (vascular and degenerative dementia, cardiovascular diseases, type 2 diabetes, abdominal obesity).
Rojas-Sepúlveda, Claudia; Ardagna, Yann; Dutour, Olivier
Major manifestations of vertebral degenerative joint disease were observed on a Pre-Columbian Muisca series from the Soacha Cemetery (11th to 13th centuries) Colombia, South America. In total, 1,646 vertebrae of 83 individuals were examined. Osteophytes, vertebral body joint surface contour change ("lipping"), and vertebral body pitting were evaluated for each vertebral body. For apophyseal joints, joint surface contour change, pitting, and eburnation were recorded. Two methods of frequency calculation and five for vertebral degenerative disease diagnosis were applied and compared, allowing discussion of methodological considerations. Our study showed that 83% of individuals and 32% of vertebrae were classified as positive when diagnosed by the presence of at least one of the following manifestations: osteophytes, vertebral body joint surface contour change ("lipping"), apophyseal joint surface contour change, or eburnation (method called "Pitting excluded"). No significant differences were found between the sexes. In the youngest cohort (15-30 years), 65% of individuals and 10% of vertebrae exhibit at least one of the previously mentioned manifestations. High prevalences suggest a high level of physical activity beginning in childhood which may have accelerated the aging process in this Pre-Columbian population. Historical data are compatible with this hypothesis. (c) 2008 Wiley-Liss, Inc.
Chu, Gregory H.; Lo, Pechin; Kim, Hyun J.; Auerbach, Martin; Goldin, Jonathan; Henkel, Keith; Banola, Ashley; Morris, Darren; Coy, Heidi; Brown, Matthew S.
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.
Lasbleiz, S; Quintero, N; Ea, K; Petrover, D; Aout, M; Laredo, J D; Vicaut, E; Bardin, T; Orcel, P; Beaudreuil, J
To assess the diagnostic value of clinical tests for degenerative rotator cuff disease (DRCD) in medical practice. Patients with DRCD were prospectively included. Eleven clinical tests of the rotator cuff have been done. One radiologist performed ultrasonography (US) of the shoulder. Results of US were expressed as normal tendon, tendinopathy or full-thickness tear (the reference). For each clinical test and each US criteria, sensitivity, specificity, negative predictive value and positive predictive value, accuracy, negative likelihood ratio (NLR) and positive likelihood ratio (PLR) were calculated. Clinical relevance was defined as PLR ≥2 and NLR ≤0.5. For 35 patients (39 shoulders), Jobe (PLR: 2.08, NLR: 0.31) and full-can (2, 0.5) test results were relevant for diagnosis of supraspinatus tears and resisted lateral rotation (2.42, 0.5) for infraspinatus tears, with weakness as response criteria. The lift-off test (8.50, 0.27) was relevant for subscapularis tears with lag sign as response criteria. Yergason's test (3.7, 0.41) was relevant for tendinopathy of the long head of the biceps with pain as a response criterion. There was no relevant clinical test for diagnosis of tendinopathy of supraspinatus, infraspinatus or subscapularis. Five of 11 clinical tests were relevant for degenerative rotator cuff disease. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Peng, Chun-Xia; Li, Gen-Lin
Recently, many studies indicated that certain medications can delay the apoptosis of retinal nerve cells at different points during the process of apoptosis and have neuroprotective effect on preventing degenerative ocular fundus diseases. N-methyl-D-aspartate receptor (NMDAR) antagonists, NMDAR-associated calcium channel blockers and acetylcholine receptor agonists have been shown to have neuroprotective effects for retinal damages by inhibiting NMDA-induced excitotoxicity. The inhibitors of nitric oxide synthase (NOS) can prevent the cell apoptosis and reduce the retinal cell loss by suppressing the activity of NOS as well as the production of the nitric oxide. Antioxidants and some Chinese traditional medicine with antioxidant activities can also have protective effect on retinal damage caused by degenerative ocular fundus diseases through their functions in decreasing the peroxidation reaction and the production of the superoxide radicals in the cells. In addition, activation of neurotrophic factor receptors by their ligands plays a key role in neuroprotective and trophic effects for the retina. All of these studies not only provide the foundation, but also offer new theoretical supports for drug neuroprotective therapies in clinical practice.
Tsai, Tsung-Ting; Cheng, Chao-Min; Chen, Chien-Fu; Lai, Po-Liang
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
Lewis, Daniel J; Attiah, Mark A; Malhotra, Neil R; Burnett, Mark G; Stein, Sherman C
Cost-effectiveness analysis with decision analysis and meta-analysis. To determine the relative cost-effectiveness of anterior cervical discectomy with fusion (with autograft, allograft, or spacers), anterior cervical discectomy without fusion (ACD), and cervical disc replacement (CDR) for the treatment of 1-level cervical disc disease. There is debate as to the optimal anterior surgical strategy to treat single-level cervical disc disease. Surgical strategies include 3 techniques of anterior cervical discectomy with fusion (autograft, allograft, or spacer-assisted fusion), ACD, and CDR. Several controlled trials have compared these treatments but have yielded mixed results. Decision analysis provides a structure for making a quantitative comparison of the costs and outcomes of each treatment. A literature search was performed and yielded 156 case series that fulfilled our search criteria describing nearly 17,000 cases. Data were abstracted from these publications and pooled meta-analytically to estimate the incidence of various outcomes, including index-level and adjacent-level reoperation. A decision analytic model calculated the expected costs in US dollars and outcomes in quality-adjusted life years for a typical adult patient with 1-level cervical radiculopathy subjected to each of the 5 approaches. At 5 years postoperatively, patients who had undergone ACD alone had significantly (P < 0.001) more quality-adjusted life years (4.885 ± 0.041) than those receiving other treatments. Patients with ACD also exhibited highly significant (P < 0.001) differences in costs, incurring the lowest societal costs ($16,558 ± $539). Follow-up data were inadequate for comparison beyond 5 years. The results of our decision analytic model indicate advantages for ACD, both in effectiveness and costs, over other strategies. Thus, ACD is a cost-effective alternative to anterior cervical discectomy with fusion and CDR in patients with single-level cervical disc disease. Definitive
Rajasekaran, S; Tangavel, Chitraa; Aiyer, Siddharth N; Nayagam, Sharon Miracle; Raveendran, M; Demonte, Naveen Luke; Subbaiah, Pramela; Kanna, Rishi; Shetty, Ajoy Prasad; Dharmalingam, K
Proteomic and 16S rDNA analysis of disc tissues obtained in vivo. To address the controversy of infection as an aetiology for disc disorders through protein profiling. There is raging controversy over the presence of bacteria in human lumbar discs in vivo, and if they represent contamination or infection. Proteomics can provide valuable insight by identifying proteins signifying bacterial presence and, also host defence response proteins (HDRPs), which will confirm infection. 22 discs (15-disc herniations (DH), 5-degenerate (DD), 2-normal in MRI (NM) were harvested intraoperatively and immediately snap frozen. Samples were pooled into three groups and proteins extracted were analysed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Post identification, data analysis was performed using Uniprotdb, Pantherdb, Proteome discoverer and STRING network. Authentication for bacterial presence was performed by PCR amplification of 16S rDNA. LC-MS/MS analysis using Orbitrap showed 1103 proteins in DH group, compared to 394 in NM and 564 in DD. 73 bacterial specific proteins were identified (56 specific for Propionibacterium acnes; 17 for Staphylococcus epidermidis). In addition, 67 infection-specific HDRPs, unique or upregulated, such as Defensin, Lysozyme, Dermcidin, Cathepsin-G, Prolactin-Induced Protein, and Phospholipase-A2, were identified confirming presence of infection. Species-specific primers for P. acnes exhibited amplicons at 946 bp (16S rDNA) and 515 bp (Lipase) confirming presence of P. acnes in both NM discs, 11 of 15 DH discs, and all five DD discs. Bioinformatic search for protein-protein interactions (STRING) documented 169 proteins with close interactions (protein clustering co-efficient 0.7) between host response and degenerative proteins implying that infection may initiate degradation through Ubiquitin C. Our study demonstrates bacterial specific proteins and host defence proteins to infection which strengthen the hypothesis of infection
Shur, Natalie; Corrigan, Alexis; Agrawal, Kanhaiyalal; Desai, Amidevi; Gnanasegaran, Gopinath
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
Shur, Natalie; Corrigan, Alexis; Agrawal, Kanhaiyalal; Desai, Amidevi; Gnanasegaran, Gopinath
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.
Koprivanac, Marijan; Kelava, Marta; Alansari, Shehab; Javadikasgari, Hoda; Tappuni, Bassman; Mick, Stephanie; Marc, Gillinov A; Suri, Rakesh; Mihaljevic, Tomislav
Given the increasing age of the US population and the accompanying rise in cardiovascular disease, we expect to see an increasing number of patients affected by degenerative mitral valve disease in a more complex patient population. Therefore, increasing the overall rate of mitral valve repair will become even more important than it is today, and the capability to provide a universally and uniformly accepted quality of repair will have important medical, economic, and societal implications. This article will describe preoperative and intraoperative considerations and the currently practiced mitral valve repair approaches and techniques. The aim of the article is to present our contemporary approach to mitral valve repair in the hope that it can be adopted at other institutions that may have low repair rates. Adoption of simple and reproducible mitral valve repair techniques is of paramount importance if we as a profession are to accomplish overall higher rates of mitral valve repair with optimal outcomes.
Kelava, Marta; Alansari, Shehab; Javadikasgari, Hoda; Tappuni, Bassman; Mick, Stephanie; Marc, Gillinov A.; Suri, Rakesh; Mihaljevic, Tomislav
Given the increasing age of the US population and the accompanying rise in cardiovascular disease, we expect to see an increasing number of patients affected by degenerative mitral valve disease in a more complex patient population. Therefore, increasing the overall rate of mitral valve repair will become even more important than it is today, and the capability to provide a universally and uniformly accepted quality of repair will have important medical, economic, and societal implications. This article will describe preoperative and intraoperative considerations and the currently practiced mitral valve repair approaches and techniques. The aim of the article is to present our contemporary approach to mitral valve repair in the hope that it can be adopted at other institutions that may have low repair rates. Adoption of simple and reproducible mitral valve repair techniques is of paramount importance if we as a profession are to accomplish overall higher rates of mitral valve repair with optimal outcomes. PMID:28203540
Newhouse, P A; Kelton, M
Advances in the understanding of the structure, function, and distribution of central nervous system (CNS) nicotinic receptors has provided the impetus for new studies examining the role(s) that these receptors and associated processes may play in CNS functions. Further motivation has come from the realization that such receptors are changed in degenerative neurologic diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Ongoing investigations of the molecular substructure of CNS nicotinic receptors and their pharmacology have begun to open up new possibilities for novel CNS therapeutics with nicotinic agents. Exploiting these possibilities will require understanding of the role(s) that these receptor systems play in human cognitive, behavioral, motor, and sensory functioning. Clues from careful studies of human cognition and behavior are beginning to emerge and will provide direction for studies of potentially therapeutic novel nicotinic agents. Modulation of these receptors with the ultimate goal of producing therapeutic benefits is the goal of these investigations and drug development. This paper will review studies from our laboratory and others that point to the importance of CNS nicotinic mechanisms in normal human cognitive and behavioral functioning as well as their role in disease states. In addition, this paper will examine potential clinical applications of nicotine and/or nicotinic agonists in a variety of CNS disorders with particular emphasis on structural brain disease including: movement disorders such as Parkinson's disease and Tourette's syndrome, cognitive/behavioral disorders such as Alzheimer's disease, attention deficit/hyperactivity disorder, and schizophrenia, and other more speculative applications. Important results from early therapeutic studies of nicotine and/or nicotinic agonists in these disease states are presented. For example, recent studies with nicotine and novel nicotinic agonists such as ABT-418 by our group
Kalbhen, D A
Due to their pharmacological properties most antiphlogistic/antirheumatic drugs are successfully used for treatment of inflammatory rheumatic diseases, but they are not able to counteract cartilage degeneration in osteoarthrosis. For specific therapy of osteoarthrosis only those drugs are suitable, which are able to inhibit enzymatic breakdown of articular cartilage, stimulate anabolic processes in cartilage, and to enhance the supply of nutritional and energy substrates for the cartilage cells. In this respect drugs such as Arteparon, Rumalon, Dona 200-S, Glyvenol or Pentosan polysulfate are of interest. A great number of pharmacological experiments have shown, that certain chondroprotective agents exert pronounced anti-degenerative effects, which can be quantitatively demonstrated in laboratory animals within 3 to 4 months by macroscopical, radiological and histological methods. Additional biochemical and in-vitro studies have elucidated some interesting chondro-protective, chondro-stimulatory or chondro-nutritive properties of certain drugs. In agreement with our experimental results clinical experiences have proved the efficacy of chondro-protective agents. Due to the bradytrophia of human articular cartilage a chondro-protective therapy may be only effective in long-term applications, resulting in a significant reduction of the intensity and progression of the degenerative joint destruction.
Yang, Xi; Song, Yueming; Kong, Qingquan; Gong, Quan; Pei, Fuxing; Tu, Chongqi
To evaluate the short-term effectiveness of nano-hydroxyapatite/polyamide-66 (n-HA/PA66) intervertebral cage for lumbar interbody fusion in the patients with lower lumbar degenerative diseases. Between January and October 2011, 20 patients with lower lumbar degenerative diseases underwent transforaminal lumbar interbody fusion with n-HA/PA66 intervertebral cage. There were 8 males and 12 females, aged 22-80 years (mean, 51 years). The disease duration was 1 to 24 months (mean, 4 months). L4,5 fusion was performed in 8 cases, L5, S1 fusion in 9 cases, and L4-S1 fusion in 3 cases. Among 20 cases, 3 were diagnosed as having recurrent lumbar disc protrusion, 5 as having lumbar degenerative spondylolisthesis, 9 as having lumbar isthmic spondylolisthesis, and 3 as having lumbar spinal stenosis. The intervertebral height and lordosis were measured on X-ray film to assess the surgical correction and postoperative sustain while osseous fusion was observed on 3-dimensional CT. The Oswestry disability index (ODI) and short-form 36 health survey scale (SF-36) scores were obtained to assess the status of clinical recovery. All patients had incision healing by first intention. The pain and numb were relieved in varying degrees after operation. No cerebrospinal leakage, nerve root injury, or wound infection was occurred. All patients were followed up 6-9 months (mean, 7 months). No cage displacement or collapse was found. The intervertebral height and lordosis of single fusion segment were significantly improved at 3 days and 3, 6 months after operation when compared with those at preoperation (P < 0.01); there was no significant difference among each time point after operation (P > 0.05). The fusion rate was 74% at 3 months after operation and 96% at 6 months after operation, with an average of 4 months (range, 3-9 months) for interbody fusion. The ODI and SF-36 scores were significantly improved at 3 days and 6 months after operation when compared with the scores at
Huang, Yijun; Meng, Qiang; Evans, Heather; Lober, William; Cheng, Yu; Qian, Xiaoning; Liu, Ji; Huang, Shuai
In this paper, we develop a novel formulation for contemporaneous patient risk monitoring by exploiting the emerging data-rich environment in many healthcare applications, where an abundance of longitudinal data that reflect the degeneration of the health condition can be continuously collected. Our objective, and the developed formulation, is fundamentally different from many existing risk score models for different healthcare applications, which mostly focus on predicting the likelihood of a certain outcome at a pre-specified time. Rather, our formulation translates multivariate longitudinal measurements into a contemporaneous health index (CHI) that captures patient condition changes over the course of progression. Another significant feature of our formulation is that, CHI can be estimated with or without label information, different from other risk score models strictly based on supervised learning. To develop this formulation, we focus on the degenerative disease conditions, for which we could utilize the monotonic progression characteristic (either towards disease or recovery) to learn CHI. Such a domain knowledge leads us to a novel learning formulation, and on top of that, we further generalize this formulation with a capacity to incorporate label information if available. We further develop algorithms to mitigate the challenges associated with the nonsmooth convex optimization problem by first identifying its dual reformulation as a constrained smooth optimization problem, and then, using the block coordinate descent algorithm to iteratively solve the optimization with a derived efficient projection at each iteration. Extensive numerical studies are performed on both synthetic datasets and real-world applications on Alzheimer's disease and Surgical Site Infection, which demonstrate the utility and efficacy of the proposed method on degenerative conditions that include a wide range of applications. Copyright © 2017 Elsevier Inc. All rights reserved.
Mattila, Ville M; Sihvonen, Raine; Paloneva, Juha; Felländer-Tsai, Li
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. 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. 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 10(5) 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 10(5) person-years in 1997 to 97 per 10(5) person-years in 2012, but not in Sweden. 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.
Byun, Kyunghee; Yoo, YongCheol; Son, Myeongjoo; Lee, Jaesuk; Jeong, Goo-Bo; Park, Young Mok; Salekdeh, Ghasem Hosseini; Lee, Bonghee
Advanced glycation end products (AGEs) and their receptor have been implicated in the progressions of many intractable diseases, such as diabetes and atherosclerosis, and are also critical for pathologic changes in chronic degenerative diseases, such as Alzheimer's disease, Parkinson's disease, and alcoholic brain damage. Recently activated macrophages were found to be a source of AGEs, and the most abundant form of AGEs, AGE-albumin excreted by macrophages has been implicated in these diseases and to act through common pathways. AGEs inhibition has been shown to prevent the pathogenesis of AGEs-related diseases in human, and therapeutic advances have resulted in several agents that prevent their adverse effects. Recently, anti-inflammatory molecules that inhibit AGEs have been shown to be good candidates for ameliorating diabetic complications as well as degenerative diseases. This review was undertaken to present, discuss, and clarify current understanding regarding AGEs formation in association with macrophages, different diseases, therapeutic and diagnostic strategy and links with RAGE inhibition.
Criscuolo, Chiara; Fabiani, Carlotta; Cerri, Elisa; Domenici, Luciano
Alzheimer’s disease (AD) and glaucoma are two distinct multifactorial neurodegenerative diseases, primarily affecting the elderly. Common pathophysiological mechanisms have been elucidated in the past decades. First of all both diseases are progressive, with AD leading to dementia and glaucoma inducing blindness. Pathologically, they all feature synaptic dysfunction with changes of neuronal circuitry, progressive accumulation of protein aggregates such as the beta amyloid (Aβ) and intracellular microtubule inclusions containing hyperphosphorylated tau, which belongs to microtubule associated protein family. During an early phase of degeneration, both diseases are characterized by synaptic dysfunction and changes of mitogen-activated protein kinases (MAPK). Common degenerative mechanisms underlying both diseases are discussed here, along with recent results on the potential use of the visual system as a biomarker for diagnosis and progression of AD. Common neuropathological changes and mechanisms in AD and glaucoma have facilitated the transfer of therapeutic strategies between diseases. In particular, we discuss past and present evidence for neuroprotective effects of brain-derived neurotrophic factor (BDNF). PMID:28289378
Veleri, Shobi; Lazar, Csilla H; Chang, Bo; Sieving, Paul A; Banin, Eyal; Swaroop, Anand
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.
Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand
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
Fat in the lumbar multifidus muscles - predictive value and change following disc prosthesis surgery and multidisciplinary rehabilitation in patients with chronic low back pain and degenerative disc: 2-year follow-up of a randomized trial.
Storheim, Kjersti; Berg, Linda; Hellum, Christian; Gjertsen, Øivind; Neckelmann, Gesche; Espeland, Ansgar; Keller, Anne
Evidence is lacking on whether fat infiltration in the multifidus muscles affects outcomes after total disc replacement (TDR) surgery and if it develops after surgery. The aims of this study were 1) to investigate whether pre-treatment multifidus muscle fat infiltration predicts outcome 2 years after treatment with TDR surgery or multidisciplinary rehabilitation, and 2) to compare changes in multifidus muscle fat infiltration from pre-treatment to 2-year follow-up between the two treatment groups. The study is secondary analysis of data from a trial with 2-year follow-up of patients with chronic low back pain (LBP) and degenerative disc randomized to TDR surgery or multidisciplinary rehabilitation. We analyzed (aim 1) patients with both magnetic resonance imaging (MRI) at pre-treatment and valid data on outcome measures at 2-year follow-up (predictor analysis), and (aim 2) patients with MRI at both pre-treatment and 2-year follow-up. Outcome measures were visual analogue scale (VAS) for LBP, Oswestry Disability Index (ODI), work status and muscle fat infiltration on MRI. Patients with pre-treatment MRI and 2-year outcome data on VAS for LBP (n = 144), ODI (n = 147), and work status (n = 137) were analyzed for prediction purposes. At 2-year follow-up, 126 patients had another MRI scan, and change in muscle fat infiltration was compared between the two treatment groups. Three radiologists visually quantified multifidus muscle fat in the three lower lumbar levels on MRI as <20% (grade 0), 20-50% (grade 1), or >50% (grade 2) of the muscle cross-section containing fat. Regression analysis and a mid-P exact test were carried out. Grade 0 pre-treatment multifidus muscle fat predicted better clinical results at 2-year follow-up after TDR surgery (all outcomes) but not after rehabilitation. At 2-year follow-up, increased fat infiltration was more common in the surgery group (intention-to-treat p = 0.03, per protocol p = 0.08) where it was related to
Jaovisidha, S; Techatipakorn, S; Apiyasawat, P; Laohacharoensombat, W; Poramathikul, M; Siriwongpairat, P
Due to a wide range of normal disk space heights at lumbosacral (LS) junction, we conducted this study to evaluate how to diagnose degenerative disk disease (DDD) of LS junction and how much information we can obtain from plain radiography regarding this condition. We retrospectively reviewed lateral LS spine films and magnetic resonance (MR) imaging in 100 patients presented with low back pain. Anterior disk height (ADH) and posterior disk height (PDH) were directly measured from plain radiographs. Signs of DDD were recorded from both plain radiographs and MR imaging. We found that ADH < 11.3 mm or PDH < 5.5 mm indicate DDD at LS junction with 95 per cent confidence interval. When spondylolisthesis presented, disks were all degenerated. Endplate sclerosis had significant relative risk (p < 0.05) for lateral neural canal stenosis and disk herniation. No radiographic finding showed significant relative risk for nerve root compression.
Nardi, G; Donato, F; Monarca, S; Gelatti, U
For many years a causal relation between drinking water hardness and cardiovascular or other chronic degenerative diseases in humans has been hypothesized. In order to evaluate the association between the concentration of minerals (calcium and magnesium) responsible for the hardness of drinking water and human health, a review of all the articles published on the subject from 1980 up to today has been carried out. The retrieved articles have been divided into 4 categories: geographic correlation studies, cross-sectional studies, case-control and cohort studies, and clinical trials. The methods for the selection of the articles and the extraction and analysis of the data are detailed in this paper. Epidemiological studies have been reviewed critically, and some conclusions have been drawn taking into account the research in basic sciences and experimental studies. However, a formal meta-analysis has not been performed, due to the heterogeneity of measures of effect among the different studies.
König, Stefan Alexander; Ranguis, Sebastian; Spetzger, Uwe
Background In different stages of cervical degenerative disk disease, the combination of dynamic and nondynamic implants may be considered. The aim of this study was to investigate the applicability of criteria to assist decision making in these cases. Methods Thirty patients with spondylotic cervical radiculopathy and a coincidence of soft disk and hard disk herniation were surgically treated with a hybrid solution (combination of total disk replacement and cage fusion). The control group included 32 patients who underwent two-level cage fusion. Pre- and postoperative Japanese Orthopaedic Association (JOA) scores and range of motion (ROM) were compared. Results Twenty-three patients underwent two-level hybrid solution and 7 underwent three-level treatment. The most frequent solution (n = 13) was a combination of a dynamic implant at C5-C6 and a nondynamic implant at C6-C7. The mean JOA score improved from 13.9 to 15.6 points after surgery (mean deviation [MD] 1.6, 95% confidence interval [CI] 2.1 to 1.2, p < 0.001). ROM showed a slight trend to increase (MD 0.8, 95% CI -0.9 to 2.6, p = 0.193). In the control group, the mean JOA score improved from 13.3 to 15.1 points after surgery (MD 1.4, 95% CI 2.1 to 1.2, p < 0.001). The comparison of the postoperative JOA scores and recovery rates between the hybrid treatment group and the control group did not show significant differences. Conclusions In cases of coincident soft and hard degenerative cervical disk disease at adjacent levels, the combination of a disk prosthesis and a nondynamic implant is a safe and effective treatment option and an alternative to multilevel fusion.
Abushkin, Ivan A.; Privalov, Valery A.; Lappa, Alexander V.; Noskov, Nikolay V.; Neizvestnykh, Elena A.; Kotlyarov, Alexander N.; Shekunova, Yulia G.
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.
Choi, Keum Hwa; Hill, Sara A
A 14-year-old male neutered domestic shorthair cat was admitted to the Veterinary Medical Center, University of Minnesota for evaluation of severe hind limb ataxia, atrophy and paresis. Diagnosis based on physical examination, neurological assessment and magnetic resonance imaging (MRI) was multifocal intervertebral disc disease (IVDD) with dorsal disc protrusion throughout the thoracic and cranial lumbar spine. The Oriental Medicine (OM) diagnosis (pattern identification) was painful obstruction (Bi) syndrome caused by phlegm-heat accumulation with blood stagnation in the spine. High dose prednisolone therapy (1.25mg/kg PO, once daily) initially did not show any significant improvement in clinical signs. The cat was then treated with several modes of acupuncture treatment including dry needle acupuncture, electro-acupuncture and scalp acupuncture along with Tui-Na (hand manipulation in OM) and physical therapy. Significant improvements in mobility, proprioception and spinal posture were noticed and the cat was able to rise, walk and run 4 months after starting acupuncture treatments. This is the first case report of feline IVDD with multiple sites of disc compression which was successfully treated with several modes of acupuncture treatment.
Wallace, Douglas C.
Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the age-related diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today. PMID:16285865
Thomason, J D; Fallaw, T L; Carmichael, K P; Radlinsky, M A; Calvert, C A
Calcium channel blocking drugs, usually nifedipine and less often amlodipine, have been reported to cause gingival hyperplasia (GH) in humans. Amlodipine, a dihydropyridine calcium channel blocking drug, can cause GH when administered chronically to older small dogs with degenerative valvular disease. From January 2004 to May 2008, 82 client-owned dogs with degenerative valvular disease and left atrial dilatation were treated with amlodipine in combination with spironolactone and enalapril and followed for >6 months. Retrospective study. A chronological observation of GH in 2 dogs treated with amlodipine in 2004 and 2006 prompted the study. Patient histories and medical records of each dog treated with amlodipine for degenerative valvular disease from January 2004 to May 2008 were reviewed. GH was observed by clients and the authors in 7 of 82 (8.5%) dogs. Histologic confirmation of the diagnosis was made in 2 dogs. The minimum duration of treatment before diagnosis of GH was 5 months. GH began to resolve within 2 weeks of discontinuing amlodipine and resolution was complete within 6 months. Amlodipine administration was reinstituted in 1 dog in which GH had resolved, and GH reoccurred within 4 months. Long-term administration of amlodipine to dogs with degenerative valvular disease may cause GH in a small percentage of patients. GH resolves quickly after withdrawal of amlodipine treatment.
Deukmedjian, Ara J.; Jason Cutright, S. T.; Augusto Cianciabella, PA-C; Deukmedjian, Arias
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
Bobinger, Tobias; May, Lisa; Lücking, Hannes; Kloska, Stephan P.; Burkardt, Petra; Spitzer, Philipp; Maler, Juan M.; Corbeil, Denis; Huttner, Hagen B.
Background: Analysis of cerebrospinal fluid (CSF) is a frequently used diagnostic tool in a variety of neurological diseases. Recent studies suggested that investigating membrane particles enriched with the stem cell marker CD133 may offer new avenues for studying neurological disease. In this study, we evaluated the amount of membrane particle-associated CD133 in human CSF in neuroinflammatory and degenerative diseases. Methods: We compared the amount of membrane particle-associated CD133 in CSF samples collected from 45 patients with normal pressure hydrocephalus, parkinsonism, dementia, and cognitive impairment, chronic inflammatory diseases and 10 healthy adult individuals as controls. After ultracentrifugation of CSF, gel electrophoresis and immunoblotting using anti-CD133 monoclonal antibody 80B258 were performed. Antigen-antibody complexes were detected using chemiluminescence. Results: The amount of membrane particle-associated CD133 was significantly increased in patients with normal pressure hydrocephalus (p < 0.001), parkinsonism (p = 0.011) as well as in patients with chronic inflammatory disease (p = 0.008). Analysis of CSF of patients with dementia and cognitive impairment revealed no significant change compared with healthy individuals. Furthermore, subgroup analysis of patients with chronic inflammatory diseases demonstrated significantly elevated levels in individuals with relapsing-remitting multiple sclerosis (p = 0.023) and secondary progressive multiple sclerosis (SPMS; p = 0.010). Conclusion: Collectively, our study revealed elevated levels of membrane particle-associated CD133 in patients with normal pressure hydrocephalus, parkinsonism as well as relapsing-remitting and SPMS. Membrane glycoprotein CD133 may be of clinical value for several neurological diseases. PMID:28396625
Deukmedjian, Ara J.; Cianciabella, Augusto; Cutright, Jason; Deukmedjian, Arias
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
Hu, Zhijun; Chen, Kai; Shan, Zhi; Chen, Shuai; Wang, Jiying; Mo, Jian; Ma, Jianjun; Xu, Wenbing; Qin, An; Fan, Shunwu
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
Petchdee, Soontaree; Sompeewong, Sarunya
Aim: The objective of this study is to investigate the improvement of heart function in dogs with chronic valvular heart disease after puppy deciduous teeth stem cells (pDSCs) administration. Materials and Methods: 20 client-owned dogs with degenerative valvular heart disease underwent multiple intravenous injections of allogeneic pDSCs. Dogs were randomly assigned to two groups: (i) Control group (n=10) with standard treatment for heart failure and (ii) group with standard treatment and multiple administrations of pDSCs (n=10). Electrocardiography, complete transthoracic echocardiography, thoracic radiography, and blood pressure were recorded before and after pDSCs injections for 15, 30 and 60 days. Results: Post pDSCs injection showed measurable improvement in left ventricular ejection fraction, American College of Veterinary Internal Medicine (ACVIM) functional class significantly improved and improved quality of life scores were observed. In the control group, there were no significant enhancements in heart function or ACVIM class. Conclusions: This finding suggests that pDSCs could be a supplement for valvular heart disease treatment. PMID:28096616
Videan, Elaine N; Lammey, Michael L; Lee, D Rick
Degenerative joint disease (DJD), also known as osteoarthritis, has been well documented in aging populations of captive and free-ranging macaques; however, successful treatments for DJD in nonhuman primates have not been published. Published data on chimpanzees show little to no DJD present in the wild, and there are no published reports of DJD in captive chimpanzees. We report here the first documented case of DJD of both the right and left femorotibial joints in a captive male chimpanzee. Progression from minimal to moderate to severe osteoarthritis occurred in this animal over the course of 1 y. Treatment with chondroprotective supplements (that is, glucosamine chondroitin, polysulfated glycosaminoglycan) and intraarticular corticosteroid injections (that is, methylprednisolone, ketorolac), together with pain management (that is, celecoxib, tramadol, carprofen), resulted in increased activity levels and decreased clinical signs of disease. DJD has a considerable negative effect on quality of life among the human geriatric population and therefore is likely to be one of the most significant diseases that will affect the increasingly aged captive chimpanzee population. As this case study demonstrates, appropriate treatment can improve and extend quality of life dramatically in these animals. However, in cases of severe osteoarthritis cases, medication alone may be insufficient to increase stability, and surgical options should be explored. PMID:21439223
Gomez, Rodolfo; Lago, Francisca; Gomez-Reino, Juan; Dieguez, Carlos; Gualillo, Oreste
The discovery of leptin in 1994 marked the beginning of a new understanding about white adipose tissue (WAT) and modified a static vision of this tissue which was viewed up to the end of the 20th century as an inert tissue, devoted to body protection from heat loss and to passively storing energy. The identification of the product of the gene obese accentuated the role of adipose tissue in the physiopathology of obesity-linked diseases, and led to the discovery of various adipokines, many of a pro-inflammatory nature. It has become progressively manifest that WAT-derived adipokines can now be considered as the fulcrum between obesity-related environmental causes, such as nutrition and lifestyle, and the biochemical shifts that lead to metabolic syndrome, inflammatory and/or autoimmune conditions, and rheumatic diseases. Herein, we review recent adipokine research, with particular emphasis to the role of leptin, adiponectin, resistin, and visfatin in chondrocyte function and skeleton, as well as in inflammatory and degenerative cartilage joint diseases.
Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Bujnak, Alyssa C.; Katz, Martin L.
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
Kelly, G S
Successful treatment of osteoarthritis must effectively control pain, and should slow down or reverse progression of the disease. Biochemical and pharmacological data combined with animal and human studies demonstrate glucosamine sulfate is capable of satisfying these criteria. Glucosamine sulfate's primary biological role in halting or reversing joint degeneration appears to be directly due to its ability to act as an essential substrate for, and to stimulate the biosynthesis of, the glycosaminoglycans and the hyaluronic acid backbone needed for the formation of proteoglycans found in the structural matrix of joints. Chondroitin sulfates, whether they are absorbed intact or broken into their constituent components, similarly provide additional substrates for the formation of a healthy joint matrix. Evidence also supports the oral administration of chondroitin sulfates for joint disease, both as an agent to slowly reduce symptoms and to reduce the need for non-steroidal anti-inflammatory drugs. The combined use of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease has become an extremely popular supplementation protocol in arthritic conditions of the joints. Although glucosamine sulfate and chondroitin sulfates are often administered together, there is no information available to demonstrate the combination produces better results than glucosamine sulfate alone.
Videan, Elaine N; Lammey, Michael L; Lee, D Rick
Degenerative joint disease (DJD), also known as osteoarthritis, has been well documented in aging populations of captive and free-ranging macaques; however, successful treatments for DJD in nonhuman primates have not been published. Published data on chimpanzees show little to no DJD present in the wild, and there are no published reports of DJD in captive chimpanzees. We report here the first documented case of DJD of both the right and left femorotibial joints in a captive male chimpanzee. Progression from minimal to moderate to severe osteoarthritis occurred in this animal over the course of 1 y. Treatment with chondroprotective supplements (that is, glucosamine chondroitin, polysulfated glycosaminoglycan) and intraarticular corticosteroid injections (that is, methylprednisolone, ketorolac), together with pain management (that is, celecoxib, tramadol, carprofen), resulted in increased activity levels and decreased clinical signs of disease. DJD has a considerable negative effect on quality of life among the human geriatric population and therefore is likely to be one of the most significant diseases that will affect the increasingly aged captive chimpanzee population. As this case study demonstrates, appropriate treatment can improve and extend quality of life dramatically in these animals. However, in cases of severe osteoarthritis cases, medication alone may be insufficient to increase stability, and surgical options should be explored.
Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Bujnak, Alyssa C; Katz, Martin L
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.
Wang, Q; Charych, EI; Pulito, VL; Lee, JB; Graziane, NM; Crozier, RA; Revilla-Sanchez, R; Kelly, MP; Dunlop, AJ; Murdoch, H; Taylor, N; Xie, Y; Pausch, M; Hayashi-Takagi, A; Ishizuka, K; Seshadri, S; Bates, B; Kariya, K; Sawa, A; Weinberg, RJ; Moss, SJ; Houslay, MD; Yan, Z; Brandon, NJ
Disrupted in schizophrenia 1 (DISC1), a genetic risk factor for multiple serious psychiatric diseases including schizophrenia, bipolar disorder and autism, is a key regulator of multiple neuronal functions linked to both normal development and disease processes. As these diseases are thought to share a common deficit in synaptic function and architecture, we have analyzed the role of DISC1 using an approach that focuses on understanding the protein– protein interactions of DISC1 specifically at synapses. We identify the Traf2 and Nck-interacting kinase (TNIK), an emerging risk factor itself for disease, as a key synaptic partner for DISC1, and provide evidence that the DISC1–TNIK interaction regulates synaptic composition and activity by stabilizing the levels of key postsynaptic density proteins. Understanding the novel DISC1–TNIK interaction is likely to provide insights into the etiology and underlying synaptic deficits found in major psychiatric diseases. PMID:20838393
Alexander, Peter G; Gottardi, Riccardo; Lin, Hang; Lozito, Thomas P; Tuan, Rocky S
Tissue engineered constructs have the potential to function as in vitro pre-clinical models of normal tissue function and disease pathogenesis for drug screening and toxicity assessment. Effective high throughput assays demand minimal systems with clearly defined performance parameters. These systems must accurately model the structure and function of the human organs and their physiological response to different stimuli. Musculoskeletal tissues present unique challenges in this respect, as they are load-bearing, matrix-rich tissues whose functionality is intimately connected to the extracellular matrix and its organization. Of particular clinical importance is the osteochondral junction, the target tissue affected in degenerative joint diseases, such as osteoarthritis (OA), which consists of hyaline articular cartilage in close interaction with subchondral bone. In this review, we present an overview of currently available in vitro three-dimensional systems for bone and cartilage tissue engineering that mimic native physiology, and the utility and limitations of these systems. Specifically, we address the need to combine bone, cartilage and other tissues to form an interactive microphysiological system (MPS) to fully capture the biological complexity and mechanical functions of the osteochondral junction of the articular joint. The potential applications of three-dimensional MPSs for musculoskeletal biology and medicine are highlighted.
Stieger, Knut; Chauveau, Christine; Rolling, Fabienne
Inherited retinal diseases are non-lethal and have a wide level of genetic heterogeneity. Many of the genes involved have now been identified and their function elucidated, providing a major step towards the development of gene-based treatments. The most widely used vectors for ocular gene delivery are based on adeno-associated virus (AAV) because they mediate long-term transgene expression in a variety of retinal cell types and elicit minimal immune responses. Extensive preclinical evaluation of gene transfer strategies in small and large animal models is key to the development of successful gene-based therapies for the retina. These preclinical studies have already allowed the field to reach the point where gene therapy to treat inherited blindness has been brought to clinical trial. In this manuscript, we focus on recombinant AAV-mediated specific gene therapy for recessive retinal degenerative diseases we describe the preclinical studies for the treatment of retinal degeneration caused by retinal pigmented epithelium (RPE) cells or photoreceptor defects and the immune response induced by retinal rAAV gene transfer.
Baird, Evan O.; Egorova, Natalia N.; McAnany, Steven J.; Qureshi, Sheeraz A.; Hecht, Andrew C.; Cho, Samuel K.
Study Design Retrospective population-based observational study. Objective To assess the growth of cervical spine surgery performed in an outpatient setting. Methods A retrospective study was conducted using the United States Healthcare Cost and Utilization Project's State Inpatient and Ambulatory Surgery Databases for California, New York, Florida, and Maryland from 2005 to 2009. Current Procedural Terminology, fourth revision (CPT-4) and International Classification of Diseases, ninth revision Clinical Modification (ICD-9-CM) codes were used to identify operations for degenerative cervical spine diseases in adults (age > 20 years). Disposition and complication rates were examined. Results There was an increase in cervical spine surgeries performed in an ambulatory setting during the study period. Anterior cervical diskectomy and fusion accounted for 68% of outpatient procedures; posterior decompression made up 21%. Younger patients predominantly underwent anterior fusion procedures, and patients in the eighth and ninth decades of life had more posterior decompressions. Charlson comorbidity index and complication rates were substantially lower for ambulatory cases when compared with inpatients. The majority (>99%) of patients were discharged home following ambulatory surgery. Conclusions Recently, the number of cervical spine surgeries has increased in general, and more of these procedures are being performed in an ambulatory setting. The majority (>99%) of patients are discharged home but the nature of analyzing administrative data limits accurate assessment of postoperative complications and thus patient safety. This increase in outpatient cervical spine surgery necessitates further discussion of its safety. PMID:25083354
Hodjat, Mahshid; Rahmani, Soheila; Khan, Fazlullah; Niaz, Kamal; Navaei-Nigjeh, Mona; Mohammadi Nejad, Solmaz; Abdollahi, Mohammad
Epigenotoxicology is an emerging field of study that investigates the non-genotoxic epigenetic effects of environmental toxicants resulting in alteration of normal gene expression and disruption of cell function. Recent findings on the role of toxicant-induced epigenetic modifications in the development of degenerative diseases have opened up a promising research direction to explore epigenetic therapy approaches and related prognostic biomarkers. In this review, we presented comprehensive data on epigenetic alterations identified in various diseases, including cancer, autoimmune disorders, pulmonary conditions as well as cardiovascular, gastrointestinal and bone disease. Although data on abnormalities of DNA methylation and their role in the development of diseases are abundant, less is known about the impact of histone modifications and microRNA expressions. Further, we discussed the effects of selected common environmental toxicants on epigenetic modifications and their association with particular abnormalities. A number of different environmental toxicants have been identified for their role in aberrant DNA methylation, histone modifications, and microRNA expression. Such epigenetic effects were shown to be tissue-type specific and highly associated with the level and duration of exposure. Finally, we described present and future therapeutic strategies, including medicines and dietary compounds for combating the toxicant-induced epigenetic alterations. There are currently seven histone deacetylase inhibitors and two DNA methyltransferase inhibitors approved for clinical use and many other promising candidates are in preclinical and clinical testing. Dietary compounds are thought to be the effective and safe strategies for treating and prevention of epigenetic pathophysiological conditions. Still more concentrated epigenetic researches are required for evaluation of chemical toxicity and identifying the causal association between key epigenetic alteration and
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
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
Hohaus, C; Ganey, T M; Minkus, Y; Meisel, H J
Low back pain is an extremely common symptom, affecting nearly three-quarters of the population sometime in their life. Given that disc herniation is thought to be an extension of progressive disc degeneration that attends the normal aging process, seeking an effective therapy that staves off disc degeneration has been considered a logical attempt to reduce back pain. The most apparent cellular and biochemical changes attributable to degeneration include a decrease in cell density in the disc that is accompanied by a reduction in synthesis of cartilage-specific extracellular matrix components. With this in mind, one therapeutic strategy would be to replace, regenerate, or augment the intervertebral disc cell population, with a goal of correcting matrix insufficiencies and restoring normal segment biomechanics. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. We designed an animal study using the dog as our model to investigate this hypothesis by transplantation of autologous disc-derived chondrocytes into degenerated intervertebral discs. As a result we demonstrated that disc cells remained viable after transplantation; transplanted disc cells produced an extracellular matrix that contained components similar to normal intervertebral disc tissue; a statistically significant correlation between transplanting cells and retention of disc height could displayed. Following these results the Euro Disc Randomized Trial was initiated to embrace a representative patient group with persistent symptoms that had not responded to conservative treatment where an indication for surgical treatment was given. In the interim analyses we evaluated that patients who received autologous disc cell transplantation had greater pain reduction at 2 years compared with patients who did not receive cells following their discectomy surgery and discs in patients that
Kepler, Christopher K; Ponnappan, Ravi K; Tannoury, Chadi A; Risbud, Marakand V; Anderson, David G
Intervertebral disc (IVD) degeneration remains a clinically important condition for which treatment is costly and relatively ineffective. The molecular basis of degenerative disc disease has been an intense focus of research recently, which has greatly increased our understanding of the biology underlying this process. To review the current understanding of the molecular basis of disc degeneration. Review article. A literature review was performed to identify recent investigations and current knowledge regarding the molecular basis of IVD degeneration. The unique structural requirements and biochemical properties of the disc contribute to its propensity toward degeneration. Mounting evidence suggests that genetic factors account for up to 75% of individual susceptibility to IVD degeneration, far more than the environmental factors such as occupational exposure or smoking that were previously suspected to figure prominently in this process. Decreased extracellular matrix production, increased production of degradative enzymes, and increased expression of inflammatory cytokines contribute to the loss of structural integrity and accelerate IVD degeneration. Neurovascular ingrowth occurs, in part, because of the changing degenerative phenotype. A detailed understanding of the biology of IVD degeneration is essential to the design of therapeutic solutions to treat degenerative discs. Although significant advances have been made in explaining the biologic mediators of disc degeneration, the inhospitable biochemical environment of the IVD remains a challenging environment for biological therapies. Copyright © 2013 Elsevier Inc. All rights reserved.
Van de Kelft, Erik; Verguts, Leo
Arthrodesis is considered to be the reference treatment for degenerative disc disease (DDD), if the symptoms are refractory to conservative management. The drawback of arthrodesis is, besides a percentage of non-union, the reduced mobility that might generate an increased load and risk for degeneration of the adjacent levels. Total disc replacement (TDR) implants may overcome this problem. The long-term clinical effect and radiographic evaluation of motion preservation after implantation, however, have been subject to several nonconclusive studies. This study evaluated the long-term clinical and radiographic results and the safety of TDR with the Maverick prosthesis for surgical treatment of monosegmental DDD. TDR was performed in 50 consecutive patients with monosegmental DDD using the Maverick device. Patients were followed prospectively for disability, quality of life, pain intensity and frequency, as well as working status and return to sports, during 48 months. Motion preservation was assessed on neutral and dynamic radiographs at 48 months. The disability, pain intensity and frequency, and quality of life improved significantly at the 6-week follow-up, which was maintained over the full 48 months following Maverick implantation. Preoperatively, 80% of the patients stopped working and 86% halted sports activities. Four years after surgery, 85% of patients were again working and 79% took up their normal sports activities. Radiographic assessment showed that motion at the index level is maintained 48 months after TDR. No major complications were encountered. In this study, TDR with the Maverick prosthesis at one lumbar segment reduced pain and disability and improved quality of life as well as the general condition. Motion was preserved at the operated level, 48 months after surgery. The long-term effect on adjacent levels needs further follow-up. Copyright © 2012 Elsevier Inc. All rights reserved.
Fujioka, Masato; Tokano, Hisashi; Fujioka, Keiko Shiina; Okano, Hideyuki; Edge, Albert S.B.
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
Janković, Slavko; Kostić, Vladimir; Susić, Veselinka
Parasomnias are defined as unpleasant and undesirable behavioral (in the sense of action) or experiential (in the sense of sensorial or perceptive) phenomena which overwhelmingly or exclusively happen during sleep. Former attitudes that parasomnias are closely related to psychiatric derangement are abandoned and newer polysomnographic research indicates that we are dealing with a number of totally different organically defined states, most of which are easy to diagnose and even cure. The frequency of parasomnias in population is much higher than so far supposed so that they are considered among the most frequent disturbance of the CNS. Another inglorious record tightly connected to parasomnias is that they belong to the most frequently undiagnosed or misdiagnosed diseases. Clinically the most important and intriguing of the parasomnias associated with REM sleep, is REM sleep behavior disorder (RBD). In the last few decades in the field of human and animal sleep, researchers have noticed that RBD represents the omen of the more complex degenerative disorders of the central nervous system--the synucleinopathies and tauopathies. RBD can precede these disorders for decades before the florid clinical picture becomes obvious.
Talaga, Stanisława; Magiera, Zofia; Kowalczyk, Bożena; Lubińska-Żądło, Bogumiła
The aim of the study was to investigate health problems in patients with degenerative disease of the spine (the main reason for deterioration of physical fitness) and to determine the need for health education. The study involved 50 people. A diagnostic survey with an ad hoc questionnaire was used. Quality of life was assessed with the WHOQOL-BREF questionnaire. The HAQ-DI indicator of disability was used to assess the respondents' health status. Biological problems in the respondents included pain (60%). Psychological problems included a sense of inferiority (54%) and feeling lonely (24%). The most frequent difficulties in fulfilling social roles were problems associated with low social and occupational activity (56%). The patients assessed their health as significantly worse (p = 0.006) than the quality of their lives. The quality of life was the highest (67.9 points) in the social sphere, and the lowest (60.9 points) in the psychological sphere. 1. The main health problems reported by the study participants were cervical and lumbar spinal pain experienced during prolonged physical activity in the course of daily living activities. 2. The quality of life decreases with increasing difficulty in performing daily activities. 3. It is important to strengthen patients' belief that physical activity, including physiotherapy, has a positive impact on physical fitness and the ability to perform daily activities. 4. An important aim of the therapeutic team is to support and motivate patients to cope with difficult situations and function in society.
Gruen, M E; Dorman, D C; Lascelles, B D X
A literature review identified six placebo-controlled studies of analgesics in client-owned cats with degenerative joint disease-associated pain. Five studies with 96 cats had available data. Caregiver responses on a clinical metrology instrument, Client-Specific Outcome Measure (CSOM), were compared to measured activity. Cats were categorised as 'successes' or 'failures' based on change in CSOM score and activity counts from baseline. Effect sizes based on CSOM score were calculated; factors that were associated with success/failure were analysed using logistic regression. Effect sizes ranged from 0.97 to 1.93. The caregiver placebo effect was high, with 54-74 per cent of placebo-treated cats classified as CSOM successes compared with 10-63 per cent of cats classified as successes based on objectively measured activity. 36 per cent of CSOM successes were also activity successes, while 19 per cent of CSOM failures were activity successes. No significant effects of cat age, weight, baseline activity, radiographic score, orthopaedic pain score or study type on CSOM success in the placebo groups were found. The caregiver placebo effect across these clinical trials was remarkably high, making demonstration of efficacy for an analgesic above a placebo difficult. Further work is needed to determine whether a potential placebo-by-proxy effect could benefit cats in clinical settings.
Yu, Ivarosa Bing-Ye; Huang, Hui-Pi
In humans, heart failure (HF) and renal insufficiency (RI) have negative reciprocal effects, and anemia can exacerbate their progression. In this retrospective study, the prevalence and prognostic significance of anemia in 114 dogs with degenerative mitral valve disease (DMVD) was investigated. Pretreatment clinical parameters, prevalence of anemia and azotemia, and survival time were analyzed in relation to HF severity. The prevalence of anemia was highest in dogs with the modified New York Heart Association (NYHA) class IV HF (33.3%), followed by classes III (15.2%) and II (0%; p < 0.001). The presence of anemia was associated with HF severity and blood creatinine > 1.6 mg/dL (both p < 0.001). Anemic dogs had a shorter median survival [13 months; 95% confidence interval (CI): 0.7-19.1] than nonanemic dogs (28 months; 95% CI: 15.3-40.7; p < .001). NYHA class IV (hazard ratio (HR): 3.1, 95% CI: 2.2-4.3; p < 0.001), left atrium/aorta ratio > 1.7 (HR: 2.7, 95% CI: 1.7-4.2; p = 0.001), and presence of anemia (HR: 1.43, 95% CI: 1.1-1.9; p = 0.004) emerged as predictors of mortality. A cardiorenal-anemia syndrome-like triangle was observed and anemia was a prognostic factor for survival in dogs with DMVD.
Yu, Ivarosa Bing-Ye
In humans, heart failure (HF) and renal insufficiency (RI) have negative reciprocal effects, and anemia can exacerbate their progression. In this retrospective study, the prevalence and prognostic significance of anemia in 114 dogs with degenerative mitral valve disease (DMVD) was investigated. Pretreatment clinical parameters, prevalence of anemia and azotemia, and survival time were analyzed in relation to HF severity. The prevalence of anemia was highest in dogs with the modified New York Heart Association (NYHA) class IV HF (33.3%), followed by classes III (15.2%) and II (0%; p < 0.001). The presence of anemia was associated with HF severity and blood creatinine > 1.6 mg/dL (both p < 0.001). Anemic dogs had a shorter median survival [13 months; 95% confidence interval (CI): 0.7–19.1] than nonanemic dogs (28 months; 95% CI: 15.3–40.7; p < .001). NYHA class IV (hazard ratio (HR): 3.1, 95% CI: 2.2–4.3; p < 0.001), left atrium/aorta ratio > 1.7 (HR: 2.7, 95% CI: 1.7–4.2; p = 0.001), and presence of anemia (HR: 1.43, 95% CI: 1.1–1.9; p = 0.004) emerged as predictors of mortality. A cardiorenal-anemia syndrome-like triangle was observed and anemia was a prognostic factor for survival in dogs with DMVD. PMID:27840827
Kimura, Shinji; Hesselink, John R; Garfin, Steven R; Kawaji, Yoichi; Hasegawa, Kazuhiro; Hargens, Alan R
The objectives of this study were to simulate the upright loading condition in the cervical spine by applying a new compression device during supine posture and to assess intervertebral angles and cross-sectional areas of the spinal cord and dural tube before and during axial compression. A magnetic resonance (MR) imaging-compatible device was developed to create axial compression with the patient in the supine position. Lateral radiographs were obtained in upright and supine positions with an axial load of 0% (supine) and by applying a cervical compression device at 7, 10, and 13% of body weight (BW) in 18 control individuals and seven symptomatic patients with cervical degenerative disc disease (DDD). Additionally, cervical MR images acquired in 17 controls and 12 patients were compared before and during an axial load of 8.4% BW in terms of anteroposterior diameter and cross-sectional area of the dural sac. The supine intervertebral angles with loads of 0, 7, 10, and 13% of the individuals' BW relative to upright posture were -8.1+/-1.3, -2.3+/-1.4, 1.3+/-1.9, and 2.8+/-2 degrees, respectively. Subsequent axial force was interpolated as 8.9% of BW to simulate upright cervical spine alignment. Under an axial loading similar to that created by the upright posture, the dural sac narrowed at the C5-6 interspace in asymptomatic individuals and at the C6-7 interspace in patients with cervical DDD. This cervical compression device may be a useful tool to simulate upright cervical spinal alignment. The results of this study help in understanding the pathophysiology of symptoms related to cervical degenerative disorders in upright posture.
Freire, M; Meuten, D; Lascelles, D
The elbow joint is one of the feline appendicular joints most commonly and severely affected by degenerative joint disease. The macroscopic and histopathological lesions of the elbow joints of 30 adult cats were evaluated immediately after euthanasia. Macroscopic evidence of degenerative joint disease was found in 22 of 30 cats (39 elbow joints) (73.33% cats; 65% elbow joints), and macroscopic cartilage erosion ranged from mild fibrillation to complete ulceration of the hyaline cartilage with exposure of the subchondral bone. Distribution of the lesions in the cartilage indicated the presence of medial compartment joint disease (most severe lesions located in the medial coronoid process of the ulna and medial humeral epicondyle). Synovitis scores were mild overall and correlated only weakly with macroscopic cartilage damage. Intra-articular osteochondral fragments either free or attached to the synovium were found in 10 joints. Macroscopic or histologic evidence of a fragmented coronoid process was not found even in those cases with intra-articular osteochondral fragments. Lesions observed in these animals are most consistent with synovial osteochondromatosis secondary to degenerative joint disease. The pathogenesis for the medial compartmentalization of these lesions has not been established, but a fragmented medial coronoid process or osteochondritis dissecans does not appear to play a role.
Magdalou, Jacques; Ouzzine, Mohamed; Netter, Patrick; Fournel-Gigleux, Sylvie
Arthritis, osteoarthritis and other degenerative diseases characterized by cartilage deterioration are the most prevalent chronic human health disorders. Despite their major socioeconomic impact there is still no satisfactory treatment. Their frequency is increasing with the lengthening of life expectancy, creating a major public health challenge for coming years. It is important to diagnose such diseases at an early stage and to develop new effective therapies. We are attempting to develop new therapeutic approaches in this context, keeping in mind that cartilage is one of the few human tissues which is unable to regenerate. We intend to identify and characterize key proteins involved in the biosynthesis of cartilage matrix components. One innovative strategy consists of gene transfer, triggering overexpression of native or recombinant factors that can stimulate chondrocyte anabolic activity in order to promote cartilage repair The loss of matrix components, and especially glycosaminoglycans (GAG), is the earliest event in cartilage degeneration. We therefore looked at glycosyltransferases, and especially galactose beta1,3-glucuronosyltransferase-I (GlcAT-1), which catalyses one of the first steps in GAG biosynthesis. We found that any variation in GlcAT-I activity in chondrocytes or cartilage explants (overexpression, or repression with antisense RNA) affected the GAG content of cartilage. Interestingly, overexpression of this enzyme completely counteracted the GAG depletion produced by the proinflammatory cytokine interleukin 1-beta. The neosynthesized GAG was qualitatively identical to that present in the original cartilage matrix. These results are encouraging for therapeutic approaches based on gene transfer We also investigated the structure-function relationship of human recombinant GlcAT-I upon expression in the methyltrophic yeast Pichia pastoris. This allowed us to determine the molecular basis of the recognition of the donor and acceptor substrates of
Gruen, Margaret E.; Griffith, Emily H.; Thomson, Andrea E.; Simpson, Wendy; Lascelles, B. Duncan X.
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
Liu, Hui; Li, Sibei; Wang, Jiranru; Wang, Taiping; Yang, Hao; Li, Zemin; Li, Xiang; Zheng, Zhaomin
A retrospective and radiological study of degenerative spinal diseases. To explore the changes in spinopelvic sagittal alignment after lumbar instrumentation and fusion of degenerative spinal diseases. Efforts have been paid to clarify the ideal postoperative sagittal profile for degenerative spinal diseases. However, little has been published about the actual changes of sagittal alignment after lumbar lordosis reconstruction. Radiographical analysis of 83 patients with spinal degeneration was performed by measuring sagittal parameters before and after operations. Comparative studies of sagittal parameters between short (1 level) and long (≥ 2 level) instrumentation and fusion were performed. Different variances (Δ) of these sagittal parameters before and after operations were calculated and compared. Correlative study and linear regression were performed to establish the relationship between variances. No significant changes were shown in the short-fusion group postoperatively. In the long-fusion group, postoperative lumbar lordosis (LL) and sacral slope (SS) were significantly increased; pelvic tilt (PT), sagittal vertical axis (SVA), pelvic incidence minus lumbar lordosis, and PT/SS were significantly decreased. Different variances of ΔLL, ΔSS, ΔPT, ΔSVA, Δ(pelvic incidence - LL), and ΔPT/SS were significantly greater in the long-fusion group than the short-fusion group. Close correlations were mainly shown among ΔLL, ΔPT, and ΔSVA. Linear regression equations could be developed (ΔPT = -0.185 × ΔLL - 7.299 and ΔSVA = -0.152ΔLL - 1.145). In degenerative spinal diseases, long instrumentation and fusion (≥ 2 levels) provides more efficient LL reconstruction. PT, SS, and SVA improve corresponding to LL in a linear regression model. Linear regression equations could be developed and used to predict PT and SVA change after long instrumentation and fusion for LL reconstruction.
The lysosome is the main catabolic hub of the cell. Owing to its role in fundamental processes such as autophagy, plasma membrane repair, mTOR signaling, and maintenance of cellular homeostasis, the lysosome has a profound influence on cellular metabolism and human health. Indeed, inefficient or impaired lysosomal function has been implicated in the pathogenesis of a number of degenerative diseases affecting various organs and tissues, most notably the brain, liver, and muscle. The discovery of the coordinated lysosomal expression and regulation (CLEAR) genetic program and its master controller, transcription factor EB (TFEB), has provided an unprecedented tool to study and manipulate lysosomal function. Most lysosome-based processes—including macromolecule degradation, autophagy, lysosomal exocytosis, and proteostasis—are under the transcriptional control of TFEB. Interestingly, impaired TFEB signaling has been suggested to be a contributing factor in the pathogenesis of several degenerative storage diseases. Preclinical studies based on TFEB exogenous expression to reinstate TFEB activity or promote CLEAR network–based lysosomal enhancement have highlighted TFEB as a candidate therapeutic target for the treatment of various degenerative storage diseases. PMID:27299292
Zekaj, Edvin; Menghetti, Claudia; Saleh, Christian; Isidori, Alessandra; Bona, Alberto R.; Aimar, Enrico; Servello, Domenico
Background: Intraforaminal disc herniations at the L5-S1 level are extremely surgically challenging lesions. Intracanal approaches frequently require partial or total facetectomy, which may lead to instability. Solely extraforaminal approaches may offer limited visualization of the more medial superiorly exiting and inferiorly exiting nerve roots; this approach is also more complicated at L5-S1 due to the often large L5 transverse process and the iliac wing. Methods: Nine patients with intraforaminal L5-S1 disc herniations, foraminal stenosis, or synovial cysts underwent contralateral interlaminar approaches for lesion resection. Preoperative and postoperative visual analog scale scores were evaluated, and complications were reviewed. Results: All 9 patients demonstrated immediate postoperative clinical improvement. None of the patients exhibited complications and none developed instability or neuropathic disorders. Conclusions: Although the number of cases in our sample was very small (9 in total), the contralateral interlaminar approach appeared to effectively address multiple degenerative L5-S1 foraminal pathologies. Large studies are needed to further evaluate the pros and cons of this approach. PMID:27713854
Zekaj, Edvin; Menghetti, Claudia; Saleh, Christian; Isidori, Alessandra; Bona, Alberto R; Aimar, Enrico; Servello, Domenico
Intraforaminal disc herniations at the L5-S1 level are extremely surgically challenging lesions. Intracanal approaches frequently require partial or total facetectomy, which may lead to instability. Solely extraforaminal approaches may offer limited visualization of the more medial superiorly exiting and inferiorly exiting nerve roots; this approach is also more complicated at L5-S1 due to the often large L5 transverse process and the iliac wing. Nine patients with intraforaminal L5-S1 disc herniations, foraminal stenosis, or synovial cysts underwent contralateral interlaminar approaches for lesion resection. Preoperative and postoperative visual analog scale scores were evaluated, and complications were reviewed. All 9 patients demonstrated immediate postoperative clinical improvement. None of the patients exhibited complications and none developed instability or neuropathic disorders. Although the number of cases in our sample was very small (9 in total), the contralateral interlaminar approach appeared to effectively address multiple degenerative L5-S1 foraminal pathologies. Large studies are needed to further evaluate the pros and cons of this approach.
Woo, Eun Jin; Pak, Sunyoung
The purpose of this research is to examine whether degenerative joint diseases (DJD) and enthesopathies can be used in conjunction in research that aims to understand the activity levels of past populations. To examine this, the relationship between DJD and enthesopathies needs to be explored while taking different peripheral joints and types of entheses into account. In addition, the present research aims to examine the frequency of DJD and enthesopathies in the Joseon Dynasty population of Korea with comparisons with data in other skeletal series of similar dates. In this research, 173 individuals who had been interred in Eunpyeong Cemetery (Seoul, Korea, mid-15th-early 20th centuries) were analyzed. The occurrence of DJD and enthesopathies at six peripheral joints - the shoulder, elbow, wrist, hip, knee, and ankle - were compared. The results presented in this study suggest that DJD and enthesopathies are positively correlated in specific joints. The overall pattern of DJD and enthesopathies by sex was not found to be aligned with each other. While both markers were strongly associated with age in similar joints and bone elements, differences by sex showed a significant association in only some enthesopathies. This result suggests that DJD and enthesopathies react in different ways to variable etiological factors because they have different levels of vulnerability to various causes. Therefore, the distribution and pattern of DJD and enthesopathies should be discussed with caution when they are used together as activity markers. In addition, the population from Eunpyeong Cemetery seems not to have experienced a great deal of habitual stress.
Cohn, E L; Maurer, E J; Keats, T E; Dussault, R G; Kaplan, P A
Diagnosing degenerative disk disease (DDD) at the lumbosacral junction (LSJ) on plain films is often difficult, compared with other disk levels. The purpose of this study was to determine whether criteria for diagnosis of DDD at the LSJ can be established for plain films. We retrospectively reviewed 100 lumbar MRI scans of patients who also had lumbar plain films. Using MRI as the reference standard, the LSJ was classified as normal (n=35) or exhibiting mild (n=45) or severe (n=20) DDD by two radiologists using accepted criteria. Measurements were performed on the plain films by two other radiologists and the average measurements were tabulated according to the three categories of DDD defined by MRI. Plain film measurements included the anterior and posterior disk heights (ADH, PDH), Farfan's ratio, determined by adding ADH to PDH and dividing that number by the measured anteroposterior (AP) length of the inferior end plate of L5 [(ADH+PDH)/AP length of L5], and lumbosacral angle (LSA). Subsequently, five additional radiologists interpreted the radiographs by visual inspection only, for DDD at the LSJ, both before and, several weeks later, after being provided with the quantitative data for normal versus DDD. There was a statistically significant difference between normal disk and increasing severity of DDD on radiographs using the parameters of PDH and Farfan's ratio. There was no statistically significant difference regarding ADH or LSA. Diagnostic accuracy by visual inspection was not significantly altered using the quantitative data for interpretation of DDD (68% correct before, 69.5% correct after). Analysis of results indicates that PDH is the most reliable and easily used criterion for detection of DDD at the LSJ. A PDH < or =5.4 mm on plain lateral film indicates DDD; PDH > or =7.7 mm indicates the absence of DDD on plain film.
Klaus, Haagen D; Spencer Larsen, Clark; Tam, Manuel E
This study tests the hypothesis that the colonial economy of the Lambayeque region of northern coastal Peru was associated with a mechanically strenuous lifestyle among the indigenous Mochica population. To test the hypothesis, we documented the changes in the prevalence of degenerative joint disease (or DJD) in human remains from the late pre-Hispanic and colonial Lambayeque Valley Complex. Comparisons were made using multivariate odds ratios calculated across four age classes and 11 principle joint systems corresponding to 113 late pre-Hispanic and 139 postcontact adult Mochica individuals. Statistically significant patterns of elevated postcontact DJD prevalence are observed in the joint systems of the shoulder, elbow, wrist, and knee. More finely grained comparison between temporal phases indicates that increases in prevalence were focused immediately following contact in the Early/Middle Colonial period. Analysis of DJD by sex indicates postcontact males experienced greater DJD prevalence than females. Also, trends between pre- and postcontact females indicate nearly universally elevated DJD prevalence among native colonial women. Inferred altered behavioral uses of the upper body and knee are contextualized within ecological, ethnohistoric, and ethnoarchaeological frameworks and appear highly consistent with descriptions of the local postcontact economy. These patterns of DJD appear to stem from a synergism of broad, hemispheric level sociopolitical alterations, specific changes to Mochica activity and behavior, regional economic intensification, and local microenvironmental characteristics, which were all focused into these biological outcomes by the operation of a colonial Spanish political economy on the north coast of Peru from A.D. 1536 to 1751. Copyright 2009 Wiley-Liss, Inc.
Birch, David G; Wen, Yuquan; Locke, Kelly; Hood, Donald C
To evaluate the effects of selective rod and/or cone loss on frequency-domain optical coherence tomography (fdOCT) measures of photoreceptor structure in patients with retinal degenerative diseases. Six patients with cone dystrophy (CD) and eight patients with retinitis pigmentosa (RP) were recruited from the Southwest Eye Registry on the basis of diagnosis and ERG findings. fdOCT horizontal line scans were segmented to obtain the thicknesses of the outer segments plus RPE (OS+) and the outer nuclear layer (ONL). The normalized product ONL*OS was obtained after dividing by mean ONL*OS values of 23 normal individuals. Visual field sensitivity profiles were obtained with a modified retinal perimeter, from the horizontal midline with short- and long-wave stimuli under dark- and light-adapted conditions. Patients with CD and normal rod-mediated sensitivity, but decreased cone-mediated sensitivity, showed normal ONL*OS outside the fovea. The total receptor layer was thinned in the fovea, consistent with loss in cone nuclei and Henle's fiber layer. Patients with RP and sensitivity in the dark that was mediated by cones showed ONL*OS thickness that was linearly related to cone sensitivity. ONL*OS thickness was linearly related to rod sensitivity in regions with greater loss of cone than rod sensitivity. Both rods and cones can support an intact IS/OS junction and normal photoreceptor thickness measures. The product of ONL and OS thicknesses is proportional to the sensitivity mediated by the less abnormal type of photoreceptor.
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
Andelman, S Y
Thirty patients from a private practice were enrolled in an investigation designed to compare the efficacy and safety of a new nonsteroidal anti-inflammatory drug, etodolac, with those of aspirin and placebo in ameliorating pain, inflammation, and functional deficits associated with degenerative joint disease. The 12-week, double-blind, parallel-group study was divided into drug-titration and maintenance periods and was preceded by a washout period of up to two weeks. There were ten patients in each of the three treatment groups. The mean daily maintenance dosages of etodolac and aspirin were 384 mg and 4,322 mg, respectively. Etodolac was significantly (less than or equal to 0.05) more effective than placebo according to 11 of 15 clinical indexes of efficacy: three assessments of the range of motion of the knee joint, and one each of pain while standing, pain while walking, pain while climbing stairs, the average of pains while bearing weight, pain at night, joint tenderness, patient's self-evaluation, and the time required to walk 50 feet. Aspirin was significantly more effective than placebo in only three assessments: two of the range of motion of the knee joint and one of pain while standing. One patient taking etodolac, three patients taking aspirin, and six patients taking placebo withdrew from the trial because of insufficient therapeutic response. There were four withdrawals due to adverse effects, two in the aspirin group and two in the placebo group. Adverse effects (tinnitus and hearing loss) leading to withdrawal of one of the two aspirin patients were probably due to drug administration. No significant side effects were reported by patients in the etodolac group.
Winocur, E; Reiter, S; Krichmer, M; Kaffe, I
The purposes of the study were to evaluate the utility of diagnosing degenerative joint disease (DJD) by the clinical finding of coarse crepitus alone, without supporting imaging studies, as defined by the RDC/TMD, and to evaluate the contribution of panoramic radiography as an aid in the diagnosis of DJD. A retrospective analysis of 372 consecutive patients with TMD was conducted. Their panoramic radiographs were evaluated for the extent of their contribution to the final diagnosis. Panoramic radiography was of no diagnostic value in 94.4% of the cases when the group was considered as a whole. When patients diagnosed with DJD were considered separately, panoramic radiography was completely sufficient for reaching the final diagnosis in 20.0% of the cases. In almost 90% of these patients, however, the clinical examination did not support the diagnosis of DJD (no coarse crepitus was found). This raises some doubts about the effectiveness of the clinical examination according to the RDC/TMD and about the utility of panoramic radiography in the definitive diagnosis of DJD, because both techniques have low accuracy (11.1% and 20%, respectively). The present study supports the current recommendations that panoramic radiography should not be ordered routinely to assess DJD, but still it is first choice when any dental problem is suspected. Further additional imaging (computerized tomography, magnetic resonance imaging) should be considered only if there is reason to expect that the findings might affect diagnosis and management. This study adds to recent criticisms of the clinical validity of the RDC/TMD, with regard to DJD.
Finno, Carrie J; Kaese, Heather J; Miller, Andrew D; Gianino, Giuliana; Divers, Thomas; Valberg, Stephanie J
A pigment retinopathy has been reported in adult horses with equine motor neuron disease (EMND) arising from chronic α-tocopherol (α-TP) deficiency. A pigment retinopathy has not been identified in horses with neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) that affects genetically susceptible young horses with α-TP deficiency. The objective of this report is to describe, for the first time, a pigment retinopathy in a family of α-TP-deficient Warmbloods (WB) with clinically apparent NAD/EDM or EMND. Twenty-five WB horses from one farm underwent complete neurologic and ophthalmic examinations and serum α-TP concentrations were assessed. Two of the most severely ataxic horses were euthanized and postmortem examinations performed. Alpha-TP deficiency was widespread on this farm (22 of 25 horses). Eleven of 25 horses were clinically normal (age range 2-12 years), one had signs of EMND (6 years of age), 10 had signs of ataxia consistent with NAD/EDM (1-10 years), and two of these were postmortem confirmed concurrent NAD/EDM and EMND. A pigment retinopathy characterized by varying amounts of granular dark pigment in the tapetal retina was observed in four clinically apparent NAD/EDM horses (two postmortem confirmed concurrent NAD/EDM and EMND) and one horse with clinical signs of EMND. A pigment retinopathy can be present in young α-TP-deficient Warmblood horses with clinical signs of EMND as well as those with signs of NAD/EDM. © 2016 American College of Veterinary Ophthalmologists.
Walter, B. A.; Torre, O. M.; Laudier, D.; Naidich, T. P.; Hecht, A. C.; Iatridis, J. C.
Multiple histologic measurements are commonly used to assess degenerative changes in intervertebral disc (IVD) structure; however, there is no consensus on which stains offer the clearest visualization of specific areas within the IVD. The objective of this study was to compare multiple tinctorial stains, evaluate their ability to highlight structural features within the IVD, and investigate how they influence the capacity to implement a degeneration scoring system. Lumbar IVDs from seven human autopsy specimens were stained using six commonly used stains (Hematoxylin/Eosin, Toluidine Blue, Safranin-O/Fast Green, Extended FAST, modified Gomori’s Trichrome, and Picrosirius Red Alcian Blue). All IVDs were evaluated by three separate graders to independently determine which stains (i) were most effective at discerning different structural features within different regions of the IVDs and (ii) allowed for the most reproducible assessment of degeneration grade, as assessed via the Rutges histological scoring system (Rutges et al. A validated new histological classification for intervertebral disc degeneration. Osteoarthritis Cartilage, 21, 2039-47). Although Trichrome, XFAST and PR/AB stains were all effective at highlighting different regions of whole IVDs, we recommend the use of PR/AB because it had the highest degree of rater agreement on assigned degeneration grade, allowed greater resolution of degeneration grade, has an inferential relationship between color and composition, and allowed clear differentiation of the different regions and structural disruptions within the IVD. The use of a standard set of stains together with a histological grading scheme can aid in the characterization of structural changes in different regions of the IVD and may simplify comparisons across the field. This collection of human IVD histological images highlights how IVD degeneration is not a single disease but a composite of multiple processes such as aging, injury, repair, and
Welch, Ian D; Cowan, Matthew F; Beier, Frank; Underhill, Tully M
Introduction Osteoarthritis (OA) is a debilitating disease with poorly defined aetiology. Multiple signals are involved in directing the formation of cartilage during development and the vitamin A derivatives, the retinoids, figure prominently in embryonic cartilage formation. In the present study, we examined the expression of a retinoid-regulated gene in murine models of OA. Methods Mild and moderate forms of an OA-like degenerative disease were created in the mouse stifle joint by meniscotibial transection (MTX) and partial meniscectomy (PMX), respectively. Joint histopathology was scored using an Osteoarthritis Research Society International (OARSI) system and gene expression (Col1a1, Col10a1, Sox9 and Crabp2) in individual joints was determined using TaqMan quantitative PCR on RNA from microdissected articular knee cartilage. Results For MTX, there was a significant increase in the joint score at 10 weeks (n = 4, p < 0.001) in comparison to sham surgeries. PMX surgery was slightly more severe and produced significant changes in joint score at six (n = 4, p < 0.01), eight (n = 4, p < 0.001) and 10 (n = 4, p < 0.001) weeks. The expression of Col1a1 was increased in both surgical models at two, four and six weeks post-surgery. In contrast, Col10a1 and Sox9 for the most part showed no significant difference in expression from two to six weeks post-surgery. Crabp2 expression is induced upon activation of the retinoid signalling pathway. At two weeks after surgery in the MTX and PMX animals, Crabp2 expression was increased about 18-fold and about 10-fold over the sham control, respectively. By 10 weeks, Crabp2 expression was increased about three-fold (n = 7, not significant) in the MTX animals and about five-fold (n = 7, p < 0.05) in the PMX animals in comparison to the contralateral control joint. Conclusions Together, these findings suggest that the retinoid signalling pathway is activated early in the osteoarthritic process and is sustained during the course of
Self-complementary adeno-associated virus serotype 6 mediated knockdown of ADAMTS4 induces long-term and effective enhancement of aggrecan in degenerative human nucleus pulposus cells: A new therapeutic approach for intervertebral disc disorders
Shenegelegn Mern, Demissew; Tschugg, Anja; Hartmann, Sebastian; Thomé, Claudius
Inhibition of intervertebral disc (IVD) degeneration, which is often accompanied by painful inflammatory and immunopathological processes, is challenging. Current IVD gene therapeutic approaches are based on adenoviral gene delivery systems, which are limited by immune reactions to their viral proteins. Their applications in IVDs near to sensitive neural structure could provoke toxicity and immunological side-effects with neurological deficits. Self-complementary adeno-associated virus (scAAV) vectors, which do not express any viral gene and are not linked with any known disease in humans, are attractive therapeutic gene delivery vectors in degenerative IVDs. However, scAAV-based silencing of catabolic or inflammatory factor has not yet been investigated in human IVD cells. Therefore, we used scAAV6, the most suitable serotype for transduction of human nucleus pulposus (NP) cells, to knockdown the major catabolic gene (ADAMTS4) of IVD degeneration. IVD degeneration grades were determined by preoperative magnetic resonance imaging. Lumbar NP tissues of degeneration grade III were removed from 12 patients by nucleotomy. NP cells were isolated and cultured with low-glucose. Titre of recombinant scAAV6 vectors targeting ADAMTS4, transduction efficiencies, transduction units, cell viabilities and expression levels of target genes were analysed using quantitative PCR, fluorescence microscopy, fluorescence-activated cell sorting, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assays, quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assays during 48 days of post-transduction. Transduction efficiencies between 98.2% and 37.4% and transduction units between 611 and 245 TU/cell were verified during 48 days of post-transduction (p<0.001). scAAV6-mediated knockdown of ADAMTS4 with maximum 87.7% and minimum 40.1% was confirmed on day 8 and 48 with enhanced the level of aggrecan 48.5% and 30.2% respectively (p<0.001). scAAV6
Bachmann, G F; Basad, E; Rauber, K; Damian, M S; Rau, W S
We examined 320 patients with MRI and arthroscopy after an acute trauma to evaluate MRI in diagnosis of degenerative joint disease of the knee in relation to sports activity and clinical data. Lesions of cartilage and menisci on MRI were registered by two radiologists in consensus without knowledge of arthroscopy. Arthroscopy demonstrated grade-1 to grade-4 lesions of cartilage on 729 of 1920 joint surfaces of 320 knees, and MRI diagnosed 14% of grade-1, 32% of grade-2, 94% of grade-3, and 100% of grade-4 lesions. Arthroscopy explored 1280 meniscal areas and showed degenerations in 10%, tears in 11.4%, and complex lesions in 9.2%. Magnetic resonance imaging was in agreement with arthroscopy in 81% showing more degenerations but less tears of menisci than arthroscopy. Using a global system for grading the total damage of the knee joint into none, mild, moderate, or severe changes, agreement between arthroscopy and MRI was found in 82%. Magnetic resonance imaging and arthroscopy showed coherently that degree of degenerative joint changes was significantly correlated to patient age or previous knee trauma. Patients over 40 years had moderate to severe changes on MRI in 45% and patients under 30 years in only 22%. Knee joints with a history of trauma without complete structural or functional reconstitution showed marked changes on MRI in 57%, whereas stable joints without such alterations had degenerative changes in only 26%. There was no correlation of degenerative disease to gender, weight, type, frequency, and intensity of sports activity. Therefore, MRI is an effective non-invasive imaging method for exact localization and quantification of chronic joint changes of cartilage and menisci that recommends MRI for monitoring in sports medicine.
Lee, Dong Young; Fletcher, Evan; Martinez, Oliver; Zozulya, Natalia; Kim, Jane; Tran, Jeannie; Buonocore, Michael; Carmichael, Owen; DeCarli, Charles
Background and Purpose Despite the critical importance of the corpus callosum (CC) to the connection between brain hemispheres, little is known about the independent contribution of degenerative and vascular processes to regional changes in the microstructural integrity of the CC. Here, we examine these changes in subjects with mild cognitive impairment (MCI), Alzheimer's disease (AD), and in cognitively normal elderly adults. Methods We used three-dimensional brain MRI with diffusion tensor imaging in 47 AD, 77 MCI, and 107 cognitively normal subjects, and calculated mean fractional anisotropy (FA) values for four CC regions corresponding to four homologous regions of cortical gray matter (GM). To assess vascular and degenerative processes, we also measured cortical GM and white matter hyperintensity (WMH) volume in corresponding regions, along with evaluation of their vascular risk. Results We found that GM volume in anterior and posterior regions was significantly related to FA findings in the corresponding regions of the CC for all three diagnostic groups. Independent of GM volume, frontal WMH volume was also associated with FA values in the corresponding CC regions, but posterior WMH volume was not. Vascular risk was associated with FA of most CC regions, while diagnosis for cognitive state was associated only with FA of the anterior and posterior CC regions. Conclusions We found differential region-specific associations between degenerative and vascular processes and the structural integrity of the CC across the spectrum of cognitive ability. Based on these results, we propose a model to explain regional disruption in the interhemispheric connection. PMID:20595668
Sakarin, S; Rungsipipat, A; Surachetpong, S D
This study aimed to determine the association of cardiac fibrosis with the galectin-3 (Gal-3) expression, a fibrosis marker in the myocardium and to compare plasma Gal-3 levels in normal and degenerative mitral valve disease (DMVD) dogs. Studies of muscle expression and plasma levels of Gal-3 were performed in separate groups of dogs. The tissue study was performed on cardiac tissues collected from 22 dogs. The plasma study was performed on 46 client-owned dogs. Papillary muscle and left ventricular (LV) wall obtained from 10 normal and 12 DMVD dogs were stained with Masson trichrome and Gal-3 immunohistochemistry to determine fibrosis areas and Gal-3 expression. Plasma samples were collected from 19 normal and 27 DMVD dogs for Gal-3 measurement by ELISA. Percentage of fibrosis was higher in papillary muscle and LV wall of DMVD dogs (66.13 ± 5.58%; 52.98 ± 8.45%) than in normal dogs (35.40 ± 8.46%; 27.41 ± 7.91%; p < 0.0001). Gal-3 was higher in papillary muscle and LV wall of DMVD dogs (27.95 ± 6.94%; 17.25 ± 8.76%) than in normal dogs (1.08 ± 0.67%; 0.52 ± 0.42%; p < 0.0001). Fibrosis areas correlated strongly with the Gal-3 expression (r = 0.821, p < 0.0001). Plasma Gal-3 levels were increased in DMVD dogs (1.50; 0.87-2.36 ng/mL) compared to normal dogs (0.42; 0.27-0.63 ng/mL; p < 0.0001). Gal-3 expression in cardiac muscle was associated with cardiac fibrosis and was higher in DMVD dogs than in normal dogs. DMVD dogs had higher plasma Gal-3 concentrations than normal dogs. Tissue Gal-3 is a candidate of fibrosis biomarker in DMVD; however, further investigation of associations between plasma Gal-3 and myocardial fibrosis is necessary. Copyright © 2015 Elsevier B.V. All rights reserved.
Li, Xiaochuan; Bai, Xuedong; Wu, Yaohong; Ruan, Dike
To construct and validate a model to predict responsible nerve roots in lumbar degenerative disease with diagnostic doubt (DD). From January 2009-January 2013, 163 patients with DD were assigned to the construction (n = 106) or validation sample (n = 57) according to different admission times to hospital. Outcome was assessed according to the Japanese Orthopedic Association (JOA) recovery rate as excellent, good, fair, and poor. The first two results were considered as effective clinical outcome (ECO). Baseline patient and clinical characteristics were considered as secondary variables. A multivariate logistic regression model was used to construct a model with the ECO as a dependent variable and other factors as explanatory variables. The odds ratios (ORs) of each risk factor were adjusted and transformed into a scoring system. Area under the curve (AUC) was calculated and validated in both internal and external samples. Moreover, calibration plot and predictive ability of this scoring system were also tested for further validation. Patients with DD with ECOs in both construction and validation models were around 76 % (76.4 and 75.5 % respectively). more preoperative visual analog pain scale (VAS) score (OR = 1.56, p < 0.01), stenosis levels of L4/5 or L5/S1 (OR = 1.44, p = 0.04), stenosis locations with neuroforamen (OR = 1.95, p = 0.01), neurological deficit (OR = 1.62, p = 0.01), and more VAS improvement of selective nerve route block (SNRB) (OR = 3.42, p = 0.02). the internal area under the curve (AUC) was 0.85, and the external AUC was 0.72, with a good calibration plot of prediction accuracy. Besides, the predictive ability of ECOs was not different from the actual results (p = 0.532). We have constructed and validated a predictive model for confirming responsible nerve roots in patients with DD. The associated risk factors were preoperative VAS score, stenosis levels of L4/5 or L5/S1, stenosis locations
MAHMOUDZADEH, Raziyeh; HEIDARI-KESHEL, Saeed; LASHAY, Alireza
After injury to the central nervous system (CNS), regeneration is often inadequate, except in the case of remyelination. This remyelination capacity of the CNS is a good example of a stem/precursor cell-mediated renewal process. Schwann cells have been found to act as remyelinating agents in the peripheral nervous system (PNS), but several studies have highlighted their potential role in remyelination in the CNS too. Schwann cells are able to protect and support retinal cells by secreting growth factors such as brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and basic fibroblast growth factor. Retinal degenerative diseases can be highly debilitating, and they are a major concern in countries with an ageing populations. One of the leading causes of permanent loss of vision in the West is a retinal degenerative disease known as age-related macular degeneration (AMD). In the United States, nearly 1.75 million people over the age of 40 have advanced AMD, and it is estimated that this number will increase to approximately 3 million people by 2020. One of the most common pathways involved in the initiation and development of retinal diseases is the oxidative stress pathway. In patients with diabetes, Schwann cells have been shown to be able to secrete large amounts of antioxidant enzymes that protect the PNS from the oxidative stress that results from fluctuations in blood glucose levels. This antioxidant ability may be involved in the mechanism by which Schwann cells are able to promote reconstruction in the CNS, especially in individuals with retinal injuries and degenerative diseases. PMID:28293647
Lin, Bin; Xu, Yang; He, Yong; Zhang, Bi; Lin, Qiuyan; He, Mingchang
Minimally invasive unilateral pedicle screw fixation for the treatment of degenerative lumbar diseases has won the support of many surgeons. However, few data are available regarding clinical research on unilateral pedicle screw fixation associated with minimally invasive techniques for the treatment of lumbar spinal diseases. The purpose of this study was to evaluate clinical outcomes in a selected series of patients with lumbar degenerative diseases treated with minimally invasive unilateral vs classic bilateral pedicle screw fixation and lumbar interbody fusion. Patients in the unilateral group (n=43) underwent minimally invasive unilateral pedicle screw fixation with the Quadrant system (Medtronic, Memphis, Tennessee). The bilateral group (n=42) underwent bilateral instrumentation via the classic approach. Visual analog scale pain scores, Oswestry Disability Index scores, fusion rate, operative time, blood loss, and complications were analyzed. Mean operative time was 75 minutes in the unilateral group and 95 minutes in the bilateral group. Mean blood loss was 220 mL in the unilateral group and 450 mL in the bilateral group. Mean postoperative visual analog scale pain score was 3.10±0.16 in the unilateral group and 3.30±1.10 in the bilateral group. Mean postoperative Oswestry Disability Index score was 15.67±2.3 in the unilateral group and 14.93±2.6 in the bilateral group. Successful fusion was achieved in 92.34% of patients in the unilateral group and 93.56% of patients in the bilateral group. Minimally invasive unilateral pedicle screw fixation is an effective and reliable option for the surgical treatment of lumbar degenerative disease. It causes less blood loss, requires less operative time, and has a fusion rate comparable with that of conventional bilateral fixation. Copyright 2013, SLACK Incorporated.
Strunz, Célia M C; Marcondes-Santos, Mário; Takada, Julio Yoshio; Fragata, Fernanda S; Mansur, Antônio de Pádua
The knowledge of the variables predicting mortality is important in clinical practice and for therapeutic monitoring in mitral valve disease. To determine whether a quality of life score evaluated with the Functional Evaluation of Cardiac Health questionnaire would predict mortality in dogs with degenerative mitral valve disease (DMVD). Thirty-six client-owned dogs with mitral valve disease underwent clinical, laboratory, and echocardiographic evaluations at baseline and were monitored for 6 months. Cardiovascular death was the primary outcome. The 36 dogs were classified as survivors or nonsurvivors. Higher values of the following variables were obtained at baseline in the nonsurviving group (12 dogs): amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, plasma norepinephrine, heart rate, quality of life score, diastolic left ventricular internal dimension to aortic root ratio, systolic left ventricular internal dimension to aortic root ratio, and left atrium to aortic root ratio. NT-proBNP levels and quality life score were independently associated with death in the multivariable analysis. The quality life score was an independent variable for cardiac death in dogs with DMVD. This result is encouraging, as this score is easy to apply and does not require any technology, only a veterinarian and an observant owner. O conhecimento das variáveis preditoras de mortalidade é importante para a prática clínica e para o acompanhamento terapêutico na doença da valva mitral. Determinar se um escore de qualidade de vida avaliado com o Functional Evaluation of Cardiac Health poderia auxiliar na predição de mortalidade em cães com doença degenerativa da valva mitral (DDVM). Trinta e seis cães de estimação com doença valvar mitral foram submetidos a avaliação clínica, laboratorial e ecocardiográfica no início do estudo e monitorizados durante 6 meses. A morte cardiovascular foi o desfecho primário. Os 36 cães foram classificados como
Roberts, Jan A.; Wolfe, Tristy M.
Objective The purpose of this article is to report the response of chiropractic care of a geriatric veteran with degenerative disk disease and diffuse idiopathic skeletal hyperostosis. Clinical Features A 74-year-old man presented with low back pain (LBP) and loss of feeling in his lower extremities for 3 months. The LBP was of insidious onset with a 10/10 pain rating on the numeric pain scale (NPS) and history of degenerative disk disease and diffuse idiopathic skeletal hypertrophy. Oswestry questionnaire was 44% and health status questionnaire was 52%, which were below average for his age. The patient presented with antalgia and severe difficulty with ambulation and thus used a walker. Intervention and Outcome Chiropractic care included Activator Methods protocol. Two weeks into treatment, he reported no back pain; and after 4 treatments, he was able to walk with a cane instead of a walker. The NPS decreased from a 10/10 to a 0/10, and his Revised Oswestry score decreased from 44/100 to 13.3/100. His Health Status Questionnaire score increased 25 points to 77/100, bringing him from below average for his age to above average for his age. Follow-up with the patient at approximately 1 year and 9 months showed an Oswestry score of 10/100 and a Health Status Questionnaire score of 67/100, still above average for his age. Conclusion The findings in this case study showed that Activator-assisted spinal manipulative therapy had positive subjective and objective results for LBP and ambulation in a geriatric veteran with degenerative disk disease and diffuse idiopathic skeletal hyperostosis. PMID:23843763
Yang, Bo; Ou, Yunsheng; Jiang, Dianming; An, Hong; Liu, Bo; Zhang, Jian; Li, Kaiting
The present study is aimed to investigate the early clinical effects of nano-hydroxyapatite/polyamide 66 intervertebral fusion cage (n-HA/PA66 cage) for the treatment of lumbar degenerative diseases. We selected 27 patients with lumbar degenerative diseases who were managed by posterior decompression or reset operation combined with n-HA/PA66 cage intervertebral fusion and internal fixation from August 2010 to January 2012. The oswestry disability index (ODI), low back and leg pain visual analogue score (VAS), and intervertebral height (IH) were evaluated at preoperation, 1 week postoperation and the last follow-up period, respectively. Intervertebral bony fusion was evaluated at the last follow-up time. The patients were followed up for 12-24 months (averaged 19 months). The ODI, VAS and IH were significantly improved at 1 week postoperation and the last follow-up time compared with those at preoperative period (P < 0.05). But there was no significant difference between 1 week postoperative and the last follow-up time (P < 0.05). Brantigan's standard was used to evaluate fusion at the last follow-up time. There were 19 patients with grade 5 fusion, 8 with grade 4 fusion, with a fusion rate of 100%, and none with grade 1-3 fusions. There was no cage translocation and internal fixation breakage. These results suggested that n-HA/PA66 cage was an ideal biological material in the posterior lumbar interbody fusion and internal fixation operation for treatment of lumbar degenerative diseases. It can effectively maintain the intervertebral height and keep a high rate of bony fusion. The early clinical effect has been satisfactory.
Sun, H L; Li, C D; Yang, Z C; Yi, X D; Liu, H; Lu, H L; Li, H; Wang, Y
To describe the application of polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar diseases with osteoporosis. Observation group included 14 cases of degenerative lumbar diseases with osteoporosis received polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws from November 2014 to July 2015, control group included 12 cases of degenerative lumbar diseases with osteoporosis received polymethylmethacrylate augmentation with traditional pedicle screws.The operation time, blood loss, number of pedicle screws and number of augmented pedicle screws in the two groups were compared. The bone cement leakage and pulmonary bone cement embolism in the two groups were also compared. The fusion rate and pedicle screws loosening by lumbar X ray and dynamic X ray were evaluated. The clinical results were assessed by visual analog scale (VAS) of pain on lumbar and lower limbers, lumbar Japanese Orthopaedic Association scores (JOA), Prolo functional scores and Oswestry disability (ODI) scores. Differences of operation time and blood loss in the two groups were not statistically significant. The average number of pedicle screws was 9.9±4.7 and the average number of augmented pedicle screws was 5.9±2.6 in observation group while the average number of pedicle screws was 7.1±2.8 and the average number of augmented pedicle screws was 3.0±1.9 in control group. The ratio of augmented pedicle screws was higher in observation group than in control group (0.69±0.30 vs.0.47±0.30,P<0.05). The bone cement leakage rate was lower in observation group than in control group (5/83 vs. 12/42, P<0.01). All the cases in observation group were without leakage to the interspinal canal while one case in control group suffered from bone cement leakage to the interspinal canal with augmentation of 3 pedicle screws. The follow up period was (10.6±2.3) months in observation group and (36.5±7
Tibiletti, Marta; Kregar Velikonja, Nevenka; Urban, Jill P G; Fairbank, Jeremy C T
Disc cell therapies, in which cells are injected into the degenerate disc in order to regenerate the matrix and restore function, appear to be an attractive, minimally invasive method of treatment. Interest in this area has stimulated research into disc cell biology in particular. However, other important issues, some of which are discussed here, need to be considered if cell-based therapies are to be brought to the clinic. Firstly, a question which is barely addressed in the literature, is how to identify patients with 'degenerative disc disease' who would benefit from cell therapy. Pain not disc degeneration is the symptom which drives patients to the clinic. Even though there are associations between back pain and disc degeneration, many people with even severely degenerate discs, with herniated discs or with spinal stenosis, are pain-free. It is not possible using currently available techniques to identify whether disc repair or regeneration would remove symptoms or prevent symptoms from occurring in future. Moreover, the repair process in human discs is very slow (years) because of the low cell density which can be supported nutritionally even in healthy human discs. If repair is necessary for relief of symptoms, questions regarding quality of life and rehabilitation during this long process need consideration. Also, some serious technical issues remain. Finding appropriate cell sources and scaffolds have received most attention, but these are not the only issues determining the feasibility of the procedure. There are questions regarding the safety of implanting cells by injection through the annulus whether the nutrient supply to the disc is sufficient to support implanted cells and whether, if cells are able to survive, conditions in a degenerate human disc will allow them to repair the damaged tissue. If cell therapy for treatment of disc-related disorders is to enter the clinic as a routine treatment, investigations must examine the questions related to
Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju
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
Berker, Nilufer; Elgin, Ufuk; Ozdal, Pinar; Batman, Aygen; Soykan, Emel; Ozkan, Seyhan S
To compare the topographic characteristics of the optic discs in patients with severe and mild ocular Behçet's disease by using Heidelberg retinal tomographaphy (HRT). This prospective study included 47 eyes of 47 patients with ocular BD who were being followed-up at the Uveitis Clinic of the Ankara Ulucanlar Eye Research Hospital, Ankara, Turkey. The patients were divided into two groups. Group 1 consisted of 21 eyes with mild uveitis, and group 2 consisted of 26 eyes with severe uveitis. All patients underwent topographic optic disc analysis by HRT II, and the quantitative optic disc parameters of both groups were compared by non-parametric Mann-Whitney U test. The mean cup volume, rim volume, cup area, disc area and cup depth in group 1 were found to be statistically significantly greater than those in group 2 (p<0.0001, p = 0.03, p = 0.021, p = 0.01 and p = 0.017, respectively), while the difference between the mean cup-to-disc ratios in group 1 and group 2 were found to be statistically insignificant (p = 0.148). A relationship was found between the severity of ocular BD and optic disc topography determined by HRT. In eyes with smaller optic discs, uveitis was observed to have a more severe course with more frequent relapses than those with larger discs.
Berker, Nilufer; Elgin, Ufuk; Ozdal, Pinar; Batman, Aygen; Soykan, Emel; Ozkan, Seyhan S
Aim To compare the topographic characteristics of the optic discs in patients with severe and mild ocular Behçet's disease by using Heidelberg retinal tomographaphy (HRT). Methods This prospective study included 47 eyes of 47 patients with ocular BD who were being followed‐up at the Uveitis Clinic of the Ankara Ulucanlar Eye Research Hospital, Ankara, Turkey. The patients were divided into two groups. Group 1 consisted of 21 eyes with mild uveitis, and group 2 consisted of 26 eyes with severe uveitis. All patients underwent topographic optic disc analysis by HRT II, and the quantitative optic disc parameters of both groups were compared by non‐parametric Mann‐Whitney U test. Results The mean cup volume, rim volume, cup area, disc area and cup depth in group 1 were found to be statistically significantly greater than those in group 2 (p<0.0001, p = 0.03, p = 0.021, p = 0.01 and p = 0.017, respectively), while the difference between the mean cup‐to‐disc ratios in group 1 and group 2 were found to be statistically insignificant (p = 0.148). Conclusion A relationship was found between the severity of ocular BD and optic disc topography determined by HRT. In eyes with smaller optic discs, uveitis was observed to have a more severe course with more frequent relapses than those with larger discs. PMID:17475703
Zhang, Wenli; Liu, Hao; Li, Tanzhu
To review the research advances in animal models of human disc degeneration. The relative articles in recent years were extensively reviewed. Studies both at home and abroad were analyzed and classified. The advantages and disadvantages of each method were compared. Studies were classified as either experimentally induced models or spontaneous models. The induced models were subdivided as mechanical (alteration of forces on the normal disc), structural (injury or chemical alteration) and genetically induced models. Spontaneous models included those animals that naturally developed degenerative disc disease. Animal model of intervertebral disc degeneration is an important path for revealing the pathogenesis of human disc degeneration, and play an important role in testing novel interventions. With recent advances in the relevance of animal models and humans, it has a great prospect in study of human disc degeneration.
Maquirriain, J; Ghisi, J P; Amato, S
Background High demands imposed to the shoulder during tennis activity can decrease the efficiency of static and dynamic constraints. Subtle or frank instability of the glenohumeral joint may occur, and long term degenerative changes may be expected. Objective To determine and compare the prevalence of primary glenohumeral osteoarthritis in senior tennis players and matched controls. Study design Cross sectional controlled study. Methods 18 asymptomatic senior tennis players were studied (17 male; mean (SD) age, 57.2 (8.8) years) with no history of shoulder surgery or major trauma. There were 18 matched controls. Radiographs were used to determine glenohumeral osteoarthritic changes: joint space narrowing, humeral and glenoid subchondral sclerosis, humeral and glenoid juxta‐articular cysts, osteophytes, humeral and glenoid flattening, humeral posterior displacement and glenoid posterior erosion. Findings were classified as normal, minimal, moderate, or severe changes. Results 33% of the players (95% confidence interval (CI), 13% to 59%) had osteoarthritic changes in their dominant shoulder (n = 6; five with minimal changes, one with moderate changes), and 11% of the controls (95% CI, 1% to 34%) had articular degeneration on their dominant side (n = 2; both minimal changes) (p = 0.04, Wilcoxon test). The osteoarthritic group was significantly older than the players without degenerative changes (p = 0.008). Conclusions The prevalence of glenohumeral osteoarthritis in the dominant shoulder was greater in former elite tennis players than in sedentary controls. Prolonged intensive tennis practice may be a predisposing factor for the development of mild degenerative articular changes in the dominant shoulder. PMID:16632577
Sakai, Daisuke; Grad, Sibylle
The healthy intervertebral disc (IVD) fulfils the essential function of load absorption, while maintaining multi-axial flexibility of the spine. The interrelated tissues of the IVD, the annulus fibrosus, the nucleus pulposus, and the cartilaginous endplate, are characterised by their specific niche, implying avascularity, hypoxia, acidic environment, low nutrition, and low cellularity. Anabolic and catabolic factors balance a slow physiological turnover of extracellular matrix synthesis and breakdown. Deviations in mechanical load, nutrient supply, cellular activity, matrix composition and metabolism may initiate a cascade ultimately leading to tissue dehydration, fibrosis, nerve and vessel ingrowth, disc height loss and disc herniation. Spinal instability, inflammation and neural sensitisation are sources of back pain, a worldwide leading burden that is challenging to cure. In this review, advances in cell and molecular therapy, including mobilisation and activation of endogenous progenitor cells, progenitor cell homing, and targeted delivery of cells, genes, or bioactive factors are discussed.
Barbagallo, G M V; Certo, F; Visocchi, M; Sciacca, G; Albanese, V
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.
Walter, B A; Torre, O M; Laudier, D; Naidich, T P; Hecht, A C; Iatridis, J C
Multiple histologic measurements are commonly used to assess degenerative changes in intervertebral disc (IVD) structure; however, there is no consensus on which stains offer the clearest visualization of specific areas within the IVD. The objective of this study was to compare multiple tinctorial stains, evaluate their ability to highlight structural features within the IVD, and investigate how they influence the capacity to implement a degeneration scoring system. Lumbar IVDs from seven human autopsy specimens were stained using six commonly used stains (Hematoxylin/Eosin, Toluidine Blue, Safranin-O/Fast Green, Extended FAST, modified Gomori's Trichrome, and Picrosirius Red Alcian Blue). All IVDs were evaluated by three separate graders to independently determine which stains (i) were most effective at discerning different structural features within different regions of the IVDs and (ii) allowed for the most reproducible assessment of degeneration grade, as assessed via the Rutges histological scoring system (Rutges et al. A validated new histological classification for intervertebral disc degeneration. Osteoarthritis Cartilage, 21, 2039-47). Although Trichrome, XFAST and PR/AB stains were all effective at highlighting different regions of whole IVDs, we recommend the use of PR/AB because it had the highest degree of rater agreement on assigned degeneration grade, allowed greater resolution of degeneration grade, has an inferential relationship between color and composition, and allowed clear differentiation of the different regions and structural disruptions within the IVD. The use of a standard set of stains together with a histological grading scheme can aid in the characterization of structural changes in different regions of the IVD and may simplify comparisons across the field. This collection of human IVD histological images highlights how IVD degeneration is not a single disease but a composite of multiple processes such as aging, injury, repair, and
Boxall, Ruth; Porteous, David J.; Thomson, Pippa A.
We re-annotated the interacting partners of the neuronal scaffold protein DISC1 using a knowledge-based approach that incorporated recent protein interaction data and published literature to. This revealed two highly connected networks. These networks feature cellular function and maintenance, and cell signaling. Of potentially greatest interest was the novel finding of a high degree of connectivity between the DISC1 scaffold protein, linked to psychiatric illness, and huntingtin, the protein which is mutated in Huntington's disease. The potential link between DISC1, huntingtin and their interacting partners may open new areas of research into the effects of pathway dysregulation in severe neurological disorders. PMID:21298101
Ohnishi, Takashi; Sudo, Hideki; Iwasaki, Koji; Tsujimoto, Takeru; Ito, Yoichi M.; Iwasaki, Norimasa
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
Barrey, Cédric; Perrin, Gilles; Champain, Sabina
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
Röllinghoff, Marc; Schlüter-Brust, Klaus; Groos, Daniel; Sobottke, Rolf; Michael, Joern William-Patrick; Eysel, Peer; Delank, Karl Stefan
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
Yavin, Daniel; Casha, Steven; Wiebe, Samuel; Feasby, Thomas E; Clark, Callie; Isaacs, Albert; Holroyd-Leduc, Jayna; Hurlbert, R John; Quan, Hude; Nataraj, Andrew; Sutherland, Garnette R; Jette, Nathalie
Due to uncertain evidence, lumbar fusion for degenerative indications is associated with the greatest measured practice variation of any surgical procedure. To summarize the current evidence on the comparative safety and efficacy of lumbar fusion, decompression-alone, or nonoperative care for degenerative indications. A systematic review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (up to June 30, 2016). Comparative studies reporting validated measures of safety or efficacy were included. Treatment effects were calculated through DerSimonian and Laird random effects models. The literature search yielded 65 studies (19 randomized controlled trials, 16 prospective cohort studies, 15 retrospective cohort studies, and 15 registries) enrolling a total of 302 620 patients. Disability, pain, and patient satisfaction following fusion, decompression-alone, or nonoperative care were dependent on surgical indications and study methodology. Relative to decompression-alone, the risk of reoperation following fusion was increased for spinal stenosis (relative risk [RR] 1.17, 95% confidence interval [CI] 1.06-1.28) and decreased for spondylolisthesis (RR 0.75, 95% CI 0.68-0.83). Among patients with spinal stenosis, complications were more frequent following fusion (RR 1.87, 95% CI 1.18-2.96). Mortality was not significantly associated with any treatment modality. Positive clinical change was greatest in patients undergoing fusion for spondylolisthesis while complications and the risk of reoperation limited the benefit of fusion for spinal stenosis. The relative safety and efficacy of fusion for chronic low back pain suggests careful patient selection is required (PROSPERO International Prospective Register of Systematic Reviews number, CRD42015020153).
Kepler, Christopher K; Hilibrand, Alan S; Sayadipour, Amir; Koerner, John D; Rihn, Jeffrey A; Radcliff, Kristen E; Vaccaro, Alexander R; Albert, Todd J; Anderson, D Greg
Lumbar degenerative spondylolisthesis (DS) is a common, acquired condition leading to disabling back and/or leg pain. Although surgery is common used to treat patients with severe symptoms, there are no universally accepted treatment guidelines. Wide variation in vertebral translation, disc collapse, sagittal alignment, and vertebral mobility suggests this is a heterogeneous disease. A classification scheme would be useful to differentiate homogenous subgroups that may benefit from different treatment strategies. To develop and test the reliability of a simple, clinically useful classification scheme for lumbar DS. Retrospective case series. One hundred twenty-six patients. Proposed radiographic classification system. A classification system is proposed that considers disc space height, sagittal alignment and translation, and the absence or presence of unilateral or bilateral leg pain. Test cases were graded by six observers to establish interobserver reliability and regraded in a different order 1 month later to establish intraobserver reliability using Kappa analysis. To establish the relative prevalence of each subtype, a series of 100 consecutive patients presenting with L4-L5 DS were classified. Four radiographic subtypes were identified: Type A: advanced Disc space collapse without kyphosis; Type B: disc partially preserved with translation of 5 mm or less; Type C: disc partially preserved with translation of more than 5 mm; and Type D: kyphotic alignment. The leg pain modifier 0 denotes no leg pain, 1 denotes unilateral leg pain, and 2 represents bilateral leg pain. The Kappa value describing interobserver reliability was 0.82, representing near-perfect agreement. Intraobserver reliability analysis demonstrated Kappa=0.83, representing near-perfect agreement. Grading of the consecutive series of 100 patients revealed the following distribution: 16% Type A, 37% Type B, 33% Type C, and 14% Type D. A new radiographic and clinical classification scheme for
Nazarov, V M; Afanasyev, A V; Zheleznev, S I; Bogachev-Prokophiev, A V; Demin, I I; Karaskov, A M
Degenerative mitral valve disease nowadays is the most common cause of mitral insufficiency in developed countries and is associated with high morbidity and mortality. In the last decades repairing the mitral valve has become the operation of choice for treatment of the mitral valve prolapse, enabling to improve the geometry and function of the left ventricle and long-term survival. Nevertheless, the problem of choice of method of management of severe mitral regurgitation in asymptomatic patients with degenerative mitral valve disease remains unsolved. In this article we present immediate results of a prospective comparative study of mitral valve surgery in asymptomatic and symptomatic patients in dependence on NYHA class of heart failure.
Kuh, Sung-Uk; Kim, Young-Soo; Cho, Young-Eun; Yoon, Young-Sul; Jin, Byung-Ho; Kim, Keun-Su; Chin, Dong-Kyu
The herniated lumbar disc (HLD) in adolescent patients is characterized by typical discogenic pain that originates from a soft herniated disc. It is frequently related to back trauma, and sometimes it is also combined with a degenerative process and a bony spur such as posterior Schmorl's node. Chemonucleolysis is an excellent minimally invasive treatment having these criteria: leg pain rather than back pain, severe limitation on the straight leg raising test (SLRT), and soft disc protrusion on computed tomography (CT). Microsurgical discectomy is useful in the cases of extruded or sequestered HLD and lateral recess stenosis due to bony spur because the nerve root is not decompressed with chymopapain. Spinal fusion, like as PLIF, should be considered in the cases of severe disc degeneration, instability, and stenosis due to posterior central bony spur. In our study, 185 adolescent patients, whose follow-up period was more than 1 year (the range was 1-4 years), underwent spinal surgery due to HLD from March, 1998 to December, 2002 at our institute. Among these cases, we performed chemonucleolysis in 65 cases, microsurgical discectomy in 94 cases, and posterior lumbar interbody fusion (PLIF) with cages in 33 cases including 7 reoperation cases. The clinical success rate was 91% for chemonucleolysis, 95% for microsurgical disectomy, and 89% for PLIF with cages, and there were no non- union cases for the PLIF patients with cages. In adolescent HLD, chemonucleolysis was the 1st choice of treatment because the soft adolescent HLD was effectively treated with chemonucleolysis, especially when the patient satisfied the chemonucleolysis indications.
Tanaka, Motomasa; Ishizuka, Koko; Nekooki-Machida, Yoko; Endo, Ryo; Takashima, Noriko; Sasaki, Hideyuki; Komi, Yusuke; Gathercole, Amy; Huston, Elaine; Ishii, Kazuhiro; Hui, Kelvin Kai-Wan; Kurosawa, Masaru; Kim, Sun-Hong; Nukina, Nobuyuki; Takimoto, Eiki; Houslay, Miles D; Sawa, Akira
Huntington's disease (HD) is a polyglutamine (polyQ) disease caused by aberrant expansion of the polyQ tract in Huntingtin (HTT). While motor impairment mediated by polyQ-expanded HTT has been intensively studied, molecular mechanisms for nonmotor symptoms in HD, such as psychiatric manifestations, remain elusive. Here we have demonstrated that HTT forms a ternary protein complex with the scaffolding protein DISC1 and cAMP-degrading phosphodiesterase 4 (PDE4) to regulate PDE4 activity. We observed pathological cross-seeding between DISC1 and mutant HTT aggregates in the brains of HD patients as well as in a murine model that recapitulates the polyQ pathology of HD (R6/2 mice). In R6/2 mice, consequent reductions in soluble DISC1 led to dysregulation of DISC1-PDE4 complexes, aberrantly increasing the activity of PDE4. Importantly, exogenous expression of a modified DISC1, which binds to PDE4 but not mutant HTT, normalized PDE4 activity and ameliorated anhedonia in the R6/2 mice. We propose that cross-seeding of mutant HTT and DISC1 and the resultant changes in PDE4 activity may underlie the pathology of a specific subset of mental manifestations of HD, which may provide an insight into molecular signaling in mental illness in general.
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
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.
Kay, Harrison F; Chotai, Silky; Wick, Joseph B; Stonko, David P; McGirt, Matthew J; Devin, Clinton J
Evaluate the factors associated with postoperative ICU admission in patients undergoing surgical management of degenerative lumbar spine disease. Patients undergoing surgery for degenerative lumbar spine disease were enrolled into a prospective registry over a 2-year period. Preoperative variables (age, gender, ASA grade, ODI%, CAD, HTN, MI, CHF, DM, BMI, depression, anxiety) and surgical variables (instrumentation, arthrodesis, estimated blood loss, length of surgery) were collected prospectively. Postoperative ICU admission details were retrospectively determined from the electronic medical record. Student's t test (continuous variables) and Chi-square test (categorical variables) were used to determine the association of each preoperative and surgical variable with ICU admission. 808 Patients (273 laminectomy, 535 laminectomy and fusion) were evaluated. Forty-one (5.1%) patients were found to have postoperative ICU admissions. Reasons for admission included blood loss (12.2%), cardiac (29.3%), respiratory (19.5%), neurologic (31.7%), and other (7.3%). For preoperative variables, female gender (P < 0.001), history of CAD (P = 0.003), history of MI (P = 0.008), history of CHF (P = 0.001), age (P = 0.025), and ASA grade (P = 0.008) were significantly associated with ICU admission. For surgical variables, estimated blood loss (P < 0.001) and length of surgery (P < 0.001) were significantly associated with ICU admission. Age, female gender, ASA grade, cardiac comorbidities, intraoperative blood loss, and length of surgery were associated with increased risk of postoperative ICU admission. Knowledge of these factors can aid surgeons in patient selection and preoperative discussion with patients about potential need for unexpected admission to the ICU.
Finger, T; Bayerl, S; Bertog, M; Czabanka, M; Woitzik, J; Vajkoczy, P
We hypothesised, that the inclusion of the ilium for multilevel lumbosacral fusions reduces the incidence of postoperative sacroiliac joint (SIJ) pain. The primary objective of this study was to compare the frequency of postoperative SIJ pain in patients undergoing multilevel stabilization with and without sacropelvic fixation for multilevel degenerative spine disease. In addition, we aimed at identifying factors that may predict the worsening or new onset of postoperative SIJ pain. A total of 63 patients with multisegmental fusion surgery with a minimum follow up of 12 months were evaluated. 34 patients received sacral fixation (SF group) and 29 patients received an additional sacropelvic fixation device (SPF group). Primary outcome parameters were changes in SIJ pain between the groups and the influence of pelvic parameters, the patient́s age, the patient́s body mass index (BMI) and the length of the stabilization on the SIJ pain. Between the two surgical groups there were no differences concerning age (p=0.3), BMI (p=0.56), length of follow up (p=0.96), length of the construct (p=0.56). In total 31.7% of the patients had a worsening/new onset of SIJ pain after surgery. An additional fixation of the SIJ with iliac screws or iliosacral plate did not have an influence on the SIJ pain (p=0.67). Likewise, pelvic parameters were not predictive for the outcome of the SIJ pain. Only an increased preoperative BMI correlated with a higher chance of a new onset of SIJ pain (p=0.037). In our retrospective study there was no influence of a sacropelvic fixation techniques on the SIJ pain in patients with multilevel degenerative spine disease after multilevel stabilization surgeries. The patients' BMI is the only preoperative factor that correlated with a higher incidence to develop postoperative SIJ pain, independently of the implantation of a sacropelvic fixation device. Copyright © 2016 Elsevier B.V. All rights reserved.
Triantafillou, Konstantinos M; Lauerman, William; Kalantar, S Babak
Each sport presents with unique risk factors and different mechanisms of injury, and therefore extrapolation of the data from one sport to another makes comparison difficult. The current evidence exploring the relationship of athletes and degenerative changes of the cervical spine leaves much to be debated, and future prospective longitudinal studies will be needed to clarify our understanding further. Such research will help structure clinical recommendations and improve sports safety and the care of athletes of all ages. Currently, there is evidence to suggest that participation in collision sports is implicated in premature degeneration of the cervical spine. There is some evidence to suggest that the same is true with noncollision sports and activities that result in direct and indirect repetitive loads to the cervical spine over time. The risk factors have yet to be clearly identified. The natural history and sequelae of premature degeneration have yet to be elucidated. Cervical spondylosis also appears to increase the severity, but not the frequency, of irreversible neurologic injury during collision sport participation. Prudence dictates that we not ignore the present evidence suggesting a link between neuropraxia and cervical stenosis. Proper screening for cervical stenosis in patients with transient neuropraxia with subsequent cessation of participation in collision sports if severe stenosis is present is suggested. There is no consensus for RTP guidelines in the setting of transient neurologic injuries in the athlete when severe degeneration is present, and each case must be considered individually with regard to the sport involved.
Park, Bert Edward; Kitya, David
The use of "stand-alone" contrast myelography (i.e., without computed tomography) has a proven track record in developing nations where few patients have access to magnetic resonance imaging, whether on the basis of prohibitive cost or the absence of such a modality altogether. To substantiate the author's 12-year experience with more than 300 myelograms performed in 16 different countries (plus some 1500 studies during 30 years of practice in the United States), a prospective pilot study was undertaken over 1 month in a community-based neurosurgical setting in western Kenya. Forty patients underwent cervical or lumbar myelography at Tenwek Hospital under the auspices of the Neurosurgery Training Program for East, Central, and South Africa (NSTP-ECSA) following failure of conservative measures to treat spine-related pathology. Thirty-five of the forty patients (88%) came to definitive surgery on the basis of a positive study that correlated with their clinical history and physical examination. There were no significant complications from the procedures, and no false-positive studies, with virtually all patients returning to normal activity and/or gainful employment within 3 weeks of their surgery. Myelography as a stand-alone diagnostic procedure is a sensitive, specific, and cost-effective means of diagnosing symptomatic degenerative spine disorders. Accordingly, its use should be encouraged at every NSTP-ECSA training site to address such ubiquitous pathology. Copyright © 2010 Elsevier Inc. All rights reserved.
Oktay, Ahmet Afşşin; Gilliland, Yvonne E; Lavie, Carl J; Ramee, Stephen J; Parrino, Patrick E; Bates, Michael; Shah, Sangeeta; Cash, Michael E; Dinshaw, Homeyar; Qamruddin, Salima
Degenerative mitral stenosis (DMS) is characterized by decreased mitral valve (MV) orifice area and increased transmitral pressure gradient due to chronic noninflammatory degeneration and subsequent calcification of the fibrous mitral annulus and the MV leaflets. The "true" prevalence of DMS in the general population is unknown. DMS predominantly affects elderly individuals, many of whom have multiple other comorbidities. Transcatheter MV replacement techniques, although their long-term outcomes are yet to be tested, have been gaining popularity and may emerge as more effective and relatively safer treatment option for patients with DMS. Echocardiography is the primary imaging modality for evaluation of DMS and related hemodynamic abnormalities such as increased transmitral pressure gradient and pulmonary arterial pressure. Classic echocardiographic techniques used for evaluation of mitral stenosis (pressure half time, proximal isovelocity surface area, continuity equation, and MV area planimetry) lack validation for DMS. Direct planimetry with 3-dimensional echocardiography and color flow Doppler is a reasonable technique for determining MV area in DMS. Cardiac computed tomography is an essential tool for planning potential interventions or surgeries for DMS. This article reviews the current concepts on mitral annular calcification and its role in DMS. We then discuss the epidemiology, natural history, differential diagnosis, mechanisms, and echocardiographic assessment of DMS.
Staal, A; Meerwaldt, J D; van Dongen, K J; Mulder, P G; Busch, H F
We studied the clinical features of 47 patients with a non-hereditary degenerative disease and with atrophy of brainstem or cerebellum or both in CT scanning. There was no relation between the CT findings and duration or severity of the disease, nor with the kind of the neurological signs which comprised ataxia, a hypokinetic rigid syndrome, oculomotor abnormalities, upper and lower motor neuron signs, orthostatic hypotension and dementia. The 2 main diagnoses were olivopontocerebellar atrophy (OPCA), or a combination of OPCA and striatonigral degeneration (SND). The differential diagnosis with Parkinson's disease and progressive supranuclear palsy was discussed. We concluded, that a CT scan is warranted in all cases of suspected Parkinson's disease, especially in those without tremor, and in cases of motoneuron disease with broad-based gait. In our patients with mainly hypokinesia and rigidity, levodopa treatment had no or brief beneficial effects. If ataxia predominated, OPCA appeared the most sensible diagnosis; if a hypokinetic-rigid syndrome predominated, the diagnoses SND plus OPCA appeared the most suitable. We assessed the degree of atrophy on CT subjectively, because an interobserver study of 60 normal CT scans, did not produce reliable measurements.
Askanas, Valerie; Engel, W King; Nogalska, Anna
Sporadic inclusion-body myositis (s-IBM) is the most common degenerative muscle disease in which aging appears to be a key risk factor. In this review we focus on several cellular molecular mechanisms responsible for multiprotein aggregation and accumulations within s-IBM muscle fibers, and their possible consequences. Those include mechanisms leading to: a) accumulation in the form of aggregates within the muscle fibers, of several proteins, including amyloid-β42 and its oligomers, and phosphorylated tau in the form of paired helical filaments, and we consider their putative detrimental influence; and b) protein misfolding and aggregation, including evidence of abnormal myoproteostasis, such as increased protein transcription, inadequate protein disposal, and abnormal posttranslational modifications of proteins. Pathogenic importance of our recently demonstrated abnormal mitophagy is also discussed. The intriguing phenotypic similarities between s-IBM muscle fibers and the brains of Alzheimer and Parkinson's disease patients, the two most common neurodegenerative diseases associated with aging, are also discussed. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A retrospective database of 40 consecutive treated cases and literature review.
Millimaggi, Daniele Francesco; DI Norcia, Valerio; Luzzi, Sabino; Alfiero, Tommaso; Galzio, Renato Juan; Ricci, Alessandro
To report our results about minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) with bilateral pedicle screw fixation, in patients with degenerative lumbosacral spine disease. To describe the indications, surgical technique and results of a consecutive series of 40 patients undergone MI-TLIF. Despite the limited number of clinical studies, published data suggest tremendous potential advantages of this technique. Forty patients with radiological findings of degenerative lumbosacral spine disease were undergone MI-TLIF between July 2012 and January 2015. Clinical outcomes were assessed by means of Oswestry Disability Index (ODI) and Health Survey Scoring (SF36) before surgery and at first year follow-up. Furthermore, the following parameters were retrospectively reviewed: age, sex, working activity, body mass index (BMI), type of degenerative disease, number of levels of fusion, operative time, blood loss, length of hospital stay. Average operative time was of 230 minutes, mean estimated blood loss 170 mL, average length of hospital stay 5 days. The ODI improved from a score of 59, preoperatively, to post-operative score of 20 at first year follow-up. Average SF36 score increased from 36 to 54 (Physical Health) and from 29 to 50 (Mental Health) at first year outcome evaluation. MI-TLIF with bilateral pedicle screw fixation is an excellent choice for selected patients suffering from symptomatic degenerative lumbosacral spine disease, especially secondary to recurrent disk herniations.
Ural, Ibrahim Halil; Alptekin, Kerem; Ketenci, Aysegul; Solakoglu, Seyhun; Alpak, Hasan; Özyalçın, Süleyman
Our study is an analysis of the histological and radiological changes in degenerated lumbar intervertebral discs, after transplantation of fibroblasts in rabbits. With that study we aimed to show the viability of the fibroblasts injected to the degenerated discs, and observe their potential for further studies. The apoptosis of the cell is one of the factors at the disc degeneration process. Fibroblasts may act as mesenchymal stem cells at the tissue to which they are injected and they may replace the apoptotic cells. The nucleus pulposus of the discs from eight rabbits were aspirated under scopic guidance to induce disc degeneration. One month later, cultured fibroblasts, which had been taken from the skin, were injected into the disc. The viability and the potential of the injected cells for reproduction were studied histologically and radiologically. Cellular formations and organizations indicating to the histological recovery were observed at the discs to which fibroblasts were transplanted. The histological findings of the discs to which no fibroblasts were transplanted, did not show any histological recovery. Radiologically, no finding of the improvement was found in both groups. The fibroblasts injected to the degenerated discs are viable. The findings of improvement, observed in this study, suggest that fibroblast transplantation could be an effective method of therapy for the prevention or for the retardation of the degenerative disease of the discs.
Ural, Ibrahim Halil; Alptekin, Kerem; Ketenci, Aysegul; Solakoglu, Seyhun; Alpak, Hasan; Özyalçın, Süleyman
Background: Our study is an analysis of the histological and radiological changes in degenerated lumbar intervertebral discs, after transplantation of fibroblasts in rabbits. With that study we aimed to show the viability of the fibroblasts injected to the degenerated discs, and observe their potential for further studies. Method: The apoptosis of the cell is one of the factors at the disc degeneration process. Fibroblasts may act as mesenchymal stem cells at the tissue to which they are injected and they may replace the apoptotic cells. The nucleus pulposus of the discs from eight rabbits were aspirated under scopic guidance to induce disc degeneration. Results: One month later, cultured fibroblasts, which had been taken from the skin, were injected into the disc. The viability and the potential of the injected cells for reproduction were studied histologically and radiologically. Cellular formations and organizations indicating to the histological recovery were observed at the discs to which fibroblasts were transplanted. The histological findings of the discs to which no fibroblasts were transplanted, did not show any histological recovery. Radiologically, no finding of the improvement was found in both groups. The fibroblasts injected to the degenerated discs are viable. Conclusion: The findings of improvement, observed in this study, suggest that fibroblast transplantation could be an effective method of therapy for the prevention or for the retardation of the degenerative disease of the discs. PMID:28603572
Resorlu, Mustafa; Gokmen, Ferhat; Resorlu, Hatice; Adam, Gurhan; Akbal, Ayla; Cevizci, Sibel; Sariyildirim, Abdullah; Savas, Yilmaz; Guven, Mustafa; Aras, Adem Bozkurt
Purpose: To assess the relation between ankylosing spondylitis (AS) and degenerative disc disease emerging in association with various intrinsic and extrinsic factors and to evaluate the correlation between degree of degeneration in intervertebral discs and apparent diffusion coefficient (ADC) values. Methods: Thirty-five patients with AS and a control group of 35 patients were included in the study. Three hundred fifty intervertebral discs were assessed in terms of degeneration by analyzing signal intensities and morphologies on T2 weighted series of a 1.5 Tesla magnetic resonance scanner. ADC values were determined in diffusion weighted images (DWI) using a “b value of 500 s/mm2”. Patients in the AS and control groups were compared in terms of intervertebral disc degeneration, and association between degree of degeneration and ADC values was analyzed. Results: The mean of total degeneration degrees for five lumbar intervertebral discs was significantly higher in the patients with AS compared to the control group (16.77±4.67 vs 13.00±4.08, respectively; P=0.001). When intervertebral discs were analyzed separately, disc degeneration was again significantly higher in patients with AS compared to the control group, with the exception of L5-S1. Age, cholesterol level, triglyceride level, duration of disease and BASFI index were significantly associated with degree of degeneration in patients with AS. A negative correlation was determined between disc degeneration and ADC value. Conclusion: AS is a risk factor for degenerative disc disease due to its systemic effects, the fact it leads to posture impairment and its inflammatory effects on the vertebrae. A decrease in ADC values is observed as degeneration worsens in degenerative disc disease. PMID:25785119
Marino, Christina L; Lascelles, B Duncan X; Vaden, Shelly L; Gruen, Margaret E; Marks, Steven L
Chronic kidney disease (CKD) and degenerative joint disease are both considered common in older cats. Information on the co-prevalence of these two diseases is lacking. This retrospective study was designed to determine the prevalence of CKD in two cohorts of cats: cats randomly selected from four evenly distributed age groups (RS group) and cats recruited for degenerative joint disease studies (DJD group), and to evaluate the concurrence of CKD and DJD in these cohorts. The RS group was randomly selected from four age groups from 6 months to 20 years, and the DJD group comprised cats recruited to four previous DJD studies, with the DJD group excluding cats with a blood urea nitrogen and/or serum creatinine concentration >20% (the upper end of normal) for two studies and cats with CKD stages 3 and 4 for the other two studies. The prevalence of CKD in the RS and DJD groups was higher than expected at 50% and 68.8%, respectively. CKD was common in cats between 1 and 15 years of age, with a similar prevalence of CKD stages 1 and 2 across age groups in both the RS and DJD cats, respectively. We found significant concurrence between CKD and DJD in cats of all ages, indicating the need for increased screening for CKD when selecting DJD treatments. Additionally, this study offers the idea of a relationship and causal commonality between CKD and DJD owing to the striking concurrence across age groups and life stages. © ISFM and AAFP 2013.
Marino, Christina L; Lascelles, B Duncan X; Vaden, Shelly L; Gruen, Margaret E; Marks, Steven L
Chronic kidney disease (CKD) and degenerative joint disease are both considered common in older cats. Information on the co-prevalence of these two diseases is lacking. This retrospective study was designed to determine the prevalence of CKD in two cohorts of cats: cats randomly selected from four evenly distributed age groups (RS group) and cats recruited for degenerative joint disease studies (DJD group), and to evaluate the concurrence of CKD and DJD in these cohorts. The RS group was randomly selected from four age groups from 6 months to 20 years, and the DJD group comprised cats recruited to four previous DJD studies, with the DJD group excluding cats with a blood urea nitrogen and/or serum creatinine concentration >20% (the upper end of normal) for two studies and cats with CKD stages 3 and 4 for the other two studies. The prevalence of CKD in the RS and DJD groups was higher than expected at 50% and 68.8%, respectively. CKD was common in cats between 1 and 15 years of age, with a similar prevalence of CKD stages 1 and 2 across age groups in both the RS and DJD cats, respectively. We found significant concurrence between CKD and DJD in cats of all ages, indicating the need for increased screening for CKD when selecting DJD treatments. Additionally, this study offers the idea of a relationship and causal commonality between CKD and DJD owing to the striking concurrence across age groups and life stages. PMID:24217707
Inherited retinal degenerative diseases (RDDs) display wide variation in their mode of inheritance, underlying genetic defects, age of onset, and phenotypic severity. Molecular mechanisms have not been delineated for many retinal diseases, and treatment options are limited. In most instances, genotype-phenotype correlations have not been elucidated because of extensive clinical and genetic heterogeneity. Next-generation sequencing (NGS) methods, including exome, genome, transcriptome and epigenome sequencing, provide novel avenues towards achieving comprehensive understanding of the genetic architecture of RDDs. Whole-exome sequencing (WES) has already revealed several new RDD genes, whereas RNA-Seq and ChIP-Seq analyses are expected to uncover novel aspects of gene regulation and biological networks that are involved in retinal development, aging and disease. In this review, we focus on the genetic characterization of retinal and macular degeneration using NGS technology and discuss the basic framework for further investigations. We also examine the challenges of NGS application in clinical diagnosis and management. PMID:24112618
Albini, Adriana; Bassani, Barbara; Baci, Denisa; Dallaglio, Katiuscia; Gallazzi, Matteo; Corradino, Paola; Bruno, Antonino; Noonan, Douglas M
Chronic, degenerative diseases are often characterized by inflammation and aberrant angiogenesis. For many of these pathologies, including rheumatoid arthritis, cardiovascular and autoimmune diseases, cancer, diabetes, and obesity, current therapies have limited efficacy, thus the validation of novel (chemo)preventive and interceptive approaches, of new or repurposed agents, alone or in combination with registered drugs, are urgently required. Phytochemicals (triterpenoids, flavonoids, retinoids) and their derivatives, non-steroidal anti-inflammatory drugs (aspirin) as well as biguanides (metformin and phenformin) originally developed from phytochemical backbones, are multi-target agents showing anti-angiogenic and anti-anti-inflammatory proprieties. Some of them target AMPK and metabolic pathways such as the mTOR axis. Here, we summarized and discussed the beneficial effects of these compounds in conferring protection and supporting therapy, suggesting that these molecules could be employed for combinatorial chemoprevention, interception approaches or chemoprevention/therapy regimens for cancer and other chronic complex diseases. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
McCann, Matthew R.; Séguin, Cheryle A.
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
Background Cardiomyopathies, degenerative diseases of cardiac muscle, are among the leading causes of death in the developed world. Microarray studies of cardiomyopathies have identified up to several hundred genes that significantly alter their expression patterns as the disease progresses. However, the regulatory mechanisms driving these changes, in particular the networks of transcription factors involved, remain poorly understood. Our goals are (A) to identify modules of co-regulated genes that undergo similar changes in expression in various types of cardiomyopathies, and (B) to reveal the specific pattern of transcription factor binding sites, cis-elements, in the proximal promoter region of genes comprising such modules. Methods We analyzed 149 microarray samples from human hypertrophic and dilated cardiomyopathies of various etiologies. Hierarchical clustering and Gene Ontology annotations were applied to identify modules enriched in genes with highly correlated expression and a similar physiological function. To discover motifs that may underly changes in expression, we used the promoter regions for genes in three of the most interesting modules as input to motif discovery algorithms. The resulting motifs were used to construct a probabilistic model predictive of changes in expression across different cardiomyopathies. Results We found that three modules with the highest degree of functional enrichment contain genes involved in myocardial contraction (n = 9), energy generation (n = 20), or protein translation (n = 20). Using motif discovery tools revealed that genes in the contractile module were found to contain a TATA-box followed by a CACC-box, and are depleted in other GC-rich motifs; whereas genes in the translation module contain a pyrimidine-rich initiator, Elk-1, SP-1, and a novel motif with a GCGC core. Using a naïve Bayes classifier revealed that patterns of motifs are statistically predictive of expression patterns, with odds ratios of 2
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
Misterska, Ewa; Jankowski, Roman; Głowacki, Maciej
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
Li, Bo; Su, Yi-Jun; Zheng, Xin-Feng; Yang, Yue-Hua; Jiang, Sheng-Dan
disc degeneration. Interference on Smad-7 might be a potential therapeutic method for the prevention and treatment of degenerative disc diseases. PMID:25811233
Casamenti, Fiorella; Grossi, Cristina; Rigacci, Stefania; Pantano, Daniela; Luccarini, Ilaria; Stefani, Massimo
The amyloid plaques and neurofibrillary tangles found in the Alzheimer's disease (AD) brain arise as a result of self-assembly into fibrillar material of amyloid-β protein (Aβ) and hyperphosphorylated tau, respectively, through a pathological process starting with the appearance of aggregation nuclei and neurotoxic oligomers. Accordingly, the search of inhibitors of oligomer nucleation and growth is considered a promising target to prevent amyloid toxicity. In recent years, a number of dietary factors including antioxidants, vitamins, and polyphenols have been characterized for their ability to protect cells stressed by several factors including the presence of amyloid deposits as well as to inhibit amyloid self-assembly and cytotoxicity and some of them are currently in clinical trial. The present review summarizes the findings on the beneficial effects against neurodegeneration and other peripheral inflammatory and degenerative diseases of oleuropein aglycone (OLE), a natural phenol abundant in the extra virgin olive oil. The data presently available suggest that OLE could provide a protective and therapeutic effect against a number of pathologies, including AD as well as obesity, type 2 diabetes, non-alcoholic hepatitis, and other natural or experimentally-induced pathological conditions. Such a protection could result, at least in part, in a remarkable improvement of the pathological signs arising from stress conditions including oxidative stress, an excessive inflammatory response, and the presence of cytotoxic aggregated material. In particular, the recent data on the cellular and molecular correlates of OLE neuroprotection suggest it could also play a therapeutic role against AD.
Benito, Javier; Gruen, Margaret E; Thomson, Andrea; Simpson, Wendy; Lascelles, B Duncan X
This study evaluated the types of items owners consider important to their cats' quality of life (QoL). We hypothesized that items contributing to QoL in cats are predominantly items requiring mobility. The objectives of the study were to describe the types of items considered important by owners for their cats' QoL; to describe the proportion of these items that involve mobility; to evaluate what patient factors, including severity of degenerative joint disease (DJD), affect this distribution; and to evaluate whether the proportion of QoL items involving mobility chosen by owners is different in cats presenting for a DJD study compared with a randomly selected population. A total of 830 client-generated items were evaluated. Regardless of DJD status, 40% of items listed by owners involved mobility, while 60% were 'inactive' items, rejecting our hypothesis. This highlights the need to assess non-active items that owners consider to constitute QoL to fully assess the impact of diseases like DJD and, therefore, the success of therapeutic interventions.
Alberti-Amador, E; García-Miniet, R
The aim of this study is to describe the capacity of bone marrow cells to limit or slow down the damage and chronic neuronal degeneration produced by degenerative diseases of the central nervous system (CNS), as well as the potential capacity of the method to provide other substances or genetic material. The search for new sources of cells that maintain the ability to divide and distinguish themselves from different cellular phenotypes opens up huge new opportunities in the restorative therapy of these clinical entities. Bone marrow cells, and especially stromal stem cells, have been seen to conserve a high capacity to distinguish and originate different strains of characteristic brain cells (neurons, astrocytes, and glial cells), and also the capacity to restore the population of stem cells when they are stimulated in a suitable fashion. Future experimental studies will be aimed at searching for new ways to enhance the composition, viability and differentiation of the cells to be implanted and will evaluate their effects on diseases of the CNS.
Zheng, Chen-Fan; Liu, Yan-Cheng; Hu, Yong-Cheng; Xia, Qun; Miao, Jun; Zhang, Ji-Dong; Zhang, Kuan
Japanese Orthopaedic Association (JOA) scoring systems were developed to evaluate the neurological function of patients with cervical or lumbar degeneration. As patient-based and multi-dimensional clinical evaluation tools, these systems should be capable of reflecting the walking disability of patients. The association between JOA scores and gait parameters, however, are not well characterized. The purpose of this study was to determine the correlations between JOA scores and gait parameters of patients with cervical spondylotic myelopathy (CSM) and lumbar intervertebral disc herniation (LDH). A total of 32 CSM and 30 LDH patients with gait dysfunction were recruited for the present study. All patients were diagnosed by two senior orthopaedic doctors and evaluated with JOA scoring systems. A body-mounted motion analyzer, the Intelligent Device for Energy Expenditure and Activity (IDEEA), was applied to measure gait parameters of patients across 30 m of flat floor in an orthopaedic ward. A linear regression model was used to determine the correlations between JOA scores and gait parameters. Multiple linear regressions were used to identify the relationships between subsections of the JOA systems and gait parameters. Japanese Orthopaedic Association scores of LDH patients from the JOA lumbar scoring system are significantly correlated with gait speed (R (2) = 0.557, P < 0.001) and stride length (R (2) = 0.544, P < 0.001). JOA scores are also correlated with double support duration, step duration, cycle duration and cadence, and weakly correlated with single support duration. For the four subsections of the JOA lumbar scoring system, "restriction of activities of daily living" is the significant predictor of all gait parameters, especially gait speed (R (2) = 0.573, P < 0.001) and stride length (R (2) = 0.553, P < 0.001). However, JOA scores of CSM patients from the JOA cervical scoring system are only weakly correlated with these measures (all R (2) < 0.3). For
Liao, Fuyuan; Wang, Jue; He, Ping
Gait rhythm of patients with Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS) has been studied focusing on the fractal and correlation properties of stride time fluctuations. In this study, we investigated gait asymmetry in these diseases using the multi-resolution entropy analysis of stance time fluctuations. Since stance time is likely to exhibit fluctuations across multiple spatial and temporal scales, the data series were decomposed into appropriate levels by applying stationary wavelet transform. The similarity between two corresponding wavelet coefficient series in terms of their regularities at each level was quantified based on a modified sample entropy method and a weighted sum was then used as gait symmetry index. We found that gait symmetry in subjects with PD and HD, especially with ALS is significantly disturbed. This method may be useful in characterizing certain pathologies of motor control and, possibly, in monitoring disease progression and evaluating the effect of an individual treatment.
Schmied, Oliver; Golini, Lorenzo; Steffen, Frank
Medical records of 41 dogs, including 15 small breed dogs (<15 kg) and 26 large breed dogs (>15 kg), with cervical intervertebral disc disease (IVDD) that underwent a hemilaminectomy were reviewed. Dogs were diagnosed using myelography, computed tomography/myelography, or MRI, and dogs were classified as having either Hansen Type I disc extrusion or Hansen Type II disc protrusion located ventrally, ventrolaterally, or laterally within the cervical spinal canal. The most common clinical presentation was ambulatory tetraparesis and/or lameness (44%). The most affected sites for cervical IVDD were between the sixth and seventh cervical vertebrae (C6-C7; 78% of Hansen Type II discs) and C2-C3 (86% of Hansen Type I discs). Treatment was effective in 88% of dogs. Five large breed dogs (12%) did not improve. In dogs with a Hansen Type I disc extrusion, clinical signs improved in 96% of the cases. In dogs with a Hansen Type II disc protrusion, an excellent and good outcome was seen in 47% and 32% of cases, respectively. Outcome was significantly better for small breed dogs and dogs with Hansen Type I disc disease compared with large breed dogs and dogs with Hansen Type II disc disease.
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
Sundquist, J; Forsling, M L; Olsson, J E; Akerlund, M
Arginine vasopressin (AVP) was determined in plasma and lumbar CSF from 46 patients with Parkinson's disease, dementia, cerebrovascular disease, multiple sclerosis and other, mostly peripheral neurological disorders. The mean plasma concentration of AVP was 1.62 microU/ml, the CSF concentration 1.14 microU/ml and the gradient CSF/plasma 0.72. There was a good correlation between the plasma and the CSF values in most patients. No sex difference could be found. A slight decrease of the CSF values could be found with increasing age. Significantly higher CSF-AVP values were found in patients with cerebrovascular disease, whereas lower CSF values were found in patients with dementia and Parkinson's disease. However there were decreased CSF/plasma gradients in patients with dementia and Parkinson's disease to about 0.30 compared to 0.98 in patients with peripheral neurological disorders. Patients with multiple sclerosis had an increased IgG index indicating an intrathecal IgG production but there was no obvious correlation between this and the AVP concentrations in plasma and CSF, nor with the total CSF protein content, nor with the albumin and IgG concentrations in plasma and CSF. PMID:6842195
Mitchell, N. S.; Cruess, R. L.
It is suggested that the former division of degenerative arthritis into idiopathic types and those secondary to some disease process is no longer valid. Recent studies have indicated that abnormal concentrations of force on cartilage lead to the development of this disease. A classification is presented that is based on the assumption that the process is initiated by abnormal concentrations of force on normal cartilage matrix, normal concentrations of force on abnormal cartilage matrix or normal concentrations of force on normal cartilage matrix that is supported by bone of abnormal consistency. PMID:907947
Nopoulos, Peggy C
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.
Nopoulos, Peggy C.
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
Bukovsky, Antonin; Copas, Pleas; Virant-Klun, Irma
The 50-year-old and currently prevailing view that all oocytes in adult human ovaries persist from the fetal period of life is controversial as it clashes with Darwinian evolutionary theory. Studies of oogenesis and follicular renewal in adult human ovaries, and of the role of hormonal signals and third-party cells (tissue macrophages and T cells), could all be helpful in providing better understanding of the causes of ovarian infertility, its prevention and potential therapy. In addition, the authors recently reported differentiation of distinct cell types and the production of new eggs in cultures derived from premenopausal and postmenopausal human ovaries. It is possible that fertilisation of such eggs will open up new opportunities for providing genetically related children to infertile women for whom conventional in vitro fertilisation has failed. As ovarian stem cells appear to represent a new type of totipotent adult stem cell, they could also be utilised for autologous stem cell therapy of degenerative diseases, without any involvement of allogeneic embryonic stem cells and somatic cell nuclear transfer.
Shetty, Prakash; Iyengar, Venkatesh; Sawaya, Ana; Diaz, Erik; Ma, Guansheng; Hernandez-Triana, Manuel; Yajnik, Chittaranjan; Forrester, Terrence; Valencia, Mauro; Rush, Elaine; Adeyemo, Adebowale; Jahoor, Farook; Roberts, Susan
Economic development in developing societies characterized by industrialization, urbanization, and globalization has seen the emergence of an epidemic of diet- and life-style-related chronic degenerative diseases. A research project was initiated under the aegis of the International Atomic Energy Agency (IAEA), Vienna, Austria under its Coordinated Research Programme (CRP) to promote the use of stable isotopic techniques to document the extent of the problem and to understand the determinants of this epidemic. The principal objectives of this CRP involving countries both in the North and the South are to define the magnitude of the problem of obesity and non-insulin dependent diabetes mellitus (NIDDM) in developing countries, to identify the vulnerable groups at increased risk, and to attempt to describe the metabolic and physiological mechanisms underlying this phenomenon. These comparative international studies of obesity and NIDDM are looking at the effects of childhood malnutrition (Brazil) and socioeconomic differentials (Mexico) on adult risk factors; the composition of the daily diet on obesity (Chile); levels of patterns of physical activity of older adults (China) as well as their influence on weight gain and obesity (Cuba, Nigeria); the impact of body composition and energy expenditure on the evolution frank diabetes from impaired glucose tolerance (Jamaica), and of body compositional changes and the role of inflammatory cytokines on impaired glucose tolerance (India). The last study conducted in New Zealand was aimed at comparing the energy expenditures of Maori (Pacific Island) with New Zealanders of European descent.
Zamprogno, Helia; Hansen, Bernie D; Bondell, Howard D; Sumrell, Andrea Thomson; Simpson, Wendy; Robertson, Ian D; Brown, James; Pease, Anthony P; Roe, Simon C; Hardie, Elizabeth M; Wheeler, Simon J; Lascelles, B Duncan X
To determine the items (question topics) for a subjective instrument to assess degenerative joint disease (DJD)-associated chronic pain in cats and determine the instrument design most appropriate for use by cat owners. 100 randomly selected client-owned cats from 6 months to 20 years old. Cats were evaluated to determine degree of radiographic DJD and signs of pain throughout the skeletal system. Two groups were identified: high DJD pain and low DJD pain. Owner-answered questions about activity and signs of pain were compared between the 2 groups to define items relating to chronic DJD pain. Interviews with 45 cat owners were performed to generate items. Fifty-three cat owners who had not been involved in any other part of the study, 19 veterinarians, and 2 statisticians assessed 6 preliminary instrument designs. 22 cats were selected for each group; 19 important items were identified, resulting in 12 potential items for the instrument; and 3 additional items were identified from owner interviews. Owners and veterinarians selected a 5-point descriptive instrument design over 11-point or visual analogue scale formats. Behaviors relating to activity were substantially different between healthy cats and cats with signs of DJD-associated pain. Fifteen items were identified as being potentially useful, and the preferred instrument design was identified. This information could be used to construct an owner-based questionnaire to assess feline DJD-associated pain. Once validated, such a questionnaire would assist in evaluating potential analgesic treatments for these patients.
Schmidt, K; Li, Z; Schubert, B; Huang, B; Stoyanova, S; Hamburger, M
A selection of 32 fungal strains, belonging to 8 genera of entomopathogenic Deuteromycetes collected in various provinces of China, were screened for activities on targets involved in degenerative diseases of the central nervous system. The strains were grown under various fermentation conditions, and a total of 256 different extracts were obtained. The bioassays included functional screens for NMDA antagonistic activity in stably transfected fibroblasts, for neuritogenic activities in PC-12 cells, and tests for MAO inhibitory and radical scavenging properties. Several extracts with promising activities were identified. Some Paecilomyces extracts induced pronounced axonal-like outgrowths in PC-12 cells. In Paecilomyces militaris RCEF 0095, the neuritogenic activity could be linked to yellow pigments. Three Beauveria and Paecilomyces strains showed radical scavenging properties, which could be localized in the extract by a bioautographic assay on TLC. An extract obtained from the mycelium of Paecilomyces tenuipes RCEF 0275 showed moderate MAO inhibitory activity, whereas extracts of Sporothrix chondracris RCEF 0187 antagonized NMDA receptor mediated cell toxicity.
Greggains, Gareth D.; Lister, Lisa M.; Tuppen, Helen A. L.; Zhang, Qi; Needham, Louise H.; Prathalingam, Nilendran; Hyslop, Louise A.; Craven, Lyndsey; Polanski, Zbigniew; Murdoch, Alison P.; Turnbull, Douglass M.; Herbert, Mary
Induced pluripotent stem cells (iPSCs) hold much promise in the quest for personalised cell therapies. However, the persistence of founder cell mitochondrial DNA (mtDNA) mutations limits the potential of iPSCs in the development of treatments for mtDNA disease. This problem may be overcome by using oocytes containing healthy mtDNA, to induce somatic cell nuclear reprogramming. However, the extent to which somatic cell mtDNA persists following fusion with human oocytes is unknown. Here we show that human nuclear transfer (NT) embryos contain very low levels of somatic cell mtDNA. In light of a recent report that embryonic stem cells can be derived from human NT embryos, our results highlight the therapeutic potential of NT for mtDNA disease, and underscore the importance of using human oocytes to pursue this goal. PMID:24457623
Andrieu, K; Allain, J; Longis, P-M; Steib, J-P; Beaurain, J; Delécrin, J
Lower back pain due to degenerative disc disease is a therapeutic challenge in young patients. Although arthrodesis is currently the gold standard for surgical treatment, improvement in total disc replacement techniques makes it possible to preserve segmental mobility with good results in one-level surgery. Nevertheless, the French National Health Authority does not recommend total disc replacement for multilevel surgery. Thus, hybrid constructs that combine one-level disc replacement with arthrodesis have been developed for multilevel indications. The outcome of two-level lumbar disc arthroplasty does not differ from hybrid constructs. The clinical and radiographic outcomes of disc arthroplasty were compared to hybrid constructs for two-level degenerative disc disease in 72 patients after a continuous follow-up of at least 2 years. The patients were divided into two groups that were similar for the indication and type of implants. There was no statistical difference in pain relief (-3.9 points versus -3.5 points for lumbar VAS) or reduction in ODI (-29.5% versus -27.0%) between TDR and hybrid constructs, respectively. There was no statistical difference in range of motion at the level of arthroplasty (8.4° versus 7.6°) and no kinematic dysfunction was identified. The re-operation rate at two years for persistent lumbar pain was respectively 6.7% for two-level disc arthroplasty and 4.3% for hybrid constructs. The complication rate was 4.8% and 8.7% respectively. No difference was found in this comparison of two homogeneous series between two-level disc arthroplasty and hybrid constructs for the treatment of degenerative disc disease after two years of follow-up. Two-level disc arthroplasty may be an alternative for young patients depending on an evaluation of long-term results. Cohort observational study level III. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Liang, Qian-Qian; Ding, Dao-Fang; Xi, Zhi-Jie; Chen, Yan; Li, Chen-Guang; Liu, Shu-Fen; Lu, Sheng; Zhao, Yong-Jian; Shi, Qi; Wang, Yong-Jun
Most chronic low back pain is the result of degeneration of the lumbar intervertebral disc. Ligustrazine, an alkaloid from Chuanxiong, reportedly is able to relieve pain, suppress inflammation, and treat osteoarthritis and it has the protective effect on cartilage and chondrocytes. Therefore, we asked whether ligustrazine could reduce intervertebral disc degeneration. To determine the effect of ligustrazine on disc degeneration, we applied a rat model. The intervertebral disc degeneration of the rats was induced by prolonged upright posture. We found that pretreatment with ligustrazine for 1 month recovered the structural distortion of the degenerative disc; inhibited the expression of type X collagen, matrix metalloproteinase (MMP)-13, and MMP3; upregulated type II collagen; and decreased IL-1 β , cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expression. In conclusion, ligustrazine is a promising agent for treating lumbar intervertebral disc degeneration disease.
Onishi, Eijiro; Ikeda, Noboru; Ueo, Toyoji
Although the prognosis of Perthes' disease at skeletal maturity is considered favorable, little is known about the long-term results after middle age. We retrospectively analyzed the radiographic and functional outcomes of 67 patients (70 hips) who had been treated for Perthes' disease. Of these patients, 28 patients (29 hips) were evaluated using JOA (Japanese Orthopaedic Association) score and radiographs at follow-up (Group 1), 39 patients (41 hips) were evaluated by a postal questionnaire (Group 2). The mean follow-up period was 36.1 years. The mean age at follow-up was 43.1 years. Group 1, good radiographic results (Stulberg class I or II) were achieved in 59% of hips. No osteoarthritis (Tönnis Grade 0) was observed in only 48% of hips. The clinical results were good (JOA score ≥ 70) in 79% of hips. Disturbance of walking ability and activities of daily living was little. The Tönnis grade and JOA score declined after 40 years of age. All patients older than 50 years showed severe osteoarthritis. The severity of osteoarthritis correlated significantly with age at follow-up. Group 2, the clinical results were good (JOA score ≥ 56) in 76% of hips. In both groups, no patient had undergone total hip arthroplasty. Younger age at diagnosis (<8 years) correlated significantly with a better result. The JOA score correlated significantly with age at follow-up. Patients who were treated for Perthes' disease have a risk of osteoarthritis and a clinically poor outcome after the age of 40-50 years.
Petilon, Julio; Roth, Jonathan; Hardenbrook, Mitchell
Evaluation of lumbar total disc arthroplasty (TDA) in military patients. To evaluate the clinical and radiographic outcomes of US military personnel who have undergone TDA for degenerative disc disease and to assess the retention versus discharge rate after undergoing this procedure. TDA was developed as an alternative to arthrodesis for the surgical management of degenerative disc disease with the goal of preserving motion and reducing adjacent segment disease. However, the indications and optimal candidates for this procedure are uncertain. Military members must maintain a certain level of physical fitness and be capable of meeting the demands of hazardous environments. This study reviews results of TDA performed on active duty military members. The surgery schedules from 2005 to 2008 were reviewed to identify military members who underwent single-level or 2-level TDA for degenerative disc disease after failing at least 6 months of conservative management. All patients had a minimum of 2-year follow-up. Preoperative and postoperative clinical assessments were completed using the Oswestry Disability Index (ODI) questionnaire and the numeric rating scale (NRS). Radiographs were evaluated to determine range of motion, height, and disc position at the operated levels. The retention rate of the patients in the military was also recorded. Statistical analysis of the data was carried out with significance assumed at the P < 0.05 level. Thirty-eight patients, implanted with a total of 56 discs, met the criteria for retrospective analysis. Twenty patients had single-level and 18 had 2-level TDA. Mean age was 35 (23 to 56 y) years. Mean follow-up was 28 months. The overall mean preoperative ODI and NRS of 53.6 and 7.3, significantly improved postoperatively to 27.7 and 3.3, respectively (P < 0.001). There was no difference in the postoperative ODI (P = 0.19) or NRS (P = 0.18) when comparing single-level and 2-level TDA. Clinical success was achieved in 79% of patients
De Boni, U
Human nervous-system cells in culture are a suitable model for the study of the degenerative changes associated with Alzheimer's disease. Alzheimer-diseased brain contains a factor which induces the formation of paired helical filaments (PHF) in cultured cells, similar to that seen in Alzheimer's disease. The excitotoxic amino acids, glutamate and aspartate, induce similar PHE formation in cultured cells. The neurotoxic element aluminium is present in high concentrations in the brain in several human neurological disorders, including Alzheimer's disease. In cultured-cell systems, aluminium interacts with acidic nuclear proteins, decreases steroid binding, produces a form of neurofibrillary degeneration and alters nucleoside metabolism.
Lee, Moonhee; Cho, Taesup; Jantaratnotai, Nattinee; Wang, Yu Tian; McGeer, Edith; McGeer, Patrick L
Oxidative stress induced by inhibition of glutathione (GSH) biosynthesis with D,L-buthionine-S,R-sulfoximine (BSO) causes human microglia, human astrocytes, THP-1 cells, and U373 cells to secrete materials toxic to human neuroblastoma SH-SY5Y cells and stimulates them to release TNF-alpha, IL-6, and nitrite ions. The effect is correlated with activation of the inflammatory pathways P38 MAP- kinase, Jun-N-terminal kinase, and NF-kappaB. The effect is reduced by adding to the medium GSH or clotrimazole (CTM), an inhibitor of Ca(2+)-influx through TRPM2 channels. It is also produced by inhibiting TRPM2 protein expression in microglia and astrocytes through introduction of its small inhibitory RNA (siRNA). TRPM2 mRNA is expressed by glial cells but not by SH-SY5Y cells. BSO in the culture medium causes an almost 3-fold increase in [Ca(2+)](i) in microglia and astrocytes over a 24-h period, which is reduced to half by the addition of CTM. The data strongly suggest that inhibiting intracellular GSH synthesis induces a neuroinflammatory response in human microglia and astrocytes, which is linked to Ca(2+) influx through TRPM2 channels. It represents a new model for inducing neuroinflammation and suggests that increasing GSH levels in glial cells may confer neuroprotection in neurodegenerative diseases, such as Alzheimer disease, which have a prominent neuroinflammatory component.
Yepes, Manuel; Winkles, Jeffrey A
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of structurally-related cytokines. TWEAK acts on responsive cells via binding to a cell surface receptor named fibroblast growth factor-inducible 14 (Fn14). TWEAK can regulate numerous cellular responses in vitro including cell proliferation, migration, survival, differentiation and apoptosis. TWEAK is also a proangiogenic and proinflammatory factor in vivo. Recent studies have indicated that pharmacological inhibition of TWEAK activity may have therapeutic efficacy in several diseases including ischemic stroke, cerebral edema, multiple sclerosis and rheumatoid arthritis. In this review we first introduce the TWEAK-Fn14 signaling system and then focus on the potential therapeutic utility of soluble Fn14-Fc fusion proteins and TWEAK neutralizing antibodies.
Wickner, Reed B; Edskes, Herman K; Bateman, David; Kelly, Amy C; Gorkovskiy, Anton
The yeast prions [URE3] and [PSI] are not found in wild strains, suggesting they are not an advantage. Prion-forming ability is not conserved, even within Saccharomyces, suggesting it is a disease. Prion domains have non-prion functions, explaining some conservation of sequence. However, in spite of the sequence being constrained in evolution by these non-prion functions, the prion domains vary more rapidly than the remainder of the molecule, and these changes produce a transmission barrier, suggesting that these changes were selected to block prion infection. Yeast prions [PSI] and [URE3] induce a cellular stress response (Hsp104 and Hsp70 induction), suggesting the cells are not happy about being infected. Recently, we showed that the array of [PSI] and [URE3] prions includes a majority of lethal or very toxic variants, a result not expected if either prion were an adaptive cellular response to stress.
Background The therapeutic efficacy of an intervention is often assessed in clinical trials by scales measuring multiple diverse activities that are added to produce a cumulative global score. Medical communities and health care systems subsequently use these data to calculate pooled effect sizes to compare treatments. This is done because major doubt has been cast over the clinical relevance of statistically significant findings relying on p values with the potential to report chance findings. Hence in an aim to overcome this pooling the results of clinical studies into a meta-analyses with a statistical calculus has been assumed to be a more definitive way of deciding of efficacy. Methods We simulate the therapeutic effects as measured with additive scales in patient cohorts with different disease severity and assess the limitations of an effect size calculation of additive scales which are proven mathematically. Results We demonstrate that the major problem, which cannot be overcome by current numerical methods, is the complex nature and neurobiological foundation of clinical psychiatric endpoints in particular and additive scales in general. This is particularly relevant for endpoints used in dementia research. 'Cognition' is composed of functions such as memory, attention, orientation and many more. These individual functions decline in varied and non-linear ways. Here we demonstrate that with progressive diseases cumulative values from multidimensional scales are subject to distortion by the limitations of the additive scale. The non-linearity of the decline of function impedes the calculation of effect sizes based on cumulative values from these multidimensional scales. Conclusions Statistical analysis needs to be guided by boundaries of the biological condition. Alternatively, we suggest a different approach avoiding the error imposed by over-analysis of cumulative global scores from additive scales. PMID:22176535
Reyes-Sánchez, Alejandro; Rosales-Olivares, Luis Miguel
Klippel-Feil syndrome (KFS) is a complex congenital condition characterized by improper segmentation of cervical motion segments that could contribute to undesirable adjacent segment degeneration. KFS patients have a strong tendency to present with disease in the adjacent segments. When this condition is present, anterior decompression followed by total disc replacement can be performed safely and can lead to good clinical results. This treatment has theoretical advantages compared with anterior decompression and fusion. Comparative studies and long-term follow-up are needed. Complications associated with fusion include loss of a motion segment, disc height loss, subsidence of the graft, progressive degenerative changes at the adjacent level, graft-related complications, and graft-site complications. Such new technologies as motion preservation spine arthroplasty represent attempts to avoid these complications. Here we present a case report of a 62-year-old female patient with type I congenital fusion at the C5–6 level, with a history of neck pain and right radiculopathy at C5–7. X-rays and MRI show evidence of adjacent segment degeneration at levels above and below congenital fusion. The patient's preoperative visual analog score (VAS) for neck pain was 7 out of a possible 10, her score for right upper extremity pain was 8 out of 10, and her Neck Disability Index (NDI) was 32%. Surgical treatment consisted of anterior decompression and total disc replacement at both levels. At 1-year follow-up, the patient's VAS for neck pain was 2 out of 10, her VAS score for right upper extremity pain was 1 of 10, and her NDI was 9%. PMID:25802590
Reyes-Sánchez, Alejandro; Zárate-Kalfópulos, Barón; Rosales-Olivares, Luis Miguel
Klippel-Feil syndrome (KFS) is a complex congenital condition characterized by improper segmentation of cervical motion segments that could contribute to undesirable adjacent segment degeneration. KFS patients have a strong tendency to present with disease in the adjacent segments. When this condition is present, anterior decompression followed by total disc replacement can be performed safely and can lead to good clinical results. This treatment has theoretical advantages compared with anterior decompression and fusion. Comparative studies and long-term follow-up are needed. Complications associated with fusion include loss of a motion segment, disc height loss, subsidence of the graft, progressive degenerative changes at the adjacent level, graft-related complications, and graft-site complications. Such new technologies as motion preservation spine arthroplasty represent attempts to avoid these complications. Here we present a case report of a 62-year-old female patient with type I congenital fusion at the C5-6 level, with a history of neck pain and right radiculopathy at C5-7. X-rays and MRI show evidence of adjacent segment degeneration at levels above and below congenital fusion. The patient's preoperative visual analog score (VAS) for neck pain was 7 out of a possible 10, her score for right upper extremity pain was 8 out of 10, and her Neck Disability Index (NDI) was 32%. Surgical treatment consisted of anterior decompression and total disc replacement at both levels. At 1-year follow-up, the patient's VAS for neck pain was 2 out of 10, her VAS score for right upper extremity pain was 1 of 10, and her NDI was 9%.
Dyka, Frank M; Boye, Sanford L; Ryals, Renee C; Chiodo, Vince A; Boye, Shannon E; Hauswirth, William W
Achromatopsia (ACHM) is caused by a progressive loss of cone photoreceptors leading to color blindness and poor visual acuity. Animal studies and human clinical trials have shown that gene replacement therapy with adeno-associate virus (AAV) is a viable treatment option for this disease. Although there have been successful attempts to optimize capsid proteins for increased specificity, it is simpler to restrict expression via the use of cell type-specific promoters. To target cone photoreceptors, a chimeric promoter consisting of an enhancer element of interphotoreceptor retinoid-binding protein promoter and a minimal sequence of the human transducin alpha-subunit promoter (IRBPe/GNAT2) was created. Additionally, a synthetic transducin alpha-subunit promoter (synGNAT2/GNAT2) containing conserved sequence blocks located downstream of the transcriptional start was created. The strength and specificity of these promoters were evaluated in murine retina by immunohistochemistry. The results showed that the chimeric, (IRBPe/GNAT2) promoter is more efficient and specific than the synthetic, synGNAT2/GNAT2 promoter. Additionally, IRBPe/GNAT2-mediated expression was found in all cone subtypes and it was improved over existing promoters currently used for gene therapy of achromatopsia.
Nakao, S; Hirakawa, A; Fukushima, R; Kobayashi, M; Machida, N
The hearts of seven elderly dogs in which bradycardia-tachycardia syndrome (BTS) had been diagnosed electrocardiographically were examined post mortem. The clinical basis of the underlying heart disease was invariably mitral or mitral and tricuspid regurgitation. Microscopical examination of the sinoatrial (SA) node and the SA junctional region consistently revealed depletion of SA nodal cells, with a corresponding increase in fibrous or fibro-fatty tissue that interrupted contiguity between the SA node and the surrounding atrial myocardium. The left and right atrial walls showed an increased amount of fibrous tissue in the myocardium and disruption of the muscle bundle architecture (interstitial myocardial fibrosis) to varying degrees. Qualitatively, these changes in the SA node and the SA node region resembled those associated with ageing in elderly people with or without BTS. Thus, it is possible that the pathological process affecting the SA node in these dogs was fundamentally related to ageing and may have caused BTS, in combination with atrial myocardial lesions caused by mitral and tricuspid regurgitation.
Dyka, Frank M.; Boye, Sanford L.; Ryals, Renee C.; Chiodo, Vince A.; Boye, Shannon E.; Hauswirth, William W.
Achromatopsia (ACHM) is caused by a progressive loss of cone photoreceptors leading to color blindness and poor visual acuity. Animal studies and human clinical trials have shown that gene replacement therapy with adeno-associate virus (AAV) is a viable treatment option for this disease. Although there have been successful attempts to optimize capsid proteins for increased specificity, it is simpler to restrict expression via the use of cell type-specific promoters. To target cone photoreceptors, a chimeric promoter consisting of an enhancer element of inter-photoreceptor retinoid-binding protein promoter and a minimal sequence of the human transducin alpha-subunit promoter (IRBPe/GNAT2) was created. Additionally, a synthetic transducin alpha-subunit promoter (synGNAT2/GNAT2) containing conserved sequence blocks located downstream of the transcriptional start was created. The strength and specificity of these promoters were evaluated in murine retina by immunohistochemistry. The results showed that the chimeric, (IRBPe/GNAT2) promoter is more efficient and specific than the synthetic, synGNAT2/GNAT2 promoter. Additionally, IRBPe/GNAT2-mediated expression was found in all cone subtypes and it was improved over existing promoters currently used for gene therapy of achromatopsia. PMID:24664760
Aires, Virginie; Delmas, Dominique
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.
Soto-Bustos, Ángel; Caro-Vadillo, Alicia; Martínez-DE-Merlo, Elena; Alonso-Alegre, Elisa González
The purpose of this research was to compare the accuracy of newly described P wave-related parameters (P wave area, Macrux index and mean electrical axis) with classical P wave-related parameters (voltage and duration of P wave) for the assessment of left atrial (LA) size in dogs with degenerative mitral valve disease. One hundred forty-six dogs (37 healthy control dogs and 109 dogs with degenerative mitral valve disease) were prospectively studied. Two-dimensional echocardiography examinations and a 6-lead ECG were performed prospectively in all dogs. Echocardiography parameters, including determination of the ratios LA diameter/aortic root diameter and LA area/aortic root area, were compared to P wave-related parameters: P wave area, Macrux index, mean electrical axis voltage and duration of P wave. The results showed that P wave-related parameters (classical and newly described) had low sensitivity (range=52.3% to 77%; median=60%) and low to moderate specificity (range=47.2% to 82.5%; median 56.3%) for the prediction of left atrial enlargement. The areas under the curve of P wave-related parameters were moderate to low due to poor sensitivity. In conclusion, newly P wave-related parameters do not increase the diagnostic capacity of ECG as a predictor of left atrial enlargement in dogs with degenerative mitral valve disease.
Harder, Lisa K; Galindo-Zamora, Vladimir; Beyerbach, Martin; Nolte, Ingo; Wefstaedt, Patrick
Canine intervertebral disc degeneration can lead to intervertebral disc disease. Mild degenerative changes in the structure of the canine intervertebral disc can be identified in magnetic resonance images, whereas these changes are not visible in computed tomographic images. Therefore, one aim of this study was to detect whether colour-coded computed tomography enhances the visibility of mild degenerative changes in the canine disc structure compared to non-contrast computed tomography. Furthermore, the study aimed to detect if intervertebral disc degeneration could be classified with a higher reliability in colour-coded images than in non-contrast images. Computed tomographic image studies of 144 canine intervertebral discs were coloured using three different lookup tables. Canine intervertebral disc degeneration was evaluated by three observers using a 5-grade classification system and compared to the evaluation of non-contrast CT and MRI images. A moderate to almost perfect intraobserver and a moderate to substantial interobserver agreement were found depending on the used colour code. On comparing non-contrast and colour-coded CT significant differences were found by one observer only. Significant differences in evaluation were found in grading intervertebral disc degeneration in MRI and colour-coded CT. Intervertebral disc degeneration could not be classified with a higher reliability on colour-coded images compared to non-contrast images. Furthermore, colour-coded CT did not enhance the visibility of mild degenerative changes in disc structure compared to non-contrast CT. However, the better intraobserver agreement and the subjective impression of the observers highlighted that the usage of colour encoded CT data sets with a wide range of tonal values of few primary and secondary colours may facilitate evaluation.
Naeem, Aabgeena; Amani, Samreen
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.
Naeem, Aabgeena; Amani, Samreen
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
Cetin, Ebru N.; Bir, Levent S.; Sarac, Gülden; Yaldızkaya, Filiz; Yaylalı, Volkan
Abstract This study was conducted to assess optic nerve and peripapillary retinal nerve fibre layer (RNFL) changes in patients with idiopathic Parkinson’s disease (PD) and its correlation with disease duration and severity. Optic nerve parameters and RNFL thickness were measured in 24 PD patients and 25 age–gender-matched controls by Heidelberg Retinal Tomography II (Heidelberg Engineering, Dossenheim, Germany). Patients with visual acuity below 20/25 were excluded. The mean RNFL in the temporal sector was significantly thinner in the study group than the control group (p = 0.020). Additionally, disease severity and duration negatively correlated with optic disc parameters in some sectors. PMID:28163751
Xie, Tuqiang; Guo, Shuguang; Zhang, Jun; Chen, Zhongping; Peavy, George M
Previous studies have demonstrated that optical coherence tomography (OCT) could be used to delineate alterations in the microstructure of cartilage, and have suggested that changes in the polarization state of light as detected by OCT could provide information on the birefringence properties of articular cartilage as influenced by disease. In this study we have used both OCT and polarization sensitive optical coherence tomography (PS-OCT) technologies to evaluate normal and abnormal bovine articular cartilage according to established structural, organizational, and birefringent characteristics of degenerative joint disease (DJD) in order to determine if this technology can be used to differentiate various stages of DJD as a minimally invasive imaging tool. Fresh bovine femoral-tibial joints were obtained from an abattoir, and 45 cartilage specimens were harvested from 8 tibial plateaus. Whole ex vivo specimens of normal and degenerative articular cartilage were imaged by both OCT and PS-OCT, then fixed and processed for histological evaluation. OCT/PS-OCT images and corresponding histology sections of each specimen were scored according to a modified Mankin structural grading scale and compared. OCT and PS-OCT imaging allowed structural evaluation of intact articular cartilage along a 6 mm surface length to a depth of 2 mm with a transverse resolution of 12 microm and an axial resolution of 10 microm. The OCT and PS-OCT images demonstrated characteristic alterations in the structure of articular cartilage with a high correlation to histological evaluation (kappa = 0.776). The OCT images were able to demonstrate early to advanced structural changes of articular cartilage while the optical phase retardation images obtained by PS-OCT imaging were able to discriminate areas where disorganization of the cartilage matrix was present, however, these characteristics are much different than those reported where OCT images alone were used to characterize tissue
Wang, F; Cai, F; Shi, R; Wang, X-H; Wu, X-T
Intervertebral disc (IVD) degeneration is a complicated process that involves both age-related change and tissue damage caused by multiple stresses. In a degenerative IVD, cellular senescence accumulates and is associated with reduced proliferation, compromised self-repair, increased inflammatory response, and enhanced catabolic metabolism. In this review, we decipher the senescence mechanism of IVD degeneration (IVDD) by interpreting how aging coordinates with age-related, microenvironment-derived stresses in promoting disc cell senescence and accelerating IVDD. After chronic and prolonged replication, cell senescence may occur as a natural part of the disc aging process, but can potentially be accelerated by growth factor deficiency, oxidative accumulation, and inflammatory irritation. While acute disc injury, excessive mechanical overloading, diabetes, and chronic tobacco smoking contribute to the amplification of senescence-inducing stresses, the avascular nature of IVD impairs the immune-clearance of the senescent disc cells, which accumulate in cell clusters, demonstrate inflammatory and catabolic phenotypes, deteriorate disc microenvironment, and accelerate IVDD. Anti-senescence strategies, including telomerase transduction, supply of growth factors, and blocking cell cycle inhibitors, have been shown to be feasible in rescuing disc cells from early senescence, but their efficiency for disc regeneration requires more in vivo validations. Guidelines dedicated to avoiding or alleviating senescence-inducing stresses might decelerate cellular senescence and benefit patients with IVD degenerative diseases. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Lee, J; Mizuno, M; Mizuno, T; Harada, K; Uechi, M
Evaluation of myocardial function is clinically challenging in dogs with degenerative mitral valve disease (DMVD). Although myocardial dysfunction is caused by pathologic degeneration, histopathologic progression is poorly understood. To characterize myocardial and pulmonary pathologic changes according to severity in dogs with naturally occurring DMVD, and to investigate whether or not pathologic degeneration is reflected by traditional clinical indices. One hundred and seventeen dogs with naturally occurring DMVD. Prospective observational study. Biopsied left atrium (LA), left ventricle (LV), and lung were evaluated histologically, and an attempt was made to correlate pathologic findings with clinical indices. Severe myocardial changes were observed in all International Small Animal Cardiac Health Council classes. In the lung, heart failure cell levels were significantly increased in class III patients (P < .0001). In a paired comparison, the LA showed significantly more severe degeneration than the LV, including myocardial fatty replacement, immune cell infiltration, and interstitial fibrosis (P < .0001). In contrast, myocardial cells were more hypertrophied in the LV than in the LA (P < .0001). Left ventricular end-diastolic dimension (LVEDd) was associated with fatty replacement (P = .033, R(2) = 0.584) and myocardial vacuolization (P = .003, R(2) = 0.588) in the LA. In DMVD, although severe pathologic changes may be evident even in early stages, there may be pathologic discrepancy between the LA and the LV. Myocardial degeneration may be reflected by clinical indices such as LVEDd and EF. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Murphy, Meghan E; Maloney, Patrick R; McCutcheon, Brandon A; Rinaldo, Lorenzo; Shepherd, Daniel; Kerezoudis, Panagiotis; Gilder, Hannah; Ubl, Daniel S; Crowson, Cynthia S; Freedman, Brett A; Habermann, Elizabeth B; Bydon, Mohamad
Patients recovering from decompressive laminectomy without fusion may require assistance with activities of daily living and physical/occupational therapy upon hospital discharge. To examine comorbidities and perioperative characteristics of patients undergoing lumbar decompression for associations with discharge status using a multicenter database. A multicenter database was used for this retrospective cohort analysis. Patients admitted from home with degenerative spine disease for lumbar decompression without fusion were included. Thirty-day outcomes and operative characteristics were compared as a function of patient discharge using chi-square and Wilcoxon Rank Sum tests. Multivariable logistic regression was used to determine factors associated with discharge to a nonhome facility. Of the 8627 patients included for analysis, 9.7% were discharged to a nonhome facility. On multivariable analysis, age (85+ vs <65, odds ratio [OR] 13.59), number of levels of decompression (3+ vs 1, OR 1.75), African American race vs Non-Hispanic or Hispanic White (OR 1.87), female vs male gender (OR 1.97), body mass index (BMI) (40+ vs 18.5-24.9, OR 1.74), American Society of Anesthesiologists physical classification status (4 vs 1 or 2, OR 2.35), hypertension (OR 1.29), dependent functional status (OR 3.92), diabetes (OR 1.47), smoking (OR 1.40), hematocrit (<35 vs 35+, OR 1.76), international normalized ratio (≥1.3 vs <1.3, OR 2.32), and operative time (3+ h vs <1 h, OR 5.34) were significantly associated with an increased odds of discharge to nonhome facilities. Preoperative status and operative course variables can influence discharge disposition in lumbar decompression patients. Identifying specific factors that contribute to a greater likelihood of dismissal to skilled facility or rehabilitation unit can further inform both surgeons and patients during preoperative counseling and disposition planning.
Noshchenko, Andriy; Hoffecker, Lilian; Lindley, Emily M; Burger, Evalina L; Cain, Christopher M J; Patel, Vikas V
Systematic review with meta-analysis. To (1) evaluate long-term patient-centered clinical outcomes after lumbar arthrodesis with or without decompression for lumbar spondylosis (LS); and (2) compare these outcomes with those of alternative treatments, including nonsurgical and surgical which maintain mobility of the lumbar spine. The effective treatment of LS is a complex clinical and economic concern for patients and health care providers. (1) randomized controlled clinical trials (RCTs) comparing treatment effects of lumbar arthrodesis with other interventions; (2) participants: skeletally mature adults with lumbar degenerative disk disease. Ovid MEDLINE, Embase, the Cochrane Library, and others. All years through February of 2013 were included. Patient-centered clinical outcomes before treatment, at 12, 24, or >24 months of follow-up, and rate of complications and additional surgical treatment were collected. A meta-analysis was performed to evaluate pooled treatment effects. The GRADE approach was applied to evaluate the level of evidence. The review included 38 studies of 5738 participants. All studies showed strong or at least moderate treatment effects of lumbar arthrodesis at 12, 24, and 48-72 months of follow-up. The level of evidence was moderate at 12 and 24 months, and low at 48-72 months. The pooled long-term treatment effect of lumbar arthrodesis exceeded those of: nonsurgical treatment (P<0.0001) with a moderate level of evidence, and decompression without fusion (P=0.005) with a low level of evidence. The treatment effect of lumbar arthrodesis showed a small inferiority versus arthroplasty at 12 and 24 months of follow-up (P<0.001), but not after 24 months postoperative. This review indicates that surgical stabilization of the lumbar spine is an effective treatment for LS; in particular, for patients with severe chronic low back pain that has been resistant to ≥3 months of conservative therapy.
Moriguchi, Yu; Alimi, Marjan; Khair, Thamina; Manolarakis, George; Berlin, Connor; Bonassar, Lawrence J.; Härtl, Roger
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
Beeravolu, Naimisha; Brougham, Jared; Khan, Irfan; McKee, Christina; Perez-Cruet, Mick; Chaudhry, G Rasul
Intervertebral disc (IVD) degeneration is characterized by the loss of nucleus pulposus (NP), which is a common cause for lower back pain. Although, currently, there is no cure for the degenerative disc disease, stem cell therapy is increasingly being considered for its treatment. In this study, we investigated the feasibility and efficacy of human umbilical cord mesenchymal stem cells (MSCs) and chondroprogenitor cells (CPCs) derived from those cells to regenerate damaged IVD in a rabbit model. Transplanted cells survived, engrafted and dispersed into NP in situ. Significant improvement in the histology, cellularity, extracellular matrix proteins, and water and glycosaminoglycan contents in IVD recipients of CPCs was observed compared to MSCs. In addition, IVDs receiving CPCs exhibited higher expression of NP-specific human markers, SOX9, aggrecan, collagen 2, FOXF1 and KRT19. The novelty of the study is that in vitro differentiated CPCs derived from umbilical cord MSCs, demonstrated far greater capacity to regenerate damaged IVDs, which provides basis and impetus for stem cell based clinical studies to treat degenerative disc disease. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Iwasaki, Laura R.; Crosby, Michael J.; Gonzalez, Yoly; McCall, Willard D.; Marx, David B.; Ohrbach, Richard; Nickel, Jeffrey C.
The likelihood of development of degenerative joint disease (DJD) of the temporomandibular joint (TMJ) is related to the integrity of the TMJ disc. Predilection for mechanical failure of the TMJ disc may reflect inter-individual differences in TMJ loads. Nine females and eight males in each of normal TMJ disc position and bilateral disc displacement diagnostic groups consented to participate in our study. Disc position was determined by bilateral magnetic resonance images of the joints. Three-dimensional (3D) anatomical geometry of each subject was used in a validated computer-assisted numerical model to calculate ipsilateral and contralateral TMJ loads for a range of biting positions (incisor, canine, molar) and angles (1–13). Each TMJ load was a resultant vector at the anterosuperior-most mediolateral midpoint on the condyle and characterized in terms of magnitude and 3D orientation. Analysis of variance (ANOVA) was used to test for effects of biting position and angle on TMJ loads. Mean TMJ loads in subjects with disc displacement were 9.5–69% higher than in subjects with normal disc position. During canine biting, TMJ loads in subjects with disc displacement were 43% (ipsilateral condyle,p=0.029) and 49% (contralateral condyle,p=0.015) higher on average than in subjects with normal disc position. Biting angle effects showed that laterally directed forces on the dentition produced ipsilateral joint loads, which on average were 69% higher (p=0.002) compared to individuals with normal TMJ disc position. The data reported here describe large differences in TMJ loads between individuals with disc displacement and normal disc position. The results support future investigations of inter-individual differences in joint mechanics as a variable in the development of DJD of the TMJ. PMID:20890385
Zhang, Jianfeng; Meng, Fanxin; Ding, Yan; Li, Jie; Han, Jian; Zhang, Xintao; Dong, Wei
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
Bitetto, W V; Brown, N O
In no other area of veterinary surgery is the selection and performance of the appropriate surgical approach more important than neurosurgery. An adequate, atraumatic, and anatomically sound exposure is an important part of the battle in most orthopaedic procedures and is an even more important consideration when related to neurosurgery. The delicate and often unforgiving nature of the tissue involved dictates that careful planning and attention to detail become high priority concerns for the veterinary neurosurgeon. Most veterinarians recommend surgery for dogs with severe impairment, recurrent disease, and progressively deteriorating neurologic signs. Difficulties remain in the timing of surgery and in the choice of what surgical approach is most appropriate for the neurologically impaired dog in question. Surgical approaches in the cervical region include ventral and dorsal. In the thoracolumbar spine, either dorsal or dorsolateral approaches are used. In the lumbosacral region, a dorsal approach is preferred. The objective of this chapter will be to compare and contrast each of these approaches and to guide the reader in the selection of the appropriate approach for each patient.
Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.
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
Structural Studies on Acetylcholinesterase and Paraoxonase Directed Towards Development of Therapeutic Biomolecules for the Treatment of Degenerative Diseases and Protection Against Chemical Threat Agents
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.
Kasdan, Richard B; Howard, Jaime L
Magnetic resonance imaging (MRI) has become a valuable noninvasive, cost-effective tool for accurately evaluating spine disorders. This article affords a comprehensive review of normal anatomy as it relates to MRI interpretation with specific attention to accurately defining nerve root abnormalities. It gives in-depth detail on disc herniation nomenclature with specific examples of disc bulge, disc protrusion, disc extrusion, and disc sequestration. In addition, there are illustrations of various forms of degenerative spine disease, including intradiscal degenerative disease, reactive end plate changes, spinal stenosis, synovial cyst formation, and spinal instability. Differentiating features for separating osteoporotic spine fracture from underlying neoplastic pathologic fracture are illustrated. Finally, examples of both benign and malignant disease are illustrated in the spine with corresponding clinical and MRI examples.
Risbud, Makarand V.; Shapiro, Irving. M
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
Nunley, Pierce D; Jawahar, Ajay; Kerr, Eubulus J; Gordon, Charles J; Cavanaugh, David A; Birdsong, Elisa M; Stocks, Marolyn; Danielson, Guy
Prospective randomized clinical trials. To compare the outcome data with respect to clinical success rates and incidence of adjacent level disease (ALD) in patients after total disc arthroplasty (TDA) or anterior cervical fusion (ACDF) for 1- and 2-level cervical disc disease. Previously published studies have provided evidence that ACDF procedure for cervical degenerative disc disease (DDD) may increase the stress on the nonoperated adjacent cervical segments, thus possibly increasing the risk of degeneration at these levels. The theoretical assumption that TDA may reduce the incidence of future ALD by preserving motion at the affected segments has, however, never been validated by clinical evidence. One hundred seventy patients with established symptomatic cervical disc disease at 1 or 2 levels participated in 3 prospective randomized clinical trials at 2 institutions. Participating subjects were randomized to receive TDA (treatment; n = 113) or ACDF (control; n = 57) by 6 independent investigating surgeons. Visual analogue pain scores (0-100), Neck Disability Index, neurological examination, and cervical spine radiographs were collected at enrollment and then 6 weeks and 3, 6, 12, 24, 36, and 48 months after surgery. Patients with persistent symptoms during the follow-up period were investigated for adjacent segment disease (ASD) with computed tomography/magnetic resonance imaging of the cervical spine, neurophysiology, and subsequent active interventions. At the median follow-up of 42 months (range: 28-54 months), 9 (14.3%) ACDF and 19 (16.8%) TDA patients developed and were actively treated for ASD. Osteopenia dust energy x-ray absorptiometry T scores of -1.5 to -2.4) (P = 0.04; 95% confidence interval [CI]: 0.007-0.223) and concurrent lumbar degenerative disease (P = 0.02; 95% CI: 0.003-0.196) significantly increased the risk of ASD. The risk of developing adjacent segment degeneration was equivalent at median 38 months after both ACDF and TDA procedures in
Zhang, Yan; Tao, Hui; Gu, Tao; Zhou, Mingyue; Jia, Zhiwei; Jiang, Gangqiang; Chen, Chun; Han, Zhihua; Xu, Cheng; Wang, Deli; He, Qing; Ruan, Dike
Cell-based therapy was a promising treatment method for disc degenerative diseases. Wharton's jelly cell (WJC) has been explored to cure various human diseases, while it still remains unknown about this MSC for disc repair. In our prior work, WJCs could differentiate into nucleus pulposus (NP)-like cells by co-culturing with NP cells in vitro. Thence, the aim of this study was further to investigate the survival and function of WJCs in vivo after transplantation into degenerated canine discs. WJCs were isolated from human umbilical cords and labeled with EGFP. The degeneration of L4-5, L5-6, and L6-7 discs of beagles was induced by aspirating the NP tissues. Four weeks after the operation, the injured discs were left to be no treatment at L4-5 (DS group), injected with 0.9 % saline at L5-6 (FS group), and transplanted with EGFP-labeled WJCs at L6-7 (TS group). In all animals, the intact disc L3-4 served as a control (CS group). The animals were followed up for 24 weeks after initial operation. Spine imaging was evaluated at 4, 8, 12, and 24 weeks, respectively. Histologic, biomechanics and gene expression analyses were performed at 24 weeks. Immunohistochemistry for aggrecan, types II collagen, SOX-9 was employed to investigate the matrix formation in the NP. The TS group showed a significantly smaller reduction in the disc height and T2-weighted signal intensity, and a better spinal segmental stability than DS and FS groups. Histologic assay demonstrated that WJCs were specifically detected in TS group at 24 weeks and the discs of TS group maintained a relatively well preserved structure as compared to the discs of DS and FS groups. Furthermore, real-time PCR and immunohistochemistry demonstrated that expressions of disc matrix genes, aggrecan, type II collagen, and SOX-9, were up-regulated in TS group compared to DS and FS groups. WJCs could not only survive in the degenerate IVDs, but also promote the disc matrix formation of aggrecan and type II collagen
Tagawa, Yoshiaki; Suzuki, Yasuo; Sakaguchi, Takatoshi; Endoh, Hiroki; Yokoi, Masahiko; Kase, Manabu
A 29-year-old fisherman exhibited optic disc oedema and peripapillary retinal detachment in the right eye, whereas in the left eye, optic atrophy and intraretinal exudates were already observed on first examination. About 6 months earlier, he noticed blurred vision of the left eye but took no medication. Visual acuity was 0.4 OD and 0.01 OS. Perimetry showed a large lower-half field defect with sparing 10° central field in the right eye and a large central scotoma in the left eye. Fluorescein angiography showed existence of arteriole or capillary nonperfusion and hyperpermeability of surrounding capillaries. Since serological examinations showed positive Bartonella immunoglobulin G (IgG) and other causes of neuroretinitis (NR) were excluded, NR in the present case was caused by cat scratch disease (CSD). Optic atrophy appeared 2 weeks after onset. Optical coherence tomography 13 weeks after onset revealed severe loss of retinal nerve fibre layer (RNFL) superior and nasal to the optic disc in both eyes and temporal in the left eye. Visual acuity of the right eye improved to 1.2 by the treatment, whereas visual field defects were persistent. CSD-NR in the present case developed abrupt appearance of optic atrophy with severe RNFL loss in the right eye, which was elicited by exudative, obliterative vasculitis in the superficial layer of the optic disc.
Iorio, Justin A.; Jakoi, Andre M.
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
Rischke, Burkhard; Ross, Raymond S.; Jollenbeck, Boris A.; Zimmers, Kari B.; Defibaugh, Neal D.
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
Biava, Pier M; Norbiato, Guido
As the modern society is troubled by multi-factorial diseases, research has been conducted on complex realities including chronic inflammation, cancer, obesity, HIV infection, metabolic syndrome and its detrimental cardiovascular complications as well as depression and other brain disorders. Deterioration of crucial homeostatic mechanisms in such diseases invariably results in activation of inflammatory mediators, chronic inflammation, loss in immunological function, increased susceptibility to diseases, alteration of metabolism, decrease of energy production and neuro-cognitive decline. Regulation of genes expression by epigenetic code is the dominant mechanism for the transduction of environmental inputs, such as stress and inflammation to lasting physiological changes. Acute and chronic stress determines DNA methylation and histone modifications in brain regions which may contribute to neuro-degenerative disorders. Nuclear glucocorticoids receptor interacts with the epigenoma resulting in a cortisol resistance status associated with a deterioration of the metabolic and immune functions. Gonadal steroids receptors have a similar capacity to produce epigenomic reorganization of chromatine structure. Epigenomic-induced reduction in immune cells telomeres length has been observed in many degenerative diseases, including all types of cancer. The final result of these epigenetic alterations is a serious damage to the neuro-endocrine-immune-metabolic adaptive systems. In this study, we propose a treatment with stem cells differentiation stage factors taken from zebrafish embryos which are able to regulate the genes expression of normal and pathological stem cells in a different specific way.
Lozano-Álvarez, C; Pérez-Prieto, D; Saló-Bru, G; Molina, A; Lladó, A; Cáceres, E; Ramírez, M
To evaluate the influence of epidemiological factors on the outcomes of surgery for degenerative lumbar disease in terms of quality of life, disability and chronic pain. A total of 263 patients who received surgery for degenerative lumbar disease (2005-2008) were included in the study. The epidemiological data collected were age, gender, employment status, and co-morbidity. The SF-36, Oswestry Disability Index (ODI), Core Outcomes Measures Index (COMI), and VAS score for lumbar and sciatic pain were measure before and 2 years after surgery. The correlation between epidemiological data and questionnaire results, as well as any independent prognostic factors, were assessed in the data analysis. The mean age of the patients was 54.0 years (22-86), and 131 were female (49.8%). There were 42 (16%) lost to follow-up. Statistically significant correlations (P<.05) were observed between age, gender, co-morbidity, permanent sick leave, and pre-operative pain with changes in the ODI, COMI, physical and SF-36 mental scales, and lumbar and sciatic VAS. Linear regression analysis showed permanent sick leave and age as predictive factors of disability (β=14.146; 95% CI: 9.09 - 29.58; P<.01 and β=0.334; 95% CI: 0.40 - 0.98, P<.05, respectively), and change in quality of life (β=-8.568; 95% CI: -14.88 - -2.26; p<.01 and β=-0.228, IC 95% CI: -0.40 - -0.06, P<.05, respectively). Based on our findings, age and permanent sick leave have to be considered as negative epidemiologic predictive factors of the outcome of degenerative lumbar disease surgery. Copyright © 2012 SECOT. Published by Elsevier Espana. All rights reserved.
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 percutaneous insertion of an expandable or a standard rigid interbody implant for patients with degenerative disk disease with or without spondylolisthesis and for revision surgery with the endoscopic posterolateral approach. 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 significant (p<0.05) 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 percutaneous 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
Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Shelton, G. Diane; Katz, Martin L.
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
Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Shelton, G Diane; Katz, Martin L
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.
Barbagallo, Giuseppe M V; Raudino, Giuseppe; Visocchi, Massimiliano; Alobaid, A Abdulrazzaq; Al-Mutair, A Abdulaziz; Naveen, Thomas; Certo, Francesco
Minimally invasive spine surgery (MISS), including percutaneous pedicle-screw fixation (PPSF), mini-open transforaminal lumbar interbody fusion (m-open TLIF), vertebroplasty, and stentoplasty, allows the preservation of neurological function and the restoration of spine stability, while reducing associated risks and complications. This study aimed to analyze the safety and efficacy of MISS in elderly patients suffering from degenerative or traumatic thoracolumbar diseases. Forty-five patients (28 females), with a mean age of 73 years (range 65-89), suffering from osteoporotic vertebral fractures (24), degenerative spondylolisthesis (15), and lumbar canal stenosis with instability and/or de novo scoliosis (6) were included.Twenty-one patients underwent PPSF and m-open TLIF. The remaining patients received PPSF without interbody fusion, and in six of these fenestrated screws were used for vertebral body cement augmentation.Functional evaluation was obtained with a visual analog scale (VAS) and the Oswestry Disability Index (ODI) pre- and postoperatively. Preoperative imaging included X-rays, computed tomography (CT), and magnetic resonance imaging (MRI). Patients were followed-up with X-rays, and a CT scan was also obtained at the last follow-up. Follow-up ranged from 6 to 59 months (mean 28 months). Follow-up CT scan documented intersomatic fusion in only 14 % of patients treated with m-open TLIF. Despite the high incidence of non-union, mean VAS and ODI scores showed a significant improvement, with a reduction of mean VAS from 9 to 4 and a reduction of mean ODI from 76.33 to 38.15 %. Only three patients developed postoperative complications. No patients showed neurological deficits.Minimally invasive spine surgery for degenerative and traumatic spinal diseases is a safe and effective treatment also in elderly patients.
Jang, Jae-Won; Lee, Jung-Kil; Lee, Jung-Heon; Hur, Hyuk; Kim, Tae-Wan; Kim, Soo-Han
Subsidence after anterior cervical reconstruction using a titanium mesh cage (TMC) has been a matter of debate. The authors investigated and analyzed subsidence and its effect on clinical and radiologic parameters after cervical reconstruction using a TMC for degenerative cervical disease. Thirty consecutive patients with degenerative cervical spine disorders underwent anterior cervical corpectomy followed by reconstruction with TMC. Twenty-four patients underwent a single-level corpectomy, and six patients underwent a two-level corpectomy. Clinical outcomes were assessed using a Visual Analogue Scale (VAS), the Japanese Orthopedic Association (JOA) score and the Neck Disability Index (NDI). Fusion status, anterior and posterior subsidence of the TMC, segmental angle (SA) and cervical sagittal angle (CSA) were assessed by lateral and flexion-extension radiographs of the neck. The mean follow-up period was 27.6 months (range, 24 to 49 months). The VAS, NDI and JOA scores were all significantly improved at the last follow-up. No instances of rad