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Sample records for degenerative diseases clinical

  1. Degenerative Nerve Diseases

    MedlinePlus

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

  2. Degenerative Nerve Diseases

    MedlinePlus

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Barrey, Cédric; Perrin, Gilles; Champain, Sabina

    2013-01-01

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

  6. Degenerative diseases of the vertebral column.

    PubMed

    Resnick, D

    1985-07-01

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

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

    PubMed

    Borgarelli, Michele; Haggstrom, Jens

    2010-07-01

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

  8. Developing Cellular Therapies for Retinal Degenerative Diseases

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. MR imaging of degenerative disc disease.

    PubMed

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

    2015-09-01

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

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

    PubMed

    Jandrić, Slavica

    2002-01-01

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

  12. Clinical experiences of dynamic stabilizers: Dynesys and Dynesys top loading system for lumbar spine degenerative disease.

    PubMed

    Hsieh, Cheng-Ta; Chang, Chih-Ju; Su, I-Chang; Lin, Li-Ying

    2016-04-01

    Dynesys (Dynamic Neutralization System) was designed to overcome the shortcomings of fusion. The Dynesys top loading (DTL) system is a new alternative Dynesys system that can be applied via a minimally invasive procedure. This study aimed to ascertain whether DTL is a suitable device for motion preservation and prevention of instability, and to compare the clinical and radiological outcomes between DTL and Dynesys. In this study, 12 patients were treated with Dynesys and 21 patients were treated with DTL. Back and leg pain were evaluated using the visual analog scale. The Oswestry Disability Index was used to evaluate the patients' function. Range of motion (ROM) at the operative level and for the whole lumbar spine was measured pre- and postoperatively. The length of wound, blood loss, length of hospital stay, and operation duration were also compared. All patients were followed up for 12-76 months. Scores on the visual analog scale and Oswestry Disability Index were significantly improved postoperatively. The median ROM of the whole spine and index level ROM in all patients showed 12.5% and 79.6% loss, respectively. The DTL group exhibited significantly better results in terms of blood loss, wound length, and operation duration, in addition to early ambulation. In conclusion, Dynesys and DTL are semirigid fixation systems that can significantly improve clinical symptoms and signs. Our results suggested that DTL was better than Dynesys as a result of it being a minimally invasive procedure. However, further study with large sample sizes and longer follow-up durations is required to validate the effects of these dynamic stabilizers. PMID:27185604

  13. Degenerative disease of the lumbar spine.

    PubMed

    Kovacs, F M; Arana, E

    2016-04-01

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

  14. Inherited Retinal Degenerative Disease Registry

    ClinicalTrials.gov

    2016-03-21

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

  15. Physiochemical basis of human degenerative disease

    PubMed Central

    Lipinski, Boguslaw

    2015-01-01

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

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

    PubMed

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

    2014-06-01

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

  17. Operative Management of Lumbar Degenerative Disc Disease

    PubMed Central

    Lee, Yu Chao; Osti, Orso Lorenzo

    2016-01-01

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

  18. Operative Management of Lumbar Degenerative Disc Disease.

    PubMed

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

    2016-08-01

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

  19. Is running associated with degenerative joint disease

    SciTech Connect

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

    1986-03-07

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

  20. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

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

  1. MRI Evaluation of Lumbar Disc Degenerative Disease

    PubMed Central

    Patel, Rupal; Mehta, Chetan; Patel, Narrotam

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. Total Disc Replacement in Lumbar Degenerative Disc Diseases

    PubMed Central

    2015-01-01

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

  6. Anabolic factors in degenerative joint disease.

    PubMed

    Sandell, L J

    2007-02-01

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

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

    PubMed Central

    SUGAWARA, Taku

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

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

    PubMed Central

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

    2015-01-01

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

  9. Immune Mechanisms in Inflammatory and Degenerative Eye Disease

    PubMed Central

    Perez, Victor L.; Caspi, Rachel R.

    2015-01-01

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

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

    PubMed

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

    2016-04-01

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

  11. Revisiting the Term Neuroprotection in Chronic and Degenerative Diseases

    PubMed Central

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

    2016-01-01

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

  12. Vitiligo: A Possible Model of Degenerative Diseases

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Synofzik, Matthis; Ilg, Winfried

    2014-01-01

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

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

    PubMed Central

    2014-01-01

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

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

    SciTech Connect

    Stuart, B.O. )

    1987-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2016-06-01

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

  19. Total Disc Arthroplasty for Treating Lumbar Degenerative Disc Disease

    PubMed Central

    2015-01-01

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

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

    PubMed

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

    1994-06-01

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

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

    PubMed Central

    Zigler, Jack E.; Delamarter, Rick B.

    2013-01-01

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

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

    PubMed Central

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

    1993-01-01

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

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

    PubMed Central

    2015-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed

    Morgan, B Paul; Harris, Claire L

    2015-12-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

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

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Greiling, H; Kleesiek, K; Reinards, R

    1987-08-01

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Forrester, J V

    2013-01-01

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

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

    SciTech Connect

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

    1980-10-01

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

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

    PubMed

    Schubert, Timm; Wissinger, Bernd

    2015-07-01

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

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

    PubMed

    Wickström, G

    1978-01-01

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

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

    PubMed

    Radcliff, Kris; Coric, Domagoj; Albert, Todd

    2016-08-01

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

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Galarza, Marcelo

    2014-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

    Perusek, Lindsay; Maeda, Tadao

    2013-01-01

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

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

    Malik, K

    2007-04-01

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

  14. The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders

    PubMed Central

    Gao, Bifeng; Doan, An; Hybertson, Brooks M

    2014-01-01

    Nuclear factor (erythroid-derived 2)-like 2 (Nrf2; encoded in humans by the NFE2L2 gene) is a transcription factor that regulates the gene expression of a wide variety of cytoprotective phase II detoxification and antioxidant enzymes through a promoter sequence known as the antioxidant-responsive element (ARE). The ARE is a promoter element found in many cytoprotective genes; therefore, Nrf2 plays a pivotal role in the ARE-driven cellular defense system against environmental stresses. Agents that target the ARE/Nrf2 pathway have been tested in a wide variety of disorders, with at least one new Nrf2-activating drug now approved by the US Food and Drug Administration. Examination of in vitro and in vivo experimental results, and taking into account recent human clinical trial results, has led to an opinion that Nrf2-activating strategies – which can include drugs, foods, dietary supplements, and exercise – are likely best targeted at disease prevention, disease recurrence prevention, or slowing of disease progression in early stage illnesses; they may also be useful as an interventional strategy. However, this rubric may be viewed even more conservatively in the pathophysiology of cancer. The activation of the Nrf2 pathway has been widely accepted as offering chemoprevention benefit, but it may be unhelpful or even harmful in the setting of established cancers. For example, Nrf2 activation might interfere with chemotherapies or radiotherapies or otherwise give tumor cells additional growth and survival advantages, unless they already possess mutations that fully activate their Nrf2 pathway constitutively. With all this in mind, the ARE/Nrf2 pathway remains of great interest as a possible target for the pharmacological control of degenerative and immunological diseases, both by activation and by inhibition, and its regulation remains a promising biological target for the development of new therapies. PMID:24520207

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

    PubMed

    Gazzeri, Roberto; Roperto, Raffaelino; Fiore, Claudio

    2012-12-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    ClinicalTrials.gov

    2016-03-28

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

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

    PubMed

    Caramia, G

    2007-01-01

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

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

    PubMed

    Nezelof, Christian

    2012-11-01

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

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

    PubMed

    Wu, Junyan; Wang, Jie; Zhang, Junlong

    2015-05-01

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

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

    PubMed

    Jeon, Sohee; Oh, Il-Hoan

    2015-04-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

    Background: Decompression and fusion is considered as the ‘gold standard’ for the treatment of degenerative lumbar diseases, however, many disadvantages have been reported in several studies, recently like donor site pain, pseudoarthrosis, nonunion, screw loosening, instrumentation failure, infection, adjacent segment disease (ASDis) and degeneration. Dynamic neutralization system (Dynesys) avoids many of these disadvantages. This system is made up of pedicle screws, polyethylene terephthalate cords, and polycarbonate urethane spacers to stabilize the functional spinal unit and preserve the adjacent motion after surgeries. This was a retrospective cohort study to compare the effect of Dynesys for treating degenerative lumbar diseases with posterior lumbar interbody fusion (PLIF) based on short term followup. Materials and Methods: Seventy five consecutive patients of lumbar degenerative disease operated between October 2010 and November 2012 were studied with a minimum followup of 2 years. Patients were divided into two groups according to the different surgeries. 30 patients underwent decompression and implantation of Dynesys in two levels (n = 29) or three levels (n = 1) and 45 patients underwent PLIF in two levels (n = 39) or three levels (n = 6). Clinical and radiographic outcomes between two groups were reviewed. Results: Thirty patients (male:17, female:13) with a mean age of 55.96 ± 7.68 years were included in Dynesys group and the PLIF group included 45 patients (male:21, female:24) with a mean age of 54.69 ± 3.26 years. The average followup in Dynesys group and PLIF group was 2.22 ± 0.43 year (range 2-3.5 year) and 2.17 ± 0.76 year (range 2-3 year), respectively. Dynesys group showed a shorter operation time (141.06 ± 11.36 min vs. 176.98 ± 6.72 min, P < 0.001) and less intraoperative blood loss (386.76 ± 19.44 ml vs. 430.11 ± 24.72 ml, P < 0.001). For Dynesys group, visual analogue scale (VAS) for back and leg pain improved from 6.87 ± 0

  5. The degenerative cervical spine.

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

    2012-01-01

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

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

    PubMed Central

    Maiese, Kenneth

    2016-01-01

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

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

    PubMed

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

    2009-08-01

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

  10. The Practical Application of Clinical Prediction Rules: A Commentary Using Case Examples in Surgical Patients with Degenerative Cervical Myelopathy

    PubMed Central

    Tetreault, Lindsay; Le, David; Côté, Pierre; Fehlings, Michael

    2015-01-01

    Study Design Commentary. Objective This commentary aims to discuss the practical applications of a clinical prediction rule (CPR) developed to predict functional status in patients undergoing surgery for the treatment of degenerative cervical myelopathy. Methods Clinical cases from the AOSpine CSM-North America study were used to illustrate the application of a prediction rule in a surgical setting and to highlight how this CPR can be used to ultimately enhance patient care. Results A CPR combines signs and symptoms, patient characteristics, and other predictive factors to estimate disease probability, treatment prognosis, or risk of complications. These tools can influence allocation of health care resources, inform clinical decision making, and guide the design of future research studies. In a surgical setting, CPRs can be used to (1) manage patients' expectations of outcome and, in turn, improve overall satisfaction; (2) facilitate shared decision making between patient and physician; (3) identify strategies to optimize surgical results; and (4) reduce heterogeneity of care and align surgeons' perceptions of outcome with objective evidence. Conclusions Valid and clinically-relevant CPRs have tremendous value in a surgical setting. PMID:26682095

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

    PubMed

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

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

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

    PubMed

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

    2011-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    PubMed Central

    Berger, Peter; Zenzmaier, Christoph

    2014-01-01

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

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

    PubMed

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

    2010-08-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Luikart, Kimberly A; Stover, Susan M

    2005-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

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

    PubMed

    McCully, Kilmer S

    2011-01-01

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

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

    PubMed Central

    2006-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2013-12-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Gutierrez-Quintana, Rodrigo; Penderis, Jacques

    2012-01-01

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

  9. Canine degenerative myelopathy.

    PubMed

    Coates, Joan R; Wininger, Fred A

    2010-09-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    1995-03-01

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

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

    PubMed

    Jackson, A; Isherwood, I

    1994-09-01

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  19. Predicting the minimum clinically important difference in patients undergoing surgery for the treatment of degenerative cervical myelopathy.

    PubMed

    Tetreault, Lindsay; Wilson, Jefferson R; Kotter, Mark R N; Nouri, Aria; Côté, Pierre; Kopjar, Branko; Arnold, Paul M; Fehlings, Michael G

    2016-06-01

    OBJECTIVE The minimum clinically important difference (MCID) is defined as the minimum change in a measurement that a patient would identify as beneficial. Before undergoing surgery, patients are likely to inquire about the ultimate goals of the operation and of their chances of experiencing meaningful improvements. The objective of this study was to define significant predictors of achieving an MCID on the modified Japanese Orthopaedic Association (mJOA) scale at 2 years following surgery for the treatment of degenerative cervical myelopathy (DCM). METHODS Seven hundred fifty-seven patients were prospectively enrolled in either the AOSpine North America or International study at 26 global sites. Fourteen patients had a perfect preoperative mJOA score of 18 and were excluded from this analysis (n = 743). Data were collected for each participating subject, including demographic information, symptomatology, medical history, causative pathology, and functional impairment. Univariate log-binominal regression analyses were conducted to evaluate the association between preoperative clinical factors and achieving an MCID on the mJOA scale. Modified Poisson regression using robust error variances was used to create the final multivariate model and compute the relative risk for each predictor. RESULTS The sample consisted of 463 men (62.31%) and 280 women (37.69%), with an average age of 56.48 ± 11.85 years. At 2 years following surgery, patients exhibited a mean change in functional status of 2.71 ± 2.89 points on the mJOA scale. Of the 687 patients with available follow-up data, 481 (70.01%) exhibited meaningful gains on the mJOA scale, whereas 206 (29.98%) failed to achieve an MCID. Based on univariate analysis, significant predictors of achieving the MCID on the mJOA scale were younger age; female sex; shorter duration of symptoms; nonsmoking status; a lower comorbidity score and absence of cardiovascular disease; and absence of upgoing plantar responses, lower

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-08-01

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

  2. Intravitreal Autologous Bone Marrow CD34+ Cell Therapy for Ischemic and Degenerative Retinal Disorders: Preliminary Phase 1 Clinical Trial Findings

    PubMed Central

    Park, Susanna S.; Bauer, Gerhard; Abedi, Mehrdad; Pontow, Suzanne; Panorgias, Athanasios; Jonnal, Ravi; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan

    2015-01-01

    Purpose. Because human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions. Methods. This prospective study enrolled six subjects (six eyes) with irreversible vision loss from retinal vascular occlusion, hereditary or nonexudative age-related macular degeneration, or retinitis pigmentosa. CD34+ cells were isolated under Good Manufacturing Practice conditions from the mononuclear cellular fraction of the BM aspirate using a CliniMACs magnetic cell sorter. After intravitreal CD34+ cell injection, serial ophthalmic examinations, microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics OCT were performed during the 6-month follow-up. Results. A mean of 3.4 million (range, 1–7 million) CD34+ cells were isolated and injected per eye. The therapy was well tolerated with no intraocular inflammation or hyperproliferation. Best-corrected visual acuity and full-field ERG showed no worsening after 6 months. Clinical examination also showed no worsening during follow-up except among age-related macular degeneration subjects in whom mild progression of geographic atrophy was noted in both the study eye and contralateral eye at 6-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in vivo imaging using adaptive optics OCT showed changes suggestive of new cellular incorporation into the macula of the hereditary macular degeneration study eye. Conclusions. Intravitreal autologous BM CD34+ cell therapy appears feasible and well tolerated in eyes with ischemic or degenerative retinal conditions and merits further exploration. (ClinicalTrials.gov number, NCT01736059.) PMID:25491299

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

    PubMed Central

    Jund, Jérôme; Noseda, Olivier; Roussouly, Pierre

    2007-01-01

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

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

    PubMed

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

    2009-11-15

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

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

    PubMed Central

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

    2010-01-01

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

  6. Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results

    PubMed Central

    Kreuz, Peter C; Müller, Sebastian; Ossendorf, Christian; Kaps, Christian; Erggelet, Christoph

    2009-01-01

    Introduction Second-generation autologous chondrocyte implantation with scaffolds stabilizing the grafts is a clinically effective procedure for cartilage repair. In this ongoing prospective observational case report study, we evaluated the effectiveness of BioSeed®-C, a cell-based cartilage graft based on autologous chondrocytes embedded in fibrin and a stable resorbable polymer scaffold, for the treatment of clinical symptomatic focal degenerative defects of the knee. Methods Clinical outcome after 4-year clinical follow-up was assessed in 19 patients with preoperatively radiologically confirmed osteoarthritis and a Kellgren-Lawrence score of 2 or more. Clinical scoring was performed before implantation of the graft and 6, 12, and 48 months after implantation using the Lysholm score, the Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee (IKDC) score, and the International Cartilage Repair Society (ICRS) score. Cartilage regeneration and articular resurfacing were assessed by magnetic resonance imaging (MRI) 4 years after implantation of the autologous cartilage graft. Results Significant improvement (P < 0.05) of the Lysholm and ICRS scores was observed as early as 6 months after implantation of BioSeed®-C and remained stable during follow-up. The IKDC score showed significant improvement compared with the preoperative situation at 12 and 48 months (P < 0.05). The KOOS showed significant improvement in the subclasses pain, activities of daily living, and knee-related quality of life 6 months as well as 1 and 4 years after implantation of BioSeed®-C in osteoarthritic defects (P < 0.05). MRI analysis showed moderate to complete defect filling with a normal to incidentally hyperintense signal in 16 out of 19 patients treated with BioSeed®-C. Two patients without improvement in the clinical and MRI scores received a total knee endoprosthesis after 4 years. Conclusions The results show that the good clinical

  7. Clinical outcomes following sublaminar decompression and instrumented fusion for lumbar degenerative spinal pathology.

    PubMed

    Peddada, Kranti; Elder, Benjamin D; Ishida, Wataru; Lo, Sheng-Fu L; Goodwin, C Rory; Boah, Akwasi O; Witham, Timothy F

    2016-08-01

    Traditional treatment for lumbar stenosis with instability is laminectomy and posterolateral arthrodesis, with or without interbody fusion. However, laminectomies remove the posterior elements and decrease the available surface area for fusion. Therefore, a sublaminar decompression may be a preferred approach for adequate decompression while preserving bone surface area for fusion. A retrospective review of 71 patients who underwent sublaminar decompression in conjunction with instrumented fusion for degenerative spinal disorders at a single institution was performed. Data collected included demographics, preoperative symptoms, operative data, and radiographical measurements of the central canal, lateral recesses, and neural foramina, and fusion outcomes. Paired t-tests were used to test significance of the outcomes. Thirty-one males and 40 females with a median age 60years underwent sublaminar decompression and fusion. A median of two levels were fused. The mean Visual Analog Scale pain score improved from 6.7 preoperatively to 2.9 at last follow-up. The fusion rate was 88%, and the median time to fusion was 11months. Preoperative and postoperative mean thecal sac cross-sectional area, right lateral recess height, left lateral recess height, right foraminal diameter, and left foraminal diameter were 153 and 209mm(2) (p<0.001), 5.9 and 5.9mm (p=0.43), 5.8 and 6.3mm (p=0.027), 4.6 and 5.2mm (p=0.008), and 4.2 and 5.2mm (p<0.001), respectively. Sublaminar decompression provided adequate decompression, with significant increases in thecal sac cross-sectional area and bilateral foraminal diameter. It may be an effective alternative to laminectomy in treating central and foraminal stenosis in conjunction with instrumented fusion. PMID:27056673

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

    Lee, Soo Eon; Kim, Hyun Jib

    2015-01-01

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

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

    PubMed

    Aires, Virginie; Delmas, Dominique

    2015-01-01

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

  12. [Features of the clinical course of intravertebral disk herniation in degenerative lumbar stenosis].

    PubMed

    Kariev, M Kh; Norov, A U; Ishmukhamedov, S N; Iugaĭ, I A

    2001-01-01

    The paper presents a clinical and neurological analysis of 110 patients with discal hernias who were divided into 2 groups: 1) 50 patients with normal sizes of the vertebral column; 2) 51 patients with its stenosis. Compression syndromes were major in all cases. In patients in whom discal hernia was concurrent with lumbar stenosis, the clinical course was characterized by dull or aching pains in the low back and legs, by symptoms of dysbasia neurasthenica intermittens, severe motor and sensory disorders with autonomic impositions. PMID:11764566

  13. Gorham's disease: clinical case☆

    PubMed Central

    Sá, Pedro; Marques, Pedro; Oliveira, Carolina; Rodrigues, André Sá; Amorim, Nelson; Pinto, Rui

    2015-01-01

    Gorham's disease, also known as idiopathic massive osteolysis, is a rare pathological condition characterized by vascular proliferation that results in destruction and reabsorption of the bone matrix, of unknown etiology. It was first described by Jackson in 1838, but it was Gorham and Stout, in 1955, who defined this disease as a specific entity. It has variable clinical presentation and generally has progressive behavior. Controversy continues regarding the treatment and there is no standard treatment. This pathological condition generally presents a favorable prognosis. Here, a case of Gorham's disease with involvement of the left hip is presented, in a male patient without relevant antecedents. PMID:26229923

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

    PubMed

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

    1980-03-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Singh, Pritish; Shekhawat, Vishal

    2016-01-01

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

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

    PubMed Central

    Ranjan, Alok; Lath, Rahul

    2014-01-01

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

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

    PubMed

    Sharma, Pankaj; Ranjan, Alok; Lath, Rahul

    2014-06-01

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

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

    PubMed Central

    Nopoulos, Peggy C.

    2016-01-01

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

  20. Rare Diseases Clinical Research Network

    MedlinePlus

    ... RDCRN? Aims of the Rare Diseases Clinical Research Network Contact Us RDCRN Members Login Accessibility Disclaimer The Rare Diseases Clinical Research Network is an initiative of the Office of Rare ...

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

    PubMed

    Cummings, Jeffrey L; Zhong, Kate

    2014-03-01

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

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

    PubMed

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

    2003-01-01

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

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

    PubMed

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

    2015-01-01

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

  4. The Degenerative Spine.

    PubMed

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

    2016-08-01

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

  5. Nanofiber Scaffold-Based Tissue-Engineered Retinal Pigment Epithelium to Treat Degenerative Eye Diseases.

    PubMed

    Hotaling, Nathan A; Khristov, Vladimir; Wan, Qin; Sharma, Ruchi; Jha, Balendu Shekhar; Lotfi, Mostafa; Maminishkis, Arvydas; Simon, Carl G; Bharti, Kapil

    2016-06-01

    Clinical-grade manufacturing of a functional retinal pigment epithelium (RPE) monolayer requires reproducing, as closely as possible, the natural environment in which RPE grows. In vitro, this can be achieved by a tissue engineering approach, in which the RPE is grown on a nanofibrous biological or synthetic scaffold. Recent research has shown that nanofiber scaffolds perform better for cell growth and transplantability compared with their membrane counterparts and that the success of the scaffold in promoting cell growth/function is not heavily material dependent. With these strides, the field has advanced enough to begin to consider implementation of one, or a combination, of the tissue engineering strategies discussed herein. In this study, we review the current state of tissue engineering research for in vitro culture of RPE/scaffolds and the parameters for optimal scaffold design that have been uncovered during this research. Next, we discuss production methods and manufacturers that are capable of producing the nanofiber scaffolds in such a way that would be biologically, regulatory, clinically, and commercially viable. Then, a discussion of how the scaffolds could be characterized, both morphologically and mechanically, to develop a testing process that is viable for regulatory screening is performed. Finally, an example of a tissue-engineered RPE/scaffold construct is given to provide the reader a framework for understanding how these pieces could fit together to develop a tissue-engineered RPE/scaffold construct that could pass regulatory scrutiny and can be commercially successful. PMID:27110730

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

    PubMed Central

    Hauser, Ross A.; Orlofsky, Amos

    2013-01-01

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

  7. Detection of neuronal damage in degenerative brain disease with cobalt-55 and positron emission tomography

    SciTech Connect

    Jansen, H.M.L.; Pruim, J.; Paans, A.M.J.

    1994-05-01

    We suggest Cobalt-55 (Co) as a Calcium (Ca)-marker to visualize Ca transport across the neuronal membrane. Elevation of intracellular Ca is closely linked with the process of neuronal cell-decay. Co-uptake is correlated with Ca-accumulation through divalent cation-permeable kainate (KA)-activated receptor-operated channels in the neuronal membrane. This hypothesis was studied with position emission tomography (PET) both in patients with a ischemic cerebro-vascular accident (CVA) and in patients with relapsing progressive multiple sclerosis (MS). Co-PET studies were performed in a dynamic mode (6 frames of 10 minutes) 20-25 hours after iv.-administration of 1-2 mCi Co. Regional specific accumulation irrespective of blood brain barrier (BBB) integrity in the (clinically appropriate) affected cerebral region could be demonstrated in CVA-patients, thus suggesting neuronal decay in (the early phase of) infarction. In MS, inhomogeneous cerebral distribution of Co was detected, in contrast to healthy volunteers. This suggests focal accumulation of Co in multiple spots of neuronal decay, possibly related to MS-lesions on MRI. In conclusion, Co-PET may prove to be a valuable tool for the early detection of neuronal decay not only in CVA and MS, but in other brain-pathology as well. The usefulness of Co-PET in imaging brain-tumors and myocardial ischemia has already been established.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Naeem, Aabgeena; Amani, Samreen

    2013-01-01

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

  10. Complications following central corpectomy in 468 consecutive patients with degenerative cervical spine disease.

    PubMed

    Sarkar, Sauradeep; Nair, Bijesh R; Rajshekhar, Vedantam

    2016-06-01

    OBJECTIVE This study was performed to describe the incidence and predictors of perioperative complications following central corpectomy (CC) in 468 consecutive patients with cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament (OPLL). METHODS The authors performed a retrospective review of a cohort of patients who had undergone surgery for CSM (n = 338) or OPLL (n = 130) performed by a single surgeon over a 15-year period. All patients underwent uninstrumented CC with autologous iliac crest or fibular strut grafting. Preoperative clinical and imaging details were collected, and the type and incidence of complications were studied. Univariate and multivariate analyses were performed to establish risk factors for the development of perioperative complications. RESULTS Overall, 12.4% of patients suffered at least 1 complication following CC. The incidence of major complications was as follows: C-5 radiculopathy, 1.3%; recurrent laryngeal nerve injury, 0.4%; dysphagia, 0.8%; surgical-site infection, 3.4%; and dural tear, 4.3%. There was 1 postoperative death (0.2%). On multivariate analysis, patients in whom the corpectomy involved the C-4 vertebral body (alone or as part of multilevel CC) were significantly more likely to suffer complications (p = 0.004). OPLL and skip corpectomy were risk factors for dural tear (p = 0.015 and p = 0.001, respectively). No factors were found to be significantly associated with postoperative C-5 palsy, dysphagia, or acute graft extrusion on univariate or multivariate analysis. Patients who underwent multilevel CC were predisposed to surgical-site infections, with a slight trend toward statistical significance (p = 0.094). The occurrence of a complication after surgery significantly increased the mean duration of postoperative hospital stay from 5.0 ± 2.3 days to 8.9 ± 6 days (p < 0.001). CONCLUSIONS Complications following CC for CSM or OPLL are infrequent, but they significantly prolong

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  14. Degenerative myelopathy.

    PubMed

    Clemmons, R M

    1992-07-01

    DM in the German Shepherd is an immune-related disorder whose clinical signs are explained by a widespread degeneration of the white matter pathways in the thoracolumbar spinal cord. Therapy includes exercise, vitamin supplementation, and EACA medication. Avoiding unnecessary surgical procedures is also important to preclude permanent deterioration that can result following surgery in DM patients. In dogs other than German Shepherds, other identifiable causes should be treated. Additional confirmation of the diagnosis of DM may be assisted by performing cell-mediated immune studies or other serodiagnostic tests as they become available. PMID:1641928

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

    NASA Astrophysics Data System (ADS)

    Sussman, Joel L.; Silman, Israel

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

  16. Comparison of Clinical and Radiological Results of Posterolateral Fusion and Posterior Lumbar Interbody Fusion in the Treatment of L4 Degenerative Lumbar Spondylolisthesis

    PubMed Central

    Kuraishi, Shugo; Mukaiyama, Keijiro; Shimizu, Masayuki; Ikegami, Shota; Futatsugi, Toshimasa; Hirabayashi, Hiroki; Ogihara, Nobuhide; Hashidate, Hiroyuki; Tateiwa, Yutaka; Kinoshita, Hisatoshi; Kato, Hiroyuki

    2016-01-01

    Study Design Multicenter analysis of two groups of patients surgically treated for degenerative L4 unstable spondylolisthesis. Purpose To compare the clinical and radiographic outcomes of posterolateral fusion (PLF) and posterior lumbar interbody fusion (PLIF) for degenerative L4 unstable spondylolisthesis. Overview of Literature Surgery for lumbar degenerative spondylolisthesis is widely performed. However, few reports have compared the outcome of PLF to that of PLIF for degenerative L4 unstable spondylolisthesis. Methods Patients with L4 unstable spondylolisthesis with Meyerding grade II or more, slip of >10° or >4 mm upon maximum flexion and extension bending, and posterior opening of >5 degree upon flexion bending were studied. Patients were treated from January 2008 to January 2010. Patients who underwent PLF (n=12) and PLIF (n=19) were followed-up for >2 years. Radiographic findings and clinical outcomes evaluated by the Japanese Orthopaedic Association (JOA) score were compared between the two groups. Radiographic evaluation included slip angle, translation, slip angle and translation during maximum flexion and extension bending, intervertebral disc height, lumbar lordotic angle, and fusion rate. Results JOA scores of the PLF group before surgery and at final follow-up were 12.3±4.8 and 24.1±3.7, respectively; those of the PLIF group were 14.7±4.8 and 24.2±7.8, respectively, with no significant difference between the two groups. Correction of slip estimated from postoperative slip angle, translation, and maintenance of intervertebral disc height in the PLIF group was significantly (p<0.05) better than those in the PLF group. However, there was no significant difference in lumbar lordotic angle, slip angle and translation angle upon maximum flexion, or extension bending. Fusion rates of the PLIF and PLF groups had no significant difference. Conclusions The L4–L5 level posterior instrumented fusion for unstable spondylolisthesis using both PLF and PLIF

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Morgenstern, Christian

    2015-01-01

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

  1. Surgical Management of Minimally Invasive Anterior Lumbar Interbody Fusion with Stand-Alone Interbody Cage for L4-5 Degenerative Disorders: Clinical and Radiographic Findings

    PubMed Central

    Hironaka, Yasuo; Morimoto, Tetsuya; Motoyama, Yasushi; Park, Young-Su; Nakase, Hiroyuki

    2013-01-01

    Surgical treatment for degenerative spinal disorders is controversial, although lumbar fusion is considered an acceptable option for disabling lower back pain. Patients underwent instrumented minimally invasive anterior lumbar interbody fusion (mini-ALIF) using a retroperitoneal approach except for requiring multilevel fusions, severe spinal canal stenosis, high-grade spondylolisthesis, and a adjacent segments disorders. We retrospectively reviewed the clinical records and radiographs of 142 patients who received mini-ALIF for L4-5 degenerative lumbar disorders between 1998 and 2010. We compared preoperative and postoperative clinical data and radiographic measurements, including the modified Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) score for back and leg pain, disc height (DH), whole lumbar lordosis (WL), and vertebral wedge angle (WA). The mean follow-up period was 76 months. The solid fusion rate was 90.1% (128/142 patients). The average length of hospital stay was 6.9 days (range, 3–21 days). The mean blood loss was 63.7 ml (range, 10–456 ml). The mean operation time was 155.5 min (range, 96–280 min). The postoperative JOA and VAS scores for back and leg pain were improved compared with the preoperative scores. Radiological analysis showed significant postoperative improvements in DH, WL, and WA, and the functional and radiographical outcomes improved significantly after 2 years. The 2.8% complication rate included cases of wound infection, liquorrhea, vertebral body fractures, and a misplaced cage that required revision. Mini-ALIF was found to be associated with improved clinical results and radiographic findings for L4-5 disorders. A retroperitoneal approach might therefore be a valuable treatment option. PMID:24140782

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2016-01-01

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

  5. Clinical manifestations of cerebellar disease.

    PubMed

    Javalkar, Vijayakumar; Khan, Misbba; Davis, Debra E

    2014-11-01

    Clinical manifestations of cerebellar disease include ataxia and tremor, as well as nystagmus, dysarthria, and cognitive dysfunction. Recognition of the cerebellar pattern of disease can aid in the prompt and correct diagnosis and lead to appropriate treatment and rehabilitation to minimize disability. PMID:25439285

  6. Beryllium disease: a clinical perspective

    SciTech Connect

    Hardy, H.L.

    1980-02-01

    A relatively new occupational disease, beryllium poisoning, is discussed. The history of this respiratory disease among workers after beryllium exposure from extraction and alloy manufacturing is not well documented in the US Attempts by industry to delay investigations into beryllium toxicity are described. The specific incidents occurring at a fluorescent lamp manufacturing plant in Salem, Massachusetts are presented. Clinical observations of chronic beryllium disease are discussed. Symptoms are described. The current status of diagnosis and treatment of beryllium poisoning is presented.

  7. Study of the Clinical Outcome between Traumatic and Degenerative (non-traumatic) Meniscal Tears after Arthroscopic Surgery: A 4-Years Follow-up Study

    PubMed Central

    Ghislain, Nietiayurk Aminake; Wei, Ji-Nan

    2016-01-01

    Introduction The meniscus is a biconcave fibrocartilage in the knee joint interpose between the femoral condyles and tibial plateau; the meniscus has functions in load bearing, load transmission, shock absorption joint stability, joint lubrication, and joint congruity. Aim The aim of this study is to provide orthopeadic surgeon a base of reference in the choice of the optimal course of management for meniscal tears. Materials and Methods One hundred and seventeen patients met the criteria of inclusion for the present study. Patients were divided in two groups T and NT according to the presence of distinct previous traumatic events to the knees. Two subgroups were formed in each groups T and NT respectively at a mean follow up of 1 and 4 years. Postoperative clinical outcome were assessed using Lysholm scores and Rand SF-36 survey. Results One hundred and seventeen patients were included in the present study with 60(51.28%) patients in the traumatic group and 57(48.71%) in the degenerative group. 95(81.19%) patients in total were satisfied with their health status at end of follow up. The mean value of Lysholm scores at 1 year were respectively 85.25±8.78 for traumatic group and 86.38±12.14 for non-traumatic group and at 4 years were respectively 92.63±7.31 for traumatic group and 72.90±20.77 for non-traumatic group. According to Rand SF-36 health, traumatic group showed better improvements compare to non-traumatic group between 1 and 4 years after arthroscopic meniscus surgery. Conclusion A total of 95(81.19%) patients in total were satisfied with their health status at follow up, however, we found that arthroscopy as a treatment for meniscal tear have a relatively better mid-term clinical outcome for traumatic meniscal tears compare to non-traumatic/degenerative meniscal tears. PMID:27190905

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

    PubMed

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

    2003-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Clinical manifestation of mitochondrial diseases.

    PubMed

    Magner, Martin; Kolářová, Hana; Honzik, Tomáš; Švandová, Ivana; Zeman, Jiří

    2015-01-01

    Mitochondrial disorders (MD) represent a clinically, biochemically and genetically heterogeneous group of diseases associated with dysfunction of the oxidative phosphorylation system and pyruvate dehydrogenase complex. Our aim was to illustrate the most common clinical presentation of MD on the example of selected diseases and syndromes. The minimal prevalence of MD is estimated as 1 to 5,000. MD may manifest at any age since birth until late-adulthood with acute manifestation or as a chronic progressive disease. Virtually any organ may be impaired, but the organs with the highest energetic demands are most frequently involved, including brain, muscle, heart and liver. Some MD may manifest as a characteristic cluster of clinical features (e.g. MELAS syndrome, Kearns-Sayre syndrome). Diagnostics includes detailed history, the comprehensive clinical examination, results of specialized examinations (especially cardiology, visual fundus examination, brain imaging, EMG), laboratory testing of body fluids (lactate, aminoacids, organic acids), and analysis of bioptic samples of muscle, skin, and liver, eventually. Normal lactate level in blood does not exclude the possibility of MD. Although the aimed molecular genetic analyses may be indicated in some of mitochondrial diseases, the methods of next generation sequencing come into focus. Examples of treatment are arginine supplementation in MELAS syndrome, ketogenic diet in pyruvate oxidation disorders or quinone analogs in patients with LHON. Conclusion: The clinical suspicion of a mitochondrial disorder is often delayed, or the disease remains undiagnosed. The correct diagnosis and adequate treatment can improve prognosis of the patient. Access to genetic counseling is also of great importance. PMID:26982751

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

    PubMed Central

    Feldman, Erica; Narayan, Anisha; Taylor, William

    2016-01-01

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

  17. Clinical manifestations of celiac disease.

    PubMed

    Green, Peter H R; Krishnareddy, Suneeta; Lebwohl, Benjamin

    2015-01-01

    Celiac disease (CD) is an immune-based condition affecting multiple organ systems. Clinical manifestations are manifold in form and number due to the multisystem nature of CD. There has been a progressive change in the clinical manifestations over the recent decades with fewer patients, both adults and children, presenting with a diarrheal, classical form. This, in children, is seen in only the youngest, while growth issues, screening at-risk groups and recurrent abdominal pain are the most common modes of presentation among children. Among adults, diarrhea is the most common presentation followed by anemia. Screening at-risk groups, metabolic bone disease and incidental recognition at endoscopy performed for reflux are the other main modes of presentation. The bulk of those with CD remain undiagnosed. The symptoms are often common, and increased medical education should lead to greater awareness in the medical community and an increased rate of diagnosis. PMID:25925914

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

    PubMed

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

    2016-01-01

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

  19. Short-Term Clinical Result of Cortical Bone Trajectory Technique for the Treatment of Degenerative Lumbar Spondylolisthesis with More than 1-Year Follow-Up

    PubMed Central

    Nishizawa, Kazuya; Nakamura, Akira; Imai, Shinji

    2016-01-01

    Study Design Retrospective follow-up study on the result of surgical treatment for patients with degenerative lumbar spondylolisthesis (DLS) using cortical bone trajectory (CBT) technique. Purpose To evaluate the capability of CBT to manage patients with DLS. Overview of Literature CBT is a recently advocated, novel, less-invasive technique of lumbar pedicle screw, which provides enhanced screw purchase by maximizing the thread contact with higher density bone surface. Despite the frequent use of CBT technique in the lumbar spine surgery, little is known of the capability of this technique to manage patients with DLS. Methods Thirty two consecutive patients (5 males, 27 females) surgically treated with single-level DLS in our institute using CBT were included. All patients were followed up at least 12 months (mean 24 months). Their clinical and radiological features were measured. Results Good leg pain relief was achieved in all patients. The mean postoperative percentage slip demonstrated significant reduction with significant neurological recovery when compared with preoperative percentage slip, and it was maintained until the latest follow-up. Loss of correction of more than 3 mm during the follow-up period was observed in 3 cases. Surgical site infection was observed in one case; however, pull-out of PSs or neurological deterioration was not found. No patient needed additional surgery during the follow-up period. Conclusions These preliminary results confirmed that CBT is useful for the treatment for patients with DLS. This technique allows good reduction of spondylolisthesis and neurological improvement. PMID:27114763

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

    PubMed

    Bergamini, Roberta; Astengo, Rossana

    2014-01-01

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

  1. Huntington's disease: a clinical review.

    PubMed

    Roos, Raymund A C

    2010-01-01

    Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD). The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation) are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which results in patients

  2. Huntington's disease: a clinical review

    PubMed Central

    2010-01-01

    Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD). The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation) are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which results in patients

  3. Degenerative myelopathy in 18 Pembroke Welsh Corgi dogs.

    PubMed

    March, P A; Coates, J R; Abyad, R J; Williams, D A; O'Brien, D P; Olby, N J; Keating, J H; Oglesbee, M

    2009-03-01

    Postmortem examination was performed on 18 Pembroke Welsh Corgi dogs (mean age 12.7 years) with clinical signs and antemortem diagnostic tests compatible with a diagnosis of degenerative myelopathy. Tissue sections from specific spinal cord and brain regions were systematically evaluated in all dogs. Axonal degeneration and loss were graded according to severity and subsequently compared across different spinal cord segments and funiculi. White matter lesions were identified in defined regions of the dorsal, lateral, and ventral funiculi. The dorsolateral portion of the lateral funiculus was the most severely affected region in all cord segments. Spinal cord segment T12 exhibited the most severe axonal loss. Spinal nerve roots, peripheral nerves, and brain sections were within normal limits, with the exception of areas of mild astrogliosis in gray matter of the caudal medulla. Dogs with more severe lesions showed significant progression of axonal degeneration and loss at T12 and at cord segments cranial and caudal to T12. Severity of axonal loss in individual dogs positively correlated with the duration of clinical signs. The distribution of axonal degeneration resembled that reported in German Shepherd Dog degenerative myelopathy but differed with respect to the transverse and longitudinal extent of the lesions within more clearly defined funicular areas. Although these lesion differences might reflect disease longevity, they could also indicate a form of degenerative myelopathy unique to the Pembroke Welsh Corgi dog. PMID:19261635

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

    PubMed

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

    2015-12-01

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

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

    PubMed

    Ames, Bruce N

    2006-11-21

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

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

    PubMed

    Attard, Everaldo; Martinoli, Maria-Grazia

    2015-01-01

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

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

    PubMed Central

    Benezech, Jacques; Garlenq, Bruno; Larroque, Gilles

    2016-01-01

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

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

    PubMed

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

    1995-01-01

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

  9. The senescence-accelerated mouse (SAM): a higher oxidative stress and age-dependent degenerative diseases model.

    PubMed

    Chiba, Yoichi; Shimada, Atsuyoshi; Kumagai, Naoko; Yoshikawa, Keisuke; Ishii, Sanae; Furukawa, Ayako; Takei, Shiro; Sakura, Masaaki; Kawamura, Noriko; Hosokawa, Masanori

    2009-04-01

    The SAM strain of mice is actually a group of related inbred strains consisting of a series of SAMP (accelerated senescence-prone) and SAMR (accelerated senescence-resistant) strains. Compared with the SAMR strains, the SAMP strains show a more accelerated senescence process, a shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to human geriatric disorders. The higher oxidative stress status observed in SAMP mice is partly caused by mitochondrial dysfunction, and may be a cause of this senescence acceleration and age-dependent alterations in cell structure and function. Based on our recent observations, we discuss a possible mechanism for mitochondrial dysfunction resulting in the excessive production of reactive oxygen species, and a role for the hyperoxidative stress status in neurodegeneration in SAMP mice. These SAM strains can serve as a useful tool to understand the cellular mechanisms of age-dependent degeneration, and to develop clinical interventions. PMID:18688709

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Gammal, Isaac D.; Bendo, John A.

    2015-01-01

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

  12. Degenerative cervical myelopathy.

    PubMed

    Kato, So; Fehlings, Michael

    2016-09-01

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

  13. D-penicillamine Induced Degenerative Dermopathy

    PubMed Central

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

    2015-01-01

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

  14. Degenerative Spinal Deformity.

    PubMed

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

    2015-10-01

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

  15. Nrf2 in health and disease: current and future clinical implications.

    PubMed

    Al-Sawaf, Othman; Clarner, Tim; Fragoulis, Athanassios; Kan, Yuet Wai; Pufe, Thomas; Streetz, Konrad; Wruck, Christoph Jan

    2015-12-01

    The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is a major regulator of oxidative stress defence in the human body. As Nrf2 regulates the expression of a large battery of cytoprotective genes, it plays a crucial role in the prevention of degenerative disease in multiple organs. Thus it has been the focus of research as a pharmacological target that could be used for prevention and treatment of chronic diseases such as multiple sclerosis, chronic kidney disease or cardiovascular diseases. The present review summarizes promising findings from basic research and shows which Nrf2-targeting therapies are currently being investigated in clinical trials and which agents have already entered clinical practice. PMID:26386022

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. Clinical Applications of Mesenchymal Stem Cells in Chronic Diseases

    PubMed Central

    Sitzia, Clementina; Erratico, Silvia; Torrente, Yvan

    2014-01-01

    Extraordinary progress in understanding several key features of stem cells has been made in the last ten years, including definition of the niche, and identification of signals regulating mobilization and homing as well as partial understanding of the mechanisms controlling self-renewal, commitment, and differentiation. This progress produced invaluable tools for the development of rational cell therapy protocols that have yielded positive results in preclinical models of genetic and acquired diseases and, in several cases, have entered clinical experimentation with positive outcome. Adult mesenchymal stem cells (MSCs) are nonhematopoietic cells with multilineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. It is obvious that much work remains to be done to increase our knowledge of the mechanisms regulating development, homeostasis, and tissue repair and thus to provide new tools to implement the efficacy of cell therapy trials. PMID:24876848

  20. Retrolisthesis as a Compensatory Mechanism in Degenerative Lumbar Spine

    PubMed Central

    Jeon, Ikchan

    2015-01-01

    Objective Posterior vertebral translation as a type of spondylolisthesis, retrolisthesis is observed commonly in patients with degenerative spinal problems. Nevertheless, there is insufficient literature on retrolisthesis compared to anterolisthesis. The purpose of this study is to clarify the clinical features of retrolisthesis, and its developmental mechanism associated with a compensatory role in sagittal imbalance of the lumbar spine. Methods From 2003 to 2012, 230 Korean patients who underwent spinal surgery in our department under the impression of degenerative lumbar spinal disease were enrolled. All participants were divided into four groups : 35 patients with retrolisthesis (group R), 32 patients with simultaneous retrolisthesis and anterolisthesis (group R+A), 76 patients with anterolisthesis (group A), and 87 patients with non-translation (group N). The clinical features and the sagittal parameters related to retrolisthesis were retrospectively analyzed based on the patients' medical records. Results There were different clinical features and developmental mechanisms between retrolisthesis and anterolisthesis. The location of retrolisthesis was affected by the presence of simultaneous anterolisthesis, even though it predominantly manifest in L3. The relative lower pelvic incidence, pelvic tilt, and lumbar lordosis compared to anterolisthesis were related to the generation of retrolisthesis, with the opposite observations of patients with anterolisthesis. Conclusion Retrolisthesis acts as a compensatory mechanism for moving the gravity axis posteriorly for sagittal imbalance in the lumbar spine under low pelvic incidence and insufficient intra-spinal compensation. PMID:25810857

  1. THERAPIES FOR CROHN'S DISEASE: a clinical update.

    PubMed

    Sobrado, Carlos Walter; Leal, Raquel Franco; Sobrado, Lucas Faraco

    2016-01-01

    The main objectives of clinical therapy in Crohn's disease are clinical and endoscopic remission without the use of corticosteroids for long periods of time, prevention of hospitalization and surgery, and improvement of quality of life. The main limitation of drug therapy is the loss of response over the long term, which makes incorporation of new drugs to the therapeutic arsenal necessary. This review analyses the main drugs currently used in clinical treatment of Crohn's disease. PMID:27438429

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

    SciTech Connect

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

    2014-06-15

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

  3. Biomechanics of Degenerative Spinal Disorders.

    PubMed

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

    2016-04-01

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

  4. Biomechanics of Degenerative Spinal Disorders

    PubMed Central

    Iorio, Justin A.; Jakoi, Andre M.

    2016-01-01

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

  5. Clinical update in sexually transmitted diseases-2014.

    PubMed

    Fanfair, Robyn Neblett; Workowski, Kimberly A

    2014-02-01

    Sexually transmitted diseases (STDs) and their associated syndromes are extremely common in clinical practice. Early diagnosis, appropriate treatment, and partner management are important to ensure sexual, physical, and reproductive health in our patients. PMID:24493491

  6. Clinical Scenarios in Chronic Kidney Disease: Cystic Renal Diseases.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Cysts are frequently found in chronic kidney disease (CKD) and they have a different prognostic significance depending on the clinical context. Simple solitary parenchymal cysts and peripelvic cysts are very common and they have no clinical significance. At US, simple cyst appears as a round anechoic pouch with regular and thin profiles. On the other hand, hereditary polycystic disease is a frequent cause of CKD in children and adults. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are the best known cystic hereditary diseases. ADPKD and ARPKD show a diffused cystic degeneration with cysts of different diameters derived from tubular epithelium. Medullary cystic disease may be associated with tubular defects, acidosis and lithiasis and can lead to CKD. Acquired cystic kidney disease, finally, is secondary to progressive structural end-stage kidney remodelling and may be associated with renal cell carcinoma. PMID:27169740

  7. Clinical-physiologic correlates of Alzheimer's disease and frontal lobe dementia

    SciTech Connect

    Jagust, W.J.; Reed, B.R.; Seab, J.P.; Kramer, J.H.; Budinger, T.F. )

    1989-01-01

    Thirty patients with degenerative dementia underwent clinical evaluation, neuropsychological testing, and single photon emission computed tomography (SPECT) with the blood flow tracer ({sup 123}I)-N-isopropyl-p-iodoamphetamine. Five of these patients were clinically and psychologically different from the others, demonstrating predominant behavioral disturbances with relative preservation of memory function. These five patients, who were felt to have a frontal lobe dementia (FLD), showed SPECT perfusion patterns which differed from the remaining 25 patients, who were diagnosed as having Alzheimer's disease (AD), and from 16 healthy control subjects. The FLD patients showed diminished perfusion in orbitofrontal, dorsolateral frontal, and temporal cortex relative to controls, while the AD patients showed lower perfusion in temporal and parietal cortex than controls. The FLD patients also showed hypoperfusion in both frontal cortical regions relative to AD patients. The pattern of performance on neuropsychological testing paralleled these differences in regional perfusion. These results suggest that clinical evaluation and physiological imaging may enable the differentiation of groups of degenerative dementia patients during life.

  8. Clinical case seminar in pediatric thyroid disease.

    PubMed

    Szinnai, G; Léger, J; Bauer, A J; Pearce, E N; Ramos, H E; Canalli, M H; Onigata, K; Elisei, R; Radetti, G; Polak, M; Van Vliet, G; Deladoëy, J

    2014-01-01

    Pediatric thyroid diseases cover a large spectrum of congenital and acquired forms, ranging from congenital primary or central hypothyroidism, autoimmune thyroid disease, iodine deficiency, rare genetic defects of thyroid hormone action, metabolism and cell membrane transport to benign nodules and malignant tumors. The previous 15 papers of the textbook Paediatric Thyroidology gave a systematic overview of the current knowledge and guidelines on all these diseases. In this final paper, the authors collected a series of patient histories from their clinics illustrating frequently encountered clinical problems and providing key learning points and references to each case. Although not fully comprehensive, it aims at providing relevant clinical knowledge on thyroid diseases of the neonate, the child, and the adolescent. PMID:25231455

  9. Disease-mongering through clinical trials.

    PubMed

    González-Moreno, María; Saborido, Cristian; Teira, David

    2015-06-01

    Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple. PMID:25863220

  10. Degenerative myelopathy in two Boxer dogs.

    PubMed

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

    2009-07-01

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

  11. [Clinical aspects of the Niigata Minamata disease].

    PubMed

    Shimohata, Takayoshi; Hirota, Koichi; Takahashi, Hitoshi; Nishizawa, Masatoyo

    2015-01-01

    The Minamata disease was discovered in the Minamata region, Kumamoto Prefecture, Japan, in 1956. Symptoms of this disease included cerebellar ataxia, sensory disturbance, narrowing of the visual field, and hearing and speech disturbances. In 1965, similar conditions were identified in persons living around the Agano River area, Niigata Prefecture, Japan and accordingly termed as the Niigata Minamata disease or the second Minamata disease. Both the diseases have been attributed to poisoning with methyl mercury that was generated during the production of acetaldehyde using mercury as a catalyst. The discharged methyl mercury accumulated in fishes and shellfishes and caused poisoning on consumption. This review discusses the history, clinical presentation including atypical forms, and autopsy findings of the Niigata Minamata disease. In addition, it highlights the problems about criteria for official recognition and the therapeutic trial for this disease. PMID:25585433

  12. Clinical experience with stem cells and other cell therapies in neurological diseases.

    PubMed

    Karussis, Dimitrios; Petrou, Panayiota; Kassis, Ibrahim

    2013-01-15

    To overcome the limited capacity of the CNS for regeneration, the theoretical alternative would be to use stem cells for more effective management of chronic degenerative and inflammatory neurological conditions, and also of acute neuronal damage from injuries or cerebrovascular diseases. Although the adult brain contains small numbers of stem cells in restricted areas, this intrinsic stem cell repertoire is small and does not measurably contribute to functional recovery. Embryonic cells carrying pluripotent and self-renewal properties represent the stem cell prototype, but there are additional somatic stem cells that may be harvested and expanded from various tissues during adult life. Stem cell transplantation is based on the assumption that such cells may have the potential to regenerate or support the survival of the existing, partially damaged cells. This review summarizes the state-of-the-art and the clinical worldwide experience with the use of various types of stem cells in neurological diseases. PMID:23107343

  13. International Union of Basic and Clinical Pharmacology. XCVI. Pattern Recognition Receptors in Health and Disease

    PubMed Central

    Orr, Selinda; Ferguson, Brian; Symmons, Martyn F.; Boyle, Joseph P.; Monie, Tom P.

    2015-01-01

    Since the discovery of Toll, in the fruit fly Drosophila melanogaster, as the first described pattern recognition receptor (PRR) in 1996, many families of these receptors have been discovered and characterized. PRRs play critically important roles in pathogen recognition to initiate innate immune responses that ultimately link to the generation of adaptive immunity. Activation of PRRs leads to the induction of immune and inflammatory genes, including proinflammatory cytokines and chemokines. It is increasingly clear that many PRRs are linked to a range of inflammatory, infectious, immune, and chronic degenerative diseases. Several drugs to modulate PRR activity are already in clinical trials and many more are likely to appear in the near future. Here, we review the different families of mammalian PRRs, the ligands they recognize, the mechanisms of activation, their role in disease, and the potential of targeting these proteins to develop the anti-inflammatory therapeutics of the future. PMID:25829385

  14. Clostridium difficile: clinical disease and diagnosis.

    PubMed Central

    Knoop, F C; Owens, M; Crocker, I C

    1993-01-01

    Clostridium difficile is an opportunistic pathogen that causes a spectrum of disease ranging from antibiotic-associated diarrhea to pseudomembranous colitis. Although the disease was first described in 1893, the etiologic agent was not isolated and identified until 1978. Since clinical and pathological features of C. difficile-associated disease are not easily distinguished from those of other gastrointestinal diseases, including ulcerative colitis, chronic inflammatory bowel disease, and Crohn's disease, diagnostic methods have relied on either isolation and identification of the microorganism or direct detection of bacterial antigens or toxins in stool specimens. The current review focuses on the sensitivity, specificity, and practical use of several diagnostic tests, including methods for culture of the etiologic agent, cellular cytotoxicity assays, latex agglutination tests, enzyme immunoassay systems, counterimmunoelectrophoresis, fluorescent-antibody assays, and polymerase chain reactions. PMID:8358706

  15. [Lyme disease--clinical manifestations and treatment].

    PubMed

    Stock, Ingo

    2016-05-01

    Lyme disease (Lyme borreliosis) is a systemic infectious disease that can present in a variety of clinical manifestations. The disease is caused by a group of spirochaetes--Borrelia burgdorferi sensu lato or Lyme borrelia--that are transmitted to humans by the bite of Ixodes ticks. Lyme disease is the most common arthropode-borne infectious disease in many European countries including Germany. Early localized infection is typically manifested by an erythema migrans skin lesion, in rarer cases as a borrelial lymphocytoma. The most common early disseminated manifestation is (early) neuroborreliosis. In adults, neuroborreliosis appears typically as meningoradiculoneuritis. Neuroborreliosis in children, however, is typically manifested by meningitis. In addition, multiple erythema migrans lesions and Lyme carditis occur relatively frequently. The most common manifestation oflate Lyme disease is Lyme arthritis. Early manifestations (and usually also late manifestations) of Lyme disease can be treated successfully by application of suitable antibacterial agents. For the treatment of Lyme disease, doxycycline, certain penicillins such as amoxicillin and some cephalosporins (ceftriaxone, cefotaxime, cefuroxime axetil) are recommended in current guidelines. A major challenge is the treatment of chronic, non-specific disorders, i. e., posttreatment Lyme disease syndrome and "chronic Lyme disease". Prevention of Lyme disease is mainly accomplished by protecting against tick bites. Prophylactic administration of doxycycline after tick bites is generally not recommended in Germany. There is no vaccine available for human beings. PMID:27348896

  16. Intervertebral disc disease.

    PubMed

    Simpson, S T

    1992-07-01

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

  17. Consensus Paper: Management of Degenerative Cerebellar Disorders

    PubMed Central

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

    2015-01-01

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

  18. In the Clinic. Gastroesophageal Reflux Disease.

    PubMed

    Harnik, Ian G

    2015-07-01

    This issue provides a clinical overview of gastroesophageal reflux disease, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic. PMID:26148292

  19. In the clinic. Sickle cell disease.

    PubMed

    Steinberg, Martin H

    2011-09-01

    This issue provides a clinical overview of sickle cell disease focusing on prevention, diagnosis, treatment, practice improvement, and patient information. Readers can complete the accompanying CME quiz for 1.5 credits. Only ACP members and individual subscribers can access the electronic features of In the Clinic. Non-subscribers who wish to access this issue of In the Clinic can elect "Pay for View." Subscribers can receive 1.5 category 1 CME credits by completing the CME quiz that accompanies this issue of In the Clinic. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including PIER (Physicians' Information and Education Resource) and MKSAP (Medical Knowledge and Self Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing division and with assistance of science writers and physician writers. Editorial consultants from PIER and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult www.acponline.org, http://pier.acponline.org, and other resources referenced within each issue of In the Clinic. PMID:21893620

  20. Stem cell treatment of degenerative eye disease☆

    PubMed Central

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

    2015-01-01

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

  1. Smart Technology in Lung Disease Clinical Trials.

    PubMed

    Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

    2016-01-01

    This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. PMID:26135330

  2. Diagnosis of Neurodegenerative Diseases: The Clinical Approach.

    PubMed

    Gómez-Río, Manuel; Caballero, Manuel Moreno; Górriz Sáez, Juan Manuel; Mínguez-Castellanos, Adolfo

    2016-01-01

    There are a number of clinical questions for which there are no easy answers, even for well-trained doctors. The diagnostic tool commonly used to assess cognitive impairment in neurodegenerative diseases is based on established clinical criteria. However, the differential diagnosis between disorders can be difficult, especially in early phases or atypical variants. This takes on particular importance when it is still possible to use an appropriate treatment. To solve this problem, physicians need to have access to an arsenal of diagnostic tests, such as neurofunctional imaging, that allow higher specificity in clinical assessment. However, the reliability of diagnostic tests may vary from one to the next, so the diagnostic validity of a given investigation must be estimated by comparing the results obtained from "true" criteria to the "gold standard" or reference test. While pathological analysis is considered to be the gold standard in a wide spectrum of diseases, it cannot be applied to neurological processes. Other approaches could provide solutions, including clinical patient follow-up, creation of a data bank or use of computer-aided diagnostic algorithms. In this article, we discuss the development of different methodological procedures related to analysis of diagnostic validity and present an example from our own experience based on the use of I-123-ioflupane-SPECT in the study of patients with movement disorders. The aim of this chapter is to approach the problem of diagnosis from the point of view of the clinician, taking into account specific aspects of neurodegenerative disease. PMID:26567736

  3. Clinical biomarkers in sickle cell disease

    PubMed Central

    Damanhouri, Ghazi A.; Jarullah, Jummanah; Marouf, Samy; Hindawi, S.I.; Mushtaq, Gohar; Kamal, Mohammad A.

    2014-01-01

    Sickle cell disease (SCD) is a hereditary blood disorder caused by a single gene. Various blood and urine biomarkers have been identified in SCD which are associated with laboratory and medical history. Biomarkers have been proven helpful in identifying different interconnected disease-causing mechanisms of SCD, including hypercoagulability, hemolysis, inflammation, oxidative stress, vasculopathy, reperfusion injury and reduced vasodilatory responses in endothelium, to name just a few. However, there exists a need to establish a panel of validated blood and urine biomarkers in SCD. This paper reviews the current contribution of biochemical markers associated with clinical manifestation and identification of sub-phenotypes in SCD. PMID:25561879

  4. Congenital von Willebrand's disease and clinical hypothyroidism.

    PubMed

    Hassan, S; Qureshi, W; Donthireddy, V; Kuriakose, P

    2013-03-01

    Data from case reports and systematic reviews suggest an association of Hypothyroidism and Acquired von Willebrand's syndrome. It is not known if congenital von Willebrand's disease is associated with hypothyroidism in a similar way. The aim of this study was to identify the association of congenital von Willebrand's disease (VWD) with clinical hypothyroidism. A total of 350 cases of congenital VWD were initially screened from our institution database from 1985 to 2010. A careful review of patient records was carried out to see if patients truly had congenital VWD and coexisting clinical hypothyroidism. Patients with uncertain diagnoses or other bleeding disorders were excluded, leading to 197 patients remaining in the final sample. A random age- and sex-matched parallel control group was also obtained from the hospital database. Of 197 patients (mean age 43.8 ± 17.5 years, women 72%) of congenital VWD, 32/197 (16%) were diagnosed with clinical hypothyroidism, while only 11/197 (5.6%) of the matched controls were clinically hypothyroid. Univariate and multivariate analysis demonstrated that VWD was an independent predictor of developing clinical hypothyroidism (OR 3.45; 95% CI 1.65-7.22, P = 0.001). The proportion of patients diagnosed with clinical hypothyroidism was more in the VWD group (P < 0.0001). Our analysis shows a strong association of clinical hypothyroidism in patients with congenital VWD, but future studies will be required to delineate a pathological mechanism. In our opinion, clinicians should consider checking thyroid function in the newly diagnosed and established cases of congenital VWD. PMID:23171382

  5. Desmopressin in adult urological disease: clinical evidences.

    PubMed

    Siracusano, Salvatore; Ciciliato, Stefano; Toffoli, Laura; Silvestri, Tommaso; Casotto, Daniela

    2015-01-01

    Desmopressin is a synthetic analogue of arginine vasopressin, commercially available since 1974. Desmopressin is proven effective for the treatment primary nocturnal enuresis and polyuria. It has been considered by several investigators for the treatment of nocturia with positive results and is now an established treatment for this indication. In this review, we assessed the available clinical data on desmopressin in adult urological disease. PMID:26541674

  6. Monogenic Autoinflammatory Diseases: Concept And Clinical Manifestations

    PubMed Central

    De Jesus, Adriana Almeida; Goldbach-Mansky, Raphaela

    2013-01-01

    The objectives of this review are to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary “periodic fever syndromes”, familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and; 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) 6. very rare conditions presenting with autoinflammation and immunodeficiency. PMID:23711932

  7. Crohn’s disease: a clinical update

    PubMed Central

    Ha, Francis; Khalil, Hanan

    2015-01-01

    Crohn’s disease is increasing in prevalence worldwide. It arises from a complex interplay between both genetic predisposition and environmental influence. A search of databases and clinical practice guidelines was performed to provide the most up-to-date evidence-based approach for diagnosing and managing patients with Crohn’s disease. No single gold standard investigation exists. Whilst full ileocolonoscopy with biopsies remains the mainstay for diagnosis, other less invasive imaging modalities are being actively considered in the workup, as well as the use of serological markers. Management should incorporate dietary and lifestyle modifications where necessary, the use of medications in induction and remission of disease, and consideration of surgical intervention where medical therapy has failed. PMID:26557891

  8. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2016-01-01

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

  10. [Neuropathologic markers in degenerative dementias].

    PubMed

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

    1998-01-01

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

  11. Uromodulin storage diseases: clinical aspects and mechanisms.

    PubMed

    Scolari, Francesco; Caridi, Gianluca; Rampoldi, Luca; Tardanico, Regina; Izzi, Claudia; Pirulli, Doroti; Amoroso, Antonio; Casari, Giorgio; Ghiggeri, Gian Marco

    2004-12-01

    The recent discovery of mutations in the uromodulin gene ( UMOD ) in patients with medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy (FJHN), and glomerulocystic kidney disease (GCKD) provides the opportunity for a revision of pathogenic aspects and puts forth the basis for a renewed classification. This review focuses on clinical, pathological, and cell biology advances in UMOD -related pathological states, including a review of the associated clinical conditions described to date in the literature. Overall, 31 UMOD mutations associated with MCKD2 and FJHN (205 patients) and 1 mutation associated with GCKD (3 patients) have been described, with a cluster at exons 4 and 5. Most are missense mutations causing a cysteine change in uromodulin sequence. No differences in clinical symptoms between carriers of cysteine versus polar residue changes have been observed; clinical phenotypes invariably are linked to classic MCKD2/FJHN. A common motif among all reports is that many overlapping symptoms between MCKD2 and FJHN are present, and a separation between these 2 entities seems unwarranted or redundant. Cell experiments with mutant variants indicated a delay in intracellular maturation and export dynamics, with consequent uromodulin storage within the endoplasmic reticulum (ER). Patchy uromodulin deposits in tubule cells were found by means of immunohistochemistry, and electron microscopy showed dense fibrillar material in the ER. Mass spectrometry showed only unmodified uromodulin in urine of patients with UMOD mutations. Lack of uromodulin function(s) is associated with impairments in tubular function, particularly the urine-concentrating process, determining water depletion and hyperuricemia. Intracellular uromodulin trapping within the ER probably has a major role in determining tubulointerstitial fibrosis and renal failure. We propose the definition of uromodulin storage diseases for conditions with proven UMOD mutations

  12. MDS clinical diagnostic criteria for Parkinson's disease.

    PubMed

    Postuma, Ronald B; Berg, Daniela; Stern, Matthew; Poewe, Werner; Olanow, C Warren; Oertel, Wolfgang; Obeso, José; Marek, Kenneth; Litvan, Irene; Lang, Anthony E; Halliday, Glenda; Goetz, Christopher G; Gasser, Thomas; Dubois, Bruno; Chan, Piu; Bloem, Bastiaan R; Adler, Charles H; Deuschl, Günther

    2015-10-01

    This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances. PMID:26474316

  13. Interdisciplinary care clinics in chronic kidney disease.

    PubMed

    Johns, Tanya S; Yee, Jerry; Smith-Jules, Terrian; Campbell, Ruth C; Bauer, Carolyn

    2015-01-01

    The burden of chronic kidney disease (CKD) is substantial, and is associated with high hospitalization rates, premature deaths, and considerable health care costs. These factors provide strong rationale for quality improvement initiatives in CKD care. The interdisciplinary care clinic (IDC) has emerged as one solution to improving CKD care. The IDC team may include other physicians, advanced practice providers, nurses, dietitians, pharmacists, and social workers--all working together to provide effective care to patients with chronic kidney disease. Studies suggest that IDCs may improve patient education and preparedness prior to kidney failure, both of which have been associated with improved health outcomes. Interdisciplinary care may also delay the progression to end-stage renal disease and reduce mortality. While most studies suggest that IDC services are likely cost-effective, financing IDCs is challenging and many insurance providers do not pay for all of the services. There are also no robust long-term studies demonstrating the cost-effectiveness of IDCs. This review discusses IDC models and its potential impact on CKD care as well as some of the challenges that may be associated with implementing these clinics. PMID:26458811

  14. Clinical Scenarios in Chronic Kidney Disease: Chronic Tubulointerstitial Diseases.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Chronic tubulointerstitial diseases are a common final pathway toward chronic renal failure regardless the primary damage (glomerular, vascular or directly the tubulointerstitium). Chronic tubulointerstitial nephritis (CTN) is characterized by interstitial scarring, fibrosis and tubule atrophy, resulting in progressive chronic kidney disease. Most frequent causes of CTN are drugs, heavy metals, obstructive uropathy, nephrolithiasis, reflux disease, immunologic diseases, neoplasia, ischemia, metabolic diseases, genetics and miscellaneous. At ultrasound (US), kidneys' morphological aspect is similar in all forms of chronic interstitial nephropathy and only chronic pyelonephritis with or without reflux shows distinguishing characteristics. In interstitial nephropathy, kidneys' profiles are finely irregular and corticomedullary differentiation is altered because of a diffused hyperechogenicity. The only indirect sign of chronic interstitial damage can be derived from the value of intrarenal resistive indexes that hardly overcome 0.75. US is mandatory in clinical chronic pyelonephritis work-up because it provides information on kidney's diameter and on growth nomogram in children. Renal profiles can be more or less altered depending on the number of cortical scars and the presence of pseudonodular areas of segmental compensatory hypertrophy. In the early stages, US diagnosis of renal tuberculosis is difficult because parenchymal lesions are non-specific. US sensitivity in the diagnosis of hydronephrosis is very high, close to 100% and, finally, US is the first choice imaging technique in the diagnosis of urinary lithiasis. PMID:27169608

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

    PubMed

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

    2016-08-01

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

  16. Advanced clinical insights & practice: ischemic heart disease.

    PubMed

    Benner, Randall W; Zavarella, Matthew S

    2008-03-01

    This issue sees the debut of a new series of continuing education articles. The series, Advanced Clinical Insights & Practice, is designed to provide continuing education to an ever-expanding realm of paramedicine that needs more of it: the critical care transport paramedic. Secondly, and equally important, are the benefits that can be reaped by other certification levels reading this feature. For EMT-Basics and Intermediates, it will provide a great enhancement to your core knowledge, although most of the interventions discussed will be beyond your traditional scope. For paramedics, it will augment both your pathophysiological understanding and clinical assessment/management skills of diseases and injuries discussed. Ultimately though, it is hoped that anyone who reads these articles will become a better clinician. The next article will appear in the July issue. PMID:18814637

  17. Clinical disease registries in acute myocardial infarction

    PubMed Central

    Ashrafi, Reza; Hussain, Hussain; Brisk, Robert; Boardman, Leanne; Weston, Clive

    2014-01-01

    Disease registries, containing systematic records of cases, have for nearly 100 years been valuable in exploring and understanding various aspects of cardiology. This is particularly true for myocardial infarction, where such registries have provided both epidemiological and clinical information that was not readily available from randomised controlled trials in highly-selected populations. Registries, whether mandated or voluntary, prospective or retrospective in their analysis, have at their core a common study population and common data definitions. In this review we highlight how registries have diversified to offer information on epidemiology, risk modelling, quality assurance/improvement and original research-through data mining, transnational comparisons and the facilitation of enrolment in, and follow-up during registry-based randomised clinical trials. PMID:24976913

  18. Rare disease clinical trials: Power in numbers.

    PubMed

    Wicklund, Matthew P

    2016-08-01

    The limb-girdle muscular dystrophies (LGMDs) encompass a collection of genetic muscle diseases with proximal-predominant weakness of the limbs. Thirty-two of these disorders are named via the common nomenclature, including 8 autosomal-dominant (LGMD1A-H) and 24 autosomal-recessive (LGMD2A-X) disorders.(1) In addition, numerous other genetic muscle diseases, including Bethlem myopathy, dystrophinopathies, ryanodine receptor-associated myopathies, and many more, may clinically present with similar proximal-predominant weakness.(2) Therefore, current genetic testing panels targeting neuromuscular weakness frequently encompass >75 genes. These disorders are quite rare, each with minimum prevalence estimates of 0.01-0.60 cases per 100,000 persons.(3) LGMD2A (attributable to mutations in the gene for calpain-3) and LGMD2B (attributable to mutations in the gene for dysferlin) consistently are the 2 most prevalent LGMD subtypes in a variety of ethnic cohorts. PMID:27540592

  19. Clinical manifestations and management of Gaucher disease

    PubMed Central

    Linari, Silvia; Castaman, Giancarlo

    2015-01-01

    Summary Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient β-glucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage. PMID:26604942

  20. Moyamoya Disease: Epidemiology, Clinical Features, and Diagnosis

    PubMed Central

    Kim, Jong S.

    2016-01-01

    Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease characterized by progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology remains unknown, recent genetic studies identified RNF213 in the 17q25-ter region as an important susceptibility gene of MMD among East Asian populations. Possibly because of genetic differences, MMD is relatively common in people living in East Asian countries such as Korea and Japan, compared to those in the Western Hemisphere. The prevalence of MMD appears to be slightly lower among Chinese, compared to Koreans or Japanese. There are two peaks of incidence with different clinical presentations, at around 10 years and 30-40 years. The peak appears to occur later in women than men. In children, ischemic symptoms, especially transient ischemic attacks, are predominant. Intellectual decline, seizures, and involuntary movements are also more common in this age group. In contrast, adult patients present with intracranial hemorrhage more often than pediatric patients. In patients with MMD, intracerebral hemorrhage is more often accompanied by intraventricular hemorrhage than in patients with hypertensive intracerebral hemorrhage. These different age peaks and different clinical presentations in each age group are also observed in MMD patients in the USA. Catheter angiography is the diagnostic method of choice. Magnetic resonance (MR) angiography and computed tomographic angiography are noninvasive diagnostic methods. High-resolution vessel wall MR imaging also helps diagnose MMD by revealing concentric vessel wall narrowing with basal collaterals. PMID:26846755

  1. Choosing Alzheimer's disease prevention clinical trial populations.

    PubMed

    Grill, Joshua D; Monsell, Sarah E

    2014-03-01

    To assist investigators in making design choices, we modeled Alzheimer's disease prevention clinical trials. We used longitudinal Clinical Dementia Rating Scale Sum of Boxes data, retention rates, and the proportions of trial-eligible cognitively normal participants age 65 and older in the National Alzheimer's Coordinating Center Uniform Data Set to model trial sample sizes, the numbers needed to enroll to account for drop out, and the numbers needed to screen to successfully complete enrollment. We examined how enrichment strategies affected each component of the model. Relative to trials enrolling 65-year-old individuals, trials enriching for older (minimum 70 or 75) age required reduced sample sizes, numbers needed to enroll, and numbers needed to screen. Enriching for subjective memory complaints reduced sample sizes and numbers needed to enroll more than age enrichment, but increased the number needed to screen. We conclude that Alzheimer's disease prevention trials can enroll elderly participants with minimal effect on trial retention and that enriching for older individuals with memory complaints might afford efficient trial designs. PMID:24119546

  2. Improving Alzheimer's disease phase II clinical trials.

    PubMed

    Greenberg, Barry D; Carrillo, Maria C; Ryan, J Michael; Gold, Michael; Gallagher, Kim; Grundman, Michael; Berman, Robert M; Ashwood, Timothy; Siemers, Eric R

    2013-01-01

    Over the past 30 years, many drugs have been studied as possible treatments for Alzheimer's disease, but only four have demonstrated sufficient efficacy to be approved as treatments, of which three are in the same class. This lack of success has raised questions both in the pharmaceutical industry and academia about the future of Alzheimer's disease therapy. The high cost and low success rate of drug development across many disease areas can be attributed, in large part, to late-stage clinical failures (Schachter and Ramoni, Nat Rev Drug Discov 2007;6:107-8). Thus, identifying in phase II, or preferably phase I, drugs that are likely to fail would have a dramatic impact on the costs associated with developing new drugs. With this in mind, the Alzheimer's Association convened a Research Roundtable on June 23 and 24, 2011, in Washington, DC, bringing together scientists from academia, industry, and government regulatory agencies to discuss strategies for improving the probability of phase II trial results predicting success when considering the go/no-go decision-making process leading to the initiation of phase III. PMID:23164548

  3. Globalization of Alzheimer's disease clinical trials

    PubMed Central

    2011-01-01

    Alzheimer's disease (AD) therapies are increasingly being tested in global clinical trials. A search of ClincalTrials.gov revealed that of 269 currently active trials, 28% are currently being conducted in the United States; the majority of trials and the majority of trial sites are ex-US. The US has the largest number of trial sites of any single country; cumulatively, nearly half of all sites are outside the US. The US conducts more trials in all phases of drug development but has a greater proportion of phase 3 trials. The increasing importance of global participants in clinical trials emphasizes the importance of considering the ethnic and international factors that may influence trial outcome. The International Conference on Harmonization guidelines divide ethnic factors that may affect drug development into intrinsic and extrinsic influences. These include language, cultural factors, educational levels, the general level of health and standard of care, as well as nutrition and diet. Ethnic influences on pharmacokinetics are known for some metabolic pathways. The biology of AD may also differ among the world's populations. The frequency of the apolipoprotein e4 allele, a major risk factor for AD, differs internationally. Genetic variations might also affect inflammatory, excitotoxic, and oxidative components of AD. Diagnostic standards and experience vary from country to country. Levels of practitioner training and experience, diagnostic approaches to AD, and attitudes regarding aging and AD may differ. Experience and sophistication with regard to clinical trial conduct also vary within and between countries. Experience with conducting the necessary examinations, as well as the linguistic and cultural validity of instrument translations, may affect trial outcomes. Operational and regulatory aspects of clinical trials vary and provide important barriers to seamless conduct of multiregional clinical trials. Collection and testing of biological samples, continuous

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2014-07-01

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

  6. A Rare Clinical Presentation of Darier's Disease

    PubMed Central

    Ferizi, Mybera; Begolli-Gerqari, Antigona; Luzar, Bostjan; Kurshumliu, Fisnik; Ferizi, Mergita

    2013-01-01

    Darier's disease, also known as keratosis follicularis or dyskeratosis follicularis, is a rare disorder of keratinization. It is an autosomal dominant genodermatosis with high penetrance and variable expressivity. Its manifestation appears as hyperkeratotic papules, primarily affecting seborrheic areas on the head, neck, and thorax and less frequently on the oral mucosa. When oral manifestations are present, the palatal and alveolar mucosae are primarily affected. They are usually asymptomatic and are discovered in routine dental examination. Histologically, the lesions are presented as suprabasal clefts in the epithelium with acantholytic and dyskeratotic cells represented by “corps ronds and grains”. This paper reports a case of a 53-year-old woman that was admitted to our clinic with more than 10-year history of keratotic papules, presented on the hands and feet, nose, ears, genitalia, and whitish lesions on palatal mucosae. PMID:23573430

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

    PubMed Central

    Misterska, Ewa; Jankowski, Roman; Głowacki, Maciej

    2013-01-01

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

  8. Use of (/sup 99m/Tc)-HM-PAO in the diagnosis of primary degenerative dementia

    SciTech Connect

    Testa, H.J.; Snowden, J.S.; Neary, D.; Shields, R.A.; Burjan, A.W.; Prescott, M.C.; Northen, B.; Goulding, P.

    1988-12-01

    The clinical value of single photon emission computed tomography (SPECT) in the differential diagnosis of dementia due to cerebral atrophy was evaluated by comparing the pattern of distribution (/sup 99m/Tc)-HM-PAO in three dementing conditions. Imaging was carried out in 26 patients with suspected Alzheimer's disease, 14 with dementia of the frontal-lobe type, and 13 with progressive supranuclear palsy. Images were evaluated and reported without knowledge of clinical diagnosis with respect to regions of reduced uptake of tracer. Reduced uptake in the posterior cerebral hemispheres was characteristic of Alzheimer's disease, while selective anterior hemisphere abnormalities characterized both dementia of the frontal-lobe type and progressive supranuclear palsy. The latter conditions could be distinguished on the basis of the appearance of integrity of the rim of the frontal cortex. The technique has an important role in the differentiation of degenerative dementias.

  9. Clinical studies in lysosomal storage diseases

    PubMed Central

    Boudes, Pol F

    2013-01-01

    Lysosomal storage disorders (LSDs) consist of over 40 diseases, some of which are amenable to treatment. In this review, we consider the regulatory context in which LSDs studies are performed, highlight design specificities and explore operational challenges. Orphan drug legislations, both in Europe and US, were effective to stimulate LSDs drug development. However, regulators flexibilities toward approval vary leading to global discrepancies in access to treatments. Study designs are constrained because few patients can be studied. This implies LSDs treatments need to demonstrate large levels of clinical efficacy. If not, an appropriate level of evidence is difficult to achieve. While biomarkers could address this issue, none have been truly accepted as primary outcome. Enrichment of study population can increase the chance of success, especially with clinical outcomes. Adaptive designs are operationally challenging. Innovative methods of analysis can be used, notably using a patient as his/her own control and responder analysis. The use of extension phases and patient registries as a source of historical comparison can facilitate data interpretation. Operationally, few patients are available per centers and multiple centers need to be initiated in multiple countries. This impacts time-lines and budget. In the future, regulators flexibility will be essential to provide patients access to innovative treatments. PMID:25003011

  10. Clinical imaging of vascular disease in chronic kidney disease.

    PubMed

    Sag, Alan A; Covic, Adrian; London, Gerard; Vervloet, Marc; Goldsmith, David; Gorriz, Jose Luis; Kanbay, Mehmet

    2016-06-01

    Arterial wall calcification, once considered an incidental finding, is now known to be a consistent and strong predictor of cardiovascular events in patients with chronic renal insufficiency. It is also commonly encountered in radiologic examinations as an incidental finding. Forthcoming bench, translational, and clinical data seek to establish this and pre-calcification changes as surrogate imaging biomarkers for noninvasive prognostication and treatment follow-up. Emerging paradigms seek to establish vascular calcification as a surrogate marker of disease. Imaging of pre-calcification and decalcification events may prove more important than imaging of the calcification itself. Data-driven approaches to screening will be necessary to limit radiation exposure and prevent over-utilization of expensive imaging techniques. PMID:26898824