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Purpose: Ossification of the posterior longitudinal ligament of the cervical spine (cervical OPLL) is associated with the lesions at the thoracic and/or lumbar spine. Multiple spinal lesions cause additional neurological deficit, affecting the outcomes of cervical laminoplasty. This study aimed to clarify the effect of multiple lesions on the outcomes of cervical laminoplasty and to compare the results with data from patients without them.Methods: From April 1981 to October 2015, 201 patients underwent laminoplasty for cervical OPLL; however, 167 patients were followed for >2 years. Twenty-four patients underwent additional surgery for multiple lesions due to spinal stenosis. The pathologies of the lesions were assessed. The patients were divided into two groups: the thoracic and thoraco-lumbar group (T-group: 8 patients) and the lumbar group (L-group: 16 patients). One-hundred patients without an additional surgery served as the control group. The maximum Japanese Orthopaedic Association (JOA) score and the most recent score for recovery was compared between the multiple and control groups.Results: The maximum score and recovery rate and the score and recovery rate at the last follow-up in the multiple group were lower than those in the control group. There was no significant difference in the postoperative JOA score and recovery rate between the T-group and the L-group.Conclusions: Neurological recovery in patients with multiple lesions was poorer than in those without lesions. Therefore, special attention should be paid to cervical OPLL with multiple spinal lesions. [ABSTRACT FROM AUTHOR]

Background: Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are characterized by replacement of ligamentous tissue by ectopic new bone formation. Although the background of both diseases might be similar, there are some differences between two diseases. Some patients have both OPLL and OLF. However, the incidence of both OPLL and OLF is still unclear and the precise lesions have not been investigated, yet. This study was conducted to evaluate OLF of the whole spine in patients with cervical OPLL and to analyze the relationship of the ossified lesions between OLF and OPLL.Methods: One hundred seventy eight patients who were diagnosed as cervical OPLL by plain radiographs were included. CT images of the whole spine were taken. Ossified lesions were checked at each level of vertebral body and intervertebral disc. The ossification index of OPLL (OPLL OS index) was determined by the sum of the levels of vertebral bodies and intervertebral discs where OPLL existed. The same index was applied for detecting the level of OLF (OLF OS index). Age, gender and OPLL characteristics were compared between the OLF(+) group, OLF was seen at any levels of the spinal canal, and the OLF(-) group, OLF was not seen.Results: The most frequent level of OPLL was at C5 vertebral level and OLF was predominant at upper and lower thoracic levels. Seventeen patients (9.6%) had OPLL and OLF at the same spinal level. The averaged OPLL OS index of the total spine in these patients was 8.7 ± 6.1, ranged from 1 to 36. The averaged OLF OS index of the total spine was 3.1 ± 2.2 (ranged from 1 to 13) in the patients who had OLF at any levels of the whole spine. One hundred fifteen patients (64.6%) with cervical OPLL had OLF at any levels of the whole spine. No relationship was found between the OPLL OS index and the OLF OS index. There was no significant difference among the data between the OLF(+) group and the OLF(-) group.Conclusions: This study demonstrated 64.6% of the patients with cervical OPLL had OLF, mainly in the thoracic spine. However, there was no relationship regarding the severity of the ossified lesions between OPLL and OLF. CT analysis of the whole spine should be carried out for the early detection of OPLL and OLF in patients with cervical OPLL. [ABSTRACT FROM AUTHOR]

Ossification of the posterior longitudinal ligament (OPLL) involves the replacement of ligamentous tissue with ectopic bone. Although genetics and heritability appear to be involved in the development of OPLL, its pathogenesis remains to be elucidated. Given previous findings that 5,8,11-eicosatrienoic acid [20:3n-9, Mead acid (MA)] has depressive effects on osteoblastic activity and anti-angiogenic effects, and that n-3 polyunsaturated fatty acids (PUFAs) have a preventive effect on heterotopic ossification, we hypothesized that both fatty acids would be involved in OPLL development. To examine the biological significance of these and other fatty acids in OPLL, we conducted this case-control study involving 106 patients with cervical OPLL and 109 age matched controls. Fatty acid composition was determined from plasma samples by gas chromatography. Associations between fatty acid levels and incident OPLL were evaluated by logistic regression. Contrary to our expectations, we found no significant differences between patients and controls in the levels of MA or n-3 PUFAs (e.g., eicosapentaenoic acid and docosahexaenoic acid). Logistic regression analysis did not reveal any associations with OPLL risk for MA or n-3 PUFAs. In conclusion, no potential role was found for MA or n-3 PUFAs in ectopic bone formation in the spinal canal. [ABSTRACT FROM AUTHOR]

Abstract: Background context: Two surgical procedures, posterior decompressive surgery (PDS) and anterior decompressive surgery (ADS), are the treatment options for cervical ossification of the posterior longitudinal ligament (OPLL). Each procedure has advantages and disadvantages. Cervical laminoplasty, a type of PDS, is relatively easy to perform and can be used for patients with multilevel cord compression. ADS can often be more technically demanding. Objective: The purpose of this study was to clarify the clinical characteristics and surgical results of the patients for whom ADS was necessary after PDS. Study design: Retrospective study. Methods: A total of 144 patients, followed for more than 3 years after cervical laminoplasty, were included. The neurologic status was graded using the Japanese Orthopedic Association (JOA score). Eleven patients underwent ADS after PDS. The clinical background and surgical outcomes were evaluated. Radiological findings of the 11 patients requiring ADS after PDS (PA group) and the 133 PDS patients not requiring ADS (P group) were compared. Results: In the PA group, the JOA score was slightly deteriorated during follow-up after cervical laminoplasty. Severe pain in the unilateral upper extremity and deterioration of cervical myelopathy were the most typical symptoms necessitating ADS. The incidence of the mixed type of OPLL was significantly higher in this group. The JOA score improved in all patients after ADS as a second surgery. Conclusions: In our strategy for the surgical treatment of cervical OPLL, PDS with laminoplasty remains as the initial treatment, and in patients with neurological deterioration and newly developed clinical symptoms during follow-up, ADS is considered as a salvage procedure. [Copyright &y& Elsevier]

Abstract: Background context: There has been no study regarding the comparison between vertebroplasty and conservative treatment for osteoporotic burst fracture. Purpose: To compare the results of vertebroplasty after intravertebral cavity formation with that of conservative treatment alone. Study design: A case-control study. Methods: The vertebroplasty group included 40 consecutive patients with primary osteoporotic burst fracture who underwent vertebroplasty using calcium phosphate cement, and the control group was made up of 40 patients given conservative treatment alone who were matched for age, gender, the injury level, and the type of fracture. Two groups of patients who had no neural deficit were prospectively examined. Clinical and radiological outcomes of these two groups were compared blindly. The authors do not report any conflict of interest in this study. Outcome measures: Outcome measures included visual analog scale (VAS) of the back pain, analgesic requirements, and mobility; in a lateral radiograph, the deformity index was measured and expressed as the ratio of the vertebral body (VB) height (sum of measurements at anterior, middle, and posterior regions of VB) to the longitudinal diameter of VB. Anteroposterior height comparison was expressed as the percentage of VB height at the anterior region compared with the height at the posterior region. Each recovery rate was calculated as a percentage by the formula: (value at the examination−value before treatment)/value before treatment×100. Results: The duration of follow-up was more than 12 months (mean; 22.5 months). The mean VAS at 12 months after injury was 2.17 cm in the conservative group and 0.61 cm in the vertebroplasty group (p=.0002). The mean duration of analgesic medication required was 157.2 days in the conservative group and 21.3 days in the vertebroplasty group (p=.0048). The mean deformity index at 12 months after injury was 1.66 in the vertebroplasty group and 1.38 in the control group, and the mean recovery rate was +7.3% and −18.4%, respectively (p<.0001). Anteroposterior height comparison at 12 months after injury was 49.1% in the conservative group and 71.2% in the vertebroplasty group, and the mean recovery rate was −26.4% and +30.1%, respectively (p<.0001). One fracture in the vertebroplasty group showed delayed union until 6 months after injury. In the control group, there were six delayed union including four pseudoarthroses at over 6 months after injury that caused leg pain and were treated by conservative therapy. Conclusions: We conclude that vertebroplasty after intravertebral cavity formation provided a better clinical and radiological result than conservative treatment for osteoporotic burst fracture. [Copyright &y& Elsevier]

Abstract: A novel class of 3,7-diphenyl-4-amino-thieno and furo[3,2-c]pyridine has been designed based on pharmacophore models of ATP competitive kinase inhibitors. Versatile synthetic methods via double Suzuki coupling to explore SAR have been established and potent inhibitors against angiogenetic targets, VEGFR2, Tie-2, and EphB4, have been successfully discovered. [Copyright &y& Elsevier]

Abstract: The visceral reflexes of the pelvic organs are mediated by connections between primary afferents innervating the pelvic organs and parasympathetic preganglionic neurons in the intermediolateral column of the sacral spinal cord. The present immunohistochemical study revealed many varicosities expressing transient receptor potential vanilloid 1 (TRPV1) that were closely apposed to the preganglionic neuronal perikarya at embryonic day 16 in mice. Many, but not all, varicosities expressing TRPV1 in the intermediolateral column were also immunopositive for calcitonin gene-related peptide. In contrast, no nerve fibers expressing TRPV1 projected to the sympathetic preganglionic cell column in the lumbar spinal cord in prenatal stages. The results of the present study raised the possibility that the primary afferents transmit signals elicited by the activation of TRPV1 receptors to the sacral parasympathetic preganglionic neurons. Thus, the functional circuit for pelvic spinal reflexes, such as micturition induced by urine influx, might develop in the prenatal stages in mice. [Copyright &y& Elsevier]

Modeling studies of a furo[2,3-d]pyrimidine GSK-3 hit compound 1 superimposed onto the X-ray crystal structure of a legacy pyrazolo[3,4-c]pyridazine GSK-3 inhibitor 2 led to the identification of 4-acylamino-6-arylfuro[2,3-d]pyrimidine template 3. Synthesis of analogues based on template 3 has resulted in a number of potent and selective GSK-3β inhibitors. The most potent and selective compound was the m-pyridyl analogue 24. [ABSTRACT FROM AUTHOR]

Background Context: Although direct vertebral rotation (DVR) is now used worldwide for the surgical treatment of adolescent idiopathic scoliosis (AIS), the benefit of DVR in reducing vertebral body rotation in these patients has not been determined. Purpose: We investigated a possible additive effect of DVR on further reduction of vertebral body rotation in the axial plane following intraoperative rod rotation or differential rod contouring in patients undergoing surgical treatment for AIS. Study Design/setting: The study was a prospective computed tomography (CT) image analysis. Patient Sample: We analyzed the results of the two intraoperative procedures in 30 consecutive patients undergoing surgery for AIS (Lenke type I or II: 15; Lenke type V: 15). Outcome Measures: The angle of reduction of vertebral body rotation taken by intraoperative CT scan was measured and analyzed. Pre- and postoperative responses to the Scoliosis Research Society 22 Questionnaire (SRS-22) were also analyzed. Methods: To analyze the reduction of vertebral body rotation with rod rotation or DVR, intraoperative cone-beam CT scans of the three apical vertebrae of the major curve of the scoliosis (90 vertebrae) were taken pre-rod rotation (baseline), post-rod rotation with differential rod contouring, and post-DVR in all patients. The angle of vertebral body rotation in these apical vertebrae was measured and analyzed for statistical significance. Additionally, differences between thoracic curve scoliosis (Lenke type I or II; 45 vertebrae) and thoracolumbar or lumbar curve scoliosis (Lenke type V; 45 vertebrae) were analyzed. Pre- and postoperative SRS-22 scores were evaluated in all patients. Results: The mean (90 vertebrae) vertebral body rotation angles at baseline, post-rod rotation or differential rod contouring, and post-rod rotation or differential rod contouring or post-DVR were 17.3°, 11.1°, and 6.9°, respectively. The mean reduction in vertebral body rotation with the rod rotation technique was 6.8° for thoracic curves and 5.7° for thoracolumbar or lumbar curves (p<.00005). The mean additional reduction in rotation with the DVR technique was 3.4° for thoracic curves and 4.9° for thoracolumbar or lumbar curves (p<.00005). Direct vertebral rotation displayed a slightly but significantly greater additive effect in reducing rotation following initial reduction with rod rotation or differential rod contouring in thoracolumbar or lumbar than in thoracic curves. In the SRS-22 results, postoperative self-image was significantly better than preoperative image in both groups. Conclusions: Direct vertebral rotation contributed an additional reduction in vertebral body rotation in thoracic and thoracolumbar or lumbar curves. The DVR technique is likely to be more useful in thoracolumbar or lumbar curve scoliosis than in thoracic curve scoliosis. [ABSTRACT FROM AUTHOR]

Background: In cervical myelopathy, significant findings are seen in flexion-extension MRI due to the increased likelihood of cord compression during neck extension. In addition, a high intramedullary signal on T2-weighted MR images has been reported to be a prognostic factor in this condition. However, the relationship between Japanese Orthopaedic Association (JOA) scores and the signal intensity in preoperative cervical flexion-extension T2-weighted images has not been evaluated. The purpose of this study was to evaluate whether preoperative flexion-extension MRI may be used to predict surgical outcomes in patients with cervical myelopathy.Methods: A total of 121 patients who underwent surgery for cervical myelopathy were included. All patients underwent preoperative cervical flexion-extension MRI followed by cervical decompression surgery, with or without spinal fusion, and postoperative follow-up for at least 2 years. Pre- and postoperative (2 years after surgery) JOA scores were recorded, and the degree of postoperative improvement was calculated. The relationship between intramedullary signal intensity on preoperative cervical dynamic MRI findings and degree of clinical recovery was examined.Results: Patients with a high intramedullary signal on the extension MRI had significantly better neurological recovery than those with a high signal on the flexion MRI (p < 0.000005). There was no significant difference in neurological recovery between patients with and without a high intramedullary signal on extension MRI.Conclusions: A preoperative high intramedullary signal on flexion MRI was associated with a poor surgical outcome, while no such association was seen with extension MRI. [ABSTRACT FROM AUTHOR]

Abstract: Onuf''s nucleus in the lumbosacral spinal cord, comprising somatic motoneurons that innervate the pelvic floor muscles via the pudendal nerve, shares some characteristics with the autonomic preganglionic neurons and functions in coordination with the autonomic nervous system. In mouse, neurons projecting to the urethral sphincter and ischiocavernosus muscles form the dorsolateral (DL) nucleus at the caudal lumbar levels, whereas neurons projecting to the limb and hip joint muscles comprise the retrodorsolateral and ventral nucleus, as well as the DL nucleus at the rostral lumbar levels. The results of the present study in mouse revealed that the expression pattern of a LIM homeodomein protein Islet-1, an embryonic marker for motoneurons in the spinal cord, was different among motoneuronal groups at the prenatal stage (embryonic days 13.5–15.5); the highest expression was observed in the DL at the caudal lumbar cord, whereas there was little expression in the lateral part of the rostral DL. Islet-1 expression was also observed in the parasympathetic preganglionic neurons at the sacral spinal cord. These findings provide evidence that the DL neurons at the caudal lumbar cord, corresponding to Onuf''s nucleus, are chemically distinct among the motoneuronal groups at the prenatal stages. This differential Islet-1 expression among the motoneuronal groups suggests that Islet-1 not only leads to a motoneuronal lineage, but also to the differentiation of motoneuronal subsets in the lumbosacral spinal cord. [Copyright &y& Elsevier]

Abstract: The synthesis of a 7-azaindole series of novel, potent B-Raf kinase inhibitors using knowledge-based design was carried out. Compound 6h exhibits not only excellent potency in both the enzyme assay (IC50 =2.5nM) and the cellular assay (IC50 =63nM), but also has an outstanding selectivity profile against other kinases. [Copyright &y& Elsevier]

Background: Differential rod contouring (DRC) is useful for periapical vertebral derotation and decreasing rib hump in patients with thoracic adolescent idiopathic scoliosis (AIS). However, it is unknown whether DRC in the thoracolumbar/lumbar spine also contributes to derotation. We assessed the contributions of rod contouring and of DRC to the reduction of apical axial vertebral body rotation in patients with AIS with thoracolumbar/lumbar curvatures.Methods: Forty-five (Lenke type 3 or 4, 17; Lenke type 5 or 6, 28) were analyzed for the contribution of DRC to thoracolumbar/lumbar spinal derotation. Rod contouring was assessed by comparing the preinsertion x-ray with the post-operative CT images. Intraoperative C-arm fluoroscopic scans of the periapical vertebrae of the thoracolumbar/lumbar curve of the scoliosis (135 vertebrae) were taken post-rod rotation (RR) and post-DRC in all patients. Three-dimensional images were automatically reconstructed from the taken x-ray images. The angle of vertebral body rotation in these apical vertebrae was measured, and the contribution of DRC to apical vertebral body derotation and rib hump index (RHi) for lumbar prominence was analyzed.Results: The pre-implantation convex rod curvatures of both Lenke 3/4 and 5/6 groups decreased after surgery. The mean further reductions in vertebral rotation with post-RR DRC were 3.7° for Lenke 3/4 and 4.4° for Lenke 5/6 (P < 0.01). Both changes in apical vertebral rotation and in RHi for evaluating lumbar prominence were significantly correlated with the difference between concave and convex rod curvature in preimplantation. Vertebral derotation was significantly higher in curves with a difference >20° (P < 0.05).Conclusions: DRC following rod rotation contributed substantial additional benefit to reducing vertebral rotation and decreasing lumbar prominence in thoracolumbar/lumbar scoliosis. [ABSTRACT FROM AUTHOR]

Background: Lumbar disc degeneration (LDD) is known to be the main cause of low back pain, although it is unclear how or when LDD progresses. The purpose of this study was to clarify the process and features of LDD progression in young women.Methods: We enrolled 480 nursing students and carried out a prospective cohort study in 84 nursing students. MRI of the lumbar spine was taken once during their time as a student and again at 9.8 years (7-14) after the first MRI when they were working as nurses. The grade of LDD was determined according to Schneiderman's grade. The progression of disc degeneration was evaluated by the change in the degenerative disc disease (DDD) score (the summation of DDD score at each disc level). The subjects were divided into two groups based on MRI findings: Group A, those without disc degeneration at the first MRI (n = 58) and Group B, those showing disc degeneration on the first MRI (n = 26). We evaluated the change in DDD score and assessed the particular disc levels that showed Schneiderman's grade worsening in each group.Results: At the time of the 2nd MRI, the DDD score increased from 5.6 (5-9) to 6.3 (5-11). The L5/S disc was the most frequent level showing the progression of LDD. In Group A, 18 subjects (31.0%) and in Group B, 15 subjects (57.7%) had degeneration progression (p = 0.02).Conclusions: This study revealed that 31% of the young adult subjects already had disc degeneration in 20's (time of first MRI) and the disc degeneration rapidly progressed in these subjects. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 49-year-old man with diabetes mellitus and an ossification of the posterior longitudinal ligament (OPLL). Topics mention include complained of drop foot and numbness of the lower thigh in the right leg, the revelation of muscle weakness and analgesia of the right L5 and S1 dermatomes through neurological examination and the xray result shows no degerative change or instability in the lumbar spine.

The article presents case studies of monoparesis of the upper extremity. It mentions the contribution of upper cervical cord compression (UCCC) on the development of the disease. It outlines the symptoms experienced by the patients including sensory abnormalities, neck pain and paraparesis. Several laboratory tests conducted to the patients are highlighted including magnetic resonance imaging and radiography.

Abstract: Background context: Ossification of the ligamentum flavum (OLF) may result in thoracic myelopathy (TM) because of narrowing of the spinal canal. Because symptoms vary and are subjective, diagnosis of TM caused by OLF is sometimes difficult when based on symptoms and physical examination. Posterior decompression is indicated in patients with TM caused by OLF because it is believed that surgery is the most effective treatment. However, surgical outcomes vary. We are unaware of reports of objective presurgical diagnostic parameters, such as neurologic and radiologic findings, relating to the postsurgical prognosis in patients with TM caused by OLF. Purpose: To determine which presurgical and surgical variables were most closely related to postsurgical prognosis of TM caused by OLF. Study design: Retrospective review of the records of the cohort of patients who had undergone surgery from 1988 through 2008 at the University of Toyama Hospital for TM caused by OLF. Patient sample: Forty-one patients who had surgery for TM caused by OLF that was progressive, severe, or both and for which the diagnosis was based on clinical, radiologic, and pathologic evaluations. Outcome measures: Relationship between the highest follow-up Japanese Orthopaedic Association (JOA) score for neurologic evaluation and of Hirabayashi's formula to indicate the extent of normalization after surgery with respect to the following 10 variables: age at surgery; sex; duration of presurgical symptoms; complications of diabetes mellitus; complications of hypertension; presence of presurgical hyperreflexia in either or both of the patellar tendon reflex and the Achilles tendon reflex; presurgical impairment of joint position sense in the big toes; number of levels affected by OLF; concurrent spinal lesions including ossification of the posterior longitudinal ligament; and intramedullary change of the spinal cord seen on magnetic resonance imaging (MRI). Methods: Multiple linear analyses were used to evaluate the variables related to postsurgical recovery. Results: Presurgical impairment of joint position sense in the big toe was the most important predictor of the highest postsurgical JOA score and of the highest percentage recovery rate. The number of affected OLF levels also predicted the postsurgical highest JOA score, but not statistically significantly so. Age at surgery, sex, and duration of symptoms presurgically did not affect postsurgical recovery. Complications of diabetes mellitus or of hypertension did not affect percentage recovery rate. The difference between recovery rate in patients with or without concurrent spinal lesions was not significant. Presurgical hyperreflexia was not correlated with recovery. Postsurgical JOA scores and percentage recovery rates of scores in patients whose presurgical MRIs had shown intramedullary signal change were not statistically significantly different from those whose MRIs had not shown signal change. Conclusions: An excellent postoperative prognosis is not always possible in patients with TM caused by OLF. It may be important to check for impairment of joint position sense in the big toe, the number of levels affected by OLF, and presurgical intramedullary signal change on MRI before continuing to surgery. [Copyright &y& Elsevier]

The article describes the case of a 67-year-old female patient who suffered from left shoulder stiffness for a decade. The patient complained that she also experienced numbness and clumsiness in her lower extremities and bilateral upper extremities for a year. She was diagnosed by medical professionals to be experiencing cervical myelopathy due to the C1 sleep apnea posterior subluxation.

Abstract: 4-Amino-5,6-diaryl-furo[2,3-d]pyrimidines have been identified as inhibitors of glycogen synthase kinase-3β (GSK-3β). One representative derivative, 4-amino-3-(4-(benzenesulfonylamino)-phenyl)-2-(3-pyridyl)-furo[2,3-d]pyrimidine (12) exhibited potent GSK-3β inhibitory activity in low nanomolar level of IC50. The binding mode was proposed from a docking study. [Copyright &y& Elsevier]

Abstract: During our effort to develop dual VEGFR2 and Tie-2 inhibitors as anti-angiogenic agents for cancer therapy, we discovered 4-amino-5-(4-((2-fluoro-5-(trifluoromethyl)phenyl)- aminocarbonylamino)phenyl)furo[2,3-d]pyrimidine (8a) possessing strong inhibitory activity at both the enzyme and cellular level against VEGFR2 and Tie-2. Compound 8a demonstrated high pharmacokinetic exposure through oral administration, and showed marked tumor growth inhibition and anti-angiogenic activity in mouse HT-29 xenograft model via once-daily oral administration. [Copyright &y& Elsevier]

Abstract: A novel class of furo[2,3-d]pyrimidines has been discovered as potent dual inhibitors of Tie-2 and VEGFR2 receptor tyrosine kinases (TK) and a diarylurea moiety at 5-position shows remarkably enhanced activity against both enzymes. One of the most active compounds, 4-amino-3-(4-((2-fluoro-5-(trifluoromethyl)phenyl)amino-carbonylamino)phenyl)-2-(4-methoxyphenyl)furo[2,3-d]pyrimidine (7k) is <3nM on both TK receptors and the activity is rationalized based on the X-ray crystal structure. [Copyright &y& Elsevier]

To examine the prenatal development of spinal visceral reflexes, primary sensory nerve fibers immunoreactive for calcitonin gene-related peptide (CGRP) were examined in the spinal cord, particularly in the autonomic preganglionic nuclei of mouse embryos. On embryonic day 16 (E16), CGRP-immunoreactive fibers were first observed in the sacral intermediolateral nucleus (IML) of the parasympathetic division as well as in the lumbar central autonomic nucleus (CA) of the sympathetic division, where they appeared in proximity to preganglionic neuronal perikarya immunoreactive for choline acetyltransferase or nitric oxide synthase. Most of the CGRP-immunoreactive varicosities were negative for substance P. Substance P-immunoreactive varicosities were scattered in these nuclei, but no appositions were seen on the preganglionic neuronal perikarya. On E18, CGRP-immunoreactive fibers were more abundant in the sacral IML and the lumbar CA. Co-expression of substance P and CGRP was frequently observed in the varicosities very close to the preganglionic neuronal perikarya on E18. CGRP-immunoreactive fibers were also observed in the lumbar IML on E18, although significantly fewer were found in this nucleus compared with the sacral IML. In contrast to the upper lumbar level, no fibers immunoreactive for CGRP were observed in the IML at the thoracic level. These results suggest that peptidergic primary sensory fibers grow to project to the selective targets of autonomic preganglionic neurons during the embryonic period. The potential direct connections between the peptidergic primary sensory fibers and preganglionic neurons innervating the pelvic viscera might provide a circuit for spinal visceral reflexes active in embryos. [Copyright &y& Elsevier]

Background Context: Although the cervical spine is only occasionally involved in rheumatoid arthritis (RA), involvement of the lumbar spine is even less common. A few reports on lumbar spinal stenosis in patients with RA have appeared. Although disc space narrowing occurs in aging, postoperative adjacent segment disease (ASD) in patients with RA has not been subject to much analysis.Purpose: The objective of this study was to investigate differences in ASD and clinical outcomes between lumbar spinal decompression with and without fusion in patients with RA.Study Design/setting: This is a retrospective comparative study.Patient Sample: A total of 52 patients with RA who underwent surgery for lumbar spinal disorders were included. Twenty-seven patients underwent decompression surgery with fusion and 25 underwent decompression surgery alone.Outcome Measures: Intervertebral disc space narrowing and spondylolisthesis of the segment immediately cranial to the surgical site were measured using a three-dimensional volume rendering software. Pre- and postoperative evaluation of RA activity and Japanese Orthopaedic Association (JOA) scores were conducted.Materials and Methods: All patients had preoperative and annual postoperative lumbar radiographs and were followed up for a mean of 5.1 years (range 3.5-10.9 years). Pre- and postoperative (2 years after surgery) JOA scores were recorded and any postoperative complications were investigated. Degrees of intervertebral disc narrowing and spondylolisthesis at the adjacent levels were evaluated on radiographs and were compared between the two groups. Analysis was performed to look for any correlation between ASD and RA disease activities.Results: Postoperative JOA scores were significantly improved in both groups. The rate of revision surgery was significantly higher in the fusion group than that in the non-fusion group. The rate of ASD was significantly greater in the fusion group than that in the non-fusion group at the final follow-up examination. Both matrix metalloproteinase 3 (MMP-3) and the 28-joint disease activity score incorporating C-reactive protein levels (DAS28-CRP) were significantly associated with the incidence and severity of ASD.Conclusions: Adjacent segment disease and the need for revision surgery were significantly higher in the fusion group than those in the non-fusion group. A preoperative high MMP-3 and DAS28-CRP are likely to be associated with postoperative ASD. [ABSTRACT FROM AUTHOR]