Search

A new method for estimating in vivo bone mineral density (BMD) and characterizing the shape of cancellous bone has been proposed using the results of ultrasonic inspection for the diagnosis of osteoporosis. The method is based on two-dimensional bone area fraction S (percent bone area between bone and bone marrow) calculated from the difference in the speed of ultrasonic wave propagation through cancellous bone. It was shown that the two-dimensional area fraction of a heel bone gives a good relationship to the BMD by DXA (dual energy x-ray absorptiometry) testing of human heel bone (calcaneus) and spine (vertebrae lumbar), as expressed by the relation, BMD (g/[cm.sup.2] = 0.0167S for heel bone (r = 0.83), and BMD (g/[cm.sup.2]) = 0.0254S + 0.123 for the spine (r = 0.77). Shape characterization is based on the image simulation procedure employing eight random variables from a computer and the statistical results of fractal analysis for numerous cancellous bone patterns. We also demonstrate the validity of the shape characterization technique using autopsy specimens as a diagnostic tool for osteoporosis.

Background: Intrathecal baclofen therapy can substantially improve symptoms in most patients with severe spasticity due to traumatic spinal cord injury, multiple sclerosis, or cerebral paresis. To the best of our knowledge, decompression surgeries at the intrathecal catheter insertion site in patients with a preexisting intrathecal pump for drug delivery have not been reported., Case Presentation: We report the case of a 61-year-old Japanese man with lumbar spinal stenosis who underwent intrathecal baclofen therapy. We performed decompression for lumbar spinal stenosis at the intrathecal catheter insertion site during intrathecal baclofen therapy. The yellow ligament was removed by partial resection of the lamina under a microscope to avoid damage to the intrathecal catheter. The dura mater was distended. No obvious cerebrospinal fluid leakage was observed. Postoperatively, lumbar spinal stenosis symptoms improved, and spasticity remained well controlled with intrathecal baclofen therapy., Conclusions: This is the first reported case of lumbar spinal stenosis decompression at an intrathecal catheter insertion site during intrathecal baclofen therapy. Preoperative preparation is necessary, as the intrathecal catheter may be replaced during surgery. We performed surgery without removing or replacing the intrathecal catheter, taking care not to damage the spinal cord by migrating the intrathecal catheter., (© 2023. The Author(s).)

Background: Patients with tethered cord syndrome often suffer severe spasticity. To the best of our knowledge, intrathecal baclofen (ITB) therapy in a patient with tethered cord syndrome has not been reported previously. We describe a case in which ITB therapy was useful for treating severe spasticity in an adult with tethered cord syndrome., Case Presentation: We present the case of a 50-year-old Japanese woman with tethered cord syndrome and related conditions suffering from severe spasticity and pain in the lower limbs. She was born with a lumbosacral myelomeningocele, which was closed in the neonatal period. For 4-5 years before this presentation, spasticity in the lower limbs had been exacerbated without any obvious cause. She received rehabilitation and pharmacotherapy from a local doctor, but symptoms were unimproved, and her previous doctor referred her to this department. A test with 50 μg of intrathecally delivered baclofen showed total relief of spasticity and pain, so a pump was implanted for continuous baclofen delivery. During 24 months of follow-up, spasticity has remained under excellent control with baclofen at 38.5-41.0 μg/day., Conclusions: ITB therapy proved extremely effective in this adult with severe spasticity from tethered code syndrome., (© 2021. The Author(s).)

Structural modification of a 1,4-benzodiazepin-2-one-based PTHR1 antagonist 5, a novel type of PTHR1 antagonist previously synthesized in our laboratories, yielded compound 10, which had better chemical stability than compound 5. Successive optimization of the lead 10 improved aqueous solubility, metabolic stability, and animal pharmacokinetics, culminating in the identification of DS37571084 (12). Our study paves the way for the discovery of novel and orally bioavailable PTHR1 antagonists., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could appear to have influenced the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

[Purpose] To evaluate the severity of symptoms before and after cervical myelopathy surgery using the Simple Test for Evaluating hand Function. Because a test ceiling effect was observed in patients with less severe forms of myelopathy, we investigated the correlation between and accuracy of several different tests in order to clarify the usefulness of the Purdue Pegboard Test for evaluation of one or both hands. [Participants and Methods] Thirty-four patients (6 females and 28 males; mean age, 64.5 years) were examined, and scores were determined for each of the following tests: Purdue Pegboard Test; Simple Test for Evaluating hand Function; Japanese Orthopedic Association assessment; and Disabilities of the Arm, Shoulder, and Hand assessment. Correlations between scores of different tests were then determined. The cut-off values used for the Purdue Pegboard Test and the Simple Test for Evaluating hand Function were determined using the area under the receiver operating characteristic curve to assess the use of chopsticks. [Results] The Purdue Pegboard Test assembly task correlated moderately with the Japanese Orthopedic Association and Disabilities of the Arm, Shoulder, and Hand scores. In the receiver operating characteristic curve analyses, the Purdue Pegboard Test cut-off value was 11 and the Simple Test for Evaluating hand Function cut-off value was 90. [Conclusion] The Purdue Pegboard Test is useful for evaluating manual dexterity and coordination in both hands in patients with cervical myelopathy., (2020©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Study Design: Clinimetric evaluation study., Introduction: Despite the availability of numerous performance tests to measure finger dexterity, there is no international consensus on hand function evaluation., Purpose of the Study: To evaluate the reliability, validity, and responsiveness of the modified version of the simple test for evaluating hand function (STEF), which is widely used in Japan., Methods: The intrarater (n = 40) and inter-rater (n = 32) reliability of the modified STEF was evaluated by calculating the intraclass correlation coefficient (ICC), models (1,1) and (2,1), respectively, in healthy individuals. The criterion validity of the modified STEF (n = 50) was evaluated by calculating the Pearson correlation coefficient relative to the STEF, the Purdue pegboard test (PPT), and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. The standardized response mean of the scores was calculated to determine responsiveness (n = 35). The modified STEF was used prospectively to measure the change in hand function in a cohort of patients with hand trauma injuries and inflammatory diseases (n = 30), as well as in a cohort of patients with cervical spondylosis (n = 20), from preoperative baseline to 1 and 3 months postoperatively., Results: ICC 1.1 and ICC 2.1 values were ≥0.80, indicative of high intrarater and inter-rater reliability. All correlation coefficients were significant (P < .05): STEF (r = 0.89), PPT (r = 0.69), and DASH (r = -0.34). The standardized response mean indicated greater responsiveness of the modified STEF (0.89) than the STEF (0.71) and PPT (0.68) but a lower responsiveness than the DASH (1.11)., Discussion: It must be mentioned that modified STEF and DASH cannot be compared without caution. The two types of tools should complement each other when measuring someone's activity and participation level., Conclusions: The modified STEF is a reliable measurement tool, with a moderate positive correlation with the PPT and a greater responsiveness than the STEF and PPT., (Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.)

Background: Aspergillus terreus, a saprophytic fungus, is recognized as an emerging pathogen in various infections in humans. However, bone and joint involvement is uncommon. To the best of our knowledge, only seven cases of spondylodiscitis caused by Aspergillus terreus have been reported previously in humans. We report a case of a patient with Aspergillus terreus spondylodiscitis following an abdominal stab wound., Case Presentation: A 74-year-old Japanese man with no particular medical history fell from a ladder and sustained a left abdominal stab wound from an L-shaped metal peg. Computed tomography showed the trace of the L-shaped metal peg from the left abdomen to the left rib and left kidney. The scan also showed an anterolateral bone avulsion of the left side of the T12 vertebral body, as well as fractures of the L1 left transverse process and the left 10th-12th ribs. He was hospitalized and treated with conservative therapy for 6 weeks. He was readmitted to the hospital with complaints of sudden back pain, numbness of both legs, and inability to walk 13 weeks after the fall. Magnetic resonance imaging findings were typical of spondylodiscitis. Gadolinium-enhanced T1-weighted magnetic resonance imaging indicated increased signal intensity at T11-T12 vertebral bodies and severe cord compression and epidural abscess at T11-T12 associated with infiltration of soft paravertebral tissues. On the seventh day after admission, he underwent partial laminectomy at T11 and posterior fusion at T9 to L2. The result of his blood culture was negative, but Aspergillus terreus was isolated from the material of T11-T12 intervertebral disc and vertebral bodies. His Aspergillus antigen was positive in a blood examination. Histological examination showed chronic suppurative osteomyelitis. On the 35th day after admission, he underwent anterior fusion at T11 and T12 with a rib bone graft. For 5 months, voriconazole was administered, and he wore a rigid corset. Posterior partial laminectomy at T11 and anterior fusion at T11 and T12 resulted in a good clinical course. The patient's neurological dysfunction was completely recovered, and his back pain disappeared. Two years after the operation, computed tomography was performed and showed bone fusion at T11 and T12. Magnetic resonance imaging revealed no evidence of increased signal intensity at T11-T12 vertebral bodies and severe cord compression and epidural abscess at T11-T12., Conclusions: To our knowledge, this is the first report of spondylodiscitis caused by Aspergillus terreus after an abdominal penetrating injury. The histological finding of chronic suppurative osteomyelitis and the radiological findings strongly suggested direct inoculation of Aspergillus terreus.

Background: Although microendoscopy-assisted lumbar discectomy for lateral or extraforaminal lumbar disc herniations via the lateral approach has previously been reported, microendoscopy-assisted lumbar discectomy for central or paramedian disc herniations via the lateral approach has not been reported. We report the first case of recurrent upper lumbar disc herniation (L2-L3) treated with microendoscopy-assisted lumbar discectomy via the transforaminal approach. No microendoscopy-assisted lumbar discectomy for recurrent upper lumbar disc herniation via the transforaminal approach has previously been reported. Percutaneous endoscopic lumbar discectomy via the transforaminal approach is very useful as a minimally invasive surgery for disc herniations. We applied percutaneous endoscopic lumbar discectomy via the transforaminal approach, and invented a new microendoscopy-assisted lumbar discectomy via the transforaminal approach., Case Presentation: A 79-year-old Japanese man was operatively managed for recurrent L2-L3 herniation. An 18 mm skin incision was made approximately 70 mm from the midline to the lateral side to allow a sufficiently angled trajectory to the extraforaminal space. The transforaminal approach was used. The exiting nerve root was identified along its course inferior to the pedicle. The lateral portion of the pars interarticularis and the facet joint was removed using a high-speed drill under the guidance of an endoscope. The tip of the endoscope was set at the lateral side of the dura mater. The dura mater was retracted medially and gently, and the herniated disc fragments were removed safely. All symptoms were relieved postoperatively. Postoperative magnetic resonance imaging demonstrated disappearance of all herniated disc fragments. A postoperative three-dimensional computed tomographic scan demonstrated the complete preservation of the facet joint., Conclusions: This is the first report of a case of recurrent upper lumbar disc herniation treated with microendoscopy-assisted lumbar discectomy via the transforaminal approach. This procedure allows for the use of a nerve retractor and other instruments to detach adhesions from the dura mater. This procedure has the advantages of clear visualization of the dura mater, exiting nerve root, and traversing nerve root, and diminished risk of nerve injury, and complete preservation of the articular surface of the facet joint.

In cardiac myocytes, regulation of mitochondrial Ca 2+ is important for cellular signaling and cardiac contraction. Ca 2+ entry into the mitochondria is mediated by a highly selective Ca 2+ channel called the mitochondrial calcium uniporter, which consists of a pore-forming subunit MCU and regulatory subunits such as MICU1. Although pharmacological regulation of the mitochondrial Ca 2+ influx is a promising approach to controlling the cellular functions, a cell-permeable and specific inhibitor of the mitochondrial calcium uniporter has not yet been developed. Here, we identify a novel cell-permeable inhibitor of the uniporter by a high-throughput screening of 120 000 small-molecule compounds. In our study, DS16570511 dose-dependently inhibited serum-induced mitochondrial Ca 2+ influx in HEK293A cells with an IC 50 of 7  μ M. DS16570511 inhibited Ca 2+ uptake of isolated mitochondria from human cells, rat heart and pig heart. Overexpression of hMCU or hMICU1 in HEK293A cells increased mitochondrial Ca 2+ influx, and the increases were completely suppressed by the pretreatment with DS16570511. DS16570511 also blocks mitochondrial Ca 2+ overload in a Langendorff perfused beating rat heart. Interestingly, DS16570511 increased cardiac contractility without affecting heart rate in the perfused heart. These results show that DS16570511 is a novel cell-permeable inhibitor of the mitochondrial calcium uniporter and applicable for control of the cardiac functions., Competing Interests: The authors declare no conflict of interest.

Background: Diffuse idiopathic skeletal hyperostosis has long been regarded as a benign asymptomatic clinical entity with an innocuous clinical course. Neurological complications are rare in diffuse idiopathic skeletal hyperostosis. However, if they do occur, the consequences are often significant enough to warrant major neurosurgical intervention. Neurological complications occur when the pathological process of ossification in diffuse idiopathic skeletal hyperostosis extends to other vertebral ligaments, causing ossification of the posterior longitudinal ligaments and/or ossification of the ligamentum flavum. Thoracic spondylolisthesis with spinal cord compression in diffuse idiopathic skeletal hyperostosis has not previously been reported in the literature., Case Presentation: A 78-year-old Japanese man presented with a 6-month history of gait disturbance. A magnetic resonance imaging scan of his cervical and thoracic spine revealed anterior spondylolisthesis and severe cord compression at T3 to T4 and T10 to T11, as well as high signal intensity in a T2-weighted image at T10/11. Computed tomography revealed diffuse idiopathic skeletal hyperostosis at T4 to T10. He underwent partial laminectomy of T10 and posterior fusion of T9 to T12. The postoperative magnetic resonance imaging revealed resolution of the spinal cord compression and an improvement in the high signal intensity on the T2-weighted image., Conclusions: We report the first case of thoracic spondylolisthesis and spinal cord compression in diffuse idiopathic skeletal hyperostosis. Neurosurgical intervention resulted in a significant improvement of our patient's neurological symptoms.

We describe the design, syntheses, and structure-activity relationships of novel zwitterionic compounds as nonthiazolidinedion-based peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists. In our previous report, we obtained compound 1 showing potent PPARα/γ dual agonistic activities, together with a sufficient glucose-lowering effect in db/db mice. However, this compound possessed an issue, i.e., the 1,3,4-oxadiazole ring was not stable in acidic conditions. Thus, we carried out further optimization to improve the stability while maintaining the other favorable profile features including potent PPARα/γ dual agonistic activity. We addressed the issue by changing the oxadiazole ring to a bioisostere amide group. These amide derivatives were stable in acidic conditions and decreased plasma glucose and plasma triglyceride levels significantly without marked weight gain.

We describe herein the design, syntheses and structure-activity relationships (SAR) of novel zwitterionic compounds as non-thiazolidinedion (TZD) based peroxisome proliferator activated receptor (PPAR) α/γ dual agonists. In the previous report, we obtained compound 1 showing potent PPARα/γ dual agonistic activities, together with a great glucose lowering effect in the db/db mice. However, this compound possessed fatal issues such as potent cytochrome P450 (CYP)3A4 direct inhibitory activity. Thus, we carried out the medicinal optimization to improve these while maintaining the potent PPAR agonistic activity. As a result, the issues were addressed by changing the furan ring to a low lipophilic 1,3,4-oxadiazole ring. Additionally, these oxadiazole derivatives exhibited a significant decrease in plasma glucose and plasma triglyceride levels without marked weight gain.

We describe here the design, syntheses and structure-activity relationships (SAR) of novel zwitterionic compounds as non-thiazolidinedion (TZD) based peroxisome proliferator activated receptor (PPAR) α/γ dual agonists. We commenced the medicinal research with compound 1 originated by Eli Lilly, which was reported to possess PPAR α/γ dual agonist activity. We incorporated an amine linker and optimized it on the nitrogen of the linker, thereby envisioning the enhancement of the PPAR α/γ dual agonist activity together with altering the physicochemical properties. As a result, we could generate compounds showing the PPAR α/γ dual activity, especially among which compound 22e had a franylmethyl group on the linker and 2,6-dimethyl phenyl ring at the carboxylic acid head group furnishing a highly potent dual agonist activity, together with a great glucose lowering effect. Moreover, it remedied the lipid profile, that is, triglyceride without body weight gain in the db/db mice model., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The synthesis of the marine neurotoxin azaspiracid-1 has been accomplished. The individual fragments were synthesized by catalytic enantioselective processes: A hetero-Diels-Alder reaction to afford the E- and HI-ring fragments, a carbonyl-ene reaction to furnish the CD-ring fragment, and a Mukaiyama aldol reaction to deliver the FG-ring fragment. The subsequent fragment couplings were accomplished by aldol and sulfone anion methodologies. All ketalization events to form the nonacyclic target were accomplished under equilibrating conditions utilizing the imbedded configurations of the molecule to adopt one favored conformation. A final fragment coupling of the anomeric EFGHI-sulfone anion to the ABCD-aldehyde completed the convergent synthesis of (+)-azaspiracid-1.

A series of 3,4-dihydro-3-hydroxy-4-[(5-oxo-3,4-diazabicyclo[4.1.0]hept- 2-en-2-yl)oxy]-2H-1-benzopyrans and their analogues were synthesized and evaluated on potassium channel opening and hypotensive activities. Compound (-)-13B with a (4-methyl-5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yl)oxy group for the 4-position of the benzopyran ring was 3 times as potent as EMD 57283 (II), the lead compound, in hypotensive activity. The results would demonstrate that 5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yloxy moieties are effective as the substituents at the 4-position of benzopyran-type potassium channel openers.