PURPOSE: Myasthenia gravis (MG) is a lifelong autoimmune disorder that affects neuromuscular transmission. The long-term treatment plan should include immunotherapy. We investigated the long-term safety and efficacy of tacrolimus for the treatment of MG in real-world clinical practice. MATERIALS AND METHODS: We retrospectively reviewed 160 MG patients treated with tacrolimus from 2005 to 2015. Myasthenia Gravis Foundation of America (MGFA) clinical classification, MGFA post-intervention status, myasthenic functional score, and dose of oral prednisolone were investigated. RESULTS: Adverse events occurred in 68 patients (42.5%), most of which were minor and well-managed. Clinical severity scales improved after administration of tacrolimus, compared to the baseline. Compared to 6 months before administration of tacrolimus, prednisolone dose significantly decreased at 12 months after treatment (2.85±0.92 mg/day, p=0.002), 18 months after treatment (3.36±0.99 mg/day, p=0.001), and 24 months after treatment (3.71±0.93 mg/day, p<0.001). CONCLUSION: Tacrolimus may be effective in reducing the severity of MG and may permit a reduction in the steroid dose prescribed to the patients. Adverse events due to tacrolimus treatment were not serious.
Americas ; Classification ; Humans ; Immunotherapy ; Myasthenia Gravis ; Prednisolone ; Retrospective Studies ; Tacrolimus ; Weights and Measures

BACKGROUND AND PURPOSE: Acetylcholinesterase inhibitors (AChEIs) are widely used to treat myasthenia gravis (MG). Although AChEIs are usually tolerated well, some MG patients suffer from side effects. Furthermore, a small proportion of MG patients show cholinergic hypersensitivity and cannot tolerate AChEIs. Because repetitive compound muscle action potentials (R-CMAPs) are an electrophysiologic feature of cholinergic neuromuscular hyperactivity, we investigated the clinical characteristics of MG patients with R-CMAPs to identify their clinical usefulness in therapeutic decision-making. METHODS: We retrospectively reviewed the clinical records and electrodiagnostic findings of MG patients who underwent electrodiagnostic studies and diagnostic neostigmine testing (NT). RESULTS: Among 71 MG patients, 9 could not tolerate oral pyridostigmine bromide (PB) and 17 experienced side effects of PB. R-CMAPs developed in 24 patients after NT. The highest daily dose of PB was lower in the patients with R-CMAPs (240 mg/day vs. 480 mg/day, p<0.001). The frequencies of PB intolerance and side effects were higher in the patients with R-CMAPs than in those without R-CMAPs [37.5% vs. 0% (p<0.001) and 45.8% vs. 12.8% (p=0.002), respectively]. The MG Foundation of America postintervention status did not differ significantly between MG patients with and without R-CMAPs, and the response to immunotherapy was also good in both groups. CONCLUSIONS: Side effects of and intolerance to AChEIs are more common in MG patients with R-CMAPs than in those without R-CMAPs. AChEIs should be used carefully in MG patients with R-CMAPs. The presence of R-CMAPs after NT may be a good indicator of the risks of PB side effects and intolerance.
Acetylcholinesterase* ; Action Potentials* ; Americas ; Cholinesterase Inhibitors* ; Humans ; Hypersensitivity ; Immunotherapy ; Myasthenia Gravis* ; Neostigmine ; Pyridostigmine Bromide ; Retrospective Studies

We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.
Animals ; Brain-Derived Neurotrophic Factor/*genetics ; *Cord Blood Stem Cell Transplantation ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Profiling ; *Gene Expression Regulation ; Humans ; Locomotion ; Nerve Growth Factor/genetics ; Rats ; Spinal Cord Injuries/*therapy

BACKGROUND AND PURPOSE: Various magnetic resonance (MR) measurements have been proposed to aid in differentiating between progressive supranuclear palsy (PSP) and idiopathic Parkinson's disease (IPD); however, these methods have not been compared directly. The aim of this study was to determine which measurement method exhibits the highest power to differentiate between PSP and IPD. METHODS: Brain MR images from 82 IPD and 29 PSP patients were analyzed retrospectively. T1-weighted 3D volumetric axial images, or sagittal images reconstructed from those axial images were examined. MR measurements included the length from the interpeduncular fossa to the center of the cerebral aqueduct at the mid-mammillary-body level, adjusted according to the anterior commissure-posterior commissure length (MB(Tegm)), the ratio of the midbrain area to the pons area (M/P ratio) as measured by both Oba's method (Oba M/P) and Cosottini's method (Cosottini M/P), and a modified MR parkinsonism index (mMRPI). RESULTS: Receiver operating characteristic (ROC) analysis indicated that the areas under the ROC curves (AUCs) exceeded 0.70, with a high intrarater reliability for all MR measurement methods. ROC analyses of four MR measurements yielded AUCs of 0.69-0.76. At the cutoff value with the highest Youden index, mMRPI had the highest sensitivity, while Oba M/P offered the highest specificity. A comparison of the ROC analyses revealed that MB(Tegm) was superior to mMRPI in differentiating PSP from IPD (p=0.049). There was no difference in discriminating power among Oba M/P, Cosottini M/P, and MB(Tegm). CONCLUSIONS: Simple measurements of MB(Tegm) on axial MR images at the mid-mammillary-body level are comparable to measurements of the M/P ratio with regard to their ability to discriminate PSP from IPD.
Area Under Curve ; Brain ; Cerebral Aqueduct ; Diagnosis, Differential* ; Humans ; Magnetic Resonance Imaging ; Mesencephalon* ; Neuroimaging ; Parkinson Disease* ; Parkinsonian Disorders ; Pons ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Supranuclear Palsy, Progressive*

HMG-CoA reductase inhibitor is widely used for the treatment of dyslipidemia, and for the prevention of stroke and cardiovascular disease. However, it is necessary to consider the adverse effects associated with this drug. Myopathy is a well-known side effect of statin therapy, but myotonic potentials in cases with statin myopathy have thus far been reported only rarely. We report four cases of myopathy with myotonic potentials on electromyography after multidrug administration. All of the patients recovered shortly after statin withdrawal.
Cardiovascular Diseases ; Dyslipidemias ; Electromyography ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Muscular Diseases* ; Oxidoreductases* ; Stroke

BACKGROUND: In mammals, the CLOCK/BMAL1 heterodimer is a key transcription factor complex that drives the cyclic expression of clock-controlled genes involved in various physiological functions and behavioral consequences. Recently, a growing number of studies have reported a molecular link between the circadian clock and metabolism. In the present study, we explored the regulatory effects of SIRTUIN1 (SIRT1), an NAD+-dependent deacetylase, on CLOCK/BMAL1-mediated clock gene expression. METHODS: To investigate the interaction between SIRT1 and CLOCK/BMAL1, we conducted bimolecular fluorescence complementation (BiFC) analyses supplemented with immunocytochemistry assays. BiFC experiments employing deletion-specific mutants of BMAL1 were used to elucidate the specific domains that are necessary for the SIRT1-BMAL1 interaction. Additionally, luciferase reporter assays were used to delineate the effects of SIRT1 on circadian gene expression. RESULTS: BiFC analysis revealed that SIRT1 interacted with both CLOCK and BMAL1 in most cell nuclei. As revealed by BiFC assays using various BMAL1 deletion mutants, the PAS-B domain of BMAL1 was essential for interaction with SIRT1. Activation of SIRT1 with resveratrol did not exert any significant change on the interaction with the CLOCK/BMAL1 complex. However, promoter analysis using Per1-Luc and Ebox-Luc reporters showed that SIRT1 significantly downregulated both promoter activities. This inhibitory effect was intensified by treatment with resveratrol, indicating a role for SIRT1 and its activator in CLOCK/BMAL1-mediated transcription of clock genes. CONCLUSION: These results suggest that SIRT1 may form a regulatory complex with CLOCK/BMAL1 that represses clock gene expression, probably via deacetylase activity.
Cell Nucleus ; Circadian Clocks ; Complement System Proteins ; Fluorescence ; Gene Expression ; Immunohistochemistry ; Luciferases ; Mammals ; Metabolism ; Transcription Factors

PURPOSE: To evaluate the clinical and radiological results, as well as the survival rate, associated with total hip arthroplasty using a hydroxyapatite (HA)-coated anatomical femoral stem at a follow-up of > or =12 years. MATERIALS AND METHODS: From April 1992 to May 1997, 86 patients (102 hips) underwent total hip arthroplasty with a HA-coated ABG I (Anatomical Benoist Giraud; Howmedica) hip prosthesis. The average age at the time of surgery was 53.4 years and the mean duration of follow-up was 17.1 years (range, 12.1-21.0 years). The Harris hip score (HHS) and radiographic assessments of thigh pain were used to evaluate the clinical results. We observed osteointegration, cortical hypertrophy, reactive line, calcar resorption and osteolysis around the femoral stems. The survival rate of the femoral stems was evaluated by using the span of time to a revision operation for any reasons was defined as the end point. RESULTS: The mean HHS was 50.5 preoperatively and 84.2 at the time of last follow-up. Osteolysis only around the HA-coated proximal portion of the femoral stem was observed in 72 hips, cortical hypertrophy all around the distal portion of the femoral stem was observed in 38 hips, and calcar resorption was observed in 44 hips. A reactive line was observed in 13 hips, but was unrelated to component loosening. Stem revision operations were performed in 24 (23%) hips due to osteolysis (14 hips), fracture (5 hips) and infection (5 hips). The femoral stem survival rate was 75% over the mean duration of follow-up. CONCLUSION: Total hip arthroplasty using a HA-coated anatomical femoral stem showed necessitated a high rate of revision operations due to osteolysis around the femoral stem in this long term follow-up study.
Arthroplasty, Replacement, Hip* ; Durapatite* ; Follow-Up Studies ; Hip ; Hip Prosthesis ; Humans ; Hypertrophy ; Osteolysis ; Survival Rate ; Thigh

The use of human umbilical cord blood-derived mesenchymal stem cells for cell transplantation therapy holds great promise for repairing spinal cord injury. Here we report the first clinical trial transplantation of human umbilical cord (hUCB)-derived mesenchymal stem cells (MSCs) into the spinal cord of a dog suspected to have fibrocartilaginous embolic myelopathy (FCEM) and that experienced a loss of deep pain sensation. Locomotor functions improved following transplantation in a dog. Based on our findings, we suggest that transplantation of hUCB-derived MSCs will have beneficial therapeutic effects on FCEM patients lacking deep pain sensation.
Animals ; Cartilage Diseases/etiology/therapy/*veterinary ; *Cord Blood Stem Cell Transplantation/veterinary ; Dog Diseases/etiology/*therapy ; Dogs ; Embolism/etiology/therapy/*veterinary ; Female ; Humans ; Mesenchymal Stromal Cells/cytology/*metabolism ; Spinal Cord Diseases/etiology/therapy/*veterinary ; Treatment Outcome

Here, percutaneous spinal cord injury (SCI) methods using a balloon catheter in adult rats are described. A balloon catheter was inserted into the epidural space through the lumbosacral junction and then inflated between T9-T10 for 10min under fluoroscopic guidance. Animals were divided into three groups with respect to inflation volume: 20 microL (n = 18), 50 microL (n = 18) and control (Fogarty catheter inserted but not inflated; n = 10). Neurological assessments were then made based on BBB score, magnetic resonance imaging and histopathology. Both inflation volumes produced complete paralysis. Gradual recovery of motor function occurred when 20 microL was used, but not after 50 microL was applied. In the 50 microL group, all gray and white matter was lost from the center of the lesion. In addition, supramaximal damage was noted, which likely prevented spontaneous recovery. This percutaneous spinal cord compression injury model is simple, rapid with high reproducibility and the potential to serve as a useful tool for investigation of pathophysiology and possible protective treatments of SCI in vivo.
Animals ; Balloon Embolectomy/*methods ; Disease Models, Animal ; Male ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Compression/*therapy

We evaluated the biological scaffold properties of canine small intestinal submucosa (SIS) compared to a those of polypropylene mesh in growing rats with full-thickness abdominal defects. SIS is used to repair musculoskeletal tissue while promoting cell migration and supporting tissue regeneration. Polypropylene mesh is a non-resorbable synthetic material that can endure mechanical tension. Canine SIS was obtained from donor German shepherds, and its porous collagen fiber structure was identified using scanning electron microscopy (SEM). A 2.50-cm2 section of canine SIS (SIS group) or mesh (mesh group) was implanted in Sprague-Dawley rats. At 1, 2, 4, 12, and 24 weeks after surgery, the implants were histopathologically examined and tensile load was tested. One month after surgery, CD68+ macrophage numbers in the SIS group were increased, but the number of CD8+ T cells in this group declined more rapidly than that in rats treated with the mesh. In the SIS group, few adhesions and well-developed autologous abdominal muscle infiltration into the SIS collagen fibers were observed. No significant differences in the tensile load test results were found between the SIS and mesh groups at 24 weeks. Canine SIS may therefore be a suitable replacement for artificial biological scaffolds in small animals.
Abdominal Wall/*surgery ; Animals ; Biocompatible Materials/*therapeutic use ; Dogs ; Female ; Intestinal Mucosa/cytology/transplantation ; Intestine, Small/cytology/*transplantation ; Polypropylenes/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Tensile Strength ; Tissue Adhesions ; *Tissue Scaffolds ; Transplantation, Heterologous/*methods ; *Wound Healing