Endothelial function and coronary spastic angina

Coronary spasm plays an important role in the pathogenesis of not only variant angina but also coronary heart disease in general including acute coronary syndromes, especially in the Japanese population. The vascular endothelium has been reported to be a multifunctional organ whose integrity is essential for normal vascular physiology. Vascular endothelial dysfunction can be a critical factor in the pathogenesis of ischemic heart disease. Acetylcholine and methacholine cause vasodilation by endothelium-derived relaxing factor when the endothelium is functioning normally, whereas they cause vasoconstriction when the endothelium is removed or damaged. Coronary spasm can be induced by a variety of stimuli with different mechanisms of action, including acetylcholine and methacholine. Patients with coronary spasm may have a disturbance in endothelial function as well as local hyperreactivity of the coronary arteries.     

Establishment of Dental Epithelial Cell Line (HAT-7) and the Cell Differentiation Dependent on Notch Signaling Pathway

Rat incisors grow continuously throughout life. Producing a variety of dental epithelial cells is performed by stem cells located in the cervical loop of the incisor apex. To study the mechanisms for cell differentiation, we established a dental epithelial cell line (HAT-7) originating from a cervical loop epithelium of a rat incisor. Immunochemical studies showed that HAT-7 produced the cells expressing amelogenin, ameloblastin, or alkaline phosphatase (ALP). To illustrate a role of Notch signaling in the determinant of the cell fate, we examined expression patterns of Notch1 and Jagged1 in HAT-7 density dependently. At lower cell density, Notch1- or Jagged1-expressing cells were not seen. However, when they were fully confluent, cells began to express Notch1 or Jagged1 strongly. Some ALP-positive cells were almost consistent with Notch1-expressing cells but not Jagged1-expressing cells. These results suggested that the determinant of direction of differentiation was associated with Notch signaling pathway.     

Intracranial and extracranial multiple arterial dissecting aneurysms in rheumatoid arthritis: A case report

ObjectiveWe describe a case of intracranial and extracranial multiple arterial dissecting aneurysms in rheumatoid arthritis (RA).Case PresentationA 29-year-old man with a medical history of RA since 18 years of age was admitted to our hospital for vomiting, dysarthria, and conscious disturbance. At 23, he underwent ligation of the left internal carotid artery (ICA) with superficial temporal artery to middle cerebral artery anastomosis because of acute infarct of the left hemisphere caused by arterial dissection of the left ICA. During the current admission, computed tomography (CT) revealed subarachnoid hemorrhage, and digital subtraction angiography (DSA) demonstrated dissecting aneurysms of the left intracranial vertebral artery (VA) and right extracranial VA. We diagnosed him with a ruptured dissecting aneurysm of the left intracranial VA and performed endovascular parent artery occlusion on the left VA. For the right unruptured VA aneurysm, we performed coil embolization simultaneously. At 2 weeks after the endovascular treatment, follow-up DSA revealed that multiple de novo dissecting aneurysms developed on the origin of the left VA and left and right internal thoracic arteries. Those aneurysms were treated with coil embolization. Other remaining aneurysms on the left thyrocervical trunk, right transverse cervical artery, and both common iliac arteries were treated by conservative therapy. While continuing medical treatment for RA, the patient recovered and was discharged to a rehabilitation hospital.ConclusionConsidering that RA-induced vasculitis can be a potential risk of vascular complications including multiple arterial dissections, physicians should carefully perform endovascular interventional procedures for patients with long-term RA.     

Efficacy,safety, and pharmacokinetics of oral valganciclovir in patients with congenital cytomegalovirus infection

ObjectivesValganciclovir (VGCV) has been shown to improve sensorineural hearing loss (SNHL) and neurological outcomes in patients with neonatal symptomatic congenital cytomegalovirus (cCMV) infection. However, reports on the pharmacokinetics, efficacy and safety of oral VGCV are limited. The aim of this study is to evaluate the pharmacokinetics of VGCV for use in the treatment of cCMV.MethodsThis was a single-center, retrospective observational study conducted at Saitama Children's Medical Center in Japan between 2012 and 2017. CMV DNA copy number, maximum plasma VGCV concentration (Cmax), and adverse events (ADEs) during treatment were evaluated.ResultsA total of 26 patients with cCMV who received VGCV were included in this study. The median age at VGCV initiation was 9.5 months (range 0–46). Twenty-one patients (81%) had SNHL at baseline. Of these, five patients (19%) presented with improved SNHL, and none experienced worsened SNHL during treatment. The mean VGCV Cmax was 3.5 μg/mL (range 2–5.3), with no significant variation among individual values, and the values were maintained during treatment. Furthermore, there were no correlations between the Cmax values and age, sex, SNHL improvement or ADEs. Neutropenia (<1000/mm³) was observed in six patients (23%); however, no serious ADEs occurred.ConclusionsVGCV prevented the progression of SNHL without serious ADEs due to its stable pharmacokinetics. This study provides safety and tolerability of VGCV for the treatment of cCMV patients.     

Simultaneous, clonally identical T cell expansion in tonsil and synovium in a patient with rheumatoid arthritis and chronic tonsillitis

In some patients with rheumatoid arthritis (RA), the disease improves following tonsillectomy. We describe a 28-year-old woman with treatment-resistant RA and chronic tonsillitis. Initially, her arthritis had been well controlled with methotrexate and corticosteroids, but the RA activity became difficult to control in spite of addition of bucillamine to the treatment regimen and repeated arthrocentesis with infusion of corticosteroid into her swollen joints. Closer examination revealed that the period of exacerbation of her chronic tonsillitis paralleled that of the systemic arthritis, and administration of antibiotics brought transient relief of the systemic symptoms. Her arthritis was ameliorated after successful tonsillectomy and synovectomy, with marked reduction of the serum rheumatoid factor concentration. Analysis of infiltrating T cell clones in tonsil and synovium using T cell receptor V(beta) repertoire and third complementarity-determining region size distribution analysis followed by nucleotide sequencing revealed common clonal T cell expansion in both tissues. This finding suggests the possible involvement of chronic focal infection in refractory RA.     

Hepatectomy for liver metastasis from ampullary cancer after pancreatoduodenectomy

A 51-year-old Japanese woman with a solitary liver metastasis originating from a carcinoma of the ampulla of Vater was successfully treated by partial hepatectomy 19 months after curative pancreatoduodenectomy with lymphadenectomy. Histologic examination revealed a stage III well-differentiated tubular adenocarcinoma (pT2, pN1, and pM0). Postoperative serum concentrations of carcinoembryonic antigen increased exponentially to 133 ng/mL. The carcinoembryonic antigen doubling time was 63 days. Computed tomography and ultrasonography of the abdomen showed a solitary metastasis in segment VI of the liver. Since neither local recurrences nor other distant metastases were detected, the patient underwent partial hepatectomy. Histologic study confirmed the presence of a metastatic liver tumor from the ampullary carcinoma. The carcinoembryonic antigen levels returned to normal immediately after the partial hepatectomy. She was well without signs of recurrence 18 months after partial hepatectomy.     

Cervical ossification of the posterior longitudinal ligament: Biomechanical analysis of the influence of static and dynamic factors

Objective

Cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL) is induced by static factors, dynamic factors, or a combination of both. We used a three-dimensional finite element method (3D-FEM) to analyze the stress distributions in the cervical spinal cord under static compression, dynamic compression, or a combination of both in the context of OPLL.

Methods

Experimental conditions were established for the 3D-FEM spinal cord, lamina, and hill-shaped OPLL. To simulate static compression of the spinal cord, anterior compression at 10, 20, and 30% of the anterior–posterior diameter of the spinal cord was applied by the OPLL. To simulate dynamic compression, the OPLL was rotated 5°, 10°, and 15° in the flexion direction. To simulate combined static and dynamic compression under 10 and 20% anterior static compression, the OPLL was rotated 5°, 10°, and 15° in the flexion direction.

Results

The stress distribution in the spinal cord increased following static and dynamic compression by cervical OPLL. However, the stress distribution did not increase throughout the entire spinal cord. For combined static and dynamic compression, the stress distribution increased as the static compression increased, even for a mild range of motion (ROM).

Conclusion

Symptoms may appear under static or dynamic compression only. However, under static compression, the stress distribution increases with the ROM of the responsible level and this makes it very likely that symptoms will worsen. We conclude that cervical OPLL myelopathy is induced by static factors, dynamic factors, and a combination of both.     

A case of primary pleural leiomyosarcoma]

A 70-year-old man was admitted to our hospital with complaints of chest pain and exertional dyspnea. Chest radiography and computed tomography (CT) revealed right pleural effusion and pleural thickening on admission. The pleural fluid was bloody. Microbiological and cytologic examinations of the fluid were negative. The chest CT revealed progress of pleural thickening after hospitalization. A thoracoscopic pleural biopsy was performed, and the histological finding of the excised specimen was leiomyosarcoma. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma. It is thought that leiomyosarcoma originating from the pleura is rare.