Interleukin-6-producing dermoid cyst associated with multicentric Castleman’s disease

Dysregulated overproduction of interleukin-6 (IL-6) from activated B cells in affected lymph nodes has been implicated in the pathogenesis of multicentric Castleman’s disease (MCD), a rare lymphoproliferative disorder accompanied by systemic manifestations. We here report the case of a 32-year-old female presenting with MCD associated with a dermoid cyst in the pelvic cavity. The co-occurrence of MCD and dermoid cyst has not been reported before. Immunohistochemical analysis of the tissue sections showed IL-6 production in CD68-positive macrophage cells, which had infiltrated the dermoid cyst. Removal of the cyst resulted in partial improvement in systemic symptoms accompanied by a decrease in serum IL-6, while complete improvement was obtained by treatment with an anti-IL-6 receptor antibody following resection of the dermoid cyst. To the best of our knowledge, this is the first study to provide evidence of IL-6 production by CD68⁺ cells in a dermoid cyst involved in MCD.     

Physical performance, bone and joint diseases, and incidence of falls in Japanese men and women: a longitudinal cohort study

Summary

This study examined whether physical performance and bone and joint diseases were risk factors for falls in 745 men and 1,470 women from the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study (mean, 69.7 years). Slower walking speed was a risk factor for falls in men and women. Knee pain was a risk factor for falls in women.

Introduction

The objective of the present study was to clarify the incidence of falls by sex and age and to determine whether physical performance and bone and joint diseases are risk factors for falls in men and women using a large-scale population-based cohort of the ROAD.

Methods

A total of 745 men and 1,470 women were analyzed in the present study (mean age, 68.5 years). A questionnaire assessed the number of falls during 3 years of follow-up. Grip strength and walking speed were measured at baseline. Knee and lumbar spine radiographs were read by Kellgren–Lawrence (KL) grade; radiographic knee osteoarthritis and lumbar spondylosis were defined as KL?=?3 or 4. Knee and lower back pain were estimated by an interview.

Results

During a mean follow-up of 3 years, 141 (18.9 %) men and 362 (24.6 %) women reported at least one fall. Slower walking speed was a risk factor for falls in men (0.1 m/s decrease; odds ratio [OR], 1.15; 95 % confidence interval [CI], 1.09–1.23) and women (0.1 m/s decrease; OR, 1.05; 95 % CI, 1.01–1.10). Knee pain was also a risk factor for falls (OR, 1.38; 95 % CI, 1.03–1.84) in women, but lower back pain was not.

Conclusion

We examined the incidence and risk factors for falls in men and women. Slower walking speed was a risk factor for falls in men and women. Knee pain was a risk factor for falls in women.     

The effect of a prostaglandin E1 derivative on the symptoms and quality of life of patients with lumbar spinal stenosis

Background

Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D).

Methods

QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after ≥6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0–100).

Results

Leg pain, leg numbness, and low back pain while walking (VAS ≥25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time <15 min. The mean EQ-5D utility value for QOL was 0.59 ± 0.12. This value was significantly associated with maximum walking time (p = 0.030) based on classification of patients into groups with walking times <7.5, 7.5–15, 15–30, and >30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by ≥10 min and the EQ-5D utility value was improved by ≥0.1 points in significantly more patients in the limaprost group than in the control group.

Conclusion

According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects.     

Construction of an osteochondral-like tissue graft combining β-tricalcium phosphate block and scaffold-free mesenchymal stem cell sheet

Background

Aiming to construct an osteochondral-like structure, the combination of a β-tricalcium phosphate (βTCP) block with a scaffold-free sheet formed using mesenchymal stem cells (MSCs) was investigated.

Methods

Human bone marrow MSCs in a cell culture insert that was set in a 24-well plate were cultivated using a chondrogenic medium containing dexamethasone, IGF-1, and TGFβ3 for 3 weeks during which a cylindrical βTCP block was put on the sheet at day 1, and the cell sheet construct was harvested. In other experiments, at day 14, the construct was put on a cell sheet that was prepared the day before and cultivated for 3 weeks.

Results

The addition of a βTCP block resulted in a combined osteochondral-like construct and comparable staining intensity by Alcian blue, while the expression levels of the aggrecan and type II collagen genes decreased a little. During the culture with the βTCP block, the expression levels of the aggrecan gene increased monotonically. The increase in the inoculum cell number from 1.86 to 3.72 × 10⁶ cells resulted in marked increases in the thickness of cell sheet parts in the βTCP block and expression levels of the aggrecan and type II collagen genes, while the thickness of cell sheet parts on the βTCP block scarcely changed. On the other hand, the addition of a cell sheet that was prepared a day before to the construct at day 14 resulted in the marked increase in thickness of the cell sheet part on the βTCP block, while the thickness of that in the βTCP block did not increase.

Conclusion

A combined osteochondral-like structure was produced by putting a βTCP block on the sheet of MSC. The thickness of the cell sheet parts in and on the βTCP block could be increased by the increase in inoculum cell number and by providing an additional cell sheet, respectively.     

Effect of VA-045, a novel apovincaminic acid derivative,on closed head injury-induced neurological dysfunction in aged rats

Abstract

Objective: The strength–duration time constant (SDTC) is a measure of axonal excitability and it can provide information about Na⁺ channel function. In this study, we sought to examine the changes in the SDTCs of motor and sensory fibers of the median nerve in patients taking colchicine, which affects axoplasmic flow and may result in axonal neuropathy.

Methods and results: The SDTCs of motor and sensory fibers of 29 patients who had been taking colchicine were measured following stimulation of the right median nerve at the wrist. The results were compared with ten healthy age-matched subjects. No significant differences were found between the groups.

Conclusions: The lack of any effect on the SDTC by colchicine might have been due to the fact that axonal degeneration caused by colchicine affects the Na⁺–K⁺ ATP pump or that it affects internodal channels other than nodal channels.     

Time-dependent risk factors associated with the decline of estimated GFR in CKD patients

Background

Targeting the modifiable risk factors may help halt the progression of CKD, thus risk factor analysis is better performed using the parameters in the follow-up. This study aimed to examine the time-dependent risk factors for CKD progression using time-averaged values and to investigate the characteristics of rapid progression group.

Methods

This is a retrospective cohort study enrolling 770 patients of CKD stage 3–4. Time-dependent parameters were calculated as time-averaged values by a trapezoidal rule. % decline of estimated GFR (eGFR) per year from entry was divided to three groups: <10 % (stable), 10–25 % (moderate progression), and ≥25 % (rapid progression). Multivariate regression analyses were employed for the baseline and the time-averaged datasets.

Results

eGFR decline was 2.83 ± 4.04 mL/min/1.73 m²/year (8.8 ± 12.9 %) in male and 1.66 ± 3.23 mL/min/1.73 m²/year (5.4 ± 11.0 %) in female (p < 0.001). % decline of eGFR was associated with male, proteinuria, phosphorus, and systolic blood pressure as risk factors and with age, albumin, and hemoglobin as protective factors using either dataset. Baseline eGFR and diabetic nephropathy appeared in the baseline dataset, while uric acid appeared in the time-averaged dataset. The rapid progression group was associated with proteinuria, phosphorus, albumin, and hemoglobin in the follow-up.

Conclusion

These results suggest that time-averaged values provide insightful clinical guide in targeting the risk factors. Rapid decline of eGFR is strongly associated with hyperphosphatemia, proteinuria, and anemia indicating that these risk factors should be intervened in the follow-up of CKD.

     

An improved cell-free system for picornavirus synthesis

Cell-free synthesis of an infectious virus is an ideal tool for elucidating the mechanism of viral replication and for screening anti-viral drugs. In the present study, the synthesis of Encephalomyocarditis virus (EMCV) from its RNA in HeLa and 293-F cell extracts was enhanced by employing a dialysis system in combination with a ribozyme technology. Although translation and processing of the EMCV polyprotein were not accelerated greatly by the dialysis system, de novo synthesis of viral RNA was enhanced considerably by dialysis, leading to a greater than eight-fold increased titer of synthesized EMCV compared with a conventional batch system. Furthermore, a synthetic EMCV RNA with a hammerhead ribozyme sequence at its 5'-end served as an efficient template for viral synthesis in the dialysis system. Therefore, this system provides opportunities for mutational analyses of EMCV in vitro.