Generation and characterization of a novel shoulder contracture mouse model

Frozen shoulder is a relatively common disorder that leads to severe pain and stiffness in the shoulder joint. Although this disorder is self‐limiting in nature, the symptoms often persist for years, resulting in severe disability. Recent studies using human specimens and animal models have shown distinct changes in the gene expression patterns in frozen shoulder tissue, indicating that novel therapeutic intervention could be achieved by controlling the genes that are potentially involved in the development of frozen shoulder. To achieve this goal, it is imperative to develop a reliable animal joint contracture model in which gene expression can be manipulated by gene targeting and transgenic technologies. Here, we describe a novel shoulder contracture mouse model. We found that this model mimics the clinical presentation of human frozen shoulder and recapitulates the changes in the gene expression pattern and the histology of frozen shoulder and joint contracture in humans and other larger animal models. The model is highly reproducible, without any major complications. Therefore, the present model may serve as a useful tool for investigating frozen shoulder etiology and for identifying its potential target genes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1732–1738, 2015.     

Hobson’s choice two-stage hepatectomy for multiple and bilobar colorectal liver metastases with portal vein embolization: report of two cases

Liver resection is recognized as the preferred treatment for patients with colorectal liver metastases (CLM) because it offers long-term survival; it is the only hope for a cure. However, in the majority of cases, liver surgery is contraindicated due to the small volume of the future remnant liver. To extend the surgical indications for CLM, a planned two-stage hepatectomy procedure with portal vein embolization (PVE) was developed specifically for patients with multiple and bilobar CLM. The rationale for performing the procedure was a concern about the possible overgrowth of intrafuture remnant liver lesions following PVE, and it was therefore recommended for all multiple bilobar CLM cases, even when one-stage hepatectomy was technically feasible. We recently performed Hobson’s choice two-stage hepatectomy in two cases for reasons different from those of the original planned two-stage hepatectomy. In the present report, we describe our Hobson’s choice two-stage hepatectomy strategy, which provided favorable short-term outcomes.     

Mechanical properties of nerve roots and rami radiculares isolated from fresh pig spinal cords

No reports have described experiments designed to determine the strength characteristics of spinal nerve roots and rami radiculares for the purpose of explaining the complexity of symptoms of medullary cone lesions and cauda equina syndrome. In this study, to explain the pathogenesis of cauda equina syndrome, monoaxial tensile tests were performed to determine the strength characteristics of spinal nerve roots and rami radiculares, and analysis was conducted to evaluate the stress-strain relationship and strength characteristics. Using the same tensile test device, the nerve root and ramus radiculares isolated from the spinal cords of pigs were subjected to the tensile test and stress relaxation test at load strain rates of 0.1, 1, 10, and 100 s^-1 under identical settings. The tensile strength of the nerve root was not rate dependent, while the ramus radiculares tensile strength tended to decrease as the strain rate increased. These findings provide important insights into cauda equina symptoms, radiculopathy, and clinical symptoms of the medullary cone.     

Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial

OBJECTIVE: Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune response, inflammation, and hematopoiesis. Overproduction of IL-6 plays pathologic roles in rheumatoid arthritis (RA), and the blockade of IL-6 may be therapeutically effective for the disease. This study was undertaken to evaluate the safety and efficacy of a humanized anti-IL-6 receptor antibody, MRA, in patients with RA. METHODS: In a multicenter, double-blind, placebo-controlled trial, 164 patients with refractory RA were randomized to receive either MRA (4 mg/kg body weight or 8 mg/kg body weight) or placebo. MRA was administered intravenously every 4 weeks for a total of 3 months. The clinical responses were measured using the American College of Rheumatology (ACR) criteria. RESULTS: Treatment with MRA reduced disease activity in a dose-dependent manner. At 3 months, 78% of patients in the 8-mg group, 57% in the 4-mg group, and 11% in the placebo group achieved at least a 20% improvement in disease activity according to the ACR criteria (an ACR20 response) (P < 0.001 for 8-mg group versus placebo). Forty percent of patients in the 8-mg group and 1.9% in the placebo group achieved an ACR50 response (P < 0.001). The overall incidences of adverse events were 56%, 59%, and 51% in the placebo, 4-mg, and 8-mg groups, respectively, and the adverse events were not dose dependent. A blood cholesterol increase was observed in 44.0% of the patients. Liver function disorders and decreases in white blood cell counts were also observed, but these were mild and transient. There was no increase in antinuclear antibodies or anti-DNA antibodies. Anti-MRA antibodies were detected in 2 patients. CONCLUSION: Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA.     

Squamous Cell Carcinoma after Endoscopic Injection Sclerotherapy for Esophageal Varices

We report two cases of squamous cell carcinoma of the esophagus following endoscopic injection sclerotherapy for esophageal varices. The interval between sclerotherapy and the development of carcinoma was 24 months in case 1 and 21 months in case 2. The sclerosant was 5% sodium morrhuate in case 1 (total dose, 10 ml) and 5% ethanolamine oleate in case 2 (45.5 ml). Although no recurrent variceal bleeding occurred after sclerotherapy, we could not perform any curative surgical treatment for esophageal cancer because of the advanced stage of the cancer and the severity of the accompanying liver dysfunction. It is difficult to determine the relationship between sclerotherapy and carcinoma; however, long-term surveillance is essential to avoid overlooking a neoplasm in the esophagus after endoscopic injection sclerotherapy.     

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.     

Acid and duodenogastroesophageal reflux after esophagectomy with gastric tube reconstruction

OBJECTIVE: Patients who undergo esophagectomy with gastric tube reconstruction incur increased risk for acid reflux and duodenogastroesophageal reflux. Few postesophagectomy studies of gastroesophageal reflux disease have included simultaneous 24-h pH and bilirubin monitoring. The aim of this study is to evaluate acid reflux and duodenogastroesophageal reflux after esophagectomy with gastric tube reconstruction. METHODS: Reflux symptom evaluation, endoscopy, and simultaneous 24-h pH and bilirubin monitoring in the cervical esophagus were performed in 25 patients who underwent Ivor Lewis esophagectomy, intrathoracic esophagogastrostomy, and digital dilation of the pyloric ring as treatment for esophageal cancer. RESULTS: Reflux symptoms were severe, mild, and absent in 2, 7, and 16 patients, respectively. Reflux esophagitis and Barrett's esophagus was observed in 11 and 1 patients, respectively. Elevated acid reflux occurred in 7 patients (28%). Elevated duodenogastroesophageal reflux was recorded in 11 patients (44%). Reflux profile analysis identified three patterns: 4 subjects (16%) with both elevated acid reflux and duodenogastroesophageal reflux; 3 (12%) with only elevated acid reflux; and 7 (28%) with only elevated duodenogastroesophageal reflux. Of 7 patients with only elevated duodenogastroesophageal reflux, 4 developed reflux esophagitis. Although reflux symptoms did not correlate with endoscopic esophagitis, a significant correlation was observed between endoscopic esophagitis and acid reflux and/or duodenogastroesophageal reflux. CONCLUSIONS: Reflux symptoms represented a poor indication of esophagitis in patients with esophagectomy and gastric tube reconstruction. Simultaneous 24-h pH and bilirubin monitoring can help in identifying patients at high risk for reflux esophagitis, as well as indicating the cause of esophagitis.