Effect of connective tissue growth factor delivered via porous sutures on the proliferative stage of intrasynovial tendon repair

Recent growth factor, cell, and scaffold‐based experimental interventions for intrasynovial flexor tendon repair have demonstrated therapeutic potential in rodent models. However, these approaches have not achieved consistent functional improvements in large animal trials due to deleterious inflammatory reactions to delivery materials and insufficient induction of targeted biological healing responses. In this study, we achieved porous suture‐based sustained delivery of connective tissue growth factor (CTGF) into flexor tendons in a clinically relevant canine model. Repairs with CTGF‐laden sutures were mechanically competent and did not show any evidence of adhesions or other negative inflammatory reactions based on histology, gene expression, or proteomics analyses at 14 days following repair. CTGF‐laden sutures induced local cellular infiltration and a significant biological response immediately adjacent to the suture, including histological signs of angiogenesis and collagen deposition. There were no evident widespread biological effects throughout the tendon substance. There were significant differences in gene expression of the macrophage marker CD163 and anti‐apoptotic factor BCL2L1; however, these differences were not corroborated by proteomics analysis. In summary, this study provided encouraging evidence of sustained delivery of biologically active CTGF from porous sutures without signs of a negative inflammatory reaction. With the development of a safe and effective method for generating a positive local biological response, future studies can explore additional methods for enhancing intrasynovial tendon repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2052–2063, 2018.

     

Peritoneal cell sheets composed of mesothelial cells and fibroblasts prevent intra‐abdominal adhesion formation in a rat model

Postoperative intra‐abdominal adhesions remain an unsolved problem despite significant progress in the surgical procedures themselves. They often lead to small‐bowel obstruction, chronic abdominal and pelvic pain, as well as female infertility. The loss of mesothelial cells and several components of the inflammatory system following injury to the peritoneum results in fibrin formation and angiogenesis. The remaining fibrin matrix and angiogenesis lead to replacement by fibroblasts and fibrous band formation. The aim of this study was to develop a new therapeutic method of preventing intra‐abdominal adhesions. We fabricated transplantable peritoneal cell sheets from the rat peritoneum by cell sheet engineering using a temperature‐responsive culture system. The peritoneal cell sheets developed were composed of an upper monolayer of mesothelial cells and underlying multilayered fibroblasts, similar to the peritoneum in vivo. Transplantation of peritoneal cell sheets prevented tissue adhesion, fibrin deposition and angiogenesis, and, moreover, lymphangiogenesis and macrophage infiltration in a rat caecum cauterization adhesion model. Copyright © 2013 John Wiley & Sons, Ltd.     

Pemphigus with thymoma improved by thymectomy: report of a case

A 53-year-old female with pemphigus vulgaris received treatment with prednisolone for 3 years. On chest computed tomography performed at follow-up, an anterior–mediastinal tumor (4 cm × 3 cm) was detected and diagnosed as a thymoma. Although amyosthenia was absent, the patient’s anti-acetylcholine-receptor antibody level was high, and she was positive for anti-desmoglein 3 antibodies. She underwent extended thymectomy in the same year, following which both the anti-acetylcholine receptor antibody and the anti-desmoglein 3 antibody levels were normalized. The patient’s skin symptoms improved, and the steroid dose was gradually lowered and finally discontinued 4 years postoperatively. Extended thymectomy may be an effective therapy for treating patients with pemphigus.     

Bone marrow transplantation in niemann-pick mice

Journal of Inherited Metabolic Disease -     

Radiofrequency ablation of pulmonary tumors and normal lung tissue in swine and rabbits

OBJECTIVE: The purpose of the present study was to examine the following during radiofrequency ablation (RFA): (1) the risk of hemorrhage from intrapulmonary large vessels; (2) the risk of incomplete ablation of pulmonary tumors; and (3) the late effect on lung tissue. MATERIALS AND METHODS: A 17-gauge, cool-tip-type radiofrequency electrode was used. The damage to the vessels and bronchi was examined by the injection of a colored silicone rubber, a liquid compound that hardens after injection. To examine the risk of hemorrhage from intrapulmonary large vessels, RFA was conducted at eight sites near the central pulmonary vessels in two swine. To examine the risk of an incomplete ablation for pulmonary tumors, 10 pulmonary nodules were made from a gelatin mixture in another two swine and were treated by RFA. To examine the late effect on lung tissue, RFA was conducted on the peripheral lung in 10 rabbits, and then the ablated regions were examined on days 1, 7, 14, 21, and 28 after RFA. RESULTS: The use of colored silicone rubber enabled us to examine the intrapulmonary vessels and bronchi for opening and leakage. RFA did not damage the large intrapulmonary vessels, even when they were located within the ablated regions. Lung tissue surrounding the gelatin nodules was hardly ablated over its entire circumference. Six of 10 gelatin nodules (60%) showed nonablated areas on the peripheral edges of the nodules. From 21 days after RFA, the ablated rabbit lung formed noninfectious cavities by communicating with the surrounding bronchi. CONCLUSION: It was improbable for hemorrhage to occur even when RFA was conducted near the large intrapulmonary large vessels. Because an incomplete ablation that left tumor cells at the site of ablation could occur during surgery due to the difficulty of ablating the entire tumor circumference, CT scan-guided RFA would be preferable to a surgical approach for making a safe margin. Cavity formation can occur beginning 21 days after RFA, which should be carefully followed up in a clinical setting to identify infection, especially in immunocompromised patients.     

False negative cases of F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in small lung cancer less than 3 cm in size]

A considerable number of false negative cases in FDG-PET were seen in small-cell lung cancer, despite the usefulness of this imaging modality. We investigated the correlation between FDG-PET results and the clinicopathological findings in small lung cancers less than 3 cm in size. Fifty-one consecutive cases of surgically resected small lung cancers scanned preoperatively by FDG-PET was assessed. The medical records of each case were reviewed for the maximum tumor size in the CT findings, histology, grade of differentiation, lymphatic and vascular invasion, pleural invasion, lymph node stage, serum level of carcinoembryonic antigen (CEA), and CT findings. All of the 5 cases (4 adenocarcinomas, 1 small-cell carcinoma) less than 1 cm in size were false negatives. In the 46 cases 1-3 cm in size (34 adenocarcinomas, 9 squamous sell carcinomas, 2 large sell carcinomas, 1 small cell carcinoma), false negative results were seen in 8 of 15 cases of well-differentiated adenocarcinoma (53%). In the 8 false negative cases, 1 (13%) lymphatic vessel invasion (ly), 0 (0%) vascular vessel invasion (v), 0 (0%) pleural invasion (p), 0 (0%) lymph node metastasis, 0 (0%) high serum level of CEA, and 5 (63%) cases showing ground-glass opacity on CT were observed. There were significant differences in the factors ly, v, CEA, and CT findings between the 8 false-negative cases and the 26 true positive cases with adenocarcinoma (p < 0.01-0.05). Lung cancers < 1 cm in size cannot be detected in FDG-PET. Adenocarcinomas of the lung 1-3 cm in size with false negatives in FDG-PET showed significantly less invasiveness than the true positives.     

T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation

Inherited deficiency of adenosine deaminase (ADA) results in one of the autosomal recessive forms of severe combined immunodeficiency. This report discusses 2 patients with ADA deficiency from different families, in whom a possible reverse mutation had occurred. The novel mutations were identified in the ADA gene from the patients, and both their parents were revealed to be carriers. Unexpectedly, established patient T-cell lines, not B-cell lines, showed half-normal levels of ADA enzyme activity. Reevaluation of the mutations in these T-cell lines indicated that one of the inherited ADA gene mutations was reverted in both patients. At least one of the patients seemed to possess the revertant cells in vivo; however, the mutant cells might have overcome the revertant after receiving ADA enzyme replacement therapy. These findings may have significant implications regarding the prospects for stem cell gene therapy for ADA deficiency.