A comparison of tenocytes and mesenchymal stem cells for use in flexor tendon tissue engineering

PURPOSE: Tissue-engineered tendon grafts will meet an important clinical need. To engineer tendons, we used acellularized allogeneic tendon as scaffold material. To determine the ideal cell type to seed the scaffolds, we studied in vitro characteristics of epitenon tenocytes, tendon sheath fibroblasts, bone marrow-derived mesenchymal stem cells (BMSCs), and adipoderived mesenchymal stem cells (ASCs). Subsequently, we implanted reseeded acellularized tendons in vivo as flexor tendon grafts. METHODS: Tenocytes, sheath fibroblasts, BMSCs, and ASCs were obtained from adult rabbits. For all cell lines, collagen 1, 2, and 3 immunocytochemistry was performed, and proliferation was assessed by hemacytometry and senescence by beta-galactosidase staining. Flexor tendons were acellularized after harvest. Tendons were assessed by histology after in vitro reseeding with each of the cell types after 1, 4, and 8 weeks. Finally, reseeded tendons and controls were implanted in a flexor profundus tendon defect. After 6 weeks, the reseeded tendons were harvested and assessed by histology. Statistical analysis for cell proliferation was performed using analysis of variance and t-tests with Bonferroni correction. RESULTS: All cell types had similar collagen expression. Cell proliferation was higher in ASCs in late passage compared with early passage and in ASCs compared with epitenon tenocytes at late passage. The other cell types were similar in growth characteristics. No senescence was detected. In vitro assessment of reseeded constructs showed the presence of cells on the construct surface. In vivo assessment after implantation showed viable cells seen within the tendon architecture in all cell types. CONCLUSIONS: This study suggests that the four cell types may be successfully used to engineer tendons. Adipoderived mesenchymal stem cells proliferate faster in cell culture, but the cell types were similar in other respects. All could be used to successfully repopulate acellularized tendon in vivo as flexor tendon grafts.     

Anaemia management in patients with chronic kidney disease: Taiwan practice guidelines

The introduction of erythropoiesis‐stimulating agents (ESAs) markedly improved the lives of many anaemic patients with chronic kidney disease (CKD). In Taiwan, the strategy of management of anaemia in patients with CKD was different from many other parts of the world. In 1996, the National Health Insurance Administration of Taiwan applied a more restrictive reimbursement criteria for ESA use in patients with CKD. ESA is to be initiated when non‐dialysis CKD patients have a serum creatinine >6 mg/dL and a hematocrit <28% to maintain a hematocrit level not exceeding 30%. The maximal dose of epoetin‐α or β was 20 000 U per month. The target haemoglobin range and dose limitation for ESAs were the same for dialysis CKD patients. Thus, long before randomized controlled trials showing an increased risk for cardiovascular events at nearly normal haemoglobin concentrations and higher ESA doses in CKD, nephrologists in Taiwan had avoided the use of disproportionately high dosages of ESAs to achieve a haemoglobin level of 10–11 g/dL. Moreover, intravenous iron supplementation was encouraged earlier in Taiwan in 1996, when we reached consensus on the diagnostic criteria for iron deficiency (serum ferritin <300 ng/mL and/or transferrin saturation <30%). The experience of CKD anaemia management in Taiwan demonstrated that a reasonable haemoglobin target can be achieved by using the lowest possible ESA dose and intravenous iron supplementation.     

Successful Treatment for BK Virus Nephropathy by Leflunomide in a Kidney Transplant Patient: A Case Report

IntroductionThe immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL.MethodsImmunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function.ResultsThe kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment.ConclusionEarly detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.     

Arthroscopic repair of Bankart lesion in traumatic anterior-inferior shoulder instability using the two-portal method: A preliminary report

BackgroundIn this report, we describe our preliminary clinical results of arthroscopic Bankart repair in traumatic anterior-inferior shoulder instability using the two-portal method.MethodFrom August 2009 to December 2011, arthroscopic repair of Bankart lesion using this method was performed in 16 consecutive patients who were prospectively enrolled. Fifteen shoulders were treated with two-anchor sutures and one was treated with three-anchor sutures. Twelve patients received metallic anchor screws and four patients received bioanchor screws. The assessments were performed using the Rowe score, the University of California at Los Angeles shoulder rating scale, the American Shoulder and Elbow Surgeons score, and the shoulder range of motion (ROM) deficit.ResultsWith an average follow-up period of 22.9 months, all shoulder scores improved after surgery (p < 0.001). The average ROM deficit of the operated shoulders was not significant as compared with the healthy side in forward elevation (p > 0.05), but was significant in external rotation (p < 0.05). All of the 16 shoulders remained stable (100%) after the arthroscopic repair surgery. All patients returned to their preinjury levels of daily activity without recurrent problems.ConclusionIn patients with traumatic anterior glenohumeral instability, arthroscopic Bankart repair with the two portal method can provide good results. It can be an alternative method of treating patients with Bankart lesion without associated major glenoid defect or rotator cuff lesion in traumatic anterior-inferior instability.     

Alterations of bone geometry, density, microarchitecture, and biomechanical properties in systemic lupus erythematosus on long-term glucocorticoid: a case–control study using HR-pQCT

Summary

Compared to controls, HR-pQCT at distal radius of SLE patients on chronic glucocorticoid (SLE/GC) revealed reduced bone area, vBMD, deteriorated microarchitecture, and unevenly distributed stresses limited to cortical bone. Despite similar trabecular quality, whole bone strength decreased in patients. These alterations may partly explain high fracture rates in SLE/GC.

Introduction

To assess bone geometric, densitometric, microarchitectural, and biomechanical properties in patients with systemic lupus erythematosus (SLE) on long-term glucocorticoid (GC) (SLE/GC) as compared with healthy controls.

Methods

A total of 180 female SLE patients and 180 healthy controls were in this cross-sectional study to assess areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) and microfinite element analysis (μFEA) was performed at distal radius.

Results

In addition to significantly lower aBMD at femoral neck, total hip and lumbar spine, cortical area, average volumetric BMD (vBMD) and cortical vBMD also significantly reduced by 5.3, 5.7, to 1.9 % in SLE patients, respectively. Deteriorations of cortical microarchitecture were pronounced in patients, with 6.3 % reduction in cortical thickness and 13.6 % higher in cortical porosity. Local stresses were more unevenly distributed through cortical bone in patients. SLE/GC patients had decreased whole bone stiffness, estimated failure load, and apparent modulus. Parameters related to trabecular bone density and microarchitecture were comparable between patients and controls.

Conclusion

In SLE/GC patients, despite a reduction in bone area, vBMD and deteriorated microarchitecture and unevenly distributed stresses limited to the cortical compartment, whole bone strength decreased. HR-pQCT and μFEA were promising in elucidating the potential underlying pathophysiology of bone loss and propensity to fracture in SLE/GC and provide us additional information about alterations of bone quality which might better predict fracture risk beyond aBMD in SLE/GC.     

Altered Serum Transforming Growth Factor-ß1 and Monocyte Chemoattractant Protein-1 Levels in Obstructive Jaundice

Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-ß1 (TGFß1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFß1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFß1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFß1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFß1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFß1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.     

Ultrasound for the detection of vegetative foreign body in hand--a case report.

Foreign bodies in soft tissues are commonly encountered in daily orthopaedic practice. While most of the metals and glass foreign bodies can be detected by plain radiograph, organic substances such as wood and vegetative materials are radiolucent. Unfortunately, these radiolucent foreign bodies are usually more prone to cause an inflammatory reaction and infection. The detection can be even more difficult in cases of multiple foreign bodies and in penetrating injuries with small innocuous skin wounds. Ultrasonography is a sensitive and reliable investigation for detection of foreign bodies in soft tissue. We present a case of penetration injury to thumb with residual radiolucent foreign bodies and demonstrate the proper role of ultrasonography in the management of foreign bodies in soft tissues.     

Laryngeal mask airway in patients with tracheal stents who are undergoing non-airway related interventions: report of three cases

The tracheal stent is an alternative nonsurgical management tool for patients with tracheal stenosis caused by disease or iatrogenic trauma. Some patients with tracheal stent may need to be anesthetized to allow invasive techniques or surgery to be performed. In these patients, general anesthesia by endotracheal intubation may dislodge the stent distally or cause lethal complications such as bleeding. We describe three patients with a tracheal stent in place, who were anesthetized using a Laryngeal Mask Airway for surgery, with smooth results.     

Enhancement of rat growth hormone binding by membrane disulfide reduction

The effect of disulfide reduction on the binding of [125I]rat GH (rGH) to rat liver plasma membranes and hepatocytes was studied to determine the role of disulfide bonds in the binding of GH to its receptor. The total amount of [125I] rGH bound to the liver receptors increased severalfold in the presence of dithiothreitol and mercaptoethanol. The nonspecific binding also increased at higher concentrations of the reductant, but the amount specifically bound was still greater in the presence of disulfide reductant. In contrast, the disulfide reductant inhibited [125I] human GH (hGH) binding and enhanced its displacement from hypophysectomized female rat hepatocytes. This was similar to the effect of reductants on [125I]hGH binding to normal female rat hepatocytes. The effect of the disulfide reductants on [125I]rGH binding could be prevented or reversed by the simultaneous or subsequent addition of an oxidizing agent such as NAD or oxidized glutathione. Sulfhydryl-reactive agents such as iodoacetamide prevented additional binding of [125I]rGH when added at 30 min of the incubation. The additional [125I] rGH bound in the presence of disulfide reductant was displaceable by excess unlabeled rGH. Both rGH and hGH exhibited similar degrees of disulfide reduction in the presence of mercaptoethanol. The disulfide reductant produced effects on binding at concentrations that resulted in less than 10% reduction of the GH disulfides. We conclude that: 1) the disulfides and sulfhydryls of the hepatocyte membrane are intimately involved in the binding of GH to hepatic receptors; 2) the locus of the disulfides and sulfhydryls may be in the subunit structure of the membrane receptor, but this will require verification using soluble receptors; and 3) the effect of disulfide reducing agents reveals basic differences in the mechanism of binding of rGH and hGH to somatotropic hormone receptors on the hepatocytes.     

Serial electrophysiologic studies of the effects of oral diltiazem on paroxysmal supraventricular tachycardia

In 16 patients with paroxysmal supraventricular tachycardia, electrophysiologic studies were done before and serially at hourly intervals for eight hours after the third oral dose of 90 mg diltiazem given every eight hours. Diltiazem increased both the longest atrial paced cycle length producing type 1 atrioventricular block and the effective refractory period of the atrioventricular conducting system at all measurements. Before diltiazem, all 16 patients had induction of sustained tachycardia. After diltiazem, sustained tachycardia could not be induced in ten patients at any measurements; in these patients, either echo or nonsustained tachycardia was induced. In the remaining six patients, sustained tachycardia was induced, particularly after six hours. Follow-up observations in 12 patients receiving the same dosage of oral diltiazem for 6 +/- 2 months (mean +/- SD), showed that of the eight patients in whom electrophysiologic testing induced either echo or nonsustained tachycardia, six were asymptomatic and two experienced transient palpitation. Of the other four patients with induction of sustained tachycardia, three had transient palpitation and one had occasional attacks of sustained tachycardia requiring modification of therapy. Thus, oral diltiazem increases atrioventricular nodal refractoriness, with an effect lasting up to eight hours. It is an effective agent for the prophylaxis of paroxysmal supraventricular tachycardia.