The role of reactive oxygen species scavenging enzymes in the development of septic loosening after total hip replacement

In this study of 41 patients, we used proteomic, Western blot and immunohistochemical analyses to show that several reactive oxygen species scavenging enzymes are expressed differentially in patients with primary osteoarthritis and those with non-loosening and aseptic loosening after total hip replacement (THR). The patients were grouped as A (n = 16, primary THR), B (n = 10, fixed THR but requiring revision for polyethylene wear) and C (n = 15, requiring revision due to aseptic loosening) to verify the involvement of the identified targets in aseptic loosening. When compared with Groups A and B, Group C patients exhibited significant up-regulation of transthyretin and superoxide dismutase 3, but down-regulation of glutathione peroxidase 2 in their hip synovial fluids. Also, higher levels of superoxide dismutase 2 and peroxiredoxin 2, but not superoxide dismutase 1, catalase and glutathione perioxidase 1, were consistently detected in the hip capsules of Group C patients. We propose that dysregulated reactive oxygen species-related enzymes may play an important role in the pathogenesis and progression of aseptic loosening after THR.     

Surface ultrastructure and mechanical property of human chondrocyte revealed by atomic force microscopy

OBJECTIVE: The mechanical properties of chondrocytes influence maintenance of the articular cartilage extracellular matrix. To differentiate the mechanical properties of chondrocytes between a young, normal modulus and an old, osteoarthritic (OA) modulus, we used an atomic force microscope (AFM) to probe the surface ultrastructure and to measure their adhesion force and stiffness. METHODS: We directly visualized a single chondrocyte cell by using AFM and quantitatively measured the dimensions of the cells. RESULTS: Profiles displayed heights of 1026+/-203 and 1668+/-352 nm for old and young cells, respectively. Contour maps revealed differences in the sizes and structures of the two groups. Mean calculated adhesion forces differed between normal and OA chondrocytes (7.06+/-3.35 and 2.97+/-1.82 nN, respectively), as did calculated stiffness values (0.0960+/-0.009 and 0.0347+/-0.005 N/m, respectively). CONCLUSION: These findings suggested that the mechanical properties of normal chondrocytes substantially differed from those of OA chondrocytes. We believe this study represents the first direct characterization of the surface ultrastructure and mechanical measurements of human chondrocytes between normal and OA stages. This new approach could be a useful technique for investigating age-related changes in the properties of human chondrocytes.     

Effects of 4-aminopyridine on motor evoked potentials in patients with spinal cord injury: a double-blinded, placebo-controlled crossover trial.

4-Aminopyridine (4-AP) is a potassium (K+) channel blocking agent that has been shown to reduce the latency and increase the amplitude of motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) in patients with chronic spinal cord injury (SCI). These effects on MEPs are thought to reflect enhanced conduction in long tract axons brought about by overcoming conduction deficits due to focal demyelination and/or by enhancing neuroneuronal transmission at one or more sites of the neuraxis. The present study was designed to obtain further evidence of reduced central motor conduction time (CMCT) and to determine whether MEPs could be recorded from paretic muscles in which they were not normally elicited. MEPs were elicited with TMS being delivered to subjects (n = 25) pre- and post-administration of 4-AP (10 mg capsule) or placebo. The principal finding was that 4-AP lowered the stimulation threshold, increased the amplitude and reduced the latency of MEPs in all muscles tested, including those that were unimpaired, but did not alter measures of the peripheral nervous system (i.e., M-wave, H-reflex, F-wave). These 4-AP-induced changes in MEPs were significantly greater than those seen with placebo (p < 0.05). The primary implication of these results is that a low dose of 4-AP (immediate-release formulation) appears to improve the impaired central motor conduction of some patients with incomplete SCI. This is most likely attributable to overcoming conduction deficits at the site of injury but may also involve an increase in cortical excitability.     

Outcome after treatment for papillary thyroid cancer

BACKGROUND: To evaluate the results of treatment and the prognostic variables of papillary thyroid carcinoma patients after long-term follow-up. PATIENTS AND METHODS: Retrospective review of 1,373 thyroid cancer patients. Of the 1,016 papillary thyroid cancer patients, 394 patients received follow-up for more than 5 years, including 305 women (mean age, 38.4 +/- 13.7 years) and 89 men (mean age, 44.0 +/- 13.4 years). Of these papillary thyroid carcinoma patients, 227, 76, 68, and 23 patients were categorized in clinical stages I, II, III, and IV, respectively, at the time of diagnosis. RESULTS: After treatment, 36 (9.1%) patients died. Only 23 (5.8%) of them died of papillary thyroid carcinoma. The 1-, 5-, 10-, and 20-year survival rates were 0.980, 0.951, 0.901, and 0.731. Mortality factors of the papillary thyroid carcinoma patients related to age, gender, tumor size, and postoperative serum thyroglobulin (Tg) levels. Twenty-four patients progressed from clinical stages I, II, and III to stage IV during the follow-up period. Of these 24 patients, 12 died during the follow-up period. In this study, age, gender, 131I accumulated dose, postoperative serum Tg levels, and the survival rate were demonstrated to be statistically significant between the patients in early stage and advanced stage groups after treatment. CONCLUSION: Twenty-four of the 47 papillary thyroid cancer patients with distant metastases were diagnosed during the follow-up period. This study suggests that distant metastasis may occur at a serum Tg level of 2.3 ng/mL with thyroxine replacement. Postoperative long-term close follow-up of these patients is recommended.     

Long-term results of transpedicle body augmenter in treating burst fractures

Background:

Short-segment fixation alone to treat thoracolumbar burst fractures is common but it has a 20-50% incidence of implant failure and rekyphosis. A transpedicle body augmenter (TpBA) to reinforce the vertebral body via posterior approach has been reported to prevent implant failure and increase the clinical success rate in treating burst fracture. This article is to evaluate the longterm results of short-segment fixation with TpBA for treatment of thoracolumbar burst fractures.

Materials and Methods:

Patients included in the study had a single-level burst fracture involving T11-L2 and no distraction or rotation element with limited neurological deficit. Patients in the control group (n = 42) were treated with short-segment posterior instrumentation alone, whereas patients in the augmented group (n = 90) were treated with a titanium spacer designed for transpedicle body reconstruction. The followup was 48-101 months. The radiographic and clinical results were evaluated and compared by Student''s t test and Fisher''s exact test.

Results:

The blood loss, operation time and hospitalization were similar in both the groups. The immediate postoperative anterior vertebral restoration rate of the augmented group was similar to that of the control group (97.6% ± 2.4% vs. 96.6% ± 3.2%). The final anterior vertebral restoration was greater in the augmented group than in the control group (93.3% ± 3.4% vs. 62.5% ± 11.2%). Immediate postoperative kyphotic angles were not significantly different between the groups (3.0° ± 1.8° vs. 5.1° ± 2.3°). The final kyphotic angles were less in the augmented group than the control group (7.3° ± 3.5° vs. 20.1° ± 5.4°). The augmented group had less (P < 0.001) implant failure [0% (n=0) vs. 23.8% (n=10)] for the control group) and more patients (P < 0.001) with no pain or minimal or occasional pain (Grade P1 or P2) than the control group [90.0% (n=81) vs. 66.7% (n=28)]. All patients in the augmented group and 39 (92.8%) patients in the control group experienced neurological recovery to Frankel Grade E. Three patients in the control group had improvement to Frankel Grade D from Frankel Grade C, but later had deterioration to Frankel Grade C because of loosening and dislodgement of the implant.

Conclusion:

Posterior body reconstruction with TpBA can maintain kyphosis correction and vertebral restoration, prevent implant failure and lead to better clinical results.     

Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids

OBJECTIVE: Our present study examined the effect of intra-articular cyclooxygenase-2 (COX-2) inhibitor parecoxib on osteoarthritis (OA) progression and the concomitant changes in excitatory amino acids' (EAAs) levels of the anterior cruciate ligament-transected (ACLT) knee joint dialysates. METHODS: OA was induced in Wistar rats by anterior cruciate ligament transection of the knee of one hindlimb, the other was left unoperated and untreated. Rats were placed into four groups: Group ACLT/P received intra-articular parecoxib injection (100 microg) in the ACLT knee once a week for 5 consecutive weeks starting at 8 weeks after surgery. Group ACLT/S received the same procedure as group ACLT/P with saline injection instead. Na?ve (Na?ve/P) rats received only intra-articular parecoxib injection in one knee once a week for 5 consecutive weeks without surgery. The sham-operated rats underwent arthrotomy only without treatment. Twenty weeks after surgery, knee joint dialysates were collected and EAAs' concentration was assayed by high-performance liquid chromatography, and gross morphology and histopathology (Mankin and synovitis grading) were examined on the medial femoral condyles and synovia. RESULTS: Parecoxib alone had no effect on cartilage and synovium of normal knees in Na?ve/P rats. In ACLT/P rats, parecoxib treatment showed a significant inhibition of cartilage degeneration of the medial femoral condyle at both the macroscopic level (1.15+/-0.17 vs 2.55+/-0.12, P<0.05) and the Mankin scores (3.03+/-0.28 vs 8.82+/-0.43, P<0.05). Intra-articular parecoxib injection also suppressed the synovial inflammation of ACLT joint compared to the ACLT/S group (3.92+/-0.41 vs 9.25+/-0.32, P<0.05). Moreover, glutamate and aspartate levels were also significantly reduced in the ACLT/P group compared to the ACLT/S group by parecoxib treatment (91.2+/-9.4% vs 189.5+/-17.0%, P<0.05 and 98.2+/-11.6% vs 175.3+/-12.4%, P<0.05, respectively). CONCLUSION: This study shows that intra-articular injection of COX-2 inhibitor parecoxib inhibits the ACLT-induced OA progression; it was accompanied by a reduction of glutamate and aspartate concentration in the ACLT joint dialysates. From our present results, we suggested that intra-articular parecoxib injection, in addition to the anti-inflammatory effect, inhibiting the EAAs' release, may also play a role in inhibiting the traumatic knee injury induced OA progression.     

SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes

OBJECTIVE-SUMO4 mRNA was recently found to be mainly expressed in the kidney, and the methionine-to-valine substitution at codon 55 (M55V) variant of SUMO4 may induce higher nuclear factor-kappaB (NF-kappaB) activity. Because NF-kappaB is known to mediate the development of diabetic nephropathy, we examined the association between the SUMO4 M55V variant and the severity of diabetic nephropathy. RESEARCH DESIGN AND METHODS-We recruited a total of 430 patients with type 2 diabetes. The M55V (rs237025, 163A-->G) polymorphism of SUMO4 was genotyped by real-time PCR, and urine albumin concentration was measured by radioimmunoassay. RESULTS-The frequencies of SUMO4 AA, GA, and GG were 52.6, 40.7, and 6.7%, respectively, in the normoalbuminuric group; 45.5, 47.3, and 7.1% in the microalbuminuric group; and 36.9, 46.2, and 16.9% in the macroalbuminuric group. We detected a significant linear trend for SUMO4 genotype between the macroalbuminuric and normoalbuminuric groups. The mean urine albumin-to-creatinine ratio (42.3 +/- 108.82 mg/mmol) in the GG group was significantly higher than in the AA (14.9 +/- 51.49 mg/mmol) and GA (17.0 +/- 43.74 mg/mmol) groups. Multivariate logistic regression analysis showed the SUMO4 M55V variant to be independently associated with the severity of diabetic nephropathy. CONCLUSIONS-This study indicates that the SUMO4 gene M55V variant is associated with severity of diabetic nephropathy in patients with type 2 diabetes.     

The experience of biliary tract complications after liver transplantation

AIM: To report the morbidity and mortality of patients who undergo liver transplantation with or without T-tube implantation after choledochocholedochostomy as well as to discuss management of biliary complications. PATIENTS AND METHODS: We performed a retrospective review of 104 liver transplantations from August 2001 to February 2006, including 51 patients who underwent choledochocholedochostomy with a T-tube (group A) and 53, without a T-tube (group B). We compared the clinical characteristics, operative methods, biliary complications, morbidity, mortality, and management of complications. RESULTS: Between the two groups, there were no significant differences in clinical characteristics, including sex, age, and indication for liver transplantation (hepatitis B virus, hepatitis C virus, alcoholic liver cirrhosis, or hepatocellular carcinoma), Child-Pugh classification, Model for End-stage Liver Disease score, and operative macroscopic/microscopic findings. Additionally, there was no significant difference in biliary complications. Among these 104 patients, 14 (13.5%) developed biliary complications: seven anastomotic strictures, two intrahepatic duct strictures, two anastomotic stricture combined intrahepatic duct stricture, one bile leakage, one bile leakage combined with anastomotic stricture, and one external biliary compression. Nine patients with anastomotic stricture underwent endoscopy with a stent, which was successful only in two patients. The other six patients underwent choledochojejunostomy with excellent results. CONCLUSIONS: This study showed choledochocholedochostomy with or without a T-tube after liver transplantation did not influence the biliary complications. The biliary complications of anastomotic stricture after liver transplantation can be managed by endoscopy with a stent. If endoscopy fails, surgical intervention should be considered immediately.