INTRODUCTIONUp to 20% of patients who underwent total knee arthroplasty (TKA) reported dissatisfaction with surgical outcome. Despite the multiple studies looking into the factors contributing to patients' dissatisfaction, little research has been done to examine the subjective reasons and complaints patients have post-arthroplasty. This study aimed to look at an Asian patient population which underwent TKA and examine the factors contributing to patient dissatisfaction and the reasons they were dissatisfied with their surgery.

MATERIALS AND METHODSA total of 3069 TKAs were performed between January 2011 to April 2013 in a single institution. Preoperative and postoperative variables were prospectively captured, such as standardised knee scores, knee range of motion and patient satisfaction scores. These variables were then analysed with a multiple logistic regression model to determine the statistically significant factors that contribute to patients' satisfaction. Dissatisfied patients were individually interviewed to find the reasons for their unhappiness. Preoperative variables were then analysed to identify the statistically significant factors associated with these subjective complaints.

RESULTSMinimum duration of follow-up was 2 years, with an overall patient satisfaction rate of 91.3%. Preoperative variables contributing to patient dissatisfaction included female gender and better knee flexion. Postoperative variables included lesser improvement in knee flexion at 6 months postoperatively, as well as poorer scores in various validated knee scores at both 6 months and 2 years postoperatively. The top reason for dissatisfaction was pain. Weakness, another reason for patient dissatisfaction, had statistically significant preoperative predictors of increased age and poorer Short-Form 36 Physical Component Score.

CONCLUSIONAlthough TKA has an impressive patient satisfaction rate in this Asian population, factors contributing to postoperative dissatisfaction suggest a targeted group of patients would benefit from preoperative counselling. The top reason for postoperative dissatisfaction in the study was pain.

OBJECTIVE: To evaluate the capacity of a computer-aided detection (CAD) system to detect lung nodules in clinical chest CT. MATERIALS AND METHODS: A total of 210 consecutive clinical chest CT scans and their reports were reviewed by two chest radiologists and 70 were selected (33 without nodules and 37 with 1-6 nodules, 4-15.4 mm in diameter). The CAD system (ImageChecker (R) CT LN-1000) developed by R2 Technology, Inc. (Sunnyvale, CA) was used. Its algorithm was designed to detect nodules with a diameter of 4-20 mm. The two chest radiologists working with the CAD system detected a total of 78 nodules. These 78 nodules form the database for this study. Four independent observers interpreted the studies with and without the CAD system. RESULTS: The detection rates of the four independent observers without CAD were 81% (63/78), 85% (66/78), 83% (65/78), and 83% (65/78), respectively. With CAD their rates were 87% (68/78), 85% (66/78), 86% (67/78), and 85% (66/78), respectively. The differences between these two sets of detection rates did not reach statistical significance. In addition, CAD detected eight nodules that were not mentioned in the original clinical radiology reports. The CAD system produced 1.56 false-positive nodules per CT study. The four test observers had 0, 0.1, 0.17, and 0.26 false-positive results per study without CAD and 0.07, 0.2, 0.23, and 0.39 with CAD, respectively. CONCLUSION: The CAD system can assist radiologists in detecting pulmonary nodules in chest CT, but with a potential increase in their false positive rates. Technological improvements to the system could increase the sensitivity and specificity for the detection of pulmonary nodules and reduce these false-positive results.
*Diagnosis, Computer-Assisted ; False Positive Reactions ; Humans ; Lung Diseases/*radiography ; Lung Neoplasms/radiography ; Radiography, Thoracic/*methods ; Sensitivity and Specificity ; Tomography, X-Ray Computed/*methods

BACKGROUNDAge-associated decrease in type IIA/B human skeletal muscle fibers was detected in human biopsies in our previous study. The relationship between change in muscle fiber typing and bone mineral density (BMD) is, however, unknown either cross-sectionally or longitudinally. We therefore conducted a cross-sectional study to investigate their correlation using human muscle biopsies.

METHODSForty human subjects aged (53.4 ± 20.2) years were recruited. Histomorphometric parameters of their muscle biopsies were measured by ATPase staining and image analysis, including average area percentage, fiber number percentage, mean fiber area, and area percentage of connective tissues. Hip and spine BMD was measured by dual-energy X-ray absorptiometry. Partial correlation with adjusting age was performed.

RESULTSType IIB muscle fiber was found positively correlated with hip BMD irrespective to age and demonstrated significantly stronger relationship with BMD among all fiber types, in terms of its cross-sectional area (r = 0.380, P = 0.029) and size (r = 0.389, P = 0.025). Type IIA muscle fibers associated with hip BMD in mean fiber area only (r = 0.420, P = 0.015).

CONCLUSIONSType IIB muscle fiber may play an important role in maintaining bone quality. This may also be a relatively more sensitive fiber type of sarcopenia and osteoporosis. These findings further consolidate the muscle-bone relationship.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Bone Density ; physiology ; Female ; Humans ; In Vitro Techniques ; Male ; Middle Aged ; Muscle Fibers, Fast-Twitch ; cytology ; metabolism ; Prospective Studies ; Young Adult

Objectives There is little information available regarding local vasomotor regulating processes in chronic heart failure. In this study, we tested the hypothesis that chronic heart failure impaired the endothelial function, and long term captopril treatment might reverse endothelial activity through tissue endothelin (ET) pathway.Methods Forty Spraque-Dawley rats were divided into 4 groups including 15 rats in each of the sham-operated with or without captopril-treated groups and 5 rats in each of large infarcted with or without captopril-treated groups.Results Concentration-response curves obtained in aortic rings without endothelium revealed no difference in nitroprusside-induced relaxation. With endothelium, rightward shifting was noted only in the untreated large infarct group during acetylcholine-induced relaxation. As compared to the non-treated group, plasma ET-1 concentrations were lower in the captopril-treated with or without large infarct groups. However, endothelin-like immunoreactivity in endothelial cells and cytoplasma of smooth muscle cells of the media of the aorta were lower only in the non-treated large infarct group.Conclusions Endothelial function was impaired in the chronic heart failure model. Coverting enzyme inhibitor might improve endothelial function through the Local endothelin pathway.

OBJECTIVE: Estrogen related receptor beta (Esrrb) is a member of the orphan nuclear receptors and may regulate the expression of pluripotency-related genes, such as Oct4 and Nanog. Therefore, in the present study, we have developed a method for delivering exogenous ESRRB recombinant protein into embryos by using cell-penetrating peptide (CPP) conjugation and have analyzed their effect on embryonic development. METHODS: Mouse oocytes and embryos were obtained from superovulated mice. The expression of Oct4 mRNA and the cell number of inner cell mass (ICM) in the in vitro-derived and in vivo-derived blastocysts were first analyzed by real time-reverse transcription-polymerase chain reaction and differential staining. Then 8-cell embryos were cultured in KSOM media with or without 2 microg/mL CPP-ESRRB protein for 24 to 48 hours, followed by checking their integration into embryos during in vitro culture by Western blot and immunocytochemistry. RESULTS: Expression of Oct4 and the cell number of ICM were lower in the in vitro-derived blastocysts than in the in vivo-derived ones (p<0.05). In the blastocysts derived from the CPP-ESRRB-treated group, expression of Oct4 was greater than in the non-treated groups (p<0.05). Although no difference in embryonic development was observed between the treated and non-treated groups, the cell number of ICM was greater in the CPP-ESRRB-treated group. CONCLUSION: Treatment of CPP-ESRRB during cultivation could increase embryos' expression of Oct4 and the formation rate of the ICM in the blastocyst. Additionally, an exogenous delivery system of CPP-conjugated protein would be a useful tool for improving embryo culture systems.
Animals ; Blastocyst ; Blotting, Western ; Cell Count ; Embryonic Development ; Embryonic Structures* ; Estrogens ; Female ; Immunohistochemistry ; Mice* ; Oocytes ; Orphan Nuclear Receptors ; Pregnancy ; RNA, Messenger

BACKGROUNDInterleukin (IL)-1beta may effectively decrease introcular pressure (IOP) when administered by subconjunctival injection in normal rabbit. However, IL-1beta is a large molecular agent and an inflammation factor. The aim of this study was to evaluate the penetrability of IL-1beta, and the concentrations of both tumor necrosis factor (TNF)-alpha and IL-6 in the aqueous humor of normal rabbits treated with IL-1beta.

METHODSA total of 170 rabbits were used in the study and were assigned to several different treatment groups as follows: 125 of the rabbits were assigned to two groups. In one group, 33 rabbits were injected subconjunctivally with IL-1beta and 39 were injected with saline alone. In the other group, 27 rabbits were given eye drops containing IL-1beta (400 ng/ml) and 26 were given saline alone. Aqueous humor (AH) was drawn and the concentration of IL-1beta within the fluid measured. The IOP was measured in another six rabbits after administration of eye drops containing IL-1beta (400 ng/ml). A further 20 rabbits were assigned to 3 groups as follows: eight untreated normal controls; six injected subconjunctivally with IL-1beta; and six injected subconjunctivally with saline alone. AH was drawn and the concentration of TNF-alpha in the fluid was measured. Another 19 rabbits were assigned to 3 groups as follows: seven untreated normal controls; and six injected subconjunctivally with IL-1beta; and six injected subconjunctivally with saline alone. AH was drawn and the concentration of IL-6 in the fluid measured. Measurement of cytokine concentration was by radio-immunoassay in all cases.

RESULTSThe IL-1beta concentration in the AH was higher in those animals in which it had been administered subconjunctivally (P < 0.01). The IL-1beta concentration in the AH of the animals given eye drops was almost the same as that in the controls (P > 0.05). The administration of IL-1beta in the form of eye drops had little effect upon IOP reduction. Lower TNF-alpha concentrations were seen in the AH after the subconjunctival administration of IL-1beta, but the concentration of IL-6 was the same as in the normal controls.

CONCLUSIONSIL-1beta shows good corneal penetrability after subconjunctival injection into normal rabbit eyes. The IOP reduction induced by IL-1beta is unlikely be associated with an inflammatory response.

Animals ; Aqueous Humor ; drug effects ; metabolism ; Interleukin-1beta ; pharmacology ; Interleukin-6 ; metabolism ; Rabbits ; Tumor Necrosis Factor-alpha ; metabolism

INTRODUCTIONThis study aimed to evaluate the efficacy and safety of intra-articular glucocorticoid (IAG) injections in our institution in children with juvenile idiopathic arthritis (JIA).

METHODSThis is a retrospective assessment of IAG injections performed by the Department of Paediatrics, National University Hospital, Singapore, from October 2009 to October 2011. A total of 26 procedures were evaluated for efficacy, considering parameters such as clinical response, changes in systemic medication, length of time between repeat injections, safety, consent-taking, pre- and post-procedural advice, compliance with aseptic technique, and post-procedural complications.

RESULTSA total of 26 IAG injections of triamcinolone hexacetonide were administered over 17 occasions (i.e. patient encounters) to ten patients with JIA during the study period. After the injections, clinical scoring by a paediatric rheumatologist showed overall improvement by an average of 2.62 points out of 15. Besides six patient encounters that had an increase in systemic medication on the day of the injection, five required an increase within six months post injection, two required no adjustments, and one resulted in a decrease in medications. In all, 21 injections did not require subsequent injections. The mean interval between repeat injections was 7.8 months. Cutaneous side effects were noted in three anatomically difficult joints. Medical documentation with regard to patient progress was found to be lacking.

CONCLUSIONAs per the recommendations of the American College of Rheumatology, we safely used IAG injections as the first-line therapy in our group of patients with oligoarticular JIA, and/or as an adjunct to systemic therapy in our patients with JIA.

Adolescent ; Anti-Inflammatory Agents ; administration & dosage ; Arthritis, Juvenile ; drug therapy ; Child ; Child, Preschool ; Female ; Glucocorticoids ; administration & dosage ; Humans ; Injections, Intra-Articular ; Male ; Pediatrics ; methods ; Retrospective Studies ; Singapore ; Skin ; drug effects ; Treatment Outcome ; Triamcinolone Acetonide ; administration & dosage ; analogs & derivatives

BACKGROUND: Leukocyte-poor platelet-rich plasma (LP-PRP) from peripheral blood is currently used as a concentrated source of growth factors to stimulate repair at sites of soft tissue injury. Fibroblasts are primary mediators of wound healing. Thus, we aimed to assess the positive effect of LP-PRP on human fibroblast proliferation in vitro. METHODS: LP-PRP was prepared from 49 donors. The fibroblasts were seeded, and at 24 hours after seeding, 1 × 107/10 µL LP-PRP was added once to each well. The cells were harvested 10 times during study period at our planned points, and we examined cell proliferation using the water-soluble tetrazolium salt-1 assay. We collected the supernatants and measured the amount of growth factors such as platelet-derived growth factor (PDGF)-AB/BB, insulin-like growth factor-1 (IGF-1), transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor (VEGF), which are known to be involved in wound healing processes, by multiplex assay. RESULTS: Human fibroblasts treated with LP-PRP showed a significant increase in proliferation when compared to untreated controls (p < 0.001 at days 4, 6, and 8). Multiplex cytokine assays revealed various secretion patterns. PDGF-AB/BB appeared at early time points and peaked before fibroblast proliferation. IGF-1 and TGF-β1 secretion gradually increased and peaked on days 4 and 6 post-treatment. The early VEGF concentration was lower than the concentration of other growth factors but increased along with cell proliferation. CONCLUSIONS: Platelets in LP-PRP release growth factors such as PDGF, IGF-1, TGF-β1 and VEGF, and these growth factors have a promoting effect for human fibroblast proliferation, one of the important mediators of wound healing. These results suggest that growth factors derived from LP-PRP enhance the proliferation of human fibroblast.
Cell Proliferation ; Fibroblasts* ; Humans* ; In Vitro Techniques* ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins* ; Platelet-Derived Growth Factor ; Platelet-Rich Plasma ; Soft Tissue Injuries ; Tissue Donors ; Vascular Endothelial Growth Factor A ; Wound Healing

Background and Objectives: The nucleotide-binding oligomerization domain-like receptor (NLRP) 3 is known as a member of the NLR family, and it has been confirmed that the NLRP3 inflammasome is associated with various diseases such as asthma, inflammatory bowel disease, metabolic disorders and multiple sclerosis, as well as other auto-immune and auto-inflammatory diseases. However, the role of NLRP3 in chronic rhinosinusitis with nasal polyps (CRSwNP) has not yet been explored.Subjects and Method Forty-four specimens of nasal polyps and 25 specimens of uncinate processes were collected from patients with chronic rhinosinusitis with nasal polyps, and 25 specimens of uncinate tissues were collected from patients who underwent other rhino-surgeries. The western blot assay was employed to analyze the expression of NLRP3; interleukin (IL)-1β and IL-17A were detected using immunohistochemistry and real-time polymerase chain reaction. The production of lipopolysaccharide (LPS) induced IL-1β and IL-17A with or without the NLRP3 inflammasome inhibitor (MCC950) was measured using an enzyme linked immunosorbent assay in cultured dispersed nasal polyp cells. Results: NLRP3 showed a high level of expression in nasal polyps than in the control group (p<0.01). The expression of IL-1β and IL-17A was significantly higher in nasal polyps in the CRSwNP group than in the control group (p<0.05). LPS-induced production of IL-1β was significantly suppressed by treatment with the NLRP3 inflammasome inhibitor (p<0.05). Conclusion The NLRP3 inflammasome plays an essential role in the pathogenesis of CRSwNP, and thus MCC950 can be considered a prospective therapeutic for NLRP3 inflammasome-mediated inflammation in nasal polyps. Our data provide new evidence that IL-17A is involved in inflammasome-associated inflammation in nasal polyps.

OBJECTIVE: The BCL2 family proteins are critical mediators of cellular apoptosis and, as such, have been implicated as determinants of cancer cell chemo-sensitivity. Recently, it has been demonstrated that the phosphorylation status of the BCL2 antagonist of cell death (BAD) protein may influence ovarian cancer (OVCA) cell sensitivity to cisplatin. Here, we sought to evaluate how kinase and phosphatase components of the BAD apoptosis pathway influence OVCA chemo-sensitivity. METHODS: Protein levels of cyclin-dependent kinase 1 (CDK1) and protein phosphatase 2C (PP2C) were measured by immunofluorescence in a series of 64 primary advanced-stage serous OVCA patient samples. In parallel, levels of cAMP-dependent protein kinase (PKA), AKT, and PP2C were quantified by Western blot analysis in paired mother/daughter platinum-sensitive/resistant OVCA cell lines (A2008/C13, A2780S/A2780CP, Chi/ChiR). BAD pathway kinase CDK1 was depleted using siRNA transfection, and the influence on BAD phosphorylation and cisplatin-induced apoptosis was evaluated. RESULTS: OVCA patient samples that demonstrated complete responses to primary platinum-based therapy demonstrated 4-fold higher CDK1 (p<0.0001) and 2-fold lower PP2C (p=0.14) protein levels than samples that demonstrated incomplete responses. Protein levels of PP2C were lower in the platinum-resistant versus that shown in the platinum-sensitive OVCA cell line sub-clones. Levels of PKA were higher in all platinum-resistant than in platinum-sensitive OVCA cell line sub-clones. Selective siRNA depletion of CDK1 increased sensitivity to cisplatin-induced apoptosis (p<0.002). CONCLUSION: BAD pathway kinases and phosphatases, including CDK1 and PP2C, are associated with OVCA sensitivity to platinum and may represent therapeutic opportunities to enhance cytotoxic efficacy.
Apoptosis ; Blotting, Western ; CDC2 Protein Kinase ; Cell Death ; Cell Line ; Cisplatin ; Cyclic AMP-Dependent Protein Kinases ; Fluorescent Antibody Technique ; Humans ; Ovarian Neoplasms ; Phosphoprotein Phosphatases ; Phosphoric Monoester Hydrolases ; Phosphorylation ; Phosphotransferases ; Platinum ; Proteins ; RNA, Small Interfering ; Transfection