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Alzheimer's disease (AD) is the most common form of dementia and is characterized by deposition of amyloid beta (A[beta]) in the brain. The components of the herb Magnolia officinalis are known to have antiinflammatory, antioxidative and neuroprotective activities. In this study we investigated the effects of ethanol extract of M. officinalis on memory dysfunction and amyloidogenesis in a transgenic mouse model of AD. Oral pretreatment of ethanol extract of M. officinalis (10 mg/kg in 0.05% ethanol) into drinking water for 3 months inhibited memory impairment and A[beta] deposition in the brain of Tg2576 mice. Ethanol extract of M. officinalis also decreased activity of [beta]-secretase, cleaving A[beta] from amyloid precursor protein (APP), and expression of [beta]-site APP cleaving enzyme 1 (BACE1), APP and its product, C99. Our results showed that ethanol extract of M. officinalis effectively prevented memory impairment via down-regulating [beta]-secretase activity. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The literature lacks studies that confirm whether the improved radiographic alignment that can be achieved with computer-navigated total knee arthroplasty improves patients’ activities of daily living or the durability of total knee prostheses. The purpose of this study was to determine whether computer-navigated total knee arthroplasty improves the clinical function, alignment, and survivorship of the components.Methods: We prospectively compared the results of 520 patients with osteoarthritis who underwent computer-navigated total knee arthroplasty for one knee and conventional total knee arthroplasty for the other. The assignment of the knee to navigation or not was done randomly. There were 452 women (904 knees) and sixty-eight men (136 knees) with a mean age of sixty-eight years (range, forty-nine to eighty-eight years) at the time of the index arthroplasty. The mean follow-up period was 10.8 years (range, ten to twelve years). The patients were assessed clinically and radiographically with the rating system of the Knee Society and with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at three months, one year, and annually thereafter.Results: Total knee scores, knee function scores, pain scores, WOMAC scores, knee motion, and activity scores did not show statistically significant differences between the two groups preoperatively or at the time of the final follow-up. Alignment and the survivorship of the components were not significantly different between the two groups. The Kaplan-Meier survivorship with revision as the end point at 10.8 years was 98.8% (95% confidence interval [CI], 0.96 to 1.00) in the computernavigated total knee arthroplasty group and 99.2% (95% CI, 0.96 to 1.00) in the conventional total knee arthroplasty group.Conclusions: Our data demonstrated no difference in clinical function or alignment and survivorship of the components between the knees that underwent computer-navigated total knee arthroplasty and those that underwent conventional total knee arthroplasty. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) is a counter-regulatory hormone that plays an important role in preventing hypoglycemia during fasting. Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin. The effects of GH and metformin were determined in the liver of wild-type, small heterodimer partner (SHP)-, PDK4-, and signal transducer and activator of transcription 5 (STAT5)-null mice. Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation. Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction. The increase in PDK4 expression and PDC phosphorylation by GH was reduced in STAT5-null mice. Metformin decreased GH-mediated induction of PDK4 expression and metabolites in wild-type but not in SHP-null mice. In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression. SHP directly inhibited STAT5 association on the PDK4 gene promoter. Metformin inhibits GH-induced PDK4 expression and metabolites via an AMPK-SHP-dependent pathway. The metformin-AMPK-SHP network may provide a novel therapeutic approach for the treatment of hepatic metabolic disorders induced by the GH-mediated pathway. [ABSTRACT FROM AUTHOR]

Purpose: The highest rates of gastric cancer occur in Eastern Asia. Fluoropyrimidine-based therapy is used initially in unresectable and metastatic disease, but no single standard of care exists following disease progression. Ixabepilone, an epothilone B analog, is a non-taxane microtubule-stabilizing agent with clinical activity across multiple tumor types approved by the United States Food and Drug Administration for treatment of metastatic breast cancer.Methods: Asian patients with unresectable or metastatic gastric adenocarcinoma who had failed fluoropyrimidine-based chemotherapy received ixabepilone 40 mg/m(2) by 3-h intravenous infusion every 3 weeks. The primary endpoint was objective response rate (ORR).Results: Fifty-two patients were treated (65.4 % men; median age: 56.5 years). The ORR was 15.4 % (95 % confidence interval [CI] 6.9-28.1); 8 patients achieved partial responses for a median duration of 3.1 months (95 % CI 2.6-4.1 months) and 26 patients (50.0 %) had stable disease. Median progression-free survival was 2.8 months (95 % CI 2.1-3.5 months). The most common grade 3 non-hematological toxicities were fatigue (9.6 %), decreased appetite (7.7 %), sensory neuropathy (5.8 %), and diarrhea (5.8 %). Grade 3/4 neutropenia occurred in 46.2 % of patients.Conclusions: Ixabepilone is active in Asian patients with advanced gastric cancer and shows a toxicity profile similar to those previously reported in other tumor types. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare the diagnostic ability of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) with that of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scan for bone metastasis in staging patients with small cell lung cancer (SCLC). Methods: Ninety-five patients with SCLC who underwent both (18)F-FDG PET/CT and (99m)Tc-MDP bone scan for initial staging work-up were retrospectively enrolled. All (18)F-FDG PET/CT and bone scan images were visually assessed. Bone metastasis was confirmed by histopathological results and all available clinical information. Results: Of 95 patients with SCLC, metastatic bone lesions were found in 30 patients, and 84 metastatic lesions were evaluated on a lesion-basis analysis. The sensitivity of (18)F-FDG PET/CT was 100 % on a per-patient basis and 87 % on a per-lesion basis, and there was no false-positive lesion on PET/CT images. In contrast, the sensitivity of the bone scan was 37 % on a per-patient basis and 29 % on a per-lesion basis. The bone scan showed 11 false-positive lesions. The bone scan detected two metastatic lesions that were not detected by PET/CT, which were outside the region scanned by PET/CT. On follow-up bone scan, 21 lesions that were not detected by the initial bone scan but were detected by PET/CT were newly detected. Conclusions: In patients with SCLC, (18)F-FDG PET/CT showed higher detection rate of bone metastasis than (99m)Tc-MDP bone scan. Thus, (18)F-FDG PET/CT can replace bone scan in staging patients with SCLC. [ABSTRACT FROM AUTHOR]

Background: The number of midterm or long-term studies on the current generation of cementless total hip replacements with alumina-on-alumina ceramic bearings in patients younger than thirty years of age is limited. The purpose of this study was to evaluate the midterm results of the cementless metaphyseal fitting anatomic total hip prosthesis in patients younger than thirty years of age, with a particular emphasis on the prevalence of thigh pain, resorption of bone due to stress-shielding of the proximal part of the femur, aseptic loosening, and osteolysis.Methods: We reviewed the cases of ninety-six patients (127 hips) who had a cementless total hip arthroplasty when they were thirty years or younger at the time of surgery. All surgical procedures were performed by a single surgeon. The most common diagnoses were osteonecrosis (54.3%) and developmental dysplasia of the hip (20.5%). Demographic data, the Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and University of California, Los Angeles (UCLA) activity scores were recorded. Radiographic evaluation was used to evaluate implant fixation and osteolysis. The minimum follow-up interval was ten years (mean, 14.6 years; range, ten to sixteen years).Results: The mean preoperative Harris hip score, WOMAC score, and UCLA activity score were 41 points, 66 points, and 3 points, respectively. At the time of final follow-up, the mean Harris hip score, WOMAC score, and UCLA activity score were 95 points, 16 points, and 8 points, respectively. No patient had thigh pain after one year postoperatively. All of the femoral stems and all but one of the acetabular components were well-fixed at the time of final follow-up. No hip exhibited squeaking, ceramic fracture, loosening, or osteolysis at the time of the final follow-up.Conclusions: These results in patients thirty years of age or younger suggest that the cementless metaphyseal fitting anatomic total hip prosthesis provides outstanding midterm fixation and substantial pain relief well into the second decade postoperatively. Moreover, the alumina-on-alumina ceramic bearing provides a high rate of survivorship without osteolysis. [ABSTRACT FROM AUTHOR]

Background: We are aware of no information about the mid-term performance of the high-flexion total knee arthroplasty, although early results have been reported. The purpose of this study was to evaluate the mid-term results of high-flexion and conventional knee prostheses.Methods: We prospectively compared the results of 100 patients with osteoarthritis who had received a NexGen Legacy Posterior Stabilized (NexGen LPS) prosthesis in one knee and a NexGen Legacy Posterior Stabilized-Flex (NexGen LPS-Flex) prosthesis in the other. Seventy-five patients (150 knees) were women and twenty-five (fifty knees) were men. The mean age was sixty-five years (range, forty-eight to eighty-five years) at the time of the index procedure. The mean duration of follow-up was 10.3 years (range, ten to 10.6 years). The patients were assessed with radiographs, with the rating system of the Knee Society, and with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at three months, one year, and annually thereafter.Results: Total knee scores, knee function scores, pain scores, WOMAC scores, knee motion, and activity scores did not differ significantly between the two designs of the implants, on the basis of the numbers studied, either preoperatively or at the time of final follow-up. One knee in the NexGen LPS-Flex group was revised because of recurrent infection. No knee in either group had aseptic loosening of the components. The Kaplan-Meier survivorship at ten years postoperatively, with revision defined as the end point, was 100% (95% confidence interval, 94 to 100) for the NexGen LPS prosthesis and 99% (95% confidence interval, 93 to 100) for the NexGen LPS-Flex prosthesis.Conclusions: After a minimum duration of follow-up of ten years, there were no significant differences between the two groups with regard to implant survivorship, functional outcome, knee motion, or prevalence of osteolysis. [ABSTRACT FROM AUTHOR]

Background: Treatment of perimitral flutter (PMF) requires bidirectional mitral isthmus (MI) block, which can be difficult with radiofrequency ablation (RFA). The vein of Marshall (VOM) is located within the MI.Objective: To test whether VOM ethanol infusion could help achieve MI block.Methods: Perimitral conduction was studied in patients undergoing ablation of atrial fibrillation. Group 1 included 50 patients with a previous atrial fibrillation ablation undergoing repeat ablation, 30 of whom had had MI ablation. Spontaneous (8 of 50) or inducible PMF (21 of 50) was confirmed by activation mapping. Group 2 included 21 patients undergoing de novo VOM ethanol infusion. The VOM was cannulated with a quadripolar catheter for pacing and with an angioplasty balloon to deliver up to four 1-mL infusions of 98% ethanol. Voltage maps were created before and after VOM ethanol infusion. Bidirectional MI block was verified by differential pacing. RFA times required to achieve it were assessed.Results: In group 1, VOM ethanol infusion acutely terminated PMF in 5 of 29 patients. RFA needed to achieve bidirectional MI block was 2.2 ± 1.6 minutes. Presence of PMF or previous MI ablation did not affect RFA times. In group 2, RFA needed to achieve bidirectional MI block was 2.0 ± 1.6 minutes (P = NS). Five patients had bidirectional MI block achieved solely by VOM ethanol infusion without RFA. In both groups, ablation after VOM ethanol infusion was required in the annular aspect of the MI. There were no acute complications.Conclusion: VOM ethanol infusion is useful in the treatment of PMF and assists in reliably achieving bidirectional MI block. [ABSTRACT FROM AUTHOR]