New combined anteversion technique in hybrid THA: cup-first procedure with CT-based navigation

European Journal of Orthopaedic Surgery & Traumatology - Combined anteversion (CA) technique (stem-first procedure) is generally accepted as the optimal technique to attain an appropriate CA...     

Downregulation of cytochrome P450scc as an initial adverse effect of adult exposure to diethylstilbestrol on testicular steroidogenesis

Reproductive toxicities and endocrine disruptions caused by chemicals in adult males are still poorly understood. It is our objectives to understand further details of the initial adverse effects leading severe testicular toxicities of a pharmaceutical endocrine disruptor, diethylstilbestrol (DES). Downregulations of both testicular regulatory proteins, such as the steroidogenic acute regulatory protein (StAR) and the peripheral benzodiazepine receptor (PBR), which play important roles in the transport of cholesterol into the mitochondria, and cytochrome P450 mediating the cholesterol side chain cleavage reaction (P450scc), were observed in the rat orally administered DES (340 μg/kg/2 days) for 2 weeks. We found that after only 1 week treatment with DES, the blood and testicular testosterone (TS) levels were drastically decreased without abnormalities of the StAR and PBR; however, the protein and mRNA levels of P450scc were diminished. Decrease in the conversion rate of cholesterol to pregnenolone was delayed in the in vitro assay using the testicular mitochondrial fraction from the rat treated with DES for 1 week. When the precursors in TS biosynthesis containing the testis were identified and determined by liquid chromatography‐mass spectrometry analysis, decreased levels of all precursors except cholesterol were observed. In conclusion, suppressed cytochrome P450scc expression in adult male rat was identified as an initial target of DES in testicular steroidogenesis disorder leading reproductive toxicities. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1452–1459, 2014.     

Percutaneous autologous concentrated bone marrow grafting in the treatment for nonunion

The purpose of this study was to evaluate the clinical and radiographic treatment effects of percutaneous autologous concentrated bone marrow grafting in nonunion cases and to evaluate the effectiveness of this grafting procedure. We enrolled 17 cases those had atrophic changes due to continuous nonunion for over 9 months after injury and had undergone low-intensity pulsed ultrasound treatment for more than 3 months. The site of nonunion was the femur in 10 cases, the tibia in 5 cases, the humerus in 1 case, and the ulna in 1 case. They underwent percutaneous autologous concentrated bone marrow grafting and continued low-intensity pulsed ultrasound stimulation treatment after grafting. Patients were evaluated using the visual analogue scale for pain at immediately before the procedure, 3, 6, and 12 months after grafting. Plain radiographs of the affected site were taken and evaluated about the healing of the nonunion site at each clinical evaluation. As quantitative assessment, CT scans were undertaken before the procedure and 6 months after grafting. The visual analogue scale pain score was reduced consistently after grafting in all patients. About the healing at the nonunion site, 11 and 13 cases of bone union were observed at 6 and 12 months after grafting. The mean volume of callus formation based on CT images was 4,147 (262–27,392) mm³ total between grafting and 6 months. Percutaneous autologous concentrated bone marrow grafting is an effective procedure for the treatment of patients with nonunion.     

Antimicrobial susceptibility surveillance of obligate anaerobic bacteria in the Kinki area

Obligate anaerobes exist as resident flora in various sites in humans, but they are also emphasized as endogenous causative microorganism of infections. We performed surveillance to understand the trend of drug susceptibility in obligate anaerobic bacteria in the Kinki area of Japan. In the experiment, we used 156 obligate anaerobe isolates collected from 13 institutions that participated in the Study of Bacterial Resistance Kinki Region of Japan. MALDI Biotyper was used to identify the collected strains, and among the 156 test strains, those that could be identified with an accuracy of Score Value 2.0 or more included 6 genera, 30 species, and 144 strains (Bacteroides spp. 77 strains, Parabacteroides sp. 2 strains, Prevotella spp. 29 strains, Fusobacterium spp. 14 strains, Porphyromonas spp. 2 strains, and Clostridioides difficile 20 strains), and they were assigned as subject strains for drug susceptibility testing. The drug susceptibility test was carried out by broth microdilution method using Kyokuto Opt Panel MP ANA (Kyokuto Pharmaceutical Industrial Co., Ltd., Tokyo, Japan) and judged according to CLSI criteria. As a result, Bacteroides and Parabacteroides species showed good sensitivities to tazobactam-piperacillin, imipenem, metronidazole and chloramphenicol, and low sensitivities to ampicillin, cefoperazone and vancomycin. Prevotella species showed good sensitivities to sulbactam-ampicillin, tazobactam-piperacillin, cefmetazole, imipenem, doripenem and metronidazole. Susceptibility rates to other drugs were slightly different depending on the bacterial species. Both Fusobacterium spp. and Porphyromonas spp. showed high sensitivities to many drugs. C. difficile was highly sensitive to vancomycin and metronidazole, having MIC₉₀s of 0.5 μg/mL and ≤2 μg/mL, respectively.     

A comprehensive gene expression analysis of human hepatocellular carcinoma cell lines as components of a bioartificial liver using a radial flow bioreactor.

BACKGROUND/AIMS: The cells constituting a bioartificial liver are crucial for an effective liver support system. We compared global gene expression profiles in a radial flow bioreactor or a monolayer culture of three functional liver cell lines previously established from human hepatocellular carcinoma. METHODS: The expressions of 60,000 genes of the FLC-4, FLC-5, and FLC-7 cell lines were analyzed by the microarray technique with the Affymetrix GeneChip system. Global gene expression profiles were compared with two-way cluster analysis. Several liver function-related genes were compared between the bioreactor and culture conditions. RESULTS: Cluster analysis revealed that gene expression profiles of bioreactor-grown cells resembled those of the normal liver. Genes related to cellular structure were highly expressed in the bioreactor-grown cells, while genes involved in proliferation or carcinogenesis were suppressed. In the bioreactor-grown cells, some genes for liver functions were expressed at a level similar to that in normal liver, although none of the cell lines expressed the complete set of genes encoding ammonium metabolism or cytochrome P450 species. CONCLUSION: The high-density three-dimensional culture in the radial flow bioreactor prompted differentiation of the cells. These data may be useful for improving the cells by genetic or pharmacological reinforcement and for monitoring bioartificial livers.     

Clinical value of abnormal findings on brain magnetic resonance imaging in patients with intravascular large B-cell lymphoma

To investigate the prevalence and clinical value of abnormal findings detected via brain magnetic resonance imaging (MRI) in patients with intravascular large B-cell lymphoma (IVLBCL), we identified 33 patients with IVLBCL pathologically diagnosed and evaluated with pretreatment brain MRI. Abnormal findings on brain MRI were categorized into four patterns: (1) hyperintense lesion in the pons on T2-weighted imaging (T2WI), (2) nonspecific white matter lesions, (3) infarct-like lesions, and (4) meningeal thickening and/or enhancement. Abnormal cerebral findings were detected in 29 patients (87.9%). Hyperintense lesion in the pons was the most common finding (n?=?19 (57.6%) patients), followed by nonspecific white matter lesions (n?=?14 (42.4%) patients), infarct-like lesions (n?=?8 (24.2%) patients), and meningeal thickening and/or enhancement (n?=?4 (12.1%) patients). Impaired consciousness was seen in most of the patients with infarct-like lesions (87.5%) but less frequently in patients with hyperintense lesion in the pons (47.4%). We reviewed brain MRI findings in 39 patients with diffuse large B cell lymphoma with central nervous system (CNS) involvement and/or high-risk extranodal lesions for CNS involvement as a control group. In contrast to the patients with IVLBCL, no patient had hyperintense lesion in the pons in the control group (P?<?0.001). Follow-up brain MRI revealed improvement of abnormal findings in most of the patients who responded to chemotherapy. This study highlighted the diagnostic implication of hyperintense lesion in the pons on T2WI and the clinical usefulness of pretreatment brain MRI in IVLBCL even in patients without impaired consciousness.     

Carnitine is associated with fatigue following chemoradiotherapy for head and neck cancer

Conclusion: Longitudinal assessments of carnitine and fatigue in patients with head and neck squamous cell carcinoma suggest that cisplatin damages the carnitine system in patients undergoing chemoradiotherapy and that carnitine deficiency increases fatigue. Objectives: The purpose of this study was to monitor carnitine levels and fatigue in patients who received cisplatin-based CRT and, for comparison, in patients treated by surgery alone. Methods: To investigate the level of carnitine, mice were administered cisplatin. Next, a prospective analysis was performed to compare plasma carnitine levels before and after cisplatin-based chemoradiotherapy and to assess the relationship between carnitine levels and fatigue. Results: The plasma levels of total carnitine (TC), free carnitine (FC), and fatty acylcarnitine (AC) were significantly lower in mice receiving cisplatin compared with control mice. Mean total carnitine and free carnitine levels were significantly lower 2 weeks after chemoradiotherapy (total carnitine: Mean = 45.6, SD = 16.5, p = 0.01; free carnitine: Mean = 37.8, SD = 12.7, p = 0.02) than before chemoradiotherapy (total carnitine: Mean = 57.7, SD = 12.2; free carnitine: Mean = 48.1, SD = 11.6). There was a significant inverse correlation between carnitine levels and fatigue after chemoradiotherapy.     

Clinical Effectiveness of Tolvaptan in Patients with Acute Decompensated Heart Failure and Renal Failure: Design and Rationale of the AQUAMARINE Study

Purpose

Over half of all admitted acute decompensated heart failure (ADHF) patients have renal failure. Although diuretics represent the mainstay of treatment strategy even in this population, there are unmet needs for safer and more effective treatment. Tolvaptan is a vasopressin-2 receptor antagonist, and we hypothesized that adding tolvaptan to standard diuretic therapy would be more effective in ADHF patients with renal function impairment.

Methods

The Answering question on tolvaptan’s efficacy for patients with acute decompensated heart failure and renal failure (AQUAMARINE) is a multicenter, randomized controlled clinical trial, which will enroll 220 patients from 17 hospitals in Japan. ADHF patients whose estimated glomerular filtration rate is above 15 and below 60 mL/min/1.72 m² will be randomly assigned within 6 h after admission to usual care with furosemide or tolvaptan add-on therapy. Primary endpoint is achieved urine output within 48 h. Secondary endpoints include dyspnea relief measured by 7-points Likert scale, incidence of worsening renal function, dose of furosemide used within 48 h, and changes of brain natriuretic peptide.

Conclusion

This study is the first multicenter study in Japan to evaluate clinical effectiveness of tolvaptan add-on therapy in ADHF patients with renal failure. The results of this study address the treatment strategy of this high-risk population (UMIN Clinical Trial Registry Number: UMIN000007109).     

Peripheral microvascular dysfunction predicts residual risk in coronary artery disease patients on statin therapy

Objective

Although lowering of low-density lipoprotein cholesterol (LDL-C) by statins is essential in treatment of coronary artery disease (CAD) patients, there is considerable residual risk of secondary coronary artery events (CAE). We examined whether microvascular dysfunction (MiD), measured by peripheral artery tonometry (PAT), can predict prognosis of CAD patients previously treated with statins.

Methods

We measured log-transformed reactive hyperemia index (L_RHI) in 213 CAD patients who had already achieved LDL-C <100 by statin therapy. Patients were followed-up for secondary CAE for a median of 2.7 years. Patients were divided into two groups: L_RHI ≥ 0.54 (n = 99) and L_RHI < 0.54 (n = 114).

Results

During follow-up, CAE occurred in 4 (4.0%) patients in the L_RHI ≥ 0.54 group and 18 (15.8%) patients in the L_RHI < 0.54 group (P = 0.006). Cox regression analysis indicated that L_RHI was an independent predictor for CAE even after adjustment by Framingham traditional risk factors (FRF; age, T-C/HDL-C ratio, systolic blood pressure, diabetes, current smoker, and gender) and estimated glomerular filtration rate (eGFR) for secondary CAE (HR 0.79, 95% CI: 0.66–0.95). ROC analysis for CAE prediction showed that the AUC for models including FRF only, FRF + eGFR, and FRF + eGFR + L_RHI were 0.60, 0.71, and 0.77, respectively. Moreover, adding eGFR to FRF only (0.63, P = 0.003) and adding L_RHI to the FRF + eGFR model were associated with significant improvement of net reclassification improvement (0.79, P = 0.007).

Conclusion

MiD measured by non-invasive PAT adds incremental predictive ability to traditional risk factors for prognosis of CAD patients successfully treated with statins.