Unveiling axial involvement in psoriatic arthritis: An ancillary analysis of the ASAS-perSpA study.

OBJECTIVE: To determine the clinical profile of axial psoriatic arthritis (PsA) in a worldwide setting. Secondly, to identify factors associated with the development of axial involvement in patients with PsA. METHODS: Data from 3684 patients with axial spondyloarthritis (axSpA) or PsA from the ASAS-perSpA study were analysed. The ASAS-perSpA is a cross-sectional study that recruited consecutive patients with SpA (as diagnosed by their rheumatologist) from 68 centers worldwide and collected patient and disease data. First, 2651 axSpA patients and 367 PsA patients with any history of axial involvement (axPsA) were compared using logistic regression to later identify predictive factors for rheumatologist diagnosis of axPsA. Secondly, 367 axPsA patients were compared with 666 PsA patients lacking axial involvement (peripheral PsA [pPsA]) and the characteristics associated with axial manifestations were explored by logistic regression analysis. RESULTS: Patients with axPsA were older and less frequently males or HLA*B27 positive in comparison with axSpA patients. Additionally, while patients with axPsA had more peripheral manifestations and psoriasis, other extra-musculoskeletal manifestations (IBD and uveitis) were more frequent in those with axSpA. In the multivariable analysis, older age at diagnosis (OR = 1.04), peripheral arthritis (OR = 7.32) and dactylitis (OR = 2.82) were significantly associated with the diagnosis of axPsA. However, uveitis (OR = 0.22), IBD (OR = 0.12), HLA*B27 carriership (OR = 0.26) or sacroiliitis on imaging (OR = 0.5) were inversely associated with axPsA diagnosis as compared to axSpA. Axial involvement in patients with PsA was significantly associated with male gender (OR = 1.68), elevated CRP (OR = 2.87) and the absence of psoriasis (OR = 0.33). CONCLUSION: In this worldwide setting axPsA was defined by rheumatologists as a unique phenotype, with disease features lying between axSpA and pure pPsA.

A case of feline gastrointestinal eosinophilic sclerosing fibroplasia limited to the mesentery.

An entire, female, mixed-breed cat of unknown age was presented with a 6-week history of lethargy, anorexia and vomiting. There was an increase in the number of white blood cells in the blood, including neutrophils and eosinophils; moderate anaemia; ascites; and possible mesenteric peritonitis. Exploratory laparotomy revealed firm, multifocal small nodules in the mesentery. As the nodules were surgically unresectable, they were biopsied. Histologically, the nodules were composed of thin trabeculae of dense collagen fibres mixed with plump fibroblasts and numerous eosinophils, consistent with feline gastrointestinal eosinophilic sclerosing fibroplasia. Bacteria were not detected on histological examination of the nodules and cytology of the ascites. Remission of disease occurred following treatment with prednisolone and ciclosporin A for 22 days and antibiotics for 40 days. After remission, ciclosporin A was administered for 236 days and then discontinued. Eosinophilia also resolved after treatment with ciclosporin A. The cat is still alive and in good condition on day 689. This report describes what may be an atypical case of feline gastrointestinal eosinophilic sclerosing fibroplasia, lacking involvement of the gastrointestinal tract, and was apparently cured by treatment that involved ciclosporin A.

Retrospective analysis of in vivo recovery and clearance during continuous infusion of recombinant factor VIII products: a single-institution study.

BACKGROUND: Continuous infusion (CI) of recombinant FVIII (rFVIII) concentrates has been reported as an effective and safe method to achieve haemostasis during major surgeries or severe bleeding events. For more effective and safer CI, better understanding of in vivo recovery (IVR) and clearance (CL) issues is imperative. OBJECTIVE: We investigated the following factors affecting IVR and CL using univariate and multivariate regression analyses during 47 CIs in 34 patients: rFVIII concentrate type, haemophilia severity, blood type, the presence of hepatitis C virus (HCV) or human immunodeficiency virus (HIV), age and body mass index (BMI). RESULTS: The mean IVR was 1.64 ± 0.49 IU dL-1 per IU kg-1 , and the mean CL during CI was 3.56 ± 1.57 mL h-1 kg-1 . The univariate and multivariate regression analyses showed that the CL of octocog alfa was significantly lower than that of rurioctocog alfa (P = 0.043 and 0.0034, respectively). There was a significant difference in BMI in the univariate and multivariate regression analyses (P = 0.0403 and 0.0376, respectively). CONCLUSIONS: This study indicated that CL during CI was potentially affected by the type of rFVIII concentrate used and BMI.

Phosphorylation of Smad2/3 at the specific linker threonine residue indicates slow-cycling esophageal stem-like cells before re-entry to the cell cycle.

UNLABELLED: The stem cell compartment in the esophageal epithelium is possibly located in the basal layer. We have identified significant expression of Smad2/3, phosphorylated at specific linker threonine residues (pSmad2/3L-Thr), in the epithelial cells of murine stomach and intestine, and have suggested that these cells are epithelial stem cells. In this study, we explore whether pSmad2/3L-Thr could serve as a biomarker for esophageal stem cells. We examined esophageal tissues from normal C57BL/6 mice and those with esophagitis. Double immunofluorescent staining of pSmad2/3L-Thr with Ki67, CDK4, p63, or CK14 was performed. After immunofluorescent staining, we stained the same sections with hematoxylin-eosin and observed these cells under a light microscope. We used the 5-bromo-2-deoxyuridine (BrdU) labeling assay to examine label retention of pSmad2/3L-Thr immunostaining-positive cells. We collected specimens 5, 10, 15 and 20 days after repeated BrdU administrations and observed double immunofluorescent staining of pSmad2/3L-Thr with BrdU. In the esophagus, pSmad2/3L-Thr immunostaining-positive cells were detected in the basal layer. These cells were detected between Ki67 immunostaining-positive cells, but they were not co-localized with Ki67. pSmad2/3L-Thr immunostaining-positive cells showed co-localization with CDK4, p63, and CK14. Under a light microscope, pSmad2/3L-Thr immunostaining-positive cells indicated undifferentiated morphological features. Until 20 days follow-up period, pSmad2/3L-Thr immunostaining-positive cells were co-localized with BrdU. pSmad2/3L-Thr immunostaining-positive cells significantly increased in the regeneration phase of esophagitis mucosae, as compared with control mice (esophagitis vs. CONTROL: 6.889 ± 0.676/cm vs. 4.293 ± 0.659/cm; P < 0.001). We have identified significant expression of pSmad2/3L-Thr in the specific epithelial cells of murine esophagi. We suggest that these cells are slow-cycling epithelial stem-like cells before re-entry to the cell cycle.

A Raman spectroscopic study of the carbon deposition mechanism on Ni/CGO electrodes during CO/CO2 electrolysis.

In situ and ex situ Raman analyses of porous Ni/CGO electrodes reveal differences in the amount, location and type of carbon formed during CO/CO2 electrolysis. The results demonstrate the limitations of optical in situ techniques applied to Solid Oxide Cells (SOCs) operated in electrolysis conditions. Increased carbon deposition close to the electrode-electrolyte interface is likely to be the result of high charge-transfer current in that area. The positive effect of a CGO interlayer on reducing carbon formation on the fuel electrode is demonstrated.

Efficacy and safety of multitarget therapy with mizoribine and tacrolimus for systemic lupus erythematosus with or without active nephritis.

The prognosis of lupus nephritis (LN) has improved since the introduction of immunosuppressant therapies, but the safety and effectiveness of treatments can also be improved. We retrospectively assessed the treatment courses of 12 patients with systemic lupus erythematosus who were treated with glucocorticoid, mizoribine (MZR) and tacrolimus. This regimen was used as initial therapy for active LN in six patients (mean glucocorticoid dose, 66.6 mg); four of these six patients also received pulse methylprednisolone therapy. The starting doses of MZR and tacrolimus were 150 and 3 mg, respectively, and they were titrated as required. Five of six patients achieved complete remission and one achieved partial remission at 6 months. Five patients who completed 12-month analysis achieved complete remission. Another six patients were given the combination regimen for treating minor flares or for steroid sparing. The mean prednisolone doses were reduced from 11.0 mg at baseline to 6.6 mg at 12 months. Six patients experienced minor adverse events, including three minor infections. One patient stopped tacrolimus because of suspected toxicity. All 12 patients were successfully treated, and none experienced severe adverse events. Multitarget therapy combining glucocorticoid, MZR and tacrolimus may have the potential to become a treatment option which is effective and safe.

Association Between 5HT1b Receptor Gene and Methamphetamine Dependence.

Several lines of evidence implicate serotonergic dysfunction in diverse psychiatric disorders including anxiety, depression, and drug abuse. Mice with a knock-out of the 5HT1b receptor gene (HTR1B) displayed increased locomotor response to cocaine and elevated motivation to self-administer cocaine and alcohol. Previous genetic studies showed significant associations of HTR1B with alcohol dependence and substance abuse, but were followed by inconsistent results. We examined a case-control genetic association study of HTR1B with methamphetamine-dependence patients in a Japanese population. The subjects were 231 patients with methamphetamine dependence, 214 of whom had a co-morbidity of methamphetamine psychosis, and 248 age- and sex-matched healthy controls. The three single nucleotide polymorphisms (SNPs), rs130058 (A-165T), rs1228814 (A-700C) and rs1228814 (A+1180G) of HTR1B were genotyped. There was no significant difference in allelic and genotypic distributions of the SNPs between methamphetamine dependence and the control. Genetic associations of HTR1B were tested with several clinical phenotypes of methamphetamine dependence and/or psychosis, such as age at first abuse, duration of latency from the first abuse to onset of psychosis, prognosis of psychosis after therapy, and complication of spontaneous relapse of psychotic state. There was, however, no asscocation between any SNP and the clinical phenotypes. Haplotype analyses showed the three SNPs examined were within linkage disequilibrium, which implied that the three SNPs covered the whole HTR1B, and distribution of estimated haplotype frequency was not different between the groups. The present findings may indicate that HTR1B does not play a major role in individual susceptibility to methamphetamine dependence or development of methamphetamine-induced psychosis.

Computed tomography of the prostate gland in apparently healthy entire dogs.

OBJECTIVES: To describe the computed tomography (CT) features of the prostate gland and determine prostate size using CT in entire male dogs. METHODS: The prostate gland was evaluated in 35 dogs. Morphological features including homogeneity, delineation, shape and intraprostatic differentiation were assessed. Height, length, width, area, volume and attenuation values of the prostate gland were measured. Ratios of prostatic height (rH), length and width to the sixth lumbar vertebral body length were calculated. Relationships of prostatic dimensions with body weight and age were evaluated. RESULTS: The prostate gland was homogeneous in 29 dogs on non-contrast images and 18 of 24 dogs on postcontrast images. Transverse images revealed a semi-oval prostate gland in 29 dogs and irregularly shaped prostate gland in 6 dogs. A prominent median septum was observed in postcontrast images. Significant positive correlations were found between body weight and age and all prostatic dimensions except between age and rH. The mean ± sd values for attenuation were 59·3 ± 9·1 and 121·3 ± 22·7 HU in non-contrast and postcontrast image, respectively. CLINICAL SIGNIFICANCE: CT can be useful for evaluating morphological features of the prostate gland. Prostatic length or width is a better measure than height for computed tomographic estimation of prostate size.

Use of a saline chaser to reduce the dose of contrast material for dynamic CT in cattle.

To investigate the effectiveness of a saline chaser in reducing the required dose of contrast material while carrying out dynamic CT scans in cattle, six clinically normal Holstein calves were subjected to CT scans of the head in a study using a crossover design. The calves were studied as three groups: group A received only contrast material (600 mgI/kg); group B received a 30 per cent lower dose of the same contrast material followed by 50 ml of saline solution; and group C received a 40 per cent lower dose of the same contrast material followed by 50 ml of saline solution. In all the animals, a power injector was used for administering the contrast material, with an injection rate of 4 ml/s and a pressure of 4.7 to 5.7 kg/cm(2). Attenuation values were obtained from the right and left maxillary arteries and dorsal sagittal sinus. There were no significant differences in the maximum enhancement value (MEV) of the maxillary arteries and dorsal sagittal sinus between groups A and B. The MEVs of the maxillary arteries and dorsal sagittal sinus in groups A and B were significantly greater than the MEV in group C (P<0.05). The use of a saline chaser allowed a 30 per cent reduction in the dose of contrast material without decreasing vascular enhancement.

Minimally required heat doses for various tumour sizes in induction heating cancer therapy determined by computer simulation using experimental data.

PURPOSE: Although induction heating cancer therapy (IHCT) using magnetic nanoparticles can be a promising approach to treatment-less multi-nodular cancers, the objective requirement for successful clinical application has not clearly been elucidated. We intended to define objective heat doses suitable for IHCT, especially focusing on the sizes of liver cancer nodules. MATERIALS AND METHODS: Alternating magnetic fields were applied to three human pancreatic cancer cell lines, the intercellular space of those cell pellets were filled with magnetic nanoparticles, and confirmed the cytotoxic effect of IHCT. Subsequently, the temperatures of liver cancer nodules in IHCT were simulated using a computer software program and the required heat dose for various sized tumours were determined. RESULTS: Heating the cancer cells up to 50 degrees C for 10 min was sufficient for complete cell killing and the heat dose of 1.7 W/g(tumour) is required for 10 mm tumour. Larger tumours require a smaller heat dose, e.g. 20 mm and 40 mm tumours require 0.7 W/g(tumour) and 0.6 W/g(tumour), respectively, whereas smaller tumours require large amounts of heat, e.g. 5 mm and 1 mm tumours require 5.1 W/g(tumour) and 105 W/g(tumour), respectively. CONCLUSIONS: Integrating the presently available technologies, including high-quality magnetic nanoparticles (1000 W/g(material)) and effective drug delivery systems (1-2 mg(material)/g(tumour)), treatment of a 10 mm tumour seems possible. Since treatment of smaller tumours less than 5 mm require substantial heat dose, researchers involved in IHCT should target cancer nodules of 10 mm or more, and develop a heat delivery system providing a minimum of 1.7 W/g(tumour).

Effect of a saline chaser for contrast enhancement of computed tomographic angiography in cattle.

Computed tomographic angiography was performed on nine normal Holstein calves in a crossover method to investigate the effect of a saline chaser for enhancement of the maxillary arteries and dorsal sagittal sinus. One group was administered a contrast injection (600 mg iodine/kg at 4 ml/s) followed by 50 ml of a saline chaser at the same rate as the contrast material. The second group was administered a contrast injection without a saline chaser. Addition of the saline chaser to the contrast material resulted in a higher peak attenuation in the maxillary artery (244.45 +/- 36.19 v 202.20 +/- 27.07, P<0.05) and dorsal sagittal sinus (241.2 +/- 31.51 v 198.88 +/- 21.09, P<0.05). These results indicate that a contrast injection followed by saline chaser increased uptake in contrast-enhanced CT.

Lenalidomide induces cell death in an MDS-derived cell line with deletion of chromosome 5q by inhibition of cytokinesis.

Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders characterized by refractory cytopenias and susceptibility to leukemic transformation. On a subset of MDS patients with deletion of the long arm of chromosome 5 (del(5q)), lenalidomide exerts hematological and cytogenetic effects, but the underlying pharmacological mechanisms are not fully understood. In this study, we have investigated the in vitro effects of lenalidomide on an MDS-derived cell line, MDS-L, which carries del(5q) and complex chromosome abnormalities. We found that the growth of MDS-L cells was specifically suppressed mainly by apoptosis, and in addition, multinucleated cells were frequently formed and finally died out in the presence of lenalidomide. Time-lapse microscopic observation and the DNA ploidy analysis revealed that lenalidomide does not affect DNA synthesis but inhibits cytokinesis of MDS-L cells. The gene expression profile showed decreased expression of M phase-related genes such as non-muscle myosin heavy-chain 10, polo-like kinase 1, aurora kinase B, citron kinase and kinesin family member 20A(KIF20A). Interestingly, KIF20A is located at 5q31. These data contribute to the understanding of action mechanisms of lenalidomide on MDS with del(5q) and complex abnormalities.

Clinical experience of using multidetector-row CT for the diagnosis of disorders in cattle.

To determine the clinical usefulness of multidetector-row CT for the diagnosis of disorders in cattle, images were obtained from 27 cattle, which were then subjected to postmortem and histopathological examinations. The cattle were divided into three categories of disorder: neurological (18 cases), skeletal (four cases) and other (five cases). In five cattle, which were suspected to have brain diseases, no abnormalities were identified by either CT or histopathological examination. Eight types of lesions were detected by CT in the cattle with neurological and vestibular disorders. The diseases diagnosed included hydrocephalus (three cases), intracranial arachnoid cysts (three cases), otitis media (five cases), cerebral abscess (one case), meningoencephalocele (one case), porencephaly (one case), bicephalus (one case) and rupture of the spinal cord (one case). Lesions were identified in all the cattle with skeletal disorders, including luxation (two cases), fracture (two cases), spondylosis (one case) and congenital disorders of the skeletal system (one case). Morphological disorders in the eyes (one case), nasal cavity (two cases), frontal sinuses (one case), thyroid glands (two cases), lung fields (two cases) and abdominal organs (two cases) were diagnosed by CT.

Gelatinous transformation of the bone marrow in systemic lupus erythematosus.

Gelatinous transformation of the bone marrow is a rare disease characterised by a focal marrow hypoplasia, fat atrophy and accumulation of extracellular mucopolysaccharides abundant in hyaluronic acid, which is often associated with extreme malnutrition and weight loss. There are only two reports describing its association with systemic lupus erythematosus (SLE). One described underlying diseases in 155 cases of gelatinous transformation of the bone marrow and found one case with clinical diagnosis of SLE, but no clinical details were provided. The other described three SLE patients with gelatinous transformation of the bone marrow; however, two of these were cachectic and one was diagnosed with concomitant tuberculosis. We describe one active SLE patient without other comorbidities whose pancytopaenia was histologically confirmed as gelatinous transformation. The combination of high-dose steroid, intravenous immunoglobulin and mycophenolate mofetil improved the peripheral blood cytopaenia and reversed the bone marrow abnormalities.

Comparison of the diagnosis of intervertebral disc herniation in dogs by CT before and after contrast enhancement of the subarachnoid space.

Eleven miniature dachshunds with a herniated intervertebral disc were examined by CT, first before and then after contrast enhancement of the subarachnoid space. The images were classified into three grades by three veterinarians. In four cases, lesions observed on the scans obtained after contrast enhancement had not been observed on the preliminary scans and in one case a lesion observed on the preliminary scan was not observed on the scan obtained after contrast enhancement. Hemilaminectomies were performed on the basis of the enhanced CT results, and a clinical improvement was observed in each of the dogs. Calcification was detected in all the samples of herniated intervertebral disc material.

An internet-based wearable watch-over system for elderly and disabled utilizing EMG and accelerometer.

An effective way for preventing injuries and diseases among the elderly is to monitor their daily lives. In this regard, we propose the use of a "Hyper Hospital Network", which is an information support system for elderly people and patients. In the current study, we developed a wearable system for monitoring electromyography (EMG) and acceleration using the Hyper Hospital Network plan. The current system is an upgraded version of our previous system for gait analysis (Yoshida et al. [13], Telemedicine and e-Health 13 703-714), and lets us monitor decreases in exercise and the presence of a hemiplegic gait more accurately. To clarify the capabilities and reliability of the system, we performed three experimental evaluations: one to verify the performance of the wearable system, a second to detect a hemiplegic gait, and a third to monitor EMG and accelerations simultaneously. Our system successfully detected a lack of exercise by monitoring the iEMG in healthy volunteers. Moreover, by using EMG and acceleration signals simultaneously, the reliability of the Hampering Index (HI) for detecting hemiplegia walking was improved significantly. The present study provides useful knowledge for the development of a wearable computer designed to monitor the physical conditions of older persons and patients.

The COX-2 inhibitor market withdrawals and prescribing patterns by rheumatologists in patients with gastrointestinal and cardiovascular risk.

OBJECTIVE: To examine effects of the COX-2 inhibitor market withdrawals on NSAID utilization among patients at increased risk of gastrointestinal (GI) and cardiovascular (CV) toxicities. METHODS: A prospective cohort study was conducted using patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) Registry. The study population included rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients prescribed NSAIDs by rheumatologists from 1/1/2003 to 12/31/2005. Three cohorts were defined based on calendar year. The primary outcome assessed whether or not an NSAID gastroprotective strategy was prescribed. Secondary outcomes included rates of COX-2 inhibitor utilization and gastroprotective co-therapy utilization, stratified by the presence of cardiac and GI risk factors. RESULTS: NSAID gastroprotection utilization decreased from 65.1% in 2003 to 47.7% (p<0.001) in 2005. COX-2 inhibitor use decreased from 55.1% to 29.2% (p<0.001), whereas nonselective NSAIDs (nsNSAIDs) use increased from 50.2% to 73.9% (p=<0.01). Among patients with two or more risk factors for NSAID related GI bleeding, gastroprotection decreased from 74.4% in 2003 to 60.9% (p<0.01). For patients with two or more CV risk factors from 2003 to 2005, COX-2 inhibitor utilization decreased significantly, whereas nsNSAID utilization increased significantly. CONCLUSIONS: The COX-2 inhibitor withdrawals resulted in a rapid decline in NSAID gastroprotection prescribed by participating U.S. rheumatologists despite the availability of other gastroprotective options. Channeling toward nsNSAID use was widespread, including among patients at increased CV risk. Longer term follow-up is required to determine the clinical significance of these changes in NSAID prescribing, particularly for NSAID-related GI and CV-related toxicities.

Submicrometer-resolution in situ imaging of the focus pattern of a soft x-ray laser by color center formation in LiF crystal.

We demonstrate high quality, single-shot in situ imaging of the focused Ag x-ray laser (XRL) at 13.9 nm with 700 nm spatial resolution by color center formation in LiF. The flux and intensity for the color center formation in LiF are evaluated from the experimental data. Comparisons with previous reports show that the threshold x-ray flux for the color center formation in LiF for the 13.9 nm, 7 ps Ag XRL is 3 orders of magnitude less than that with the 46.9 nm, 2 ns capillary discharge Ar XRL.

Direct observation of the critical relaxation of polarization clusters in BaTiO3 using a pulsed x-ray laser technique.

We have developed a new method to investigate the relaxation time of the dipole moment in polarization clusters in BaTiO3. Time correlation of speckle intensities was measured by the use of a double pulsed soft x-ray laser. The evolution of the relaxation time of the dipole moment near the Curie temperature (T(C)) was investigated. The maximum relaxation time (approximately 90 ps) is shown to appear at a temperature of 4.5 K above the T(C), being coincident with the one where the maximum polarization takes place. This method is widely applicable to any other critical decay processes at phase transitions.