[Effect of Reconstruction Technique for Metal Artifact Reduction in Computed Tomography by Changing Display Field of View].

We evaluated the effect of orthopedic-metal artifact reduction (O-MAR) for metal artifact in computed tomography with 73 simulated seeds for brachytherapy in different sizes of display field of view (DFOV) obtained by helical scan under the same clinical scan condition. The metal artifacts were analyzed with the Gumbel's method by changing DFOV sizes 80 mm, 160 mm, and 320 mm. Gumbel distribution, scale parameter (γ), and location parameter (ß) of the metal artifacts with O-MAR were compared with that of the metal artifacts with filtered back projection (FBP). In conclusion, it was considered that the effect of metal artifact reduction with O-MAR was influenced by DFOV size in this study. The reduction rates of scale parameter (γ) were 22.3%, 21.3%, and 10.0% in DFOV 80 mm, 160 mm, and 320 mm, respectively. The reduction rates of location parameter (ß) were 27.4%, 23.4 %, and 9.8%. Therefore, the effect of metal artifact reduction with O-MAR showed the tendency of increasing with decreasing DFOV size.

[Increased body mass index in young adults is associated with metabolic syndrome].

OBJECTIVES: Specific Health Examinations and Guidance (Tokutei kenko shinsa/Tokutei hoken shido) are provided for people over 40 years of age to reduce the incidence of metabolic syndrome (MetS). In the present study, we evaluated the importance of weight control in people below 40 years of age. METHODS: Male subjects (n = 877), aged 30 years, without MetS, were examined. Subjects were classified into 3 groups based on body mass index (BMI): non-obese (BMI < 22), pre-obese (22 ≤ BMI < 25), and obese (BMI ≥ 25). Cox proportional hazards regression analysis was performed for each group to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of MetS in individuals in their 40s on the basis of changes in their BMI, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, high-density lipoprotein, and triglyceride levels between 30 and 35 years of age. In addition, subjects were classified into 3 sub-groups based on changes in BMI: stable-decrease (BMI change < 1), slight increase (1 ≤ BMI increase<2), and increase (2 ≤ BMI increase). HRs for the 3 BMI change sub-groups for MetS were calculated for non-obese and pre-obese subjects. RESULTS: There was a significant association between changes in BMI and the incidence of MetS for non-obese individuals in their 40s (HR: 2.80, 95% CI: 1.61-4.88) and pre-obese subjects (HR: 2.00, 95% CI: 1.44-2.77). There were also significant associations between the stable/decrease and increase (HR: 9.39, 95% CI: 1.52-57.70) sub-groups and MetS in the non-obese group, as well as for the slight increase (HR: 2.30, 95% CI: 1.03-5.11) and increase (HR: 10.13, 95% CI: 4.30-23.80) sub-groups in the pre-obese group. CONCLUSIONS: BMI change in young adults is an important risk factor for MetS among individuals in their 40s. Even subjects with a BMI lower than 25 had differences in the risk of developing MetS based on their BMI change sub-group. In the field of occupational health, it will be necessary to promote stable weight control in young adults to reduce the incidence of MetS.

[Investigation of Region of Interest (ROI) for measurement of slice thickness in Computed Tomography (CT)].

We evaluated an appropriate region of interest (ROI) size for the measurement of full width at half maximum (FWHM) in the bead method (0.1 mm and 0.5 mm diameter; lead) and the microdisk method (0.05 mm thickness and 1.0 mm diameter; tungsten) using multislice computed tomography (CT). The FWHM of preset slice thicknesses 0.625 mm, 1.25 mm, 5.0 mm and 7.5 mm were measured by varying helical pitch, location of measurement [center and off-center of scan field of view (SFOV)] and ROI size, and they were compared with the tolerance stated in the Japanese Industrial Standards (JIS). It was conlcuded that the appropriate ROI size was influenced by preset slice thickness in this study. At the center of SFOV, measurements of FWHM were enabled within the tolerance of the JIS with small variations in all preset slice thicknesses if the ROI sizes were set between 0.4 times and equal to the size of the bead or microdisk indicating the maximum CT value in the series of CT images. At the off-center of SFOV, the tendency of increasing FWHM was confirmed, but it was shown that variations of the off-center in thicker slice thickness were larger regardless of helical pitch when the orbital synchronized helical scan technique was not used.

Aberrant splicing of the milk fat globule-EGF factor 8 (MFG-E8) gene in human systemic lupus erythematosus.

Milk fat globule-EGF factor 8 (MFG-E8) promotes the phagocytosis of apoptotic cells by serving as a bridging molecule between apoptotic cells and phagocytes. Many apoptotic cells are left unengulfed in the germinal centers of the spleen of MFG-E8(-/-) mice, which develop a human systemic lupus erythematosus (SLE)-like autoimmune disease. Here, we analyzed the MFG-E8 gene in human SLE patients, and found in two out of 322 female patients a heterozygous intronic mutation, which caused a cryptic exon from intron 6 to be included in the transcript. The cryptic exon contained a premature termination codon, generating a C-terminally truncated MFG-E8 protein. The mutant MFG-E8 was aberrantly glycosylated and sialylated, but bound to phosphatidylserine and enhanced the phagocytosis of apoptotic cells. When intravenously injected into mice, the mutant MFG-E8 was sustained longer in the blood circulation than wild-type MFG-E8. Repeated administrations of the mutant MFG-E8 protein induced the production of autoantibodies, such as anti-cardiolipin and anti-nuclear antibodies, at a lower dose than that required for the wild-type protein. These results suggested that the intronic mutation in the human MFG-E8 gene can lead to the development of SLE.

Exercise-induced delayed onset of left ventricular early relaxation in association with coronary microcirculatory dysfunction in patients with diabetes mellitus.

BACKGROUND: The initiation of ventricular diastole is an energy-dependent phase of cardiac cycle. Delayed onset of left ventricular (LV) relaxation has been proposed to identify myocardial ischemia. Diabetes mellitus (DM) is known to be associated with coronary microangiopathy, but its influence on LV early relaxation is not established. METHODS AND RESULTS: Ninety-two subjects consisting of 70 DM patients without overt cardiac disease and 22 normal controls were evaluated. Using strain rate imaging, time from R-wave on the electrocardiogram to onset of LV relaxation (Tr) was measured at rest and peak exercise. Using myocardial contrast echocardiography, myocardial blood flow (MBF) was measured at rest and peak exercise, enabling MBF reserve. Tr at rest was similar between DM patients and controls, but Tr at peak exercise was significantly longer in DM patients than controls. MBF reserve was significantly reduced in DM patients compared with controls. There was a significant negative correlation between Tr at peak exercise and MBF reserve. In a multivariate analysis, MBF reserve was an independent determinant of Tr at peak exercise. CONCLUSIONS: This study demonstrates that DM patients have exercise-induced delayed onset of LV relaxation in association with impaired coronary microcirculatory function in the absence of coexistent heart disease.

Cardiac Raynaud's phenomenon induced by cold provocation as a predictor of long-term left ventricular dysfunction and remodelling in systemic sclerosis: 7-year follow-up study.

AIMS: The clinical importance of cold-induced reversible myocardial ischaemia, known as cardiac Raynaud's phenomenon (C-Raynaud), has not been established in systemic sclerosis (SSc). This prospective study investigated the impact of C-Raynaud on long-term irreversible left ventricular (LV) functional and morphologic deterioration in SSc. METHODS AND RESULTS: Fifty-one SSc patients with no clinical evidence of cardiac involvement were prospectively followed up for 7.1 +/- 2.2 years. Systolic LV dysfunction was defined as a LV ejection fraction <50%. Left ventricular remodelling was defined as an increase in LV volume during follow-up of more than 20% compared with baseline values. At the initial evaluation, C-Raynaud was found in 15 patients (29.4%). Of these, eight patients had severe C-Raynaud. None of the patients had systolic LV dysfunction. At the final evaluation, five patients had developed systolic LV dysfunction. In four of these five patients, the development of systolic LV dysfunction was associated with LV remodelling. At multivariate analysis, severe C-Raynaud was a strong independent determinant of the development of long-term systolic LV dysfunction. CONCLUSION: This study documents for the first time that severe C-Raynaud is a strong long-term predictor of systolic LV dysfunction in SSc patients. Detection of C-Raynaud is clinically important for identifying SSc patients at high risk of cardiac deterioration at latent stage.

Usefulness of initial histological features for stratifying Sjogren's syndrome responders to mizoribine therapy.

OBJECTIVES: To evaluate the response of patients with SS to mizoribine therapy in relation to histological features of minor salivary glands. METHODS: Forty patients definitely diagnosed as having SS were treated with mizoribine (150 mg/day). Thirty-four untreated patients matched for age, baseline salivary secretion, etc., served as controls. Salivary secretion volume (measured by the Saxon test) and serum IgG level were measured before and after 24 weeks of treatment. Each histological finding (lymphocytic infiltration, acinar atrophy and intralobular fibrosis) was graded at baseline and the therapeutic responses were compared with the grade at 24 weeks in both the groups. RESULTS: There was a significant increase of the salivary secretion volume after treatment with mizoribine as compared with the untreated control group. The effect of mizoribine on salivary secretion was more marked in patients having moderate lymphocytic infiltration and moderate or less severe acinar atrophy and intralobular fibrosis at baseline. CONCLUSIONS: Mizoribine was clinically effective in patients with SS whose minor salivary glands had moderate cell infiltration and were free of intralobular fibrosis. The drug was less effective in patients who presented intralobular fibrosis. Histological evaluation of the minor salivary glands may serve to predict the response of SS patients to mizoribine therapy.

Multiple myeloma with a variant Burkitt-type translocation, t(2;8)(p12;q24), associated with hyperammonemia.

We report an 82-year-old Japanese woman with multiple myeloma (MM). She developed disorientation due to hyperammonemia after melphalan and prednisolone therapy and abruptly died with a rapid clinical course. Karyotypic analysis of bone marrow showed complex abnormalities including a variant Burkitt-type translocation, t(2;8)(p12;q24), but the patient had IgG-lambda type M-proteinemia. Although patients with MM associated with hyperammonemia have been sporadically reported and their prognosis is poor, specific chromosomal abnormalities in the lesion have not been well characterized. It is, therefore, important to accumulate such patients to find a possible relationship between hyperammonemia and chromosomal abnormalities.

Atrophic change of tongue papilla in 44 patients with Sjögren syndrome.

OBJECTIVE: The purpose of this study was to investigate the atrophic change of tongue papilla in Sjögren syndrome (SjS) patients and the correlation with characteristic features of the disease. STUDY DESIGN: Atrophic change of tongue papilla, investigated by a digital microscope, was classified from score 0 (normal) to score 6 (severe) and compared among 44 SjS patients, 20 xerostomia patients, and 20 healthy subjects. In SjS patients, correlation of the atrophic score of tongue papilla with characteristic changes in sialometry, sialography, lip biopsy, and serologic tests was also investigated. RESULTS: The atrophic score of tongue papilla was significantly higher in SjS patients and correlated with the decrease of salivary secretion, the stage on sialography, and the histologic grade of the minor salivary gland. CONCLUSION: Atrophic change of tongue papilla is significant in SjS patients and is correlated with the characteristic features of the disease.

Interleukin 12, interleukin 18, and tumor necrosis factor alpha release by alveolar macrophages: acute and chronic hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is characterized by a granulomatous inflammation and may show various forms of clinical presentation, such as the acute, subacute, and chronic forms. The TH1-associated cytokines interleukin (IL) 12 and IL-18 and tumor necrosis factor alpha (TNF-alpha) may be involved in the pathogenesis of both the acute and chronic forms of HP. OBJECTIVE: To compare the release of IL-12, IL-18, and TNF-alpha from bronchoalveolar lavage (BAL) macrophages in these 2 forms of HP. METHODS: Patients underwent BAL 0 to 6 days after the last antigen exposure. Alveolar macrophages (AMs) from BAL in 6 patients with acute HP, 16 with chronic HP, and 11 controls were cultured for 24 hours. Cytokines in the culture supernatants were measured by enzyme-linked immunosorbent assay. RESULTS: The production of IL-12, IL-18, and TNF-alpha by AMs was increased in patients with both acute and chronic forms in either the absence or presence of lipopolysaccharide compared with controls. The levels of IL-12, IL-18, and TNF-alpha showed no difference between patients with acute and chronic HP. The spontaneous production of IL-12, IL-18, and TNF-alpha did not correlate with the CD4/CD8 ratio in BAL. The spontaneous and lipopolysaccharide-stimulated release of IL-12 showed a positive correlation with the percentage of lymphocytes (r = .470, P = .03; r = .496, P = .02; respectively) in BAL. CONCLUSIONS: This study demonstrates that an increased release of IL-12, IL-18, and TNF-alpha by AMs is associated with both the acute and chronic forms of HP.

Influence of living style and situation on the compliance of taking antihypertensive agents in patients with essential hypertension.

BACKGROUND: As the reason for insufficient control of blood pressure (BP), poor compliance of taking antihypertensive agents is an important issue. In Japan, no prospective study on the compliance of antihypertensive agents has been done. In this study we prospectively investigated the details of the relationship between the compliance of taking antihypertensive agents and living style and situation in hypertensive patients. METHODS: We prospectively examined 121 outpatients with essential hypertension treated with antihypertensive agents for 12 months. Using an oral interview based on the questionnaire sheet, the factors about living style and situations which worsen the compliance were assessed. Also we evaluated the relationship of BP control and season, which was compared between patients with poor compliance and those with good compliance. RESULTS: As for the background of the poor compliance, many factors related to the patients' living style and situation were clarified. On average for 12 months the levels of the compliance and BP showed a significant negative correlation and BP was significantly higher in patients with poor compliance than those with good compliance. However, in the summer season BP did not differ between patients with poor and good compliance, CONCLUSION: Many factors regarding the patients' living style and situation were related to poor compliance. The development of strategy that changes these factors is a future task for improving compliance. This study may also imply that unnecessary antihypertensive agents are prescribed in some patients with poor compliance in the summer season. Determination of the suitable prescription by which to attain optimal individual patients' compliance is important in the treatment of hypertensive patients.

Effects of microbubbles on ultrasound-mediated gene transfer in human prostate cancer PC3 cells: comparison among Levovist, YM454, and MRX-815H.

We compared the enhancement effects of three different echo contrast agents (ECAs); Levovist, YM454, and MRX-815H as artificial microbubbles on ultrasound mediated gene transfection (USMGT) with 1MHz ultrasound at 0.2MPa using a luciferase expression vector in PC3 cells and elucidated the mechanisms of differences of USMGT facilitation by these ECAs. At a concentration of each ECA that induced iso-survival, ECAs with lipid shell (YM454 and MRX-815H) facilitated USMGT higher than those without shell (Levovist), and the order of the ECAs facilitating free radical formation by sonication was; YM454>MRX-815H>Levovist. These results suggested that the lipid shell type ECAs facilitated gene transfer higher than that by the non-shell type ECA.

Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus.

Mouse milk fat globule epidermal growth factor 8 (MFG-E8), which is secreted by a subset of activated macrophages, binds to apoptotic cells by recognizing phosphatidylserine and promotes their engulfment. Many apoptotic cells are left unengulfed in the germinal centers of the spleen in MFG-E8(-/-) mice, and these mice develop an autoimmune disease resembling human systemic lupus erythematosus (hSLE). Here, we report that hMFG-E8 bound to phosphatidylserine and an integrin alpha(v)beta(3) complex. Increasing concentrations of MFG-E8 generated a bell-shaped response curve for the efficiency of phagocytosis. That is, in NIH3T3 and MFG-E8(-/-) thioglycollate-elicited peritoneal macrophages that do not express MFG-E8, hMFG-E8 enhanced engulfment at low concentrations but inhibited it at high concentrations. On the other hand, hMFG-E8 dose-dependently inhibited the engulfment of apoptotic cells by MFG-E8(+/+) thioglycollate-elicited peritoneal macrophages, indicating that an excess of MFG-E8 has an inverse effect on the engulfment of apoptotic cells. To investigate the role of MFG-E8 in human disease, we generated two mAb against MFG-E8 and screened human blood samples for MFG-E8 using an ELISA. We found that some childhood-onset and adult SLE patients carried a significant level of MFG-E8 in their blood samples. These results suggested that the aberrant expression of MFG-E8 is involved in the pathoetiology of some cases of hSLE.

Effects of ultrasound on apoptosis induced by anti-CD20 antibody in CD20-positive B lymphoma cells.

AIM: The present study was conducted to examine the thermal and non-thermal effects of ultrasound on apoptosis induced by anti-CD20 monoclonal antibody (rituximab). MATERIALS AND METHODS: SU-DHL-4 cells, a CD20-positive cell line derived from B cell lymphomas with a BCL2 gene rearrangement, were exposed to continuous 1 MHz ultrasound for therapeutic use under an air- or CO(2)-saturated condition to control cavitation. Early apoptosis (EA) and secondary necrosis (SN) were examined by flow cytometry. Cavitation was determined by detecting the hydroxyl radicals derived from pyrolysis of water molecules using electron paramagnetic resonance-spin trapping. To assess thermal effects, cells were treated in a temperature-controlled water bath. RESULTS: There was a significant additive increase in EA and EA+SN observed in cells treated with rituximab combined with heat at 42 degrees C or non-thermal ultrasound at 0.5 W/cm(2) under an air-saturated condition, where heat or ultrasound induced some cell death. A significant synergistic increase in EA and EA+SN was observed in cells treated with rituximab and ultrasound at 2.5 W/cm(2) under CO(2)-saturated conditions, where inertial cavitations were completely suppressed. No enhancement was observed at a temperature less than 40 degrees C or ultrasound at 0.5 W/cm(2) under CO(2)-saturated conditions. CONCLUSION: These results suggest that the immuno-therapeutic application of ultrasound at relatively high-intensities combined with rituximab thus produces synergistic effects under conditions where the non-thermal and non-cavitational effects are predominant.

Non-invasive quantitation of myocardial fibrosis using combined tissue harmonic imaging and integrated backscatter analysis in dilated cardiomyopathy.

BACKGROUND: Echocardiographic modalities have challenged the myocardial tissue characterization, but this reliability has not reached to the clinical use. This study investigated whether combined tissue harmonic imaging (THI) and integrated backscatter analysis (IB) provide the reliable and quantitative information about myocardial fibrosis in idiopathic dilated cardiomyopathy (DCM) in comparison with myocardial biopsy findings. METHODS: We studied 56 patients with DCM. All patients underwent left ventricular endomyocardial biopsy and IB with fundamental imaging (FI) and THI. RESULTS: In patients with good echocardiographic image quality, excellent correlations between the percentage of area occupied by myocardial fibrosis (% fibrosis) and the mean of integrated backscatter during a cardiac cycle (m-IB) measured with FI or THI were seen, and the correlation was closer with THI compared with FI. While in patients with poor image quality the correlation between m-IB and % fibrosis was only modest with FI, but the correlation was excellent with THI. Four cut-off values of m-IB with THI obtained from receiver operating characteristic curve discriminated between % fibrosis of more and less than 25, 30, 35, and 40% with high sensitivity and specificity. Multivariate analysis revealed that m-IB with THI was an independent predictor for discrimination of the severity of myocardial fibrosis. CONCLUSION: Combined IB and THI are a clinically applicable method and may be an alternative to myocardial biopsy in evaluating quantitatively myocardial fibrosis in DCM.

Impact of metabolic syndrome on brachial-ankle pulse wave velocity in Japanese.

The aim of this study was to determine the effect of metabolic syndrome on brachial-ankle pulse wave velocity (baPWV) by using the new guidelines for diagnosis of this syndrome in Japan. We examined 525 men and women without a history of cardiovascular disease or cancer, and an ankle-brachial index < 0.9. The baPWV was measured using a device (Form PWV/ABI) that simultaneously monitored bilateral brachial and ankle pressure wave forms. Metabolic syndrome was defined as a waist circumference > or = 85 (90) cm in men (women) and two or more of the following risk factors: hypertension, dyslipidemia, and glucose intolerance diagnosed by a 75 g oral glucose tolerance test. The baPWV showed a significant linear relationship with waist circumference, waist-to-hip ratio, body fat, systolic and diastolic blood pressure, triglycerides, fasting glucose, 2-h-postload glucose, fasting insulin, and glycosylated hemoglobin-A1c, after adjusting for sex and age. These factors were also strongly related to fasting insulin levels. When subjects were classified into six groups based on waist circumference and the number of risk factors for metabolic syndrome (0, 1, and > or =2), we found that more risk factors clearly increased the odds ratios for an elevated baPWV in those subjects in the highest quartile of the baPWV distribution in multivariate logistic models. An increase in odds ratio was observed despite a normal waist circumference and may well have been due to increased fasting insulin and blood pressure levels. An increase in the number of risk factors for metabolic syndrome was highly correlated with an increased baPWV, probably due to insulin resistance.