Comparison of the Probability of Meeting Up with Premature Contraction during Scanning in 320-area Detector Computed Tomography with That in 64-multidetector CT Coronary Angiography

Background: Because coronary computed tomography angiography (CCTA) by 320-area detector CT (320-ADCT) can be obtained in a short time, the probability of meeting up with premature contraction (PC) during scanning may be lower in 320-ADCT compared to 64-MDCT. The purpose is to compare the probability of meeting up with PC, scanning time, and image quality in patients with PC between the 2 groups (320-ADCT vs 64-MDCT). Methods: We have never rejected any CCTA examination due to arrhythmias. The 320-ADCT was performed in 2424 consecutive patients to include 70 atrial fibrillations (Afibs) and 64-MDCT in 1905 consecutive patients to include 51 Afibs. After exclusion of the patients with Afibs, we studied the probability of meeting up with PC during scanning and we compared the scanning time, image quality, and reconstruction phase for patients with PC between the 2 groups. Results: The probability of meeting up with PC during scanning in 320-ADCT (2.0%) is significantly lower (P<0.0001) than 64-MDCT (5.6%). For patients with PC, scanning time in 320-ADCT (2.9±0.6 s) was significantly shorter (P<0.0001) than 64-MDCT (9.5±1.9 s) and image quality in 320-ADCT (2.9±0.3 points) was significantly higher (P<0.0001) than 64-MDCT (2.2±0.8 points). CCTA was reconstructed in mid-diastolic phase in 93% of patients with PC using the 320-ADCT with arrhythmia rejection system. Conclusion: The scanning time of 320-ADCT was 1/3 in comparison with that of 64-MDCT, and the probability of meeting up with PC during scanning in 320-ADCT was 1/3 in comparison with that in 64-MDCT.     

A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging

Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN)³ as a dendritic cell (DC)-targeting double mucosal adjuvant elicited ovalbumin-specific secretory IgA (S-IgA) antibody (Ab) responses, we examined whether this double adjuvant could induce influenza-specific protective immunity in aged mice. A double adjuvant plus A/Puerto Rico/8/34 (PR8) hemagglutinin (HA) induced increased numbers of CD11b⁺ CD11c⁺ DCs and both CD4⁺ Th1- and Th2-type responses in the nasopharyngeal-associated lymphoreticular tissue, nasal passages and cervical lymph nodes. Further, increased levels of PR8 HA-specific S-IgA Ab responses were detected in the upper respiratory tact (URT) of aged and young adult mice given nasal PR8 HA with this double adjuvant. Thus, when mice were challenged with PR8 virus via the nasal route, both aged and young adult mice given nasal vaccine exhibited complete protection. Further, IgA-deficient mice nasally immunized with a double adjuvant influenza vaccine failed to provide protection against PR8 challenge. These results indicate that a nasal double adjuvant successfully induces PR8 HA-specific IgA Ab responses in both young adult and aged mice, which are essential for the prevention of influenza infection in the murine URT.     

Systematic measurement of lineal energy distributions for proton, He and Si ion beams over a wide energy range using a wall-less tissue equivalent proportional counter

The frequency distributions of the lineal energy, y, of 160 MeV proton, 150 MeV/u helium, and 490 MeV/u silicon ion beams were measured using a wall-less tissue equivalent proportional counter (TEPC) with a site size of 0.72 μm. The measured frequency distributions of y as well as the dose-mean values, y(D), agree with the corresponding data calculated using the microdosimetric function of the particle and heavy ion transport code system PHITS. The values of y(D) increase in the range of LET below ~10 keV μm(-1) because of discrete energy deposition by delta rays, while the relation is reversed above ~10 keV μm(-1) as the amount of energy escaping via delta rays increases. These results indicate that care should be taken with the difference between y(D) and LET when estimating the ionization density that usually relates to relative biological effectiveness (RBE) of energetic heavy ions.     

Differences in Transport Mechanisms of trans-1-Amino-3-[18F]Fluorocyclobutanecarboxylic Acid in Inflammation,Prostate Cancer,and Glioma Cells: Comparison with l-[Methyl-11C]Methionine and 2-Deoxy-2-[18F]Fluoro-d-Glucose

Purpose

We aimed to elucidate trans-1-amino-3-[¹⁸F]fluorocyclobutanecarboxylic acid (anti-[¹⁸F]FACBC) uptake mechanisms in inflammatory and tumor cells, in comparison with those of l-[methyl-¹¹C]methionine ([¹¹C]Met) and 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG).

Procedures

Using carbon-14-labeled tracers, in vitro time-course, pH dependence, and competitive inhibition uptake experiments were performed in rat inflammatory (T cells, B cells, granulocytes, macrophages), prostate cancer (MLLB2), and glioma (C6) cells.

Results

Anti-[¹⁴C]FACBC uptake ratios of T/B cells to tumor cells were comparable, while those of granulocytes/macrophages to tumor cells were lower than those for [¹⁴C]FDG. Over half of anti-[¹⁴C]FACBC uptake by T/B and tumor cells was mediated by Na⁺-dependent amino acid transporters (system ASC), whereas most [¹⁴C]Met transport in all cells was mediated by Na⁺-independent carriers (system L).

Conclusions

The low anti-[¹⁸F]FACBC accumulation in granulocytes/macrophages may be advantageous in discriminating inflamed regions from tumors. The significant anti-[¹⁸F]FACBC uptake in T/B cells may cause false-positives in some cancer patients who undergo FACBC-positron emission tomography (PET).     

Serum pulmonary and activation-regulated chemokine/CCL18 levels in patients with systemic sclerosis: a sensitive indicator of active pulmonary fibrosis

OBJECTIVE: To clarify the clinical significance of serum levels of pulmonary and activation-regulated chemokine (PARC) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc) and to compare PARC levels with KL-6 antigen or surfactant protein D (SP-D) levels. METHODS: Serum PARC levels were determined by enzyme-linked immunosorbent assay in 123 SSc patients. In a retrospective longitudinal study, correlation of serum PARC levels with the activity of PF was assessed in 21 SSc patients with active PF. RESULTS: PARC levels at the first visit were higher in patients with SSc than in patients with systemic lupus erythematosus (SLE) or healthy controls. Increased serum PARC levels were associated with involvement of PF, decreased diffusing capacity for carbon monoxide, and decreased vital capacity in SSc patients. In the longitudinal study, serum PARC levels were significantly decreased in SSc patients with inactive PF compared with those with active PF. CONCLUSION: Elevated serum PARC levels correlated with PF and more sensitively reflected the PF activity than did serum KL-6 or SP-D levels in SSc. Serum PARC levels may be a useful new serum marker for active PF in SSc.     

Histiocytic sarcoma of the spleen: case report of asymptomatic onset of thrombocytopenia and complex imaging features

Histiocytic sarcoma of the spleen, in which the malignant cells display morphologic and immunophenotypic features similar to those of mature tissue histiocytes, is a rare but potentially lethal condition that can remain asymptomatic or only mildly symptomatic for a long period of time. We studied a case of histiocytic sarcoma of the spleen in an 82-year-old woman with prolonged chronic thrombocytopenia that was non-responsive to steroid therapy. Ultrasonography, computed tomography, and magnetic resonance imaging showed a characteristically enlarged spleen and liver. Palliative irradiation therapy was clinically effective; however, disease progression proved lethal. Autopsy revealed the proliferation of tumor cells within the splenic sinus and the liver sinusoids, which displayed extreme hemophagocytosis and strong expression of the histiocytic markers CD68 (KP1 and PG-M1) and CD163. The postmortem diagnosis showed histiocytic sarcoma of the spleen with liver infiltration. This and previous reports indicate that early detection (facilitated by imaging and clinical features) and management may improve patient prognosis and survival. Histiocytic sarcoma of the spleen should be considered as a differential diagnosis in therapeutically unresponsive patients with chronic thrombocytopenia.     

Left ventricular endomyocardial biopsy findings in patients with essential hypertension and hypertrophic cardiomyopathy with special reference to the incidence of bizarre myocardial hypertrophy with disorganization and biopsy score

Summary To investigate whether bizarre myocardial hypertrophy with disorganization (BMHD) is characteristic of hypertrophic cardiomyopathy (HCM), the histopathology of the biopsied left ventricular myocardium in 18 patients with essential hypertension (HT) and 14 patients with HCM was studied. A biopsy score was devised for a more quantitative evaluation of the BMHD and a comparative study on the biopsy score of the left ventricular biopsied specimen was also performed. The patients with HT were judged to be in stages I or II of the WHO criteria and had a history of hypertension of more than 5 years. The BMHD was defined as myocardial cells showing hypertrophy, disorganization, and bizarre nuclei. Disorganization of myocardial cells was distinguished both by the terminology and histopathological characteristics from disarrangement of myocardial cells. The biopsy score employed four factors and was determined according to the following formula: Biopsy score = hypertrophy of myocardial cells + (disorganization of myocardial cells) ×2+ bizarre nuclei + whorling of muscle bundles. Both the hypertrophy and the disorganization of myocardial cells were regarded as essential conditions indicating the presence of BMHD. The BMHD was found in 2 of 18 patients with HT (11%) and in 10 of 14 patients with HCM (71%) in the left ventricular biopsied specimens (P<0.005). However, disarrangement of myocardial cells was found in 13 of 18 HT patients (72%) and in 10 of 14 HCM patients (71%) in the left ventricular biopsied specimens, showing no difference between the two groups. The biopsy score in HCM patients was larger than that found in HT patients. It was concluded that BMHD is highly specific (89%) for HCM but that disarrangement of myocardial cells is not specific or diagnostic for HCM. The biopsy score is, therefore, useful for diagnosing HCM histologically and for distinguishing HCM from HT.     

Clinical characteristics of patients with not well-controlled severe asthma in Japan: Analysis of the Keio Severe Asthma Research Program in Japanese population (KEIO-SARP) registry

BackgroundMultiple phenotypes exist within the classification of severe asthma. However, characteristics of patients with not well-controlled severe asthma have not been well identified.MethodsJapanese patients with asthma (age ≥ 20 years) were enrolled at the Keio University Hospital and its affiliated hospitals in this observational study (Keio Severe Asthma Research Program). Among them, patients with severe asthma (those undergoing Global Initiative for Asthma [GINA] 2018 step 4 or 5 treatment) were included in this analysis and investigated clinical characteristics based on asthma control status.ResultsOf the 154 patients (men, 46.8%; age, 60.1 ± 14.9 years), 87 (56.5%) had not well-controlled (partly controlled and uncontrolled) asthma (GINA step 4, 42 patients; step 5, 45 patients). Overall, there were no significant differences in clinical characteristics between patients with well-controlled and not well-controlled asthma. However, cluster analysis revealed that distinct 5 clusters (cluster 1, well-controlled; cluster 2, eosinophilic; cluster 3, non–type 2 inflammation; cluster 4, high periostin; and cluster 5, late-onset type 2 inflammation), and clusters 2–5 were not well-controlled. Among them, cluster 3 was characterized by low eosinophil counts, low periostin levels, and less frequent olfactory disturbance, and this cluster had the worst asthma control.ConclusionsJapanese patients with severe asthma were divided into well-controlled and not-well controlled asthma, and we confirmed heterogeneity of not well-controlled severe asthma. These patients, especially non-type 2 phenotype, require a further therapeutic approach. (University Hospital Medical Information Network Clinical Trials Registry, UMIN000002980)     

Effect of pilsicainide on atrial electrophysiologic properties in the canine rapid atrial stimulation model.

The heterogeneous process of atrial electrical remodeling (AER) in the canine rapid atrial stimulation model has been previously reported although it has been reported that a sodium channel blocker might suppress the shortening of the atrial effective refractory period (AERP), its effect on long-term electrical remodeling is unknown. In the present study, the effect of pilsicainide on AER was evaluated. The right atrial appendage (RAA) was paced at 400 beats/min for 2 weeks. In the RAA, Bachmann's bundle (BB), the right atrium near the inferior vena cava (IVC) and in the left atrium (LA), AERP, AERP dispersion (AERPd) and the inducibility of atrial fibrillation (AF) were evaluated at several time points of the pacing phase and the recovery phase (1 week). The same protocol was performed during the administration of pilsicainide (4.5 mg/kg per day) and the parameters were compared with the controls. In the control dogs, the AERP was significantly shortened by rapid pacing at all atrial sites studied and the AERP shortening (DeltaAERP) was larger at the RAA and LA sites (p<0.03). However, pilsicainide decreased these DeltaAERPs at all 4 atrial sites. AERPd was increased during the pacing phase whereas it was decreased during the recovery phase in the control dogs. In contrast, this pacing-induced AERPd was attenuated by the administration of pilsicainide. The AF inducibility was highest at the LA site in both groups, and the inducibility was lower in the pilsicainide group than the control group at all atrial sites. During the rapid pacing phase, the ventricular heart rate was significantly lower in the pilsicainide group than the control because of intra-atrial conduction block. In a canine rapid right atrial stimulation model, pilsicainide suppressed the shortening of the AERP at all atrial sites, possibly through the improvement of the hemodynamics as well as the action of the Na - Ca exchanger.