Familial clustering of hypereosinophilic diseases treated with mepolizumab: a case report from Japan.

Summary: We describe a female diagnosed with non-allergic asthma. On March 24, 2016, examination of the skin-biopsy specimen revealed dense eosinophilic infiltration, and the Fip-1-like 1-platelet-derived growth factor receptor a fusion gene in peripheral blood mononuclear cells was negative. She was diagnosed with idiopathic hypereosinophilic syndrome. She was treated with intravenous methylprednisolone (MPSL), and subsequent oral MPSL. Then, she started to receive a monthly mepolizumab in June 2016, and successfully withdrew from daily use of oral MPSL. The patient has a mother diagnosed with non-allergic asthma. In February 2005, she was diagnosed with eosinophilic granulomatosis with polyangitis because of elevated antineutrophil myeloperoxidase antibodies, and the skin-biopsy specimen findings. She started to receive a monthly mepolizumab in June 2016. Corticosteroid therapy was successfully withdrawn. To our knowledge, this is the first case report suggesting mepolizumab may be a useful treatment for familial clustering of hypereosinophilic diseases.

Long-term treatment with anti-interleukin 5 antibodies in a patient with chronic eosinophilic pneumonia

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A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional expression.

Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health-related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome-wide association study (GWAS) on coping behaviors in 14088 participants aged 35 to 69 years as part of the Japan Multi-Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving and disengagement) were measured and analyzed. A GWAS analysis was performed using a mixed linear model adjusted for study area, age and sex. Variants with suggestive significance in the discovery phase (N = 6403) were further examined in the replication phase (N = 7685). We then combined variant-level association evidence into gene-level evidence using a gene-based analysis. The results showed a significant genetic contribution to emotional expression and disengagement, with an estimation that the 19.5% and 6.6% variance in the liability-scale was explained by common variants. In the discovery phase, 12 variants met suggestive significance (P < 1 × 10-6 ) for association with the coping behaviors and perceived stress. However, none of these associations were confirmed in the replication stage. In gene-based analysis, FBXO45, a gene with regulatory roles in synapse maturation, was significantly associated with emotional expression after multiple corrections (P < 3.1 × 10-6 ). In conclusion, our results showed the existence of up to 20% genetic contribution to coping behaviors. Moreover, our gene-based analysis using GWAS data suggests that genetic variations in FBXO45 are associated with emotional expression.

Spectral interferometric optical coherence tomography with nonlinear beta-barium borate time gating.

A high-speed, all optical coherence tomography system was designed and constructed. This tomography system employs spectral interferometry and optical Fourier transformation to reduce the number of mechanical scanning dimensions required for multidimensional profilometry. The system also employs a time gate comprising a beta -barium borate crystal driven by a femtosecond laser pulse to improve measurement time. This system has 43-mum depth resolution and 150-fs temporal resolution and is capable of taking 1000 cross-sectional image frames per second.

Birefringence imaging of human skin by polarization-sensitive spectral interferometric optical coherence tomography.

We have developed a spectral interferometric optical coherence tomography (OCT) system with polarization sensitivity that is able to measure a two-dimensional tomographic image by means of one-dimensional mechanical scanning. Our system, which has an axial resolution of 32 mum , calculates the distribution of each element of the Müller matrix of a measured object from 16 OCT images. The OCT system successfully reveals the birefringent nature of human skin tissue.

Phase-resolved correlation and its application to analysis of low-coherence interferograms.

A new signal-processing technique is proposed that involves a phase-resolved correlation method that one can use to determine the phase distribution of low-coherence interferograms. This method improves the sensitivity and resolution of low-coherence interferometers. The depth structure of an aluminum oxide-coated aluminum mirror was determined by use of a low-coherence interferometer with this method. Three signal peaks were successfully extracted from a noisy interferogram.

Effects of dynamic cardiomyoplasty on left ventricular systolic and diastolic performance in an acute canine model.

Although dynamic cardiomyoplasty (DCMP) is currently being evaluated as an alternative to end-stage congestive heart failure, the overall results of DCMP are variable and inconclusive. We evaluated the effect of classic DCMP on systolic and diastolic cardiac function in normal heart using reliable indicators which minimize the influences of load conditions. Six experimental dogs were evaluated with the acute nonpreconditioning model. The slope of the linear preload recruitable stroke work relationship (Mw) showed a significant increase with latissimus dorsi muscle (LDM) stimulation (postwrap non-stimulation 59.1+/-6.3, postwrap stimulation 98.6+/-9.7 erg cm(-3) x 10(3); P < 0.01), and the x-intercept (V0) was unchanged; these were utilized as the indicators of left ventricular systolic function. The constant of pressure decay (tau) increased after LDM wrap (prewrap 45.8+/-6.0, postwrap nonstimulation 69.3+/-10.3, postwrap stimulation 72.3+/-13.9 ms; P < 0.05), and the peak filling rate was unchanged after LDM wrap, which were utilized as the indicators of diastolic function. We concluded that classic dynamic cardiomyoplasty is effective in assisting systolic cardiac function, but may to some degree have a detrimental effect on the diastolic cardiac function.

Effects of free latissimus dorsi dynamic cardiomyoplasty on left ventricular function.

In their experimental approach to dynamic cardiomyoplasty (DCMP), the authors hypothesized that a wrapping method using the proximal part of a free latissimus dorsi muscle (LDM) graft might augment ventricular contractility more than the classic Carpentier's wrapping method. The authors divided 12 mongrel dogs into a pedicled LDM graft group (Group 1, n = 6) and a free LDM graft group (Group 2, n = 6) to evaluate the properties of the different wrapping methods. To evaluate the effect of DCMP on left ventricular systolic and diastolic function, the authors used precise indicators that minimize the influences of load conditions. The slope of the linear preload recruitable stroke work relationship (Mw) and an X-intercept (Vo) were utilized as the indicator of left ventricular systolic function. The constants of pressure decay (tau) and peak filling rate (PFR) were measured to determine diastolic function. All experimental animals were evaluated with the acute, non preconditioning model. Mw was significantly increased with LDM stimulation in both groups (postwrap non stimulation 59.1 +/- 6.3; postwrap stimulation 98.6 +/- 9.7 erg.cm-3. 10(3); p < 0.01 in Group 1, postwrap non stimulation 66 +/- 6.7; postwrap stimulation 155 +/- 15.7 erg.cm-3.10(3), p < 0.001 in Group 2). Stimulated free LDM grafts significantly increased the Mw in comparison to pedicled grafts (p = 0.011). Vo was unchanged in both groups and there was no significant difference between the two groups. Tau increased after LDM wrap in both groups (p < 0.05), but there was no difference between the two groups (tau; prewrap 45.8 +/- 6.0; postwrap non stimulation 69.3 +/- 10.3; postwrap stimulation 72.3 +/- 13.9 msec in Group 1, prewrap 50.0 +/- 6.0; post wrap non stimulation 61.8 +/- 5.0; post wrap stimulation in 64.3 +/- 4.7 msec in Group 2). Peak filling rate was unchanged after LDM wrap in both groups. Free LDM grafts significantly increased left ventricular systolic function compared to the pedicled LDM. Although myocardial relaxation was impaired after LDM wrap in both groups, there was no difference between the two groups. The authors' results emphasize the explicit benefit of utilization of a free LDM graft in respect to left ventricular systolic function; the free LDM grafts have no gross detrimental effect on diastolic function when compared with a pedicle graft in the acute model.

[Successful aorto-coronary bypass grafting and concomitant left ventricular myotomy-myectomy in a patient with coronary artery disease associated with hypertrophic obstructive cardiomyopathy].

A 65-year-old man complained chest oppression at rest and dizziness. Echocardiography showed subaortic stenosis with outflow gradient of 100 mmHg, although interventricular septal thickness was only 12 mm and left ventricular posterior wall thickness was 11 mm, and mild mitral regurgitation. Selective coronary angiography demonstrated 90% stenosis in left main truncus, 50% stenosis in first diagonal branch, and hypoplastic right coronary artery. Emergent coronary artery revasculization concomitant with left ventricular myotomy myectomy was performed. Immediately after weaning off the cardiopulmonary pump, IABP was employed for cardiac assistance, because of residual left ventricular outflow pressure gradient, which was provoked by cathecholamine and amyl nitrite. He was discharged in 1 month in NYHA class I. Echocardiography 3 months after operation showed no residual outflow pressure gradient, no systolic anterior motion of mitral anterior leaflet, and mild approximately mitral regurgitation. Careful operative management, including myocardial protection and avoiding perforation of ventricular septum and postoperative medical care are mandatory to this group of patients. This case is the first successful coronary artery bypass grafting and concomitant left ventricular myotomy-myectomy reported in Japan.

Massive fetomaternal hemorrhage.

We evaluated the potential prognostic factors for fetomaternal hemorrhage (FMH). Sinusoidal heart rate pattern and decrease in fetal movement are considered important signs of FMH. However these findings were detected in only two of six cases of FMH and were thought to be late signs of FMH. Fetal hemoglobin levels in the maternal circulation for infants born alive following FMH were less than 5%. Our findings suggest that this amount of blood loss could cause fetal death.

Cutaneous sarcoidosis showing multiple papular eruptions with keratotic plugs.

A 26-year-old woman developed 249 discrete papules on her lower extremities. Twenty-three of them had keratotic plugs. Histologic examination demonstrated granulomatous foci consisting of epithelioid cells and a epidermal invagination which was disrupted at the base and lateral sites. This invagination was considered to represent transepithelial elimination.

[Percutaneous ethanol injection of parathyroid adenoma under US guidance].

A patient with post-operative recurrent parathyroid adenoma was treated with percutaneous injection of absolute ethanol under ultrasonographic guidance. Serum calcium and PTH level were both successfully normalized, while recurrent nerve palsy was encountered as side effect. Six months later, she was suffered from hyperparathyroidism again, because of local tumor recurrence. Her recurrent nerve palsy was cured at that time. This technic could be a simple and non-invasive alternative for the conventional surgical procedure, but the indication for larger adenomas like this case should be carefully considered.