Aya Watanabe

Prevalence of atopic dermatitis determined by clinical examination in Japanese adults

Dear Editor, Atopic dermatitis (AD) is an inflammatory skin disease that is characterized by pruritic and eczematous lesions persisting chronically. Studies on the prevalence of AD have produced widely varying figures which may be due to several factors such as subjects’ age, their community and the investigative methodology. There have been numerous studies on the prevalence of AD in children and adolescents, however, there have been few studies on AD in adults. Furthermore, most of these studies were based on hospital patient records or questionnaires. To the best of our knowledge, there has been no study of the prevalence of AD conducted by clinical examination in the general adult Japanese population. The objective of this study was to evaluate the prevalence of AD based on regular health check-ups by dermatologists in Japanese adults. The target population was government officials visiting the Health Service Center of Tokyo University for annual health check-ups in September 2004. Permission was obtained from the Board of the Health Service Center of Tokyo University. The government officials were told the purpose of the study, and those who granted consent participated in this study. AD was diagnosed by experienced dermatologists based on the Japanese Dermatological Association criteria for the disease. The severity of AD was graded as mild, moderate, severe or very severe according to the following criteria: (i) mild, skin involvement of mild eruption only; (ii) moderate, <10% surface area involvement of eruption with severe inflammation (severe eruption); (iii) severe, 710% but <30% skin involvement of severe eruption; and (iv) very severe, >70% of body involvement of severe eruption. The χ test was used to analyze the results, and P < 0.05 was considered statistically significant. A total of 2123 (1220 men and 903 women) officials were examined in this study. The average age was 38.8 ± 10.4 years (men: 39.6 ± 10.5; women: 37.7 ± 10.4) ranging 20–69 years. The prevalence of AD was 6.9% overall, and 9.8%, 8.7%, 4.4% and 2.6%, respectively, for those in their 20s, 30s, 40s and 50s/60s (Table 1). The prevalence of 30s was significantly higher than that of 40s (P < 0.0001). The prevalence of women was higher than that of men overall (9.3% vs 5.1%, P < 0.001), especially in 20s (13.1% vs 5.7%, P < 0.05) and 30s (11.5% 6.9%, P < 0.05). Table 2 depicts the severity of AD. Overall, 76.7%, 18.5%, 3.4% and 1.4% of those afflicted were in the mild, moderate, severe and very severe groups, respectively. There was no severe or very severe AD in those beyond their 40s, nor was there any very severe AD in men. This is the first study of the prevalence of AD determined by clinical examination in the general adult Japanese population. In 1999, Plunkett et al. reported the prevalence of AD based on clinical examination by dermatologists in adults in central Victoria, Australia. A total of 1457 people (670 men and 787 women) whose ages ranged 20–94 years were examined in their study. The prevalence of AD was 6.9% overall, and 5.7% and 8.1%, respectively, for men and women. There was a clear age-related variation: the prevalence was approximately 10%, 8%, 7%, 3%, 2%, respectively, for men in their 20s, 30s, 40s, 50s and 60s, and 22%, 13%, 7%, 7%, 2%, respectively, for women in their 20s, 30s, 40s, 50s and 60s. They classified AD into three categories: mild, moderate and severe. Of those with the disease, 82.8% were classified as being mild, 14.6% moderate, and 2.6% severe. Interestingly, their results and ours suggested the same tendency: (i) the overall prevalence of adult AD was approximately 7%; (ii) the prevalence of women was higher than that of men; (iii) the prevalence decreased with age; and (iv) approximately 80% of AD cases were in the mild group.

CDKL5 controls postsynaptic localization of GluN2B-containing NMDA receptors in the hippocampus and regulates seizure susceptibility

Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5 knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid; however, they displayed significant hyperexcitability to NMDA. In concordance with this result, electrophysiological analysis in the hippocampal CA1 region disclosed an increased ratio of NMDA/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs) and a significantly larger decay time constant of NMDA receptor-mediated EPSCs (NMDA-EPSCs) as well as a stronger inhibition of the NMDA-EPSCs by the GluN2B-selective antagonist ifenprodil in Cdkl5 -/Y mice. Subcellular fractionation of the hippocampus from Cdkl5 -/Y mice revealed a significant increase of GluN2B and SAP102 in the PSD (postsynaptic density)-1T fraction, without changes in the S1 (post-nuclear) fraction or mRNA transcripts, indicating an intracellular distribution shift of these proteins to the PSD. Immunoelectron microscopic analysis of the hippocampal CA1 region further confirmed postsynaptic overaccumulation of GluN2B and SAP102 in Cdkl5 -/Y mice. Furthermore, ifenprodil abrogated the NMDA-induced hyperexcitability in Cdkl5 -/Y mice, suggesting that upregulation of GluN2B accounts for the enhanced seizure susceptibility. These data indicate that CDKL5 plays an important role in controlling postsynaptic localization of the GluN2B-SAP102 complex in the hippocampus and thereby regulates seizure susceptibility, and that aberrant NMDA receptor-mediated synaptic transmission underlies the pathological mechanisms of the CDKL5 loss-of-function.

Juvenile pustular psoriasis associated with steroid withdrawal syndrome due to topical corticosteroid

Dear Editor, A 4-year-old girl was admitted to our hospital due to erythroderma, abdominal pain, anorexia, malaise and fever in July 2003. Her great-grandmother had had psoriasis vulgaris and she herself had been diagnosed with psoriasis vulgaris at the age of 3 years. She had been receiving the strongest topical class of corticosteroid (clobetasol propionate) mixed with the same volume of antibiotic ointment (gentamicin sulfate) for approximately 4 months which had been discontinued 2 days before admission. On clinical examination, she had an obvious moon face, hypertrichosis on the forehead (Fig. 1a) and erythroderma with scales and pustules (Fig. 1b,c). Her body temperature was 39.0°C. Laboratory data showed elevated C reactive protein (2.5 mg/dL), lowered cortisol (1.0 μg/dL) and adrenocorticotropic hormone (ACTH; 6 pg/mL). The corticotropinreleasing factor test disclosed poor response to both ACTH and cortisol. Skin biopsy from the pustules on the lower abdomen (Fig. 1c) revealed subcorneal neutrophils with Kogoj’s spongiform pustules (Fig. 2a). She was diagnosed as pustular psoriasis associated with steroid withdrawal syndrome. She was administered topical vitamin D3 (2 μg/g tacalcitol) and a weak class of corticosteroid (dexamethasone) therapy for pustular psoriasis and there was gradual improvement of the skin lesions. She also received oral hydrocortisone therapy for steroid withdrawal syndrome which was begun at 30 mg/day and tapered until it was discontinued at approximately 1 year (30, 20, 15 and 10 mg each day; 8 mg for a week; 7 mg for 1 week; 6 mg for 2 weeks; 4 mg for 3 months; and 2 mg for 7 months). Thereafter, her skin lesions were generally under good control although they were sometimes

Improvement of endothelial function in parallel with the amelioration of dry cough and dyspnea due to interstitial pneumonia by intravenous cyclophosphamide pulse therapy in patients with systemic sclerosis : a preliminary report of two cases

Intravenous cyclophosphamide pulse therapy (IVCY) exerts its efficacy against interstitial lung disease (ILD) associated with systemic sclerosis (SSc) by restoring vascular injuries as well as aberrant immune activation. We recently experienced two patients with SSc-ILD in whom the values of brachial flow-mediated dilation (FMD) reflected the efficacy of IVCY. We herein report the details of these cases and discuss the potential of FMD to predict and evaluate the effect of IVCY on SSc-ILD.

Effect of add-on aliskiren to type 1 angiotensin receptor blocker therapy on endothelial function and autonomic nervous system in hypertensive patients with ischemic heart disease.

The aim of this study was to evaluate the add‐on effect of aliskiren to valsartan on endothelial‐dependent vasodilation in hypertensive patients with ischemic heart disease (IHD). After 4 weeks of treatment with 80 mg of valsartan, 28 patients were allocated to either continued treatment with valsartan or an add‐on treatment with valsartan plus 150 mg of aliskiren. Aliskiren significantly decreased plasma renin activity, whereas endothelium‐dependent vasodilation measured by flow‐mediated dilation (FMD) did not change. In contrast, heart rate significantly decreased (73.1 ± 9.8 to 66.3 ± 7.0 beats per minute at baseline and 24 weeks, respectively [P = .009]) and the standard deviation of the R‐R intervals (SDNN) significantly increased in the aliskiren group. The add‐on aliskiren to valsartan therapy may not improve endothelial functions, although it significantly reduced resting heart rate via regulation of the autonomic nervous system in hypertensive patients with IHD.

Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory

Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the specific mechanisms of these deficits in the CDKL5 deficiency disorder.

Cancer Transitional Care for Terminally Ill Cancer Patients Can Reduce the Number of Emergency Admissions and Emergency Department Visits

Background: Emergency admissions and emergency department visits (EAs/EDVs) have been used as quality indicators of home care in terminally ill cancer patients. We established a cancer transitional care (CTC) program to monitor and manage terminally ill cancer patients receiving care at home. The purpose of this study was to evaluate the effectiveness of CTC by the frequency of EAs/EDVs. Methods: In a retrospective chart review, we identified 133 patients with cancer admitted to our department, of whom 56 met study eligibility criteria. The CTC consisted of at least 1 or more following components: (1) a 24-hour hotline for general physicians or home care nurses to reach hospital-based physicians, (2) periodic phone calls from an expert hospital-based oncology nurse to home care medical staff, and (3) reports sent to our department from home care medical staff. The primary outcome variable was the frequency of EAs/EDVs. Results: There were 32 EAs/EDVs and 69 planned admissions during the observation period. In the last 30 days of life, 16 patients (28.6%) had 1 EA/EDV and none had multiple EAs/EDVs. Compared with previous studies, our study found a similar or lower frequency of EAs/EDVs. Conclusion: Our findings suggest that the implementation of CTC reduces the number of EAs/EDVs by replacing them with planned admissions. Further prospective studies to evaluate CTC are warranted.

Elevated C-reactive protein levels and enhanced high frequency vasomotion in patients with ischemic heart disease during brachial flow-mediated dilation

Purpose The physiological role of vasomotion, rhythmic oscillations in vascular tone or diameter, and its underlying mechanisms are unknown. We investigated the characteristics of brachial artery vasomotion in patients with ischemic heart disease (IHD). Methods We performed a retrospective study of 37 patients with IHD. Endothelial function was assessed using flow-mediated dilation (FMD), and power spectral analysis of brachial artery diameter oscillations during FMD was performed. Frequency-domain components were calculated by integrating the power spectrums in three frequency bands (in ms2) using the MemCalc (GMS, Tokyo, Japan): very-low frequency (VLF), 0.003–0.04 Hz; low frequency (LF), 0.04–0.15 Hz; and high frequency (HF), 0.15–0.4 Hz. Total spectral power (TP) was calculated as the sum of all frequency bands, and each spectral component was normalized against TP. Results Data revealed that HF/TP closely correlated with FMD (r = −0.33, p = 0.04), whereas VLF/TP and LF/TP did not. We also explored the relationship between elevated C-reactive protein (CRP) levels and vasomotion. HF/TP was significantly increased in subjects with high CRP levels (CRP;>0.08 mg/dL) compared with subjects with low CRP levels (0.052±0.026 versus 0.035±0.022, p<0.05). The HF/TP value closely correlated with CRP (r = 0.24, p = 0.04), whereas the value of FMD did not (r = 0.023, p = 0.84). In addition, elevated CRP levels significantly increased the value of HF/TP after adjustment for FMD and blood pressure (β = 0.33, p<0.05). Conclusion The HF component of brachial artery diameter oscillation during FMD measurement correlated well with FMD and increased in the presence of elevated CRP levels in subjects with IHD.

Presence of desaturated hemoglobin enhances the contribution of blood cells to flow-mediated dilation in subjects with systemic sclerosis.

flow-mediated dilation in subjects with systemic sclerosis Eisuke Amiya , Munenori Takata , Masafumi Watanabe ⁎, Takehiro Takahashi , Yoshihide Asano , Masaru Hatano , Atsuko Ozeki , Aya Watanabe , Shuichi Kawarasaki , Zenshiro Tamaki , Takashi Taniguchi , Yohei Ichimura , Tetsuo Toyama , Ryozo Nagai , Shinichi Sato , Issei Komuro a,d a Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Japan b Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Japan c Jichi Medical School, Japan d Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Japan

Prevalence of myofascial pain syndrome in patients with incurable cancer

BACKGROUND Myofascial pain syndrome (MPS) is a condition that involves skeletal muscles. It is caused by overload or disuse of muscles and is characterized by extreme tenderness in the muscles with taut bands. Treatment for MPS is different from that for cancer-related pain. Cancer patients have many factors that cause restriction of body movement and posture. Although cancer patients appear to demonstrate risk factors for MPS, its prevalence has not been reported in patients with incurable cancer. This study was conducted to investigate the prevalence of MPS in patients with incurable cancer. METHODS A retrospective chart review. The data for patients with incurable cancer who received palliative care at our department between September 2015 and March 2016 were investigated. We examined the prevalence of MPS, which was diagnosed on the basis of the Rivers criteria (RC) and Simons criteria (SC). We also examined the following factors associated with MPS: performance status (PS), use of medical devices, and primary cancer sites. The primary outcome was the prevalence of MPS based on RC. Secondary outcomes included the prevalence of MPS based on SC and the relationship between MPS and either PS or medical devices. RESULTS Thirty-four patients with incurable cancer were identified. MPS based on RC or SC was detected in 10 (29%) and 20 (59%) patients, respectively. Twenty-two of 34 patients who complained of pain, 10 (45%) had MPS based on RC and 20 (90%) had MPS based on SC. Age and central venous port were risk factors for MPS by multivariate analysis. CONCLUSION A very high prevalence of MPS was detected in our study population. MPS should be considered when patients with incurable cancer complain of pain.