Dermoscopic features of hidroacanthoma simplex: Usefulness in distinguishing it from Bowen's disease and seborrheic keratosis

Hidroacanthoma simplex (HAS) is a rare benign eccrine adnexal tumor. HAS is sometimes clinically or pathologically misdiagnosed as squamous cell carcinoma in situ (Bowen's disease; BD), seborrheic keratosis (SK) or other adnexal tumor. To date, there has never been a report focusing on dermoscopic features to distinguish HAS from BD and SK. We found the following dermoscopic findings to be characteristic of HAS: fine black dots/globules (75% of cases) and fine scales arranged annularly (100% of cases). In contrast, glomerular vessels, which are typically observed in BD, were not seen in any of the four cases. Cerebriform appearance and milia‐like cysts, which are typically observed in SK, were also not seen in any of the four cases. The existence of “scattered fine black dots/globules” and “fine scales arranged annularly”, and the absence of the glomerular vessels, may contribute to precise diagnosis of HAS. Even though HAS resembles BD or SK clinically, it can be distinguished from these by the characteristic dermoscopic features.     

Role of Sialylglycoconjugate(s) in the Initial Phase of Metastasis of Liver-metastatic RAW117 Lymphoma Cells

To elucidate the early events of blood-borne metastasis under actual blood flow, real-time trafficking of RAW117 large cell lymphoma cells, namely parental RAW117-P and liver-metastatic RAW117-H10 cells, was investigated using positron emission tomography (PET). Both types of cells accumulated in the liver immediately after injection via the portal vein, and were eliminated from the liver time-dependently. The elimination rate of RAW117-H10 cells, however, was slower than that of RAW117-P cells, suggesting that RAW117-H10 cells interact more strongly with hepatic sinusoidal endothelium than the parental cells. This result correlated with the metastatic potential of these cells: RAW117-H10 cells metastasized in the liver to a greater extent than RAW117-P cells after injection via this route. To investigate the role of sialylglycoconjugates in the interaction of RAW117-H10 cells with the hepatic endothelium after injection via the portal vein, the trafficking of RAW117-H10 cells was examined after the cells had been treated with sialidase. The elimination rate of RAW117-H10 cells from liver was observed to be greatly accelerated by sialidase treatment. To elucidate what kind of sialylglycoconjugates is related to this phenomenon, we analyzed the distribution of sialyl Lewis A and sialyl Lewis X antigens of both sublines of RAW117 by using flow cytometry. RAW117-H10 cells were found to express a much higher level of sialyl Lewis A than RAW117-P cells, whereas the amount of sialyl Lewis X did not differ significantly. These findings suggest that some sialylglycoconjugates, perhaps sialyl Lewis A in particular, play an important role in the initial interaction of RAW117-H10 cells with the hepatic endothelium, leading to metastasis.     

Role of sialylglycoconjugate(s) in the initial phase of metastasis of liver-metastatic RAW117 lymphoma cells.

To elucidate the early events of blood-borne metastasis under actual blood flow, real-time trafficking of RAW117 large cell lymphoma cells, namely parental RAW117-P and liver-metastatic RAW117-H10 cells, was investigated using positron emission tomography (PET). Both types of cells accumulated in the liver immediately after injection via the portal vein, and were eliminated from the liver time-dependently. The elimination rate of RAW117-H10 cells, however, was slower than that of RAW117-P cells, suggesting that RAW117-H10 cells interact more strongly with hepatic sinusoidal endothelium than the parental cells. This result correlated with the metastatic potential of these cells: RAW117-H10 cells metastasized in the liver to a greater extent than RAW117-P cells after injection via this route. To investigate the role of sialylglycoconjugates in the interaction of RAW117-H10 cells with the hepatic endothelium after injection via the portal vein, the trafficking of RAW117-H10 cells was examined after the cells had been treated with sialidase. The elimination rate of RAW117-H10 cells from liver was observed to be greatly accelerated by sialidase treatment. To elucidate what kind of sialylglycoconjugates is related to this phenomenon, we analyzed the distribution of sialyl Lewis A and sialyl Lewis X antigens of both sublines of RAW117 by using flow cytometry. RAW117-H10 cells were found to express a much higher level of sialyl Lewis A than RAW117-P cells, whereas the amount of sialyl Lewis X did not differ significantly. These findings suggest that some sialylglycoconjugates, perhaps sialyl Lewis A in particular, play an important role in the initial interaction of RAW117-H10 cells with the hepatic endothelium, leading to metastasis.     

Pharmacodynamic analysis of apremilast in Japanese patients with moderate to severe psoriasis: Results from a phase 2b randomized trial

We evaluated the pharmacodynamic effects of apremilast in 69 patients who were included in biomarker subanalyses of a phase 2b study that demonstrated the long‐term safety and efficacy of apremilast in Japanese adults with moderate to severe psoriasis. The association between cytokine levels and Psoriasis Area and Severity Index (PASI) improvement was evaluated using linear regression and Spearman’s rank correlation coefficient analysis. At baseline, median plasma levels of interleukin (IL)‐17A, IL‐17F and IL‐22 were elevated versus reference values for healthy individuals, whereas tumor necrosis factor‐α levels were close to normal. With apremilast 30 mg b.i.d., there were significant associations between percentage change in PASI score and percentage change in IL‐17A, IL‐17F and IL‐22 levels at week 16. Findings demonstrate that the efficacy of apremilast in psoriasis is associated with inhibition of key cytokines involved in the pathology of psoriasis.     

Anthropometric characteristics and comorbidities in Japanese patients with neurofibromatosis type 1: A single institutional case–control study

Neurofibromatosis type 1 (NF1) is a well‐known genetic disorder characterized by café‐au‐lait spots and neurofibromas, but many other clinical characteristics and associated comorbidities also have been reported. This study aimed to characterize NF1 further by investigating its association with anthropometric characteristics and other diseases. We performed a case–control study of 227 NF1 patients (101 male, 126 female) and a randomly selected age‐ and sex‐matched control group of 681 non‐NF1 patients (303 male, 378 female) who visited our institution in Japan. We examined adult (≥20 years) height and body mass index (BMI), and, in the total sample, allergic diseases (bronchial asthma [BA], atopic dermatitis [AD] and allergic rhinitis) and other respiratory cardiovascular and psychiatric disorders. In adults, the mean BMI was lower in the NF1 group than in the control group, and was significantly statistically different among men (P = 0.0238). In the whole sample, the prevalences of BA (P = 0.0184), AD (P = 0.0144) and valvular heart disease (P = 0.0166) were significantly greater in the NF1 group than in the control group. To date, no similar research on the BMI or the prevalence of allergic disease in NF1 patients has been reported. Our results suggest that NF1 patients tend to have lower BMI and may have alterations in specific metabolic pathways and altered allergic immunity.     

Hypertension in patients on chronic hemodialysis: the role of the renin-angiotensin system

The effects of volume-loading and removal on mean blood pressure were evaluated in patients with high blood pressure and on chronic hemodialysis. Simultaneous measurements of plasma renin activity, plasma angiotensin II and plasma norepinephrine were made. The patients were divided into two groups according to their levels of plasma renin activity. Group 1 (n = 10) had a basal plasma renin activity below 2.5 ng/ml/hr while the level in group 2 (n = 5) exceeded 2.5 ng/ml/hr. The mean blood pressure of the two groups was 105 +/- 5 mmHg and 107 +/- 4 mmHg, respectively. On the day of hemodialysis, saline loading (0.5 ml/kg/min for 20 min) was followed by routine hemodialysis. The mean blood pressure rose to 113 +/- 6 mmHg in group 1. However, the patients in group 2 did not respond to volume loading and hemodialysis. The plasma renin activity, plasma angiotensin II and plasma norepinephrine were not changed by volume loading in both group 1 and 2. Volume removal by hemodialysis caused a reduction in mean blood pressure in group 2 without alteration of vasoactive hormones. In group 1, the mean blood pressure was not reduced by hemodialysis, accompanied by increases in plasma renin activity, plasma angiotensin II, and plasma norepinephrine. In the high renin group, elevated circulating angiotensin II maintained a high blood pressure and in the low renin group, the renin-angiotensin system influenced the prevention of fall in blood pressure after hemodialysis. These results suggest that the renin-angiotensin system plays an important role in the regulation of blood pressure in relation to volume status regardless of whether the plasma renin activity is high or low.     

Sampling variables in examinees--skin site differences in the measurements of bleeding time and self-monitoring of blood glucose

Differences in bleeding time and self-monitoring blood glucose (SMBG) level at various skin sites have been scarcely examined in humans. The within-run variation (n=6) of bleeding time in earlobes (Duke's method) ranged from 1 min to 3 min and 30 sec (mean = 1 min and 40 sec), and in day-to-day variation (n= 8), it ranged from 1 min to 3 min (mean = 1 min and 36 sec). Site difference in bleeding time was speculated. In SMBG, firstly, sequential measurement of blood collected from 10 sites in the left forearm was performed, and secondly, comparative measurements of venous blood and blood from finger tips (1-5th), palm (3 sites), forearm (4 sites) and earlobe (1 site) were sequentially performed within 30 min before and after glucose (Trelan-G, 75g) intake. Glucose levels in blood from the fingertips, palm and forearm were generally higher than that of venous blood, and site differences were observed among fingertips, palm and forearm. It was speculated that bleeding time and capillary blood glucose or SMBG level differ among skin sites.     

The wound/burn guidelines – 2: Guidelines for the diagnosis and treatment for pressure ulcers

The Wound/Burn Guidelines Committee consists of members commissioned by the Board of Directors of the Japanese Dermatological Association (JDA). It held several meetings and evaluations in writing since October 2008, and drafted five guidelines for the diagnosis and treatment including commentaries on wounds in general and the Guidelines for the Diagnosis and Treatment for Pressure Ulcers by taking opinions of the Scientific Committee and Board of Directors of JDA into consideration.     

Amenamevir,a novel helicase–primase inhibitor,for treatment of herpes zoster: A randomized,double‐blind,valaciclovir‐controlled phase 3 study

Amenamevir is a potent helicase–primase inhibitor and a novel class of antiviral agent other than nucleoside compounds, such as aciclovir, valaciclovir and famciclovir. This study is the first randomized, double‐blind, valaciclovir‐controlled phase 3 study to evaluate the efficacy and safety of amenamevir in Japanese patients with herpes zoster when treated within 72 h after onset of rash. A total of 751 patients were randomly assigned to receive either amenamevir 400 mg or 200 mg p.o. once daily or valaciclovir 1000 mg three times daily (daily dose, 3000 mg) for 7 days. The primary efficacy end‐point was the proportion of cessation of new lesion formation by day 4 (“day 4 cessation proportion”). The day 4 cessation proportions for amenamevir 400 and 200 mg and valaciclovir were 81.1% (197/243), 69.6% (172/247) and 75.1% (184/245), respectively. Non‐inferiority of amenamevir 400 mg to valaciclovir was confirmed by a closed testing procedure. Days to cessation of new lesion formation, complete crusting, healing, pain resolution and virus disappearance were evaluated as secondary end‐points. No significant differences were observed in any of the treatment groups. Amenamevir 400 and 200 mg were well tolerated as well as valaciclovir. The proportions of patients who experienced drug‐related adverse events were 10.0% (25/249), 10.7% (27/252) and 12.0% (30/249) with amenamevir 400 and 200 mg and valaciclovir, respectively. In conclusion, amenamevir 400 mg appears to be effective and well tolerated for treatment of herpes zoster in immunocompetent Japanese patients.