Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis

Aim: In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3-positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians. Methods: We investigated 160 consecutive patients with type 1 autoimmune hepatitis (20 males and 140 females; median age, 55 years; range, 16-79 years). Results: Forty-seven patients (29%) had zone III necrosis, and these patients had lower serum levels of albumin and higher serum levels of total bilirubin, aspartate aminotransferaseand alanine aminotransferase. Histologically, zone III necrosis was found more frequently in patients with acute hepatitis than in those with chronic hepatitis. However, there was no difference in the frequency of cirrhosis between patients with and without zone III necrosis. In addition, normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was slightly more frequent in patients with zone III necrosis (95% vs. 88%). Conclusion: In Japanese patients, zone III necrosis may reflect not only acute autoimmune hepatitis, but also acute exacerbation of pre-existing chronic disease. Furthermore, patients with zone III necrosis may respond better to corticosteroid treatment than those without.     

Postexercise blood flow restriction does not enhance muscle hypertrophy induced by multiple‐set high‐load resistance exercise

To test the applicability of postexercise blood flow restriction (PEBFR) in practical training programmes, we investigated whether PEBFR enhances muscle hypertrophy induced by multiple‐set high‐load resistance exercise (RE). Seven men completed an eight‐week RE programme for knee extensor muscles. Employing a within‐subject design, one leg was subjected to RE + PEBFR, whereas contralateral leg to RE only. On each exercise session, participants performed three sets of unilateral knee extension exercise at approximately 70% of their one‐repetition maximum for RE leg first, and then performed three sets for RE + PEBFR leg. Immediately after completion of the third set, the proximal portion of the RE + PEBFR leg was compressed with an air‐pressure cuff for 5 min at a pressure ranging from 100 to 150 mmHg. If participants could perform 10 repetitions for three sets in two consecutive exercise sessions, the work load was increased by 5% at the next exercise session. Muscle thickness and strength of knee extensor muscles were measured before and after the eight‐week training period and after the subsequent eight‐week detraining period. There was a main effect of time but no condition × time interaction or main effect of condition for muscle thickness and strength. Both muscle thickness and strength increased after the training period independent of the condition. This result suggests that PEBFR would not be an effective training method at least in an early phase of adaptation to high‐load resistance exercise.     

A Cross-sectional Survey of Patients with Suspected Diabetic Peripheral Neuropathic Pain in Japan

Objective The burden of diabetic peripheral neuropathic pain (DPNP) is poorly understood. The present study reported on the current status of DPNP in Japan, to improve our understanding of this condition among healthcare providers and inform future clinical research on its prevalence, diagnosis, and management. Methods A cross-sectional, observational study (UMIN000037023) was conducted via a web-based survey. The primary endpoints were the frequency of patients with bilateral foot symptoms, consulting a doctor, understanding DPNP, and reporting problems in daily life, as well as the treatment awareness of patients. Patients Adults ≥20 years old who were registered in the Rakuten Insight Disease Panel and receiving anti-diabetic therapy in Japan were included. Results Bilateral foot pain symptoms were reported by 1,768/7,754 (22.8%) respondents, most commonly intense numbness (13.0%). Of those with symptoms, 55.3% consulted a doctor; the most common reason for not seeking consultation was feeling that symptoms were insufficiently severe to bother their doctor (89.4%). Nearly 60% reported understanding the causes of their symptoms, with diabetes-associated neurologic deficits (58.8%) most commonly identified. About one-quarter reported daily life problems, including an inability to walk for long periods (58.3%) and feeling anxious (58.1%). Treatment awareness was reported by 18.2%; oral medications were commonly recognized (64.6%). Conclusion In Japan, 22.8% of patients with diabetes have bilateral foot pain symptoms; some experience problems in their daily life without understanding the causes of their symptoms. This supports the importance of actions to increase awareness and minimize DPNP-associated impairment of daily life in patients with diabetes.     

Combined coronary artery bypass grafting and abdominal aortic aneurysm repair

The purpose of this paper was to assess the results and feasibility of simultaneous coronary artery bypass grafting and abdominal aortic aneurysm repair. Twenty nine patients with a mean age of 65 years underwent simultaneous coronary artery bypass grafting and abdominal aortic aneurysm repair between June 1990 and March 2002. All patients had significant coronary artery disease and were considered as indicated for coronary artery bypass grafting. This was performed first in 28 patients and simultaneously with abdominal aortic aneurysm repair in one, with a mean number of grafts of 2.5, a mean aortic cross-clamp time of 40 minutes, and a mean bypass time of 115 minutes. Eight straight and 21 bifurcated grafts were employed. The total operating time averaged 400 minutes. The median postoperative hospital stay was 18 days. One patient died of stroke and mediastinitis, for a mortality rate of 3.5%. This experience suggests that combined coronary artery bypass grafting and abdominal aortic aneurysm repair is both safe and effective.     

Involvement of Rho-kinase in prostaglandin F2alpha-stimulated interleukin-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts

We have previously reported that prostaglandin F(2alpha) (PGF(2alpha)) stimulates interleukin-6 (IL-6), a potent bone resorptive agent, through p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether Rho-kinase is implicated in the PGF(2alpha)-stimulated IL-6 synthesis in MC3T3-E1 cells. PGF(2alpha) time-dependently induced the phosphorylation of myosin phosphatase targeting subunit (MYPT-1), a Rho-kinase substrate. Y27632, a specific Rho-kinase inhibitor, significantly reduced the PGF(2alpha)-stimulated IL-6 synthesis as well as the MYPT-1 phosphorylation. Fasudil, another inhibitor of Rho-kinase, suppressed the PGF(2alpha)-stimulated IL-6 synthesis. Y27632 and fasudil failed to affect the PGF(2alpha)-induced phosphorylation of p44/p42 MAP kinase. SB203580 and BIRB0796, potent inhibitors of p38 MAP kinase, suppressed the IL-6 synthesis induced by PGF(2alpha). While SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), failed to reduce the synthesis. Y27632 as well as fasudil attenuated the PGF(2alpha)-induced phosphorylation of p38 MAP kinase. These results strongly suggest that Rho-kinase regulates PGF(2alpha)-stimulated IL-6 synthesis via p38 MAP kinase activation in osteoblasts.     

Anomalous right coronary artery originating from the distal left circumflex artery: single coronary artery with choronic atrial fibrillation

This report describes a patient with a single coronary artery in whom the right coronary artery originated from the distal left circumflex artery. Single coronary artery is a rare congenital anomaly of the coronary circulation which is often associated with other congenital cardiac malformations. This anomaly is thought to be clinically significant especially in patients with atrial fibrillation, although no other associated cardiac anomaly was detected.     

Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407)

Gemcitabine is one of the standard treatments for locally advanced pancreatic cancer. Recent studies on metastatic pancreatic cancer have shown that combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP) prolonged the overall survival compared with gemcitabine alone. To select the most promising chemotherapy, a randomized phase II selection design trial was started in July 2016 to compare between modified FOLFIRINOX and GnP for patients with locally advanced pancreatic cancer. A total of 124 patients will be enrolled from 36 Japanese institutions within 2.5 years. The primary endpoint is the proportion of 1-year overall survival, and secondary endpoints are progression-free survival, distant metastasis-free survival, response rate in patients with target lesions, CA19-9 response, adverse events, treatment-related death, early death, grade 4 non-hematological toxicity, and dose intensity. This trial has been registered with the UMIN Clinical Trials Registry [http://www.umin.ac.jp/ctr/index.htm], and the registration number is UMIN000023143.     

D2‐40‐positive lymphatic vessel invasion is not a poor prognostic factor in stage I lung adenocarcinoma

The present study investigates whether lymphatic vessel invasion (LVI) detected by D2‐40 staining is a prognostic factor for stage I adenocarcinoma of the lung. We retrospectively reviewed 124 patients who underwent complete resection for stage I adenocarcinoma of the lung from January 1983 to June 2003. LVI was microscopically evaluated using D2‐40 immunostaining. The median follow‐up was 71 months. The LVI positive rate was 37%. The 5‐year cancer‐specific survival rates of the D2‐40 positive LVI and negative groups were 88.8% and 84.3%, respectively (P = 0.630). The stage I lung adenocarcinoma patients who were determined to be LVI positive based on D2‐40 immunostaining did not have a significantly poorer prognosis than the LVI negative cases. Thus, lymphatic microinvasion may not be a prognostic indicator in early lung cancer, although advanced LVI does appear to correlate with survival. It is therefore unnecessary to use D2‐40 immunostaining to diagnose LVI in practical settings, and Hematoxylin‐Eosin and Elastica van Gieson staining should continue to be used to predict the prognosis of patients with stage I lung adenocarcinoma.