Relationship between the long-term preventive effect of combined treatment with antiarrhythmic drugs plus angiotensin-converting enzyme inhibitors and circadian variation in the onset of paroxysmal atrial fibrillation

We examined the relationship between the efficacy of combined treatment with antiarrhythmic drugs (AAD) plus enalapril for maintaining sinus rhythm and circadian variation in the onset of paroxysmal AF.Three hundred and forty-four patients with paroxysmal AF (239 men, mean age, 69 ± 11 years) who could be followed up ≥ 12 months were divided into 3 groups on the basis of circadian variation in the onset of AF: a diurnal group (7:00 AM-5:00 PM, n = 57), a nocturnal group (5:00 PM-7:00 AM, n = 108), and a mixed group (onset during both periods, n = 169). The maintenance rate of sinus rhythm during the follow-up period was compared between combined therapy (AAD plus enalapril) and AAD alone.In the diurnal group, the maintenance rates of sinus rhythm at 12, 36, 60, and 90 months were 100%, 100%, 100%, and 100%, respectively, for patients treated with AAD plus enalapril (n = 22) versus 97%, 91%, 89%, and 80% for patients treated with AAD alone (n = 35, P < 0.05). In the nocturnal group, the maintenance rates of sinus rhythm at 12, 36, 60, and 90 months were 96%, 96%, 96%, and 92%, respectively, in patients treated with AAD plus enalapril (n = 24) versus 100%, 100%, 100%, and 100% in patients treated with AAD alone (n = 84, P = NS). In the mixed group, maintenance rates of sinus rhythm at 12, 36, 60, and 90 months were 90%, 71%, 61%, and 57%, respectively, in patients treated with AAD plus enalapril (n = 49) versus 88%, 78%, 68%, and 61% in patients treated with AAD alone (n = 120, P = NS). Our findings suggest that the preventive efficacy of combined therapy with AAD plus enalapril is dependent on the timing of onset of paroxysmal AF, and this regimen seems to be most beneficial for the diurnal type of paroxysmal AF.     

Pentosan reduces osteonecrosis of femoral head in SHRSP

Increased oxidative stress is considered one of the main causes of steroid-induced osteonecrosis of the femoral head (ONFH). The aim of this study was to evaluate the effects of a steroid hormone and pentosan polysulfate sodium (pentosan), a heparin analog, in stroke-prone spontaneously hypertensive rats (SHRSP) as a model of ONFH. One hundred twenty-three 13-week-old male SHRSP/Izm rats were divided into four groups: a control group (group C), pentosan-administered group (group P), steroid-administered group (group S), and group administered pentosan plus steroid (group PS). Methylprednisolone acetate, as the steroid hormone, at a dose of 4 mg (15 mg/kg) was administered at 15 weeks of age. Pentosan at a dose of 3 mg/day/kg was continuously administered intraperitoneally from 13 weeks of age for 4 weeks. Rats were sacrificed at 17 weeks of age, and heart blood and both femora were collected. Triglyceride levels were significantly lower in group PS than in group S, indicating that pentosan improves lipid metabolism. The incidence of histologic ONFH was significantly lower in group P, at 14.8% (10/71 femoral heads), than in group C, at 30.4% (17/56 femoral heads), and significantly lower in group PS, at 40.8% (29/71 femoral heads), than in group S, at 91.3% (42/46 femoral heads), indicating that pentosan markedly inhibits ONFH. Immunohistochemical staining for oxidative stress showed that the stainability was significantly lower in group PS than in group S. Pentosan seems to reduce the incidence of ONFH in SHRSP by improving lipid metabolism and decreasing oxidative stress.     

Effects of 1‐O‐hexyl‐2,3,5‐trimethylhydroquinone on carbon tetrachloride‐induced hepatic cirrhosis in rats

Aim: The present study was undertaken to evaluate the effects of 1‐O‐hexyl‐2,3,5‐trimethylhydroquinone (HTHQ), a synthesized vitamin E derivative, on carbon tetrachloride (CCl₄)‐induced cirrhosis. Methods: Rats were treated with hypodermic injections of CCl₄ twice a week to induce the hepatic cirrhosis, and given drinking water containing HTHQ or solvent. Primary cultures of rat hepatocytes were performed to evaluate the effects of HTHQ on the expression of inducible nitric oxide synthase (iNOS). Results: Masson's staining of rat livers showed fibrosis around pseudo‐lobules in the CCl₄ group, the lesions being reduced in the CCl₄ HTHQ group. Increases in liver tissue hydroxyproline and α₁(I) collagen, α‐smooth muscle actin and iNOS induced by CCl₄, were also markedly diminished by HTHQ. Furthermore, both HTHQ and vitamin E attenuated interleukin‐1β‐induced iNOS protein expression in cultured hepatocytes, the potency of HTHQ being 10‐times higher than that of vitamin E. Conclusion: HTHQ may inhibit development of hepatic cirrhosis in rats, more potently than vitamin E, by inhibiting the iNOS expression in hepatocytes. Because vitamin E has a radical scavenging action, roles of NO and peroxynitrite will be discussed in the effects of HTHQ on the fibrosis.     

Phenotypic change and accumulation of smooth muscle cells in strictures in Crohn’s disease: relevance to local angiotensin II system

Background

Intestinal stricture lesions in Crohn’s disease are characterized as submucosal fibromuscular accumulation. There has been a controversy about whether the fibrogenic cells in stricture lesions in Crohn’s disease originate from a smooth muscle cell or a fibroblast lineage. In the present study, we aimed to elucidate: (1) the origin of the fibrogenic cells in stricture lesions; and (2) the roles of the local angiotensin II system, including mast cell chymase, in stricture formation.

Methods

Methanol-Carnoy’s-fixed colonic tissues, obtained from the stricture sites of 18 patients with Crohn’s disease, were analyzed by immunostaining for vimentin, smooth muscle actin (1A4 and CGA7), angiotensin II type-1 receptor, angiotensin II-converting enzyme, and mast cell tryptase and chymase. As controls, unaffected (normal) portions of 11 colonic tumor specimens were also investigated.

Results

Submucosal fibromuscular accumulation was seen in every stricture lesion. The majority of mesenchymal cells accumulated in the stricture lesions were moderately differentiated intestinal smooth muscle cells [vimentin(+), 1A4(+), and CGA7(+)]. Moreover, occasional intestinal smooth muscle cells in the muscular layers, adjacent to the site of the submucosal fibromuscular response, showed distinct positivity for vimentin, indicating phenotypic modulation toward an immature, or dedifferentiated state. These smooth muscle cells accumulated in the stricture lesions were positive for angiotensin II type-1 receptor. Abundant chymase-positive mast cells were distributed in these lesions.

Conclusions

These results suggest that the proliferation and migration of moderately differentiated intestinal smooth muscle cells from the muscular layers are the major pathologicalmechanisms in stricture formation in Crohn’s disease, and the angiotensin II system is involved in this process.     

Atypical Takayasu arteritis with solitary stenosis in the short segment of right axillary artery

Takayasu arteritis is a rare, idiopathic, and chronic inflammatory large vessel vasculitis, involving mainly the aorta and its major branches. Takayasu arteritis predominantly affects women. The clinical presentation is characterized by an acute phase with constitutional symptoms, followed by a chronic phase in which symptoms relate to stenosis or occlusion of vessels. We here report a rare case of Japanese male patient with a fever of unknown origin, and showed a solitary stenosis in the short segment of right axillary artery.     

Identification of potential serum markers for endometrial cancer using protein expression profiling

Objectives

Screening method of endometrial cancer (EC) has not been established yet. Our study was to explore serum biomarkers of EC patients using surface-enhanced laser desorption and ionization-time-of-flight mass spectrometry (SELDI-TOF MS).

Methods

Serum samples from 65 EC patients and 40 controls were analyzed by SELDI-TOF MS (training set). Single- and multi-variant analyses were performed to compare protein profiles in serum of EC patients and healthy controls. Subsequently, blind test set including 40 EC patients and 40 controls were analyzed for validation.

Results

A panel of four biomarker candidates were selected in training set analysis. These markers could also distinguish stage I patients from controls. Among them, two biomarkers were purified and identified as apolipoprotein A1 and a modified form of apolipoprotein C1. Screening for blind test set using dual-biomarker analysis yielded a sensitivity of 82% and a specificity of 86%.

Conclusions

Involvement of apolipoproteins with EC is first suggested in this study. In addition to possibility of screening method for EC, findings of these new biomarkers might be related with carcinogenesis or predisposition to EC.     

A case of giant esophageal leiomyoma successfully resected by endoscopic submucosal dissection followed by retrieval via laparotomy

A 30-year-old woman with chest discomfort at swallowing and occasional vomiting was referred to our department with a diagnosis of esophageal submucosal tumor. CT visualized a mass 70 mm in diameter in the middle esophagus. Esophagogastroduodenoscopy revealed a pedunculated submucosal tumor, and endoscopic resection was considered. As the size of the tumor was so large, retrieval of the resected specimen via the stomach following incision, laparotomy was planned. En bloc resection by endoscopic submucosal dissection with a Hook-knife was performed. Retrieval of the resected specimen was carried out as planned. The specimen, which was 53×48×43mm in size with a distinct margin, was diagnosed as leiomyoma derived from the muscularis mucosae histologically. Her postprocedural course was uneventful. Endoscopic resection can be chosen when an esophageal submucosal tumor is pedunculated with abundant mobility, making it possible to avoid invasive surgery.     

Long‐term treatment of localized gastric marginal zone B‐cell mucosa associated lymphoid tissue lymphoma including incidence of metachronous gastric cancer

Background and Aim: According to a few recent reports on the long‐term clinical outcome of gastric marginal zone B‐cell mucosa associated lymphoid tissue lymphoma (MALT lymphoma); localized gastric MALT lymphoma generally has a favorable prognosis. However, the risk of metachronous gastric cancer has not been evaluated. In this study, we analyzed long‐term outcomes of localized gastric MALT lymphoma including the incidence of metachronous gastric cancer. Methods: Between April 1996 and May 2008, 60 patients (31 men and 29 women; mean age 58.1 years) with localized gastric MALT lymphoma (stage I and II¹ according to Lugano classification) were analyzed retrospectively. Results: Forty‐eight patients (82.6%) achieved complete remission by eradication therapy. Radiation therapy was conducted on eight patients as second‐line treatment, and all of them achieved remission. The median follow‐up period was 76 months (range, 12–157 months). One patient had local relapse after remission for 5 years and three patients developed early gastric cancer without recurrence of lymphoma (5%). All of the three gastric cancers appeared in the same areas where MALT lymphoma had been eradicated. Conclusion: Eradication therapy and radiation therapy for localized gastric MALT lymphoma have a favorable long‐term outcome, though regular follow‐up endoscopy should be performed for detecting metachronous early gastric cancer.     

The PACIFIC (Prevention of AtherothrombotiC Incidents Following Ischemic Coronary attack) Registry: Rationale and Design of a 2-Year Study in Patients Initially Hospitalised with Acute Coronary Syndrome in Japan

Purpose  

Atherothrombotic disease is a major and increasing health problem in Japan. Effective secondary prevention of atherothrombotic events after acute coronary syndrome (ACS) is required, but clinical evidence regarding the current state of preventive treatment and the rate of subsequent atherothrombotic events after ACS in Japan is limited. Up-to-date Japanese epidemiological real world data are required to construct optimal evidence-based Japanese guidelines for the management of patients with ACS.