Development of Tolerance to Inhibitory Effect of Ethanol on Endothelium-dependent Vascular Relaxation in Ethanol-fed Rats

Rats were maintained on liquid diets containing ethanol (35% of total calories) or an equicaloric volume of sucrose instead of ethanol for 10 wk. Vascular strips of isolated rat aortas were mounted in organ chambers to record isometric tension. Ethanol in vitro inhibited the endothelium-dependent relaxation responses to acetylcholine and ATP in both pair-fed control and ethanol-fed rats. The inhibitory effect of ethanol was greater in the pair-fed rats. In addition, the magnitudes of these relaxation responses in the absence of ethanol in vitro in pair-fed rats were similar to those in the presence of ethanol in ethanol-fed rats. In the absence of ethanol in vitro, the relaxations in response to acetylcholine and ATP in the ethanol-fed rats were greater than in the pair-fed rats. These results suggest that chronic ethanol consumption can induce tolerance to ethanol-induced inhibition of endothelium-dependent relaxation responses to acetylcholine and ATP, and that the relaxations can become adapted to the presence of plasma levels of ethanol, which may inhibit the relaxation in vivo. The augmented relaxation in the ethanol-fed rats may result from the mechanism causing tolerance to the inhibitory effect of ethanol.     

Vascular surgery using argatroban in a patient with a history of heparin-induced thrombocytopenia.

For patients with a history of heparin-induced thrombocytopenia (HIT) who undergo cardiac or vascular surgery, the optimal anticoagulation substitute for heparin has yet to be established. Recombinant hirudin has been recommended; however, this agent is unsuitable for patients with renal dysfunction. Argatroban was used in the present patient who had a history of HIT and renal dysfunction and required peripheral vascular surgery. Argatroban was easy to monitor and control, regardless of renal function, and has advantages over other anticoagulants for such patients.     

Superb microvascular imaging (SMI) findings of splenic artery pseudoaneurysm: a report of two cases

Splenic artery pseudoaneurysm (SAPA) is a relatively infrequently encountered but clinically important vascular change, because it carries a high risk of rupture that warrants prompt treatment regardless of its size. Thus, sufficient knowledge is indispensable when seeing chronic pancreatitis patients or post-traumatic patients. Here, we report two such cases. The first case was a 52-year-old woman known to have chronic pancreatitis who presented with hematemesis and hemodynamic instability in which X-ray computed tomography (CT) and color Doppler sonography (CDS) had difficulty visualizing slow blood flow in SAPA, but superb microvascular imaging (SMI) clearly demonstrated the slow blood flow in SAPA, prompting our therapeutic decision to perform rapid embolization. The second case was a 51-year-old woman with post-traumatic SAPA in which 3D SMI enabled us to understand more clearly the topographic relationship between multiple SAPAs as compared with conventional US, leading to a decision to provide immediate surgical treatment. SMI was thought to provide a new insight into the US diagnosis of SAPA. When examining patients suspected of having a SAPA, SMI is an indispensable diagnostic tool at present.     

Sonographic findings in two cases of lymphangioma of the mesocolon in adults

Lymphangioma of the mesocolon is very rare. We report two cases of surgically resected and histologically proven mesocolic lymphangioma in adults. In both cases, ultrasound revealed a large cystic mass with multiple thin septa in the lower abdomen. A peculiar finding was the large craniocaudal sliding movement of the mass synchronized with the patient's respiration, which was a clue to the diagnosis of mesenteric lymphangioma. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46 :78–81, 2018;     

Type 1 Autoimmune Pancreatitis Extending along the Main Pancreatic Duct: IgG4-related Pancreatic Periductitis

We herein report a unique form of autoimmune pancreatitis (AIP) spreading along the main pancreatic duct (MPD). A 70-year-old man was referred for a small lesion at the pancreatic neck, accompanying an adjacent cyst and dilated upstream MPD. Four years earlier, health checkup images had shown a pancreatic cyst but no mass lesion. Endoscopic ultrasonography showed a contrast-enhanced, tumorous lesion, mainly occupying the MPD. With a preoperative diagnosis of ductal neoplasms mainly spreading in the MPD, Whipple''s resection was performed. The resected specimens showed MPD periductitis with IgG4-related pathology, indicating type 1 AIP. Clinicians should practice caution concerning the various AIP forms.     

Clinical effects of nitrendipine on variant angina pectoris

The clinical effects of nitrendipine, a new calcium antagonist, were investigated in a single-blind test on 21 patients with variant angina pectoris. The efficacy of the drug was evaluated on the basis of frequency of anginal attacks and Holter electrocardiographic findings during different treatment periods at doses of 10 mg once a day (period I) and 20 mg once a day (period II). The number of anginal attacks decreased significantly from a pretreatment level of 2.1 +/- 0.3 per day to 0.7 +/- 0.2 per day in treatment period I and 0.3 +/- 0.1 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with the observation period before treatment (p less than 0.01, p less than 0.001, respectively). In 20 patients with continuous ECG monitoring, the frequency of ST-segment elevation was 4.5 +/- 1.0 per day during the pretreatment period; it decreased significantly to 0.9 +/- 0.6 per day in treatment period I and 0.5 +/- 0.3 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The duration and the maximum magnitude of ST-segment elevation also improved significantly in both treatment periods. These results demonstrate the efficacy of nitrendipine in the treatment of variant angina at a single daily dose of 10 mg.     

Association of <Emphasis Type="Italic">SLC22A4/5</Emphasis> Polymorphisms with Steroid Responsiveness of Inflammatory Bowel Disease in Japan

Purpose We investigated the association between steroid responsiveness and single nucleotide polymorphisms of SLC22A4/A5 located within inflammatory bowel disease 5 locus. Our goal is personalized steroid therapy adjusted to match individual variations in drug responsiveness in each inflammatory bowel disease patient. Methods Unrelated Japanese cohorts of 94 patients with Crohn’s, 94 patients with ulcerative colitis, and 257 healthy control subjects were consecutively enrolled in this study. Genotyping and haplotype analysis focusing on steroid responsiveness was performed by using 15 single nucleotide polymorphisms. Results The G allele of −368T > G in SLC22A5, in which strong linkage disequilibrium was observed and the limited diversity of three haplotypes was estimated, was significantly associated with steroid resistance in Japanese patients with Crohn’s disease (P = 0.016). Haplotype analysis between −446C > T and −368T > G in the SLC22A5 promoter region showed that the CG allele appeared to be a risk haplotype for steroid resistance (CG: odds ratio, 4.13; 95 percent confidence interval, 1.41–12.1; P = 0.016). Conclusions This extensive linkage disequilibrium may form a general risk haplotype for steroid resistance in Crohn’s disease in Japanese. Further analyses of the pharmacogenomics of steroid responsiveness are warranted to achieve the goal of individualized steroid therapy against inflammatory bowel disease. Supported by a grant-in-aid from the Ministry of Health, Labour and Welfare (K.I.), Japan. Address of correspondence: Yoshiaki Arimura, M.D., First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan. E-mail: arimura@sapmed.ac.jp     

Impact of reflux esophagitis on the esophageal function before and after laparoscopic fundoplication

Background

High-resolution manometry (HRM), which is breakthrough testing equipment to evaluate esophageal motor function, was developed in Europe and United State and has garnered attention. Moreover, multichannel intraluminal impedance pH (MII-pH) testing has allowed us to grasp all liquid/gas reflux including not only acid but also non-acid reflux. We examined the impact of the presence of reflux esophagitis (RE) on esophageal motor function before and after laparoscopic fundoplication.

Materials and methods

The subjects included 100 patients (male: 63 patients, mean age: 54.1?±?15.8) among 145 patients who underwent laparoscopic fundoplication for GERD associated diseases during a 4-year period from October 2012 to September 2016, excluding 6 patients who underwent further surgery, 32 patients on whom HRM was not performed, 3 patients who had technical errors during testing, and 4 patients for whom the status of RE was unknown. Regarding HRM, Mano Scan from Given Imaging Ltd. was used, and for the analysis, Mano View version 3.0 from the same company was used, after which data was calculated based on the Chicago Classification advocated by Pandolfino et al. Moreover, for the MII-pH testing, Sleuth manufactured by Sandhill Scientific. Inc. was used and automatic analysis was conducted by a computer. Postoperative assessments were conducted 3 months following surgery for all. Data was described in the median value and inter-quartile range, with a statistically significant difference defined as p?<?0.05 by Chi square, Mann–Whitney, and Wilcoxon tests.

Results

RE+?group (Los Angeles classification A:B:C:D?=?7:9:16:12 patients) included 44 patients (44%), of older age compared to the RE? group (62 vs. 50 years, p?=?0.012) and a higher Body Mass Index value (24.0 vs. 22.5, p?=?0.045); however, no differences were observed in terms of gender and duration of symptoms. In the preoperative findings on MII-pH, the RE+?group demonstrated significantly longer acid reflux time (4.7 vs. 1.3%, p?=?0.005), while in the HRM findings, the RE? group demonstrated a significantly longer abdominal esophagus (0 vs. 0.4 cm, p?=?0.049) and maintained esophageal body motor function (DCI: 1054 vs. 1407 mmHg s cm, p?=?0.021, Intact peristalsis ratio: 90 vs. 100%, p?=?0.037). As to the comparison of the treatment effect before and after laparoscopic fundoplication (Toupet fundoplication for all), significant improvements were observed in both groups in various parameters regarding reflux including acid reflux time, total number of liquid reflux episodes and total number of reflux episodes. Moreover, for both groups, the total length of the lower esophageal sphincter (LES) (RE+?group: 2.7 vs. 3.2 cm, p?=?0.001, RE? group: 3.0 vs. 3.4 cm, p?=?0.003) and the total length of the abdominal esophagus (RE+?group: 0 vs. 1.6 cm, p?<?0.001, RE? group: 0 vs. 1.8 cm, p?=?0.001) were significantly extended following surgery; however, no change was observed in DCI before and after surgery.

Conclusions

Regardless of the presence of RE, cardiac function and LES function were improved following laparoscopic Toupet fundoplication, but no changes were observed in esophageal body motor function.

     

Effect of a new calcium antagonist, nilvadipine, on variant angina pectoris evaluated by 24-hour Holter electrocardiography

The clinical effect of nilvadipine, a new calcium antagonist, was investigated in a single blind trial in 19 patients with variant angina pectoris. The efficacy of the drug was evaluated on the basis of frequency of anginal attacks and Holter electrocardiographic findings during observation periods and during two treatment periods when the drug was given in doses of 4 mg twice a day or 4 mg 3 times a day. The frequency of anginal attacks and the consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with those in the observation period before treatment, but in the observation period after treatment tended to increase in comparison with those during the second treatment period. The frequency and duration of ST-segment elevation and the maximum ST-segment elevation confirmed by Holter electrocardiography also improved significantly in both treatment periods, compared with those in the observation period before treatment. Our findings show that nilvadipine is effective for variant angina pectoris at doses of 4 mg twice a day.