prospective trials. 8,9 However, the incidence of hemorrhage The incidence and the risk factors of hemorrhage from from FV has not been fully investigated. 3,7 Although several gastric fundal varices (FV) have not been fully evaluauthors have mentioned the incidence of hemorrhage from ated. We therefore conducted a retrospective and pro-FV, 3,7 to our knowledge, there has been no prospective study spective study to define the incidence and risk factors documenting the cumulative risk for FV hemorrhage in a for such episodes. We investigated 132 patients with cirlarge number of patients. The aim of this study was to define rhosis and gastric FV. Of these 132 patients, 15 patients the incidence and the risk factors for hemorrhage from FV. had hemorrhagic FV at the time of enrollment. The clinical characteristics were compared between these pa-PATIENTS AND METHODS tients and those without a first hemorrhage from FV. In Baseline Clinical Assessment. From January 1985 through Decemthe patients who had never previously bled, the inciber 1995, a total of 1,392 cirrhotic patients consecutively underwent dence and risk factors were prospectively investigated.upper gastrointestinal endoscopy at our institute. Of these patients, The size of FV was greater and red-spot on the FV were 540 patients had esophageal varices, 96 patients had gastric varices, more prevalent in patients with hemorrhagic FV. Child's and 253 patients had both esophageal and gastric varices. In the status was also more severe in these patients. In the 117 patients with gastric varices, 143 patients had FV, while the repatients who had never bled, 34 hemorrhages from FV maining 206 patients had varices in the cardia. In the 143 patients occurred during the follow-up period. The cumulative with FV, 11 patients were subsequently excluded from further evaluation because of their refusal to participate in the study. We thus risk for such hemorrhage at 1, 3, and 5 years was 16%, investigated a total of 132 patients with FV in the current study. 36%, and 44%, respectively. A multiple regression analy-The subjects consisted of 89 men and 43 women ranging in age from 1 The blood flow of such collaterals is abundant, 2 and apy. All patients were informed of the scientific nature of the investihemorrhage from FV is more serious than that of esophageal gation and gave their informed consent. The study protocol was apvarices. [3][4][5][6] The treatment of hemorrhagic FV by endoscopic proved by the Hospital Ethics Committee. procedures sometimes fails to cease the bleeding, and surgiAssessment of Endoscopic Findings. The diagnosis of FV was made cal modalities are thus often required for hemostasis.3-6 As a based on endoscopy with the agreement of two experienced endoscoresult, the mortality rate is high in patients with hemor-pists when one or more distinct venous channels were found in the rhagic FV. [3][4][5][6] In addition, because hemorrhagic esophageal gastric fundus. In patients with hemorrhagic FV, the endoscopic findings were analyzed after the cessation o...

We investigated the effects of nifedipine on splanchnic haemodynamics in 13 patients with cirrhosis and portal hypertension, and in 10 control subjects using hepatic venous catheterization and pulsed Doppler ultrasound. There were no significant changes in systemic or splanchnic haemodynamics in control patients. In contrast, systemic vasodilatation, evidenced by significant decreases in mean arterial pressure and systemic vascular resistance, was observed in patients 20 min after sublingual application of 10 mg nifedipine. Moreover, hepatic venous pressure gradient and portal vein blood flow significantly increased after nifedipine administration. There was a significant correlation between the percentage increases in portal vein blood flow and in hepatic venous pressure gradient. However, no correlation was found between the percentage change in cardiac output and that in portal vein blood flow. Thus the increase in portal vein blood flow appears to be related to splanchnic arterial vasodilatation by nifedipine. Consequently, nifedipine has deleterious effects on portal haemodynamics in patients with cirrhosis. As nifedipine may potentially increase the risk of variceal haemorrhage in patients with less advanced varices, this drug should be used with caution in patients with chronic liver disease.

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Nitric oxide (NO) is known to play an important role in modulating both the hepatic and mesenteric circulation under physiological and pathological conditions. We investigated how L-arginine, a precursor of NO, modifies the hepatic and mesenteric circulation in patients with cirrhosis. The study design was a single-blind controlled study. We measured the systemic and portal hemodynamics before and following intravenous L-arginine and saline infusion using pulsed Doppler ultrasonography in 20 patients with cirrhosis, and then the effects were compared with those found in 20 healthy subjects. In these patients, the effects of L-arginine on hepatic circulation were investigated using hepatic catheterization. L-Arginine infusion induced systemic vasodilation in both the healthy controls and the cirrhotic patients in a similar hemodynamic manner. In these patients, the L-arginine-induced increase in the portal flow was significantly higher than that of cardiac output (CO); however, the relation was the inverse in healthy subjects. Moreover, the L-arginine-induced increase in the portal flow was greater in the cirrhotic patients than that seen in healthy subjects. As a result, L-arginine infusion was thus found to selectively augment the hepatopetal portal blood flow in the cirrhotic liver. In patients, L-arginine infusion induced marked hepatic vasodilation as demonstrated by the reduced hepatic sinusoidal resistance (HSR) and increased estimated hepatic blood flow (EHBF) associated with the ameliorated intrinsic clearance of indocyanine green. Despite the fall in HSR, the hepatic venous pressure gradient (HVPG) increased following L-arginine infusion. The mesenteric and hepatic vascular areas of cirrhosis exhibited an increased susceptibility to the dilator action of L-arginine. These findings suggest that the enhanced NO production in the splanchnic vascular area has an important role in the hepatic circulation in patients with cirrhosis. (HEPA-TOLOGY 1998;27:377-382.)Patients with cirrhosis exhibit circulatory abnormalities such as perturbation of the hepatic microcirculation, as well as systemic and mesenteric hyperemia. 1,2 It has recently been proposed that hepatic stellate cells play an important role in regulating hepatic sinusoidal tonus and the blood flow under physiological and pathological conditions. 3-7 The contractility of hepatic stellate cells depends on the dynamic control of the balance of two endothelium-derived vasoactive substances, endothelin 1 and nitric oxide (NO). [3][4][5][6][7] Endothelin produces sustained vasoconstriction in the liver, which appears to be related to the contraction of hepatic stellate cells. 3,4 In addition, NO is also a potent modulator of stellate cell contractility 5,6 and inhibits the vasoconstriction induced by endothelin in the perfused rat liver. 7 Therefore, both endothelin and NO play a critical role in modulating hepatic microcirculation.L-Arginine, a precursor of NO, induces systemic vasodilation and natriuresis when infused intravenously in humans. [8][9][10][...

SummaryTo identify proteins related to the pathophysiology of aortic valve stenosis (AS), we investigated the protein profiles of AS aortic valves. Specifically, proteins were extracted from a thickened and calcified area (AS-C) and an apparently non-thickened and non-calcified area (AS-N) in an identical aortic valve leaflet in each of 6 AS patients. The proteins were then separated by 2-dimensional gel electrophoresis (2DE). Protein spots detected by 2DE were compared between the AS-C and AS-N samples. Protein spots of interest were subjected to protein identification by mass spectrometry.In total, 670 protein spots were detected by 2DE, 28 of which showed more than 1.5-fold different intensity (P < 0.05) between the AS-C and AS-N samples. Proteins were identified in 17 out of the 28 spots. Fibrinogen and lumican were identified in 9 and 3 spots, respectively. Intensity of these 12 spots was lower in the AS-C samples than in the AS-N samples. In the 1D-Western blot analysis, 4 lumican bands (80 kDa, 75 kDa, 65 kDa, and 53 kDa) were detected, of which 2 bands with 80 kDa and 75 kDa showed lower intensity in the AS-C samples than in the AS-N samples. When de-glycosylated protein samples were used in the 1D-Western blot, only a single lumican band with ~40 kDa was detected, indicating that lumican was variously glycosylated and that highly glycosylated lumican molecules were decreased in AS-C.Collectively, insufficient glycosylation of lumican in the thickened and calcified areas of AS aortic valves may be involved in the pathophysiology of AS. (Int Heart J 2016; 57: 104-111) Key words: Calcification, 2-dimensional gel electrophoresis, Mass spectrometry, Peptide:N-glycosidase F, Proteoglycan A ortic valve stenosis (AS) is one of the most common cardiovascular diseases. Several decades ago, the main cause of AS used to be rheumatic fever, however, it was recently replaced by degenerative changes with calcification.