[Japanese clinical statistical data of patients with hepatitis type A].
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Biomedical subjects
Publications and source records attributed to K Tanikawa.
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We investigated the chronic effects of isosorbide dinitrate on systemic and splanchnic hemodynamics and liver function in 13 patients with liver cirrhosis and portal hypertension. Placebo administration for 4 wk (n = 4) had no significant effects on these parameters. In contrast, oral administration of 40 mg/day of isosorbide dinitrate for 4 wk (n = 9) caused a significant fall in portal pressure (-18%, p less than 0.02), as evaluated by measurements of the hepatic venous pressure gradient with no modification in hepatic blood flow (from 0.72 +/- 0.29 to 0.71 +/- 0.34 L/min, NS), suggesting decreased intrahepatic or collateral vascular resistance. On the other hand, there was no significant correlation between the changes in mean arterial pressure and hepatic venous pressure gradient (r = 0.42). Thus, it seems unlikely that a reduction in portal blood inflow by baroreceptor-mediated reflex splanchnic vasoconstriction contributed to the fall in portal pressure. In addition, this drug had no adverse effects on liver function, as evaluated by measurements of the intrinsic clearance. These results suggest that chronic administration of isosorbide dinitrate could be a potentially useful and associated with cirrhosis.
We report a case diagnosed as bilateral ureteritis cystica by ureteroscopic examination. A 51-year-old female was admitted with pyuria and proteinuria. Retrograde pyelography revealed multiple, small, smooth and round punched-out defects in the bilateral lower ureters. Ureteroscopic examination and punch biopsy were performed with a suspected diagnosis of ureteritis cystica. The histological examination revealed chronic ureteritis. This patient was given conservative treatment (chemotherapy) and careful follow-up.
We studied the effects of the combination of nitroglycerin and vasopressin on portohepatic hemodynamics, hepatic function, and blood gases in nine patients with cirrhosis and portal hypertension. Vasopressin infusion at a dose of 0.4 U/min caused a significant fall in portal pressure, which is evaluated by portal venous pressure gradient (-34%, p less than 0.01), associated with a decrease in hepatic perfusion (-33%, p less than 0.01) and intrinsic clearance (-20%, p less than 0.01) after 30 min. The arterial oxygenation, however, was not modified (paO2; from 73 +/- 8 to 72 +/- 7 mm Hg, NS). Nitroglycerin infusion at a dose of 100 micrograms/min was then administered for 20 min. The addition of nitroglycerin produced a further reduction in free portal venous pressure (-12%, p less than 0.01), but this was not associated with a significant improvement in both hepatic perfusion (+16%, NS) and intrinsic clearance (-7%, NS). In addition, there was a significant fall in arterial oxygenation (paO2; from 72 +/- 7 to 59 +/- 5 mm Hg, p less than 0.01). We conclude that the addition of nitroglycerin to vasopressin has a beneficial effect on free portal venous pressure, but does not have hepatic benefit. Moreover, sufficient care must be taken, when treating portal hypertension with this combination, to avoid arterial hypoxemia.
The significance of interleukin-6 (IL-6) in patients with inflammatory bowel disease (IBD) was studied by measuring the IL-6 level in serum and colonic tissue by means of an enzyme-linked immunosorbent assay (ELISA), and by examining its localization using an immunohistochemical method. The serum IL-6 level reflected the degree of disease activity, and the extent of affected area, and was also correlated with the serum C-reactive protein (CRP) level. In the colonic mucosa of active IBD, the tissue IL-6 level was markedly elevated, and immunoreactive products of anti-IL-6 antibody were present in infiltrative mononuclear cells in the lamina propria. This indicates that IL-6 production in these cells is enhanced at the site of affected intestine. These results, together with its biological activity and the type of cell producing it, suggest that IL-6 is an available marker to assess disease conditions of IBD and that it might be also involved in the pathophysiology of IBD.
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We observed 18 patients with portal hypertension and cirrhosis to compare the effects of intraportal nitroglycerin on portosystemic hemodynamics with the i.v. route. Patients received 1 microgram/kg/min of nitroglycerin intravenously (n = 9) or the same dose of nitroglycerin directly into the portal vein (n = 9). Both routes of nitroglycerin significantly reduced mean arterial pressure and this effect was higher with the i.v. route (-28.0% versus -19.3%, p less than 0.02). The portal pressure, as evaluated by the portal venous pressure gradient or hepatic venous pressure gradient, was also reduced significantly in both groups. The fall in portal pressure was higher in the intraportal group, but the difference was not significant (intravenous versus intraportal, -23.9 versus -25.1% in portal venous pressure gradient, -25.2 versus -33.4% in hepatic venous pressure gradient). The hepatic blood flow was maintained despite the significant reduction in portal pressure by both routes. These results indicate that intraportal nitroglycerin decreases portal pressure with a smaller effect on systemic hemodynamics than the i.v. route. We conclude that the oral administration of nitroglycerin, which is a pathway equivalent to the intraportal route, may be more useful than the i.v. (i.e., sublingual) route in the treatment of portal hypertension.
Sixty-three patients with unresectable hepatocellular carcinoma (HCC) were treated with cisplatin-phosphatidyl-choline-Lipiodol (CPL) suspension. Partial response (PR) and minor response (MR) were obtained in 3 of 14 cases (21.4%) by one shot therapy, and in 13 of 43 cases (30.2%) by TAE therapy. AFP decreased in 11 of 15 patients (73.3%) by one shot therapy, and in 32 of 33 patients (97%) by TAE therapy. PIVKA II also decreased. The one-year survival rate was 74% in TAE therapy, and 52% in one shot therapy. The two-year survival rate was 53% in TAE therapy, and 28% in one shot therapy. Nausea, vomiting and fever were noted in most cases as adverse effects, but they were slight. The concentration of free-CDDP in the peripheral venous blood was lower and continued longer than that of CDDP on the market. These results suggest that CPL was useful as an anticancer agent for arterial chemotherapy or TAE therapy for unresectable HCC.
In 14 cases of hepatocellular carcinoma with capsule, we studied the mechanism of capsule formation by the immunoperoxidase technique using antibodies to types I, III, and IV collagen, antilaminin antibody, and anti-prolyl hydroxylase antibody. Marked round cell infiltration was observed in the noncancerous side of the capsule and around compressed hepatocytes near the capsule. Thin capsules were composed primarily of type III collagen produced by an increased number of fibroblasts, transitional Ito cells, and hepatocytes near the capsule. In thickened capsules, the noncancerous side consisted primarily of type III collagen and the cancerous side of types I and III collagen. Type I as well as type III collagen was produced by fibroblasts, transitional Ito cells, and hepatocytes. The capsule thus formed is suggested to be part of the defense mechanisms against the growth of hepatocellular carcinoma.
The localization of substance P (SP) and vasoactive intestinal peptide (VIP) in 12 normal human liver tissues was examined by light and electron immunohistochemistry using immunoperoxidase methods. SP and VIP immunoreactive nerve fibers were observed around portal veins, bile ducts, and hepatic arteries in portal areas, along sinusoids and hepatocytes in hepatic lobules, and around central veins. More SP and VIP immunoreactive nerve fibers were present in the portal areas than in other regions. Moreover, SP and VIP containing nerve endings were localized close to myofibroblasts, Ito cells, fibroblasts and endothelial cells of blood vessels, and sinusoids. The results suggested that part of the innervation of the human liver may be related to the contraction and relaxation of the cells close to nerve endings, and to the regulation of hemodynamic processes by the neurotransmitters such as SP and VIP at the hepatic lobular level.
Thirty-eight patients with small hepatocellular carcinomas (HCCs), size less than 20 mm, initially detected by ultrasound (US) and histologically confirmed, were examined by magnetic resonance (MR) imaging, computed tomographic (CT) scan, and angiography. MR imaging demonstrated HCC nodules in nine (75.0%) of 12 patients with tumors less than 10 mm in diameter and in 22 (84.6%) of 26 patients with tumors 10-20 mm in diameter. In total, HCC nodules were detected in 31 of 38 patients (81.6%) by MR imaging. On the other hand, HCC lesions were found on CT scan in 14 of 26 patients (53.8%) and in 27 of 35 patients (77.1%) by angiography. With MR imaging, HCC nodules were demonstrated in 21 of 31 patients on both T1 and T2 weighted images, and 13 of 21 patients (61.9%) were shown to have low intensity areas or iso intensity areas on T1 weighted image, whereas the other eight patients (38.1%) were shown to have high intensity areas. All 21 patients were shown to have high intensity areas on T2 weighted image. Among 15 resected cases, four patients had a high intensity area on T1 weighted image, and a significant fatty change was noted in HCC nodules by histological study of the resected specimen. We suggest that MR imaging is a useful diagnostic imaging modality, even in small HCC of less than 20 mm.
We studied 14 patients with portal hypertension and cirrhosis using portal and hepatic vein catheterizations to determine the effects of transdermal application of nitroglycerin tape (containing 10 mg of nitroglycerin and capable of releasing 6 to 7 mg of nitroglycerin in 12 hr) on splanchnic hemodynamics. Patients randomly received nitroglycerin (n = 7) or a placebo (n = 7). No significant changes were observed after the administration of the placebo. In contrast, transdermal nitroglycerin caused a significant reduction in portal pressure, as evaluated by measurements of the portal venous pressure gradient (-22%, p less than 0.01). The reduction of portal pressure was due to a decrease in the portal venous pressure, with no changes in the free hepatic venous pressure. Despite the fall in portal pressure, the hepatic blood flow was maintained. These findings suggest that transdermal nitroglycerin could be potentially useful in the treatment of portal hypertension associated with cirrhosis.
We developed a new assay method for the evaluation of Le(Y) antigen expression on human peripheral T-lymphocytes using the monoclonal antibodies BM-1, CD4 and CD8 by two-color flow cytometry. Le(Y) antigen expressed on human peripheral T-lymphocytes was stained with fluorescein isothiocyanate (FITC)-labelled BM-1 (anti Le(Y) monoclonal antibody). Le(Y) positive cells were simultaneously stained with phycoerythrin (PE)-labelled CD4 or CD8, then analyzed by flow-cytometer. Coefficients of variations in this double staining assays were 4.2% for BM-1 in CD4 and 5.3% for BM-1 in CD8, respectively. In 124 healthy volunteers 0.2-13.1% of CD4 and 2.5-12.5% of CD8 positive cells were BM-1 positive. Lymphocytes from 200 patients with acute or chronic viral hepatitis showed marked increase in BM-1 expression of CD8 positive cells during the acute phase and exacerbation of the disease. Moreover, BM-1 expression of CD4 cells was positively related with the course of the chronic hepatitis and the prognosis of each patients. Therefore, this new assay using BM-1 and CD4, CD8 monoclonal antibodies would reflect progression of viral hepatitis and its related immunological condition.
The distribution of several extracellular matrix components in the liver of patients with acute viral hepatitis was studied by light and electron microscopy using indirect immunoperoxidase methods. Light microscopy revealed type III and type V collagen and fibronectin in the portal tracts and the area of focal necrosis, showing cell infiltration. Type III and type V collagen were more strongly stained in the periphery of focal necrosis. Type IV collagen was seen around the vessels and hepatocytes near the focal necrosis. Electron microscopy showed many transitional Ito cells in the area of focal necrosis and fibroblasts were observed in the portal tracts, showing collagen fiber deposition. Numerous collagen fibrils were observed around fibroblasts, Ito cells and hepatocytes. Using immunoelectron microscopy, type III and type IV collagen and fibronectin were observed in the rough endoplasmic reticulum of Ito cells and hepatocytes localized near the area of focal necrosis or fiber deposition. In addition, type IV collagen was seen in the rough endoplasmic reticulum of endothelial cells forming capillary vessels. These results suggest that several extracellular matrix components such as types III, IV and V collagen and fibronectin, produced by Ito cells, hepatocytes or endothelial cells, play important roles in the healing of liver damage in acute viral hepatitis.
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The present study was intended to assess the incidence and the nature of gastric red spots (GRS) in patients with liver cirrhosis. Endoscopically, GRS was more frequently observed in patients with cirrhosis (n = 146) than those without cirrhosis (n = 103) (43.2% vs. 4.8%; P less than 0.001). There was no relationship between the incidence of GRS and the severity of cirrhosis or the size of varices. Portal venous pressure was higher in cirrhotics with GRS (n = 21) than those without GRS (n = 25) (33.7 +/- 6.0 mmHg vs. 28.2 +/- 4.8 mmHg; P less than 0.001). Morphometric analysis using the biopsied specimens was made in 16 cirrhotics with GRS, 12 cirrhotics without GRS, and 15 non-cirrhotics. The capillary bed occupation ratio (vascular area/mucosal area) was higher in cirrhotics with GRS (9.3 +/- 4.0%) than those without GRS 84.1 +/- 1.1%) or the non-cirrhotics (3.4 +/- 9.8%) (P less than 0.005, P less than 0.005), while there was no significant differences in the number of capillaries per unit area. Infiltrating inflammatory cell count was similar among the three groups. Extravascular red blood cell count per unit area was higher in cirrhotics with GRS (29.7 +/- 31.4) than those without GRS (5.4 +/- 5.1) or non-cirrhotics (5.4 +/- 6.3) (P less than 0.05, P less than 0.01). Furthermore, extravasation of red blood cells through defective portion of the endothelium and interposition of red blood cells in interepithelial spaces were observed electron microscopically in cirrhotics with GRS.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of sofalcone on the glandular structure and cell proliferation in the gastric mucosa of rats with gastritis induced by the administration of sodium taurocholate (TCA) for 6 months was examined by histoquantitative analysis and [3H]thymidine autoradiography. Morphometric observation revealed that, with TCA treatment, mucosal thickness, parietal cell mass, and the ratios of the length of the glandular portion/total length of the gastric gland were decreased in both the fundic and pyloric glands. Inflammatory cell infiltration and collagenous fiber proliferation were present in the gastric mucosa following TCA and indicated the presence of atrophic gastritis. These atrophic changes and inflammatory cell infiltration were reversed by a 3 week administration of sofalcone. Cellular proliferative activity assessed by the labeling indices of the gastric mucosa increased in TCA-induced gastritis in rats. The administration of sofalcone to rats with TCA-induced gastritis significantly increased labeling indices, particularly in the pyloric glands. From these results, it appears that sofalcone stimulates the compensatory increase in proliferative activity of generative cells, which then may become available to heal the gastritis.