Transposition of the spleen in rats with portal hypertension

Portal hypertension was induced in rats by progressive occlusion of the portal vein or by dimethylnitrosamine (DMNA) cirrhosis. Portasystemic venous connections did not develop in relation to the spleen when this organ was intraperitoneal, but after subcutaneous transposition most of the collaterals were parasplenic and the portal venous pressure fell.     

Adrenoceptors on blood cells in patients with primary hypertension: correlation with blood pressure and related variables

OBJECTIVE: Alterations in platelet alpha 2-adrenoceptor and mononuclear leucocyte beta 2-adrenoceptor characteristics in primary hypertension have been extensively studied. The results of the reports have not been consistent, possibly because of the small number of subjects in most of the studies. We therefore studied the blood-cell adrenoceptor characteristics in a relatively large group of primary hypertensive and normotensive subjects. DESIGN: Platelet alpha 2-adrenoceptor characteristics were compared in 65 hypertensive and 51 normotensive subjects. Mononuclear leucocyte beta 2-adrenoceptor characteristics were compared in 72 hypertensives and 67 normotensives. Untreated hypertensive subjects were selected from the outpatient clinic and the normotensive controls were recruited by a newspaper announcement. METHODS: Platelets and mononuclear leucocytes were isolated from blood samples obtained after at least 10 min supine rest. The alpha 2- and beta 2-adrenoceptor characteristics were determined with [3H]-rauwolscine and [125I]-(-1)cyanopindolol, respectively. Correlations between the adrenoceptor characteristics and clinical parameters of the subjects were studied. RESULTS: No differences in alpha 2- or beta 2-adrenoceptor densities were observed between the two groups. However, a significantly lower equilibrium dissociation constant for [3H]-rauwolscine was observed in the hypertensive group. The correlations between the adrenoceptor characteristics and clinical parameters were weak and mostly not statistically significant. The results were compared with the most relevant studies in the literature. CONCLUSIONS: From our study and the literature, we conclude that blood-cell adrenoceptor characteristics are unchanged in primary hypertension.     

Oral ammonia tolerance test in patients with portal hypertension

Eighty patients with portal hypertension due to various hepatic diseases were subjected to the oral ammonia tolerance test (OATT). Blood samples were collected before and at 30-min intervals after the administration of ammonium chloride (50 mg/kg). The ammonia levels, and the OATT curve patterns and sigma NH3-N values were determined and it was investigated whether there are correlations between these values and various other parameters of hepatic function. The results of OATT correlated with the plasma disappearance rate of indocyanine green and the molar ratio of branched chain amino acids to aromatic amino acids. Our findings suggest that the OATT may reflect the degree of hepatic parenchymal disorders rather than the hepatic circulatory abnormalities and that they may represent a valuable aid in the differential diagnosis of hepatic diseases and in determining the operative indication.     

Modulation of insulin secretion by hepatic vagotomy in cirrhotic rats

A soluble protein kinase (PK) was purified from bovine and human follicular fluids (FF) by ultrafiltration through a PM-10 membrane followed by chromatography on heparin-agarose, DEAE-cellulose and cellulose phosphate columns. The PK phosphorylated calf thymus histones and endogenous FF proteins having estimated Mrs of 40, 62, 128 and 180 KD. cAMP enhanced PK activity; whereas protein kinase A (PKA)-inhibitor peptide blocked the activity. The present findings suggest that the enzyme is a cAMP-dependent PK.     

Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy

Seventy-five cirrhotic patients with hyperammonemia in the past or at the time of the study were randomly divided into two groups (treated with lactulose or nontreated) in 14 hospitals in Japan. Thirty-six cirrhotic patients were diagnosed as having subclinical hepatic encephalopathy (SHE), and 39 were diagnosed as non-SHE. SHE was diagnosed when the results of all three of the quantitative psychometric tests used (number connection test, and symbol digit and block design tests of the Wechsler adult intelligence scale [revised]) were abnormal as compared with age-matched normal values. The mean number of abnormal psychometric test results and the prevalence of SHE were used for a quantitative evaluation of the efficacy of the lactulose treatment. Twenty-two of the SHE patients were treated with lactulose (45 mL/d) for 8 weeks, and the other 14 SHE patients did not receive lactulose. In the SHE patients administered lactulose, the results of the quantitative psychometric evaluation were significantly improved at 4 and 8 weeks after the beginning of the lactulose administration. The SHE had disappeared in 10 (50%) of the 20 treated patients at week 8, but it persisted in 11 (85%) of the untreated 13 patients. We concluded that lactulose treatment in cirrhotic patients with SHE is effective with respect to psychometric tests.     

Changes in lymph vessels and portal veins in the portal tract of patients with idiopathic portal hypertension: a morphometric study

Little is known about the effects of the pathological process associated with idiopathic portal hypertension (IPH) on hepatic lymph vessels or lymph flow. We used morphometric analysis to examine IPH-associated changes in lymph vessels and branches of the portal vein, with use of immunohistochemical staining for alpha smooth muscle actin. We also quantitated these changes using an image analysis system. The study was conducted with use of liver wedge biopsy material from 10 patients with advanced IPH and 10 control samples from patients with gastric carcinoma without liver disease. The number of lymph vessels, identified by a lack of smooth muscle layer in the wall, and the ratio of the total area of these vessels to that of the portal tract were higher in IPH samples than in the control samples, but the ratio of the area of a single lymph vessel to that of the portal tract in IPH samples was not different from control samples. The number of portal vein branches, characterized by hypertrophy of the smooth muscle layer in IPH samples was not different from control samples. The ratio of the total area of these branches to that of the portal tract, and the ratio of a single portal vein branch to that of the portal tract, were lower in IPH samples than in the control samples. Our results suggest that these morphometric changes in IPH may be associated with a reduction in portal blood flow and increased lymph flow, and that the latter may in turn reduce the high portal vein pressure in idiopathic portal hypertension.     

Nitric oxide levels in cirrhotic patients]

The tumor suppressor p53 is degraded by the ubiquitin-proteasome system. p53 was polyubiquitinated in the presence of E1, UbcH5 as E2 and MDM2 oncoprotein. A ubiquitin molecule bound MDM2 through sulfhydroxy bond which is characteristic of ubiquitin ligase (E3)-ubiquitin binding. The cysteine residue in the carboxyl terminus of MDM2 was essential for the activity. These data suggest that the MDM2 protein, which is induced by p53, functions as a ubiquitin ligase, E3, in human papillomavirus-uninfected cells which do not have E6 protein.     

Hemodynamic effects of combined treatment with somatostatin analogue (SMS 201-995) and low-dose isosorbide dinitrate on portal hypertension in conscious cirrhotic rats

The authors investigated whether combined treatment with the somatostatin analogue, SMS 201-995, and low-dose isosorbide dinitrate enhanced the hemodynamic effects of the individual agents on rats with thioacetamide-induced cirrhosis. Four groups of cirrhotic rats received SMS 201-995 (0.1 microgram.min-1.kg-1), isosorbide dinitrate (10 micrograms.min-1.kg-1), both agents, or placebo, respectively. Hemodynamics were measured serially in conscious rats, using a radioactive microsphere method. SMS 201-995 reduced portal venous inflow 21 +/- 4% and portal pressure 17 +/- 3%. Isosorbide dinitrate decreased portal venous inflow 20 +/- 4%, by inducing splanchnic vasoconstriction mediated by low pressure baroreflexes, and this agent also decreased portal pressure, by 14 +/- 2%. Portal venous resistance rose 7.6 +/- 3% with isosorbide dinitrate alone, but decreased 18 +/- 4% with combination therapy. This effect may have been induced by the pronounced vasodilatory effect of isosorbide dinitrate on the venous vasculature, since the reflex splanchnic vasoconstriction that occurs with low-dose isosorbide dinitrate disappears when this agent is combined with SMS 201-995. The decrease in portal pressure was more marked (22 +/- 4%) and changes in systemic hemodynamics were milder with the combined treatment. It was concluded that combination therapy with SMS 201-995 and low-dose isosorbide dinitrate may be beneficial for portal hypertension in liver cirrhosis.     

Alterations in colonic mucosal vessels in patients with cirrhosis and noncirrhotic portal hypertension

The purification, biochemical characterization and functional features of a novel extracellular matrix protein are described. This protein is a component of the basal lamina found in embryos from the sea urchin species Paracentrotus lividus and Hemicentrotus pulcherrimus. The protein has been named Pl-200K or Hp-200K, respectively, because of the species from which it was isolated and its apparent molecular weight in SDS-PAGE under reducing conditions. It has been purified from unfertilized eggs where it is found packed within cytoplasmic granules, and has different binding affinities to type I collagen and heparin, as assessed by affinity chromatography columns. By indirect immunofluorescence experiments it was shown that, upon fertilization, the protein becomes extracellular, polarized at the basal surface of ectoderm cells, and on the surface of primary mesenchyme cells at the blastula and gastrula stages. The protein serves as an adhesive substrate, as shown by an in vitro binding assay where cells dissociated from blastula embryos were settled on 200K protein-coated substrates. To examine the involvement of the protein in morphogenesis of sea urchin embryo, early blastula embryos were microinjected with anti-200K Fab fragments and further development was followed. When control embryos reached the pluteus stage, microinjected embryos showed severe abnormalities in arms and skeleton elongation and patterning. On the basis of current results, it was proposed that 200K protein is involved in the regulation of sea urchin embryo skeletogenesis.     

Hepatocyte volume as an indicator of hepatic functional reserve in cirrhotic patients with liver tumours

Using computed tomography (CT), measurements of whole liver volume have been used for the assessment of pre-operative functional reserve in cirrhotics. However, measurements of hepatocyte volume, which exclude stromal fibrous tissue, are considered to more directly reflect hepatic functional reserve. We investigated the relationship between total hepatocyte volume and each of the parameters of conventional liver function. Indocyanine green (ICG) tests and blood analyses for the assessment of liver function were performed prior to surgery in cirrhotic patients with liver tumours. Pre-operative liver volume was determined by integrating images of each liver area obtained by CT. Liver area was measured by an image processing program that traced the profile of the liver image while excluding the tumorous area. Sections of normal tissue stained by the haematoxylin-eosin method, were obtained from the resected liver. Using these sections, a hepatocyte area: whole tissue area ratio was calculated using the image processing program, by tracing the profiles of the hepatocyte nodules. The total volume of hepatocytes was then calculated by multiplying the liver volume by this ratio. The hepatocyte volume per unit bodyweight was significantly correlated with ICG tests and with many other parameters of normal liver function. However, the liver volume per unit bodyweight was correlated only with the plasma ICG disappearance rate and with the blood platelet count. These observations suggest that the functional reserve of the cirrhotic liver is assessed more precisely by hepatocyte volume than by liver volume.     

Intrasplenic venous flow patterns demonstrated by Doppler ultrasound in patients with portal hypertension

The flow pattern in the splenic vein has been previously reported in patients with portal hypertension, but with no reference to the flow within the intrasplenic venous radicles. Using Doppler ultrasound, this study describes the intrasplenic venous flow direction in 176 adult patients with intrahepatic portal hypertension. In our series, a normal flow pattern was maintained in all except four patients (2.3%) who had either reversed or dual venous drainage patterns resulting in trans-splenic portosystemic shunts. These abnormal patterns are Doppler signs of portal hypertension which might be associated with a higher risk of oesophageal variceal bleeding. It is recommended that the intrasplenic venous flow pattern should be assessed before surgical intervention involving the spleen in patients with portal hypertension.     

Pre- and postoperative correction of hyposiderosis in surgical treatment of portal hypertension]

The pharmacological properties of the new nondepolarizing myorelaxant IEM-1213 and of its mixture with tercuronium were studied in experiments on anesthetized cats. Intravenous infusion of a blocking dose of IEM-1213 did not cause a change in the level of arterial pressure and blockade of the sympathetic ganglia but induced blockade of the heart muscarine receptors. The effect of IEM-1213 develops more rapidly and lasts for a shorter time than that of dithylin. Intravenous infusion of a mixture of IEM-1213 and tercuronium constituting 35 and 60% of the blocking dose of the former and, respectively, 35 and 20% of the blocking dose of the latter causes an effect similar in the time of its development to that of intravenous infusion of a total dose of IEM-1213 alone.     

Liver resections and operations in portal hypertension viewed via the experience of our practice]

After listing the indications for liver resection, the operative technique used is discussed with a special reference to an original modification implemented in practice. The case material is made of 52 liver resections and 6 lobectomies with a favourable outcome. In one lobectomy with subtotal proximal resection jejunogastroplasty is performed, supplemented by isolated antireflux anisoperistaltically interposed invagination esophagojejunostomy, duplicated by suturing its two portions. Application of catheter, inserted into the recanalized umbilical vein, is described under the heading of locoregional chemotherapy. In carcinomas involving the confluence of hepatic ducts a variant of Rodney Smith's operation is used while in hepatocholedochus resection plastic repair is done over Kerr drainage. In portal hypertension, after discussing the various methods existing, attention is called to the indirect shunts: splenectomy with omentoreno- and omentoparietopexy, Charsky and fenestration of Glisson's capsule using electric knife and argon with omentohepato- and hepatoparietopexy, as well as implantation of the recanalized v. umbilicalis into m. rectus abdominis dexter. In 15 cases operated on by parenchyma stimulating procedures, survivorship ranging from 3 to 26 years is achieved. For the purpose of prophylaxis against cholangiohepatitis and cirrhosis the following operations are performed: 68 papillotomies and plastic repairs over balloon catheter, passed through the choledochus and papilla, using an electric knife, 12 choledochoduodenostomies type "frog mouth", and 11 deperitonizations-desympathizations with a successful cure being attained.     

Portal-hepatic venous shunt through a portal aneurysm complicated by hepatic encephalopathy and pulmonary hypertension

We report a rare case of portal-hepatic venous shunt through an enormous portal aneurysm complicated by pulmonary hypertension. A 66-year-old woman was admitted to our hospital for hepatic encephalopathy. Chest roentgenography revealed pulmonary hypertension. Computed tomography and ultrasound examination demonstrated a shunt between the portal and hepatic veins through an enormous portal aneurysm. The diagnoses of portal-hepatic venous shunt and pulmonary hypertension were confirmed by hepatic venous catheterization and cardiac catheterization. Pulmonary hypertension might result from the effects of vasoconstrictive agents, which should be metabolized by the liver in normal subjects, passing through the intrahepatic shunt into the lung.