Autoimmune hemolytic anemia and posthepatitis-C liver cirrhosis

Here we are presenting the case of a 70-years-old woman who has hepatic cirrhosis anti-HCV and insulin-dependent diabetes mellitus, without relevant epidemiologic ascendants or previous transfusions and HBV, HIV negatives. On admission to our hospital she showed signs of autoimmune hemolytic anaemia (AHA) which was confirmed by positive direct Coombs test and an improvement in blood test after corticoid treatment. Having discarded other possible causes such as drugs infectious diseases or essential mixed cryoglobulinemia (CME), we put forward the possible association between AHA and infection by HCV, where AHA was an extrahepatic immunological manifestation of HCV. This fact has never been brought to light in previous medical literature.     

Hypergastrinaemia in cirrhosis of liver

The basal acid output (BAO), post-pentagastrin acid output (MAO), fasting and post-prandial gastrin levels in 40 patients with proven cirrhosis of the liver were compared with those in 20 normal controls. The mean BAO and MAO were significantly lower than normal, the mean fasting gastrin level was significantly higher than normal, and the postprandial gastrin response was significantly increased and prolonged. These differences were still significant even when the patients were divided into cryptogenic and alcoholic subgroups. A significant inverse relationship between MAO and the integrated gastrin response to meal was observed both in the normal controls and in the cirrhotic patients. The MAO and integrated gastrin response of the cirrhotic patients did not correlate with the degree of liver function impairment. In five cirrhotic patients fasting and postprandial gastrin levels were unchanged after splenorenal shunt operation. A more consistent abnormality of the gastric mucosa as assessed by endoscopy and biopsies appeared to be mucosal congestion with occasional atrophic gastritis. the severity of mucosal abnormality, however, was unrelated to the degree of hypoacidity. these results indicate, firstly, that the hypergastrinaemia in cirrhotic patients is a reflection of gastric hypoacidity and bears no direct relationship to hepatic dysfunction. Secondly, the gastric hypoacidity does not accrue solely from mucosal abnormality. It is suggested that this hypoacidity may result from the presence of excessive amounts of circulating acid-inhibiting intestinal peptides, which the diseased liver fails to metabolise.     

Gastrointestinal lesions in liver cirrhosis

The gastrointestinal bleeding commonly observed in patients with liver cirrhosis is usually from esophageal and gastric varices, gastroduodenal ulcer, and congestive gastropathy. Portal hypertension is the major causative factor of pathogenesis of GI lesions. In the present review, we focus in gastric mucosal defense and Helicobacter pylori infection in liver cirrhosis. Gastric mucosal defense is reduced in liver cirrhosis, especially prostaglandins which play a role in the gastric mucosal defense decreased in the gastric mucosal of patients with liver cirrhosis and rat portal hypertension model. Although H. pylori is strongly associated with peptic ulcer disease and chronic gastritis, several studies showed no relationship between H. pylori infection and gastroduodenal ulcer or the infection and congestive gastropathy in liver cirrhosis. Reduced gastric mucosal defense may account for the pathogenesis of GI lesions in liver cirrhosis.     

Congestive gastropathy in liver cirrhosis

Congestive gastropathy has emerged as a new nosological entity that can be included among the complications of advanced liver cirrhosis. It has been defined as the macroscopic changes of gastric mucosa occurring in portal hypertension that are associated with vascular mucosal and submucosal dilatation and ectasia without significant inflammatory changes. The pathogenesis of congestive gastropathy has not been completely cleared up. Many epidemiological and clinical studies and some tests on animals lead most Authors to think that the cause of this disease is a chronic increase of pressure in the portal vascular system. However the involvement of humoral factors cannot be excluded as, for example, the presence of high plasma levels of gastrin and histamine or a decrease of E2 prostaglandin in the gastric mucosa. The macroscopic lesions typical of congestive gastropathy can be seen through endoscopy. Up to now mosaic-like pattern, red points, cherry-red and black-brown spots and erosions have been observed. These changes are prominent in the area near the gastric body and cardias, but can be present in all parts of the stomach. The frequently reported spontaneous bleeding corresponding to cherry-red spots make the presence of these lesions to be considered a sign of severe congestive gastropathy. The prevalence of congestive gastropathy in cirrhotic patients is between 30% and 70%. This condition is more frequent in patients with large esophageal varices and severe liver disease and in patients submitted to endoscopic variceal sclerotherapy. Congestive gastropathy is a frequent cause of acute and chronic bleeding: 10-20% of gastrointestinal bleeding episodes occurring in cirrhotic patients are caused by this condition and about 30% of cirrhotics with portal hypertension will have one or more acute bleeding in a four year follow-up. The percentage of subjects with chronic hemorrhage in the same period can reach 90%. At the moment is not possible to suggest a therapy able to prevent or cure the acute or chronic bleeding associated with congestive gastropathy. beta-blockers seem to be a promising treatment. However, further and larger clinical trials are necessary to settle definitively their efficacy.     

Endotoxinemia in liver cirrhosis]

Ribosomes isolated from either dry viable or non-viable pea embryonic axis tissue were equally effective in the support of polyphenylalanine synthesis in a poly(U)-directed cell-free protein-synthesising system. Ribosomes isolated from imbibed non-viable axis tissue were impaired in their ability to support polyphenylalanine synthesis in the cell-free system. RNA isolated from ribosomes and 40-S ribosomal subunits of dry or imbibed viable axis tissue was found not to be degraded, whereas the equivalent RNA species isolated from non-viable axis tissue showed an increased degree of breakdown as imbibition proceeded. Even though rRNA of imbibed non-viable axis tissue was degraded, the ribosomes and ribosomal subunits of these embryos appeared intact. In viable embryonic axis tissue the percentage of ribosomes present in the cell in the form of polysomes increased during imbibition whereas no polysomes could be detected in ribosomal preparations from dry or imbibed non-viable axis tissue. The breakdown of rRNA in ribosomal particles from non-viable axis tissue may be a contributory factor to senescence and loss of viability in Pisum arvense.     

Effect of hemin in treating hemorrhagic anemia and toxicity

AIM: To study the effect of hemin in treating hemorrhagic anemia and toxicity. METHODS: Fifty rats with hemorrhagic anemia were randomly divided into 5 groups with different dosage of hemin (93, 168, 300 mg.kg-1.d-1), ferrous gluconate (FG 300 mg.kg-1.d-1), and water, ig for 7 d. Twenty mice fed with hemin (6.0 g.kg-1.d-1) in 24 h for observing acute toxicity effects. Long-term toxicity were observed in 80 rats given hemin (0.65, 1.3, 2.6 g.kg-1.d-1) in 3 months. RESULTS: Hb of the rats of corresponding groups were 66-->121, 71-->141, 66-->148, 69-->140, and 67-->112 g.L-1. There were no adverse effects observed on acute toxicity test. No abnormalitis were found in hemogram, liver renal function test, and autopsy. CONCLUSION: Hemin had a better effect than FG and no adverse effect was found in hemin.     

The role of splenectomy in treating severe aplastic anemia

A hypotensive effect of clonidine in non-narcotized intact and aorta baro-denervated rats is studied under conditions of minimization of stress actions (radiotelemetry) and under standard conditions of direct recording arterial pressure (AP). Direct AP recording is shown to determine an increase in background AP in baro-denervated rats, but not in control rats. An increase in background AP level under conditions of direct recording is not accompanied with decreasing hypotensive effect of clonidine in baro-denervated rats.     

Malignant lymphoproliferative disorders in liver cirrhosis

BACKGROUND: Lymphoproliferative disorders in patients with liver cirrhosis, although uncommon, have been reported in at least 49 cases. Some authors have suggested that the association between chronic liver disease and lymphoma is not coincidental, that immune mechanisms may be pathogenetically involved. PATIENTS AND METHODS: In the present study we calculated the incidence rate of lymphoproliferative disorders in 334 liver cirrhosis patients (201 males, mean age 59 +/- 12; 133 females, mean age 61 +/- 11) treated at the Gastroenterology Department of the Mauriziano Hospital in Turin from January 1987 to September 1990. RESULTS: We diagnosed 12 lymphoproliferative disorders, corresponding to an incidence of 9.56/1,000 person-years, a figure much higher than expected on the basis of the incidence rate registered in the Turin general population. Six of the 12 lymphoproliferative disorders were non-Hodgkin's lymphomas of the stomach, a proportion by far exceeding expectation. CONCLUSIONS: Our data support the hypothesis that the association between chronic liver disease and lymphoproliferative disorders is not just coincidental, and suggest that liver cirrhosis might be considered an immunological disturbance which entails an increased risk of developing lymphoproliferative disorders. Mechanisms causing lymphoproliferative disorders to develop in the course of chronic liver disease have been hypothesized.     

Functional dyspepsia in liver cirrhosis]

Precolumn fluorescence derivatization for the determination of the antagonist [Arg6,D-Trp7,9,MePhe8]-Substance P?6-11? (antagonist G) using benzoin in HPLC was studied. Under the conditions chosen (0.067 M NaOH, heating at 100 degrees C for 10 s), a good yield of fluorescent derivatives was obtained and no methodology-related degradation occurred. The detection limit of antagonist G was 0.21 nmol/ml. The method has been applied to the selective and sensitive detection of arginine-containing fragments in degradation products of antagonist G.     

Alcohol and liver cirrhosis in Switzerland

The question wheter in Switzerland, too, there exists an association between alcoholism and cirrhosis of the liver was examind by the use of Federal Statistics. E.M. Jellinek devised an internationally applicable formula which shows a linear relationship between these two conditions. Three hypotheses were tested to validate the assumption that there are no alternate causes of cirrhosis of the liver. The results show: a) that in Switzerland as elsewhere, a direct relationship exists only between alcoholism and cirrhosis of the liver; b) that, in consequence, other causes of the condition have only small significance; c) that mortality from cirrhosis shows a distinct sex difference, with a surprisingly great increase amongst women in recent years.     

Diffusion disorders in patients with liver cirrhosis

In 17 patients with cirrhosis of theliver and in 11 controls the pulmonary diffusing capacity for CO (DLCO) was determined at three different levels of alveolar oxygen tensions. The diffusing capacity of the alveolar membrane (DMCO) and the intra-pulmonary capillary volume (VC) were calculated following the formula given by Roughton and Forster. The following results were obtained: 1) Both DLCO and DMCO were lower (p less than 0,01) in the patient group than in the controls. 2) VC showed larger variations in thepatient group than in the controls (p less than 0,01). The mean values did not differ, however. 3) There was a significant linear correlation (p less than 0,001) between DM and 1/VC in the patient group (DM and VC in % of the predicted value). The results suggest, that a change in the configuration of the capillary bed may be responsible for the transfer defect found in cirrhosis.     

Hepatocarcinogenesis in liver cirrhosis: imaging diagnosis

Point mutations in the ras proto-oncogenes, notably at codon 12, are found in high frequency of human malignancies and, thus, may be appropriate targets for the induction of tumor-specific T cell responses in cancer immunotherapy. In this study, we examined the mutant ras protein sequence reflecting the substitution of Gly to Val at position 12 as a putative point-mutated determinant for potential induction of an HLA-A2-reactive, CD8+ cytotoxic T lymphocyte (CTL) response. We identified the ras 4-12(Val12) sequence as a minimal 9-mer peptide, which displayed specific binding to HLA-A2 by T2 bioassays. Peptide binding to HLA-A2 on T2 cells was weak and required coincubation with exogenous beta(2)-microglobulin to facilitate and enhance complex formation. In contrast, the wild-type ras 4-12(Gly12) peptide failed to bind to HLA-A2 even in the presence of beta(2)-microglobulin, consistent with the hypothesis that the point mutation creates a C-terminus anchor residue. A CD8+ CTL line against the ras 4-12(Val12) peptide was derived in vitro from a normal HLA-A2+ donor using a model culture system consisting of T2 cells as antigen presenting cells pulsed with exogenous mutant ras peptide and beta(2)-microglobulin plus cytokines (interleukin-2 and 12). Functional characterization of CD8+ CTL line revealed (1) peptide-specific and HLA-A2-restricted cytotoxicity against a panel of peptide-pulsed targets; (2) no specific lysis using the normal ras peptide sequence; (3) half-maximal lysis with exogenous peptide of approximately 0.3 microM; (4) lysis of HLA-A2+ B cell lines infected with a recombinant vaccinia virus construct encoding the point-mutated human K-ras gene; and (5) specific lysis of the HLA-A2+ SW480 colon carcinoma cell line expressing the naturally occurring K-ras Val12 mutation. Maximal lysis of SW480 cells occurred following interferon (IFN)-gamma pretreatment, which correlated with enhanced HLA-A2 and ICAM-1 (CD54) expression. Specificity of lysis was revealed by the absence of lysis against a HLA-A2+ melanoma cell line (+/- IFN-gamma), which lacked the mutant Val12 mutation, and the inability of an irrelevant CD8+ CTL line to lyse SW480 (+/- IFN-gamma) unless the appropriate exogenous peptide was added. These findings demonstrated that tumor cells may endogenously process and express mutant ras epitopes, such as the 4-12(Val12) sequence, albeit in limiting amounts that may be potentiated by IFN-gamma treatment. These data support the biological relevance of this sequence and, thus, may have important implications for the generation of ras oncogene-specific CTL responses in clinical situations.     

Safety of single large oral doses of guanethidine

The cardiovascular effects of single 100-mg doses of guanethidine were assessed in hypertensive patients by measurement of arterial pressure, heart rate, and systolic time intervals. In the 3-hr period following a dose there was no evidence of an inotropic effect. Therefore, large doses of guanethidine as required for the guanethidine loading regimen would seem to be safe even in patients in whom inotropic effects of released catecholamines would be contraindicated.     

肝硬化肝切除术后肝再生及评估指标研究

原发性肝癌是我国的常见病、多发病,且90%的患者合并有肝硬化,肝切除术是主要的治疗方法,而肝脏在受到损害或切除之后,可以显示出强大的再生能力,这一现象早已被人们所发现并研究.就肝硬化肝切除术后肝再生、肝再生受损机制以及肝再生评估予以综述.