Metallothionein concentration in the liver of patients with Wilson''s disease, primary biliary cirrhosis, and liver metastasis of colorectal cancer

In patients with primary biliary cirrhosis and Wilson's disease liver copper concentrations become elevated during the evolution of the disorder. The accumulated copper is thought to be detoxified by metallothionein, a protein which binds copper and zinc. In liver metastasis of colorectal cancer, copper and zinc concentrations are usually decreased compared to normal liver tissue, but little is known about the concomitant metallothionein levels. In the present study metallothionein concentrations were determined in archival liver samples from patients with primary biliary cirrhosis and Wilson's disease, and in both normal and malignancy-containing liver samples from patients with metastasis from a colorectal adenocarcinoma. Twenty-seven control liver samples contained 3.98 +/- 1.55 mg metallothionein/g protein. From the 21 liver samples of patients with primary biliary cirrhosis, which had a mean metallothionein concentration of 6.06 +/- 5.03 mg/g protein, 6 were above the highest control level. Liver metallothionein concentrations for the 8 patients with Wilson's disease were significantly elevated (10.98 +/- 6.93 mg/g protein, p < 0.005 vs. controls and p < 0.05 vs. primary biliary cirrhosis). In the 11 liver metastases from colorectal adenocarcinomas metallothionein concentrations (1.17 +/- 0.90 mg/g protein) were significantly (p < 0.005) lower than surrounding normal liver tissue (4.25 +/- 1.75 mg/g protein). We conclude that in primary biliary cirrhosis and Wilson's disease increased liver metallothionein concentrations may detoxify the accumulated copper. Furthermore, liver metastasis of colorectal cancer contains less metallothionein than the surrounding normal liver tissue.     

Reticuloendothelial Phagocytic Function in Human Liver Disease and its Relationship to Haemolysis

Summary . This study was undertaken to examine the hypothesis that enhanced reticuloendothelial (RE) phagocytosis and splenic sequestration of red blood cells are important aetiological factors in the haemolysis accompanying liver disease. RE phagocytic capacity (REPC) was measured by the rate of plasma disappearance of radio-iodinated microaggregated human serum albumin (¹²⁵I-MAA) in 57 patients with acute or chronic liver disease, and its relationship to splenic size, RBC survival and splenic sequestration of RBC was analysed. In addition, RE perfusion was measured using a tracer dose of ¹²⁵I-MAA, and the RE phagocytic index (REPI), an index of the individual cellular RE activity, independent of perfusion, was calculated. An increased REPI was found in all forms of liver disease, largely independent of aetiology or severity. REPC was normal in most forms of cirrhosis but was decreased in patients with alcoholic cirrhosis, many of whom had diminished RE perfusion, associated with clinical or radiographic evidence of portal systemic shunting. This decreased REPC was due to decreased RE perfusion since a close correlation between REPC and RE perfusion was demonstrated. The relationship between spleen size and REPC in patients with cirrhosis depended on the aetiology of the disease, since in alcoholic cirrhosis splenomegaly was usually indicative of portal hypertension, whereas in patients with active chronic hepatitis splenomegaly was often an integral part of the disease. A shortened RBC survival was demonstrated in 24 of 30 patients studied, but the degree of haemolysis did not correlate with REPC, REPI or splenic size. Furthermore, splenic sequestration of RBC could be demonstrated in only two patients. It would appear that in hepatic cirrhosis, the RE system, whether its phagocytic capacity is increased or decreased, removes effete RBC presented to it, but is not primarily responsible for the mild haemolytic process.     

Impaired tuftsin activity in cirrhosis: relationship with splenic function and clinical outcome

BACKGROUND: Cirrhotic patients show increased susceptibility to bacterial infections. It is not known whether tuftsin deficiency, which is associated with an increased incidence of infections in many disease states, is present in cirrhosis. Our aims were to determine whether tuftsin activity is deficient in cirrhosis and if so, whether this deficiency is related to splenic function, contributes to altered neutrophil granulocyte function, or influences the occurrence of bacterial infections and patient survival. METHODS: Tuftsin activity and splenic function were assessed in 31 patients with liver cirrhosis and 31 healthy subjects. The phagocytic activity of neutrophil granulocytes from 23 patients was tested in vitro with addition of both autologous and pooled sera from healthy subjects. In 10 patients and eight controls it was also tested with addition of synthetic tuftsin. Patients were followed up until death or liver transplantation. RESULTS: Patients had reduced tuftsin activity (median 8% (range 3-24.5)) compared with controls (17% (11.5-37)) (p<0.001) and a higher pitted red cell count (p<0.001). Tuftsin activity was correlated with pitted cell count (p=0.02) and the Child-Pugh score (p=0.002). Nineteen of 23 patients showed deficient phagocytic activity of neutrophil granulocytes, which was correlated with tuftsin activity (p<0.001), improved in all cases but one with addition of serum from healthy subjects, and normalised with addition of synthetic tuftsin. Reduced tuftsin activity did not influence patient survival but was associated with a higher incidence of bacterial infections (p=0.029). COMMENT: Tuftsin activity was reduced in cirrhosis, and contributed to impaired phagocytic activity of neutrophil granulocytes. Such an abnormality appears to be related to impaired splenic function and severity of cirrhosis, and probably favours the occurrence of bacterial infections.     

Depletion of immunoglobulin M memory B cells is associated with splenic hypofunction in inflammatory bowel disease

OBJECTIVES: IgM memory B cells that are responsible for the protection against infections by encapsulated bacteria, require the spleen for their generation and/or survival. Since the association between inflammatory bowel disease and functional hyposplenism is well described, our aim was to verify whether IgM memory B cells mirror the reduced splenic function in Crohn's disease and ulcerative colitis patients. METHODS: Peripheral blood samples were obtained from 32 Crohn's disease and 29 ulcerative colitis patients, 33 healthy controls, and 27 splenectomized patients. Perendoscopic intestinal biopsies were also collected from 15 of 32 Crohn's disease patients, 14 of 29 ulcerative colitis patients and 13 of 33 control subjects. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function and flow cytometry was performed to analyze both peripheral and mucosal B cells. RESULTS: Twelve of 32 Crohn's disease patients and 13 of 29 ulcerative colitis patients had pitted red cell values >4% and were considered to be hyposplenic. In inflammatory bowel disease patients circulating IgM memory B cells were significantly lower than in control subjects. We observed a significant inverse correlation between the frequency of circulating IgM memory B cell and the pitted red cell values in inflammatory bowel disease patients with hyposplenism. To exclude the possibility that the reduction of circulating IgM memory B cells reflected their recruitment in the inflamed bowel mucosa, lamina propria B-cell populations were also characterized. We found that the frequency of IgM memory B cells was similar in the blood and in the lamina propria of the same patient. CONCLUSIONS: Our findings show that peripheral IgM memory B cells are reduced in inflammatory bowel disease patients and this defect seems to be related to the impairment of splenic function.     

A clinical biochemist's view of the investigation of suspected inherited metabolic disease

The copper content of and radiocopper uptake in fibroblast cultures were studied to evaluate their usefulness for the diagnosis of Wilson's disease. We used methods closely related to those described in the literature, and applied these to cell lines of six patients with Wilson's disease and 12 controls. The results were: (1) The copper content of the cytosol of skin fibroblasts derived from patients with Wilson's disease was lower than that of controls when the cells were grown in a medium with a low copper concentration (0.7 mumolL-1); increased copper concentration (157 mumol L-1 in the medium failed to demonstrate any difference between normal fibroblasts and those derived from patients with Wilson's disease. (2) Radiocopper uptake studies did not differentiate between normal fibroblasts and fibroblasts from patients with Wilson's disease. We conclude that the cytosolic copper content of fibroblasts grown in a low copper medium is a potential diagnostic tool in Wilson's disease. At present not all controls can be distinguished from the Wilson cells; ways must be sought, therefore, of improving the technique.     

Evaluation of oxidant stress in Wilson's disease and non-Wilsonian chronic liver disease in childhood.

BACKGROUND/AIMS: Oxygen free radicals have an important role in the pathogenesis of acute and chronic liver disease. Free radical formation and oxidative damage, probably mediated with copper accumulation, are important in Wilson's disease pathogenesis. This study was performed to determine if accumulating copper in Wilson's disease is a cause of further oxidant stress compared to non-Wilsonian liver disease. METHODS: In this study, we investigated plasma malondialdehyde and nitric oxide levels to estimate the oxidant stress and total antioxidant capacity and vitamin E/cholesterol, vitamin C and beta-carotene levels to estimate the antioxidant status of patients. The groups investigated included 24 patients with Wilson's disease (group I), 25 patients with non-Wilsonian chronic liver disease (group II) and 23 healthy controls (group III). Wilson's disease and non-Wilson's disease patients were divided into subgroups according to disease stage (i.e. chronic hepatitis and cirrhosis) and all parameters were compared between subgroups and controls. RESULTS: Malondialdehyde and nitric oxide levels were higher than controls in groups I and II (p=0.013, p=0.01), but these levels did not differ between the Wilson's disease and non-Wilson's disease groups. The parameters were also evaluated with respect to the disease stage (i.e. chronic hepatitis and cirrhosis), and there was no difference between groups I and II. Although malondialdehyde and nitric oxide levels were significantly different between both disease stage groups and the controls, we observed decreased vitamin C and beta-carotene levels only in cirrhosis stage (p=0.01, p=0.01). CONCLUSIONS: We observed the presence of oxidant stress unrelated to the etiology of the liver disorder in our study. Deficiency of the major antioxidants, vitamin C and beta-carotene, develops as the disease stage advances from chronic hepatitis to cirrhosis.     

Copper kinetics in liver disease

The plasma clearance and the liver uptake of intravenously administered (64)Cu were significantly impaired in four patients with Wilson's disease. These defects were unlikely to be simply expressions of the high liver copper concentration as the plasma clearance and hepatic uptake of (64)Cu were normal in four patients with primary biliary cirrhosis, in whom the liver copper concentration was raised to a degree comparable to that in Wilson's disease. The normal liver uptake and plasma clearance of (64)Cu in three patients with other forms of hepatocellular disease suggest that impaired liver cell function does not have a significant effect. The precise nature of the defect in copper transport in Wilson's disease remains to be elucidated; it is possible that delayed uptake of copper by the hepatic lysosomes may account for the toxic effects of the metal.     

Splenic function in alcoholic liver disease.

Splenic function was assessed in 42 patients with alcoholic liver disease by counting the percentage of erythrocytes with indentations or pits, seen by differential interference contrast microscopy. These pits represent cellular debris normally removed by the spleen. The findings were compared with 42 age and sex matched controls. Mean (SEM) pitted red cell counts in the patients was 2.7 (0.4)% and in the controls 0.7 (0.07)% (p < 0.001). In all of the eight reformed drinkers (five with biopsy proven cirrhosis), cell counts were normal. Six patients with alcoholic liver disease had had serious infections within the past year. Of these, one had had a recent pneumococcal pneumonia and another of the patients died from overwhelming pneumococcal septicaemia. Both of these patients had evidence of functional hyposplenism as judged by high pitted erythrocyte counts. A total of 18 patients were considered to have pitted red cell counts above the normal, and 11 of these had proven cirrhosis and/or gross ascites. This study is the first to show the presence of functional hyposplenism in alcoholic liver disease and provides further evidence of the predisposition that these patients have to infection. At present, it is unclear whether the hyposplenism is a direct toxic effect of alcohol or the result of cirrhosis; further studies are warranted.     

Hereditary spherocytosis. II. Observations on the role of the spleen

1. Three patients with hereditary spherocytosis and 1 patient with the Fanconi syndrome (pancytopenia and multiple congenital abnormalities) were transfused prior to splenectomy with normal erythrocytes of types which could bedifferentiated serologically from those of the recipients. The proportionsof donated and patient’s cells in peripheral blood and in blood washed from theminced spleens were determined by differential agglutination, and the osmoticand mechanical fragilities of the two types of cells in peripheral and splenic bloodwere measured by differential agglutination of the corpuscles remaining in eachtest tube after partial hemolysis had occurred.

2. In each case of hereditary spherocytosis the proportion of recipient’s cellswas much higher in splenic than in peripheral blood, indicating selective retentionof the thicker corpuscles within the spleen. Osmotic fragility of thie patient’s redcells was much greater in samples of splenic mince blood than in peripheral venoussamples, while the fragility of the donated red corpuscles was normal or nearlynormal in both splenic and peripheral blood.

In the patient exhibiting the Fanconi syndrome, on the other hand, neitherthe patient’s red cells nor donated red cells were retained to any extent in thespleen and the fragility of neither type of cell was altered.

3. Spleens removed surgically from 3 patients with idiopathic thrombocytopenic purpura were perfused with mixtures of normal A or B cells and groupO cells drawn from a splenectomized individual with hereditary spherocytosis.During perfusion the spheroidal cells were selectively removed from the mixtures and at the end of each experiment red cells of this type predominated inthe blood samples washed from the minced spleens. A fourth excised spleen wasperfused with a mixture of two types of normal cells, neither of which was retained to any extent by the spleen during perfusion. The perfusion experimentsshow that spleens from patients with nonhemolytic disease are also capable ofselective trapping of spheroidal cells.

4. The experiments described indicate that the spleen acts as a filter and trapand as an "incubator" in accelerating destruction of red corpuscles in patientswith hereditary spherocytosis.

Submitted on April 16, 1951 Accepted on May 10, 1951     

Value of portal hemodynamics and hypersplenism in cirrhosis staging

AIM: To determine the correlation between portal hemodynamics and spleen function among different grades of cirrhosis and verify its significance in cirrhosis staging. METHODS: The portal and splenic vein hemodynamics and spleen size were investigated by ultrasonography in consecutive 38 cirrhotic patients with cirrhosis (Child's grades A to C) and 20 normal controls. The differences were compared in portal vein diameter and flow velocity between patients with and without ascites and between patients with mild and severe esophageal varices. The correlation between peripheral blood cell counts and Child's grades was also determined. RESULTS: The portal flow velocity and volume were significantly lower in patients with Child's C (12.25±1.67 cm/s vs 788.59±234 mm/min, respectively) cirrhosis compared to controls (19.55±3.28 cm/s vs 1254.03±410 mm/min, respectively) and those with Child's A (18.5±3.02 cm/s vs 1358.48±384 mm/min, respectively) and Child's B (16.0±3.89 cm/s vs 1142.23±390 mm/min, respectively) cirrhosis. Patients with ascites had much lower portal flow velocity and volume (13.0±1.72 cm/s vs1078±533 mm/min) than those without ascites (18.6±2.60 cm/s vs1394±354 mm/min). There was no statistical difference between patients with mild and severe esophageal varices. The portal vein diameter was not significantly different among the above groups. There were significant differences in splenic vein diameter, flow velocity and white blood cell count, but not in spleen size, red blood cell and platelet counts among the various grades of cirrhosis. The spleen size was negatively correlated with red blood cell and platelet counts (r= -0.620 and r= -0.8.34, respectively). CONCLUSION: An optimal system that includes parameters representing the portal hemodynamics and spleen function should be proposed for cirrhosis staging.     

Polycythemia in primary carcinoma of the liver

In a series of 176 consecutive patients with hepatocarcinoma an increasein red cell count and in hemoglobin significantly above normal levels wereencountered in 17 (10 per cent).

An investigation of 28 patients with hepatocarcinoma developing in acirrhotic liver is reported. In three of the patients (10 per cent), the redcell counts and hemoglobin levels were significantly above those encounteredin healthy Chinese.

In these 28 patients it has been shown that the plasma volume is increased,and this increase does not differ significantly from that encountered in uncomplicated cirrhosis of the liver. The total red cell volume, on the otherhand, is significantly greater than in uncomplicated cirrhosis of the liver. Whilethe mean total red cell volume in hepatocarcinoma is not significantly different from that in healthy controls, consideration of this finding in individualpatients shows that it was above normal in 17, normal in six, and in the remaining five it was below normal.

It is concluded that the polycythemia encountered is a true polycythemiasecondary to the development of the hepatocarcinoma. The expanded plasmavolume is considered probably attributable to the pre-existing cirrhosis ofthe liver. Unfortunately, in the course of this investigation we did not encounter a patient in whom the carcinoma had developed in a liver whichwas not cirrhotic.

Submitted on April 8, 1957 Accepted on November 18, 1957     

多潘立酮对肝硬化患者门脉系统血流量的影响

背景:肝硬化病程迁延且内外科治疗效果均不理想,寻找有效的治疗药物一直是该领域研究的热点。目的:探讨多潘立酮对肝硬化患者门脉系统血流量的影响。方法:以20名健康人作为正常对照,用多普勒超声分别测定32例肝硬化患者服用多潘立酮前和服用2周后的门静脉、脾静脉和肠系膜上静脉血流参数。多潘立酮的用法为10mg tid口服。结果:多潘立酮治疗前,肝硬化患者的门静脉血流量(PVF)显著低于正常对照组(P<0.01),脾静脉血流量(SVF)和肠系膜上静脉血流量(SMVF)显著高于正常对照组(p<0.01);治疗后,肝硬化患者的PVF较治疗前无显著差异,SVF和SMVF虽显著低于治疗前(P<0.01),但仍高于正常对照组(P<0.05)。结论:多潘立酮可能对肝硬化患者的内脏高动力循环状态有改善作用。     

Hereditary Spherocytosis: The Metabolism of Erythrocytes in the Peripheral Blood and in the Splenic Pulp

S ummary . Na⁺ transport was studied in intact red cells and membrane preparations ('ghosts') of patients with hereditary spherocytosis (h. s.). Ouabain-insensitive efflux was greater than normal in ghost preparations as well as in intact cells, findings which arc consistent with a membrane defect in h.s. red cells. Ouabain-sensitive ('pump') sodium efflux was normal in h.s. membrane preparations, but was increased in intact cells and the latter probably reflects changes secondary to the increased Na⁺ influx in these cells.
In h.s., red cells are trapped and destroyed in the spleen and we studied splenic pulp red cells in a group of h.s. patients at splenectomy. These cells showed greater osmotic fragility, higher Na⁺ and lower K⁺ concentrations than did peripheral red cells. Membrane permeability to Na⁺ was not greater than in peripheral red cells but the ouabain-sensitive ('pump') Na⁺ efflux was reduced. Despite this, ATP concentration and ATPase activity were found to be normal. Low levels of 2,3-diphosphoglyceric acid were noted in splenic red cells but ATP turnover was normal. Since failure of the Na⁺ pump occurs in h.s. splenic red cells despite adequate substrate (ATP) and an intact ATPase system, it is suggested that the abnormality results from a change in the red cell membrane 4 which reduces the function of the pump. These characteristics of splenic red cells are similar to those found in normal red cells following in vitro incubation at 37°C. This supports the concept that cell death in h.s. results from a deterioration in membrane function secondary to substrate deprivation in the stagnant circulation of the splenic pulp.     

肝硬化患者红细胞免疫功能与脂质过氧化关系的研究

探讨肝硬化患者红细胞免疫功能的变化及其与脂质过氧化的关系。应用红细胞酵母菌花环法测定红细胞免疫功能 ,并采用化学比色法测定血浆丙二醛 (MDA)、超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH -Px)含量。其中肝硬化患者 31例 ,健康对照 30例。肝硬化组RBC -IC花环率明显提高 ,P <0 .0 5 ;而RBC -C3b受体花环率与正常人无显著性差异 (P >0 .0 5 )。肝硬化组SOD、GSH -Px、SOD/MDA低于正常 (P <0 .0 1) ;而MDA明显高于正常 (P <0 .0 1)。线性相关分析显示 ,RBC -C3b花环率与MDA呈显著负相关 (r= 0 .42 3,P <0 .0 5 )。RBC -ICR与MDA明显正相关 (r=0 .5 2 3,P <0 .0 5 )。肝硬化患者红细胞免疫粘附功能降低 ,与活性氧代谢紊乱密切相关     

Role of spleen in hereditary spherocytosis: evidence for increased in vitro proteolysis of red cell membrane

In vitro proteolysis of red cell membranes has been studied by means of electrophoretic separation on SDS-polyacrylamide gel of solubilized ghost proteins and subsequent densitometry of separated, stained bands; the amounts of major membrane proteins were measured in ghosts either with inhibited or with allowed proteolysis in the following cases: 15 patients suffering from hereditary spherocytosis (HS) with variable degree of spleen enlargement, eight cirrhotic patients with spleen enlargement and 12 healthy blood donors as control group. Proteolysis was present to a greater extent in HS patients with larger splenomegaly, lesser in HS with smaller splenomegaly, and was comparable to healthy controls both in splenectomized HS and in patients with spleen enlargement due to liver cirrhosis. The results suggest the involvement of splenomegaly in the enhancement of in vitro proteolysis in HS red cell membrane; it is probably attributable to joint effects of the damage induced in red cells by prolonged retention within haemolysing spleen together with the abnormalities genetically affecting the structure of HS red cell membrane.     

Enhanced growth and Na+/H+ antiport activity response to serum in cultured fibroblasts of diabetic patients with nephropathy

To explore whether elevated red blood cell sodium-lithium countertransport in type 1 (insulin-dependent) diabetic patients with nephropathy is related to the physiological Na⁺/H⁺ antiport activity, we measured the activity of this antiport in serially passaged cultured skin fibroblasts from insulin-dependent diabetic patients with and without nephropathy and from non-diabetic controls. Na⁺/H⁺ antiport activity (measured as the rate of amiloride-sensitive Na⁺ influx) was significantly elevated in patients with nephropathy compared with patients without nephropathy and normal controls (13.35±3.8 vs 8.54±2.0 vs 7.33±2.3 nmol Na⁺/mg protein per min;P<0.006 andP<0.001 respectively). This raised activity in patients with nephropathy was due to an increasedV _max for extracellular Na⁺.K _m values were similar in the three groups. Amiloride-sensitive Na⁺ influx was also higher in cells under baseline conditions and after serum stimulation from patients with nephropathy. Intracellular pH values were significantly higher, both during active proliferation and after 10 min of exposure to serum, in cells from patients with nephropathy compared with patients without nephropathy and normal controls. Serum-stimulated incorporation of [³H]thymidine into DNA was greater in patients with nephropathy than in the other two groups. These data in cultured fibroblasts suggest that intrinsic abnormalities in cell function, independently of the metabolic disturbances of diabetes, are a feature of diabetic patients who develop nephropathy.     

A reassessment of splenic hypofunction in celiac disease

OBJECTIVES: Because there is controversy regarding the prevalence, familial occurrence, and possible factors inducing splenic hypofunction in celiac disease, we have reassessed them in a large series of untreated patients and their first-degree relatives. METHODS: Pitted red cell counting was used to measure splenic function and the effect that age at diagnosis has on it, while severity of intestinal lesions and nutritional status were estimated by multiple linear regression analysis. Moreover, serum tuftsin activity was assayed by measuring its ability to stimulate phagocytosis of opsonized Staphylococcus aureus. RESULTS: We found that 32.8% of untreated celiacs and none of their relatives had pitted red cell values in the range of splenic hypofunction (>4%). Only age at diagnosis, but not the other two covariates, was significantly associated with the degree of splenic hypofunction. Tuftsin activity was depressed in celiac disease and this reduction was significantly greater in hyposplenic patients. CONCLUSIONS: In celiac disease the prevalence of splenic hypofunction is lower than formerly believed. The duration of preexposure to gluten is a crucial factor for the prevalence and severity of this complication that does not affect celiac relatives. In celiac disease splenic hypofunction is accompanied by a reduced phagocyte activity linked to the decreased release of tuftsin.     

Moving Boundary Electrophoresis of Red Cells on Differently Treated Polycythaemic Patients

Red cells of polycythaemia vera (PV) patients have a significantly higher rate of electrophoresis than red cells of normal controls and stress polycythaemia patients. The highest increment in the electrophoretic velocity was noted for PV patients treated with phlebotomy or hydroxy urea. The red cells of PV patients treated with ³²P and those that progressed to myeloid metaplasia showed a normal rate of electrophoresis. We assume that the increased negative charge found on the red cells of PV patients is typical of the abnormal clone proliferating in this disease. The normal electrophoretic velocity found for the red cells of the ³²P treated patients or those that progressed to myeloid metaplasia might indicate that the circulating red cells of these patients are no longer descendants of the abnormal stem cell.     

Gastric mucosal hexosamine content in various liver diseases.

Since gastric mucosal lesions are frequently encountered in patients with liver disease, we measured the levels of gastric mucosal hexosamine. In chronic hepatitis patients, hexosamine levels were reduced in both the antrum and corpus as compared with those in normal controls, while values in the advanced liver cirrhosis group (total bilirubin greater than 5 mg/dl) were lower than in the less advanced group. Although the presence or absence of esophageal varices had no influence on hexosamine, higher concentrations were found in patients with the red color sign (+) in comparison with those with negative red color sign (-). One month after endoscopic injection sclerotherapy of esophageal varices, hexosamine did not change, but decreases were seen in both the antrum and corpus at 3 months. We observed an increase in gastric mucosal blood flow after treatment with teprenone, a new antiulcerative agent, in normal controls. Gastric mucosal hexosamine increased significantly after teprenone treatment in both chronic hepatitis and liver cirrhosis groups. From these results, we conclude that hexosamine has a defensive action against gastric lesions in various liver diseases.     

Splenic Function in Adult Coeliac Disease

S ummary . The rate of clearance of ¹⁵Cr-labelled, heat-damaged red cells from the circulation has been measured in 18 patients with adult coeliac disease. This has been combined with scintillation scanning of the spleen using a colour scanning method. Only two of the patients had clearance times within normal limits. Five had a peripheral blood picture suggestive of splenic atrophy. In these the half time of clearance was greater than 50 min and the scintillation scan showed either no evidence of functioning splenic tissue or only minimal localization of radioactivity suggesting marked hyposplenism. Nine patients had a somewhat prolonged clearance time, the half time of clearance varying between 19 and 44 min. The scan, however, showed an apparently normal spleen and the characteristic changes of splenic atrophy were not present in the peripheral blood film. Two patients had clearance rates faster than that found in control subjects. Both of these patients had enlarged spleens. In one this was associated with hepatic cirrhosis and in the other with an unexplained neutropenia.