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An infant was found to have abetalipoproteinemia, substantial hepatomegaly, and persistent elevation of the serum transaminases. Liver biopsies were obtained prior to treatment with medium chain triglyceride (MCT) and at 2, 14, and 20 months after initiation of treatment with the MCT-substituted low fat diet. The initial liver biopsy contained 38% lipid, 91% of which was triglyceride. The hepatocytes contained large fat droplets which ruptured to form centrilobular fatty lakes. Ultrastructurally, the Golgi was nearly completely deficient in trans-Golgi vacuole formation. Endogenous triglyceride particles could not be found, and the circum-Golgi smooth endoplasmic reticulum was absent. When the infant was fed a medium chain triglyceride diet, steatorrhea improved and the liver cell cytoplasmic fat droplets became smaller and less numerous. During the 14 months of MCT feedings, however, there was progression of the initially mild hepatic fibrosis to an advanced micronodular cirrhosis, and alcoholic hyalin appeared in the hepatocytes. It is speculated that the evolution of alcoholic hyalin may be related to the accumulation of 2-carbon fragments derived from MCT in the face of defective hepatic triglyceride secretion. Because of the destructive but asymptomatic lesion in this infant’s liver, liver function should be carefully investigated in all children with abetalipoproteinemia. Diagnostic liver biopsy is indicated if hepatomegaly or chemical signs of liver dysfunction persist, particularly if diet manipulation is contemplated.

SummaryThe pathological significance of giant cells, inspissitated bile plugs and hepatic fibrosis in the liver of infants is critically reviewed. Evidence is presented suggesting that a wide variety of pathological change in the paediatric liver results from the interaction of the effects of growth, metabolic maturity, genetic metabolic variability and infection. Understanding of the bile retention syndromes might increase if the diagnosis of ‘Neonatal Hepatitis’ and ‘biliary atresia’ as finite conditions, were to cease and their pathogenesis considered in such a multifactorial way.

The type of hepatic injury observed by Weichselbaum ('35) in rats after a few weeks on a low casein diet was recognized by Gyorgy and Goldblatt ('39) to be acute necro sis. That it differed from cirrhosis was suggested by Daft, Sebrell and Lillie ('42). Both types of hepatic injury were induced independently by Himsworth and Glynn ('44a) on diets deficient in sulfur-containing amino acids : massive he patic necrosis appeared in some weeks, while diffuse hepatic fibrosis followed fatty infiltration of the liver and appeared in some months. Methionine and cystine prevented necrosis (Weichselbaum, '35; Himsworth and Glynn, '44b; Gyorgy and Goldblatt, '42; Hock and Fink, '43), but choline was without effect (Gyorgy and Goldblatt, '49). Fatty infiltration of the liver, which leads to diffuse hepatic fibrosis, was prevented by lipotropic factors such as choline and methionine (Best and Huntsman, '32 ; du Vigneaud, Cohn, Chandler, Schenck and Simmonds, '41) ; it was intensified by cystine (Beeston and Channon, '36; Tucker and Eckstein, '37; Earle and Vic tor, '41; Daft, Sebrell and Lillie, '42; Gyorgy and Goldblatt, '42). 1A cooperative project with the Agricultural Experiment Station of the

It is now time to consider what conclusions are possible from the foregoing discussion. My purpose in writing this paper has been to draw attention to the distinction between portal cirrhosis and post-necrotic scarring, because I believe that these conditions are distinct and that it is of value to separate them where possible. The view has been adopted that the majority of cases of true portal cirrhosis, or diffuse hepatic fibrosis, result either from long continued fatty infiltration or, less frequently, from repeated attacks of zonal necrosis. For the latter little can be done at present, but for the former much may be possible in the way of prevention. Fatty infiltration is nutritional in origin. It is frequently associated with alcoholism, but may result from a wide range of nutritional deficiencies, or oxygen lack, from vascular or haematological conditions which indirectly result in deficient nutrition of the liver cells. If the cause of fatty infiltration is one which can be removed, such as a dietary deficiency or a haematological or cardiac condition amenable to treatment, it may be possible by judicious therapy to do much to prevent the onset of cirrhosis or to slow its progress when developed. If this paper should stimulate the wider use of punch biopsy as a means of detecting the presence of fatty infiltration with a view to treatment it will have served its purpose.

Having shown that fatty and cirrhotic livers occur in hypophysectomized-thyroidectomized (HT) dogs (Entenman et al., 1948), we next directed our attention to explaining the mechanism of development of these lesions. It has been repeatedly shown that fatty livers can be produced by the administration of diets low in protein and other lipotropic factors. But the fatty livers of the HT dogs could not have resulted from a deficient intake of lipotropic factors, for, as already pointed out in the preceding paper, these dogs were fed a high protein (lean meat) diet adequate in all respects. It is shown here, however, that the addition of free choline to the diet of these doubly operated dogs not only completely prevents the accumulation of fat in their livers but results, as well, in an almost complete suppression of the hepatic fibrosis.

An ultrastructural investigation of CCl 4 -induced cirrhotic and control livers has indicated that fibroblastic proliferation and new collagen formation were the significant factors in the development of fibrosis in the livers of the CCl 4 -treated rats. There was no evidence that collapse or condensation of pre-existing hepatic stroma contributed to the formation of the fibrous bands. The newly formed collagen fibers could be distinguished from those of the pre-existing hepatic reticulum by morphologic features and structural associations. If these distinguishing characteristics pertain in human disease, the pathogenesis of hepatic fibrosis in the various forms of human cirrhosis could be assessed in terms of these structural parameters. In the CCl 4 -induced cirrhosis, certain sinusoids were widened and appeared as sites of intense fibroblastic proliferation and new collagen formation. In general, the new fibers were deposited in direct apposition to the flanking hepatic parenchymal cells, without the intervention of a recognizable basement membrane or space devoid of newly formed collagen. The fibers tended toward deposition in cross-orientated layers. The widened sinusoids invariably included proliferated biliary ductules.

Changes in hepatic acid mucopolysaccharides were examined by testicular hyaluronidase digestion and hexosamine analysis of the acid mucopolysaccharides extracted from rat livers having chronic hepatic damage caused by serial inhalation of carbon tetrachloride. Chronic hepatic damage gave rise to an increase of hyaluronic acid in the early stages of hepatic damage and of chondroitin sulfate B in the advanced stages, the latter being more prominent. The amount of chondroitin sulfate A and/or C was also increased, but the change in its ratio to the total acid mucopolysaccharides was not significant throughout the experiment. Another result was that galactosamine-containing acid mucopolysaccharide was found to exist in the non-sulfated fraction which increased in the early stage. The possibility is suggested that chondroitin sulfate B is related to the progress of hepatic fibrogenesis.

The changes in the thoracic duct were studied in schistosomatic hepatic fibrosis, particularly in cases with ascites. The postmortem findings, lymphangiography, and clinical thoracic duct cannulation showed that, particularly in cases with ascites, the thoracic duct is dilated, pressure within is raised, and the lymph flow is increased. The significance of these findings is discussed in relation to the site and the treatment of ascites.

Fine structural changes in the space of Disse were of similar character in hepatitis and cirrhosis.

Ultrastructural and biochemical observations in hepatic fibrosis have been reviewed. Recent advances in our knowledge of collage metabolism have helped in understanding the kinetics of fibrosis in the hepatic parenchyma. Instead of fiber accumulation from collapse previously emphasized, new formation of fibers is now considered of major importance. Three processes have to be distinguished, namely, stimulation of fibroblasts, maturation and deposition of fibers, and catabolism of fibers. These considerations may eventually become useful in development of a rational therapy of fibrosis and cirrhosis, particularly since some agents like corticosteroids may have antagonistic effects on the three stages. Hepatic fibrosis probably stimulated by hepatocellular injury may, in turn, damage the hepatic parenchyma, and this may be more important in the self-perpetuation of liver injury than the immunologic components of hepatic inflammation. This damage is produced by local interference with hepatocellular nutrition and by some of the hemodynamic alterations characteristic of cirrhosis which are exerted by the formation of septums. The observations presented may also be useful in developing clinical parameters for determining the extent of active hepatic fibrogenesis.

Previous observations indicated that the hydroxyproline in collagen is synthesized by the hydroxylation of proline which has been incorporated into a large polypeptide precursor of collagen called protocollagen, and that the hydroxylation of protocollagen is one of the terminal reactions in the intracellular synthesis of collagen. Significant levels of protocollagen proline hydroxylase activity were demonstrated both in normal rat liver and in a single specimen of human liver. The enzymatic activity in rat and human liver was similar to protocollagen proline hydroxylase isolated from chick embryos in that it was inhibited by poly-L-proline II, and it required ascorbate, α-ketoglutarate, and ferrous iron. When hepatic fibrosis was produced in rats with carbon tetrachloride or with a choline-deficient diet, liver levels of protocollagen proline hydroxylase increased over 4-fold. In all of the experiments the increase in protocollagen proline hydroxylase activity occurred more promptly and it was more marked than the increase in collagen hydroxyproline.

Summary Blood NH3-N, urea, glutamine and keto acids were measured in 29 patients with hepatic fibrosis associated with advanced schistosomiasis and malnutrition. Routine hepatic function tests (BSP clearance, thymol turbidity and bilirubin index) were elevated in all cases. Despite evidence of liver failure and pathologic involvement, none of the biochemical parameters measured were significantly elevated relative to the controls.

Serum levels of monoamine oxidase (SMO) have been determined in 16 normal adults, in 76 patients with hepatic diseases and in 44 patients with non-hepatic diseases. Elevated enzyme levels were found i

20 patients were seen with the hepatic histological features of chronic persistent hepatitis—namely, portal inflammatory infiltration, preserved lobular architecture, and slight-to-absent hepatic fibrosis. 13 had a history strongly suggesting acute virus hepatitis one year before and 7 presented insidiously. Fatigue was the commonest symptom and hepatomegaly the commonest physical sign. Signs of chronic liver disease were absent. After one year, serum-bilirubin and total serum-globulin were usually normal whereas aspartate-transaminase values were marginally increased. In 14 patients, hepatitis associated (Australia) antigen was absent from the serum. The patients were followed for a mean of almost six years. The 12 who underwent serial liver biopsy showed no progression to cirrhosis.

The sequential changes in the livers of 5 calves fed several levels of ragwort ( Senecio jacobea ) in their diet were studied by serial biopsy. Parenchymal megalocytosis, hepatic fibrosis and veno-occlusive lesions developed in all the calves. One calf given 1·2 lb. ragwort per day, showed centrilobular hepatic necrosis. Histochemical enzyme studies showed an early and progressive fall in alkaline phosphatase activity in the parenchymal cells, and a late reduction in succinic dehydrogenase and cytochrome oxidase activity. Non-specific esterase activity persisted in the megalocytes at a high level. There was little if any relationship between the progress of the liver changes and the pattern of changes in the serum enzyme concentration. The changes in enzymes and other constituents of serum are reported in detail in a subsequent paper.

One hundred consecutive patients with Crohn's disease were studied for evidence of liver disease with histological and biochemical mehods. Jaundice occurred in 13, blood transfusions had been given to 85, and many had had hepato-toxic drugs. None of these factors were related to incidence or type of hepatic abnormality observed. Histological abnormalities were present in 94% of 49 biopsies, and these abnormalities were more than minor in 71%. Increased hepatic fibrosis was more common in patients with extensive intestinal involvement with Crohn's disease. Hepatic granulomata and amyloid disease were noted. There was poor correlation between the biochemical and histological abnormalities demonstrated.

SummaryDescription of a case of Schistosoma Intercalation schistosomiasis in which severe hepatic fibrosis was associated with haemolytic anemia. The presence of cold agglutinins and of other unusual antibodies could be demonstrated. This observation favours the role of immune mechanisms in the pathogenesis of schistosomiasis.

Collagen and bile ductular cells, which are rapidly formed during subacute ethionine intoxication, disappear speedily after replacement of ethionine by methionine. The half-life of hepatic DNA was not shortened during recovery, indicating that lack of renewal rather than active catabolism accounts for the disappearance of cells. By contrast, during recovery the half-life of collagen was greatly reduced. Its susceptibility to collagenase and trypsin was increased, and the specific activity of the soluble collagen rose, suggesting depolymerization and denaturation of hepatic collagen. It is suggested that the removal of proliferated ductular cells, which serve as a framework upon which collagen is laid down, leads to secondary changes in the collagen, facilitating its removal.

SummaryOral administration of ethionine produces severe liver cell damage and an intralobular type of hepatic fibrosis with reduction of the fat depots of the entire body and of the normally present fat in the liver. The lesion is prevented by simultaneous administration of methionine.

The effect of 12.5% ethanol ingestion as the only source of fluid intake on cirrhosis induced in rats by the intraperitoneal injection of a 10% carbon tetrachloride solution in olive oil, (0.3 m/ per 100g body weight twice a week for 10 weeks), was studied and the follwoing results were obtained: 1) In the group treated with the combined use of alcohol and carbon tetrachloride, the growth of the rats was limited as compared with that of the group treated with carbon tetrachloride alone. Ten weeks after the beginning of the experiment, the difference in body weight increase between the twc groups was statistically significant. 2) Although the weight of the liver failed to show a significant difference between the alcohol and non-alcohol groups, the weight of the spleen was significantly heavier in the former than in the latter. The amount of lipids in the liver was the same in both groups. 3) The degree of hepatic fibrosis was definitely more intense in the alcohol group, suggesting the facilitating action of alcohol on the development of cirrhosis induced by carbon tetrachloride administration.

Factors responsible for elevation of the portal pressure in Banti's syndrome were analyzed in 82 cases of the authors' department. Although the elevation of the portal pressure was more common and usually more remarkable in extent in cases with chronic inflammation or fibrosis than in those with liver cirrhosis, no definite correlation was revealed between the extent of the hepatic fibrosis and the portal pressure. However, the grade of intrahepatic obliteration of portal branches appeared to be a significant factor influencing the portal pressure. A correlation was indicated between the grade of splenomegaly and the portal pressure, although there were a considerable number of exceptional cases. Moreover, splenectomy was generally followed by a decrease in portal pressure, especially in the case of markedly elevated pressure, although the post-operative level was still above normal in most instances. From these observations both the splenic and the hepatic factors seem to be concerned with the increased portal pressure.

Thirty-six patients with bilharzial hepatic fibrosis were investigated, and five other patients were studied before and after portacaval shunt operation. The liver parenchyma is well preserved in bilharzial hepatic fibrosis and this is reflected in the almost normal results of liver function tests. In 40% of the patients bromsulphalein was retained to an abnormal degree and retention was increased post-operatively in the patients studied before and after portacaval shunt operations. The increased retention of bromsulphalein was found to be the result of prehepatic factors, namely, diminished hepatic blood flow and increased systemic portal collateral circulation either singly or in combination.

The sequential changes in the livers of 10 goats, 3 sheep and 2 calves given daily oral doses of 5 g./kg. body weight of fresh leaves of Ipomoea carnea were studied by serial biopsy. Seven goats and 2 sheep died during the 5 to 107 day period and 3 other goats and 1 sheep were killed in a moribund state, 121 days after the commencement of dosing. Neither of the 2 calves died during the experiment. Inappetence, dullness, dyspnoea and paresis of the hind limbs were prominent clinical signs of Ipomoea poisoning in both goats and sheep. Gradual deterioration of the general condition and debility were seen in one of the calves. Both calves were killed on the 121st day. Reduction in cytoplasmic basophilia of the liver cells, fatty change, loss of glycogen, focal hepatocellular necrosis, accumulation of mononuclear cells and polymorphs, new bile ductule formation and portal fibrosis developed between the 21 and 121 days in goats and sheep. None of the calves showed hepatic portal fibroplasia. Regression of the parenchymal-cell changes was seen in one of the calves. All animals showed an increase in the concentrations of glutamate-oxaloacetate transaminase and arginase in the serum. Glutamate pyruvate transaminase activity did not change. Post-mortem examination of goats, sheep and one of the calves revealed excess fluid in the serous cavities, oedema of the lungs, congestion of the kidneys, subendocardial haemorrhage and necrosis of the liver and hepatic fibrosis.

Overwhelming pneumococcal septicemia, disseminated intravascular coagulation and evidence of splenic hypofunction were observed in a seventy year old woman. A striking finding was the presence of multiple pneumococcal organisms in all of the observed circulating neutrophils. The postmortem findings of splenic and hepatic fibrosis in association with widespread deposits of Thorotrast ® in the spleen, liver and bone marrow suggested the presence of significant functional reticuloendothelial blockade in this patient. Thorotrast is known to produce fibrosis of the liver and spleen, and this material has been used experimentally to produce reticuloendothelial blockade in order to accelerate endotoxin-mediated intravascular coagulation. The degree of pneumococcal septicemia and the evolution of disseminated intravascular coagulation in this patient appeared to have been related to severe reticuloendothelial malfunction. This unusual long-term complication resulting from previous Thorotrast administration was considered to represent the clinical equivalent of a well recognized experimental model.

鉄の組織障害性の有無,特に肝障害と肝鉄沈着の関係は, hemochromatosisの成因などに関連した興味ある問題である.鉄が単独で肝障害を惹起させる可能性は,現在まで否定的であるが,ある種の肝障害が,鉄によつて助長されることは実験的に確認されている事実である.著者らは,四塩化炭素肝障害に鉄経口負荷を行なつたラットの肝組織学的検索から,肝線維化の進展が増強される成績をえ,さらに,鉄吸収吸収鉄の赤血球今の利用,肝貯蔵鉄の検索から,肝線維化の過程で,肝にhemosiderinとしての鉄量の増加することが観察された.これらの結果から,肝障害に肝に多量に沈着してくるhemosiderinも,肝線維化促進の一因子として関与しているものと考えられる.

1. The reactions of the dog's liver to (a) thyroidectomy and (b) both hypophysectomy and thyroidectomy are described. 2. Fatty changes of varying severity were detected in 8 of the 9 hypophysectomized-thyroidectomized dogs, hepatic fibrosis in 7, and severe cirrhosis in 4 animals of this group. Among the thyroidectomized animals histologically demonstrable fatty livers were present in all 8, mild fibrosis was observed in 4, while early and mild cirrhosis was diagnosed in only one dog. 3. Two pathogenetically distinct forms of cirrhosis were present in the livers of dogs with the two operations, namely (a) cirrhosis initiated and developing around the radicles of the hepatic veins, and (b) periportal cirrhosis. Both forms of cirrhosis occurred in dogs that were subjected to the same experimental procedures, and both forms could be found in the same liver. The pathogenesis of these two forms of cirrhosis is described. 4. The relation between fatty change in the liver and the genesis of fibrosis is discussed, and it is suggested that, while fatty change may facilitate the evocation of cirrhosis, this reaction on the part of the supporting and vascular elements of the liver is not solely dependent on the fatty change in the liver cells. 5. The relation between the endocrines and hepatic cirrhosis is discussed. Since cirrhosis was slight in the fatty livers of thyroidectomized dogs, whereas it was often advanced in hypophysectomized-thyroidectomized dogs, it is suggested that in the absence of the pituitary cirrhogenic mechanisms are facilitated in the dog.

A man maintained on 3 g of aluminum nicotinate daily for four years developed impaired carbohydrate metabolism and intraliepatic obstructive jaundice with hypoalbuminemia and edema. All evidence of toxicity reversed with cessation of nicotinic acid therapy. The patient died of cardiac disease two ye

By prolonged immunization of an inbred rat strain with isologous liver homogenate in Freund's complete adjuvant a low grade autoimmune `cholangitis' with periductular fibrosis has been demonstrated. The lesion could be transferred to isogeneic animals by serial spleen cell injections and was associated with mild but variable delayed skin sensitivity to a supernatant fraction of the liver homogenate. It is thought to be due to a combined cellular and antibody-mediated immune response, directed against bile duct constituents. Pulmonary (peribronchial) lesions have also been described in the same animals and are considered to be of similar origin and to represent a cross reaction with tissue of similar embryological (entodermal) origin. This appears to be the first description of periductular hepatic fibrosis clearly resulting from an autoimmune reaction and may provide a model for further study of rather similar histological reactions known to occur in man.

Experimental infections of lambs with Fasciola hepatica are described. The growth rate of the parasite, time of entry to the bile ducts, and time of patency are recorded and a preferential migration of the parasite in the liver parenchyma noted. The gross and histological lesions produced in the liver from 1 to 40 weeks after infection are described and compared with previous observations in cattle.The parenchymal migration of the parasite is shown to consist of two phases, a free migrating phase up to the 6th week, and a localized phase after the 6th week prior to entry into the bile ducts. Hepatic cell regeneration is observed and hepatic fibrosis is minimal. The localized phase of migration is associated with a unique peripheral palisade of giant cells in the fluke tracts and with the formation of pseudofollicular aggregation of lymphocytes. The presence of flukes in the bile ducts produces fibrosis of the duct walls. The walls, however, remain pliable and expanded to accommodate the parasites and calcification was never observed.

The present report on experimental hepatic injury is based on observations amassed during the last 9 years, comprising 1922 rats. It has been shown that there are several dietary factors which may intervene, singly or in combination, in the development of massive or zonal hepatic necrosis. Deficiency of sulfur-containing amino acids is only one of them. From the present studies, tocopherol emerges as an additional protective dietary factor. With regard to the development of massive hepatic necrosis tocopherol may compensate for the absence of sulfur-containing amino acids (cystine, methionine) and vice versa. As a further factor, the quality of dietary fat should be taken into consideration. Fats, like lard and cod liver oil, with a high content of unsaturated fatty acids enhance, whereas fats low in unsaturated fatty acids, such as crisco and butter, retard or prevent the development of massive hepatic necrosis. It is questionable whether with all these dietary factors the etiology of massive hepatic necrosis is completely defined. The interchangeability of sulfur-containing amino acids (cystine, methionine) and vitamin E as leading etiologic factors makes it difficult to accept pure deficiency as the basis of massive hepatic necrosis. The rôle of possible endogenous hepatotoxic substances and their neutralization by cystine (methionine) or tocopherol are discussed. Diffuse hepatic fibrosis is a regular occurrence in rats kept for 100 to 150 days on a diet low in lipotropic factors. Cystine, and, among the fats, lard and especially cod liver oil, have an enhancing effect on the production of hepatic cirrhosis. In rats fed rations free from cod liver oil, and with vegetable shortening such as crisco as source of fat, the incidence and severity of cirrhosis are reduced. Ceroid deposit accompanies cirrhosis only in rats which have been kept on a cirrhosis-producing diet containing fats with a high content of unsaturated fatty acids (cod liver oil, lard). Tocopherol, even when given in excessively large doses (30 mg. daily) will not prevent the formation of ceroid, and will reduce only slightly its total quantity. Under the same treatment the incidence and intensity of cirrhosis remain uninfluenced. Cellular injury in the form of degenerated or necrotic hepatic parenchymal cells, found singly or in small groups in and around the fibrous bands in the cirrhotic liver of rats, is a common occurrence. The fibrotic changes seem to begin, not in the portal spaces, but close to the central vein, although they are not as distinctly and exclusively pericentral as, for instance, in cardiac cirrhosis. Thus, experimental dietary cirrhosis is non-portal. The role of fat infiltration is discussed with special reference to the other microscopic changes found in hepatic cirrhosis. Acute necrotizing nephrosis or various stages of healing of this process are often found with great frequency in rats kept on a cirrhosis-producing diet.

A case of Letterer-Siwe disease with the unusual features of massive splenomegaly, marked hepatic fibrosis and a leucoerythroblastic picture in the peripheral smear, is reported.

Diseases that can afflict children's livers include galactosemia, cystic fibrosis, glycogen-storage disease, polycystic disease and hepatic fibrosis, and sickle cell anemia. Although Wilson's disease and hemochromatosis also start in childhood, their effect on the liver may not become evident until adult life. It is important to recognize both diseases, for Wilson's disease responds to penicillamine and hemochromatosis to repeated bloodletting.

Liver histological appearances were studied in 44 patients treated for psoriasis with methotrexate. Cirrhosis was found in six and hepatic fibrosis in another 11. Of these 17 patients 12 had received methotrexate by a regimen of frequent small dosage, two had been treated by a regimen of intermittent large dosage, while three had been treated at different times by both methods. The prevalence of cirrhosis and fibrosis was significantly greater in patients treated by frequent small dosage than in those treated by intermittent large dosage, though the dose level (mg/month) was similar in both groups. Hepatic fibrosis, sometimes preceding cirrhosis, seems to develop invariably if treatment with small frequent dosage is sufficiently prolonged. In the few circumstances in which this drug is indicated for psoriasis intermittent large dosage is the treatment regimen of choice.

Benzthiadiazine diuretics were administered for 2 weeks to 30 patients with schistosomal hepatic fibrosis who had a high intrasplenic pressure, and their effect on this pressure was studied. The intrasplenic pressure dropped by 80 to 110 mm. saline in 17 per cent. of cases, by 50 to 75 mm. saline in 27 per cent. and by 20 to 40 mm. saline in 20 per cent.; in 36 per cent. the change in pressure was negligible or absent. The pressure rose to the pre-treatment level after discontinuation of the drugs except in two cases in which it remained appreciably lower. The lowering of the intrasplenic pressure was generally proportional to the amount of diuresis induced, and is most probably due to a reduction in the patient's plasma and extracellular fluid volumes rather than to sodium depletion per se.

SummaryThe L- and D-isomers of ethionine are equally effective in producing pancreatic and renal changes in the rat as well as fatty infiltration of the liver and pancreatic damage in the albino mouse. Chronic ethionine administration produces intralobular hepatic fibrosis which is preceded by severe fatty infiltration in both male and female mice.

1) Activities of collagenase-like peptidase and other enzymes were examined on cirrhotic or fibrous liver tissues, and that of Colg was found to be almost in parallel with oxyproline content in the liver tissues of human. But, s-gl activity was not high, when cirrhosis was completed. 2) Proline analogs synthesized for the prevention of fiber formation of the liver were tested against agar-induced granuloma and liver fibrosis experimentally induced in rats. 4-Amino proline or 4-amino-5-methyl proline seemed to be promising.

A new syndrome is described in a brother and a sister who show a similar range of minor dysmorphic features (frontal bossing, high palate, anteverted flares, hypertelorism, carp mouth), colobomata, and a diffuse encephalopathy in association with congenital hepatic fibrosis and childhood polycystic kidney disease. The relationship of the major features to each other is discussed and a differential diagnosis is outlined.