T. Kanetaka

Drug-induced generalized phospholipidosis.

Drug‐Induced generalized phosphollpldosis in human beings is described. Detailed study of phospholipid fatty liver, which was first reported by us in 1968, disclosed that phospholipid accumulation is not only found in the liver but is also distributed throughout the body. From clinical as well as experimental survey, it may be concluded that this phospholipido‐sls was caused by administration of 4.4′‐diethylamlnoethoxy hexestrol. Three autopsy cases showed liver cirrhosis of a peculiar form, such as fine granular thln‐septal cirrhosis with phospholipid deposition and alcoholic hyalines. This septal cirrhosis may have resulted from phospholipid deposition. The relationship between alcoholic hyaline and lipid metabolism is discussed. ACTA PATH. JAP. 22: 517–531, 1972.

PHOSPHOLIPID FATTY LIVER: A PROPOSAL OF A NEW CONCEPT AND ITS ELECTRON MICROSCOPICAL STUDY

A new type of fatty liver, in which a large amount of phospholipids deposited in the liver parenchymal cells, is presented. Electron microscopically, numerous myelin figures filled up the cytoplasm of the enlarged liver parenchymal cells. They showed a typical concentric lamellar structure and existed singly or gathered together in the cytoplasm. Sometimes they were limited by a single membrane. This new type of fatty liver was found in the patient with markedly enlarged liver and probably with some chronic inflammation. Morphogenesis of these myelin figures and causal relationship to chronic infiammation were discussed, and a new concept as phospholipid fatty liver was proposed.

TOXIC LIVER INJURIES

Recently, toxic liver injury has become an issue facing modern medicine. Unfortunately, some organic solvents or drugs might be toxic, particulary to the liver. Although there might be no active drugs without side-effects, being assured of complete safety in clinical use, drugs are to be needed for practice. It is, therefore, essential to have an accurate knowledge of their possible but undesirable effects, and prophylactic caution too must be preferential for industry.

Prognosis of liver cirrhosis

Clinical surveys on 224 patients with liver cirrhosis were made to assess the recent advance in the treatment for liver cirrhosis. These patients consisted of those received treatment in our Department in the years from 1938 to 1965.SummaryClinical surveys on 224 patients with liver cirrhosis were made to assess the recent advance in the treatment for liver cirrhosis. These patients consisted of those received treatment in our Department in the years from 1938 to 1965.Of the principal causes of death in cirrhotics studied, hepatic coma has recently decreased and bleeding from the alimentary tract has increased. Cachexia or infection as the cause of death has also decreased.Such an improvement is likely to be attributable to introducing a high protein, high caloric diet. Alternatively, the therapeutic use of potent diuretic drugs has brought success in the treatment of ascites and edema, however, there has been found no betterment in the survival rate of cirrhotics with ascites.Among the abnormal findings which were shown in cirrhotics, icterus index more than 30, bromsulphalein retention exceeding 30 percent in 45 min, albumin/globulin ratio less than 0.5, zinc sulfate test more than 30, and reduced albumin less than 1.5 g/dl were of much omnious significance. The majority of those died within a year. Prothrombin time, total protein values, and transaminase activities in sera were not to be related to the prognosis.Most of deaths without any marked abnormalities in laboratory findings died of massive hemorrhage from the alimentary tract.

Statistical studies on morphology and clinical features of fulminant hepatitis A survey of 118 cases in the authors’ department

SummaryFulminant hepatitis is a name based on its clinical symptoms, and it will be agreed to define the disease characterized by severe necrosis of hepatic parenchyma and serious clinical features: peracute course, progressive jaundice, hepatic coma and death by hepatic failure. However, there are at least two different opinions as to the term from onset to death, or the duration of serious conditions of the disease: the term is to 2 to 3 weeks or to 8 to 12 weeks. The latter was suggested recently by Trey and Chalmer’s group in Boston, as well as by Takahashi’s group in our Country, to which the authors have belonged.Nevertheless, some other investigators focus chiefly on the psychoneurotic symptoms even without morphological findings of hepatic necrosis. Actually, we also encountered one case having no trace of hepatic necrosis, though she had been accompanied with psychoneurotic symptoms. Since biopsy specimens are examined after pulling through the peak of the disease, the morphological changes might be already cured. Although such cases are also preferable to be treated as fulminant hepatitis, they should be clearly distinguished from the fulminant in the review of the disease, particularly of the prognosis.Incidentally there may be another essential problem of the hepatitis or morphological hepatic necrosis caused by poisoning other than by a virus, which is commonly presumed to be the cause of fulminant hepatitis.This paper deals with these problems, based on the cases, which were observed in the past ten years.

A consideration on the treatment of acute virus hepatitis with glucocorticoid

Fif ty percen t surv iva l of s teroid g roup was 4 y e a r s and 3 m o n t h s wh ich was longer t h a n t ha t of 3 y e a r s and 3 m o n t h s in control group. F i f ty cases of our pa t i en t s in th is s tudies were in a d e c o m p e n s a t e d s t age of c i r rhos is a t the t ime of first admiss ion in ou r hospital , of w h o m 17 were on s teroid reg ime and the o the r 33 were in control g roup . T h e 3 y e a r s su rv iva l ra te of those pa t i en t s in d e c o m p e n s a t e d s tage were 71 pe rcen t in s teroid g roup and 50 pe rcen t in control g roup , but aga in no di f ference be tween 2 g r o u p s was found in 5 y e a r s su rv iva l ra te . In the next , the di f ference of the effects of the s teroid h o r m o n e be tween types of hepat ic c i r rhosis , portal and postnecrot ic , was s tudied. T h r e e yea r s survival ra te of pa t i en t s wi th portal c i r rhos is was 90 pe rcen t in s teroid g roup and 72 pe rcen t in control group, and tha t of postnecrot ic cases was 67 pe rcen t in steroid g r o u p and 54 percen t in control g roup . But in postnecro t ic cases, 4 yea r s su rv iva l rate was be t te r in control g roup (44%) t h a n in s teroid g roup (26%).

A comment on concept of subacute hepatitis

T h i s pape r r epo r t s t he r e su l t s of an i nves t i ga t i on of l iver f u n c t i o n s of 531 chron ic alcoholics a d m i t t e d to Sohbu Hospi ta l be t ween 1965 and 1969. T h e l iver f unc t i on t e s t s used for the s tudy are as fo l lows: BSP tes t , S-GOT, S-GPT, S-LDH, to ta l bi l i rubin, ;--globulin, to ta l cholesterol, and t he s e r u m L D H i sozyme was m e a s u r e d in s o m e cases . Of t he r e su l t s of t he b r o m s u l p h a l e i n exc re t ion tes t , 70% was cons ide red as a b n o r m a l , and especial ly 20% of the to ta l sub j ec t s was classif ied as h igh ly a b n o r m a l (BSP over 15%). Moreover , in cons ide rab le n u m b e r of cases S-GOT, S-GPT, and S-LDH were p roved to be increased each , and s o m e alcohol ic pa t i en t s revea led the severe cl inical p ic tu res of a cu t e or s u b a c u t e hepat i t is . Of t he 531 pa t i en t s tes ted , 3 were dead wi th in 1-2 m o n t h s a f t e r admi s s ion . In t he s e r u m L D H i sozyme p a t t e r n of t he pa t i en t s who showed a inc reased r a t e of S-GOT, S -GPT and of S-LDH, t he r e a p p e a r e d t he hepa t i t i s l ike p a t t e r n wh ich was cha rac t e r i zed by dec reased LDH 1 and by inc reased LDH5~ (Authors abstract)

Clinical observation on acute hepatitis, with special reference to cases shown unusual course

94 cases of acute hepat i t is were observed in our clinic dur ing past 3 years. They included 48 cases of infect ious hepat i t is and 46 cases of serum hepati t is . F luminan t hepat i t is were 7 cases (7.5%), cholangioli t ic type were 11 ones (11.7%), included 6 who were older than 60 years. 3 cases (3.2%) of them were fatal, 6 (6.4%) progressed to l iver cirrhosis . 6 (12.5%) of infect ious hepat i t is progressed to prolonged or chronic hepati t is , while 14 (21.2%) of serum hepat i t i s did to them. Case report Case 1 was 61 years old female wi th dominant jaundice (total b i l i r u b i n > 2 0 m g / d l , total cho le s t e ro l>380mg/d l and a lka l inephospha tase>5 Bessey unites), under the diagnosis of extrahepat ic obs t ruct ion or in t rahepat ic cholestasis operat ion was done, but ext rahepat ic obstruct ion was not found. Her illness progressed to chronic cholangioli t is . Case 2 was 32 years old female. Dominant elevations of t r ansaminase act ivi ty were observed at six t imes dur ing 3 years, and she was diagnosed to acute hepat i t is by liver biopsy. In interval, her l iver funct ion tes ts showed normal value and biopsy specimens did normal feature. She was dignosed to chronic reccurent hepat i t is .

Hepatocellular adenoma: A case with a solitary huge one surgically excised successfully

SummaryA case of hepatocellular adenoma was reported, who showed bleeding tendency, coagulation abnormalities, amenorrhea, hypertention, and albuminuria which all returned to normal negative after successful right hepatic lobectomy. Laboratory data on blood coagulation was suggstive of incrcases of Ac-globulin (Factor V, Proaccelerin) and/or fibrin-stabilizing-factor in the plasma probably released from the adenoma although they were not determined. Hypertention and albuminuria might be induced by downward displacement of the right kidney and stretching of the right renal arterties by a huge tumor, and it is most likely that this adenoma was the cause of these adnomalities: bleeding tendency and also amenorrhea.Hepatocellular adenoma is a rare tumor of the liver, besides that with some metabolic abnormalities is extremely rare. Hepatomas accompanying some metabolic functions have been already reported as “paraneoplastic syndromes”, but none of such a case as shown here was presented. This case is probably the first one of hepatocellular adenoma with probable increases of Ac-globulin and/or fibrin-stabilizing-factor in the plasma and with some other syndromes which all disappeared after removing the adenoma.

Studies on lipid metabolism in biopsy specimens of human livers

tively. 0.4g ot sulfonated polyetyrene cation exchanger (mesh beat 40, I .R. 120) which was washed previously was mixed with 2.0m/ of heparinized test plasma in a stoppered test tube. After 5 minutes of stirring, the mixture was centrifuged and the sedimented resine was washed with about 4ml of destilled water 4 times. And then 2 m / o f sodium phenoxide solution (phenol 25g, 78ml of 4.0N NaOH in 1000ml of destilled water), 3ml of 0.01 per cent sodium nitroprusside and 3ml of sodium hypochloride were added. Each of these addition was followed by st irr ing for 1 minute. Thereaf ter these mixture was incubated at 37~ for 5 minutes. It was determined by colourimetry of 610m/~ of wave length. The colourimeterically obtained results were multiplyed by 17/14 to get the blood ammonia level. There was found a good correlation between the results of the two methods and also the recovery test was quite satistactory. Basing on our experiences, it was thought that this new method using the ion exchanger gave a correct result and was so simple to be done as a clinical laboratory use.