Disturbed Liver Function Research Articles

EXPERIMENTAL CLONOCHIASIS SINENSIS

Rabbits which were experimentally infected with Clonorchis sinensis demonstrated gross anatomic changes in liver tissue characterized by proliferation of connective tissue beginning at the margin of the liver and by nodule formation along impaired intrahepatic bile ducts containing the worms. Hepatomegaly, liver cirrhosis, swelling of the gall bladder, dilatation of the extrahepatic bile duct and ascites were also distinctive findings. Liver function tests, SGOT, SGPT, ALP and total cholesterol, showed abnormally higher values in the infected rabbits than in the control group from the 13th to the 20th day after infection. After the 35th day, as gross anatomic changes became obvious, the liver function tests had almost completely returned to the normal range. Changes in the serum protein fractions, however, maintained the pattern of decreased albumin and increased globulin during the experiment. These data suggest confirmed injury to liver parenchyma and disturbance of liver function.

Effects of potential blood substitutes (perfluorochemicals) on rat liver and spleen.

The effect of an emulsion of perfluorochemicals (PFC) (7 parts perfluorodecalin and 3 parts perfluorotripropylamine, 4.4 g PFC/kg body weight) on organ function was determined. Whereas maximal storage of PFC was reached in the spleen as early as 12 h after PFC administration, the liver attained a maximal PFC content only after 2 days. The increase in weight also differed: a maximum occurred in the spleen on the 4th day, in the liver on the 8th day. Indocyanine green (ICG) clearance showed a small decrease, statistically significant after 12 and 24 h. Colloidal carbon clearance, used as a measure of the function of the reticuloendothelial system (RES) decreased instantly after PFC to less than half the control value; after full recovery a second decrease was seen which lasted till the 4th day after PFC. Pretreatment with C 48/80 or with increasing doses of E. coli endotoxin could largely obviate the depressive effect of PFC-loading on carbon clearance. Serum transaminases increased to about twice the control levels but were normal by the 2nd day, and thereafter. Alkaline phosphatase showed a 2.5 fold increase but returned to control level after the 2nd day. It is concluded that while a severe disturbance of liver function did not occur, the reduction in the capacity of the RES can become a serious factor in the defence against a simultaneously appearing infection if not compensated by activating the RES.

Rifampicin-induced porphyria cutanea tarda

Summary A patient who developed porphyria cutanea tarda and disturbed liver function tests following treatment with rifampicin and isoniazid for a tuberculous psoas abscess is reported. The patient had normal liver function tests prior to receiving anti-tuberculosis chemotherapy, but was subsequently demonstrated to have cholelithiasis. Challenge testing with both drugs incriminated rifampicin as the agent precipitating porphyria cutanea tarda and disturbance of the liver function tests particularly the serum bilirubin. The association between rifampicin and porphyria cutanea tarda has not previously been described but might be expected because of the ability of rifampicin to induce various liver enzyme systems including delta aminolevulinic acid synthetase activity. This further illustration of rifampicin hepatotoxicity emphasizes the need for regular monitoring of liver function when rifampicin is prescribed. Rifampicin should be used with extreme caution in any patient with a previous history of porphyria cutanea tarda.

A Double-Blind Controlled Study on the Antihypertensive Effectiveness of Uricosu-ric Diuretic FR 3068 in Essential Hypertension as Compared with Methyclothiazide

The antihypertensive effectiveness, influence on laboratory parameters and adverse reaction of FR 3068 (tienilic acid, FR), a new nonthiazide diuretic developed by Albert Rolland Co. of France with uricosuric properties, were evaluated by double-blind parallel group comparison with methyclothiazide (MCTZ).Placebo was initially administered for a period of at least 2 weeks. Patients with systolic blood pressure of≥150 mHg and diastolic blood pressure of≥90 mmHg at the termination of the placebo control period were enrolled as subjects .FR and MCTZ were administered in fixed dosages of 250 mg/day and 5 mg/day respectively. The duration of treatmentwas 8 weeks.Blood pressure significantly decreased in both groups in 2 weeks. In MCTZ group, blood pressure showed a continuous, gradual decrease until Week 8. In FR group, a mild reduction in blood pressure was seen from Week 2 onwards, at Week 8 there being a further decrease.Comparison of laboratory data before and after treatment revealed increase in BUN and serum Na+ in FR group.In MCTZ group, increase in some hematological indexes and serum creatinine value and decrease in serum Na+, K+ and Cl- were seen. Severe liver function disturbance was noted in one patient of FR group.Serum uric acid increased in MCTZ group.In contrast, it decreased in FR demonstrating a distinct uricosuric effect.Symptoms appearing during the treatment period which did not occur during the control period consisted of those of central nervous, autonomic nervous and gastrointestinal systems. These symptoms occurred in 15 of 50 patients in the FR group and 7 of 46 patients in the MCTZ group.The usefulness of both drugs was globally assessed based on symptomatic change, antihypertensive effectiveness, adverse reaction, laboratory data abnormalities, etc. There was no significant intergroup difference at 5% level.

Hormone Secretion in Alcohol-Induced Pseudo-Cushing's Syndrome

We describe the clinical and biochemical characteristics of alcohol-induced pseudo-Cushing's syndrome in two patients with signs and symptoms of Cushing's syndrome and slight disturbances in liver function. An insufficient suppression of plasma cortisol to the overnight administration of 1 mg of dexamethasone was accompanied by an absent diurnal rhythm of plasma cortisol and an increased cortisol secretion rate. The plasma cortisol levels at 8 AM normalized during hospital admission (ie, alcohol withdrawal) at the same rate or parallel with the serum gamma-glutamyl transferase concentration. A normal increase of plasma cortisol, adrenocorticotropic hormone, and growth hormone in response to an insulin induced hypoglycemia was not compatible with the diagnosis Cushing's syndrome. However, the result of a differential diagnostic test with metyrapone was compatible with the presence of Cushing's disease. An erroneous diagnosis of Cushing's disease can be easily made in patients with alcohol-induced pseudo-Cushing's syndrome.

The incidence of urinary tract calculi after small-intestinal bypass operations for treatment of obesity

Jejunoileal bypass operations have been used for more than 20 years for the treatment of massive obesity. This treatment results in malabsorption with diarrhoea, especially during the first year after the operation. A high incidence of urinary tract calculi have been found in these patients (4, 5, 15, 19, 24). Other known late complications are transient disturbances in liver function and electrolyte balance (5).

Transplantation of isolated islets of langerhans in diabetic dogs. I. Results after allogeneic intraportal islet transplantation

Twenty partially inbred German shepherd dogs were made diabetic by intravenous administration of streptozotocin (25 mg/kg) 1 and 3 days after partial pancreatectomy. Ten diabetic dogs received intraportal transplants of allogeneic islets of Langerhans isolated by collagenase digestion and Ficon gradient separation. After transplantation the mean fasting serum glucose level fell from 368 ± 74 to 108 ± 52 mg/dl. Normal glycemia was maintained for at least 3 weeks before rejection occurred. The mean survival time of the 10 recipients was 76 ± 30 days, while the 10 diabetic control dogs had a mean survival time of 30 ± 7 days. Intravenous glucose tolerance test curves were clearly better in recipient dogs than in the diabetic control dogs for at least 4 weeks after islet transplantation. Concentrations of immunoreactive insulin (IRI) in the portal vein in the superior vena cava were also significantly higher than in the diabetic control dogs 4 weeks after islet transplantation. The mean peak concentration of IRI in the superior vena cava of transplanted dogs after glucose administration was higher than that in the portal vein, indicating that the transplanted islets secreted insulin in response to glucose stimulation. Portal hypertension or disturbance of liver function did not occur after transplantation of isolated islets. These results show that the intrahepatic site is appropriate for transplantation of isolated islets in a large animal model of diabetes, and provide a basis for future application in man.

Transplantation of isolated islets of langerhans in diabetic dogs. III. Donor selection by mixed lymphocyte reaction and immunosuppressive treatment

By means of collagenase digestion and the Ficoll gradient separation technique, viable islets of Langerhans were isolated from canine pancreas. These islets were transplanted into the livers of diabetic dogs. Experimental diabetes was induced by subtotal pancreatectomy and two injections of 25 mg streptozotocin/kg body wt. Five recipients received islets from weakly histocompatible donors and were immunosuppressed by administration of azathioprine and anti-thymocyte serum. Diabetes was ameliorated over a period of 1 year. Glucose tolerance test curves and immunoreactive insulin concentrations in the portal and superior vena cava were significantly impaired in comparison to the diabetic control dogs. No signs of portal hypertension or of disturbances of liver function were observed in recipient dogs during the duration of the experiment.

A Bile-acid-rich High-density Lipoprotein (HDL) in Acute Hepatitis

Severe liver dysfunction is often associated with alterations of plasma lipids and lipoproteins. In this study the high-density lipoprotein (HDL) class has been further investigated. HDL from patients with acute, cholestatic hepatitis (n = 10) was isolated and compared with that of normals. Lipid and protein analyses were performed during the acute stage of the disease, with consequent follow-up studies. It was found that (1) only apo A-I was decreased by 50% in the isolated HDL fractions, whereas apo A-II remained unchanged; apo A-I in total plasma was normal; (2) immunoelectrophoresis of hepatitis HDL against monospecific anti-A-II revealed one precipitin line but two or more bands against anti-A-I; (3) concomitant with an increase of phospholipids and a decrease of triglycerides and the total cholesterol fraction, hepatitis HDL contained 10--12 times more bile acid than normal HDL. Chenodeoxycholic acid was the predominant bile acid. These alterations were fully reversible when patients recovered. These parameters seem to be sensitive markers for the degree of disturbance and restoration of liver function. The structural-functional implications of the observed compositional changes of HDL during cholestasis are discussed.

Liver function after massive transfusions of packed red cells

The liver function was studied in 16 dogs after experimental transfusion of massive doses of packed red cells in order to identify which component of the blood influences the liver function. Transfusion of massive doses of packed red cells was found not to cause any significant changes in the excretory, assimilative, and protein-forming functions or in the content of transaminases. In the control group receiving transfusions of massive doses of whole homologous blood considerable disturbances of liver function were found. The results confirm the view that one cause of disturbances of liver function in the “massive blood transfusion syndrome” is incompatibility of the plasma proteins of the donor and recipient.

Regulation of blood ammonia.

Disturbance of ammonia metabolism is an important but not the only factor in the genesis of hepatic coma. In this review mechanisms controlling the concentration of ammonia in the blood other than disturbed liver function have been discussed. The key function of ammonia in the pyridine nucleotide cyde has been outlined and it is suggested that the function of this cycle in patients with liver disease would repay further study.

LIVER FUNCTION TESTS FOLLOWING ANAESTHESIA

Liver function tests were performed in 41 patients who required repeated anaesthetics for genitourinary surgery, and who had received multiple halothane anaesthetics in the past, first following anaesthesia using halothane and then following an anaesthetic without halothane. There was a smaller frequency of disturbance of liver function after halothane than after the non-halothane anaesthetic. There was no obvious relationship between the number of anaesthetics, or the total duration of anaesthesia, and the disturbance of liver function tests.

和服しみ抜き作業者にみられたパークロル・エチレン中毒と思われる２症例

1) Recently, dry cleaning with perchloroethylene has become available in Japan, and this dry cleaning has become to be used even for cleaning Japanese clothes made of silk. Two patients visited us one after another, who were engaged in cleaning Japanese clothes and thought to be poisoned by perchloroethylene. Their health states and working conditions were examined from the viewpoint of occupational hygiene.2) The patients complained similarly of memory disturbance, easy fatigability and decrease of tolerance to alcohol after contact with perchloroethylene. The medical examination at the Nagoya University hospital revealed a slight disturbance of liver function, a slight narrowness of left visual field, and diffuse distribution of α rhythm, sporadic θ activities and mixed fast wave in EEG in the first patient. And, evident disturbance of liver function, decrease of retinal potential and diffuse distribution of a rhythm and mixed fast wave in EEG were revealed also in the second patient. Liver function and function of the central nervous system were commonly disturbed in the two patients, although the degree of the disturbance was different between them.3) A large amount of perchloroethylene was used in the work room of the first patient, and his work room was narrow. Therefore, high concentrations of perchloroethylene were detected at the time of survey. The concentration of perchloroethylene was 30-70 ppm under his nose at washing Japanese clothes by hand brush, and 100-400 ppm near Japanese clothes wetted with perchloroethylene and hanged on.the wash-line poles.As regards to the second patient, the work room was fairly improved after his health disturbance. But high concentrations of perchloroethylene were detected at the out of the fun for ventilation and at the exhaust opening, and this fact proposes another kind of environmental pollution problem.4) Japanese clothes wetted with perchloroethylene were hung on wash-line poles to become dry naturally in the room so that the clothes did not become wrinkled and remain soft after cleaning. Consequently, perchloroethylene is consumed about 60 % by weight of Japanese clothes and on top of that, most of perchloroethylene is vaporized in the work room, whereas in the ordinary dry cleaning perchloroethylene is consumed at about 5% by clothes weight, most of which is exhausted from the cleaner to the outdoor. Accordingly, the concentration of perchloroethylene in the work room may become very high and the worker may have a danger to be poisoned with perchloroethylene. As there are many workers engaged in this kind of work in Japan, it is necessary to make countermeasures for them from the viewpoint of occupational hygiene.

Lactic acidosis and diffuse histiocytic lymphoma (DHL)

Four patients with advanced diffuse histiocytic lymphoma who developed lactic acidosis are described. All four patients demonstrated disturbed liver function tests. In two of the patients, the lactic acidosis was unresponsive to treatment. The third patient responded successfully to the early initiation of combination chemotherapy with achievement of a clinical remission and correction of the lactic acidosis. The fourth patient responded to the initiation of chemotherapy with abatement of his lactic acidosis, but expired probably as the result of a pulmonary embolus. It seems likely that extensive hepatic infiltration may be one of the factors contributing to lactic acidosis in patients with diffuse histiocytic lymphoma. The early initiation of antineoplastic therapy may be important in the management of patients with histiocytic lymphoma and lactic acidosis.

Ferastral®, an Iron‐poly (sorbitol‐gluconic acid) complex, in the Treatment of Severe Iron‐deficiency Anaemia in Pregnancy

Thirteen pregnant women with iron-deficiency anaemia have been treated with Ferastral. In a further seven women, Ferastral was given 24 hours before delivery, when induction of labour was indicated, to investigation of iron concentration in maternal serum, cord blood and amniotic fluid simultaneously. The efficacy of Ferastral was demonstrated by a significant increase in haemoglobin and haematocrit. No serious reactions occurred and no evidence was found of disturbance of liver or renal function. It was shown that Ferastral does not pass the placental barrier and that no direct transport takes place through the uterine wall or amnion. No effects on the newborn were demonstrated.

Diagnostic Usefulness of Plasma Carcinoembryonic Antigen Levels in Acute and Chronic Liver Disease

Raised plasma carcinoembryonic antigen (CEA) levels were found in over 90% of 71 patients with chronic liver disease and 50% of 16 patients with acute liver damage. Levels increasing chronicity and clinical severity of disease. In individual patients, the plasma CEA level fluctuated with the clinical condition. Persistently normal levels were never found in patients with chronic liver disease in poor clinical condition. A very high level suggests a bad prognosis. If CEA is considered together with SGPT, a discriminant function can be calculated, separating patients with acute liver damage and those with an acute exacerbation of chronic active hepatitis, with a high degree of certainty. In acute damage, peak CEA levels occur later than the time of maximum liver necrosis, suggesting that the rise is not owing to release of CEA from damaged cells. There is no significant difference in CEA level between patients with and without spontaneous or surgical portosystemic shunts, suggesting that high levels are not attributable to bypass of the liver. The timing of the rise in CEA in acute liver damage suggests that raised levels may be associated with regeneration. The tendency for higher levels to occur in those patients with greater disturbances of liver function suggests altered metabolism or excretion of CEA.

The activity of γ-glutamyl transferase in the serum of multiple sclerosis and other neurological diseases

1. 1. In the sera of 142 neurological patients, including 35 cases with multiple sclerosis (MS), and 20 normal controls the γ-glutamyltransferase (γ-GT) activity was determined. The result of this investigation was compared with the “combined hippuric acid test” formerly often used in MS patients. 2. 2. The MS patients are the only group which significantly differs from the normal controls. There are also small differences between them and some of the other neurological patient groups. About one-third of the MS patients show moderately pathological serum activites. On the other hand, patients with a definite liver affection, especially chronic alcoholics, regularly show an even more important elevation of the values, which makes this test a sensitive tool for the screening of alcohol-induced liver intoxications. 3. 3. Although the γ-GT test in not quite as sensitive in indicating organic defects in MS patients, it seems to reflect a disturbed liver function in the same way as the more complicated “combined hippuric acid test”. It may therefore be used as a simple tool for finding and following up organic defects in MS patients.

A field survey on the health status of workers in dye-producing factories.

Health status of the workers in dye-producing plants were examined repeatedly in winter and in summer. The items studied cover 1) diazo-positive metabolites in urine 2) methemoglobinaemia, Heinz bodies, methemoglobin reductases and anaemia, and 3) liver function. The urinary diazo-positive metabolite level in the exposed was higher than that in the non-exposed and marked a conspicuous increase in summer as compared in winter, indicating significant intake of the aromatic nitro-amino compounds, while no significant methemoglobinaemia, Heinz bodies, anaemia nor disturbed liver function was observed in any group of the examinees. The results were discussed in connection with the dose-effect relationship, and compared with the experiences in the past.

LIVER FUNCTION TESTS FOLLOWING ANAESTHESIA

Liver function tests were performed in 41 patients who required repeated anaesthetics for genito-urinary surgery, and who had received multiple halothane anaesthetics in the past, first following anaesthesia using halothane and then following an anaesthetic without halothane. There was a smaller frequency of disturbance of liver function after halothane than after the non-halothane anaesthetic. There was no obvious relationship between the number of anaesthetics, or the total duration of anaesthesia, and the disturbance of liver function tests.

Clinical and Laboratory Studies in Cholestasis of Pregnancy

Summary: A prospective study was made of 44 patients with cholestatic jaundice of pregnancy. Serial urinary oestriol, pregnanediol and plasma progesterone levels were measured in addition to liver function tests. Spontaneous premature labour occurred in 41% of patients, and there were three unexplained stillbirths (7%). Whilst the occurrence of premature labour and the severity of pruritus was often related to the degree of hyperbilirubinaemia and cholestasis, this was not invariable. Furthermore, perinatal wastage did not correlate closely with the disturbance of liver function or with steroid levels within 72 hours of delivery.