Indices Of Hepatic Function Research Articles

Specific 125I-radioimmunoassay for cholyglycine, a bile acid, in serum.

The concentration of the conjugated bile acid, cholylglycine, in serum is a sensitive and specific indicator of hepatic function. We describe a convenient, specific, and precise radioimmunoassay for cholylglycine, in which 125I-labeled cholylglycyltyrosine is used as tracer. In addition, a blocking agent in the buffer system eliminates binding of bile acids to serum albumin. Therefore no extraction is required. We found no interference by (a) abnormal concentrations of albumin or gamma-globulin, (b) lipemic sera, (c) hemolyzed sera, (d) anticoagulants, or (e) various commonly used drugs. The reference interval for fasting subjects is estimated to be 0.0 to 0.6 mg/L. Our clinical studies show that serum cholylglycine concentrations are usually abnormal in most hepatobiliary diseases, such as viral hepatitis, alcoholic liver disease, cirrhosis, and pediatric liver diseases.

Hepatic and renal effects of low concentrations of methoxyflurane in exposed delivery ward personnel.

During five alternating three-week periods either methoxyflurane-nitrous oxide or nitrous oxide alone was used for obstetrical analgesia. Delivery ward personnel were followed by venous blood samples once a week. Analyses of blood urea nitrogen, serum uric acid, SGOT and SGPT showed significantly elevated levels three days after exposure to methoxyflurane. This study demonstrates the importance of the scavenging of anesthetic gases to reduce the exposure of personnel to inhalational agents used in delivery suites. Since definite alterations in the indices of both hepatic and renal functions were recognized in obstetrical personnel following exposure, a re-evaluation of the use of methoxyflurane for obstetrical analgesia is suggested.

Control of late postoperative ventricular arrhythmias with phenytoin in young patients

Ventricular arrhythmias probably initiate the events leading to sudden death in patients who have recovered uneventfully from surgery for congenital heart disease. It is therefore recommended that antiarrhythmic therapy be given to all patients who have had surgery for congenital heart defects and who have ventricular arrhythmias found in a routine electrocardiogram taken after the immediate postoperative period. The response of ventricular arrhythmias to treatment was studied in six ambulatory patients aged 7 to 27 years (mean 16.5) who had had surgery a mean of 10.7 years before the arrhythmia was recognized. Four patients had unsatisfactory repair of the congenital defect; the two other patients had only a palliative operation. Each patient's electrocardiogram was monitored continually by tape recording. Each received phenytoin, 3.75 mg/kg body weight, every 6 hours for four doses, then 1.9 mg/kg every 6 hours until the serum concentration of phenytoin was 15 to 20 μg/ml. This serum concentration was maintained with the daily administration of 2.5 to 3 mg/kg every 12 hours. In the 24 hours before treatment, two patients had ventricular tachycardia, two had paired premature ventricular complexes and two had 10 or more single premature ventricular complexes/hour. After treatment, all patients had “effective control” (one or less premature ventricular complex/hour for 12 consecutive hours). This control was achieved with phenytoin in five patients, but one patient required the addition of disopyramide (2 mg/kg every 6 hours). All five patients undergoing a treadmill test before treatment had premature ventricular complexes during or after exercise; after treatment, only one had premature ventricular complexes after exercise. The patient who required two drugs was unable to perform a treadmill test. The mean effective serum phenytoin concentration, 15.7 μg/ml (range 8.5 to 20.0), was reached at a mean time of 61.2 hours (range 42 to 80) after the start of phenytoin therapy. Ataxia occurred in two patients with serum phenytoin concentrations of 16 and 20 μg, but not in the other four, three of whom had serum concentrations greater than 20 μg/ml. Echocardiographic, hematopoletic, hepatic and renal function indexes remained constant with treatment. It is concluded that (1) phenytoin suppressed ventricular arrhythmias in six children and young adults after surgery for congenital heart disease; (2) the effective serum concentration of phenytoin was approximately 15 μg/ml, but varied widely; and (3) this concentration was achieved within 48 to 72 hours when an oral loading dose was administered.

α-Fetoprotein as a marker for hepatic regeneration in the dog

A radioimmunoassay for human α-fetoprotein (AFP) was utilized to quantitate AFP following partial liver resection in the dog. Nine dogs were studied; seven underwent 70% hepatectomy and two received sham operations. Serum AFP, alkaline phosphatase, glutamic-oxaloacetic transaminase (SGOT), glutamic-pyruvate transaminase (SGPT), total bilirubin, and galactose elimination capacity (GEC), a quantitative index of hepatic function, were measured preoperatively and at regular intervals postoperatively. Following 70% hepatectomy, AFP was first noted to be increased from the preoperative level (94 ± 7 SEM ng AFP activity/ml) on the fourth postoperative day (556 ± 75; P < 0.05) with a peak value being reached between Days 8 and 12 (1008 ± 111; P < 0.025). AFP then gradually decreased, returning to normal by Day 24 (116 ± 12; P > 0.5). These changes in AFP concentration parallel, in a slightly delayed fashion, hepatic proliferative activity as measured by DNA synthesis following hepatic resection in the dog. No alteration in AFP concentration was seen in the control animals. Elevations in SGOT, SGPT, and alkaline phosphatase were observed in all dogs following liver resection from Day 2 through 26. In contrast to AFP, changes in the serum concentrations of these enzymes were highly variable in both magnitude and duration. GEC was not significantly altered following liver resection in any dog. The results indicate that AFP is superior to liver enzymes and GEC as a marker for hepatic regeneration in the dog.

High molecular weight alkaline phosphatase: A clinical study

High molecular weight alkaline phosphatase activities have been measured in the sera of 72 patients with a variety of forms of liver disease, 14 patients with bone disease and 8 healthy volunteers. These measurements have been compared with measurements of other indices of hepatic function in order to establish the place of this enzyme in the diagnosis of liver disease. High molecular weight alkaline phosphatase proved to be a sensitive and specific test for detecting liver disease, particularly obstructive liver disease. It was better than all the other liver function tests in distinguishing liver metastases from other hepatobiliary diseases. It may therefore prove especially useful in the early detection of liver metastases.

Alterations in brain octopamine and brain tyrosine following portacaval anastomosis in rats.

Abstract— Following portacaval anastomosis in the rat, plasma and brain tyrosine are markedly elevated, although brain tyrosine is increased to a significantly greater degree than plasma tyrosine. Both plasma and brain tyrosine as well as brain octopamine correlated well with a presumed index of impaired hepatic function, the ratio of liver weight to body weight in shunted rats. A significant positive correlation was observed between brain octopamine and brain tyrosine. The significance of these findings to the etiology and treatment of clinical hepatic encephalopathy is discussed.

Gyrate Atrophy of the Choroid and Retina with Hyperornithinemia

A case of gyrate atrophy of the choroid and retina and hyperornithinemia in a 28-year-old man was subjected to extensive clinical and biochemical investigation. The familial occurrence of the ocular disease and of abnormality of amino acids was unique to this patient, being absent in parents and siblings. He presented with progressive visual loss, and had cataracts and large areas of peripheral lacumar atrophy. Clinically there was no other abnormality. However, he was hyperuricemic and had an abnormal electroencephalogram. Despite otherwise normal biochemical indices of hepatic, renal, and muscle function, selective catheterization of an artery, the hepatic vein, the renal vein, and a deep forearm vein showed all of these circulatory beds to be producing ornithine according to arteriovenous difference measurements. Cerebrospinal fluid and urine contained increased amounts of ornithine. Though electromyography was normal a muscle biopsy specimen was abnormal. Clinical tests including arginine loading, glucose tolerance testing, and other measurements of blood variables provided inferences as to the metabolic locus of the abnormality. The syndrome is a systemic multiorgan disorder in which the choriod and retina would appear to be target organs and the hyperornithinemia to be of as yet undetermined cause and pathogenic significance.

Behavioral effects of a new dopamine-β-hydroxylase inhibitor (fusaric acid) in man

Publisher Summary This chapter discusses behavioral effects of a new dopamine-β-hydroxylase (DβH) inhibitor (fusaric acid) in man. DβH, an enzyme localized in noradrenergic neurons, converts dopamine to norepinephrine. Thus, the administration of a DBH inhibitor would be expected to decrease central norepinephrine selectively while producing either no change or an increase in central dopamine. Fusaric acid is well tolerated with a minimal effect on blood pressure and no alteration in indices of hepatic, hematologic, renal, or endocrine function. An increase in psychosis could be a nonspecific reaction to a drug-inducedorganic brain impairment rather than a direct result of DBH inhibition. Fusaric acid on the other hand, of the available DβH inhibitors, appears to be the most specific, particularly in that it does not inhibit aldehyde dehydrogenase. Also of importance is the fact that fusaric acid has not been associated with any signs of an organic brain syndromein any of its clinical trials.

HYPERAMMONEMIA DUE TO A DEFECT IN HEPATIC ORNITHINE TRANSCARBAMYLASE

A 9-year-old girl with vomiting, changes in behavior, coma, and evidence of hepatic dysfunction at 3½ years of age was found to have hyperammonemia and decreased activity of liver ornithine transcarbamylase. When her dietary protein was reduced, she had improvement in her clinical condition and a return to normal of all hepatic function indices. Despite a defect in an enzyme of ornithine metabolism, she did not have hyperaminoacidemia, specifically hyperornithinemia, even when she had hyperammonemia. When she ingested a large amount of ornithine (300 mg/kg) she developed hyperornithinemia and hyperornithinuria. She also had orotic aciduria despite having normal activities of red cell orotidylic decarboxylase and pyrophosphorylase. Treatment with a low protein diet and citric acid supplements has been successful in preventing hyperammonemia and promoting growth and development.

Alterations in indices of liver function in congestive heart failure with particular reference to serum enzymes

Serial liver function tests were performed in 175 patients with right-sided heart failure of diverse etiology. The cases were classified as acute or chronic depending on the duration and severity of congestive failure. The indices of liver function studied and the incidence of abnormal values obtained were as follow. Excretory function: serum bilirubin (31 per cent), bromsulfalein retention (80 per cent), alkaline phosphatase (10 per cent). Parenchymal cell destruction: serum glutamic oxalacetic transaminase (33 per cent), serum glutamic pyruvic transaminase (11 per cent). Abnormal serum protein production: serum globulins (51 per cent), thymol turbidity (2 per cent). Biosynthetic functions: plasma prothrombin concentration (80 per cent), serum albumin (30 per cent), cephalin flocculation (19 per cent), cholinesterase activity (48 per cent), cholesterol (46 per cent), cholesterol esters (37 per cent). The causes of the right heart failure did not appear to influence the pattern of altered liver function as much as whether failure was acute or chronic. The liver indices reflecting parenchymal cell destruction and excretory activity were most affected during acute failure. Elevated levels of transaminase (up to 1,200 units) and bilirubin (up to 8 mg. per cent) were obtained in half of the patients with acute failure, in the absence of myocardial or pulmonary infarction. A much greater incidence of elevated transaminase levels was found in acute failure (49 per cent) than in chronic failure (5 per cent). These changes correlated with the presence of centrilobular hepatocellular necrosis. The majority of indices of hepatic function returned to normal within one to two weeks following cardiac compensation, except for those reflecting biosynthesis by the liver, which improved more slowly, and hyperglobulinemia, which tended to persist. Repeated attacks of failure (as in rheumatic heart disease) were associated with more severe impairment in liver function.

A Fatal Reaction to Sulfobromophthalein

Widespread clinical use of the sulfobromophthalein (Bromsulphalein [BSP]) test since its introduction by Rosenthal in 19241has confirmed the efficacy of this procedure as an index of hepatic parenchymal function. Less commonly appreciated are the hazards associated with the administration of the sulfobromophthalein dye. Of greatest importance is the rare, but frequently fatal, anaphylactoid reaction. This communication will summarize the serious reactions to sulfobromophthalein thus far reported and present the fifth known case of a fatal reaction. This represents the second reported case in which administration of sulfobromophthalein for the first time caused a fatal anaphylactoid reaction. Report of a Case This patient was a 41-year-old woman admitted to Hahnemann Hospital in 1959 with a chief complaint of epigastric and upper abdominal distress. She had noted upper abdominal fulness and bloating for six months, accompanied by eructations, nausea, and occasional vomiting. The symptoms were persistent and aggravated by most

ALKALINE AND ACID PHOSPHATASE LEVELS IN THE SERUM OF DOGS AFTER LIGATION OF THE COMMON BILE DUCT

Use of values of phosphatase activity in the serum as an index of hepatic function was first studied by Roberts, 1 in 1933. who found that there was a marked increase of alkaline phosphatase activity with obstructive jaundice, a slight increase with catarrhal jaundice and no increase with hemolytic jaundice. He stated the belief at this time that, in addition to indicating an increased osteoplastic activity, an increased alkaline serum phosphatase activity might also act as a differential diagnostic measure in some types of hepatic disease. In 1934 Davies, 2 Bamann and Riedel 3 found that the spleen, kidneys and liver of swine and cattle contained phosphatases which had optimum activities at two ranges of p h. One of these was at approximately p h4.8 and the other at p h9 to 9.5. After the original demonstrations of phosphatases with optimum activities at two ranges of p h

Clinical studies of liver function: I. The effect of anesthesia and certain surgical procedures

The effect of certain anesthetics and various operative procedures on liver function was studied in eighty-four patients before and after operation, using the hippuric acid test as an index of hepatic function. All of the patients studied were considered good operative risks and were without evidence of functional liver insufficiency before operation. Spinal anesthesia produced the least evidence of hepatic dysfunction in twentyone patients subjected to a variety of operative procedures. In eighteen patients (85 per cent) liver function averaged 104 per cent before operation and 96 per cent on the first or second day after operation. In two patients in whom a transient fall in blood pressure occurred on the operating table, the postoperative hippuric acid tests fell to 74 and 49 per cent, respectively, and then returned to normal within seventeen days. Ether anesthesia produced transient subnormal hepatic function in all of sixteen patients. An average liver function of 101 per cent before operation was reduced to 67 per cent. By the end of one week normal values were again obtained. Avertin given as a basal anesthetic in combination with novocain infiltration reduced liver function by 5 to 30 per cent in seven patients. Amytal and morphine given as preoperative sedation to forty patients operated upon under novocain infiltrated locally produced no change in the functional state liver as reflected by the hippuric of the acid test.

STUDIES OF HEPATIC FUNCTION BY THE QUICK HIPPURIC ACID TEST

In a previous communication1we have discussed in detail the rationale of the Quick hippuric acid test for hepatic function and have considered its reliability as an index of hepatic damage in cases of hepatic disease and of disease of the biliary tract. In this second communication we shall consider its value as an index of hepatic function in the presence of thyroid disease, for which purpose we have been employing it for the past eighteen months. Before discussing it from this aspect, however, it is necessary to consider the justification for any test of hepatic function under these circumstances, which means that we must trace the relation between the liver and the thyroid gland. It is surprising to find how commonly that relation is ignored. The majority of writers list hyperthyroidism as the chief cause of death of toxic thyroid disease, but they make no attempt to explain