Hippuric Acid Test Research Articles

Evaluation of liver function by co-administration methodology using 13C-labelled benzoic acid and hippuric acid coupled with nuclear magnetic resonance spectroscopy.

The amount of hippuric acid synthesized and excreted in the urine after benzoic acid loading (hippuric acid test) is a useful index of liver function. However, the hippuric acid test gives erroneous results in the event of failure of renal excretory function. A new stable isotope co-administration methodology using nuclear magnetic resonance (NMR) spectroscopy has been developed to overcome this defect. [7-(13)C]Benzoic acid and [glycine carbonyl-13C]hippuric acid ([gly-13C]hippuric acid), each 0.4-0.6 mmol kg(-1) were simultaneously administered intravenously as probes to normal or liver-injured rats and the urine was analysed by 100 MHz 13C NMR spectroscopy. Consequently, urinary excretion of [7-(13)C]hippuric acid formed from [7-(13)C]benzoic acid and [gly-13C]hippuric acid was successfully traced with very simple and convenient procedures. The urinary excretion of [7-(13)C]hippuric acid indicated the combined functions of hippuric acid synthesis and renal excretion, whereas that of [gly-13C]hippuric acid was indicative of renal excretion of hippuric acid only. The heights of resonances for C7 of [7-(13)C]hippuric acid and the glycine carbonyl carbon of [gly-13C]hippuric acid were used to calculate the concentrations of labelled hippuric acids. [7-(13)C]Hippuric acid was excreted more slowly than [gly-13C]hippuric acid by both normal and liver-injured rats. The liver-injured rats excreted the labelled hippuric acids more slowly than the normal rats. The kinetic parameters were computed for the individual rats on the basis of Michaelis-Menten elimination for benzoic acid and first-order elimination for hippuric acid. The maximum rates of metabolism (Vmax) (4.8-5.8 micromol min(-1) kg(-1)) and the renal elimination rate constants of hippuric acid (Kre) (0.010-0.021 min(-1)) in the liver-injured rats were lower than those (Vmax 6.7-11.8 micromol min(-1) kg(-1); Kre 0.026-0.045 min(-1)) in the normal rats. These results have demonstrated that liver function can be evaluated from the Vmax value even though the renal function of hippuric acid excretion (Kre) is impaired. Thus the co-administration methodology is feasible and can remove the defect of the previous hippuric acid test. These results could form the basis for a more convenient and reliable hippuric acid test in man.

Liver function profile and benzom

Objective: To determine the outcome of hippuric acid test on both subjects and control used in order to evaluate the conjugating capacity of the liver in the two groups. Materials and Methods: 34 patients with idiopathic hypertension and 18 normal subjected use as the control were subjected to different laboratory investigation of liver functions following an informal consent. The hippuric acid test was conducted in all of them to evaluate the conjugating capacity of the liver. Results: A marked derangement of hippuric acid test was seen in patients with idiopathic hypertension when compared with normal subjects used as control. Conclusion: The result of this preliminary investigations is no conclusive evidence that this defect bears any direct relationship to the hypertension seen in this group, they must however be considered significant. It is suggested that the disturbance of this mechanism which inevitablt would interfere with elimination of certain hypertension inducing hormones and their breakdown products may at least be partially contributory to the elevated blood pressure seen in this group. Keywords: primary hypertension, hippuric acid conjugation test, Nigerians Highland Medical Research Journal Vol. 3(2) 2005: 38-44

Armand J. Quick: pioneer and prophet of coagulation research.

During a professional career spanning more that 50 years, the American physician, biochemist, and teacher Armand J. Quick made numerous important contributions to medicine, particularly in the field of hemostasis. His hippuric acid test (1933) was the first quantitative test of liver function. In 1935 he reported the technique most closely associated with his name, the prothrombin time test, which was used by other investigators in the isolation of vitamin K and the identification of the coumarin anticoagulants. Later the test came into wide use for the control of anticoagulant therapy. Quick studied hereditary bleeding disorders and devised tests for their identification. He also uncovered several basic principles of normal hemostasis. He was among the first to draw attention to the anticoagulant properties of aspirin, and at the end of his career postulated the existence of a vitamin besides C and K that is essential for hemostasis.

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.

The sensitivity of function tests in detecting liver damage in the rat

The sensitivity of a group of tests in detecting the effects of liver damage was investigated in groups of rats treated with carbon tetrachloride or sodium selenate for 5 months. The tests included determinations for the activity of plasma glucose-6-phosphatase, glutamic-pyruvic transaminase, cholinesterase, bilirubin concentration, protein fractions, colloidal red flocculation, zinc sulfate turbidity, urine coproporphyrin and urobilinogen determination, the sulfobromophthalein (BSP) and hippuric acid tests, relative liver weight and gross and histopathologic examination of the liver. The consequence of carbon tetrachloride administration differed from the effects of sodium selenate in the morphological form of liver injury and in the type of functional impairment (as shown by the BSP and hippuric acid tests). The hippuric acid test, the electrophoretic pattern of plasma proteins, and the BSP test were the most effective tests in revealing long-term impairment of liver function. Histopathologic evaluation and the determination of plasma glutamic-pyruvic transaminase were sensitive parameters in detecting structural abnormality. However, function tests alone did not give reliable information about structural changes in the liver; both types of tests are necessary for a satisfactory assessment of hepatic integrity. Restriction of food intake had no effect on the results of any of these tests.

Urinary hippuric acid excretion as an index of toluene exposure.

Abstract A simple procedure is described for the analysis of hippuric acid in urine. The sample is extracted with an isopropyl alcohol-diethyl ether mixture, and the hippuric acid is measured in the extractant by ultraviolet spectrophotometry. The excretion of hippuric acid in urine as a metabolic product of toluene was studied in relation to its usefulness in industrial exposures to toluene. Good correlation of hippuric acid content of end-of-shift samples and toluene exposure was found in studies performed in leather-finishing and rubber-coating plants. The hippuric acid test was also found to be useful in measuring the adequacy of cartridge-type respirators in tank painting work.

Investigations in Protein Metabolism in Nervous and Mental Diseases with Special Reference to the Metabolism of Amlnes

Publisher Summary This chapter demonstrates that a disturbance in the protein metabolism, as found in endogenous psychosis, in model psychosis and, though in a different way, in organic diseases of the CNS, shows an effect throughout the entire catabolic system and is manifested even in the lowest level of the amine metabolism. It is highly desirable that other research teams put more interest into amine metabolism in the sense of basic research. It is found that in schizophrenics, correlated with the clinical status, there is stability in the blood and plasma colloids. This stability disappears with the improvement of the patient. This cerebrally controlled, physicochemical change in the plasma proteins is in contrast to the plasma changes in condition of protein catabolism. To check the ways and means of protein catabolism, the Quick hippuric acid test is modified and used as an indicator for the state in detoxifying abilities of the liver.

The hippuric acid index: application of the hippuric acid test as an index of human free anxiety.

The hippuric acid index: application of the hippuric acid test as an index of human free anxiety.

Über den aussagewert der peroralen und intravenösen hippursäure-proben

1. 1. The question of the role played by the urine volume has been investigated by means of 83 classical and 27 modified hippuric acid tests (Quick) carried out by the intravenous (i.v.) method. Our grounds for calling attention to the dependence of the urine volume are discussed. 2. 2. The reduced normal ranges are given and compared with a collection of figures given in the literature for unreduced normal ranges obtained by the intravenous test. 3. 3. On the basis of the method defined a comparison is drawn between the results obtained on the same person by intravenous and oral application (59 double trials). From this it was obvious that the intravenous test shows almost twice as great a dispersion as the oral test. 4. 4. For these and other reasons, also discussed, it is concluded that the i.v. test is much the less reliable of the two. 5. 5. It appears that at least in our patients resorption difficulties, whose avoidance is ensured by the i.v. test, played no role at all. 6. 6. In cases in which the quantity of benzoic acid administered orally in the 4-hour test is incompatible, a 3-hour modification with reduced quantities is proposed, with an estimate of the normal ranges to be expected under these conditions.

Liver function tests in rheumatoid arthritis.

Interest in liver function in rheumatoid arthritis has arisen from investigations into the aetiology of the disease and from the observation that an attack of jaundice may induce a remission (Hench, 1940). Laboratory studies have, however, given conflicting results. Impaired glucose tolerance was found by Pemberton and Foster (1920) and by Andrews and Muether (1941) and Flynn and Irish (1946). Rawls, Weiss, and Collins (1937, 1939) in a detailed study of 100 cases came to the conclusion that liver function was definitely impaired. Using the dye azorubin S they found that 550% of the cases gave abnormal results. In many of these, however, the dye appeared in the bile much more rapidly than normal, a phenomenon which the authors ascribed to liver irritability. This interpretation has been criticized by Lyon and Wirts (1937), and exclusion of these cases reduces the abnormal results to 190. This test has never become widely used, because it requires duodenal intubation, though Rosenberg and Soskin (1940) found it at least as sensitive as the more familiar bromsulphalein test. Bromsulphalein (B.S.P.) was used by Robinson (1943) with negative results; he had, however, considerably modified the test as commonly used, and his B.S.P. index was based on blood levels found during 7.25 minutes following injection of 3.5 mg. per kg. Recent work on the fate of injected B.S.P. has shown that this time is too short for the demonstration of all but severe liver damage; the percentage disappearance rate from plasma does not fall off unless a larger dose of B.S.P. is used and time is allowed for the liver to become saturated with the dye (Ingelfinger, Bradley, Mendeloff, and Kramer, 1948 ; Mendeloff, Kramer, Ingelfinger, and Bradley, 1949). Movitt and Davis (1953) have also used B.S.P. in rheumatoid arthritis, and found a small degree of dye retention (up to 3 %) in seven out of 15 cases. Abnormal results have been obtained with the hippuric acid test by several workers (Rawls, Weiss, and Collins, 1939 ; Lovgren, 1953 ; Kersley, Mandel, and Jeffrey, 1953) ; this test is, however, open to the objection that impairment of renal function may also give low values. The occurrence of serum protein changes in rheumatoid arthritis is now well established, and they account for the positive flocculation tests which are found in a proportion of cases (Carter and Maclagan, 1946; Kersley et al., 1953 ; Poulsen, 1949), but they are not necessarily indicative of impairment of liver function.

INFLUENCE OF CITRATE ON THE LIVER FUNCTION

Citrate is a very important medicament in clinical use. Recently injection of this medicament is becoming very common with the increase of massive blood transfusion. Although the infusion of citrate is very much concerned with liver function, there have been published few studies upon the relation of citrate to liver function. Accordingly, the present writer observed the effect of citrate on the function of liver and R.E.S. in healthy and liver-damaged rabbits.The following liver function tests were performed: hippuric acid test, santosol test, fructose tolerance test, azorubin S test, B.S.P. retention test, prothrombin test and congored test. As citrate solution 10% sodium citrate was used.The following results were obtained.1) After injection of 50 mg/kg citrate in healthy rabbits, several kinds of liver function, especially the ability of detoxication, were greatly increased.2) By daily injection of 50 mg/kg citrate in healthy rabbits, the ability of detoxication was increased during the period from the 4th to the 7th day, but it could not be increased further.3) In the cases of liver-damaged rabbits, the group of citrate injected (daily) showed earlier healing of detoxication ability than the control group.In a word, some kinds of the liver function are accelerated by citrate injection, and the mechanism of this accelerating action is analogous with that of glucose or fructose. Considering that the acceleration and protection of liver function are necessary for most cases of blood transfusion, this action of citrate is clinically very important.

An Evaluation of Factors Influencing the Discriminative Effectiveness of a Group of Liver Function Tests

Summary The nature of the interrelationships among nine liver function tests in acute viral hepatitis has been studied in detail. As a group the highest intercorrelations among the tests were observed with the urine coproporphyrin and per cent cholesterol esters, the lowest with the zinc sulfate turbidity and urine urobilinogen tests. The observed effectiveness of each test in differentiating between hepatitis patients and normal individuals was wholly dependent upon factors accounting for the independent significance of four tests-the Bromsulf alein, zinc turbidity, hippuric acid, and urine coproporphyrin tests. Coproporphyrin factors contributed the largest amount to the observed eff ectivenes of the total bilirubin, thymol turbidity, per cent cholesterol esters, galactose tolerance, and urine urobilinogen tests. They also contributed significantly to the effectiveness of the Bromsulfalein and hippuric acid tests, but were relatively independent of the zinc turbidity test. Factors accounting for the independent significance of the hippuric acid test contributed appreciably to the observed effectiveness of each of the other tests, though less extensively than the coproporphyrin factors in all instances except that involving the zinc turbidity test. Bromsulfalein factors were most important in determining the observed effectiveness of the hippuric acid test. Though being of secondary importance, they also contributed significantly to the observed effectiveness of the galactose tolerance, per cent cholesterol esters, and urine coproporphyrin tests. All but two of the tests were relatively independent of zinc turbidity factors. The same four sets of basic physiologic factors are involved in both acute hepatitis and cirrhosis; however, the relative importance of each set differs greatly. In cirrhosis, the set of factors accounting for the independent significance of the Bromsulf alein test are by far of greatest importance. In acute hepatitis, the set of factors accounting for the independent significance of the urine coproporphyrin test are most important.

An Evaluation of Factors Influencing the Discriminative Effectiveness of a Group of Liver Function Tests

Summary The nature of the interrelationships among nine liver function tests in acute viral hepatitis has been studied in detail. As a group the highest intercorrelations among the tests were observed with the urine coproporphyrin and per cent cholesterol esters, the lowest with the zinc sulfate turbidity and urine urobilinogen tests. The observed effectiveness of each test in differentiating between hepatitis patients and normal individuals was wholly dependent upon factors accounting for the independent significance of four tests-the Bromsulf alein, zinc turbidity, hippuric acid, and urine coproporphyrin tests. Coproporphyrin factors contributed the largest amount to the observed eff ectivenes of the total bilirubin, thymol turbidity, per cent cholesterol esters, galactose tolerance, and urine urobilinogen tests. They also contributed significantly to the effectiveness of the Bromsulfalein and hippuric acid tests, but were relatively independent of the zinc turbidity test. Factors accounting for the independent significance of the hippuric acid test contributed appreciably to the observed effectiveness of each of the other tests, though less extensively than the coproporphyrin factors in all instances except that involving the zinc turbidity test. Bromsulfalein factors were most important in determining the observed effectiveness of the hippuric acid test. Though being of secondary importance, they also contributed significantly to the observed effectiveness of the galactose tolerance, per cent cholesterol esters, and urine coproporphyrin tests. All but two of the tests were relatively independent of zinc turbidity factors. The same four sets of basic physiologic factors are involved in both acute hepatitis and cirrhosis; however, the relative importance of each set differs greatly. In cirrhosis, the set of factors accounting for the independent significance of the Bromsulf alein test are by far of greatest importance. In acute hepatitis, the set of factors accounting for the independent significance of the urine coproporphyrin test are most important.

An Evaluation of Factors Influencing the Discriminative Effectiveness of a Group of Liver Function Tests

Summary An evaluation has been made of the relative effectiveness of nine representative liver function tests in differentiating between a group of patients with cirrhosis and a group of normal subjects. The Bromsulfalein test was the most effective single test. The intravenous galactose tolerance and hippuric acid tests were approximately three-fourths as effective as the Bromsulfalein test; the zinc sulfate turbidity, 24-hour urine coproporphyrin, and per cent cholesterol ester tests were approximately three-fifths as effective; and the 24-hour urine urobilinogen, thymol turbidity, and total serum bilirubin tests were approximately two-fifths as effective. After allowing for interdependence among the tests, only four tests—the Bromsulfalein, zinc turbidity, hippuric acid, and urine coproporphyrin—were found to contribute independently to the discrimination between the normal and cirrhotic groups. The other five tests made little contribution beyond that already represented in the four independently significant tests. A weighted linear combination of these four tests, called the cirrhosis abnormality score, was significantly, though not greatly, more effective than the Bromsulfalein test alone for purposes of group distinction. It also misclassified fewer abnormal individuals. The independent contribution of the Bromsulfalein test to the optimal combination was one and one-half times that of the coproporphyrin test and two and one-half times that of the zinc turbidity and hippuric acid tests.

CLINICAL FEATURES OF SERUM HEPATITIS WITH SPECIAL REFERENCE TO ITS TRANSITION AND VARIATIONS IN THE LIVER FUNCTION

Cases reported here are 18 cases hospitalized in our Clinic from 1952 to date, of which 15 persons received transfusion of whole blood, 2 cases of plasma and 1 both of blood and plasma. The occurrence of jaundice was seen 26 to 198 days after the first transfusion and 34 to 219 days after the last.Anorexia and fatigue were observed in most cases as symptoms in the preicteric stage, and the average duration was 4 days which is shorter than that in infectious hepatitis observed in our Clinic.One case with a complication of bronchiectasis died 46 days after the onset of jaundice.Duration of jaundice ranged from 20 to 90 days, the average being 34 days, which is not so different from that of infectious hepatitis.The following chief characteristics were found in the function tests performed in its course.Among serum reactions, thymol turbidity test showed a tendency to give positive results of long duration as compared with other reactions; cephalin cholesterol flocculation test had a tendency to show positive results in the early stage; Takata's reaction showed a tendency to give negative results earlier than other reactions. Santsol and hippuric acid tests had a tendency to show positive results while serum reactions were negative. It is also desirable to test urobilinogenuria, especially to perform its quantitative determination, and excretory function test by hepatosulphalein which gave a positive result for a long time.Disturbances in the liver function by many tests were testified in all cases, and it is clinically noteworthy that some cases showed disturbances of the liver function even after the disappearance of jaundice, shifting to non-icteric chronic hepatitis.

BLEEDING esophageal varices.

Esophageal varices develop secondarily to partial or complete obstruction of the portal blood flow at the junction of the esophagus and cardia of the stomach between the coronary vein, a branch of the portal circulation, and the esophageal veins, branches of the azygos vein of the systemic circulation. Portal hypertension may be one of two types, intrahepatic or extrahepatic, or a combination of both. A high retention of sulfobromophthalein in the blood 30 minutes after intravenous injection, a positive reaction to the hippuric acid test, and reversal of the albumin-globulin ratio all point to the diagnosis of cirrhosis of the liver with intrahepatic portal block. In the absence of these findings, one can assume that the block is extrahepatic. Intrahepatic block may be caused by portal cir[ill]hosis of the Laennec type or by thrombosis of the hepatic veins, the so-called Chiari syndrome. The extrahepatic block may be congenital or the

»Hippuric Acid Test» as a Measure of Liver Function

»Hippuric Acid Test» as a Measure of Liver Function

Liver dysfunction following abdominal operations; the significance of postoperative hyperbilirubinemia.

SEVERAL reports in the literature deal with the effect of surgical operations on liver function. 1 The hippuric acid and sulfobromophthalein (bromsulphalein ® ) sodium tests have been used in several studies. Tagnon, Robbins and Nichols 2 reported changes in the sulfobromophthalein clearance following extra-abdominal operations. In their series of patients there was no consistent postoperative alteration in the thymol turbidity or cephalin flocculation reactions. The work reported below describes the effect of abdominal operation on the sulfobromophthalein clearance, cephalin flocculation and thymol turbidity. Abnormalities of the two former reactions were observed in a high proportion of the cases reported here. In addition, since sulfobromophthalein clearance parallels bilirubin clearance in dogs, 3 an attempt was made to correlate the incidence of postoperative hyperbilirubinemia in this series of patients with the impairment of the sulfobromophthalein clearance. MATERIAL AND METHODS The observations were made on patients admitted to the surgical services at Memorial

Present fundamentals of some liver function tests

1. No single liver function test exists but a series of partial tests. 2. A high grade icterus is usually not indicative of serious hepatic damage, whereas moderate icterus of long standing generally is. 3. Tests based on elimination of bromsulfalein and similar dye stuffs are of no use in parenchymatous affections unless obstructive jaundice can be eliminated. On the other hand cholecystography is dependent on a normal excretory power of the liver cells. 4. The direct and indirect diazo reaction of H. v. d. Bergh is without much value for the differentiation of icterus. 5. Every testing of liver function should include the galactose tolerance test. A practical modification of this test with simultaneous peroral administration of gelatine is outlined. 6. Supplemental information can be obtained from use of the bromsulfalein test, the hippuric acid test, the citric acid and phosphatase test, from the prothrombin level, the Takata test and some hematological findings. 7. As a routine procedure the galactose-gelatine test, the bromsulfalein test, icterus index, the Takata test, determination of the prothrombin level and a leukocyte and differential count are recommended. The other tests may be used if necessary.

Relationship of Hippuric Acid Excretion to Urinary Volume.

SummaryThe rate of excretion of hippuric acid is independent of urine volume, indicating that the present standards for the interpretation of the hippuric acid test are valid. It is suggested that hippuric acid excretion is a function of the renal tubules.