Effects of transjugular intrahepatic portosystemic shunt (TIPS) on quantitative liver function tests

BACKGROUND/AIMS: The transjugular intrahepatic portosystemic stent-shunt (TIPS) has been established as a new effective treatment for portal hypertension in advanced liver disease. Impairment of liver function due to reduced portal venous perfusion is considered to be a major risk of TIPS, and the shunt leads to an increase in the incidence of hepatic encephalopathy (HE). Known complications, like the increase in the incidence of HE or TIPS stenosis, are diagnosed either clinically or by doppler ultrasound. It is not practicable to use quantitative liver function tests in the diagnostic work-up of HE, and medical or interventional therapy can be established after clinical diagnosis. Still, information is limited about the influence of TIPS on quantitative liver function tests in patients with liver cirrhosis. Therefore, the aim of this prospective study was to assess the effects of TIPS on various liver function tests. METHODOLOGY: Fifteen patients with liver cirrhosis, a hepatopetal portal flow before TIPS, and an uncomplicated course without stenosis after elective TIPS were analysed. Liver function was quantitatively measured using the [14C]aminopyrine breath test (ABT), considered to be independent of hepatic blood flow, the monoethylglycinexylidide test (MEGX), believed to be largely dependent on hepatic blood flow, serum bilirubin, serum albumin, and prothrombin time. Measurements were performed before, 1, 3 and 6 months after TIPS. RESULTS: TIPS decreased the portal venous pressure gradient from 31.0+/-2.0 cm (SEM) H2O to 16.9+/-1.8 cm H2O (p<0.01). One, 3 and 6 months after TIPS there was no significant deterioration of liver function as assessed by ABT, MEGX or serum bilirubin, serum albumin, and prothrombin time compared to baseline values before TIPS. ABT and MEGX were significantly correlated before TIPS (r=0.72; p<0.01) and after TIPS (r=0.76; p<0.05). CONCLUSIONS: These data show no significant deterioration of microsomal liver function as measured by the quantitative liver function tests ABT and MEGX over a period of 6 months after elective TIPS. In particular, there was no significant reduction of the MEGX-test considered to depend predominantly on hepatic blood flow. Thus, there is no need for the quantitative liver function tests ABT and MEGX in the routine management of patients following the TIPS procedure.     

Photochemical formation of singlet molecular oxygen (1O2) in illuminated aqueous solutions of p-aminobenzoic acid (PABA)

Evidence is presented for the photochemical formation of singlet molecular oxygen (1O2) in air-saturated buffered aqueous solutions of p-aminobenzoic acid (PABA) using sunlight-range illumination. This is significant because PABA is widely used as an active ingredient in sunscreen preparations that are applied to the surface of the skin and 1O2 is known to cause oxidative damage to cells via the formation and subsequent reactions of lipid peroxides. Furfuryl alcohol (FFA), a well known chemical trap for 1O2, was added to aqueous PABA solutions prior to illumination. The FFA was consumed when the solution was illuminated, but no loss of FFA occurred in the dark and loss by direct photolysis was negligibly slow. Further evidence for the formation of 1O2 in illuminated aqueous PABA solutions is provided by the results of experiments in which individual solutions containing PABA and FFA that were diluted with D2O exhibited an increased rate of FFA consumption due to the increased lifetime and concentration of 1O2 in this solvent.     

The use of lidocaine as a test of liver function in liver transplantation

The hepatic metabolism of lidocaine to monoethyl-glycinexylidide (MEGX) is the basis of a dynamic test of liver function. To understand its potential value in liver transplantation, the latter has been considered in the following three separate stages: pretransplantation assessment of potential candidates, potential liver donors, and the transplant recipient. In pretransplantation patients, data support its role in assessing risk of morbidity and mortality. In assessment of the liver transplant donor, there are differences concerning apparent usefulness, and these must be resolved. In the liver transplant recipient, serial measurements are useful to measure real-time hepatic metabolic activity. Low MEGX values reflect the clinical condition of the patient, and the importance of entirely assessing the patient, not just noting the test result, is paramount. This review has considered the role of the MEGX test in liver transplantation.     

The 13C-methacetin breath test for quantitative noninvasive liver function analysis with an isotope-specific nondispersive infrared spectrometer in liver cirrhosis

BACKGROUND AND OBJECTIVE: Cytochrome-P450-dependent liver function can be measured with the 13C-methacetin breath test (MBT). This has heretofore been done with the use of a mass-spectrometer. This study was undertaken to evaluate the MBT (NDIRS) done with the isotope-selective nondispersive infrared spectrometer. PATIENTS AND METHODS: 20 healthy volunteers (ten women, ten men, aged 22-76 years) and 16 patients (ten women, six men, aged 48-71 years) with histologically confirmed liver cirrhosis (Child-Pugh stage A [n = 7], B [n = 5] or C [n = 4]) were given 13C-methacetin in 100 ml of tea after a 12-hour fasting period. Breath tests were performed before the test drink and 5, 10, 15, 20, 30, 40, 50, 60, 80, 100, 120, 150 and 180 min thereafter. The ratio of 13C to 12C was determined, as delta (/1000), and from it the maximal percentage rate (PDRmax) calculated, as well as the cumulative rate (cPDRmax) after 30, 60, 120 and 180 min (Median and 5th and 95th percentiles). RESULTS: For patients with liver cirrhosis there were significantly lower values for cPDRmax and cPDR after 30, 60, 120 and 180 min than in the healthy subjects (P < 0.002): PDR [%]/h: 3.9 (0.7-15.9) vs. 36.5 (23.1-50.0); cDPR 30 min [%]: 1.1 (-0.2-6.0) vs. 12.4 (7.6-17.1); cDPR 3 h [%]: 9.8 (-2.3-27.5) vs. 36.0 (29.9-45.1). There were significant differences among the patients, depending on their Child-Pugh staging. CONCLUSION: The MBT with the cost-effective NDIRS can reliably and noninvasively distinguish between healthy subjects and patients with liver cirrhosis. The test is therefore suitable for the quantitative analysis of liver functions.     

Relationship between liver function and splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 2)

A case is reported of persistent primitive trigeminal artery associated with recurrent facial pain and noncomitant strabismus by partial ipsilateral oculomotor palsy. Transcranial Doppler disclosed indirectly persistent carotid-basilar anastomosis. CT and angiography allowed complete diagnosis excluding a posterior communicating artery aneurysm, a Tolosa-Hunt syndrome and an ophthalmoplegic migraine. Steroid therapy is recommended treatment. Surgery should be considered when symptoms are intractable to medical therapy.     

Monoethylglycinexylidide (MEGX) liver function test is not compromised by 3-hydroxy MEGX in humans

A simple membrane immunoassay assay system, Quik Pack, for the detection of hepatitis C virus antibody was compared with two enzyme-linked immunosorbent assays (ELISAs) in a study of 600 serum samples. Quik Pack exhibited excellent sensitivity and specificity: 96.0 and 99.7%, respectively, versus the ELISA-2 and 99.7 and 99.4%, respectively, versus the ELISA-3.     

Basic studies of adreno-sympathetic function test-glucagon test and histamine test (author''s transl)

Sera from 74 patients with polymyalgia rheumatica or giant cell arteritis or both were tested for immune complexes by using the Raji cell radioimmunoassay. Levels in patients with active disease were higher than in patients whose disease had become inactive. There was no difference in levels of immune complex-like materials between patients with polymyalgia rheumatica alone and those with giant cell arteritis. Density gradient analysis of one serum showed immune complex-like materials mainly in the 19S region. Immune complexes may be important in the pathogenesis of these conditions.     

Glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB): interindividual variability in human liver, lung, kidney and intestine

The rate of glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) was measured in specimens of human liver (n = 93), sigmoid colon (n = 56), renal cortex (n = 67) and lung (n = 68). In the liver there was a weak but significant (r = - 0.247 p = 0.017) negative correlation between the activity of glutathione transferase and the liver donor's age. Such a correlation was not found in the renal cortex, lung and colon. In the renal cortex and in lung the rate of glutathione conjugation with CDNB was a little but significantly (p < 0.05) higher in women than men, whereas no sex-dependent difference was observed in the liver and colon. The distribution of glutathione transferase activity was polymorphic in the mucosa of colon and renal cortex of men but not in that of women. Smoking seems not to affect the glutathione conjugation rate with CDNB in lung. The activity of glutathione transferase was 2-, 6-, and 7-fold greater in liver than in the renal cortex, lung and colon, respectively. There was a large interindividual variability of the hepatic glutathione transferase activity, and because this variability, 15% of the population studied catalyzed the glutathione conjugation with CDNB at a rate similar to those of the renal cortex and duodenum. The subjects with low expression of the hepatic glutathione transferase should be more exposed to the effects of toxic and carcinogenic compounds.     

Branched-chain amino acid biosynthesis in Salmonella typhimurium: a quantitative analysis

We report here the first quantitative study of the branched-chain amino acid biosynthetic pathway in Salmonella typhimurium LT2. The intracellular levels of the enzymes of the pathway and of the 2-keto acid intermediates were determined under various physiological conditions and used for estimation of several of the fluxes in the cells. The results led to a revision of previous ideas concerning the way in which multiple acetohydroxy acid synthase (AHAS) isozymes contribute to the fitness of enterobacteria. In wild-type LT2, AHAS isozyme I provides most of the flux to valine, leucine, and pantothenate, while isozyme II provides most of the flux to isoleucine. With acetate as a carbon source, a strain expressing AHAS II only is limited in growth because of the low enzyme activity in the presence of elevated levels of the inhibitor glyoxylate. A strain with AHAS I only is limited during growth on glucose by the low tendency of this enzyme to utilize 2-ketobutyrate as a substrate; isoleucine limitation then leads to elevated threonine deaminase activity and an increased 2-ketobutyrate/2-ketoisovalerate ratio, which in turn interferes with the synthesis of coenzyme A and methionine. The regulation of threonine deaminase is also crucial in this regard. It is conceivable that, because of fundamental limitations on the specificity of enzymes, no single AHAS could possibly be adequate for the varied conditions that enterobacteria successfully encounter.     

Impaired limb position sense after stroke: a quantitative test for clinical use

OBJECTIVE: A quantitative measure of wrist position sense was developed to advance clinical measurement of proprioceptive limb sensibility after stroke. Test-retest reliability, normative standards, and ability to discriminate impaired and unimpaired performance were investigated. DESIGN: Retest reliability was assessed over three sessions, and a matched-pairs study compared stroke and unimpaired subjects. Both wrists were tested, in counterbalanced order. SETTING: Patients were tested in hospital-based rehabilitation units. PATIENTS AND OTHER PARTICIPANTS: Reliability was investigated on a consecutive sample of 35 adult stroke patients with a range of proprioceptive discrimination abilities and no evidence of neglect. A consecutive sample of 50 stroke patients and convenience sample of 50 healthy volunteers, matched for age, sex, and hand dominance, were tested in the normative-discriminative study. Age and sex were representative of the adult stroke population. MAIN OUTCOME MEASURES: The test required matching of imposed wrist positions using a pointer aligned with the axis of movement and a protractor scale. RESULTS: The test was reliable (r = .88 and .92) and observed changes of 8 degrees can be interpreted, with 95% confidence, as genuine. Scores of healthy volunteers ranged from 3.1 degrees to 10.9 degrees average error. The criterion of impairment was conservatively defined as 11 degrees (+/-4.8 degrees) average error. Impaired and unimpaired performance were well differentiated. CONCLUSIONS: Clinicians can confidently and quantitatively sample one aspect of proprioceptive sensibility in stroke patients using the wrist position sense test. Development of tests on other joints using the present approach is supported by our findings.     

Protein sidechain conformer prediction: a test of the energy function

BACKGROUND: Homology modeling is an important technique for making use of the rapidly increasing number of protein sequences in the absence of structural information. The major problems in such modeling, once the alignment has been made, concern the positions of loops and the orientations of sidechains. Although progress has been made in recent years for sidechain prediction, current methods appear to have a limit on the order of 70% in their accuracy. It is important to have an understanding of this limitation, which for energy-based methods could arise from inaccuracies of the potential function. RESULTS: A test of the CHARMM function for sidechain prediction was performed. To eliminate the multiple-residue search problem, the minimum energy positions of individual sidechains in ten proteins were calculated in the presence of all other sidechains in their crystal orientations. This test provides a necessary condition that any energy function useful for sidechain placement must satisfy. For chi1 x chi2 rotations, the accuracies were 77.4% and 89.5%, respectively, and in the presence of crystal waters were 86.5% and 94.9%, respectively. If there was an error, the crystal structure usually corresponded to an alternative local minimum on the calculated energy map. Prediction accuracy correlated with the size of the energy gap between primary and secondary minima. CONCLUSIONS: The results indicate that the errors in current sidechain prediction schemes cannot be attributed to the potential energy function per se. The test used here establishes a necessary condition that any proposed energy-based sidechain prediction method, as well as many statistically based methods, must satisfy.     

Quinoxaline-2-carboxylic acid (QCA) in swine liver and muscle

The concentration of quinoxaline-2-carboxylic acid (QCA) determined by HPLC after alkaline hydrolysis of liver and muscle of swine, ranged from < 3 ng/g to 45.3 ng/g in liver, and from < 3 ng/g to 10.8 ng/g in muscle samples. After the 77th day of therapy QCA was found in samples of liver (9.7 ng/g). Recoveries obtained for both liver and muscle were 70% at 5 ng/g, 77% and 75% respectively at 10 ng/g, and 90% for both liver and muscle at 30 ng/g. This experiment was performed within the frame of the National Monitoring Programme of Residues in Animal Tissues in the Republic of Croatia.     

Relations of test item characteristics to test preparation/test practice effects: A quantitative summary.

Examined 10 studies on the effects of test preparation or test practice to provide information relevant to the strategy of developing tests that do not exhibit significant susceptibility to test preparation. Only studies that reported effects by individual item type and used aptitude tests for post-secondary admissions or employment were included in the analysis. The item-level effects were related to a number of test item characteristics, including item format, difficulty level, and complexity of test directions. Strong relations were noted between test preparation and/or practice effects and (a) the length and complexity of test directions and (b) the item format used. The number of words used to convey directions seemed to be a significant aspect of the complexity, as did the fixed-format nature of many of the most susceptible item types. It is suggested that only studies conducted at the level of individual item types are likely to yield results that will help test developers construct relatively "uncoachable" tests. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Poly(2-aminoadenylic acid): interaction with poly(uridylic acid)

Poly(2-aminoadenylic acid) forms both double and triple helices with poly(uridylic acid) [poly(U)]. The 2-amino group forms a third hydrogen bond, elevating the 2 leads to 1 transition temperature by 33 degrees C. The third strand, however, has about the same stability as poly(A)-2poly(U), as measured by Tm 3 leads to 2. This selective stabilization of the two-stranded helix results in a much greater resolution of the differnt thermal transitions than that observed in analogous polynucleotide systems. In contrast to other A, U systems 3 leads to 1 and 2 leads to 3 transitions are not observed under any conditions, and the triple helix always undergoes a 3 leads to 2 transition even at very high ionic strength. A 1:1 mixture of poly(2NH2A) and poly(U) exhibits no transient formation of 1:2 complex, unlike similar mixtures of poly(A) with poly(U) and poly(T). This difference is evidently due to a more rapid displacement reaction: [poly(2NH2A) + poly(2NH2A)-2poly(U) leads to 2 poly(2NH2A)-poly(U)] With poly(2NH2A) than with poly(A). We describe a method for establishing the combining ratios of polynucleotide complexes which used a computer to calculate the angles of intersection of mixing curves as explicit and continuous functions of the wavelength. The wavelength dispersions of the angles of intersection determine optimum wavelengths for establishing stoichiometry and can also provide reliable negative evidence that presumably plausible complexes are not formed. Analogous computer procedures have been developed to determine wavelengths which are selective for the formation of both 1:1 and 1:2 complexes. Infrared spectra of the 1:1 and 1:2 complexes resemble those of other A, U homoribopolynucleotide helices in having two and three strong bands, respectively, in the region of carbonyl stretching vibrations. CD spectra of the two complexes are unusual in having negative first extrema of moderate intensity. We attribute these extrema to intrastrand interactions of strong, well-resolved transitions at 278 nm (B2u) of the 2-aminoadenine residues. The CD spectra are correlated with those of other polynucleotide helices.