Biomedical subjects

W Hübl

Publications and source records attributed to W Hübl.

At least 19 recordsLinked to original sources

PubMed2006

Homocysteine and early re-stenosis after carotid eversion endarterectomy.

BACKGROUND: Homocysteine (Hcy) appears to be involved in the development of intimal hyperplasia and arterial thrombosis. The purpose of this study was to evaluate the association of plasma Hcy with early re-stenosis following carotid eversion endarterectomy. PATIENTS AND METHODS: Of 398 consecutive patients, 363 were included in this study. 62% of patients had symptomatic internal carotid artery (ICA) stenosis. Patients had preoperative assessment of Hcy and other well established atherosclerosis risk factors. Intraoperatively, completion angiography was performed in 2 planes. Patients had clinical, Hcy and duplex follow up at 1, 3, 18 and 36 months postoperatively. RESULTS: Complete follow up data were available for 312 patients. Five patients suffered from strokes and 2 patients died during the peri-operative period (combined stroke and death rate of 2%). Mean follow up was 26+/-5 months (range 17 to 36 months). Seventeen and six patients (5.5%) developed a 50-69% and >70% re-stenosis, respectively. Serum creatinine was significantly higher in patients with early re-stenosis, occlusion or stroke after CEA (P=0.043). High grade re-stenosis, occlusion and stroke ipsilateral to the operated side (17 patients) was associated with HbA1C and creatinine (P=0.043 and 0.046, respectively) but not Hcy. CONCLUSION: While Hcy is a recognized independent risk factor for atherothrombosis, our study suggests that there is no association of Hcy with early re-stenosis after eversion endarterectomy.

Adult↗

PubMed2005

Plasma D-lactate as a potential early marker for colon ischaemia after open aortic reconstruction.

BACKGROUND AND AIM: The breakdown of mucosal barrier function due to intestinal hypo-perfusion is the earliest dysfunction of ischaemic colitis. Severe colon ischaemia after aortic reconstruction is associated with mortality rates up to 90%. Therefore, early detection and treatment of patients with extensive ischaemic colitis is of crucial importance. In experimental studies, both D-lactate and bacterial endotoxin have been reported as markers of intestinal mucosal barrier impairment. However, evidence of their value in clinical practice is lacking. The aim of this pilot prospective cohort study was to assess the association between ischaemia of the colon (assessed histologically) and plasma levels of D-lactate and endotoxin in patients undergoing open aortic reconstruction. PATIENTS AND METHODS: Twelve consecutive patients underwent surgery between February and April 2003. Six patients underwent emergency surgery and six patients elective aortic surgery. D-Lactate and endotoxin levels were measured in blood samples collected according to a standardised protocol. For histological examination biopsies were obtained by sigmoidoscopy on days 4-6 after surgery, or earlier if indicated clinically. RESULTS: As early as 2 h postoperatively, elevated plasma levels of d-lactate were measured in patients with histologically proven ischaemic colitis. The peak of D-lactate elevation was on postoperative days 1 and 2. Concentration of plasma endotoxin was not significantly different in patients with or without ischaemic colitis. CONCLUSION: Our data suggest that plasma D-lactate levels are a useful marker for early detection of ischaemic colitis secondary to aortic surgery.

Aged↗

PubMed2005

Carotid endarterectomy under local anaesthesia does not increase plasma homocysteine concentration.

INTRODUCTION: The purpose of this cohort study was to evaluate the effect of carotid endarterectomy under local anaesthesia on homocysteine (Hcy) concentrations. PATIENTS AND METHODS: Of 100 patients with internal carotid artery (ICA) stenosis >70%, the complete data set was available for 91 patients (39 asymptomatic and 52 symptomatic). All patients underwent eversion endarterectomy of the ICA under regional anaesthesia. RESULTS: Thirty-two percent of the examined patients had a total Hcy above 15 micromol/l. The mean Hcy levels preoperatively were 13.9+/-4.8 micromol/l. The Hcy levels on day 5 were 13.1+/-5.0 micromol/l and after 6 months 14.0+/-5.8 micromol/l. There was no significant change during follow-up. No intraoperative strokes and deaths were observed and during the 6 months follow-up no recurrent strokes, TIAs or deaths occurred. CONCLUSION: Patients undergoing carotid endarterectomy under regional anaesthesia do not have an increase in total Hcy postoperatively. This finding is in contrast to results from cardiac surgery and carotid endarterectomy in a recently published animal study, both performing surgery under general anaesthesia.

Adult↗

PubMed2001

Immunofluorescence assays (IFA) and enzyme-linked immunosorbent assays (ELISA) in autoimmune disease diagnostics--technique, benefits, limitations and applications.

Autoimmune diseases are relatively frequent disease complexes, affecting approximately five to seven percent of the population. After cardio-vascular and malignant diseases they come third in mortality. As the clinical diagnosis of rheumatic autoimmune diseases is difficult, laboratory tests are helpful in differential diagnosis and for verification of the clinical diagnosis. The most commonly used assay is the determination of ANAs (anti nuclear antibodies) by indirect immunofluorescence (IFA). However, this method lacks reliable standardisation and is very dependable on the qualification of the observer. Enzyme Immunoassays (EIA) and Immunoblotting techniques, on the contrary, attain good standardisation and comparability. However, the latter methods are limited to the presentation of defined autoantibodies only. There is a need to select a suitable strategy for the use of laboratory parameters in order to support the clinical diagnosis more efficiently. A possible strategy is to replace IFA as a first line screening-step by second-generation ANA-EIA kits.

Antibodies, Antinuclear↗

PubMed2000

A simple method for measurement of CD14weak CD16strong monocytes in peripheral blood.

Mounting evidence for the clinical significance of the CD 14weak CD16strong monocyte subpopulation in peripheral blood induced the demand for an efficient method for its determination. We propose a simple, fast, no-wash flow cytometric method using fluorescence-labelled anti-CD14, anti-CD16, and anti-HLA-DR antibodies and ammonium chloride-based erythrocyte lysis. This type of analysis can be performed on a standard three-colour flow cytometer. The method avoids interference by NK-cells and neutrophil granulocytes without defining monocytes by stringent light scatter criteria that might lead to a loss of CD14weak CD16strong monocytes. It, therefore, offers high reliability and accuracy. Its performance recommends the method to be used for routine clinical measurements of CD14weak CD16strong monocytes.

Flow Cytometry↗

PubMed1999

Differential expression of tumor necrosis factor receptor subtypes on leukocytes in systemic inflammatory response syndrome.

OBJECTIVE: To determine the expression of tumor necrosis factor (TNF) receptor in patients with systemic inflammatory response syndrome (SIRS). DESIGN: Prospective study. SETTING: Intensive care unit and central laboratory. PATIENTS: Blood specimens from 18 healthy volunteers (controls) and 16 patients with SIRS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using monoclonal antibodies, fluorescence labeling, and high sensitivity flow cytometry, we measured the expression of membrane TNF receptor subtypes TNF-R55 and TNF-R75 on peripheral blood leukocytes. Receptor expression is expressed as mean fluorescence intensity +/- SD (units: detection channel number). In controls, TNF-R55 was only weakly expressed (monocytes: 2.5+/-1.8; neutrophils: 0.7+/-0.8), whereas expression of TNF-R75 was higher (monocytes: 28.6+/-9.0; neutrophils: 4.8+/-1.0) and was also found on lymphocytes (on CD8+ lymphocytes: 5.7+/-1.8; CD16+: 5.5+/-1.2; CD4+: 9.7+/-3.7). In SIRS, we observed increased expression of TNF-R55 on monocytes (6.9+/-3.4, p<.001) and neutrophils (2.2+/-1.9, p<.01), as well as decreased expression of TNF-R75 on monocytes (17.3+/-13.2; p<.001). The extent of TNF-R55 up-regulation did not correlate with that of TNF-R75 down-regulation. TNF-R55 on monocytes and neutrophils strongly correlated with body temperature but not with survival, whereas monocyte TNF-R75 was considerably lower in nonsurvivors, albeit not significantly (12.3+/-7.1 vs. 23.9+/-16.7; p = .07). CONCLUSIONS: These data indicate that leukocyte TNF-R55 and TNF-R75 react differentially and probably serve different functions in SIRS, which prompts the investigation of receptor subtype-specific therapeutic approaches.

Adult↗

PubMed1998

Measurement of absolute concentration and viability of CD34+ cells in cord blood and cord blood products using fluorescent beads and cyanine nucleic acid dyes.

Conventional flow cytometric methods for CD34+ cell counting may be affected by the high number of nucleated red blood cells or nonviable cells in cord blood and its products. We developed a simple flow cytometric no-wash procedure that avoids these shortcomings because it provides absolute CD34+ cell counts and assesses cell viability. Samples were incubated with phycoerythrin (PE)-labeled anti-CD34 (Becton Dickinson Immunocytometry Systems [BD], San Jose, CA) and peridinin chlorophyll protein (PerCP)-labeled anti-CD45 (BD) in bead-containing TRUCOUNT tubes (BD). After red cell lysis with a fixative-free reagent, the impermeant nucleic acid dye YO-PRO-1 (Molecular Probes, Eugene, OR) was added and samples were analyzed on a single-laser FACSCalibur (BD). A comparison with the ProCOUNT progenitor cell assay (BD) in 57 samples revealed excellent correlation of results (r = 0.98, intercept -0.2 cells/microl, slope 1.01). Precision studies conveyed coefficients of variation of 6.4 and 8.9% at concentrations of 35 and 16 CD34+ cells/microl, respectively. In untreated and leukocyte-enriched cord blood 4.5+/-3.8% of CD34+ cells were stained by YO-PRO-1, representing apoptotic or necrotic cells. In post-thawing cryopreserved samples this number increased to 10.4+/-5.5%. Isotype controls showed very low blank values of viable cells (0.1+/-0.4 cells/microl, maximum 2.4) and seemed unnecessary. We found no washing-related alteration of results in 35 samples, indicating that the method may also be performed with cell washing. Replacing YO-PRO-1 with TO-PRO-3 facilitated four-color analysis of subpopulations of viable CD34+ cells on a FACSCalibur equipped with a second (diode) laser. We found the proposed method to be a rapid, efficient, and flexible procedure that improved validity of CD34+ cell counts.

Antigens, CD34↗

PubMed1998

FMC7 antigen expression on normal and malignant B-cells can be predicted by expression of CD20.

Most antibody panels proposed for flow cytometric immunophenotyping of non-Hodgkin's lymphomas and chronic lymphoid leukemias include anti-CD20 and FMC7 antibodies. As in our experience, reactivity of B-cells with these antibodies seemed to be correlated, we evaluated whether the simultaneous use of anti-CD20 and FMC7 antibodies is justified. Using flow cytometry, we measured the binding of these 2 antibodies to the B-cells of 67 bone marrow aspirates, 31 lymph node biopsies, 18 peripheral blood specimens, and 12 tissue samples from other locations. The diagnoses included 50 cases without overt abnormalities, 5 reactive lymphadenopathies, 56 lymphomas and chronic lymphoid neoplasias, and 17 cases with other malignancies. Although CD20 expression was consistently higher, we observed a significant and strong correlation between CD20 and FMC7 antigen expression on B-lymphocytes, irrespective of the nature of the sample or disease (r=0.910; P < 0.001). Moreover, FMC7 antigen expression on B-cells could be predicted by CD20 expression with a sensitivity of 96%, a specificity of 94% and an efficiency of 96%. Our results show that although differing in intensity, expression of CD20 on B-cells closely parallels that of FMC7 antigen. We, therefore, conclude that little additional information is revealed by using FMC7 in immunophenotyping of non-Hodgkin's lymphomas or chronic lymphoid leukemias if intensity of CD20 expression is taken into consideration.

Antibodies, Monoclonal↗

PubMed1997

Toward a new reference method for the leukocyte five-part differential.

A flow cytometric method performing a five-part leukocyte differential based on three-color staining with anti-CD45-fluorescein isothiocyanate (FITC), anti-CD-14-phycoerythrin (PE)/Cy5, and a cocktail of PE-labeled anti-CD2, anti-CD16, and anti-HLA-DR antibodies was evaluated. Results obtained by using three different sample preparation procedures and two different flow cytometers were compared with those of a 1,000-cell manual differential for evaluation of accuracy. We observed excellent correlations with the manual differential for all leukocyte subclasses and even higher correlations between the different flow cytometric methods. Flow cytometric basophil results were identical to the manual counts, regardless of which sample preparation technique or flow cytometer was used. Therefore, we propose our flow cytometric method as the first acceptable automated reference method for basophil counting. The flow cytometric results for the other leukocyte subclasses were apparently influenced by the sample preparation, which could not be explained by cell loss during washing steps. Moreover, a small influence of the flow cytometer was also observed. Assessing the influence of sample storage, we found only minimal changes within 24 h. In establishing reference values, high precision of flow cytometric results facilitated detection of a significantly higher monocyte count for males (relative count: 7.08 +/- 1.73% vs. 6.44 +/- 1.33%, P < 0.05; absolute count: 0.536 +/- 0.181 x 10(9)/liter vs. 0.456 +/- 139 x 10(9)/liter, P < 0.01). Our data indicate that monoclonal antibody-based flow cytometry is a highly suitable reference method for the five-part differential: It also shows, however, that studies will have to put more emphasis on methodological issues to define a method that shows a high interlaboratory reproducibility.

Antibodies, Monoclonal↗

PubMed1997

Value of neutrophil CD16 expression for detection of left shift and acute-phase response.

Fc gamma RIII (CD16) expression of neutrophil granulocytes was measured in 156 patients by means of fluorescence-labeled antibodies with a flow cytometer. Results were compared with (1) 400-cell manual differential count; (2) left shift flagging on hematology analyzers; (3) absolute neutrophil count; and (4) acute-phase protein levels. Asynchrony was noted between neutrophil CD16 expression and microscopically defined neutrophil stage, particularly in heavily left-shifted samples, which made it impossible to reliably enumerate immature neutrophils on the basis of CD16 expression. According to receiver operating characteristics, the absolute count of CD16-negative neutrophils was highly discriminatory for detection of left shift, with an area under the curve (AUC) of 0.842 +/- 0.03 (SE) and maximum efficiency of 81% +/- 3%, but absolute neutrophil count was not significantly inferior (0.821 +/- 0.03 and 76% +/- 3%). STKS and SE9000 flagging demonstrated efficiency of 76% +/- 3% and 81% +/- 3%, respectively. For detection of acute-phase response, absolute neutrophil count (AUC, 0.836 +/- 0.04; maximum efficiency, 80% +/- 4%) outperformed both quantitative neutrophil CD16 expression (0.760 +/- 0.05; 75% +/- 4%) and absolute CD16-negative neutrophil count (0.757 +/- 0.05; 71% +/- 4%); absolute band count performed similarly (0.853 +/- 0.04; 79% +/- 4%) and showed high efficiency at high sensitivity and specificity. Efficiency of analyzer flagging for detection of acute-phase response was not superior to absolute neutrophil count (STKS, 77% +/- 4%; SE9000, 78% +/- 4%). In conclusion, the diagnostic value of measuring neutrophil CD16 expression was generally similar to that of less complicated analytes.

Acute-Phase Reaction↗

PubMed1997

Increased serum levels of soluble CD44-isoform v5 in rheumatic diseases are restricted to seropositive rheumatoid arthritis.

Serum levels of sCD44v5 were measured in 134 patients with definite inflammatory rheumatic diseases (IRD) using a sandwich type ELISA. 94 patients suffered from erosive IgM-rheumatoid factor positive rheumatoid arthritis (RA+), 20 with undifferentiated seronegative polyarthritis, 12 with osteoarthropathia psoriatica and psoriasis vulgaris, 3 with systemic lupus erythematosus, 3 with scleroderma and 2 with reactive arthritis. Elevated serum levels (> 58 ng/ml to 221 ng/ml; median: 93 ng/ml) were only detected in 54/94 (57%) patients with RA+, but not in other IRD. They correlated with advanced stages of disease (Steinbrocker stages III + IV; p < 0.05), elevated CRP-levels (p < 0.01) and higher measurements of IgM rheumatoid factor.

Adult↗

PubMed1996

Proposed reference method for peripheral-blood monocyte counting using fluorescence-labelled monoclonal antibodies.

Flow cytometry using fluorescence-labelled monoclonal antibodies has been proposed as a possible new reference method to evaluate the monocyte counting performance of automated hematology analyzers. Since in previous studies only one such technique was applied, we investigated how different flow cytometric techniques compared to the manual differential and a hematology analyzer. Relative monocyte counts of 60 samples of the daily routine were determined on a Coulter Profile II flow cytometer after incubation with two different CD45-FITC/CD 14-PE antibody combinations and subsequent preparation with two whole-blood lysis techniques, including one no-wash technique. Results were compared to those of a 600-cell manual differential and to those of the Coulter STKS hematology analyzer. All flow cytometric methods correlated very well with the manual differential (r > or = 0.925) and none showed a significant bias. The Coulter STKS relative monocyte counts were slightly higher than those of the manual differential (8.76% vs. 8.18%). The correlations between the methods employing monoclonal antibodies were excellent (r > or = 0.995) and the mean monocyte counts identical although a small, non-systematic influence of sample preparation techniques was noted. An influence of the antibody clones was not observed. The precision of the Profile II results was far superior to that of the manual differential and the STKS. Our data show that flow cytometry employing fluorescence-labelled monoclonal antibodies is a potentially ideal new reference method for monocyte counting. However, they also show that establishing a new reference method will require extensive investigation and exact definition of the sample preparation procedure to be used.

Antibodies, Monoclonal↗

PubMed1996

Evaluation of automated basophil counting by using fluorescence-labelled monoclonal antibodies.

The shortcomings of current methods of basophil enumeration detract from the clinical value of the basophil count. Moreover, sophisticated and costly techniques of automated basophil counting hardly can be validated for lack of a suitable reference method. We investigated whether a flow cytometric technique using double staining with fluorescence-labelled monoclonal antibodies (mAb) CD45-FITC and CD14-PE on a Coulter Epics Profile II could be used to evaluate basophil counting performance of hematology analyzers. The technique was compared with the 800-cell manual differential, the Coulter STKS, and the Cobas Argos 5 Diff. Precision: STKS, Argos and Profile II showed a precision analogous to a 2,173, 2,250-, and 14,705-cell differential, respectively, illustrating the superiority of automated methods. Accuracy (150 normal and abnormal samples): Using the Profile II as reference the STKS showed a notably weaker correlation than the Argos (r = 0.581 and 0.718, respectively), although this difference was nearly concealed when the imprecise manual differential served as reference (r = 0.517 and 0.562, respectively). The Profile II correlated relatively well with the manual differential (r = 0.730). Analyzing 137 healthy adult subjects, we obtained a reference range of 0.33 to 1.35% (0.020 to 0.102 x 10(9) basophils/L) for the mAb-based method. These data would recommend mAb-based basophil counting as a valuable tool for instrument evaluation. However, an observed bias of 0.09% against the manual differential suggests that modifications are necessary before this technique can be considered as new reference method.

Adult↗

PubMed1996

Use of precision profiles to evaluate precision of the automated leukocyte differential.

The commonly used methods of assessing the precision of the automated leukocyte differential have certain drawbacks that affect the validity and comparability of results. In the present report, we introduce a procedure based on building precision profiles from a large number of within-run imprecision experiments. The profiles are fitted to the function for the CV of proportions, which yields the number of theoretically differentiated leukocytes. Differences between fitted curves are evaluated for statistical significance by the F-test. As an example, we compared the precision of two hematology analyzers, a flow-cytometric technique involving fluorescence-labeled monoclonal antibodies, and the manual differential. We were able to establish definite differences in precision between different analyzers and different leukocyte classes. Our data also indicated that conventional within-run imprecision studies may completely misjudge analyzer precision. Furthermore, we could demonstrate that the precision of analyzers that analyze a fixed amount of blood rather than a fixed number of leukocytes is strongly influenced by the leukocyte count of the sample, leading to high imprecision for leukopenic samples. We believe the proposed procedure is a useful addition to currently used protocols; it yields clear results and creates a statistical basis of comparison between various instruments and techniques of differentiation.

Autoanalysis↗

PubMed1995

Precision and accuracy of monocyte counting. Comparison of two hematology analyzers, the manual differential and flow cytometry.

The Coulter STKS (Coulter, Hialeah, FL), the Abbott CD3500 (Abbott Diagnostics, Abbott Park, IL), a 400-cell manual differential, and flow cytometry using double-staining with fluorescence-labelled monoclonal antibodies (CD45-FITC and CD14-PE) on a Coulter Epics Profile II were evaluated for precision and accuracy in relative monocyte counting. STKS, CD3500, and Profile II achieved a precision analogous to a 3,542-, 1,835-, and 11,998-cell differential, respectively, demonstrating the superiority of automated methods. Analysis of 156 normal and abnormal samples revealed that the mean relative monocyte counts of the manual differential, CD3500 and Profile II were not significantly different. Only the STKS results showed a positive bias (0.79% +/- 1.65), which was increased in lymphocytic samples. Linear regression between the Profile II as independent viable, and the other techniques yielded acceptable correlation coefficients (STKS: 0.861, CD3500: 0.844, manual differential:0.833). Profile II results were also compared to those of a Becton Dickinson FACScan (Becton Dickinson, Mountain View, CA), which yielded an excellent correlation (r = 0.991) but a slightly smaller relative monocyte count (bias-0.39% +/- 0.60) of the latter. On the basis of these data, the authors recommend the use of monoclonal antibodies as a new reference method, but also indicate the need for further methodological investigations.

Antibodies, Monoclonal↗

PubMed1995

Peripheral blood monocyte counting: towards a new reference method.

Flow cytometric enumeration of monocytes stained with fluorescence-labelled monoclonal antibodies has been proposed as a possible reference method for monocyte counting. We compared precision and accuracy of monocyte counting of the Coulter STKS, the Cobas Argos 5 Diff, the 800-cell manual differential, and the Coulter Epics Profile II flow cytometer using double-staining with fluorescence-labelled monoclonal antibodies (CD45-FITC and CD14-PE). Precision: STKS, Argos and Profile II achieved a precision analogous to a 3423-, 1298-, and 11089-cell differential, respectively, confirming the superiority of automated methods. Accuracy (136 normal and abnormal samples): Correlation of automated methods with the manual differential was good (STKS: r = 0.934, Argos 5 Diff: r = 0.808, Profile II: r = 0.924; Spearman's rank correlation coefficient). The mean relative STKS monocyte result was 0.52 +/- 1.63% (mean +/- SD) higher than the manual differential, whereas the Argos 5 Diff results were 1.22 +/- 2.51% lower (p < 0.001). Profile II results showed a small bias against the manual differential (-0.18 +/- 1.44%, p < 0.05). Analysing 135 healthy adult subjects on the Profile II, males were found to have a higher mean monocyte count (relative count: 6.95 +/- 1.43% vs. 5.86 +/- 0.98%; absolute count: 0.48 +/- 0.15 x 10(9)/l vs. 0.39 +/- 0.11 x 10(9)/l, p < 0.001) and a higher and wider normal range than females (relative count: 4.97 to 9.78% vs. 4.26 to 7.81%, absolute count: 0.30 to 0.84 x 10(9)/l vs. 0.25 to 0.65 x 10(9)/l). Flow cytometry based on fluorescence-labelled monoclonal antibodies for monocyte enumeration seems an efficient tool to evaluate the monocyte counting performance of haematology analysers and an ideal successor to the manual differential as reference method for monocyte counting.

Adult↗

PubMed1995

Utilization of tyrosine-containing dipeptides and N-acetyl-tyrosine in hepatic failure.

The impact of hepatic dysfunction on the elimination and hydrolysis of three potential tyrosine sources for total parenteral nutrition, the dipeptides L-alanyl-L-tyrosine (Ala-Tyr) and glycyl-L-tyrosine (Gly-Tyr), and N-acetyl-L-tyrosine (Nac-Tyr) were evaluated in six patients with hepatic failure (five chronic, one acute) and seven healthy subjects. In controls, whole-body clearance (Cltot) of Ala-Tyr was higher than of Gly-Tyr (3,169 +/- 214 vs. 1,780 +/- 199 mL/kg/min, P < .01), and both exceeded clearance of Nac-Tyr (309 +/- 29 mL/kg/min, P > .01). Both dipeptides were hydrolyzed and released tyrosine immediately. In hepatic failure, elimination and hydrolysis of Ala-Tyr and Gly-Tyr were comparable to controls, but Cltot of Nac-Tyr was reduced (236 +/- 26 mL/kg/min). Neither in controls nor in patients an increase in plasma tyrosine concentration was seen after Nac-Tyr, and the major part of Nac-Tyr infused was lost in urine. The Cltot of tyrosine as evaluated after Ala-Tyr infusion (with the immediate release of tyrosine) was severely reduced in hepatic failure (152.7 +/- 38.4 vs. 484.4 +/- 41.4 mL/kg/min, P < .001) and half-life (kle) was retarded from 14.4 +/- 1.4 to 90.2 +/- 32.2 minutes (P < .03). The authors conclude that acute and chronic hepatic dysfunction does not affect elimination and hydrolysis of the dipeptides Ala-Tyr and Gly-Tyr and the constituent amino acids are released immediately. Nac-Tyr elimination was not grossly affected by hepatic failure, but neither in healthy subjects nor in hepatic failure patients was an increase of tyrosine seen. Both dipeptides but not Nac-Tyr may serve as a tyrosine source in parenteral nutrition. Moreover, by its rapid hydrolysis, the use of Ala-Tyr, for the first time, enables a simple rapid nonisotope evaluation of tyrosine kinetics for assessment of liver function.

Adult↗

PubMed1994

Importance of liver and kidney for the utilization of glutamine-containing dipeptides in man.

The impact of hepatic and renal failure on the metabolism of L-alanyl-L-glutamine (Ala-Gln) and glycyl-L-glutamine (Gly-Gln) was investigated in 11 healthy volunteers, five patients with liver cirrhosis, and six patients with chronic renal failure. The clearance (mL.kg-1.min-1) of Ala-Gln was significantly higher than that of Gly-Gln in all three groups. Renal failure significantly reduced clearances of both Ala-Gln and Gly-Gln (13.27 +/- 0.71 and 3.06 +/- 0.28) when compared with control values (21.68 +/- 1.21 and 7.08 +/- 0.38). Liver failure had no significant influence on the clearances of Ala-Gln and Gly-Gln (22.62 +/- 2.89 and 6.20 +/- 0.88). Liver failure delayed and renal failure almost abolished the increases in plasma concentrations of free amino acid residues after peptide injection. It is concluded that other organs can substitute for the peptide-clearing function of the liver, but not of the kidney. Kidney is the most important organ for the clearance of dipeptides and the release of amino acid residues into circulation. Our data show that clearance rates of both Ala-Gln and Gly-Gln are sufficient to avoid accumulation of either peptide if infused in the presently recommended doses. Both Ala-Gln and Gly-Gln could therefore be used as sources for glutamine in parenteral nutrition even in patients with chronic renal failure.

Adult↗