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Biomedical subjects

T Sauerbruch

Publications and source records attributed to T Sauerbruch.

At least 145 records · Page 8Linked to original sources
PubMed2000

Is the increase in serum cystathionine levels in patients with liver cirrhosis a consequence of impaired homocysteine transsulfuration at the level of gamma-cystathionase?

BACKGROUND: It has been suggested that the major metabolic block in the methionine catabolic pathway in cirrhotics exists at the level of the enzyme S-adenosylmethionine synthetase because in previous studies using conventional amino-acid analyzers, no intermediates of transmethylation/transsulfuration were found to accumulate in plasma downstream of S-adenosylmethionine synthesis. We therefore measured serum concentration intermediates of methionine transmethylation/transsulfuration using an improved gas chromatography/mass spectrometry technique. METHODS: Serum concentrations of methionine, homocysteine, cystathionine, N,N-dimethylglycine, N-methylglycine, methylmalonic acid, 2-methylcitric acid and alpha-aminobutyric acid were determined by gas chromatography/mass spectrometry in 108 consecutive patients with liver cirrhosis at Child stages A (mild cirrhosis, n = 27) and B/C (severe cirrhosis, n = 81), 18 outpatients with non-cirrhotic liver disease, and 55 healthy individuals. RESULTS: Serum levels of methionine, N,N-dimethylglycine, N-methylglycine, cystathionine, and homocysteine were significantly higher in patients at Child stages B/C compared with those of healthy controls (P < 0.01), and they were also significantly higher than in patients with non-cirrhotic liver disease (P < 0.01 and P < 0.05 for homocysteine, respectively). They also correlated with the Child-Pugh score (P < 0.01). Homocysteine, cystathionine, N,N-dimethylglycine, N-methylglycine, methylmalonic acid, and 2-methylcitric acid correlated with serum creatinine. The mean cystathionine concentration was significantly higher in patients with creatinine > or = 1.4 mg/dl than in patients with normal creatinine values (P < 0.01). However, the differences between cirrhotics and healthy controls were still significant after correcting for creatinine. CONCLUSIONS: Our data provides indirect evidence for two hitherto unrecognized alterations of methionine metabolism in cirrhotics, i.e. impairment of the transsulfuration of homocysteine at the level of cystathionine degradation and a shift in remethylation of homocysteine towards the betaine-homocysteine-methyltransferase reaction.

Adolescent↗
PubMed2000

Comparison of portal vein velocity and the hepatic venous pressure gradient in assessing the acute portal hemodynamic response to propranolol in patients with cirrhosis.

OBJECTIVE: The aim of this prospective study was to compare noninvasive Doppler sonography and invasive measurement of the hepatic venous pressure gradient (HVPG) to determine the acute portal hemodynamic response to propranolol in patients with liver cirrhosis. METHODS: In a blinded study design, portal vein velocity (PVV) and HVPG were simultaneously assessed in 11 cirrhotic patients for 4 h after oral ingestion of 40 mg propranolol. RESULTS: Both HVPG (17.2% +/- 4.3%, p < 0.0001) and PVV (15.6% +/- 2.1%, p < 0.0002) showed a highly significant reduction during the study period versus baseline. Based on HVPG measurements, four patients (36%) were classified as nonresponders. These patients had a significantly lower PVV reduction compared to the responders (responders: 18.8% +/- 2.0% vs nonresponders: 10.0% +/- 2.1%, p < 0.05). Nonresponders were identified by Doppler sonography with a sensitivity of 1.0, specificity of 0.86, and positive predictive value of 0.9 when a threshold of 20% PVV reduction 120 min after drug intake was applied. CONCLUSIONS: Doppler sonography is a useful tool for assessment of the acute portal hemodynamic effect of propranolol. To distinguish portal hemodynamic nonresponders from responders to propranolol, PVV measurements should be carried out 2 h after drug administration, and PVV reduction should be not <20% in propranolol responders.

Administration, Oral↗
PubMed2000

Long term outcome after transjugular intrahepatic portosystemic stent-shunt in non-transplant cirrhotics with hepatorenal syndrome: a phase II study.

BACKGROUND: Recent small studies on hepatorenal syndrome (HRS) indicate some clinical benefit after transjugular intrahepatic portosystemic stent-shunt (TIPS) but sufficient long term data are lacking. AIM: We studied prospectively feasibility, safety, and long term survival after TIPS in 41 non-transplantable cirrhotics with HRS (phase II study). PATIENTS AND METHODS: HRS was diagnosed using current criteria (severe (type I) HRS, n=21; moderate (type II) HRS, n=20). Thirty one patients (14 type I, 17 type II) received TIPS (8-10 mm) while advanced liver failure excluded shunting in 10. During follow up (median 24 months) we analysed renal function and survival (Kaplan-Meier). RESULTS: TIPS markedly reduced the portal pressure gradient (21 (5) to 13 (4) mm Hg (mean (SD)); p<0.001) with one procedure related death (3.2%). Renal function deteriorated without TIPS but improved (p<0.001) within two weeks after TIPS (creatinine clearance 18 (15) to 48 (42) ml/min; sodium excretion 9 (16) to 77 (78) mmol/24 hours) and stabilised thereafter. Following TIPS, three, six, 12, and 18 month survival rates were 81%, 71%, 48%, and 35%, respectively. As only 10% of non-shunted patients survived three months, total survival rates were 63%, 56%, 39%, and 29%, respectively. Multivariate Cox regression analysis revealed bilirubin (p<0.001) and HRS type (p<0.05) as independent survival predictors after TIPS. CONCLUSIONS: TIPS provides long term renal function and probably survival benefits in the majority of non-transplantable cirrhotics with HRS. These data warrant controlled trials evaluating TIPS in the management of HRS.

Feasibility Studies↗
PubMed2000

Effects of ursodeoxycholic acid on splanchnic and systemic hemodynamics. A double-blind, cross-over, placebo-controlled study in healthy volunteers.

BACKGROUND: Recently, the beneficial effects of ursodeoxycholic acid (UDCA) on the portal hypertensive state have been demonstrated in patients with primary biliary cirrhosis. However, it is not known whether UDCA has direct or indirect effects on the vascular smooth muscles in humans, thereby leading to a change in splanchnic or systemic hemodynamics. AIMS: We therefore evaluated the hemodynamic effects of UDCA as to its established effect on gallbladder motility under fasting and postprandial conditions in healthy volunteers. METHODS: In a double-blind, cross-over study of 20 healthy volunteers, placebo or UDCA (750 mg/d) were randomly administered over 4 weeks with an interim 4-week washout period. Portal blood flow, cardiac output and gallbladder motility were measured using echo-Doppler and b-mode sonography before and after placebo and verum, respectively. ECG, blood pressure, heart rate and blood chemistry were also measured. RESULTS: UDCA did not significantly change fasting portal flow or meal-induced portal hyperemia. Both fasting and postprandial gallbladder volumes increased (26.5 +/- 6.0 vs. 40.7 +/- 13.8 ml, p < 0.05, and 11.2 +/- 6.2 vs. 14.8 +/- 6.7 ml, p < 0.05). Diastolic blood pressure decreased under UDCA (71.2 +/- 8.7 vs. 66.5 +/- 6.5 mm Hg, p < 0.05). Serum levels of chloride and gamma-glutamyltransferase decreased slightly, while alkaline phosphatase increased. CONCLUSIONS: UDCA affected systemic but not portal hemodynamics. The increase in gallbladder volume is obviously mediated by factors that do not influence the splanchnic vascular bed.

Adult↗
PubMed2000

Elevated soluble tumour necrosis factor receptor serum concentrations and short-term mortality in liver cirrhosis without acute infections.

BACKGROUND: Serum concentrations of the soluble 75-kDa tumour necrosis factor receptor (sTNF-R 75) are elevated in patients with severe liver disease and may be linked to mortality as well as to prognostic markers related to clinical outcome and metabolic functions in patients with liver cirrhosis. PATIENTS AND METHODS: We prospectively studied the relation of sTNF-R 75 to Child-Pugh score points and serum markers of bile acid (total serum bile acids and 7alpha-hydroxycholesterol), lignocaine (lignocaine metabolite (MEGX) liver function test results) and albumin metabolism (albumin and prealbumin) in 10 healthy individuals and 30 patients with cirrhosis, all free of acute infections. In patients with cirrhosis mortality was recorded for 15 months. RESULTS: Soluble TNF-R 75 concentrations correlated with Child-Pugh score points (r = 0.440, p = 0.015), MEGX test results (r(S) = -0.604, p < 0.001) and prealbumin (r(S) = -0. 527, p < 0.001) in cirrhosis. Nonsurviving patients had almost threefold higher median sTNF-R 75 concentrations (29 ng/ml) than survivors (11 ng/ml) (p = 0.003). Soluble TNF-R 75 serum concentrations with an optimal cut off > 14 ng/ml were significantly more accurate in predicting patient mortality than Child-Pugh score points in a receiver-operator characteristic curve analysis. CONCLUSION: Soluble TNF-R 75 serum concentrations appear to be a promising new risk factor for mortality in patients with cirrhosis without acute infections.

Adult↗
PubMed2000

Liver perfusion scintigraphy prior to and after transjugular intrahepatic portosystemic shunts (TIPS) in patients with portal hypertension.

PURPOSE: This investigation was performed to compare the hemodynamic results of the transjugular intrahepatic portosystemic shunt, a new interventional treatment for portal hypertension, with those observed after the established surgical shunt interventions. METHODS: We examined 22 patients with portal hypertension due to liver cirrhosis before and after elective TIPS by liver perfusion scintigraphy. The relative portal perfusion was determined before and after the shunt procedure. Additionally, we measured the portal pressure gradient (PPG: portal-central venous pressure, mmHg). RESULTS: Prior to TIPS, the relative portal perfusion was significantly reduced to 22 +/- 9.1%. After the intervention we calculated values of 23.1 +/- 10.7% in the TIPS-group (p = 0.67; not significant). In spite of unchanged portal perfusion, the portal pressure was significantly (p < 0.001) reduced from 25.6 +/- 5.3 to 14.8 +/- 4 mm Hg. CONCLUSION: These results suggest that the reduction of portal hypertension by TIPS is effective. The portal perfusion is maintained by TIPS suggesting that liver perfusion is preserved to a higher degree.

Adult↗
PubMed1999

Antigen-specific cytokine response to hepatitis C virus core epitopes in HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: Epidemiological data indicate that hepatitis C virus (HCV) infection runs a more rapid and severe course of disease in HIV-coinfected patients, probably because of an altered immune response. DESIGN: We investigated whether HCV-specific cytokine responses are affected by HIV coinfection. METHODS: Using triple colour flow cytometry on peripheral blood lymphocytes after stimulation with the four major immunodominant HCV core T cell epitopes, CT1-CT4, we determined intracytoplasmic production of IFN-gamma, IL-2, IL-4, IL-10 and CD30 expression, a putative surrogate marker of type 2 cells. Fifteen patients with asymptomatic HIV/HCV coinfection (group A), 15 patients with chronic HCV infection (group B) and 10 HIV-infected patients without hepatitis C (group C) were included in the study. RESULTS: In group A, HCV antigens induced significantly higher IL-2 and IFN-gamma production than groups B and C (P < 0.05). Groups A and B showed a similar induction of CD30, which was significantly higher than in group C (P < 0.001). Remarkably, in group A HCV antigens induced IL-4 production in addition to IL-10 and IFN-gamma in the CD30 subset, whereas in groups B and C no IL-4 induction was observed in this T cell subset (P < 0.002). CONCLUSION: Our data suggest that asymptomatic HIV coinfection importantly alters the HCV-specific cytokine response towards a greater production of proinflammatory type 1 cytokines. Moreover, the antiviral activity of type 1 cytokines may be modified by an increased production of type 2 cytokines in the CD30 subset. The altered cytokine pattern may contribute to the adverse natural course of hepatitis C in HIV coinfection.

Adult↗
PubMed1999

Semiquantitation of human chemokine mRNA levels with a newly constructed multispecific competitor fragment.

Chemokines are a group of inducible, locally acting proinflammatory cytokines which have been implicated in the pathogenesis of a variety of diseases. Important members of the group include monocyte chemoattractant protein (MCP)-1, -2, -3, macrophage inhibitory protein (MIP)-1alpha, -1beta and RANTES (regulated upon activation, normal T expressed and secreted). To facilitate further investigation of the human chemokines, we have constructed a novel multispecific competitor fragment containing primer binding sites for the CC-chemokines MCP-1, MCP-2, MCP-3, MIP-1alpha, MIP-1beta and RANTES, the CXC-chemokines MIP-2alpha, MIP-2beta as well as for the housekeeping gene beta-actin. Using this competitor fragment we can demonstrate reliable semiquantitation of reverse transcribed chemokine mRNAs. The assay should be useful for further studies, in particular for the semiquantitation of chemokine mRNA species from small cell or tissue specimens.

Actins↗
PubMed1999

Enhanced expression of CD80 (B7-1), CD86 (B7-2), and CD40 and their ligands CD28 and CD154 in fulminant hepatic failure.

To define a possible role for changes in the regulation of antigen presentation in fulminant hepatic failure (FHF), we studied the expression of co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 along with their ligands CD28 and CD154. We analyzed the liver tissue from patients with FHF (n = 18), chronic liver disease (n = 30), and acute hepatitis (n = 3) and from normal controls (n = 9) by immunohistochemistry and examined the temporal relationship between CD80/CD86 and CD40 expression and disease in the mouse models of galactosamine-lipopolysaccharide and galactosamine-tumor-necrosis-factor-induced FHF. In human controls, faint CD80/CD86 immunoreactivity was restricted to Kupffer cells, and CD40 expression was expressed on bile ducts, macrophages, and sinusoidal endothelial cells (SECs). In FHF, immunoreactivity for CD80 and CD86 was observed on significantly higher numbers of cells, including SECs. Increased CD80/CD86 expression corresponded to increased numbers of CD28-positive lymphocytes. The expression of CD40 was also clearly elevated on virtually all cell types in FHF. In both murine models, CD40 and CD80/CD86 expression was up-regulated before tissue damage could be detected. Our data suggest that up-regulated expression of co-stimulatory molecules might lead to an excessive antigen presentation in FHF as an early step in the pathogenesis before the onset of tissue damage.

Animals↗
PubMed1999

Altered adrenergic responsiveness of endothelium-denuded hepatic arteries and portal veins in patients with cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis are characterized by a reduced splanchnic vascular resistance and a hyporeactivity to adrenergic vasoconstrictors. So far, their adrenergic splanchnic vascular responsiveness has not been evaluated in vitro. We compared responses to alpha1- and beta2-adrenoceptor stimulation of hepatic arteries and portal veins of patients with cirrhosis undergoing transplantation with those of organ donors. METHODS: Isometric contractions of endothelium-denuded vessel rings were induced cumulatively by methoxamine and relaxations by isoproterenol. Results are expressed as percentage of the contraction obtained by 85 mmol/L KCl or of the relaxation obtained by 100 micromol/L papaverine, respectively. RESULTS: Maximal methoxamine-induced contractions were reduced in cirrhotic hepatic arteries (cirrhosis, 51.8% +/- 6.8%; donor, 89.9% +/- 6.6%; P < 0.01) and portal veins (cirrhosis, 49.2% +/- 6.4%; donor, 94.0% +/- 5.3%; P < 0.01). In cirrhosis, isoproterenol induced a less marked relaxation of hepatic arteries (cirrhosis, 46.6% +/- 3.2%; donor, 100.3% +/- 4.4%; P < 0. 01) but an increased relaxation of portal veins (cirrhosis, 41.9% +/- 6.2%; donor, 26.2% +/- 2.8%; P < 0.01). CONCLUSIONS: In cirrhosis, endothelium-free hepatic arteries are hyporeactive to alpha1- and beta2-adrenoceptor agonists, and portal veins are hyporeactive to alpha1- but hyperreactive to beta2-adrenoceptor agonists. These findings support the in vivo findings of a hyporesponsiveness to adrenergic vasoconstrictors in patients with cirrhosis.

Adrenergic Agonists↗
PubMed1999

Vitamin E status in patients with liver cirrhosis: normal or deficient?

The study aim was to compare the ratio of vitamin E to serum cholesterol with the serum vitamin E level alone as a measure of vitamin E status in patients with different degrees of liver dysfunction. Assessment of serum vitamin E and total serum cholesterol was performed in 85 patients with liver cirrhosis at Child's stage A (n = 26), B (n = 26), and C (n = 33) and 50 patients with noncirrhotic liver disease. As surrogate markers of liver function, 7alpha-hydroxycholesterol and prealbumin concentrations and the plasma prothrombin time were determined. Mean serum vitamin E concentrations in Child A, B, and C patients were 27.4%, 36.9%, and 37.3% lower, respectively, than in healthy controls (P<.01). Twelve of 26 Child A, 14 of 26 Child B, and 14 of 33 Child C patients had vitamin E deficiency with respect to the absolute values, i.e., serum levels less than 13.76 micromol/L (5% percentile of healthy controls). In contrast, only two of 26 Child A, five of 26 Child B, and five of 33 Child C patients (P<.01 for Child A/B and P<.05 for Child C) were vitamin E-deficient according to the serum vitamin E to cholesterol ratio, i.e., less than 2.86 micromol/mmol. Serum vitamin E was correlated significantly with prealbumin, 7alpha-hydroxycholesterol, and the plasma prothrombin time, but the vitamin E to cholesterol ratio was not. Correcting serum vitamin E for total serum cholesterol in patients with liver cirrhosis leads to the phenomenon of reduced serum vitamin E levels inadvertently shifted toward normal values. In patients with liver cirrhosis, the absolute vitamin E concentration correlates better with the typical clinical and biochemical findings of the disease than the vitamin E to cholesterol ratio. Therefore, a considerable number of patients with advanced liver cirrhosis might actually be vitamin E-deficient.

Adult↗
PubMed1999

Interferon/antioxidant combination therapy for chronic hepatitis C--a controlled pilot trial.

The effects of two forms of antioxidative co-therapy were analyzed in 24 interferon-alpha (IFN)-naive patients with chronic hepatitis C who were randomized to either receive IFN monotherapy (3 x 4.5 million units IFN-alpha 2a per week), (group A), or IFN and N-acetylcysteine (N-acetylcysteine (NAC) 1.800 mg/day) plus sodium selenite (400 microg/day) supplementation (group B), or treatment as in group B plus vitamin E (544 IU/day) (group C), over 24 weeks. Changes in histology, normalization of ALT, reduction of viral RNA, serum levels of glutathione, selenium, vitamin E, erythrocyte glutathione peroxidase, trolox equivalent antioxidative capacity (TEAC), thiobarbituric acid reactive substances (TBARS) and protein carbonyl groups were measured. Low baseline TEAC and elevated TBARS indicated increased oxidative stress before therapy, which was not affected by antioxidant supplementation. At the end of treatment complete responses were found in 3/8, 2/8 and 6/8 patients in groups A, B and C, respectively, but liver histology had not significantly improved. Vitamin E treated patients had a 2.4 greater chance (95% CI: 1.05-5.5) of obtaining a complete response and had significantly greater reduction in viral load (P = 0.028) than patients without vitamin E. Relapses, i.e. re-appearance of detectable hepatitis C virus (HCV) RNA and/or re-elevation of ALT-activity occurred in 7 out of the 11 responders within 6 months after termination of therapy (group A: 2/3, group B: 1/2 and group C: 4/6). Thus, no overall beneficial effect of antioxidant/IFN therapy was detected. However, the apparent trend towards a more favorable outcome with vitamin E supplementation warrants to further study this substance as an adjuvant to IFN therapy in chronic hepatitis C.

Acetylcysteine↗
PubMed1999

Decreased frequency of HCV core-specific peripheral blood mononuclear cells with type 1 cytokine secretion in chronic hepatitis C.

BACKGROUND/AIM: Since the outcome of hepatitis C infection appears to be correlated with the immune response to the HCV core protein, the aim of this study was to investigate the T cell response to hepatitis C virus core and core-derived antigens. METHODS: As this response may be regulated importantly by differential secretion of cytokines, we determined the number of peripheral blood mononuclear cells (PBMC) that secreted IL-2, IL-4, IL-10, and IFN-gamma in response to a recombinant HCV core protein and a panel of 19 core-derived peptides, using the ELI-Spot-technique. Two groups of patients were studied: group A: 11 patients with previously self-limited HCV infection; group B: 12 patients with chronic hepatitis C. RESULTS: In group B significantly less IFN-gamma spot forming cells (SFC) could be detected, both after stimulation with the core protein (0.083+/-0.083 SFC vs. 1.3+/-0.4 SFC/10(5) PBMC; p = 0.005 and with the core-derived peptides (1.3+/-0.5 vs. 4.4+/-1.1 SFC SFC/10(5) PBMC; p = 0.007). By analyzing the cytokine response to each single peptide, we found IFN-gamma responses to peptides aa 39-63 and aa 148-172 in group A but not in group B (p<0.03). In group B also, fewer IL-2 secreting cells were found after peptide stimulation (p = 0.04). Whereas subjects of group B showed IL-10-specific responses to HCV peptides more frequently than patients with self-limiting hepatitis C (p = 0.03), the number of IL-4-producing cells was not different between the two groups. CONCLUSIONS: The data suggest that patients with persistent viremia and chronic liver disease (group B) have less PBMC showing type 1 cytokine (IL-2, IFN-gamma) responses to HCV core protein than patients with self-limited HCV infection (group A).

Chronic Disease↗