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T Sauerbruch

Publications and source records attributed to T Sauerbruch.

At least 163 records · Page 9Linked to original sources
PubMed1999

Autoimmunity induced by interferon-alpha therapy for chronic viral hepatitis.

Type I interferons, which are mostly alpha-interferons (either as single agents or in combination with antiviral drugs), are currently the standard therapy for chronic viral hepatitis B, B/D, and C. Side-effects are not uncommon and include exacerbation of pre-existing autoimmune disorders or the de novo induction of autoimmunity. These adverse effects are attributed to the immunomodulatory properties of type I interferons, and should be distinguished from autoimmunity associated with chronic viral hepatitis in which interferon treatment may indeed be beneficial. The major autoimmune side-effects of interferon therapy for chronic viral hepatitis are thyroid or liver disease. Therefore, screening for thyroid antibodies and auto-antibodies indicative of autoimmune hepatitis both before, during, and after interferon therapy is strongly recommended. The presence of high concentrations of thyroid auto-antibodies or antibodies associated with autoimmune hepatitis can be contraindicative to interferon therapy. However, treatment is not contraindicated in viral hepatitis (in particular chronic hepatitis C) associated with autoimmune phenomena--including low-titer thyroid antibodies or other non-organ specific auto-antibodies. If interferon-induced autoimmunity occurs, the necessity of therapy has to be balanced carefully against the risks of autoimmune disease. Further research is needed to identify the factors which determine susceptibility to interferon-associated autoimmunity in individual patients.

Autoimmunity↗
PubMed1999

Propranolol stereoisomer plasma concentrations and portal haemodynamic response in patients with liver cirrhosis.

BACKGROUND: The haemodynamic effect of propranolol on portal pressure in patients with portal hypertension is highly variable and does not correlate with propranolol racemate plasma concentrations. AIM: To investigate the stereoselective metabolism of the propranolol enantiomers and its impact on portal haemodynamics in patients with liver cirrhosis since only S-propranolol is haemodynamically active. METHODS: Twenty patients with liver cirrhosis and portal hypertension received 40 mg propranolol orally. Portal blood velocity (PBV) and propranolol stereoisomer plasma concentrations were determined. RESULTS: During the 4 h examination period we observed a significant reduction in PBV (18.3 +/- 2.2%, P < 0.0001) vs. baseline. The area under the curve (AUC) during the study period was significantly different for the two isomers (S-propranolol 1217.0 +/- 118.5 nmol.h/L; R-propranolol 728.8 +/- 103.8 nmol.h/L, P < 0.0001). Seven patients (35%) were portal haemodynamic non-responders to propranolol. Propranolol stereoisomer AUC values were no different between responders (S-propranolol 1133. 3 +/- 132.0 nmol.h/L; R-propranolol 718.0 +/- 129.7 nmol.h/L) and non-responders (S-propranolol 1371.8 +/- 250.5 nmol.h/L; R-propranolol 746.9 +/- 200.3 nmol.h/L); neither was there a correlation between propranolol enantiomer plasma concentrations and the portal haemodynamic effect. CONCLUSIONS: Our data demonstrate a stereoselective metabolism of propranolol enantiomers in liver cirrhosis. However, following oral propranolol administration, stereoisomer plasma concentrations do not predict the portal haemodynamic effect.

Adrenergic beta-Antagonists↗
PubMed1999

Increased frequency of the HLA-DR15 (B1*15011) allele in German patients with self-limited hepatitis C virus infection.

BACKGROUND: A genetically determined resistance or susceptibility to chronic hepatitis C virus infection (HCV) may make an important contribution to the course of liver disease and may be linked to the human major histocompatibility complex. DESIGN: Twenty-one subjects with self-limited HCV infection as assessed by the presence of HCV antibodies, absence of HCV-RNA and normal levels of aminotransferases for 2 years were identified from a large pool of blood donors. The frequency of HLA serotypes of these individuals was compared with 49 consecutive patients with chronic hepatitis C. RESULTS: We detected a significantly higher prevalence of HLA-DR15 in patients with self-limited HCV infection than in patients with chronic hepatitis C (10/21 vs. 6/49; relative risk 6.5; P = 0.02; corrected for multiple comparisons). To confirm HLA assignments by serotyping we also performed sequencing of HLA-DR types in the 27 patients (9 with self-limited infection, 18 with chronic hepatitis C) who had been enrolled during 1995-96. This analysis confirmed the predominance of HLA-DR15 (HLA-DRB1*15011) in self-limited HCV infection (4/9 vs. 1/18; relative risk 13.6; P = 0.03). CONCLUSIONS: Our data suggest that HLA-DR15 (B1*15011) might constitute an important genetic factor for the elimination of the hepatitis C virus in Germany.

Adolescent↗
PubMed1999

Hepatitis C virus core protein does not inhibit apoptosis in human hepatoma cells.

BACKGROUND: Viral persistence is a major problem after infection with the hepatitis C virus. Recently, it has been reported that hepatitis C virus core protein inhibits cis-platin induced apoptosis in human cervical carcinoma cells and apoptosis induced by overexpression of c-myc in Chinese hamster ovary cells. MATERIALS AND METHODS: This study investigated whether different variants of hepatitis C virus core or E2 protein interfere with tumour necrosis factor alpha or Fas (CD95/ APO-1) antibody-induced programmed cell death in transiently transfected human hepatoma (HepG2) cells. RESULTS: While neither full length or C-terminally truncated variants of hepatitis C virus core protein nor hepatitis C virus E2 protein inhibited tumour necrosis factor alpha- or Fas antibody-induced apoptosis, a strong inhibition was observed with the cowpox virus cytokine response modifier A protein. CONCLUSIONS: Thus, it is unlikely that hepatitis C virus core or E2 protein inhibit apoptosis mediated by apoptosis-signalling pathways sensitive to cytokine response modifier A protein. Discrepancies to previous reports probably reflect specific effects of hepatitis C virus core protein on different apoptotic pathways and/ or cell lines.

Animals↗
PubMed1999

Fungal surveillance cultures during antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia.

Fungal colonization has been associated with an increased rate of invasive fungal infections in neutropenic patients. This study evaluates weekly fungal surveillance cultures from the oropharyngeal and perianal space as well as other suspected sites in 219 courses of myelosuppressive chemotherapy with itraconazole antifungal prophylaxis in 116 neutropenic patients with acute leukaemia. Itraconazole was given from the start of chemotherapy in one of six different dosing regimens. Fungal colonization occurred in 68 (31%) of courses, which was lower than in a historical control group without prophylaxis (53%, P = 0.004). Twenty-six per cent of these 116 isolates had a growth rate of more than 50 colony forming units (CFU) per culture. Candida glabrata (51%), Candida albicans (18%) and Candida krusei (4%) were the most frequently isolated species. Higher median itraconazole trough concentrations were associated with a lower growth rate in the cultures (< or = 50 CFU/culture versus > 50 CFU/culture): 710 (430-1180) ng ml-1 versus 900 (560-1650) ng ml-1 (P = 0.015). The use of itraconazole solution--compared with capsules--led to a reduced growth rate (P = 0.035). In conclusion, compared with historical controls itraconazole antifungal prophylaxis reduces the incidence and the extent of fungal colonization during neutropenia in patients with acute leukaemia.

Acute Disease↗
PubMed1999

Breakthrough invasive fungal infections in neutropenic patients after prophylaxis with itraconazole.

This study analyses invasive fungal infections in neutropenic patients with haematological malignancies during antifungal prophylaxis with itraconazole. From September 1994 to December 1998 20 patients developed fungal infections. Two patients suffered from disseminated infections by yeasts and 18 patients suffered from pulmonary infections by moulds (eight proven, 10 highly probable in high-resolution CT scans). In these patients the itraconazole trough concentrations exceeded 500 ng ml-1 (measured by high performance liquid chromatography) significantly less often (median 48%, interquartile range 0-100%) than in another group of 150 leukaemia patients without invasive fungal infections who received 287 courses of prophylaxis with itraconazole at our institution (median 100%, interquartile range 38-100%, P = 0.039). Twelve patients died, six of these had refractory disease. Patients with fatal invasive fungal infections had lower median itraconazole concentrations immediately before occurrence of the infection than patients with non-fatal infections: 120 (0-478) ng ml-1 versus 690 (305-1908) ng ml-1 (P = 0.039). In conclusion, this analysis of breakthrough invasive fungal infections during prophylaxis with itraconazole demonstrates that patients with itraconazole trough concentrations below 500 ng ml-1 were significantly more likely to develop fungal infections and that the last itraconazole trough concentration before occurrence of the infection was significantly lower in patients with fatal invasive fungal infections.

Adult↗
PubMed1999

Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl-beta-cyclodextrin oral solution or coated-pellet capsules.

We have previously shown that a trough concentration of at least 500 ng ml-1 itraconazole is necessary for an effective antifungal prophylaxis in neutropenic patients. Since the bioavailability of itraconazole is reduced in these patients, a satisfactory dosing regimen remains to be defined. In this study, six dosing regimens with itraconazole capsules 400, 600 or 800 mg day-1, itraconazole solution 400 mg day-1 (additional loading dose: 400 mg day-1 solution for 2 days), 800 mg day-1 or 400 mg day-1 (additional loading dose: 800 mg day-1 capsules for 7 days, s/c1200) were compared during 160 courses of myelosuppressive chemotherapy in 123 patients with acute leukaemia. After the first week, patients taking 800 mg day-1 or 400 mg day-1 (s/c1200) itraconazole solution achieved significantly higher trough concentrations (high-performance liquid chromatography) than patients in other groups (P < 0.05) and 87 and 100%, respectively, of these had concentrations > 500 ng ml-1. Contrary to a dose of 400 mg day-1, a dose of 800 mg day-1 itraconazole solution induced severe nausea and vomiting in 46% of the patients. We conclude that 400 mg day-1 itraconazole solution with a loading dose of 800 mg day-1 capsules for 7 days resulted in sufficient trough concentrations from the first week onwards and appears to be suitable for antifungal prophylaxis in neutropenic patients.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1999

Nitrite and nitrate levels in patients with cirrhosis of the liver: influence of kidney function and fasting state.

BACKGROUND: Increased serum nitrite/nitrate (NOx) levels, the stable metabolites of nitric oxide (NO), have been reported in patients with cirrhosis. NOx levels, however, are influenced not only by endogenous NO synthesis but also by urinary NOx excretion and dietary intake. We attempted to elucidate factors that influence NOx levels independently of endogenous NO production and to determine the conditions under which NOx levels reflect endogenous production in patients with cirrhosis and healthy controls. METHODS: NOx serum concentrations and urinary NOx excretion were determined by means of the Griess reaction in relation to Child-Pugh score, kidney function, fasting state, and after exposure to tap water. RESULTS: Multifactor regression analysis showed inulin clearance (P = 0.0074) and Child-Pugh score (P = 0.0001) to be independent factors predicting NOx levels in patients with cirrhosis. NOx serum levels correlated negatively with the inulin clearance (P < 0.0001), which deteriorated with progressive loss of liver function. NOx levels decreased by about 30% within a 24-h fasting period. After 24 h fasting urinary NOx excretion was not significantly increased in patients with advanced cirrhosis. CONCLUSION: NOx serum levels, taken as a surrogate for endogenous NO formation, have to be viewed with caution in patients with cirrhosis because they often have impaired kidney function. However, in steady-state conditions after an adequate fasting period NOx levels might be good prognostic markers in patients with cirrhosis since they reflect two possible sequelae of liver insufficiency-namely, increased NO formation and impaired kidney function.

Case-Control Studies↗
PubMed1999

Intrahepatic expression of interleukin-1beta and tumor necrosis factor-alpha in chronic hepatitis C.

The intrahepatic expression of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha was studied in liver specimens from patients with chronic hepatitis C (n=29) and primary biliary cirrhosis (PBC; n=12) and from normal controls (n=19). IL-1beta and TNF-alpha immunoreactivity was predominantly localized in sinusoidal cells, with IL-1beta immunoreactivity being weaker in chronic hepatitis C samples than in PBC or control samples, whereas no difference in staining intensity could be observed for TNF-alpha. On semiquantitation by reverse transcription/competitive polymerase chain reaction, IL-1beta mRNA levels were significantly lower in chronic hepatitis C than in PBC or control samples (chronic hepatitis C, 0.87+/-0.77; PBC, 7.96+/-3.32; control, 3.78+/-2.56 amole IL-1beta mRNA/fmole beta-actin mRNA; P<.001). In contrast, no significant differences in TNF-alpha mRNA levels were observed between the groups. The data suggest insufficient IL-1beta production by sinusoidal cells in chronic hepatitis C, which might facilitate viral persistence.

Hepatitis C, Chronic↗
PubMed1999

Enhancement of antibody dependent cellular cytotoxicity (ADCC) by combination of cytokines.

Monoclonal antibodies (MAb) specific for tumor-associated antigens (TAA) can induce an immunological cellular attack of tumor cells by a process termed antibody dependent cellular cytotoxicity (ADCC). Cytokines may augment ADCC by direct activation of immune cells or by enhancement of TAA on tumor cells. Thus, we investigated whether ADCC by MAb 17-1A and BR55-2, which recognize TAA on colorectal tumor cells, can be augmented by 3-day incubation with different concentrations of IL-2, IL-4, IL-6, IL-12, IFN-alpha, IFN-gamma, GM-CSF, M-CSF, and TNF-alpha. ADCC was assessed by a new flowcytometric cytotoxicity assay (Flieger et al. Immunol Methods 1995; 180:1-13) using PKH-2 labeled HT29 cells as targets and PKH-26 labeled peripheral blood mononuclear cells from three healthy volunteers as effector cells. We found three reaction patterns with the cytokines tested: (a) cytokines, which increase ADCC (IL-2, IL-12, IFN-alpha, and IFN-gamma, which represent Thl cytokines); (b) cytokines with no effect (GM-CSF, M-CSF, and TNF-alpha); and (c) cytokines, which decrease ADCC (IL-4 and IL-6, which represent Th2 cytokines). Then, we tested cytokines that increase ADCC in combination with the other cytokines. We found that the combinations IL-2/IFN-alpha, IL-2/IFN-gamma, IL-2/IL-12, and IL-12/IFN-alpha potentiated ADCC. By contrast, IL-4 reduced the IL-2, IL-12, and IFN-alpha-induced ADCC. Since the Thl response, cooperation of monocytes and CD4 cells is involved, we plan to elucidate by magnetic cell sorting (MACS) separation techniques, which cells are involved in cytokine-induced ADCC. Our results may be useful for finding combinations of cytokines and MAb for the locoregional treatment of colorectal cancer.

Antibodies, Monoclonal↗
PubMed1999

Hepatic disease.

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Carrier Proteins↗
PubMed1999

Microsatellite instability-a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer.

BACKGROUND: Clinical diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is based on a typical family history. As molecular genetic testing is predominantly restricted to these families, gene carriers not meeting the clinical criteria may be missed. AIMS: To examine the value of microsatellite instability (MSI) as a tool to increase the likelihood for uncovering a mismatch repair germline mutation in patients with colorectal cancer and to identify a genotype-phenotype relation in families with verified mutations. METHODS: Systematic search for germline mutations (hMSH2 and hMLH1 genes) was performed in 96 patients: 57 fulfilled the Amsterdam criteria (group 1) and 12 the looser HNPCC criteria (group 2). Seventeen patients showed familial clustering of cancers (group 3) and 10 patients under 50 years had sporadic cancer (group 4), the latter of whom all exhibited MSI+ tumours. RESULTS: A similar proportion of germline mutations was found in patients who fulfilled the clinical criteria of HNPCC and had MSI+ tumours (groups 1 and 2; 15/39) compared with patients who did not meet these clinical criteria but who had MSI+ tumours (groups 3 and 4; 8/27 patients). Affected relatives of patients with hMLH1 mutations showed a significantly higher frequency of colorectal cancer but a lower frequency of endometrium cancer than those with hMSH2 mutations. CONCLUSIONS: MSI in tumour tissue is a useful criterion for selecting patients who should be tested for germline mutations in the mismatch repair genes hMSH2 and hMLH1 irrespective of their family history. Among carriers of hMSH2 mutations the tumour spectrum was broader than among carriers of hMLH1 mutations.

Adult↗
PubMed1999

Intestinal hyperabsorption of oxalate in calcium oxalate stone formers: application of a new test with [13C2]oxalate.

In up to one-third of patients with calcium oxalate stones, a hyperoxaluria can be detected. Hyperoxaluria can result from increased endogenous production, from excessive oxalate content of the food, or from intestinal hyperabsorption. For a causal therapy, it is important to discriminate between metabolic and hyperabsorptive hyperoxaluria. Our new 13C-oxalate test allows this differentiation. Under standardized conditions, 50 mg of disodium salt of [13C2]oxalic acid was applied. From the amount of labeled oxalate excreted in urine as measured by a gas chromatographic-mass spectrometric assay, the intestinal absorption was calculated. Seventy patients with recurrent calcium oxalate urolithiasis who had no signs of inflammatory bowel disease were tested. Their mean intestinal oxalate absorption was 9.2+/-5.1%. This was significantly higher than the mean absorption of 50 healthy volunteers (6.7+/-3.9%). There was no difference in oxalate absorption between male (n = 25) and female volunteers. Oxalate absorption correlated with the oxalate excretion in the 24-h urine (volunteers: r = 0.46, P < 0.01; patients: r = 0.62, P < 0.001). Oxalate hyperabsorption was defined as an absorption exceeding 10%. According to this definition, 34% of the patients had oxalate hyperabsorption; 20% of the volunteers showed a hyperabsorption, too. The 13C-oxalate absorption test allows reliable determination of intestinal oxalate absorption. Because of the use of a stable isotope, this test may be repeated as often as required. It will allow the control of therapeutic regimens and also help to unravel genetic influences in stone formation.

Adolescent↗
PubMed1998

[Progress of acute liver failure and indications for liver transplantation].

OBJECTIVE: To analyse the course of acute liver failure and the indications for liver transplantation. PATIENTS AND METHODS: In 16 patients who developed acute liver failure between July 1992 and July 1997 the indications for liver transplantation and total survival time were analysed retrospectively. RESULTS: Intensive medical care (ventilation, dialysis) was necessary in 60% of the patients to bridge organ failure until liver transplantation. In 14 patients liver transplantation was indicated. Eleven of the patients, with a minimal Quick value of less than 10%, presented with the prognostically poorest London criteria. In two patients the combination of three additional criteria of the London classification led to liver transplantation being indicated. In one patient with Wilson's disease the transplantation was undertaken despite good clotting factor synthesis, because an encephalopathy occurred. In two patients liver transplantation was not undertaken even though indicated, in one because liver functions improved, in the other because necrotizing pancreatitis had occurred. In another patient, who had been poisoned by eating the mushroom Amanita phalloides, the attempted transplantation was cut short, because intestinal necrosis had developed, and the patient died during the operation. Nine of the eleven patients who had a transplantation and three of the four treated conservatively survived. CONCLUSION: The 60-day survival rate in this series, achieved in a recently established transplantation programme, is high (12 of 16; 75%), being comparable to those in larger transplantation centres.

Adult↗