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T Sauerbruch

Publications and source records attributed to T Sauerbruch.

At least 181 records · Page 10Linked to original sources
PubMed1998

Atypical antineutrophil cytoplasmic antibodies with perinuclear fluorescence in chronic inflammatory bowel diseases and hepatobiliary disorders colocalize with nuclear lamina proteins.

Antineutrophil cytoplasmic antibodies (ANCA) are frequently associated with chronic inflammatory bowel diseases (IBD) and hepatobiliary disorders. However, their target antigens have not been identified yet. Recently, we observed an atypical perinuclear ANCA fluorescence (p-ANCA) together with an intranuclear staining using ANCA-positive sera from patients with IBD and hepatobiliary disorders. This observation suggests that the target antigens are localized within the nucleus of neutrophilic granulocytes. To further investigate this hypothesis, we examined sera from patients with ulcerative colitis, primary sclerosing cholangitis, autoimmune hepatitis or systemic vasculitis on ethanol or formaldehyde-fixed neutrophils using confocal laser scanning microscopy and immunoelectron microscopy. Counterstaining with propidium iodide, a DNA-specific dye, showed that ANCA-positive sera in IBD and heptobiliary disorders react with intranuclear antigens at the nuclear periphery of the neutrophils. Double immunolabeling techniques revealed that nuclear lamina proteins, lamins A, C and B1, and lamin B receptor were colocalized with the antigen(s) recognized by atypical p-ANCA. No colocalization was observed with classical p-ANCA and antibodies against histones (H1-H4). Our study showed that atypical p-ANCA are antinuclear antibodies reactive with granulocyte-specific antigens present in the nuclear lamina.

Adolescent↗
PubMed1998

The combination of interleukin-2 and interferon alpha effectively augments the antibody-dependent cellular cytotoxicity of monoclonal antibodies 17-1A and BR55-2 against the colorectal carcinoma cell line HT29.

Monoclonal antibodies (mAb) are promising substances for the treatment of colorectal carcinoma, but the efficiency of this therapy still needs further improvement. We used a flow-cytometric cytotoxicity test to determine the efficacy of the cytokines interferon alpha (IFNalpha) and gamma (IFNgamma), interleukin-2 (IL-2), macrophage-colony-stimulating factor (M-CSF), granulocyte/macrophage-CSF (GM-CSF) and tumor necrosis factor alpha (TNFalpha) in enhancing the antibody-dependent cellular cytoxicity (ADCC) of the mAb 17-1A and the mAb BR55-2 against the colorectal carcinoma cell line HT29. In experiments performed at an effector to target ratio of 9:1, with peripheral blood mononuclear cells from five healthy volunteers as effector cells, we found that IFNalpha, IFNgamma and IL-2 significantly augmented the ADCC of both mAb at concentrations between 3 ng/ml and 30 ng/ml. The other three cytokines were not effective. In further experiments we examined combinations of the three effective cytokines in different concentrations. The combination of IFNalpha and IL-2 proved to be optimal in enhancing ADCC of both mAb. Thus, the examination of ADCC by flow cytometry may reveal potentially useful combinations of cytokines and mAb for the treatment of colorectal carcinoma.

Antibodies, Monoclonal↗
PubMed1998

Changing role of invasive aspergillosis in AIDS--a case control study.

OBJECTIVE: From December 1993 until January 1996 we observed 10 cases of invasive aspergillosis in a cohort of 140 patients with AIDS (7%). By contrast, no invasive aspergillosis was diagnosed in a cohort of 278 patients with AIDS between 1986 until 1993. METHODS: Case controls were assigned randomly to each patient with invasive aspergillosis from the total pool of HIV-infected patients. Patients with invasive aspergillosis were studied retrospectively by matched-pairs analysis with respect to risk factors, radiological, microbiological and autopsy findings. RESULTS: Patients with aspergillosis had more AIDS-defining events (3.5 [2-5] vs. 2 [2-3], median [range], P < 0.05) and a longer median survival time with full-blown AIDS (31.5 [14-45] months vs. 20.5 [5-32] months, P < 0.005) than their case controls. Patients with invasive aspergillosis tended to have lower white blood cell counts and exhibited significantly decreased median CD4 counts (7 [0-44]/mm3 vs. 27 [8-57]/mm3, P < 0.05). CONCLUSIONS: Due to better management of opportunistic diseases and improved antiretroviral therapy, the lifespan of patients with full blown AIDS is prolonged. Patients who have survived four or more AIDS-defining events are at risk for invasive aspergillosis. This risk is associated with low white blood cell counts and CD4 cell counts.

AIDS-Related Opportunistic Infections↗
PubMed1998

Protein levels of interleukin-12 p70 holomer, its p40 chain and interferon-gamma during advancing HIV infection.

BACKGROUND: a switch from T helper 1 (TH1) to T helper 2 (TH2)-like cytokine production has been proposed for progressive HIV infection. OBJECTIVE: to study whether this hypothesis is reflected by altered IL-12 and IFN-gamma serum levels in HIV patients. METHODS: we measured serum levels of IL-12 p40 and p70 and IFN-gamma in 90 HIV seropositive patients at differing disease stages and in 10 healthy controls by radioimmunoassays. These cytokines were compared to established surrogate markers of immunodeficiency. RESULTS: IFN-gamma, as well as IL-12 p40 and p70, levels were significantly increased in HIV patients compared to controls. However, IFN-gamma and IL-12 showed no significant variations with progressive stages of immunodeficiency. IFN-gamma levels showed a significant positive correlation to the progression marker beta2-microglobulin and correlated negatively with CD4+ lymphocyte counts. In addition, IFN-gamma concentrations were related to sTNF-R p55 and p75 serum levels. Interestingly. IFN-gamma was related to IL-12 only with respect to p40, but not to p70. CONCLUSIONS: although our data do not necessarily reflect cytokine secretion at the single cell level or the cytokine milieu in the lymphoid microenvironment, our results from peripheral blood fail to demonstrate progressively decreased IL-12 and IFN-gamma serum levels in HIV infected patients.

Adult↗
PubMed1998

Endoscopic manometry of esophageal varices: evaluation of a balloon technique compared with direct portal pressure measurement.

BACKGROUND/AIMS: Recently, a non-invasive endoscopic balloon technique for esophageal manometry was published. In the present study, we assess its methodological aspects together with the relationship to portal pressure. METHODS: In 20 patients with liver cirrhosis who had received an intrahepatic portosystemic stent-shunt (TIPS), we evaluated portal and variceal pressure before and after balloon occlusion of TIPS (random order). Portal pressure was measured continuously via a portal venous catheter, and variceal pressure was determined at the same time independently by two endoscopists using two balloon techniques (inflation until varix collapses; deflation until varix reappears). RESULTS: Overall, mean (+/-SD) portal pressure (28.5+/-7 mmHg) was significantly higher (p<0.001) than mean variceal pressure (24.4+/-6 mmHg). Balloon manometry-determined variceal pressure values were 10+/-15% higher with the inflation technique (26.2+/-7 mmHg) than with the balloon deflation technique (22.6+/-6 mmHg, p<0.001). Portal pressure and variceal pressure correlated significantly (p<0.001; balloon inflation: r=0.61, balloon deflation: r=0.66, mean values of inflation and deflation: r=0.68). Short-term TIPS occlusion led to mean increases of 52% and 35% in portal pressure and variceal pressure, respectively. The manometry results of both endoscopists correlated well with either balloon technique (r> or =0.93; p<0.001) and we saw no adverse effects. CONCLUSIONS: Variceal balloon manometry provides non-invasive variceal pressure data which correlate to portal pressure assessed prior to and after short-term TIPS occlusion. However, probably due to variance in collateral anatomy, variceal pressure does not exactly predict portal pressure and its acute changes in the individual patient. The averaged variceal pressure of the inflation and deflation balloon technique provides the best relation to portal pressure combined with a good interobserver reliability and warrants further clinical evaluation.

Adult↗
PubMed1998

Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia.

The efficacy of antifungal prophylaxis with itraconazole capsules and its serum concentrations were evaluated in patients intensively treated for acute leukaemia. A consecutive group of patients without systemic antifungal prophylaxis (January 1993 to August 1994, period 1) was compared with another consecutive group of patients (period 2) who received itraconazole capsules (September 1994 to April 1995 400 mg/day, from May 1995 onwards 600 mg/day). All patients admitted with acute leukaemia and standard or high-dose chemotherapy were included into the study. Clinical endpoint was mortality from proven fungal infection. Seventy-six patients and 148 courses of cytotoxic chemotherapy were analysed in the control group as well as 47 patients and 112 treatment courses in the intervention group. Antifungal prophylaxis led to a significant decrease of mortality from invasive fungal infections (8.8%-0.9%, P = 0.005). The median trough concentration of itraconazole of all measurements was 520 ng/ml (range 230-793) in patients who received 400 mg/day and 760 ng/ml (370-1200) in patients receiving a dosage of 600 mg/day (P = 0.002). These findings suggest that itraconazole is an effective drug for antifungal prophylaxis but also that a considerable number of patients do not reach the desired trough levels (>500 ng/ml) with itraconazole capsules.

Acute Disease↗
PubMed1998

The lignocaine metabolite (MEGX) liver function test and P-450 induction in humans.

AIMS: The N-deethylation of lignocaine to monoethylglycinexylidide (MEGX) is partially catalysed by the rifampicin inducible P-450 isoenzyme CYP3A4. This has led to the use of the MEGX test (MEGX plasma concentrations after i.v. lignocaine) as a marker of CYP3A4 activity. To test this hypothesis, we studied lignocaine and MEGX plasma pharmacokinetics. METHODS: Ten healthy volunteers received rifampicin (600 mg day(-1)) for 6 days, resulting in a four- to sixfold increase in urinary 6beta-hydroxycortisol output. On days 1 and 7 (pretreatment), day 11 (treatment), and day 14 (48 h after rifampicin), 50 mg lignocaine i.v. was administered. MEGX concentrations at 30 min [MEGX30min] were assessed and normalised to MEGX test results after 1 mg kg(-1) lignocaine. On days 7 and 14 the lignocaine and MEGX plasma concentrations were measured over a 300 min period. MEGX test results and lignocaine and MEGX plasma pharmacokinetics before and after induction with rifampicin were compared. RESULTS: The lignocaine plasma clearance increased from 7.5+/-1.2 ml min(-1) kg(-1) before to 8.6+/-2ml min(-1) kg(-1) (P=0.026) after induction. The normalised MEGX30min concentrations increased from 61+/-14 (day 7) to 82+/-34 microg l(-1) (day 14) by a mean of 21 microg l(-1) (95% confidence interval: -3 to 44 microg l(-1)) (P=0.055). CONCLUSION: An insignificant increase of MEGX plasma concentrations was found in 10 volunteers after induction of CYP3A4 activity by rifampicin. Therefore, the MEGX test is not a sensitive marker of P-450 induction in healthy human liver.

Adult↗
PubMed1998

Sodium selenite and N-acetylcysteine in antiretroviral-naive HIV-1-infected patients: a randomized, controlled pilot study.

BACKGROUND: The aim of this work was to study the effects of combined oral administration of N-acetylcysteine (NAC) and sodium selenite (Se) on plasma glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human immunodeficiency virus (HIV)-infected patients. METHODS: We used a prospective, randomized and controlled therapy trial with partial crossover. Twenty-four antiretroviral-naive HIV-infected outpatients at Centers for Disease Control (CDC)'93 stages I and II were randomized to receive the antioxidant combination NAC 600 mg t.i.d. and Se 500 micrograms per day for either 24 weeks (group A, n = 13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus, group B served as untreated control during the first 12 weeks. RESULTS: There was (a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6 weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P = 0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38 count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033 respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared with the control period of group B. The effects observed in group A were, however, not paralleled to the same extent by group B after crossing-over to treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH-Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the reduced/total GSH ratio were not affected by the treatment. Serum selenium levels increased significantly (P < 0.001) upon treatment. Viral load was not altered. CONCLUSIONS: The changes in lymphocyte subsets after NAC/Se treatment were not comparable to those after standard antiretroviral drug therapy. This, however, does not preclude per se possible benefits of antioxidant supplementation in HIV disease.

Acetylcysteine↗
PubMed1998

Independent cycles of exocrine pancreatic secretion, hormones and gastroduodenal motility in healthy fasting humans: reassessment of a complex partnership.

BACKGROUND: Interdigestive pancreatic secretion cycles in close association with the phases of the migrating motor complex (MMC) and release of regulatory hormones. The extrinsically denervated pancreas exhibits an intrinsic cyclic rhythm. We hypothesized that this intrinsic rhythm is normally present in the intact human pancreas. METHODS: 19 healthy males (age range 26-35 years) were studied after 12 h fasting. A manometry catheter was positioned with four pressure ports in the antrum and three in the duodenum, and motility was recorded for a complete MMC cycle or 5 h. Duodenal aspirates were sampled at 15-min intervals, and immediately analysed for amylase, lipase and chymotrypsin activities; enzyme outputs were calculated by standard marker perfusion techniques. Plasma levels of pancreatic polypeptide (PP) and motilin were also determined (RIA) at 15-min intervals. RESULTS: Output of amylase, lipase and chymotrypsin occurred in parallel. All phase III motility fronts were accompanied by a pancreatic secretory peak. However, in 12 subjects at least one secretory peak was observed without the concomitant occurrence of phase III. A total of 16 out of 51 secretory peaks identified across all subjects were independent (31%). These phase III-independent peaks of pancreatic secretion occurred in subjects with a longer MMC cycle (160 +/- 19 min vs 102 +/- 13 min, P < 0.05). Phase III-associated and -independent peaks had a similar magnitude (amylase output: 21.6 +/- 3.9 kUh-1 vs 21.1 +/- 2.8 kUh-1, respectively). Irrespective of MMC phases, antral but not duodenal motor activity was closely correlated with fluctuations of pancreatic secretion (P < 0.05). Cycling of PP and motilin were also closely coordinated with pancreatic enzymes, with a particularly tight link between endocrine and exocrine secretion from the pancreas. CONCLUSIONS: Peaks of pancreatic secretion invariably occur when a phase III motor activity occurs, but additional secretory peaks occur without a concomitant phase III. Interdigestive phasic pancreatic secretion is tightly coordinated with PP and motilin release as well as with antral motor activity. An intrinsic rhythm of the pancreas distinct from other cyclic activity may be present in healthy humans, expressed as peaks of pancreatic secretion independent of a motor phase III.

Adult↗
PubMed1998

Noninvasive endoscopic determination of intravariceal pressure in patients with portal hypertension: clinical experience with a new balloon technique.

BACKGROUND AND STUDY AIMS: Recently, details of a noninvasive balloon manometry technique for endoscopic measurement of variceal pressure (VP) have been published. However, to date, only few data exist on its feasibility and virtually none on its relation to endoscopic or clinical variables of portal hypertension. PATIENTS AND METHODS: We investigated a total of 64 patients with esophageal varices using a scaled transparent balloon and a calibrated pressure manometer. Averaged from both fivefold balloon insufflation (variceal collapse) or desufflation (variceal appearance), we took measurements of the VP (mmHg) using the two techniques. These measurements were correlated between two investigators as well as to both clinical and endoscopic signs of portal hypertension. Furthermore, pressures were assessed prospectively before and during propranolol application. RESULTS: Measurements were successful in > 95% of all sessions without side effects. The intraobserver variance was 11.0 +/- 13.1%. Measurements correlated significantly between two observers (r = 0.80, insufflation technique, p < 0.01/r = 0.81, desufflation technique, p < 0.01). Pressures correlated positively to variceal sizes (p < 0.05). The presence of fundic varices was strongly associated with higher pressures (p < 0.02). In patients without medical decompressive therapy we found a significant relationship between VP and the presence of red colour signs or previous bleeding episodes. Clinical parameters did not correlate with VP (p > 0.05). As assessed by this technique, 8/11 patients receiving propranolol showed a decrease in VP (18.6 +/- 19.5% after 1.5 months and 33.3 +/- 11.9% after 3 months). CONCLUSIONS: This noninvasive balloon technique is a safe and practical method for estimating VP in patients with portal hypertension. As found by invasive methods, patients with large varices and concomitant fundic varices have higher VP. A drop in intravariceal pressure after propranolol therapy appears to be assessable.

Adult↗
PubMed1998

[TIPSS: technical and clinical results after 4 years].

PURPOSE: Retrospective analysis of the technical and clinical results after transjugular portosystemic stent shunt (TIPSS) procedure. METHOD: Between 1992 and 1996 we tried to establish a TIPSS in 90 patients. The indications were: recurrent variceal haemorrhage (n = 74), refractory ascites (n = 12), hepatorenal syndrome (HRS) (n = 4). Due to advanced liver cirrhosis 16 patients suffered of severe renal dysfunction (HRS). 57 patients had ascites. RESULTS: TIPSS implantation was technically successful in 96.7% (1992-1994: 5.1%, 1995-1996: 100%) of the patients. Complications occurred in 14.9% (1992-1994: 25.6%, 1995-1996: 6.3%). TIPSS-associated mortality was 2.3% (1992-1994: 5.1%, 1995-1996: 0%). 76.1% of the patients required reinterventions. 85.3% of reinterventions were necessary in the first year after TIPSS placement. The survival rate without reintervention was 28%, 21% and 9% for Child A, B, and C patients, respectively. Recurrent variceal haemorrhage occurred in 12.7%. De novo hepatic encephalopathy developed in 13.8%. Ascites improved in 79.2% and renal function in 75% of the patients. CONCLUSION: TIPSS is an effective method to treat recurrent variceal haemorrhage, refractory ascites and HRS. Complication and mortality rate depend on the investigator's experience and on the technique used.

Adult↗
PubMed1998

Effect of omeprazole treatment on plasma concentrations of the gastric peptides, xenin, gastrin and somatostatin, and of pepsinogen.

The peptide xenin 25 is a gastric mucosal constituent like gastrin, somatostatin and pepsinogen. Gastrin and pepsinogen plasma concentrations increase when the secretion of gastric acid is reduced by proton pump inhibitors. In the present investigation, treatment with omeprazole led to an increase in fasting and postprandial plasma concentrations of xenin, gastrin and pepsinogens A and C (P < 0.05, in each instance), whereas somatostatin plasma levels remained unchanged. Because subcutaneous injection of pentagastrin did not raise xenin plasma concentrations, a direct effect of gastrin on xenin production seems unlikely. This study indicates that xenin plasma concentrations are regulated by intragastric pH, as are those of gastrin and pepsinogen.

Adult↗
PubMed1998

Fibrotic entrapment of the small bowel in congenital intestinal lymphangiectasia.

Congenital intestinal lymphangiectasia is a rare protein-losing enteropathy that is characterized by diarrhea and peripheral edema. This report presents a 37-yr-old woman who had suffered from recurrent diarrhea and peripheral edema since her early childhood and who was admitted for severe attacks of abdominal pain. A diagnosis of intestinal lymphangiectasia was made endoscopically, histologically, and radiographically. Laparotomy revealed complete fibrotic entrapment of the small bowel, which caused partial mechanical bowel obstruction. Surgical decortication led to recovery. To the best of our knowledge, this is the first report on fibrotic entrapment of the small bowel in a patient with long lasting intestinal lymphangiectasia.

Adult↗
PubMed1998

Erythromycin, a motilin agonist, increases postprandial gallbladder emptying during therapy with ursodeoxycholic acid.

Sufficient gallbladder emptying accelerates early gallstone clearance after extracorporeal shock wave lithotripsy (ESWL). Litholytic therapy with ursodeoxycholic acid (UDC) subsequent to ESWL increases fasting volume (FV) and postprandial residual volume (RV) of the gallbladder. This may lead to retention of cholesterol crystals and small fragments within the gallbladder. In order to find out whether erythromycin, a motilin agonist, improves gallbladder emptying, we tested gallbladder motility after administration of ursodeoxycholic acid with and without oral application of erythromycin. Ten healthy males (age 26-35 years) obtained 10 mg/kg/d of UDCA as a single bedtime dose for three weeks. Prior and after UDCA administration, gallbladder FV was determined sonographically after overnight fasting. After a test meal (490 kcal), gallbladder volume was measured every 5 min until the gallbladder had reached its minimal RV. The next day the same procedure was repeated with 500 mg erythromycin p.o. 45 min prior to test meal application. FV, RV, ejection volume (EV = FV-RV) and ejection fraction (EF = EV/FV x 100) were calculated and differences were compared by the student's t-test. FV (29 ml +/- 8 ml vs. 38 ml +/- 10 ml), RV (12 ml +/- 6 ml vs. 17 ml +/- 6 ml) and EV (17 ml +/- 5 ml vs. 21 ml +/- 6 ml) increased significantly during therapy with UDCA (p < 0.05). EF did not change significantly. After erythromycin application RV decreased to its original values (13 ml +/- 6 ml), whereas EV (24 ml +/- 6 ml) and EF (58% +/- 9% vs. 66% +/- 11%) increased significantly (p < 0.05). Thus, administration of a motilin agonist blunts unwanted effects on gallbladder motility during litholytic therapy with UDC.

Administration, Oral↗
PubMed1998

Labelling studies for structure elucidation of a new hydroxymetabolite of tramadol.

Tramadol, racemic 1-(3-methoxyphenyl)-2-(dimethylaminomethyl)cyclohexane-1-ol, is an effective analgesic drug. Metabolites of tramadol described so far originate from O- and N-demethylation and are excreted in urine directly or after conjugation. A further metabolite was found in human liver microsome incubations and in the urine of volunteers after ingestion of tramadol. To elucidate the structure of the new metabolite, seven deuterated isotopomers of tramadol have been synthesized and ingested by volunteers. The mass spectra of the metabolites derived showed (i) that it was a hydroxy metabolite, (ii) that the hydroxy group was not located on the aromatic ring, the side chain, or the positions 2 and 6 of the cyclohexane ring, (iii) that the hydroxy-group was introduced to one of the the positions 3, 4 or 5 of the cyclohexane ring. The hydroxy metabolite was formed preferentially from the (-)-enantiomer, (1S,2S)-tramadol.

Analgesics, Opioid↗
PubMed1997

CD30 induction and cytokine profiles in hepatitis C virus core-specific peripheral blood T lymphocytes.

Since an efficient control of virus infections may depend on the appropriate lymphokine profile, we studied cytokine responses and CD30 induction, a recently proposed surrogate marker of type 2 cells, in 10 healthy anti-hepatitis C virus (HCV)-seropositive blood donors without viremia (group A) and in 15 patients with hepatitis C (group B). Intracytoplasmic IFN-gamma, IL-2, IL-4, and IL-10 were determined by triple-color flow cytometry in the CD3+ and CD3+/CD30+ lymphocyte subsets after stimulation of PBMC with rHCV core protein and five core-derived peptides corresponding to the four immunodominant Th epitopes C.T1 to C.T4. In group A, more type 1 cytokines were induced by the rHCV core protein and all immunodominant core peptides (p < 0.05), whereas IL-10-producing T cells were found more frequently in group B. Induction of CD30+ T cells was found almost exclusively in group B (p < 0.01). The difference in cytokine responses was due to the CD3+/CD30- T cell subset and not the CD3+/CD30+ subset, which predominantly produced both IL-10 and IFN-gamma, but only small amounts of IL-2 and IL-4. We conclude that immunodominant HCV core peptides induce preferentially type 1 cytokines in healthy anti-HCV-positive blood donors and CD30 expression in patients with chronic hepatitis C. However, in both groups, CD30+ T lymphocytes produce an intermediate Th0-like cytokine profile. Thus, chronicity in HCV infection may reflect a lack of type 1 cytokine production.

Adult↗