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Biomedical subjects

Christian Müller

Publications and source records attributed to Christian Müller.

At least 91 records · Page 5Linked to original sources
PubMed2003

Prognostic significance of the hepatopulmonary syndrome in patients with cirrhosis.

BACKGROUND AND AIMS: The hepatopulmonary syndrome (HPS) has been defined by chronic liver disease, arterial deoxygenation, and widespread intrapulmonary vasodilation. Mortality of patients with HPS is considered to be high, but the effect of HPS on survival in patients with cirrhosis remains unclear. METHODS: A total of 111 patients with cirrhosis were studied prospectively by using transthoracic contrast echocardiography for detection of pulmonary vasodilation, blood gas analysis, and pulmonary function test. Twenty different clinical characteristics and survival times were noted. RESULTS: Twenty-seven patients (24%) had HPS. Their mortality was significantly higher (median survival, 10.6 months) compared with patients without HPS (40.8 mo, P < 0.05), even after adjusting for liver disease severity (2.9 vs. 14.7 months in Child-Pugh class C with [n = 15] and without HPS [n = 35, P < 0.05]; 35.3 vs. 44.5 months in Child-Pugh class B with [n = 7] and without HPS [n = 23, P = NS]), and exclusion of patients who underwent liver transplantation during follow-up (median survival 4.8 vs. 35.2 months, P = 0.005). Causes of death were mainly nonpulmonary and liver-related in the 19 patients with and the 35 patients without HPS who died. In multivariate analysis, HPS was an independent predictor of survival besides age, Child-Pugh class, and blood urea nitrogen. Mortality correlates with severity of HPS. CONCLUSIONS: The presence of HPS independently worsens prognosis of patients with cirrhosis. This should influence patient management and scoring systems and accelerate the evaluation process for liver transplantation.

Adult↗
PubMed2003

Elevated donor cardiac troponin T and procalcitonin indicate two independent mechanisms of early graft failure after heart transplantation.

BACKGROUND: Cardiac troponin T (cTnT) >0.1 microg/l and procalcitonin (PCT) >2 microg/l in the serum of heart donors are predictors of early graft failure after heart transplantation (HTx). The current study investigates the relationship between these two markers and their prognostic value when one or both of them are elevated. METHODS: Cardiac TnT and PCT were measured in serum from 92 consecutive brain-dead donors accepted for HTx. The donors were retrospectively divided into two groups: group I (n=78) donors of hearts with good function, group II (n=14) donors of hearts with early graft failure after transplantation. RESULTS: There were no correlations between cTnT and PCT values (r=0.12, P=0.27). In eight donors in group I one or both markers were elevated. In one donor both markers were above the cut-off levels. In 12 donors (86%) in group II one or both markers were elevated. In two donors both markers were above the cut-off levels and in a further two below. There was no significant interaction between the two markers in either group using a logistic regression model (P=0.28). CONCLUSIONS: Elevated cTnT and PCT levels in the serum of heart donors were independent prognostic markers of early graft failure. This fact may suggest two different mechanisms of early graft failure: primary myocardial damage and damage related to systemic inflammatory response. The combination of both markers had a higher sensitivity than each parameter on its own. Their use as additional parameters may improve heart donor selection.

Adult↗
PubMed2003

Minimal inflammation, acute phase response and avoidance of misclassification of vitamin A and iron status in infants--importance of a high-sensitivity C-reactive protein (CRP) assay.

The acute phase response is known to affect many biological parameters used to assess the iron and vitamin A status. Usually, C-reactive protein (CRP) values higher than 5 to 10 mg/L are taken as indicative of this response. Here we report changes occurring at much lower CRP values. A range of parameters (clinical chemistry, retinol, vitamin E, carotenoids, thyroid status, blood count, immunology) were measured in 101 healthy one-year-old children with no or only minimal symptoms of airway infection and CRP values below 6 mg/L on routine testing. Additionally, CRP values were measured by a high-sensitivity assay (detection limit 0.2 mg/L). When determined by a more sensitive assay, CRP values (median, 0.26 mg/L) revealed highly significant associations with parameters known to be influenced by the acute phase response. Using a limit of 0.6 mg/L (75th percentile), significantly lower levels were observed for transthyretin, iron, retinol, and beta-carotene in the group with the higher CRP levels. This relationship was confirmed intra-individually in a subgroup of 21 children who underwent a second blood draw about four weeks after the first one. The acute phase response is triggered at very low inflammatory levels with CRP values considerably lower than 5 to 10 mg/L, and can occur in apparently healthy children. A high-sensitivity CRP assay is necessary to detect this low level, and in the case of iron or vitamin A, it can help to avoid misclassification of the nutritional status.

Acute-Phase Reaction↗
PubMed2003

Mutations of the HFE gene in patients with hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a late consequence of severe liver disease. Patients with genetic hemochromatosis may be at risk for HCC, but limited information is available on the relationship of HCC and heterozygosity for the HFE gene mutations. METHODS: HFE mutations (C282Y and H63D) were assessed in 162 consecutive patients (131 men/31 women) with HCC. A total of 159 patients had cirrhosis. The most common etiologies of cirrhosis were chronic viral hepatitis (hepatitis C 39%, hepatitis B 9%) and alcoholic liver disease (36%). RESULTS: Five patients were C282Y homozygotes, four C282Y/H63D compound heterozygotes, and three H63D homozygotes. The C282Y and H63D allele frequencies in HCC were 8.3 (95% confidence limit = 5.3-11.3) and 11.1 (7.8-14.6), respectively, and not different from previously published data in healthy subjects or patients with chronic hepatitis C in Austria. Furthermore, there was no difference in the age at diagnosis in patients with or without HFE gene mutations. C282Y homozygotes had a 19-fold increased risk to develop HCC. In contrast, all other HFE allele constellations were not associated with such a risk. CONCLUSIONS: Except for C282Y homozygotes, HFE gene mutations do not increase the risk to develop HCC in patients with cirrhosis.

Arthralgia↗
PubMed2003

The streptococcal exotoxin streptolysin O activates mast cells to produce tumor necrosis factor alpha by p38 mitogen-activated protein kinase- and protein kinase C-dependent pathways.

Streptolysin O (SLO), a major virulence factor of pyogenic streptococci, binds to cholesterol in the membranes of eukaryotic cells and oligomerizes to form large transmembrane pores. While high toxin doses are rapidly cytocidal, low doses are tolerated because a limited number of lesions can be resealed. Here, we report that at sublethal doses, SLO activates primary murine bone marrow-derived mast cells to degranulate and to rapidly induce or enhance the production of several cytokine mRNAs, including tumor necrosis factor alpha (TNF-alpha). Mast cell-derived TNF-alpha plays an important protective role in murine models of acute inflammation, and the production of this cytokine was analyzed in more detail. Release of biologically active TNF-alpha peaked approximately 4 h after stimulation with SLO. Production of TNF-alpha was blunted upon depletion of protein kinase C by pretreatment of the cells with phorbol-12 myristate-13 acetate. Transient permeabilization of mast cells with SLO also led to the activation of the stress-activated protein kinases p38 mitogen-activated protein (MAP) kinase and c-jun N-terminal kinase (JNK), and inhibition of p38 MAP kinase markedly reduced production of TNF-alpha. In contrast, secretion of preformed granule constituents triggered by membrane permeabilization was not dependent on p38 MAP kinase or on protein kinase C. Thus, transcriptional activation of mast cells following transient permeabilization might contribute to host defense against infections via the beneficial effects of TNF-alpha. However, hyperstimulation of mast cells might also lead to overproduction of TNF-alpha, which would then promote the development of toxic streptococcal syndromes.

Animals↗
PubMed2003

Early experience with a rotational thrombectomy device for treatment of acute and subacute infra-aortic arterial occlusions.

PURPOSE: To evaluate a rotational thrombectomy device in the treatment of acute and subacute/chronic thrombotic infra-aortic occlusions of native vessels and bypass grafts. METHODS: From July 2000 to February 2002, 98 patients (65 men; mean age 66+/-9 years, range 47-90) with 100 thrombotic occlusions (mean age of occlusion 31+/-33 days, range 0-140) measuring an average of 21+/-11 cm long (range 2-40) were treated with rotational thrombectomy (Rotarex). There were 33 acute (</=14 days) thrombotic/embolic native artery occlusions (group I), 58 subacute/chronic (>14 days) native artery occlusions (group II), and 9 acute bypass graft occlusions (group III). RESULTS: The device activation time was 4.9+/-1.4 minutes, during which 4.0+/-1.4 passes of the device were performed. The amount of aspirated fluid was 240+/-119 mL. Slightly less than half the arteries (48%) were stented. Primary success (residual stenosis <30%) was achieved in 92% (94% for group I, 93% for group II, and 78% for group III; 100% for the ipsilateral approach, 56% for the crossover approach). Among the 18 complications, 3 were serious (2 amputations after unsuccessful intervention and 1 death); there were 8 vessel perforations and 7 cases of peripheral embolization. Thirty-day survival and limb salvage was 88% for group I, 100% for group II, and 66% for group III. CONCLUSIONS: The device is an easy-to-handle, useful tool for ipsilateral treatment of acute and subacute thrombotic arterial and bypass graft occlusions. The use of this device is limited by the 8-F diameter of the catheter and the limited capacity for crossover interventions.

Acute Disease↗
PubMed2003

Survival after stenting of severe atherosclerotic ostial renal artery stenoses.

PURPOSE: To examine long-term survival after angioplasty and stenting of atherosclerotic renal artery stenosis (RAS). METHODS: Over a 5-year period, 241 consecutive patients (153 men; mean age 67+/-9 years, range 44-84) were treated with angioplasty and stent implantation for 355 ostial renal stenoses >70%. The procedures were performed in standard fashion using a variety of stents. For survival analysis, the patients were divided into 3 groups based on baseline creatinine levels: group 1: 115 (48%) patients with normal renal function (creatinine <1.2 mg/dL); group 2: 93 (39%) patients with moderately impaired renal function (creatinine 1.2 to 2.5 mg/dL); and group 3: 33 (13%) patients with severely impaired renal function (creatinine >2.5 mg/dL). RESULTS: All patients were treated successfully without any procedure-related mortality. The 30-day mortality was 0.4% (1/241). Twenty-two patients died during a follow-up of 27+/-15 months (range 1-60) (overall survival 91%). The causes of death were cardiac (congestive heart failure or myocardial infarction, 73%), stroke (13.5%), and malignant disease (13.5%). The survival rate was significantly lower (29.6%) in patients with a baseline serum creatinine >2.5 mg/dL (p<0.0001) than in groups 2 (89.1%) or 1 (95.4%). Long-term survival without hemodialysis or restenosis was 66.6% at 48 months. Independent predictors for a reduced survival were left ventricle function (HR 2.59, 95% CI 1.45 to 4.63, p=0.001 for each 15% incremental decrease), age (HR 1.13, 95% CI 1.03 to 1.25, p=0.011), and baseline renal function (HR 1.58, 95% CI 1.10 to 2.29, p=0.014). CONCLUSIONS: Survival after successful stenting for severe ostial RAS depends on baseline serum creatinine and left ventricle function. Efforts must be made to avoid the development of advanced ischemic nephropathy and congestive heart failure.

Adult↗
PubMed2003

Technological advances in the design of catheters and devices used in renal artery interventions: impact on complications.

PURPOSE: To analyze the impact of technical improvements in stent devices and guiding catheters (e.g., reduced device diameter, increased flexibility) on the complication rates associated with percutaneous renal artery interventions. METHODS: During a 5-year period (1997-2001), 268 consecutive patients (178 men; mean age 67+/-9 years) had 370 atherosclerotic renal artery stenoses (RAS) > or =70% treated with angioplasty/stenting in 320 procedures. The guiding catheter technique was used routinely until 2000; in 2001, a guiding sheath was used in 29% of cases. From 1997 to 2000, sealing devices were frequently used for sheath removal; during the last year, the sheaths were removed using the Femostop device. RESULTS: In 320 interventions, 32 (10%) complications occurred, with a decreasing frequency during the last 2 years (1996/97: 13% [7/53]; 1998: 16% [9/57]; 1999: 15% [11/74]; 2000: 4% [3/70]; 2001: 3% [2/66]). There were 21 (6.6%) local complications, including 4 cases requiring permanent hemodialysis after the intervention and 11 (3.4%) access site complications. No procedure-related death occurred. During the study period, the average sheath diameter was reduced from 8.15+/-0.76 F to 6.15+/-0.63 F (p<0.05). Mean procedural time was reduced from 42+/-13 minutes to 23+/-11 minutes (p<0.05). The initial heparin dose was reduced from 10,000 to 5000 units. CONCLUSIONS: In parallel with the use of more flexible catheters and premounted stents of lower profile, the complication rate of renal angioplasty/stenting of atherosclerotic RAS has been reduced significantly during a 5-year period.

Aged↗
PubMed2002

Measuring the number of independent emitters in single-molecule fluorescence images and trajectories using coincident photons.

A simple new approach is described and demonstrated for measuring the number of independent emitters along with the fluorescence intensity, lifetime, and emission wavelength for trajectories and images of single molecules and multichromophoric systems using a single PC plug-in card for time-correlated single-photon counting. The number of independent emitters present in the detection volume can be determined using the interphoton times in a manner similar to classical antibunching experiments. In contrast to traditional coincidence analysis based on pulsed laser excitation and direct measurement of coincident photon pairs using a time-to-amplitude converter, the interphoton distances are retrieved afterward by recording the absolute arrival time of each photon with nanosecond time resolution on two spectrally separated detectors. Intensity changes that result from fluctuations of a photophysical parameter can be distinguished from fluctuations due to changes in the number of emitters (e.g., photobleaching) in single chromophore and multichromophore intensity trajectories. This is the first report to demonstrate imaging with contrast based on the number of independently emitting species within the detection volume.

Journal Article↗
PubMed2002

Blood alcohol concentration for monitoring ethanol treatment to prevent alcohol withdrawal in the intensive care unit.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a serious complication during postoperative treatment in chronic alcoholics. Despite prophylactic treatment, AWS occurs in at least 25% of these patients after elective surgery. An established protocol for the prevention of AWS is ethanol administration. The aim of this study was to evaluate possible differences in ethanol dose and levels between successfully treated patients and those who developed AWS. DESIGN: Prospective, observational study with retrospective post hoc analysis. SETTING: Intensive care unit (ICU). PATIENTS: Thirty-two alcohol-dependent patients undergoing elective or emergency surgery after trauma with postoperative admission to ICU. INTERVENTIONS: Continuous postoperative i.v. ethanol substitution. MEASUREMENTS AND RESULTS: Despite treatment, 13 patients developed AWS (failure group) and therapy was successful in the other 19 patients (success group). Major complications occurred more frequently in the failure group. The total dose of ethanol treatment and ethanol levels did not differ between the groups. Ethanol levels were determined in whole arterial blood (aBAC) and simultaneously taken in venous blood (vBAC), urine (UAC) and exhaled air (EAC). The following bias and precision, compared with aBAC, were found: vBAC less than UAC less than EAC. CONCLUSIONS: There is a high failure rate for i.v. ethanol prophylaxis. None of the methods to determine alcohol concentration were sufficient to monitor suitable ethanol treatment. It therefore seems to be more useful to titrate the individual dose for each patient by closer monitoring of the clinical status, adding additional therapy to counteract AWS if higher ethanol doses are required.

Alcoholism↗
PubMed2002

Visual prognosis of second eyes in patients with unilateral late exudative age-related macular degeneration.

PURPOSE: A prospective longitudinal study was initiated to analyze the correlation between the prognosis for the second eyes of patients with unilateral late exudative AMD and the disease phenotype. METHODS: Of the187 patients with unilateral late exudative AMD recruited, 130 (69.5%) had predominantly classic CNV without pigment epithelium detachment (PED) (CNV group), and 57 (30.5%) had occult CNV with serous PED (PED group). Patients were reexamined by ophthalmoscopy and angiography every 6 months for up to 80 months. The end point was ETDRS visual acuity change of 3 lines or more due to late AMD in the second eye. RESULTS: During follow-up 53 (28.3%) patients reached the end point: 32 (24.6%) in the CNV group and 21 (36.8%) in the PED group. The major prognostic factor for the risk of visual loss in the second eye was the type of late AMD in the first eye (CNV group 6-7% per year, PED group 15-16% per year ( P<0.001). There was significant symmetry between the new exudative lesion in the second eye and that in the first, and significant differences in the density and fluorescence of drusen in the second eye between the two groups. CONCLUSIONS: Patients with occult CNV with serous PED in the first eye have a significantly higher risk of visual loss in the second eye than patients with CNV without PED. This distinction may be important for future clinical studies. In addition, segregation of AMD by phenotype is necessary in the analysis of genes conferring risk of AMD.

Aged↗
PubMed2002

Results of long-term follow-up after curative resection of Dukes A colorectal cancer.

Patients with Dukes A (UICC I) colorectal cancer have a good prognosis after curative resection. It is not known, however, if the outcome is significantly different for UICC Ia and Ib patients or if patients with reduced risks of recurrences can be identified early after surgery. This is of interest, as it would permit a more cost-effective, patient-oriented, and tumor stage-oriented follow-up program. To study these questions, a prospective follow-up database, including 1375 patients after curative resection of colorectal cancer, was analyzed. A total of 296 patients with Dukes A colorectal cancer with a median follow-up of 44 months were studied. Perioperative and follow-up mortality rates were 3% and 14%, respectively. Recurrent disease developed in 10% of Dukes A patients after a disease-free interval of 16 months. Significantly more patients suffering from pT2 (UICC Ib) cancer had recurrent disease than patients with pT1 (UICC Ia) cancer (13% vs. 4%; p <0.05). Preoperative CEA levels in patients with recurrent disease were significantly higher than in long-term disease-free patients (5.3 +/- 1.8 vs. 3.5 +/- 0.6 ng/ml; p <0.05). Curative resection of recurrent disease was achieved in 38% of the patients with recurrences (4% of all patients). Survival analysis showed significantly better survival in patients with Dukes A cancer than in those at higher tumor stages (log rank, <0.0001), and only 39% of all Dukes A patients who died during follow-up had recurrent disease. Dukes A (UICC Ia and Ib) colorectal cancer was diagnosed in 22% of our patients treated for cure, and long-term survival was 86%. There were significantly fewer cases of recurrent disease after curative resection of UICC Ia (pT1N0M0) cancer, so we propose a novel, less intensive follow-up regimen for these patients, leading to a more cost-effective, patient-oriented, and tumor stage-oriented follow-up program.

Adult↗
PubMed2002

Effect of preoperative radiochemotherapy on lymph node retrieval after resection of rectal cancer.

HYPOTHESIS: Preoperative radiochemotherapy for advanced rectal cancer results in fewer lymph nodes detected in the tumor-bearing specimen. DESIGN: Nonrandomized control trial with analysis of a prospective perioperative database. SETTING: Department of Surgery of a large-volume university hospital. PATIENTS: All patients who underwent conventional open surgery to cure rectal cancer between January 1, 1996, and March 31, 2001. INTERVENTIONS: During the study period 184 patients (81%, control group) underwent surgery without receiving preoperative radiochemotherapy. Forty-two patients (19%, study group) who had advanced rectal cancer (modified Dukes stages B [tumors that have penetrated the muscle layer of the bowel wall or have gone through the bowel] or C [tumors that have spread to the lymph nodes in the same region]) received preoperative radiochemotherapy (2 cycles of fluorouracil, 4500 rad) during this period. Most patients underwent anterior rectal resection in both groups (77.7% of those who did not receive preoperative radiochemotherapy and 71.8% of those who did), the remaining patients were treated with abdominoperineal resection. RESULTS: A mean (SEM) of 19 (1) lymph nodes per specimen were detected in the control patients, while significantly fewer lymph nodes were detected in study patients (13 [1]; P<.05). The rate of inadequate lymph node staging (pNx) increased from 7% in the control group to 12% in the study group (P =.06). Pathological lymph node staging disclosed that significantly more study patients who received preoperative radiochemotherapy had modified Dukes stage A (tumors that are found only in the inner wall or rectum) cancer when compared with the control group (17% vs 0%, respectively; P<.05). CONCLUSIONS: Preoperative radiochemotherapy for advanced rectal cancer results in a significant decrease of lymph nodes detected within the tumor-bearing specimen. Preoperative radiochemotherapy induces significant downstaging with fewer positive lymph nodes and more patients presenting with Dukes stage A rectal cancer. Great care must be taken to remove an adequate number of lymph nodes and more sophisticated pathological techniques of lymph node detection are required since the tumors of ever-increasing numbers of patients are inadequately classified.

Analysis of Variance↗
PubMed2002

Late aortic dislocation of a stent following stent angioplasty for ostial renal artery stenosis.

A patient with left RAS was treated by stent angioplasty followed by a multivessel percutaneous coronary intervention. Six months later, an aortic dislocation of the stent was diagnosed. The fully expanded stent was caught with a balloon catheter and fixed in the left external iliac artery. Stent migration after initially successful stent angioplasty for RAS is possible. Fully expanded, dislocated balloon-expandable stents can be secured by implanting them into the iliac artery.

Catheterization↗
PubMed2002

The nasal epithelium as a factory for systemic protein delivery.

We have previously shown that recombinant Sendai virus (SeV) produces efficient in vivo airway epithelial gene transfer. The ability to produce therapeutic levels of circulating proteins following noninvasive gene transfer would have widespread clinical application. Here, we compared nose, lung, and skeletal muscle for the ability to produce circulating levels of the secreted mouse antiinflammatory cytokine interleukin-10 (IL10) following SeV-mediated gene transfer. High levels of serum IL10 were obtained from each site with a potency order of lung > nose > muscle for a given viral titer. Serum levels from each site were within the likely required range for anti-inflammatory effects. The combination of a high-efficiency gene transfer agent (SeV) and sites that can be assessed noninvasively (nose or lung) may circumvent several current challenges to gene therapy.

Animals↗
PubMed2002

Diagnostic value of peripheral blood T-cell activation and soluble IL-2 receptor for acute rejection in liver transplantation.

BACKGROUND: T-cells play an important role in the pathogenesis of rejection. Monitoring T-cells activation markers in peripheral blood may contribute to diagnosis of acute rejection after liver transplantation (LTX). METHODS: Lymphocyte subset distribution, expression of T-cell activation markers (flow cytometry), concentration of soluble (s) interleukin-2 receptor (IL-2R) (solid phase chemiluminescence immunoassay), and liver enzymes as well as bilirubin were prospectively tested in peripheral blood samples of LTX patients with (n=69) and without acute rejection (n=50). Acute rejection was assessed by standard criteria including liver biopsies. RESULTS: Intra-individual monitoring of immune parameters revealed an up-regulation of IL-2 receptor (CD25) expression on CD4 and CD8 T-cells together with increases in sIL-2R levels in patients with acute rejections. Measuring sIL-2R levels resulted in highest diagnostic efficiency (>85%). This level of diagnostic efficiency was not reached by any other marker tested. From all conventional markers of hepatocellular integrity and function, alkaline phosphatase reached the highest level of diagnostic efficiency with 70%. CONCLUSIONS: Monitoring of up-regulation of the IL-2/IL-2R pathway represents a useful tool for assessment of acute rejection after LTX.

Acute Disease↗