PubMed Health⌕ Search

Biomedical subjects

Thomas Kraus

Publications and source records attributed to Thomas Kraus.

At least 19 recordsLinked to original sources

Evidence of an association of leptin serum levels and craving in alcohol dependence.

Recent studies have described an association of leptin serum levels and craving in alcohol dependent patients. The aim of the present study was to investigate a large patients' sample using a power-based statistical analysis. We included 156 male and 33 female patients suffering from alcohol dependence admitted for detoxification treatment. Leptin serum levels were measured using a commercial ELISA kit. The Obsessive Compulsive Drinking Scale (OCDS) was used to assess alcohol craving at admission. For both genders Spearman's correlation revealed significant results. These findings could be confirmed using multiple linear regression models (males: r=1.881, t=4.338, p<0.001; females: r=6.160, t=5.793, p<0.001) with a power of 1.00. In contrast to previous results describing an association only in female patients, this power-based analysis shows that leptin is associated with alcohol craving in both genders.

Adult↗

Asbestos Surveillance Program Aachen (ASPA): initial results from baseline screening for lung cancer in asbestos-exposed high-risk individuals using low-dose multidetector-row CT.

The purpose of this study was to assess the prevalence of lung cancer in a high-risk asbestos-exposed cohort using low-dose MDCT. Of a population of 5,389 former power-plant workers, 316 were characterized as individuals at highest risk for lung cancer according to a lung-cancer risk model including age, asbestos exposure and smoking habits. Of these 316, 187 (mean age: 66.6 years) individuals were included in a prospective trial. Mean asbestos exposure time was 29.65 years and 89% were smokers. Screening was performed on a 16-slice MDCT (Siemens) with low-dose technique (10/20 mAs(eff.); 1 mm/0.5 mm increment). In addition to soft copy PACS reading analysis on a workstation with a dedicated lung analysis software (LungCARE; Siemens) was performed. One strongly suspicious mass and eight cases of histologically proven lung cancer were found plus 491 additional pulmonary nodules (average volume: 40.72 ml, average diameter 4.62 mm). Asbestos-related changes (pleural plaques, fibrosis) were visible in 80 individuals. Lung cancer screening in this high-risk cohort showed a prevalence of lung cancer of 4.28% (8/187) at baseline screening with an additional large number of indeterminate pulmonary nodules. Low-dose MDCT proved to be feasible in this highly selected population.

Aged↗

Differentially expressed genes in postperfusion biopsies predict early graft dysfunction after liver transplantation.

BACKGROUND: Preservation induced injury is a major contributing factor to early graft dysfunction in liver allograft recipients. We hypothesized that changes in gene expression represent the earliest indicator of ischemia/reperfusion-related injuries measurable in the graft and could be used as prognostic marker for the occurrence of graft-related complications. METHODS: We studied the expression of 67 genes, known to play a role in acute inflammatory processes by real-time polymerase chain reaction in 59 postperfusion biopsies. The level of expression was correlated with the occurrence of graft-related complications. RESULTS: We identified six genes that were significantly correlated with the occurrence of early graft dysfunction (Spearman test, two-tailed; P<0.05). High C-reactive protein (CRP) gene expression levels correlated significantly with the need of therapeutic interventions due to graft-related complications (P=0,011). Furthermore, five genes related to vascular endothelial cell physiology (CTGF, WWP2, CD274, VEGF. and its receptor FLT1) showed significantly reduced expression in the postperfusion biopsies of patients with need of therapeutic interventions due to graft-related complications in the first month (P<0.05). Using a risk score based on the expression of these five genes, complications could be predicted with 96% sensitivity (ROC analysis, specificity: 74%, positive predictive value: 72%, negative predictive value: 96%). CONCLUSION: Quantitative gene expression analysis in postperfusion biopsies may be a valuable tool to prospectively identify patients at risk for early clinical allograft dysfunction after liver transplantation.

Acute Disease↗

Analysing the causes of chronic cough: relation to diesel exhaust, ozone, nitrogen oxides, sulphur oxides and other environmental factors.

Air pollution remains a leading cause of many respiratory diseases including chronic cough. Although episodes of incidental, dramatic air pollution are relatively rare, current levels of exposure of pollutants in industrialized and developing countries such as total articles, diesel exhaust particles and common cigarette smoke may be responsible for the development of chronic cough both in children and adults. The present study analyses the effects of common environmental factors as potential causes of chronic cough. Different PubMed-based researches were performed that related the term cough to various environmental factors. There is some evidence that chronic inhalation of diesel can lead to the development of cough. For long-term exposure to nitrogen dioxide (NO2), children were found to exhibit increased incidences of chronic cough and decreased lung function parameters. Although a number of studies did not show that outdoor pollution directly causes the development of asthma, they have demonstrated that high levels pollutants and their interaction with sunlight produce ozone (O3) and that repeated exposure to it can lead to chronic cough. In summary, next to the well-known air pollutants which also include particulate matter and sulphur dioxide, a number of other indoor and outdoor pollutants have been demonstrated to cause chronic cough and therefore, environmental factors have to be taken into account as potential initiators of both adult and pediatric chronic cough.

Journal Article↗

Method optimization and validation for the simultaneous determination of arachidonic acid metabolites in exhaled breath condensate by liquid chromatography-electrospray ionization tandem mass spectrometry.

BACKGROUND: Determinations of inflammatory markers in exhaled breath condensate were used to assess airway inflammation. The most applied method for this kind of determination is enzyme immunoassay. For research purposes to find new or to relate concrete biomarkers to different pulmonary diseases, a simultaneous determination of different inflammatory markers would be advantageous. METHODS: We developed an analytical method with on-line clean up and enrichment steps to determine 12 different inflammatory markers in exhaled breath condensate. A specific detection method ensures the unequivocally determination of each analyte at the same run. The method was optimized and validated to achieve a low limit of quantification up to 10 pg/mL each analyte. The precision of the method ranged between 4 and 16%. CONCLUSION: The presented method should serve as an easy and fast tool to assess the utility of inflammatory markers in exhaled breath condensate to different pulmonary diseases and for several related disciplines in medicine.

Journal Article↗

Aluminosis--detection of an almost forgotten disease with HRCT.

The aim of this study was to investigate whether it is possible to detect high-resolution computed tomography (HRCT) findings in aluminium powder workers, which are consistent with early stages of aluminosis.62 male workers from 8 departments of two plants producing aluminium (Al) powder were investigated using a standardized questionnaire, physical examination, lung function analysis, biological monitoring of Al in plasma and urine, chest X-ray, HRCT and immunological tests. Chronic bronchitis was observed in 15 (24.2%) of the workers, and four workers (6.5%) reported shortness of breath during exercise. HRCT findings in 15 workers (24.2%) were characterized by ill-defined centrilobular nodular opacities. Workers with ill-defined centrilobular nodular opacities had a lower vital capacity than workers who had no such HRCT-findings (90.9 % pred. vs. 101.8 % pred., p = 0.01). Biological monitoring in plasma and urine revealed higher internal exposure to Al in affected workers (33.5 microg/l plasma to 15.4 microg/l plasma, p = 0.01) and (340.5 microg/g creat. to 135.1 microg/g creat., p = 0.007). Years of exposure and concentration of aluminum in urine and plasma appear to be the best predictors for HRCT findings. Age and decreased vital capacity show borderline significance.We conclude that aluminosis is still relevant in occupational medicine. With HRCT it is possible to detect early stages of aluminosis and biological monitoring can be used to define workers at high risk.

Journal Article↗

Determination of N epsilon-(carboxymethyl)lysine in exhaled breath condensate using isotope dilution liquid chromatography/electrospray ionization tandem mass spectrometry.

In order to identify new biomarkers for pulmonary diseases in exhaled breath condensate (EBC) it was the aim of this study to develop an analytical method for the identification and quantification of N epsilon-(carboxymethyl)lysine (CML) in EBC. As detection by liquid chromatography with positive electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) offers the advantage of structurally related detection with the necessary specificity required for the identification of a substance, it was the method chosen for the determination of the non-volatile compound. Specific mass transitions and comparison of retention times with standards under given conditions were used for the unequivocal identification of CML in EBC of healthy subjects. Synthesis of isotopically labelled CML was performed and used as an internal standard for an accurate determination. It was possible to identify the advanced glycation end-product CML in 8 out of 10 healthy subjects. The concentration range determined in the quantifiable examined samples ranged between 35 and 110 pg/mL. EBC samples from 11 patients with different diseases such as diabetes and chronic obstructive pulmonary disease were also measured. In one patient with pneumonia a concentration of 1509 pg CML/mL EBC could be detected. This is the first time that CML has been identified and determined in EBC. The developed LC/ESI-MS/MS method could be used to address the utility of CML as a biomarker in pulmonary diseases.

Aged↗

Pharmacokinetic characterization of amantadine in human brain tissue.

Amantadine concentrations in human brain tissue were assessed in order to estimate population pharmacokinetic parameters using the computer program NONMEM. The elimination constant in brain tissue was determined to be 0.00447 [1/h], resulting in a t1/2 of 6.5 days for the mean patient in the population investigated (n = 19). An estimate of 65.5 L was obtained for the apparent volume of distribution. The elimination half-life of amantadine from brain tissue is much longer than from blood and is comparable to the previously investigated neuroleptic drugs haloperidol and levomepromazine.

Amantadine↗

Mesocaval stenting for therapy of portal hypertension after orthotopic liver transplantation.

A 20-year-old patient underwent liver transplantation (LT) because of chronic hepatitis-associated cirrhosis. After transplantation, the patient developed partial portal vein thrombosis without deterioration of liver function. However, in the long-term follow-up, the patient developed refractory portal hypertension with recurrent episodes of severe upper gastrointestinal bleeding. Extensive nonoperative treatment including multiple esophageal ligatures and sclerotherapy was not successful. Thus, the patient had to be treated surgically with a mesocaval H-shunt. Pathophysiology, therapy and prognosis of this rare complication after LT are discussed with regard to the literature.

Adult↗

Small pulmonary nodules: effect of two computer-aided detection systems on radiologist performance.

PURPOSE: To prospectively compare the effects of two computer-aided detection (CAD) systems on the detection of small pulmonary nodules at multi-detector row computed tomography (CT) by using a consensus panel decision as the reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Multi-detector row CT scans were randomly chosen and prospectively evaluated in 25 patients. Two dedicated CAD systems-ImageChecker CT (R2 Technologies, Sunnyvale, Calif) and Nodule Enhanced Viewing (NEV) (Siemens Medical Solutions, Forchheim, Germany)-were used. Results were interpreted by three radiologists with 1, 3, and 6 years of experience. Images were evaluated without and with CAD software. The reference standard was assessed by a consensus panel consisting of all three radiologists and an adjudicator with 8 years of experience. RESULTS: A total of 116 pulmonary nodules (average diameter, 3.4 mm; average volume, 32.05 mm3) were found in all data sets during consensus interpretation, which included findings from the CAD software and all radiologists. Overall sensitivity was 73% with ImageChecker CT and 75% with NEV. Overall sensitivity without CAD was 68% for radiologist 1, 78% for radiologist 2, and 82% for radiologist 3. With ImageChecker CT, sensitivity increased to 79% for radiologist 1, 90% for radiologist 2, and 84% for radiologist 3. With NEV, sensitivity increased to 79% for radiologist 1, 90% for radiologist 2, and 86% for radiologist 3. The average number of false-positive findings was six (range, 0-14) with ImageChecker CT and eight (range, 0-22) with NEV. CONCLUSION: Radiologist performance in the interpretation of multi-detector row CT scans can be improved by using CAD systems, with a reduction in the number of false-negative diagnoses. No statistically significant difference in sensitivity was found between the two CAD systems.

Adult↗

Treatment of hepatitis C virus reinfection after liver transplantation.

Most liver transplant recipients become reinfected with hepatitis C virus after OLT followed by allograft dysfunction, transplant cirrhosis and graft failure in a significant proportion of patients. Both in the pre-emptive prophylactic setting and in the treatment setting sustained virological response rates are poor compared to the precirrhotic hepatitis state. Patients with significant hepatitis should be always treated before developing cirrhosis or even with early cirrhosis. After transplantation pegylated interferon in combination with ribavirin is the most successful treatment opportunity to date, however the best time point and treatment duration as well as doses for pegylated interferons and rebavirin have to be defined.

Antiviral Agents↗

Enhanced oral tolerance in transgenic mice with hepatocyte secretion of IL-10.

Several cytokines derived from Th3 and Tr1 cells, including IL-10, are believed to regulate oral tolerance, but direct evidence is lacking. We have explored the potential role of IL-10 by generating transgenic (TG) mice with sustained hepatocyte-specific expression of rat IL-10. TG mice expressed rat IL-10 downstream of a transthyretin promoter, which led to serum levels that were increased 10- to 100-fold compared with normal animals. Animals were orally administered 1 mg of whole OVA for 5 consecutive days, with control animals receiving PBS. There were six animal groups: Either OVA or PBS were fed orally to rat IL-10 TG mice, non-TG wild-type mice without IL-10 administration, and non-TG wild-type mice administered rat IL-10 systemically. On day 8, all mice were immunized with two injections of OVA, and then analyzed on day 18. T cell proliferation responses were reduced by 65.8 +/- 14.3% after feeding of OVA in rIL-10 TG animals, compared with 39.4 +/- 15.6% in the non-TG mice (p = 0.02). Anti-OVA titers were expressed as fold increase over naive non-TG mice. After feeding, titers decreased by approximately 33% (from 3- to 2-fold) in TG animals and, to a lesser extent, in non-TG animals. IFN-gamma secretion by cultured popliteal lymphocytes decreased in TG animals by 83% after feeding and by 69% in non-TG animals. IL-4 secretion increased 4-fold in TG-fed mice, but did not significantly change in non-TG OVA-fed animals. In contrast to hepatic TG expression of rIL-10, systemic administration of rIL-10 had only a modest effect on tolerance. IL-10, when transgenically expressed in the liver enhances mucosal tolerance to an oral Ag.

Administration, Oral↗

Sensitive and accurate analyses of free 3-nitrotyrosine in exhaled breath condensate by LC-MS/MS.

The quantitative determination of 3-nitro-l-tyrosine, a biological marker for inflammatory processes, in exhaled breath condensate (EBC) is described. The clean-up and preconcentration was performed by solid phase extraction (SPE). After liquid chromatography the specific detection was performed by tandem mass spectrometry using electron spray ionisation and selected reaction monitoring (SRM). 13C9-3-nitrotyrosine was used as an internal standard. For reliability, tests for the precision of the method, the losses during preparation, a test for nitrating artifacts and the comparibility of calibrants in EBC and buffer solution were performed. The calibration of the method was linear over a range of 10-500 pg/mL. The within-run coefficients of variation (CV) of the samples were found to be 8.4% at 25 pg/mL and 8.3% at 250 pg/mL. The day-to-day CV was found to be 11.2%. The limit of quantification was 3.9 pg/mL. The losses during preparation were 15%. The discrepancy between the calibration with EBC and buffer solution was below 10%. No artificial production of 3-nitrotyrosine was observed during the procedure. The application of the method on the EBC samples of healthy smokers (N=10) and non-smokers (N=10) showed no difference between the two groups. The concentration of 3-nitrotyrosine ranged between the limit of quantification and 184 pg/mL and was distinctly lower than data detected by an immunoassay procedure. The procedure was proven to be accurate, sensitive and in contrast to GC methods less elaborate and is recommended for the determination of 3-nitrotyrosine in exhaled breath condensate.

Adult↗

Recurrent herpes simplex virus hepatitis after liver retransplantation despite acyclovir therapy.

Herpes virus hepatitis (HSV) represents a form of acute necrotizing hepatitis, which most frequently develops in immunocompromised patients. Therapeutic options include high-dose intravenous acyclovir and liver transplantation. We report the first case of recurrent HSV hepatitis after liver retransplantation, which occurred despite continuous administration of high-dose intravenous antiviral therapy. Because explant histology pointed to initial therapy response, we thought that the reason for recurrence might be due to acyclovir resistance. Most acyclovir resistance is caused by inactivating mutations in the herpes virus thymidine kinase gene. HSV infection was detected by histology and proofed by immunohistochemistry. PCR amplification of the herpes virus thymidine kinase gene was performed on histology specimens to demonstrate the course of viral infection in liver tissue. Genotypic resistance testing of the herpes virus was performed by sequencing the thymidine kinase amplicon. In serial biopsy, HSV-DNA sequences were only detectable when histology revealed herpes hepatitis. Whereas the primary explant exhibited the wild-type thymidine kinase gene, a biopsy of the second graft one month after retransplantation, which showed recurrent herpes virus hepatitis, had a single base insertion within a homopolymeric cytosine stretch. This mutation causes a frame shift leading to a premature stop codon and results in a known acyclovir-resistant herpes strain. In conclusion, we believe that testing for acyclovir-resistant herpes strains should be considered in high-risk patients in whom viral clearance is not achieved serologically to prevent fatal recurrence of disease by using antiviral drugs such as inhibitors of HSV-DNA polymerase or viral helicase primase inhibitors.

Acyclovir↗

Influence of beer, wine and spirits consumption on craving.

The importance of craving in alcoholism and the efficacy of treatment has been the subject of various studies. This study focuses on the consumption of different alcoholic beverages and their effect on craving, which has not yet been investigated. Therefore we assessed 197 inpatients using the Obsessive Compulsive Drinking Scale (OCDS) on the day of admission and after 1 week, distinguishing between the total score, the obsessive and the compulsive subscale. Socio-demographic data and the type of alcoholic beverage were recorded. Analysing data, the amount of beer consumption showed a significant influence on craving in male but not in female patients. These results were significant for the total score and both subscales of the OCDS (OCDS total score; day 0: Spearman's rho = 0.31; p = 0.001; logistic regression, dependent variable dichotomized OCDS total score day 0: OR = 1.18; 95% CI = 1.04 - 1.34; p = 0.011). On the other hand we, did not find any significant results for the amount of other beverages such as wine and spirits. Receiver operating curves analysis showed that beer consumption significantly predicts craving [area under the curve (AUC) = 0.66; p = 0.002]. We conclude that higher beer consumption is associated with higher withdrawal craving, at least in male patients. In addition, it is an important predictor for both obsessive and compulsive craving. Further studies are needed to clarify the pathophysiological basis of this finding.

Adult↗

Ghrelin levels are increased in alcoholism.

BACKGROUND: The neuropeptides leptin and ghrelin are involved in the appetite regulating network consisting of distinct orexigenic (ghrelin) and anorexigenic (leptin) circuitries. Recently, it has been shown that elevated leptin levels are associated with alcohol craving in patients suffering from alcoholism. Therefore, the aim of the present pilot study was to determine whether the gut-derived peptide ghrelin which increases hunger and food intake is altered and associated with alcohol craving in alcoholic patients METHODS: Two types of alcoholic inpatients, group A (active drinker, acutely intoxicated, n=97) and group B (early abstainer, who had stopped drinking 24-72 hrs before, n=21) were consecutively included in a prospective study from the first day of hospitalization. Ghrelin plasma levels and craving data were assessed on days 0, 1, 2 and 7(-10) and compared to those of 24 healthy controls RESULTS: At each time-point ghrelin plasma levels of alcoholic patients were significantly increased compared to healthy subjects. Furthermore, early abstainers showed significantly higher ghrelin levels than active drinkers. In the group of active drinkers ghrelin plasma levels were significantly increased at each time point compared to baseline. No correlations were found between ghrelin levels and craving data measured by the visual analogue scale or the Obsessive Compulsive Drinking Scale CONCLUSIONS: Ghrelin levels are elevated in alcoholism and seem to further increase during alcohol withdrawal. However, ghrelin levels do not seem to be associated with alcohol craving.

Adult↗