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Biomedical subjects

Michael Weber

Publications and source records attributed to Michael Weber.

At least 19 recordsLinked to original sources

A culturomics approach reveals cross-feeding capacity of intestinal pig bacteria upon release of inositol from phytate.

BACKGROUND: Phytate is the primary phosphorus storage molecule of plants and plays a major role in animal nutrition. To enhance phosphate availability and absorption in livestock, and to reduce eutrophication by liquid manure, bacterial phytases are often added to animal feed. The dephosphorylated form of phytate, the polyol myo-inositol (myo-Ins) with multiple functions in eukaryotes, is metabolized by approximately 30% of all bacterial species. RESULTS: Here, we employed a culturomics approach to identify possible metabolic interactions between phytase-producing and myo-Ins degrading bacteria in intestinal samples from pigs. Selective cultivation revealed an unexpectedly high abundance of myo-Ins degrading bacteria, suggesting substantial phytate dephosphorylation in the pig gut. Phytase activity assays performed on gut isolates showed a high degree of variability, suggesting the presence of a diverse set of phytases yet to be characterized. Furthermore, using supernatants of phytase-positive gut strains cultivated in the presence of phytate, we observed cross-feeding of myo-Ins from phytase producers to phytase-negative strains, including the pathogen Salmonella enterica serovar Typhimurium. CONCLUSIONS: The data demonstrate that a wide range of commensal bacteria can potentially benefit from phytase activity by utilizing myo-Ins, released through phytate hydrolysis, as a growth substrate. Video Abstract.

Animals↗

Comparative genomics of Mycobacterium avium subsp. hominissuis strains within a group of captive lowland tapirs.

Within a group of three captive lowland tapirs (Tapirus terrestris) suffering from clinically apparent mycobacteriosis, non-tuberculous Mycobacterium avium subsp. hominissuis (MAH) strains were isolated from the animals and the tapir's enclosure. Based on MIRU-VNTR findings, which identified two closely related INMV profiles (124 and 246), a micro-evolutionary event was assumed, and four available MAH strains were submitted to whole genome sequencing (short- and long-read technologies). Surprisingly, the differences based on single nucleotide polymorphisms (SNPs) were exceptionally high between the four strains, i.e., between 841 and 11,166 bases, due to a strong impact of homologous recombination. Thus, an ad hoc core genome multilocus sequence typing (cgMLST) scheme was created and pangenome analysis was conducted for determining the genomic similarity between the strains. The INMV246 isolate obtained from sputum on the enclosure floor and one INMV124 isolate of tapir #2 showed the highest congruence, suggesting that both originated from a shared source. The other two INMV124 isolates were genomically distinct from these strains. Nevertheless, in all four strains two plasmids were detected, which were highly conserved between the strains. The study showed that the genomic variability between MAH strains isolated from the same site within a short period of time can be exceptionally high and the influence of homologous recombination needs to be considered when determining MAH strain relationships, particularly via SNP analyses.

Animals↗

MRI investigation of normal fetal lung maturation using signal intensities on different imaging sequences.

To purpose of this paper is to study the relation between normal lung maturation signal and changes in intensity ratios (SIR) and to determine which magnetic resonance imaging sequence provides the strongest correlation of normal lung SIs with gestational age. 126 normal singleton pregnancies (20-37 weeks) were examined with a 1.5 Tesla unit. Mean SIs for lungs, liver, and gastric fluid were assessed on six different sequences, and SIRs of lung/liver (LLSIR) and lung/gastric fluid (LGSIR) were correlated with gestational age for each sequence. To evaluate the feasibility of SIRs in the prediction of the state of the lung maturity, accuracy of the predicted SIRs (D*) was measured by calculating relative residuals (D*-D)/D for each sequence. LLSIRs showed significant changes in every sequence (p<0.05), while LGSIRs only on two sequences. Significant differences were shown for the mean of absolute residuals for both LLSIRs (p<0.001) and for LGSIRs (p=0.003). Relative residuals of LLSIRs were significantly smaller on T1-weighted sequence, whereas they were significantly higher for LGSIRs on FLAIR sequence. Fetal liver seems to be adequate reference for the investigation of lung maturation. T1-weighted sequence was the most accurate for the measurement of the lung SIs; thus, we propose to determine LLSIR on T1-weighted sequence when evaluating lung development.

Feasibility Studies↗

Multidetector CT of pancreas: effects of contrast material flow rate and individualized scan delay on enhancement of pancreas and tumor contrast.

PURPOSE: To prospectively assess whether high contrast material flow rate (8 mL/sec) and individualized scan delay improve enhancement of normal pancreas with multidetector computed tomography (CT) and, as a result, tumor-to-pancreas contrast of pancreatic adenocarcinoma. MATERIALS AND METHODS: Informed consent was obtained in 40 patients (21 women, 19 men; mean age, 67.1 years); the institutional review board approved this protocol. Patients were referred for multidetector CT because they were suspected of having a pancreatic tumor and were randomized to receive 150 mL of nonionic contrast material (300 mg of iodine per milliliter) at a flow rate of 4 mL/sec (n = 21) or 8 mL/sec (n = 19). Patients underwent dynamic scanning at one level every 2 seconds for 66 seconds after intravenous administration of contrast material. Contrast enhancement of pancreas and tumors was measured with circular regions of interest (analysis of variance and Bonferroni-Holm corrected post hoc t tests). RESULTS: Peak contrast enhancement in pancreas was observed significantly earlier (mean +/- standard deviation, 28.7 seconds +/- 3.5 vs 48.2 seconds +/- 5.3; P < .05) and was significantly higher (129.0 HU +/- 25.7 vs 106.2 HU +/- 35.4, P < .05) with a flow rate of 8 mL/sec than with a flow rate of 4 mL/sec. Tumor-to-pancreas contrast greater than 40 HU lasted significantly longer with a flow rate of 8 mL/sec than with a flow rate of 4 mL/sec (26.4 seconds +/- 11.9 vs 8.6 seconds +/- 8.3, P < .05). With a flow rate of 8 mL/sec, an individualized scan delay of 19 seconds after aortic transit time revealed higher tumor-to-pancreas contrast than did a fixed scan delay, and tumor conspicuity was better. CONCLUSION: With 16-section CT, increased contrast material flow rate of 8 mL/sec and individualized scan delay were associated with improved pancreatic enhancement and tumor-to-pancreas contrast compared with flow rate of 4 mL/sec and fixed scan delay.

Adenocarcinoma↗

Multiple episodes of a transient global left ventricular dysfunction reminiscent to apical ballooning.

A new cardiac syndrome with transient left ventricular dysfunction has been recently reported and is referred to as Tako-Tsubo cardiomyopathy, which is characterized by a transient akinesia of the apex and compensatory basal hyperkinesis. Today, the etiology remains unknown. We report for the first time of a patient with multiple episodes of a transient global left ventricular dysfunction which is reminiscent to apical ballooning. These episodes were always preceded by severe emotional stress proposing a potential common pathomechanism.

Cardiomyopathies↗

JPEG2000 compression of thin-section CT images of the lung: effect of compression ratio on image quality.

PURPOSE: To assess retrospectively the effect of the Joint Photographic Experts Group 2000 (JPEG2000) compression ratio on the quality of thin-section computed tomographic (CT) images. MATERIALS AND METHODS: In this institutional review board-approved investigation (protocol 238/2004), thin-section CT images were subjected to irreversible JPEG2000 compression by using five compression ratios (3:1, 5:1, 7:1, 9:1, and 11:1). Three radiologists independently evaluated 60 thin-section CT images, of various diseases, that were obtained with single-detector (weighted dose index, 14.4 mGy) and multidetector (weighted dose index, 9.8 mGy) CT. Toggling between the original and compressed images, readers had to identify the original image by using a forced-choice two-alternative model and to subjectively rank the quality of what they believed to be the compressed image. To assess the reader's ability to distinguish the compressed from the original image, a binomial test was used. Bonferroni correction was applied for all multiple tests. RESULTS: Images compressed with a ratio of 3:1 were not distinguishable from original images (P > .2 for all readers). With use of the 5:1 ratio, minor differences in appearance between the compressed and original images were seen by one of the three readers. With use of higher compression ratios (>/=7:1), all readers (P < .001) recognized the original image. The quality of more than 90% of the images compressed with a 7:1 or higher ratio was substantially degraded. Single-detector and multidetector CT results were not significantly different. CONCLUSION: The highest ratio that yielded visually lossless compression of thin-section CT images was 3:1. With the 5:1 ratio, there was minor image quality loss, while use of higher compression ratios (>/=7:1) caused substantial degradation of image quality and potential loss of diagnostic information.

Adult↗

Comparison of expandable electrodes in percutaneous radiofrequency ablation of renal cell carcinoma.

OBJECTIVE: To compare two different expandable electrodes in radiofrequency ablation of renal cell carcinoma. METHODS: Percutaneous ablation was performed at two centers using either an expandable 7F umbrella-shaped LeVeen probe (diameter 2-4 cm) and a 200-W generator (group A), or an expandable Starburst XL electrode with a 150-W generator (group B). From each center, eight patients with one tumor each were matched retrospectively with regard to tumor volume, which was 9.71+/-6.43 cm3 for group A and 8.74+/-4.35 cm3 for group B (mean tumor diameter: 2.47+/-0.9 cm versus 2.50+/-0.4 cm, respectively). An unpaired t-test showed no significant difference in tumor volume between the two groups (p=0.820). RESULTS: Sixteen patients with 16 tumors were treated. The primary technical success of radiofrequency ablation was 94% (15 of 16 patients). After retreatment of residual tumor in one patient from group B, secondary technical success was 100%. No major complications were observed. The resulting mean volume of the almost spherical necroses was 21.1+/-9.1 cm3 versus 14.6+/-6.7 cm3 for groups A and B (diameter of necrosis: 3.5+/-0.7 cm versus 3.1+/-0.6 cm, respectively). A Mann-Whitney U-test showed no significant difference in necrosis volume between the two groups (CI [-0.215; 0.471]; p=0.2892). The calculated shape value of S (ratio of length to height of the coagulation necrosis) was 0.9+/-0.1 and 1.0+/-0.1 for groups A and B, respectively. No local recurrence was observed during a mean follow-up of 14.8+/-11.6 months, while extrarenal tumor progression occurred in three patients. CONCLUSIONS: No significant differences in coagulation volume and shape were found after RF ablation of renal cell carcinoma using two different expandable electrodes. To avoid local recurrence, however, accurate placement of probes and appropriate expansion of the electrode is necessary.

Aged↗

Temporary third-degree atrioventricular block in a case of apical ballooning syndrome.

Apical ballooning is characterized by severe but reversible contractile dysfunction. The causative factor and the pathomechanism remain unknown. Several arrhythmias are reported to occur in apical-ballooning. We present a unique case of a 58-year-old man presenting with apical ballooning complicated by a prolonged third-degree atrioventricular block requiring the implantation of a pacemaker.

Cardiac Pacing, Artificial↗

Bone marrow-derived cells contribute to infarct remodelling.

OBJECTIVE: The paradigm that cardiac myocytes are non-proliferating and terminally differentiated cells has recently been challenged by several studies reporting the ability of bone marrow-derived cells (BMC) to transdifferentiate into cardiomyocytes. However, these results are controversial and could not be reproduced by others. Therefore, we studied the contribution and potential transdifferentiation of BMC into different cell types during the remodelling process in mouse hearts with experimental myocardial infarction. METHODS: Mice (C57BL/6J) were sublethally irradiated, and BM from enhanced green fluorescent protein (eGFP)-transgenic mice was transplanted. Coronary artery ligation was performed 3 months later. The hearts were studied 7 days (n=13) and 21 days (n=12) after infarction. Immunohistochemical staining was performed using antibodies against titin, connexin 43, vimentin, SMemb alpha-smooth muscle actin, CD45, CD34, F4/80, BS-1, CD31, and eGFP. Sections were analyzed using fluorescence and confocal laser microscopy. RESULTS: Success of BM transplantation was confirmed by FACS analysis. Occlusion of the coronary artery resulted in infarct sizes of 41+/-6% of the left ventricle. CD45+/eGFP+ inflammatory cells were found frequently after 7 days and to a lesser degree after 21 days. In 25 examined hearts, only 3 eGFP-positive cardiomyocytes were found. However, numerous BMC-derived fibroblasts and myofibroblasts were found in the infarct area. BMC contributed to scar tissue neoangiogenesis but not to angiogenesis in the periinfarct and remote zones. CONCLUSION: Transdifferentiation of BMC into viable cardiomyocytes is a negligible event in normal repair processes after myocardial damage. BMC-derived fibroblasts and myofibroblasts as well as neoangiogenesis significantly contribute to post-infarction scar formation and might be important in scar tissue remodelling.

Animals↗

Percutaneous radiofrequency ablation of renal tumors: midterm results in 16 patients.

PURPOSE: To evaluate the outcome of 16 patients after percutaneous radiofrequency ablation of renal tumors. MATERIALS AND METHODS: Sixteen patients (nine women, seven men; mean age, 61+/-9 years) with 24 unresectable renal tumors (mean volume, 4.3+/-4.3 cm3) underwent CT-guided (n=20) or MR imaging-guided (n=4) percutaneous radiofrequency ablation using an expandable electrode (Starburst XL, RITA Medical Systems, Mountain View, CA) with a 150-W generator. The initial follow-up imaging was performed within 1-30 days after RF ablation, then at 3-6 month intervals using either CT or MRI. Residual tumor volume and coagulation necrosis was assessed, and statistical correlation tests were obtained to determine the strength of the relationship between necrosis volume and number of ablations. RESULTS: Overall, 97 overlapping RF ablations were performed (mean, 3.5+/-1.5 ablations per tumor) during 24 sessions. Five or more RF ablations per tumor created significant larger necrosis volumes than 1-2 (p=.034) or 3-4 ablations (p=.020). A complete ablation was achieved in 20/24 tumors (primary technical success, 83%; mean volume of coagulation necrosis: 10.2+/-7.2 cm3). Three of four residual tumors were retreated and showed complete necrosis thereafter. Three major complications (one percuatneous urinary fistula and two ureteral strictures) were observed after RF ablation. No further clinically relevant complications were observed and renal function remained stable. During a mean follow-up of 11.2 months (range, 0.2-31.5), 15/16 patients (94%) were alive. Only one patient had evidence of local recurrent tumor. CONCLUSION: The midterm results of percutaneous RF ablation for renal tumors are promising and show that RF ablation is well-suited to preserve renal function.

Aged↗

Multiple isotope effect study of the acid-catalyzed hydrolysis of formamide.

Multiple isotope effects were measured at the reactive center of formamide during acid-catalyzed hydrolysis in water at 25 degrees C. The mechanism involves a rapid pre-equilibrium protonation of the carbonyl oxygen, followed by the formation of at least one tetrahedral intermediate, which does not appreciably exchange its carbonyl oxygen with the solvent (kh/kex = 55). The pKa for formamide was determined by 15N NMR and found to be about -2.0. The formyl-hydrogen kinetic isotope effect (KIE) is indicative of a transition state that is highly tetrahedral (Dkobs = 0.79); the carbonyl-carbon KIE (13kobs = 1.031) is in agreement with this conclusion. The small leaving-nitrogen KIE (15kobs = 1.0050) is consistent with some step prior to breaking the C-N bond as rate-determining. The carbonyl-oxygen KIE (18kobs = 0.996) points to attack of water as the rate-determining step. On the basis of these results, a mechanism is proposed in which attachment of the nucleophile to a protonated formamide molecule is rate determining.

Acids↗

Influence of sample type and storage conditions on soluble CD40 ligand assessment.

BACKGROUND: Several studies have consistently shown that soluble CD40 ligand (sCD40L) concentrations are increased in patients with acute coronary syndromes and can serve as a biomarker for risk stratification. However, few data are available on preanalytic conditions that impact sCD40L values. Thus, the aim of our prospective study was to evaluate the impact of sampling techniques and storage conditions on sCD40L concentrations. METHODS: We included a total of 30 patients with no, stable, or unstable coronary heart disease. Blood samples were collected in gel-filled tubes without additives, in EDTA-filled tubes, and in citrate-filled tubes and were kept at various storage conditions. RESULTS: Median (interquartile range) sCD40L values at baseline were higher in serum samples [5.29 (3.89-6.33) microg/L] than in either EDTA plasma [0.78 (0.39-1.12) microg/L; P <0.001] or citrate plasma [0.37 (0.22-0.51) microg/L; P <0.001]. Serum values increased with delayed processing [7.94 (5.97-9.62) microg/L after 1.5 h (P <0.001) vs baseline; 10.55 (7.58-11.55) microg/L after 3 h (P <0.001) vs baseline]. However, after centrifugation, sCD40L values remained stable for all 3 sample types. CONCLUSION: Plasma, but not serum, samples are appropriate for sCD40L measurements. In general, preanalytic conditions are critical in the assessment of sCD40L concentrations and thus should be carefully considered for future studies.

Biomarkers↗

Epigenomics: mapping the methylome.

DNA methylation is integral to normal development and disease processes. However, the genomic distribution of methylated sequences--the methylome--is poorly understood. We have recently developed a platform technology for rapid assessment of methylation status throughout the human genome in a high-resolution, high-throughput manner. This is achieved by coupling a methylated DNA immunoprecipitation (MeDIP) method for isolating methyl cytosine rich fragments with array-based comparative genomic hybridization (array CGH). Using a combination of whole genome tiling path BAC arrays and CpG island microarrays, DNA methylation profiles are obtained simultaneously at both genome-wide and locus-specific levels. A comparison between male and female DNA using MeDIP-array CGH revealed unexpected hypomethylation of the inactive x-chromosome in gene-poor regions. Furthermore, comparisons between cancer and noncancer cell types yielded differential methylation patterns that link genetic and epigenetic instability offering a new approach to decipher misregulation in cancer. Finally, we provide new data showing epigenomic instability in lung cancer cells with concurrent regions of genetic and epigenetic alterations harboring known oncogenes.

Chromatin Immunoprecipitation↗

Direct detector radiography versus dual reading computed radiography: feasibility of dose reduction in chest radiography.

The image quality of dual-reading computed radiography and dose-reduced direct radiography of the chest was compared in a clinical setting. The study group consisted of 50 patients that underwent three posteroanterior chest radiographs within minutes, one image obtained with a dual read-out computed radiography system (CR; Fuji 5501) at regular dose and two images with a flat panel direct detector unit (DR; Diagnost, Philips). The DR images were obtained with the same and with 50% of the dose used for the CR images. Images were evaluated in a blinded side-by-side comparison. Eight radiologists ranked the visually perceivable difference in image quality using a three-point scale. Then, three radiologists scored the visibility of anatomic landmarks in low and high attenuation areas and image noise. Statistical analysis was based on Friedman tests and Wilcoxon rank sum tests at a significance level of P<0.05. DR was judged superior to CR for the delineation of structures in high attenuation areas of the mediastinum even when obtained with 50% less dose (P<0.001). The visibility of most pulmonary structures was judged equivalent with both techniques, regardless of acquisition dose and speed level. Scores for image noise were lower for DR compared with CR, with the exception of DR obtained at a reduced dose. Thus, in this clinical preference study, DR was equivalent or even superior to the most modern dual read-out CR, even when obtained with 50% dose. A further dose reduction does not appear to be feasible for DR without significant loss of image quality.

Adult↗

[Biomarkers for the evaluation of valvular aortic stenosis].

Aortic valve diseases, namely aortic stenosis (AS) and aortic regurgitation (AR), are common in developed countries with AS being the most common valvular heart disease. Symptomatic status and echocardiography are the most important clinical parameters to confirm the diagnosis, to assess the severity and to monitor progression of AS. Aortic valve replacement (AVR) is indicated in symptomatic patients with severe AS, but in asymptomatic patients with severe AS there is an ongoing controversial discussion whether these patients should undergo AVR or should be treated conservatively. For patients with moderate AS, surgical treatment is generally not recommended, even though recent data suggest that the outcome of these patients is worse than commonly assumed.In several studies that included patients with valvular AS, an elevation of BNP and NT-proBNP serum concentrations related to disease severity has been reported (Figure 1). Consequently, in a longitudinal study it was found, that NT-proBNP concentrations decrease after successful surgical therapy but increase in conservatively treated patients with AS (Figure 2). These changes of NT-proBNP values over time were related to changes of the transvalvular pressure gradient (Figure 3). Furthermore, it has been demonstrated in clinical outcome studies that elevated NT-proBNP and BNP values, respectively, were associated with an unfavorable clinical course especially in patients who were treated conservatively (Figure 4).Thus, these results suggest that natriuretic peptides can be used as biomarkers for the diagnostic work-up of patients with AS and might be helpful to decide on the optimal timing of AVR (Table 1).

Aortic Valve↗

[Acute coronary syndrome with and without ST elevation].

Coronary artery disease accounts for most deaths in western communities. The acute coronary syndrome subsidizes ST elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina pectoris. They are characterized by an acute onset of chest pain. The high number of acute coronary syndromes of more than 400,000 per year in Germany demonstrates the necessity of guidelines. Such guidelines are available from different cardiac societies. The implementation of the guidelines of the German Cardiac Society and the European Society of Cardiology in the daily clinical practice are demonstrated in this review by means of two case presentations. Special attention has been given to diagnostic measures, risk stratification, and different therapeutic options. For the diagnostic work-up in the acute phase, the ECG and the assessment of cardiac biomarkers play the central role. For patients with ST elevation myocardial infarction, primary interventional diagnostics and therapy are the first choice. For patients presenting with acute coronary syndromes without ST elevation, a risk-adapted therapeutic approach should be chosen. High-risk patients (elevated troponins, clinical, rhythmologic, and hemodynamic instability, ST depression, or diabetes mellitus) should be treated with an early invasive approach within 48-72 h. Low-risk patients can be treated primarily conservatively. For all patients who undergo interventional treatment, administration of an aggressive antiaggregatory therapy, including acetylsalicylic acid, clopidogrel, glycoprotein IIb/IIIa receptor antagonists, and heparin, is indicated in the acute phase. In the chronic phase, an adequate treatment of cardiovascular risk factors is of paramount importance.

Acute Disease↗

Outcomes in subgroups of hypertensive patients treated with regimens based on valsartan and amlodipine: An analysis of findings from the VALUE trial.

BACKGROUND: In the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial the primary outcome (cardiac morbidity and mortality) did not differ between valsartan and amlodipine-based treatment groups, although systolic blood pressure (SBP) and diastolic blood pressure reductions were significantly more pronounced with amlodipine. Stroke incidence was non-significantly, and myocardial infarction was significantly lower in the amlodipine-based regimen, whereas cardiac failure was non-significantly lower on valsartan. OBJECTIVES: The study protocol specified additional analyses of the primary endpoint according to: sex; age; race; geographical region; smoking status; type 2 diabetes; total cholesterol; left ventricular hypertrophy; proteinuria; serum creatinine; a history of coronary heart disease; a history of stroke or transient ischemic attack; and a history of peripheral artery disease. Additional subgroups were isolated systolic hypertension and classes of antihypertensive agents used immediately before randomization. METHODS: The 15,245 hypertensive patients participating in VALUE were divided into subgroups according to baseline characteristics. Treatment by subgroup interaction analyses were carried out by a Cox proportional hazard model. Within each subgroup, treatment effects were assessed by hazard ratios and 95% confidence intervals. RESULTS: For cardiac mortality and morbidity, the only significant subgroup by treatment interaction was of sex (P = 0.016), with the hazard ratio indicating a relative excess of cardiac events with valsartan treatment in women but not in men, but SBP differences in favour of amlodipine were distinctly greater in women. No other subgroup showed a significant difference in the composite cardiac outcome between valsartan and amlodipine-based treatments. For secondary endpoints, a sex-related significant interaction was found for heart failure (P < 0.0001), with men but not women having a lower incidence of heart failure with valsartan. CONCLUSION: As in the whole VALUE cohort, in no subgroup of patients were there differences in the incidence of the composite cardiac endpoint with valsartan and amlodipine-based treatments, despite a greater blood pressure decrease in the amlodipine group. The only exception was sex, in which the amlodipine-based regimen was more effective than valsartan in women, but not in men, whereas the valsartan regimen was more effective in preventing cardiac failure in men than in women.

Aged↗