Search PubMed⌕ Search

Biomedical subjects

M Ebert

Publications and source records attributed to M Ebert.

At least 19 recordsLinked to original sources

Prevalence of equine herpesvirus type 2 (EHV-2) DNA in ocular swabs and its cell tropism in equine conjunctiva.

Equine herpes virus 2 (EHV-2), a gamma(2)-herpesvirus, is common in horses of all ages. Its role as a primary pathogen is unclear but there is an association between EHV-2, respiratory disease and keratoconjunctivitis. The purpose of this study was to gain more information on the prevalence of EHV-2 DNA in conjunctival swabs from horses with and without ocular disease and to define the anatomical site and cell type harbouring viral genome or antigen. By polymerase chain reaction (PCR) 22 out of 77 (28.6%) ocular swabs of clinically healthy and only 4 out of 48 (8.3%) samples from diseased horses were positive. To define the main virus reservoir ocular tissue from 13 randomly selected horses without pathological evidence of ocular disease were analysed by nested PCR. In two horses optic nerve, lacrimal gland and conjunctiva, in further two cases lacrimal gland and conjunctiva and in four horses the conjunctiva only were EHV-2 PCR positive. For specifying the target cell we focused on conjunctivae and selected 3 out of 15 clinically healthy slaughterhouse horses positive for EHV-2 by PCR. In situ hybridisation on sections of these paraffin embedded conjunctivae localized viral genome in histiocyte-like cells of the submucosa. Immunohistochemical staining with an EHV-2 or S100 specific polyclonal antiserum demonstrated that Langerhans cells were co-localized in the same region of the sample section where virus positive cells were detected. Furthermore, we concluded that detection of viral antigen revealed a productive virus infection.

Animals↗

[Sonographic diagnosis of a liver abscess caused by an enterohepatic fistula in a patient with Crohn's disease].

Liver abscesses in patients with Crohn's disease are rare. We report on a patient with Crohn's disease and a liver abscess of the left lobe caused by an enterohepatic fistula. With treatment of antibiotics and Infliximab the abscess showed complete regression. Percutaneous drainage of the liver abscess was not performed because the abscess was shown not to be completely liquefied at echo-enhanced ultrasound. This case report demonstrates the usefulness of percutaneous conventional and echo-enhanced ultrasound for the diagnosis of liver abscesses. Furthermore, this case also shows that enterohepatic fistulas can be diagnosed precisely with percutaneous ultrasound.

Adult↗

Diagnostic and therapeutic impact of double-balloon enteroscopy.

BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) is a new endoscopic method for examining the small intestine. Most reports of DBE have been from Japan, and very few data on this new technique have been reported by centers outside Japan. The aim of the present study was to determine the diagnostic yield of DBE, measure the frequency of management changes made on the basis of the results, and evaluate the clinical outcome for patients undergoing the procedure. PATIENTS AND METHODS: All patients undergoing DBE using a Fujinon enteroscope (length 200 cm, diameter 8 mm) during a 11-month period were studied. All of the patients had previously undergone esophagogastroduodenoscopy and colonoscopy. They underwent small-bowel cleansing on the day before the procedure using a standard colon lavage solution. RESULTS: Seventy DBE procedures were carried out in 53 patients (34 men, 19 women; mean age 60 years, range 24 - 80) by the oral route in 46 cases and the anal route in 24. The indications for the examination were gastrointestinal bleeding (n = 29), suspected Crohn's disease (n = 6), abdominal pain (n = 4), polyp removal or evaluation in polyposis syndromes (n = 6), chronic diarrhea (n = 4), and surveillance or tumor search (n = 4). The mean duration of the procedure was 72 min (range 25 min - 3 h). The mean radiation exposure was 441 dGy/cm (range 70 - 1462), and the mean depth of small-bowel insertion was 150 cm (range 1 - 470 cm). It was possible to evaluate the entire small bowel in four patients (8 %). A new diagnosis was obtained in 26 of the 53 patients (49 %). The findings in the 70 procedures were angiodysplasia (n = 13), ulcerations or erosions (n = 5), jejunitis or ileitis (n = 5), tumors (n = 5), stenosis (n = 4), polyps (n = 5), lymphangiectasias (n = 4), Crohn's disease (n = 4), and normal (n = 17). DBE resulted in a therapeutic intervention (endoscopic, medical or surgical, excluding blood transfusions) in 57 % of the patients (30 of 53). The only complication (1.4 %) observed was one case of intraprocedural postpolypectomy bleeding, which resolved with injection of epinephrine. CONCLUSION: In almost two-thirds of the patients examined, DBE was clinically useful for obtaining a new diagnosis and starting new treatments, changing existing treatments, carrying out surgical intervention, or providing therapeutic endoscopy. DBE is a useful and safe method of obtaining tissue for diagnosis, providing hemostasis, and carrying out polypectomy.

Adult↗

Ectopeptidases in tumour biology: a review.

Cell membrane-bound proteolytic enzymes (ectopeptidases) are integral membrane proteins, orientated asymmetrically with the catalytic site exposed to the extracellular surface, which enables a versatile range of physiological and pathological functions. Ectopeptidases may regulate the release of many growth factors and their receptors into the circulation, as well as activating or inactivating circulating signalling molecules, thereby regulating the availability of ligands for the corresponding receptors. Additionally, many of these ectopeptidases have functions not limited to proteolysis, but are able in themselves to function as receptors, transducing intracellular signals. A versatile range of functions, such as the modulation of cell-signalling, matrix degradation, cell adhesion and migration, which are particularly important for tumour cell growth and dissemination, are attributed largely to the ectopeptidases. Even a minor disruption in the normal proteolytic equilibrium can influence tumor progression, and a range of ectopeptidases, including neutral endopeptidase 24.11, aminopeptidase N, dipeptidyl peptidase IV, angiotensin-converting enzyme, and the disintegrin-metalloproteinases, have been shown to be involved in tumour development and metastasis. The ability to degrade and inactivate peptide hormones and growth factors, with the resultant modulation of the tumour-host interface, may play an important role in the pathogenesis, development or progression of a range of cancers, and the extracellular orientation of the ectopeptidases makes them particularly accessible, and therefore interesting, with regard to therapeutical applications.

Humans↗

Removal of arsenic from groundwater by zerovalent iron and the role of sulfide.

Several recent investigations have shown encouraging potential for the removal of arsenic (As) from groundwater by granular zerovalent iron (Fe0). In contrast to previous studies conducted, we have investigated the applicability of this method and the nature of As bonding under conditions with dissolved sulfide. Three column tests were performed over the period of 1 year using solutions with either As(V) or As(II) (2-200 mg/L) in the input solution. Arsenic outflow concentrations decreased from initially 30-100 microg/L to concentrations of below 1 microg/L with time. XANES (X-ray absorptions near edge structure) and EXAFS (expanded X-ray absorption fine structure) spectra indicated that As in the solid phase is not only directly coordinated with oxygen, as is the case in adsorbed or coprecipitated arsenite and arsenate. Samples with high sulfur content showed additional bonding, for which Fourier transformations of EXAFS data exhibited a peak between 2.2 and 2.4 A. This bonding most likely originated from the direct coordination of sulfur or iron with As, which was incorporated in iron sulfides orfrom adsorbed thioarsenites. The formation of this sulfide bonding supports the removal of As by Fe0 because sulfide production by microbial sulfate reduction is ubiquitous in permeable reactive barriers composed of Fe0.

Arsenic↗

Helicobacter pylori genotypes and expression of gastritis in erosive gastro-oesophageal reflux disease.

BACKGROUND: Epidemiological studies suggest a negative association between Helicobacter pylori and gastro-oesophageal reflux disease (GORD). Moreover, cagA-positive strains are reported to protect from complications of GORD. The aim of this study was to determine virulence factors (cagA, vacA and iceA) of H. pylori strains and the pattern of gastritis in patients with GORD in comparison with patients with duodenal ulcer (DU) or functional dyspepsia (FD). METHODS: H. pylori strains isolated from gastric biopsies of 105 consecutive patients with mild to moderate erosive GORD (n = 35, LA grade A-B), and from sex- and age-matched patients with DU (n = 35) or FD (n = 35 without reflux symptoms) were investigated. CagA, vacA, and iceA genotypes were determined by PCR analysis of the isolates. Gastritis was classified in accordance with the updated Sydney classification. RESULTS: The prevalence of all three H. pylori virulence factors was higher in patients with GORD (cagA+ 80%, vacA s1 77%, iceA1 71%) and DU (cagA+ 83%, vacA s1 80%, iceA1 74%) than in patients with FD (cagA+ 40%, vacA s1 49%, iceA1 46%). Gastritis activity in the antrum and corpus did not differ between the three groups. However, lymphocytic infiltration of the gastric antral mucosa was more pronounced in DU patients than in those with GORD or FD. CONCLUSIONS: H. pylori strains obtained from patients with mild to moderate erosive GORD show a virulence pattern similar to that found in DU patients. The presence of these virulence factors does not appear to protect against erosive lesions in the oesophagus.

Antigens, Bacterial↗

IMRT verification by three-dimensional dose reconstruction from portal beam measurements.

A method of reconstructing three-dimensional, in vivo dose distributions delivered by intensity-modulated radiotherapy (IMRT) is presented. A proof-of-principle experiment is described where an inverse-planned IMRT treatment is delivered to an anthropomorphic phantom. The exact position of the phantom at the time of treatment is measured by acquiring megavoltage CT data with the treatment beam and a research prototype, flat-panel, electronic portal imaging device. Immediately following CT imaging, the planned IMRT beams are delivered using the multiple-static field technique. The delivered fluence is sampled using the same detector as for the CT data. The signal measured by the portal imaging device is converted to primary fluence using an iterative phantom-scatter estimation technique. This primary fluence is back-projected through the previously acquired megavoltage CT model of the phantom, with inverse attenuation correction, to yield an input fluence map. The input fluence maps are used to calculate a "reconstructed" dose distribution using the same convolution/superposition algorithm as for the original planning dose calculation. Both relative and absolute dose reconstructions are shown. For the relative measurements, individual beam weights are taken from measurements but the total dose is normalized at the reference point. The absolute dose reconstructions do not use any dosimetric information from the original plan. Planned and reconstructed dose distributions are compared, with the reconstructed relative dose distribution also being compared to film measurements.

Feasibility Studies↗

Expression of thrombospondin-1 in pancreatic carcinoma: correlation with microvessel density.

Thrombospondin-1 (TSP-1) is a multifunctional platelet and extracellular matrix protein that is involved in angiogenesis. Under certain pathological conditions, e.g., malignant tumors, high concentrations of TSP-1 work as an angiogenic agonist. Here we examined 98 pancreatic carcinomas with respect to TSP-1 immunoreactivity and its correlation to intratumoral microvessel density (MVD), a representation of the overall degree of angiogenesis in carcinomas. Northern blot analysis for TSP-1 mRNA was performed in seven additional cases. Eighty-seven tumors showed strong TSP-1 immunoreactivity, nine carcinomas were only weakly positive, and two lesions were negative for TSP-1. TSP-1 immunoreactivity was detected in the extracellular matrix, mostly at the invasion front of the tumor. Using Northern blot analysis, we observed high levels of TSP-1 mRNA in three out of seven pancreatic carcinomas. The mean MVD in pancreatic carcinoma was 38.8 vessels per mm2. Tumors with a high expression of TSP-1 showed a higher MVD and the correlation between TSP-1 immunoreactivity and microvessel density was highly significant (P=0.003). As a modulator of angiogenesis, TSP-1 is strongly expressed in most pancreatic adenocarcinomas and is likely to contribute to the extensive neovascularization and spread of this highly aggressive tumor.

Adenocarcinoma↗

Correction of scatter in megavoltage cone-beam CT.

The role of scatter in a cone-beam computed tomography system using the therapeutic beam of a medical linear accelerator and a commercial electronic portal imaging device (EPID) is investigated. A scatter correction method is presented which is based on a superposition of Monte Carlo generated scatter kernels. The kernels are adapted to both the spectral response of the EPID and the dimensions of the phantom being scanned. The method is part of a calibration procedure which converts the measured transmission data acquired for each projection angle into water-equivalent thicknesses. Tomographic reconstruction of the projections then yields an estimate of the electron density distribution of the phantom. It is found that scatter produces cupping artefacts in the reconstructed tomograms. Furthermore, reconstructed electron densities deviate greatly (by about 30%) from their expected values. The scatter correction method removes the cupping artefacts and decreases the deviations from 30% down to about 8%.

Artifacts↗

Differentiation of chronic pancreatitis from pancreatic cancer: recent advances in molecular diagnosis.

Chronic pancreatitis is an inflammatory disease of the pancreas, characterized by a progressive destruction of the exocrine and endocrine pancreas, leading both to exocrine and endocrine insufficiency. In recent years, our knowledge of this disease has improved, an epidemiological link between chronic pancreatitis and pancreatic cancer has been established, and the molecular alterations underlying their pathogenesis have been partly revealed. Nevertheless, the differentiation of chronic inflammation of the pancreas from cancer of the pancreas remains a great challenge. This overview will point out the present knowledge of the molecular pathogenesis of chronic pancreatitis and pancreatic cancer and will focus on the role of molecular markers for differentiating chronic pancreatitis from pancreatic cancer.

Animals↗

Prognostic parameters determining survival in pancreatic carcinoma and, in particular, after palliative treatment.

Prognosis and outcome of patients with pancreatic carcinoma is poor. The aim of the study was to investigate (1) which factors of medical history and clinical status as well as which laboratory parameters determine survival in pancreatic carcinoma and (2) whether specific data can be used as prognostic parameters or for early diagnosis of pancreatic carcinoma. In total, 287 patients with pancreatic carcinoma were enrolled in the study. In 193 subjects, only palliative treatment was possible. Survival was assessed using univariate survival probability curves by Kaplan-Meier. Comparison of patient groups with regard to survival was achieved using the log-rank test. Multivariate analysis was carried out using the Cox regression model. Overall, 22 factors, showing a significant impact on survival in pancreatic carcinoma were found, e.g., tumor-associated factors such as (1) tumor stage according to the UICC classification including TNM-based staging, grading, tumor site, and vascular infiltration; (2) preoperative habits and signs and symptoms (physical condition, pain, loss of appetite, ethanol consumption); (3) change of laboratory parameters (CA 19-9, bilirubin, prothrombin time, urea, C-reactive protein), and (4) type of intervention (surgical approach, R0/1/2 resection). Using multivariate analysis, seven factors (UICC tumor stage and site, surgical intervention including number of resected lymph nodes, chemotherapy, occurence of a carcinoma in relatives, preoperative physical condition, night sweat) were determined. In the 193 patients with palliative treatment, only ten factors (among them UICC tumor stage including the presence of metastases; data from the medical history such as physical condition, loss of appetite, and carcinoma in relatives, and laboratory parameters including prothrombin time, protein content, and aspartate aminotransferase levels) were found to be important. Chemotherapy had the strongest impact on survival which was confirmed by multivariate analysis, followed by tumor stage (UICC) and preoperative appetite. Besides tumor-associated determinants, data from the medical history, and pathological laboratory parameters, the prognosis in pancreatic carcinoma is considerably determined by the treatment such as interventional and/or using antineoplastic agents.

Adult↗

(3)he-MRI-based measurements of intrapulmonary p(O2) and its time course during apnea in healthy volunteers: first results, reproducibility, and technical limitations.

We applied a recently developed method of following the time course of the intrapulmonary oxygen partial pressure p(O2)(t) during apnea by (3)He MRI to healthy volunteers. Using two imaging series with different interscan times during two breathholds (double acquisition technique), relaxation of (3)He due to paramagnetic oxygen and depolarization by RF pulses were discriminated. In all four subjects, the temporal evolution of p(O2) was found to be linear, and was described by an initial partial pressure p(0) and a decrease rate R. Also, regional differences of both p(0) and R were observed. A correlation between p(0) and R was apparent. Finally, we discuss limitations of the double acquisition approach.

Adult↗

Quantification of regional intrapulmonary oxygen partial pressure evolution during apnea by (3)He MRI.

We present a new method to determine in vivo the temporal evolution of intrapulmonary oxygen concentrations by functional lung imaging with hyperpolarized (3)Helium ((3)He-->). Single-breath, single-bolus visualization of (3)He--> administered to the airspaces is used to analyze nuclear spin relaxation caused by the local oxygen partial pressure p(O(2))(t). We model the dynamics of hyperpolarization in the lung by rate equations. Based hereupon, a double acquisition technique is presented to separate depolarization by RF pulses and oxygen induced relaxation. It permits the determination of p(O(2)) with a high accuracy of up to 3% with simultaneous flip angle calibration using no additional input parameters. The time course of p(O(2)) during short periods of breathholding is found to be linear in a pig as well as in a human volunteer. We also measured the wall relaxation time in the lung and deduced a lower limit of 4.3 min.

Adult↗

Alteration of fibroblast growth factor and receptor expression after acute pancreatitis in humans.

After an episode of acute pancreatitis (AP) in humans, the pancreas exhibits varying degrees of fibrosis, acinar cell regeneration, and the formation of tubular complexes. The mechanisms underlying these changes are unknown. By using Northern blot analysis and immunohistochemistry, we assessed the expression and distribution of fibroblast growth factors (FGFs) and their receptor in human pancreatic tissues obtained from patients with AP. By comparison with the normal pancreas, acidic FGF (aFGF) and FGF-receptor 1 (FGFR-1, flg), mRNA levels were significantly decreased in human pancreatic tissues, which were obtained approximately 8 days after onset of AP. In the normal pancreas, acidic FGF, basic FGF, and FGFR-1 immunoreactivity was present at low to moderate levels in a heterogeneous pattern in the cytoplasm of acinar and ductal cells. Two patterns of immunoreactivity were observed in the AP group. In regions that have undergone necrosis, there was complete loss of aFGF, bFGF, and FGFR-1 immunostaining. In contrast, in the regenerating areas, aFGF and bFGF were readily evident in exocrine-type cells, in association with a marked increase in FGFR-1 immunoreactivity. These findings indicate that FGF/receptor expression is altered after AP, and raise the possibility that FGFs may be involved in the process of pancreatic exocrine regeneration during recovery from AP.

Acute Disease↗

Analysis of intrapulmonary O(2) concentration by MR imaging of inhaled hyperpolarized helium-3.

Inhalation of hyperpolarized (3)He allows magnetic resonance imaging (MRI) of ventilated airspaces. (3)He hyperpolarization decays more rapidly when interacting with paramagnetic O(2). We describe a method for in vivo determination of intrapulmonary O(2) concentrations ([O(2)]) based on MRI analysis of the fate of measured amounts of inhaled hyperpolarized (3)He in imaged regions of the lung. Anesthetized pigs underwent controlled normoventilation in a 1.5-T MRI unit. The inspired O(2) fraction was varied to achieve different end-tidal [O(2)] fractions (FET(O(2))). With the use of a specifically designed applicator, (3)He (100 ml, 35-45% polarized) was administered at a predefined time within single tidal volumes. During subsequent inspiratory apnea, serial two-dimensional images of airways and lungs were acquired. At least once in each animal studied, the radio-frequency excitation used for imaging was doubled at constant FET(O(2)). Signal intensity measurements in regions of interest of the animals' lungs (volume range, 54-294 cm(3)), taken at two different radio-frequency excitations, permitted calculation of [O(2)] in these regions of interest. The [O(2)] fractions in the regions of interest correlated closely with FET(O(2)) (R = 0.879; P < 0.0001). O(2)-sensitive (3)He-MRI may allow noninvasive study of regional distribution of ventilation and alveolar PO(2) in the lung.

Administration, Inhalation↗

Prenatal stress alters brain biogenic amine levels in primates.

In this study, we assessed behavioral responses to social separation at 8 months of age and cerebrospinal fluid (CSF) concentrations of biogenic amines and metabolites at 8 and 18 months of age in 12 rhesus monkeys derived from either stressed or undisturbed pregnancies. Compared to controls from undisturbed pregnancies, prenatal stress-derived monkeys had higher concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), and 3,4-dihydroxyphenylacetic acid in CSF than controls. Norepinephrine and MHPG response to stress were both correlated between 8 and 18 months of age. There were few group differences in behavior during social separation; however, several behavioral differences between groups were found when monkeys were reunited with cage mates. Prenatally stressed monkeys spent more time clinging to their surrogates and exploring (including eating and drinking), while controls showed more locomotion and social play with their cage mates. Collectively, our findings suggest that chronic unpredictable psychological stress during pregnancy has long-lasting effects on noradrenergic and dopaminergic activity and behavior in the offspring of gestationally stressed primate mothers.

3,4-Dihydroxyphenylacetic Acid↗

Overexpression of platelet-derived growth factor (PDGF) B chain and type beta PDGF receptor in human chronic pancreatitis.

Platelet-derived growth factors (PDGF) are mitogenic polypeptides that are involved in cellular proliferation and tissue repair. The expression of PDGFs and type beta PDGF receptor was examined in the normal human pancreas and in chronic pancreatitis, a fibrotic disease associated with fibroblastic proliferation, atrophy, and acinar cell dedifferentiation. In the normal human pancreas, PDGF A chain mRNA levels were relatively abundant, whereas PDGF B chain mRNA levels were not detected, and type beta PDGF receptor mRNA transcripts were present at low levels. In the normal pancreas, PDGF immunoreactivity was present in islet cells, whereas type beta PDGF receptor immunoreactivity was present in acinar cells. In chronic pancreatitis, PDGF A chain mRNA transcripts were also abundant, and 11 of 19 samples exhibited the PDGF B chain mRNA transcript. In addition, there was a significant increase in the mRNA levels of type beta PDGF receptor in the pancreatitis samples by comparison with the normal pancreas (P < 0.001). In chronic pancreatitis tissues, PDGF and type beta PDGF receptor immunoreactivity were present in acinar, ductal, islet, and endothelial cells, fibroblasts, and leukocytes. The concomitant overexpression of PDGFs and of the type beta PDGF receptor points to the existence of autocrine and paracrine PDGF-dependent loops in human chronic pancreatitis.

Blotting, Northern↗