Recurrent atrial sarcoma presenting as an atrial myxoma. Long-term survival due to surgical intervention and chemotherapy.
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Adult↗
Biomedical subjects
U Werner
Publications and source records attributed to U Werner.
Electron density imaging of protein films on gold-particle surfaces with transmission electron microscopy.
BACKGROUND: Surface bound proteins on colloid particles are widely used in biotechnological applications such as diagnostics or separation. Analysis of colloid surfaces by imaging methods provides information on the structure of these protein films, and an understanding of the functional relationships of biomolecules immobilised on solid surfaces. METHODS: In order to visualise protein molecules organised in films on surfaces of nano-sized gold-particles, an electron-microscopic approach based on the scattering absorption contrast of the specimen was applied. RESULTS: Analysing protein conjugated gold particles with a transmission electron microscope, protein films on gold particle surfaces cause a significant scattering absorption contrast based on the materials' electron density. Thus, the thickness of such films becomes directly measurable in planar projection and the shape of these films are visualised without negative staining methods. The insertion of Ruthenium-labelled antibodies instead of non-labelled antibodies as a marker with increased electron-density in these films yields a contrast enhancement of the whole film. Additional labelling with anti-Mouse IgG Gold conjugates localises the position of the surface bound antibodies in such protein films. CONCLUSIONS: The power of transmission electron microscopy to resolve protein-films on colloid surfaces without staining or labelling as a sample preparation procedure has been demonstrated. Thus, this direct method provides an analytical tool for studying protein films and their structural features on particle surfaces.
Animals↗
Solid-pseudopapillary tumor of the pancreas--a rare and frequently misdiagnosed neoplasm.
INTRODUCTION: We describe a young woman with an unusual pancreatic tumor. FINDINGS AND DISCUSSION: Intraoperatively, a smoothly demarcated and encapsulated tumor was exposed. It was large (5 cmx4 cm) and of solid consistency, with a small stalk attached to the uncinate process. The tumor was partially surrounded by the pancreatic head. The macroscopic appearance suggested a benign tumor. Frozen sections revealed a benign pancreatic tumor, most likely of endocrine nature. Based on these findings, tumor enucleation was performed. The patient recovered rapidly from the intervention and was discharged from hospital after 2 weeks. One year after surgical treatment, the patient is without recurrence. The final diagnosis of the tumor was a solid pseudo-papillary tumor.
Adult↗
Ejection associated injuries within the German Air Force from 1981-1997.
From 1981-1997 there were 86 ejections from 56 aircraft within the German Air Force. Of these, 24 accidents were associated with the F-104 Starfighter, 14 with the PA 200 Tornado, 12 from the F-4 Phantom, 5 from the Alpha Jet and 1 from a MiG 29 Fulcrum. One case involved a front seat pilot, who had already sustained fatal injuries from midair collision, being command ejected by the rear seat pilot. The remaining 85 ejections are the basis of this study. One weapons system officer died from hypothermia after landing in the sea and another from bleeding into the medulla oblongata after flailing; all other participants survived. This is an overall success rate of 97.6%. Of all 85 participants, 12 (14%) were uninjured, 41 (48.2%) were slightly injured, and 30 (35.3%) were severely injured. Typical injuries were those of the spine and lower limbs. The most common severe injury was a vertebral fracture caused by ejection acceleration. This is followed by lower limb injuries received during the parachute landing fall. At the time of ejection, all uninjured crews were flying below 3500 ft altitude and below 260 kn airspeed. Of all ejections from each aircraft type, the percentage of vertebral fractures is highest with the F-4 Phantom (31.8%), followed by the F-104 (16.6%) and the PA 200 Tornado with only 14.8%. The PA 200 is equipped with the most modern type of ejection seat of these aircraft. A conclusion of the gained data is that more modern ejection seat types provide lower injury severity but not fewer total injury numbers, and that the medical data taken during accident investigation should be taken more accurately and in a more standarized fashion to be comparable.
Accidents, Aviation↗
Nasal delivery of peptides: an in vitro cell culture model for the investigation of transport and metabolism in human nasal epithelium.
We investigated the transport- and metabolism properties of three peptides in monolayers of human nasal epithelial cells. The effective permeability coefficients of thyrotropin-releasing hormone, met-enkephalin and human recombinant insulin were found to be 4.5, 4.4 and 0.4 x 10(-7) cm/s, respectively. The permeability was inversely proportional to the molecular weight and one order of magnitude lower than in excised nasal mucosa of rabbits. The metabolic cleavage of thyrotropin-releasing hormone (TRH) to the free acid by cytosolic prolyl-endopeptidase was also detected in human nasal cell monolayers, suggesting that ca. 10% of the total amount of TRH is transported via a transcellular pathway. Met-enkephalin is a substrate for aminopeptidases, located on the apical membrane of nasal epithelial cells. Metabolites and enzyme activity are comparable with literature data. Our studies demonstrate that not only morphological, but also functional properties of human nasal epithelial cells are preserved under in vitro conditions. Such a cell culture model based on human nasal cells could be beneficial for the characterization of peptide transport on a cellular level and for investigation of the absorption enhancer mechanism. Further studies are necessary, however, to establish correlations between in vitro permeabilities in cell cultures and nasal drug absorption in animals and humans.
Administration, Intranasal↗
Continuous biological waste gas treatment in stirred trickle-bed reactor with discontinuous removal of biomass.
A new reactor for biological waste gas treatment was developed to eliminate continuous solvents from waste gases. A trickle-bed reactor was chosen with discontinuous movement of the packed bed and intermittent percolation. The reactor was operated with toluene as the solvent and an optimum average biomass concentration of between 5 and 30 kg dry cell weight per cubic meter packed bed (m3pb). This biomass concentration resulted in a high volumetric degradation rate. Reduction of surplus biomass by stirring and trickling caused a prolonged service life and prevented clogging of the trickle bed and a pressure drop increase. The pressure drop after biomass reduction was almost identical to the theoretical pressure drop as calculated for the irregular packed bed without biomass. The reduction in biomass and intermittent percolation of mineral medium resulted in high volumetric degradation rates of about 100 g of toluene m-3pb h-1 at a load of 150 g of toluene m-3pb h-1. Such a removal rate with a trickle-bed reactor was not reported before.
Air Pollutants↗
Selective inhibition of hepatic collagen accumulation in experimental liver fibrosis in rats by a new prolyl 4-hydroxylase inhibitor.
Fibrosis and cirrhosis of the liver are often the result of chronic liver damage by a variety of different agents. Pathological accumulation of collagen, disruption of the lobular structure, and impaired hepatocellular function frequently lead to systemic involvement and fatal complications. Drugs inhibiting collagen hydroxylation and accumulation are expected to improve this situation, making prolyl 4-hydroxylase (P4H), the key enzyme of intracellular collagen processing, a rational target for pharmacological intervention. S 4682, a novel inhibitor of purified P4H (Ki = 155 nmol/L), reduced hydroxyproline (Hyp) synthesis in chicken embryo calvaria (IC50 = 8.2 micromol/L) and in cultured hepatic stellate cells (HSC) (IC50 = 39 micromol/L). S 4682 inhibited hepatic collagen hydroxylation in vivo after metabolic labeling with [14C]proline. In the CCl4 model of chronic hepatic injury, characterized by histologically and biochemically evident fibrosis and highly elevated levels of serum procollagen type III N-peptide, S 4682 reduced hepatic collagen accumulation, decreased prevalence of ascites, and lowered serum procollagen type III N-peptide (PIIINP) levels. The hepatic Hyp content of drug-treated animals was closely correlated with serum levels of PIIINP S 4682 had no influence on Hyp content of heart, lung, and kidney.
Animals↗
[Computer-based training exemplified by the carotid artery].
The purpose of computer-based training (CBT) is interactive use of multimedia components, such as text, graphics, animation, sound, digital slide shows, and videos. This CD-ROM illuminates different aspects of carotid surgery: cerebrovascular insufficiency, sonographic and neuroradiological diagnostics, indications and results of carotid surgery in the literature, perioperative complications and new developments such as interventional procedures. Digital imaging (60 minutes of video sequences and 250 graphics) especially focus on operative standard procedures (conventional and eversion technique) and alternative methods. CBT is an evolving supplement to improve education programs in vascular surgery.
CD-ROM↗
Pharmacokinetics of mezlocillin and sulbactam under continuous veno-venous hemodialysis (CVVHD) in intensive care patients with acute renal failure.
OBJECTIVE: In intensive care medicine, continuous detoxication methods, such as continuous veno-venous hemodialysis (CVVHD), are used for treating acute renal failure. However, in contrast to conventional hemodialysis, little is known about the pharmacokinetics of many drugs administered in this setting and guidelines for dosages of drugs often do not exist. This holds particularly true for broad-spectrum antibiotics, which are often required during intensive care. METHODS: In this study, we investigated the pharmacokinetics of the acylureidopenicillin mezlocillin and the beta-lactamase inhibitor sulbactam during CVVHD and deduced dosage recommendations from the kinetic parameters with the goal of maintaining trough levels of above 10 mg.l-1 for mezlocillin and 5 mg.l-1 for sulbactam. Six intensive care patients with acute renal failure, receiving mezlocillin (n = 5) and/or sulbactam (n = 4), were examined during CVVHD and during intervals between CVVHD. The serum concentrations and the amounts of the drugs excreted into the dialyzate and into the urine within one dosage interval were measured using high performance liquid chromatography (HPLC). Three of the patients were jaundiced, indicating functional impairment of the liver. RESULTS: The clearances by CVVHD (CLCVVHD) for mezlocillin ranged between 11.0 and 44.9 ml.min-1 and the half lives ranged between 1.12 and 8.84 h. Low CL and long half lives were observed in the patients with jaundice. For sulbactam, CLCVVHD ranged between 10.1 and 22.8 ml.min-1 and serum half lives were 4.25-6.11 h, independent of liver function. CONCLUSION: Due to high hepatobiliary clearance of mezlocillin, dosage adjustments in patients with acute renal failure, treated by CVVHD, are needed only with concurrent impaired liver function. For sulbactam, the optimal dose was found to be 0.5 g, administered every 12 h, regardless of liver function.
Acute Kidney Injury↗
Effects of peptide structure on transport properties of seven thyrotropin releasing hormone (TRH) analogues in a human intestinal cell line (Caco-2).
We conclude that TRH and its analogues permeate mainly via paracellular routes in this particular clone of Caco-2 cells because variation in lipophilicity, polar surface properties, or hydrogen bonding potential-all influencing the transcellular pathway-do not give meaningful relationships. On the other hand, the variations in molecular size of the TRH analogues were too small to detect any influence on the paracellular transport properties. Further studies concerning the solution conformation and the hydrodynamical radii of the molecules probably give more information about the structure-permeability relationship of TRH transport across Caco-2 cell monolayers. The influence of the structural variations of these 7 TRH analogues on the binding affinity to the di- and tripeptide transporter, using another Caco-2 cell clone, are currently under investigation in our laboratory.
Biological Transport↗
Diagnosis and treatment of papillary cystic tumor of the pancreas in children.
We report on 3 children with a papillary cystic tumor of the pancreas. The patients presented with abdominal pain or a palpable tumor. All of them underwent complete tumor resection and spleen preservation was possible in 2 patients. Histologic examination showed a papillary cystic tumor of the pancreas. This tumor is characterized by a non-invasive growth pattern and metastasis is very rare. The boy described is the youngest male patient reported in the English literature. All patients are alive 6-51 months after diagnosis. Recognition of this entity is important because treatment differs from that of other pancreatic malignancies. Tumor resection without large safety margins is adequate for treatment. Therefore, preservation of pancreatic tissue and the spleen should be attempted in every child.
Adolescent↗
Effects of permeation enhancers on the transport of a peptidomimetic thrombin inhibitor (CRC 220) in a human intestinal cell line (Caco-2).
PURPOSE: The effects of five different permeation enhancer systems on the transport properties of a peptidomimetic thrombin inhibitor. CRC 220, were investigated in monolayers of a human intestinal cell line (Caco-2). METHODS: The transepithelial transport rates and additionally the cytotoxic properties of these enhancers were characterized using the following tests: measurement of the transepithelial electrical resistance (TEER), the MTT-transformation, the protein content and the release of cytosolic lactate dehydrogenase (LDH), as well as FITC-phalloidin and propidium iodide staining. RESULTS: All permeation enhancer systems showed concentration-dependent effects on cell permeability and toxicity. The most prominent effects on peptide transport were seen at the highest concentration (40 mM), yielding the rank order, NaTC > NaTC/Cholesterol > Solulan C24 > NaTC/Oleic acid > NaTC/PC18. Using the TEER after 120 min exposure as the most sensitive parameter describing cytotoxicity, the following order was obtained: Solulan C24 > NaTC > NaTC/PC18 = NaTC/Cholesterol > NaTC/Oleic acid > NaTC/PC. Generally, efficient enhancement of peptide transport was associated with a noticeable influence on cell viability under in-vitro conditions. CONCLUSIONS: Taking into account permeation and cytotoxicity as a function of concentration, both NaTC at 15 mM and the mixed micellar system NaTC/oleic acid at 0.75 mM offer interesting enhancement properties, showing an 18-fold increase in CRC 220 transport rates. The effects on cell viability and cytotoxicity were comparatively low and of reversible nature.
Antithrombins↗
In-vitro cell culture models of the nasal epithelium: a comparative histochemical investigation of their suitability for drug transport studies.
PURPOSE: To evaluate different in-vitro cell culture models for their suitability to study drug transport through cell monolayers. METHODS: Bovine turbinate cells (BT; ATCC CRL 1390), human nasal septum tumor cells (RPMI, 2650; ATCC CCL 30), and primary cell cultures of human nasal epithelium were characterized morphologically and histochemically by their lectin binding properties. The development of tight junctions in culture was monitored by actin staining and transepithelial electrical resistance measurements. RESULTS: The binding pattern of thin-sections of excised human nasal respiratory epithelium was characterized using a pannel of fluorescently-labelled lectins. Mucus in goblet cells was stained by PNA, WGA and SBA, demonstrating the presence of terminal N-acetylglucosamine, N-acetylgalactosamine and galactose residues respectively in the mucus of human nasal cells. Ciliated cells revealed binding sites for N-acetylglucosamine, stained by WGA, whereas Con A, characteristic for mannose moieties, labelled the apical cytoplasm of epithelial cells. Binding sites for DBA were not present in this tissue. Comparing three different cell culture models: BT, RPMI 2650, and human nasal cells in primary culture using three lectins (PNA, WGA, Con A) as well as intracellular actin staining and transepithelial electrical resistance measurements we found, that only human nasal epithelial cells in primary culture showed differentiated epithelial cells, ciliated nasal cells and mucus producing goblet cells, which developed confluent cell monolayers with tight junctions. CONCLUSIONS: Of the in-vitro cell culture models studied, only human nasal cells in primary culture appears to be suitable for drug transport studies.
Actins↗
The convergence of abortion regulation in Germany and the United States: a critique of Glendon's Rights Talk thesis.
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Abortion, Legal↗
[Liver metastases in breast carcinoma. Results of partial liver resection].
Within 11 years we performed 35 liver resections in 34 patients with liver metastases of breast cancer. The median age was 47 years. The median interval between the primary operation and the liver resection was 27.3 months. 59% of the patients had a solitary metastases. A curative (R0) resection was possible in 86%. Operative mortality was 3% (n = 1). Overall 5-year survival was 18.4% (median 27 months). Prognosis was significantly (p < 0.001) better following R0-resection (22%, median 41.5 months) than after R1/2-resection (maximum 20 months, median 5 months). Beside the radicality an unfavorable influence on the prognosis could be demonstrated only for a prior local recurrence of the primary tumor (p < 0.05). If a R0-resection was possible stage of the primary tumor, number and size of the metastases, and extension of the operative procedure were without prognostic significance. We conclude that patients with isolated liver metastases of breast cancer can have a long lasting benefit from liver resection. In individual cases even cure may be possible.
Adult↗
3D imaging of the collision-induced Coulomb fragmentation of water molecules.
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Journal Article↗
Development of a human nasal epithelial cell culture model and its suitability for transport and metabolism studies under in vitro conditions.
A human nasal epithelial cell culture model has been adapted to observe transport and metabolism of drugs, e.g., peptides. Human nasal epithelial cells, isolated by protease treatment of human nasal conchae, grew to confluency after 6-8 days using DMEM supplemented with 1% nonessential amino acids, 1% glutamine, 10% FCS and 1% antibiotics. These cultures expressed microvilli and actively beating cilia as documented by light microscopy and scanning electron microscopy (SEM). Tight junctions were confirmed by dome formation and positive actin staining using FITC-labelled phalloidin. Preliminary transport studies, carried out with FITC-labelled Dextran (FD 4, MW 4400) and Sulforhodamine (SR 101, MW 607), demonstrated the intact barrier function of the cultured monolayer, grown on filter membranes. In addition, the cultured cells metabolized Leu-Enkephalin to Des-Tyr-Leu-Enkephalin demonstrating the presence of aminopeptidase, a naturally occurring enzyme in the human nasal mucosa.
Actins↗
Effects of flezelastine and its enantiomers on LPS-induced IL-1 beta generation in vitro and LPS-induced pyrexia in vivo.
The effects of the novel antiasthmatic/antiallergic compound flezelastine on LPS-induced actions were investigated in vitro and in vivo. In monocytes, IL-1 beta generation stimulated by LPS was inhibited dose dependently. In vivo, LPS-induced fever in rats, which is at least partly driven by the release of IL-1 beta, was also inhibited by flezelastine. These findings suggest that flezelastine inhibits IL-1 synthesis and/or release in vitro and in vivo.
Animals↗