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Biomedical subjects

W Beyer

Publications and source records attributed to W Beyer.

At least 19 recordsLinked to original sources

Localized metallic conductivity and self-healing during thermal reduction of SrTiO3.

The occurrence of metallic conductivity in SrTiO3 single crystals is reported for reduction under low partial pressure of oxygen at 800 degrees C. This transition is shown to result from the formation of a high concentration of vacancy defects along a network of extended defects within the skin region. A self-healing phenomenon is observed for progressive reduction which causes the concentration of initially introduced defects to decrease in the course of heat treatment and leads to a breakdown of the metallic conductivity as well as a substantial loss of optical subgap absorption.

Journal Article↗

Lightdosimetric quantitative analysis of the human petrous bone: experimental study for laser irradiation of the cochlea.

BACKGROUND AND OBJECTIVE: Application of laser irradiation targeting the inner ear has to be investigated for therapeutic effectiveness in cochlear injury and dysfunction. In vitro data demonstrate low-level laser-induced photochemical and photobiologic cell response, depending on cell type and irradiation parameters such as light dose. The aim of the presented study was to determine the light dose received by the cochlear hair cells by using different irradiation modalities for the human petrous bone. STUDY DESIGN/MATERIALS AND METHODS: Lightdosimetric assessment was performed in human cadaver temporal bones (n = 13) after removing the cochlear membranous labyrinth. The external auditory meatus, the tympanic membrane (quadrants), and the mastoid bone were illuminated by a helium-neon laser (lambda = 593 nm) and diode lasers of different wavelengths (lambda = 635, 690, 780, and 830 nm). The spatial distribution of transmitted light in the cochlear windings was measured by means of a retrocochlearly positioned endoscopic CCD camera for image processing and was assigned to acoustic frequencies according to the tonotopic organization of the cochlea. For an estimation of the corresponding space irradiance in an intact cochlea, correction factors have been calculated by a Monte Carlo procedure on the basis of experimentally determined optical properties of skull bone. RESULTS: The transmission of light across the tympanic cavity and the promontory depends strongly on wave-length of the laser and the position of the radiator. Transtympanal irradiation results in spatial intensity variations of a factor 4 to 10 within the cochlear windings. The space irradiance in an intact cochlea is 10 to 20 times the measured irradiance. For an irradiation of the mastoid, the light transmission within the cochlea is 10(3) to 10(5) times smaller compared with an irradiation of the tympanic membrane and is extremely variable for different specimens. CONCLUSION: The strong dependence of the cochlear light distribution on various irradiation parameters demonstrates the impact of preclinical lightdosimetric investigations for effective individual laser irradiation of the human cochlea. Because of the observed spatial intensity variations, the optimal external light dose has to be chosen with regard to the tonotopy of the human cochlea. The obtained results are enabling us to apply defined laser light doses to different cochlear winding areas. Mastoidal irradiation leads to therapeutically insufficient light doses within reasonable treatment times, whereas transmeatal irradiation is recommendable. Further studies are mandatory for development of clinical devices for transmeatal irradiation of the cochlea.

Cadaver↗

Immunisation with Salmonella typhimurium-delivered glyceraldehyde-3-phosphate dehydrogenase protects mice against challenge infection with Echinococcus multilocularis eggs.

Recombinant glyceraldehyde-3-phosphate dehydrogenase of the cestode parasite Echinococcus multilocularis was expressed in Escherichia coli and in Salmonella typhimurium. The potential of different forms of the recombinant antigen to protect BALB/c mice against oral challenge infections with E. multilocularis eggs was evaluated. Oral or intraperitoneal immunisation with live attenuated S. typhimurium as a carrier for recombinant glyceraldehyde-3-phosphate dehydrogenase of the E. multilocularis resulted in significant protection, reducing the number of developing metacestodes up to 79.8%. The sera of protected animals did not contain detectable amounts of antibody against glyceraldehyde-3-phosphate dehydrogenase of E. multilocularis. By contrast, although anti-glyceraldehyde-3-phosphate dehydrogenase of E. multilocularis antibodies were detectable in the sera, immunisation with E. coli-expressed recombinant glutathione-S-transferase-fusion protein or with glyceraldehyde-3-phosphate dehydrogenase of E. multilocularis fused to a 6HIS-tag failed to protect the animals against oral challenge infections. These data emphasise that antigen delivery systems play a critical role in vaccination and the induction of protective immunity against helminth parasites.

Amino Acid Sequence↗

Reduction of striatal glucose metabolism in McLeod choreoacanthocytosis.

McLeod syndrome is a distinct form of neuroacanthocytosis. Its defining feature is the depression of erythrocyte Kell antigens. The underlying X chromosomal mutations cause a dysfunction of an erythrocyte membrane protein Kx. A choreatic movement disorder with caudate atrophy in CT and MRI has been reported in McLeod syndrome later in the course of the disease. Positron emission tomography with 18F-deoxyglucose (FDG) was performed in two unrelated affected men. In the older patient, progressive chorea was seen from the 5th decade. In the second patient there were no signs of a movement disorder at the age of 28. Positron emission tomography disclosed a reduction of the striatal FDG uptake in both patients, with accentuation in patient 1. Frontal lobe metabolism was not affected. Basal ganglia dysfunction with early impairment of striatal glucose metabolism thus seems obligatory for McLeod syndrome, as found in other forms of chorea with or without acanthocytosis.

Adolescent↗

Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan.

UNLABELLED: FDG PET is increasingly performed in patients with differentiated thyroid cancer who present with elevated human thyroglobulin (hTG) levels and negative 131I scan. The aim of this study was to evaluate the impact of FDG PET on treatment in these patients. METHODS: A total of 118 FDG PET studies were performed on 64 patients, and follow-up data were available for all patients. Whole-body images were acquired 1 h after intravenous injection of 370 MBq (10 mCi) FDG using a PET scanner with an axial field of view of 16.2 cm. Tumor-suspicious FDG PET studies were evaluated by histology, cytology, 131I uptake, CT or MRI, and follow-up of hTg levels. The therapeutic consequence was noted for each patient. Moreover, results of FDG PET were correlated with hTg levels. RESULTS: Forty-four patients had positive scans, which were proven to be true-positive in 34 patients, whereas 7 patients had false-positive findings. Two patients exhibited a secondary malignancy. One patient did not fit in any category, having true-positive, false-positive, and false-negative findings. On the other hand, 20 patients had negative scans. These were true-negative findings in 5 patients, whereas the remaining 15 patients had false-negative results. Accordingly, the positive predictive value of FDG PET was 83% (34/41), whereas the negative predictive value was 25% (5/20). Treatment was directly changed in 19 of 34 patients with true-positive PET studies: 18 patients had further surgery, and 4 patients were referred for external irradiation, 3 of them after incomplete removal of local recurrences. FDG PET showed widespread disease in 7 patients; thus, palliative treatment, rather than curative therapy, was initiated. True-positive FDG PET findings were correlated positively with increasing hTg levels (i.e., FDG PET was true-positive in 11%, 50%, and 93% of patients with hTg levels of <10, 10-20, and >100 microg/L, respectively). CONCLUSION: FDG PET is a valuable diagnostic tool in patients with differentiated thyroid cancer who present with increased hTg levels and negative 131I scans because it permits selection of patients for surgery, which may be curative. FDG PET is most promising at hTg levels of >10 microg/L.

Adult↗

Activation of the erythropoietin receptor by the gp55-P viral envelope protein is determined by a single amino acid in its transmembrane domain.

The spleen focus forming virus (SFFV) gp55-P envelope glycoprotein specifically binds to and activates murine erythropoietin receptors (EpoRs) coexpressed in the same cell, triggering proliferation of erythroid progenitors and inducing erythroleukemia. Here we demonstrate specific interactions between the single transmembrane domains of the two proteins that are essential for receptor activation. The human EpoR is not activated by gp55-P but by mutation of a single amino acid, L238, in its transmembrane sequence to its murine counterpart serine, resulting in its ability to be activated. The converse mutation in the murine EpoR (S238L) abolishes activation by gp55-P. Computational searches of interactions between the membrane-spanning segments of murine EpoR and gp55-P provide a possible explanation: the face of the EpoR transmembrane domain containing S238 is predicted to interact specifically with gp55-P but not gp55-A, a variant which is much less effective in activating the murine EpoR. Mutational studies on gp55-P M390, which is predicted to interact with S238, provide additional support for this model. Mutation of M390 to isoleucine, the corresponding residue in gp55-A, abolishes activation, but the gp55-P M390L mutation is fully functional. gp55-P is thought to activate signaling by the EpoR by inducing receptor oligomerization through interactions involving specific transmembrane residues.

Amino Acid Sequence↗

Photodynamic therapy in women with cervical intraepithelial neoplasia using topically applied 5-aminolevulinic acid.

Photodynamic therapy (PDT) is a novel treatment modality that produces local tissue necrosis with laser light after prior administration of a photosensitizing agent. We performed a study of topically applied 5-aminolevulinic acid (5-ALA) in the photodynamic treatment of women with high-grade cervical intraepithelial neoplasia (CIN) using fixed 5-ALA doses and application protocols derived from previous in vitro and in vivo results. Three to 5 hr prior to PDT, 10 ml of a 20% solution of 5-ALA was topically applied using a cervical cap. PDT was performed with irradiation of 100 J/cm2 at an irradiance of 100-150 mW/cm2 with an argon-ion-pumped dye laser at 635 nm. For the endocervix, a specifically designed cylindrical applicator was used. Ten treatment cycles of PDT using 5-ALA were performed in 7 patients with high-grade CIN. Non-thermal laser treatment with 100-150 mW/cm2 was well tolerated. Local toxicity was minor as several patients reported burning sensations and vaginal discharge, but no necrosis, sloughing or scarring occurred. After 3 months, a significant reduction in the size of the ectocervical CIN lesions was noted in only 3 patients, who underwent a second PDT cycle. However, no significant improvement in CIN lesions was noted since cold knife conization revealed persistent CIN in all 7 cases. Therefore, PDT after topical application of 5-ALA using an irradiation of 100 J/cm2 produces only minimal side effects. However, it does not appear to be effective in treating CIN.

Administration, Topical↗

Polymerase chain reaction-ELISA to detect Bacillus anthracis from soil samples-limitations of present published primers.

A polymerase chain reaction (PCR)-ELISA technique to detect Bacillus anthracis from soil samples has been developed. The application of streptavidine-coated microtitre plates as well as plates covered with covalently linked oligonucleotides as catching probes led to a test sensitivity of about 100 fg pure genomic DNA or of less than 10 spores seeded into 100 g soil material. Some non-suspicious soil samples collected from different locations yielded positive results with presently published primers or probes targeting the B or C gene of pX02 and with primers targeting the chromosomal sequence B813. The former PCR products were sequenced. The number and mode of base exchanges led to the assumption that there will exist at least one unknown soil organism with high similarity within highly conserved capsule-encoding genes.

Amino Acid Sequence↗

Ecstasy--long-term effects on the human central nervous system revealed by positron emission tomography.

BACKGROUND: The main psychotropic agent of the popular illicit drug ecstasy is 3,4-methylenedioxymethamphetamine (MDMA). In the light of animal studies and examinations of human cerebrospinal fluid, MDMA is suspected of causing neurotoxic lesions to the serotonergic system. AIMS: To postulate a relationship between ecstasy use and lasting alterations to the cerebral glucose metabolic rate. METHOD: Positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) was performed on seven ecstasy users and seven subjects without any known history of illicit drug use. Data were compared for a limited number of brain regions. RESULTS: By comparison with the control group, the glucose metabolic uptake of the ecstasy user group was altered within the amygdala, hippocampus and Brodmann's area II. CONCLUSIONS: The results suggest the possibility that ecstasy use has lasting effects on central neuronal activity in humans.

Adult↗

[The use of molecular fingerprinting techniques in environmental hygiene].

The analysis of epidemiological pathways for the transmission of pathogens via the environment is a fundamental task in the field of environmental hygiene. The task demands for a precise differentiation between isolates. This can be done by sophisticated techniques for differentiation which are based on phenotypic or genotypic features. The fingerprinting of DNA is a powerful tool in this context. A survey is given for different kinds of RFLP-analysis, plasmid profiling, and PCR fingerprinting as well regarding their principles, methodical variations and published applications. Notable limitations of the applications are also discussed.

Animal Diseases↗

[Recent methods for the detection of airborne microorganisms and source identification].

The detection of airborne microorganisms including selected cell constituents (e.g. allergens or endotoxins) depends on suitable methods and instruments for their collection. Furthermore, microbiological methods are necessary for their quantification and qualification. In the past these methods were largely based on the classical cultivation dependent approach. Modern molecular methods, e.g. direct staining procedures, hybridization assays with nucleic acids including the PCR-technology or immunological assays are promising new tools for a more sophisticated detection of bioaerosols. They allow a better detection rate, a more precise identification of certain members of the aerosol including cell constituents. With respect to speed and lower costs they are an important alternative to established detection methods.

Air Microbiology↗

[Phosphate deficiency as a rare cause of osteomalacia--case report of several years of enteral feeding and antacid therapy].

HISTORY AND CLINICAL FINDINGS: Floor-of-the-mouth cancer had been diagnosed and surgically treated in a 55-year-old man 4 years before the latest admission. For the last 3 years he had been fed through a percutaneous endoscopic gastrostomy (PEG). Since then he had experienced reflux oesophagitis which was being treated with aluminium-containing antacids. He was hospitalized for the surgical treatment of bilateral fractures of the neck of the femur. A surgical biopsy revealed osteomalacia but no metastasis. INVESTIGATIONS: The serum phosphate level was significantly reduced (0.21 mmol/l) and there was no detectable phosphate excretion in the 24-hour urine. Serum calcium concentration was unremarkable, but there was hypercalciuria (34.4 mmol/d). Alkaline phosphate activity was significantly raised (393 U/l) and parathormone level reduced (7 ng/l). Vitamin D concentration was unremarkable. TREATMENT AND COURSE: The phosphate content in the parenteral feed was at first increased and additional phosphate was given by mouth. The calcium and phosphate levels slowly became normal only after medication had been changed from antacids to H2-blockers. CONCLUSIONS: In this case osteomalacia was caused not by vitamin D deficiency but by a lack of phosphate. The reduced intestinal phosphate absorption by the antacids only partially explains the pronounced clinical signs. If antacids are taken over long periods the phosphate balance should be carefully monitored to avoid osteomalacia.

Alkaline Phosphatase↗

The anemic Friend virus gp55 envelope protein induces erythroid differentiation in fetal liver colony-forming units-erythroid.

The gp55 envelope proteins of the spleen focus-forming virus initiate erythroleukemia in adult mice. Because the gp55 from the polycythemic strain (gp55-P), but not from the anemic strain (gp55-A), activates the erythropoietin receptor (EpoR) for proliferation of hematopoietic cell lines, the mechanism by which gp55-A initiates erythroleukemia has remained a mystery. We show here that gp55-A activates the EpoR in fetal liver cells. In contrast to previous studies using bone marrow cells from phenylhydrazine-treated, anemic mice, we find that both gp55-A and gp55-P induce erythroid differentiation from colony-forming unit-erythroid (CFU-E) progenitors in fetal liver cells. The effects on CFU-Es of both gp55-A and -P are mediated by the EpoR, because no colonies are seen upon expression of either gp55 in EpoR-/- fetal liver cells. However, only gp55-P induces erythroid bursts from burst-forming unit-erythroid progenitors and only gp55-P induces Epo independence in Epo-dependent cell lines. Using chimeric gp55 P/A proteins, we extend earlier work showing that the transmembrane sequence determines the capacity of gp55 proteins to differentially activate EpoR signaling. We discuss the possibilities for different signaling capacities of gp55-A and -P in fetal liver and bone marrow-derived erythroid progenitor cells.

Animals↗

Histological verification of positive fluorine-18 fluorodeoxyglucose findings in patients with differentiated thyroid cancer.

Fluorine-18 fluorodeoxyglucose and positron emission tomography (FDG-PET) is a new imaging modality used in the follow-up of patients with differentiated thyroid cancer if the results of (131)I scintigraphy are negative in spite of an elevated thyroglobulin level. The aim of this retrospective analysis was to estimate the value of FDG-PET regarding the operability of patients with positive findings. From January 1994 to October 1997, we investigated 60 patients with differentiated thyroid carcinoma by FDG-PET. Thirteen patients were operated on after positive findings. Most of these lesions were suspected of having lymph-node involvement or local recurrences in the thyroid bed. One patient showed a solitary distant metastasis in the scapula. Thirteen of 16 operations in these 13 patients confirmed the suspected involvement of thyroid cancer. The false-positive findings were caused by inflamed lymph nodes in two cases and benign thymus tissue in one case. We conclude that PET is a useful diagnostic tool to guide early surgical therapy in patients with (131)I negative differentiated thyroid carcinoma.

Adenocarcinoma, Follicular↗

[Computerized tomography and F-18-FDG positron emission tomography in staging of malignant lymphomas: a comparison].

PURPOSE: To determine the value of F-18-FDG-positron emission tomography (FDG-PET) compared with computed tomography (CT) in the staging of malignant lymphomas. MATERIAL AND METHOD: 50 patients with biopsy-proven lymphoma were studied with FDG-PET and CT. The results in initial, posttherapeutic and staging of recurrence were compared. RESULTS: 37 of 65 FDG-PET were identical with CT. 28 studies showed differences. 14 post-therapeutically and one of the initial studies led to downstaging by FDG-PET were as upstaging resulted in one case of initial staging. In two cases false positive pulmonary FDG accumulations caused an upstaging. CONCLUSION: FDG-PET was at least comparable to CT in recording the extension of a newly diagnosed lymphoma, or its recurrence. Upstaging according to FDG-PET occurred only once in initial staging. FDG-PET plays its most important role in the evaluation of residual mass in CT after therapy by accumulating FDG in viable tumour rather than in fibrotic tissue. 14 cases of downstaging according to FDG-PET resulted.

Adolescent↗

Suitability of repetitive-DNA-sequence-based PCR fingerprinting for characterizing epidemic isolates of Salmonella enterica serovar Saintpaul.

Three molecular typing methods, repetitive-sequence-based PCR (rep-PCR) fingerprinting, plasmid profiling, and arbitrarily primed PCR fingerprinting, were used to characterize isolates of Salmonella enterica serovar Saintpaul. Most of the isolates were obtained from epidemic human cases of food-borne salmonellosis, together with some from the food material suspected to be the source of infection, and a few were obtained from other cases apparently not related to the epidemic. All three methods adequately discriminated the epidemic strain from other strains of the serovar. In addition several isolates from human cases which are not identical to the epidemic strain were found. These isolates therefore must have been responsible for some sporadic infections, which were only temporally related to the epidemic. These strains showed a high degree of similarity to a strain isolated from a turkey. rep-PCR fingerprinting with REP-Dt primers and primer ERIC1R, applicable even to crude cell lysates, offers an attractive choice as a primary method for the discrimination of various Salmonella serotypes as well as isolates within serotype Saintpaul.

Bacterial Typing Techniques↗

[Chest X ray: routine indication in the follow-up of differentiated thyroid cancer?].

AIM: This retrospective study sought to elucidate whether routine chest x-ray is still useful for detection of pulmonary metastases in low risk patients despite the high sensitivity of the tumor marker thyroglobulin. METHOD: The hospital files of 609 patients with well-differentiated thyroid cancer were analysed. Pulmonary formation of metastases was diagnosed in 50 patients. The thyroglobulin value at the time of diagnosis was compared with the chest x-ray findings and, if present, additional diagnostic information such as Iodine-131 whole body scintigraphy (WBS) and thorax CT. RESULTS: The sensitivity of the chest x-ray to detect pulmonary metastases was at 52% lower than that of WBS (64%), thorax CT (82%) and thyroglobulin during suppression therapy (86%). Among the patients with papillary carcinoma stage I and II (UICC 1987), only 1 patient developed pulmonary metastases during follow up. In this low risk group of patients, detection of lung metastases exclusively by chest x-ray, without elevation of thyroglobulin level is extremely rare (calculated probability 1/4000) and associated with considerable costs. CONCLUSION: Routine, life long chest x-ray in low risk patients without a suspected recurrence (e.g. positive thyroglobulin) needs to be reconsidered.

Carcinoma, Papillary↗

Whole-body positron emission tomography (PET) for diagnosis of residual mass in patients with lymphoma.

BACKGROUND: PET using 18fluorodesoxyglucose (FDG) may offer the possibility of differentiating vital from necrotic residual masses. PATIENTS AND METHODS: Seventeen patients with HD and 17 patients with NHL underwent FDG-PET following therapy. According to staging by routine methods at diagnosis, 7 patients presented stage I, 13 stage II, 5 stage III, and 9 stage IV. A dose of 250-400 MBq FDG was injected and whole-body PET was performed 30-60 minutes later. RESULTS: Residual mass was found in 32 patients with routine methods. FDG-PET was negative in 17 patients, who were considered to be in CR. None of them relapsed (median follow-up 63 weeks ). FDG-PET was positive in 17 patients. Sixteen patients had residual mass with routine methods. Four patients received radiation after PET. Their median follow-up is 58 weeks without relapse. Two other patients with lasting CR had FDG uptake outside the residual mass--one with confirmed pneumonia. Five patients had histologically confirmed lymphoma, 2 patients relapsed according to routine methods. One patient is likely to be false positive because of fracture at lymphoma site. Seven of 10 patients with FDG uptake in the residual mass after completed therapy relapsed. According to routine restaging, 2 patients achieved CR. In 1 patient an additional focus was found in the humerus in spite of normal scintigraphy with histologically confirmed lymphoma. There were no false-negative results, but 3 false-positive results inside and 2 false-positive results outside the residual mass after completed therapy. CONCLUSIONS: PET performed for evaluation of residual mass after treatment of lymphoma has a high predictive value.

Adult↗