28 results on '"Helmuth R"'
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2. Decomposing kernels of iterated operators—a unified approach
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Ren, Guangbin and Malonek, Helmuth R.
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For any operator Dacting in an Abelian group, we study the kernel of its iterates Dkand describe a general approach for decomposing it through the kernel of the operator Ditself and some other given operators T1,…,Tk−1. Due to Almansi's famous theorem for polyharmonic functions the different types of decomposition are characterized in terms of strong, weak and restricted Almansi decomposition properties. Sufficient conditions are given for the existence of such decompositions. The case of the iterated Dirac operator (cf. Math. Meth. Appl. Sci.2002; 25:1541–1552) follows as a special case. Several other special cases are discussed. Finally we prove corresponding decomposition theorems for the iterated weighted Laplacian (|x|αΔ)k, α∈(−∞, 2), and the iterated Helmholtz type operator (Δ−λ)k, λ∈C. Copyright © 2006 John Wiley & Sons, Ltd.
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- 2007
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3. Characterization and Localization of Drug Resistance Determinants in Multidrug-Resistant, Integron-Carrying Salmonella enterica Serotype Typhimurium Strains
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Guerra, B., Junker, E., Miko, A., Helmuth, R., and Mendoza, M.C.
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The genetic background of the antimicrobial resistance of 10 selected multiresistant Salmonella serotype Typhimurium (S. Typhimurium) strains (including the emerging monophasic variant [4,5,12:i:- ]) was investigated. All strains shared class 1 integrons (with seven types of variable regions) and belonged to different lineages (L1–L6) according to their phage types, DNA polymorphisms by XbaI-pulsed-field gel electrophoresis (PFGE), integrons, and/or resistance patterns. The strains were screened for the presence and localization (chromosomal or plasmid) of 32 DNA sequences representing integron-, Tn21-like transposon-, resistance-, and virulence-plasmid genes. Strains belonging to lineage L1 (definitive phage type DT104) carried the 90-kb Salmonella virulence plasmid together with the complete or partial chromosomally located Salmonella Genomic Island 1 (SGI1). All strains belonging to the other five lineages carried their resistance determinants on various resistance plasmids. Two of these strains showed complex plasmid profiles, which included a 95kb virulence plasmid together with two or four resistance plasmids. Two strains carried a resistance plasmid that lacked the virulence-plasmid-encoding sequences. The remaining two strains carried two different hybrid virulence-resistance plasmids. Twenty-three of the DNA sequences could be assigned to distinct XbaI genomic restriction patterns (PFGE profiles). In this way, the influence of the resistance and virulence plasmids on the PFGE profiles was determined, and several groups of resistance genes could be identified. The data obtained represent a useful epidemiological tool for tracing the emergence and distribution of multiresistant S. Typhimurium worldwide.
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- 2004
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4. Almansi-type theorems in Clifford analysis
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Malonek, Helmuth R. and Ren, Guangbin
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In this paper, we consider functions defined in a star-ike omain Ω⊂ℝn with values in the Clifford lgebra Cℓ
0,n which are polymonogenic with respect to the (left) Dirac operator D=∑j=1 n ej ∂/∂xj , i.e. they belong to the kernel of Dk. We prove that any polymonogenic function f has a ecomposition of the formf=f , where x=x1 +xf2 +···+xk−1fk 1 e1 +···+xn en and fj, j=1, ,k, are monogenic functions. This generalizes classical Almansi theorem for polyharmonic functions as well e Fischer decomposition of polynomials. Similar results tained for the powers of weighted Dirac operators of the form &Dtilde;=∣x∣−αxD, α∈ℝ\{0}. Copyright © John Wiley & Sons, Ltd.- Published
- 2002
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5. Almansi‐type theorems in Clifford analysis
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Malonek, Helmuth R. and Ren, Guangbin
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In this paper, we consider functions defined in a star‐ike omain Ω⊂ℝnwith values in the Clifford lgebra C𝓁0,nwhich are polymonogenic with respect to the (left) Dirac operator D=∑j=1nej∂/∂xj, i.e. they belong to the kernel of Dk.
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- 2002
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6. Monitoring of antibiotic resistance in bacteria of animal origin: epidemiological and microbiological methodologies
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Caprioli, A., Busani, L., Martel, J. L., and Helmuth, R.
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- 2000
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7. A hypercomplex derivative of monogenic functsions in [image omitted] and its Applications
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Gürlebeck, K. and Malonek, Helmuth R.
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We generalize the definition of a certain derivative of regular functions of variables from the four-dimensional real associative algebra of quaternions to monogenic functions of hypercomplex variables in Rn+1. Using this concept of derivation we look for primitives of monogenic functions in the set of monogenic functions. The results will be applied for proving a final result about the invertibility of a hypercomplex II-operator.
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- 1999
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8. Ideomotor Apraxia in Left Thalamic Hemorrhage: Discrepancy between Clinical Course and SPECT
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Schnider, Armin, Landis, Theodor, and Rösler, Helmuth R.
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We present a patient who developed severe ideomotor apraxia (IA) and subcortical aphasia after a hemorrhage involving the posterior part of the left thalamus and the posterior limb of the internal capsule. The cerebral blood flow (CBF) of the left hemisphere as measured by 99Tc-HM-PAO SPECT was initially diminished as compared to the right hemisphere. The apraxia and aphasia eventually resolved. Despite this clinical improvement CBF of the left hemisphere worsened. Our findings do not support the view that apraxia and aphasia following lesion of deep subcortical structures is due to cortical derangement induced by disruption of unspecific activating thalamo-cortical pathways. The results call for caution in the functional interpretation of perfusion deficits detected by SPECT.
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- 1991
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9. Reappraisal of the Autoclave Expansion Test
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Helmuth, R and West, PB
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This report re-examines the technical basis for the AET as presented in PCA Research Department Bulletin RX45 as well as more recent research. The focus is on the potential for disruptive expansions caused by crystalline MgO in portland cements hydrated under various conditions, including the AET. Much of the data indicates that the AET would be a good test for unsoundness caused by free CaO alone, but that expansions in the AET caused by MgO and C3A do not correlate well with disruptive expansions under ordinary conditions. Consideration of expansive reaction mechanisms and the published data indicate that MgO continues to hydrate slowly under a wide range of conditions and that stress-relief mechanisms and stabilization processes apparently operate to prevent disruptive expansions in moist environments. Since these mechanisms may not operate as well in dry environments, there are undetermined risks with respect to reliance on performance tests that do not cause hydration of MgO. Investigation of these mechanisms is recommended so that portland cement soundness and performance can be assured, perhaps without reliance on the AET.
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- 1998
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10. Toward a population genetic analysis of Salmonella: genetic diversity and relationships among strains of serotypes S. choleraesuis, S. derby, S. dublin, S. enteritidis, S. heidelberg, S. infantis, S. newport, and S. typhimurium.
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Beltran, P, Musser, J M, Helmuth, R, Farmer, J J, Frerichs, W M, Wachsmuth, I K, Ferris, K, McWhorter, A C, Wells, J G, and Cravioto, A
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Variation in the chromosomal genomes of 1527 isolates of eight common serotypes (O and H antigen profiles) of Salmonella was assessed by analysis of electrophoretically demonstrable allelic polymorphism at 23 metabolic enzyme loci. Seventy-one distinctive electrophoretic types, representing multilocus genotypes, were identified. A basically clonal population structure was indicated by the presence of strong linkage disequilibrium among enzyme loci, the association of each serotype with a relatively small number of multilocus enzyme genotypes, and the global distribution of certain genotypes. For each of six of the serotypes, 83-96% of isolates were members of a single clone. The occurrence of each of four serotypes (S. derby, S. enteritidis, S. infantis, and S. newport) in isolates of clones belonging to several evolutionary lineages, some of which are distantly related, suggests that the horizontal transfer and recombination of chromosomal genes mediating expression of cell-surface antigens has been a significant process in the evolution of the salmonellae. Two divergent clone clusters of S. derby differ in the relative frequency with which they cause disease in birds versus mammals, and two major lineages of S. newport differ in the frequency with which their clones are associated with disease in humans versus animals.
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- 1988
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11. DR2 haplotypes (DRB1, DQA1, DQB1) associated with systemic lupus erythematosus
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Bettinotti, María P., Hartung, Klaus, Deicher, Helmuth R. G., Keller, Elisabeth, Mikschl, Sabine, and Albert, Ekkehard
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- 1993
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12. Cloning of enterotoxin gene from Aeromonas hydrophila provides conclusive evidence of production of a cytotonic enterotoxin
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Chakraborty, T, Montenegro, M A, Sanyal, S C, Helmuth, R, Bulling, E, and Timmis, K N
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Culture filtrates of two Aeromonas hydrophila strains which were isolated from patients with diarrhea and assumed to be causative agents of the infections were shown to contain enterotoxic, cytotoxic, and hemolytic activities. Modest heat treatment of the filtrates inactivated the cytotoxic and cytolytic activities, but not the enterotoxic activity. The construction of cosmid gene banks in Escherichia coli of DNA from both A. hydrophila strains demonstrated that the determinants of the three activities are located on three different segments of the A. hydrophila chromosome. Both heated culture filtrates of A. hydrophila and nonheated filtrates of an E. coli clone containing the A. hydrophila enterotoxin gene provoked fluid accumulation in the rabbit ileal loop and suckling mouse models and caused elongation of Chinese hamster ovary cells. Differences in the responses of the models to the A. hydrophila enterotoxin and to the heat-labile and heat-stabile toxins of E. coli indicated that the former is distinct from the latter two types of toxin. These results constitute conclusive evidence for the production by A. hydrophila of a cytotonic enterotoxin that is distinct from the A. hydrophila cytotoxin and hemolysin and known E. coli enterotoxins.
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- 1984
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13. Discussion: The effect of pulverized-fuel ash upon the workability of cement paste and concrete*
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Jensen, Jens Kr. Jehrbo, Hobbs, D. W., Ong, L. T., Ellis, C., Helmuth, R. A., Munday, J. G. L., Dhir, R. K., and Banfill, P. F. G.
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- 1981
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14. Evolutionary genetic relationships of clones of Salmonella serovars that cause human typhoid and other enteric fevers
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Selander, R K, Beltran, P, Smith, N H, Helmuth, R, Rubin, F A, Kopecko, D J, Ferris, K, Tall, B D, Cravioto, A, and Musser, J M
- Abstract
Multilocus enzyme electrophoresis was employed to measure chromosomal genotypic diversity and evolutionary relationships among 761 isolates of the serovars Salmonella typhi, S. paratyphi A, S. paratyphi B, S. paratyphi C, and S. sendai, which are human-adapted agents of enteric fever, and S. miami and S. java, which are serotypically similar to S. sendai and S. paratyphi B, respectively, but cause gastroenteritis in both humans and animals. To determine the phylogenetic positions of the clones of these forms within the context of the salmonellae of subspecies I, comparative data for 22 other common serovars were utilized. Except for S. paratyphi A and S. sendai, the analysis revealed no close phylogenetic relationships among clones of different human-adapted serovars, which implies convergence in host adaptation and virulence factors. Clones of S. miami are not allied with those of S. sendai or S. paratyphi A, being, instead, closely related to strains of S. panama. Clones of S. paratyphi B and S. java belong to a large phylogenetic complex that includes clones of S. typhimurium, S. heidelberg, S. saintpaul, and S. muenchen. Most strains of S. paratyphi B belong to a globally distributed clone that is highly polymorphic in biotype, bacteriophage type, and several other characters, whereas strains of S. java represent seven diverse lineages. The flagellar monophasic forms of S. java are genotypically more similar to clones of S. typhimurium than to other clones of S. java or S. paratyphi B. Clones of S. paratyphi C are related to those of S. choleraesuis. DNA probing with a segment of the viaB region specific for the Vi capsular antigen genes indicated that the frequent failure of isolates of S. paratyphi C to express Vi antigen is almost entirely attributable to regulatory processes rather than to an absence of the structural determinant genes themselves. Two clones of S. typhisuis are related to those of S. choleraesuis and S. paratyphi C, but a third clone is not. Although the clones of S. decatur and S. choleraesuis are serologically and biochemically similar, they are genotypically very distinct. Two clones of S. typhi were distinguished, one globally distributed and another apparently confined to Africa; both clones are distantly related to those of all other serovars studied.
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- 1990
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15. Cell-cell interactions in conjugating Escherichia coli: purification of F pili with biological activity.
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Helmuth, R and Achtman, M
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A mutant of the F sex factor has been isolated that produces more F pili per cell than does the wild-type F factor. F pili have been purified in milligram amounts from cells carrying either the mutant or the wild-type sex factor. The technique described yields F pili of up to 99% purity that can specifically bind to Escherichia coli cells and that bind to and reversibly inactivate male-specific bacteriophages. The F pilin subunit has a molecular weight of 10,750 and purified F pili have a buoyant density of 1,200 g/cm3.
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- 1978
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16. Epidemiology of virulence-associated plasmids and outer membrane protein patterns within seven common Salmonella serotypes
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Helmuth, R, Stephan, R, Bunge, C, Hoog, B, Steinbeck, A, and Bulling, E
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Antibiotic-sensitive Salmonella isolates belonging to seven common serotypes and originating from 29 different countries from all continents were investigated for their plasmid DNA content (337 isolates) and their outer membrane protein profiles (216 isolates). Of the S. typhimurium, S. enteritidis, S. dublin, and S. choleraesuis isolates, 90% or more carried a serotype-specific plasmid. The molecular sizes of the plasmids were 60 megadaltons (Md) for S. typhimurium, 37 Md for S. enteritidis, 56 Md for S. dublin, and 30 Md for S. choleraesuis. The outer membrane protein profiles were homogeneous within each of the seven serotypes, except that a minority of S. enteritidis and S. dublin strains were lacking one major outer membrane protein. Virulence studies were performed with 39 representative strains by measuring the 50% lethal doses (LD50S) after oral infection of mice. The LD50 values obtained for plasmid-positive strains of S. typhimurium, S. enteritidis, and S. dublin were up to 10(6)-fold lower than the values obtained for the plasmid-free strains of the same serotype. Only the plasmid-positive strains could invade the livers of orally infected mice, and only they were resistant to the bactericidal activity of 90% guinea pig serum. Strains of S. infantis were generally plasmid free, whereas S. panama and S. heidelberg isolates carried heterogeneous plasmid populations. The virulence properties of the latter three serotypes could not be correlated with the predominant plasmids found in these strains.
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- 1985
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17. Detection of the induction of Salmonellaenterotoxin gene expression by contact with epithelial cells with RT‐PCR
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Dinjus, Ute, Hänel, Ingrid, Müller, W, Bauerfeind, R, and Helmuth, R
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All strains of Salmonella entericainvestigated were found to carry the Salmonellaenterotoxin gene (stn) as determined by PCR and hybridization studies. However, when using CHO‐K1 cells for testing the toxicity of the strains, not all strains showed a toxic effect (cell elongation) on the cells or did so only at a low level. The cultivation of Salmonellain contact with epithelial cells (IEC‐6) led to an increase in the production of toxin. The stngene expression was detectable with the help of the RT‐PCR after 3 h of incubation. The RNA of the strains was isolated, transcribed into cDNA (with MMLV‐reverse transcriptase) and amplified using PCR. The PCR products were separated electrophoretically using a polyacrylamide gel and detected by silver staining.
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- 1997
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18. Molecular marker analysis ofSalmonella typhimurium from surface waters, humans, and animals
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Graeber, I., Montenegro, M. A., Bunge, C., Boettcher, U., Tobias, H., Heinemeyer, E-A., and Helmuth, R.
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Salmonella contamination of North Sea water was detected for the first time in 1988 in Germany during routine examinations of bathing areas. Since then, subsequent isolations along the coast have been reported regularly. To define the source of contamination, strains isolated from seawater and rivers were studied by molecular marker methods. Their properties were compared with those of strains originating from possible sources of contamination such as humans, cattle, and sewage treatment plant water. Plasmid profile analysis of whole bacterial populations and the determination of antibiotic resistance patterns demonstrated, that contamination through the surrounding cattle industry could be excluded. Cattle isolates belonged to a widespread clone of phage type 204c which was multiresistant and exhibited an unique plasmid pattern which was never found in sea water isolates. Outer membrane protein and lipopolysaccharide analysis failed to demonstrate differences among theSalmonella populations and proved in this case insufficient for molecular marker discrimination.
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- 1995
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19. Salmonella enteritidis phage types in Germany
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Schroeter, A., Ward, L. R., Rowe, B., Protz, D., Hartung, M., and Helmuth, R.
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In order to monitor the epidemiological situation ofS. enteritidis in Germany, in 1990–91 1138 isolates from more than 180 locations in West Germany were phage typed. 1124 strains (98.8%) from all sources were typeable, belonging to 21 different phage types (PT). PT4 strains were isolated most frequently (70.8%). In addition, PT7, 25, 34 and 8 were of epidemiological relevance with incidences of 7.2 to 4.5%. The comparison of data shows that in Germany, like in other parts of Europe, PT4 predominates. This phage type is, however, infrequent in North America, where PT8 has the highest incidence.
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- 1994
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20. Outbreak of Salmonella typhimurium infection traced to contaminated chocolate and caused by a strain lacking the 60-megadalton virulence plasmid
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Kapperud, G, Gustavsen, S, Hellesnes, I, Hansen, A H, Lassen, J, Hirn, J, Jahkola, M, Montenegro, M A, and Helmuth, R
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We describe an outbreak of Salmonella typhimurium infection, caused by contaminated chocolate produced by one Norwegian company, which occurred in Norway and Finland in 1987. A total of 349 bacteriologically verified cases were recorded in Norway, and 12 cases were recorded in Finland. There was a predominance of young children among the patients (median age, 6 years), many of whom developed acute hemorrhagic diarrhea. The outbreak strain exhibited a rare phage lysis pattern and a characteristic plasmid profile lacking the 60-MDa virulence-associated plasmid. DNA hybridization failed to demonstrate any DNA sequence homology between the outbreak strain and the virulence plasmid. The outbreak strain was nonlethal for orally infected mice. The finding of only less than or equal to 10 S. typhimurium cells per 100 g of chocolate in about 90% of the positive samples obtained from retail outlets suggested that an inoculum of fewer than 10 organisms may have been sufficient to cause symptomatic disease.
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- 1990
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21. Detection and characterization of fecal verotoxin-producing Escherichia coli from healthy cattle
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Montenegro, M A, Bülte, M, Trumpf, T, Aleksic, S, Reuter, G, Bulling, E, and Helmuth, R
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Verotoxin-producing Escherichia coli isolates from feces of healthy cattle were identified by DNA hybridization with verotoxin 1- and verotoxin 2-specific gene probes. Among 259 animals investigated, 28 (10.8%) were found to carry verotoxin-producing E. coli strains. Characterization of the verotoxin-producing isolates revealed a heterogeneous population in terms of serotype and toxin type. Nearly 40% of the strains belonged to serogroups known to be pathogenic for humans, i.e., O22, O39, O82, O91, O113, O116, O126, and O136. Two isolates from different bulls were identified as serotype O157:H7. Results obtained in this study indicate that cattle may be an important source of verotoxigenic E. coli involved in human disease.
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- 1990
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22. R-factor cointegrate formation in Salmonella typhimurium bacteriophage type 201 strains
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Helmuth, R, Stephan, R, Bulling, E, van Leeuwen, W J, van Embden, J D, Guinée, P A, Portnoy, D, and Falkow, S
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The genetic and molecular properties of the plasmids in Salmonella typhimurium phase type 201 isolated are described. Such strains are resistant to streptomycin, tetracycline, chloramphenicol, ampicillin, kanamycin, and several other antimicrobial drugs, and are highly pathogenic for calves. These strains have been encountered with increasing frequency since 1972 in West Germany and The Netherlands. We show that isolates of this phage type constitute a very homogeneous group with regard to their extrachromosomal elements. These bacteria carry three small plasmids: pRQ3, a 4.2-megadalton (Md) colicinogenic plasmid; pRQ4, 3.4-Md plasmid that interferes with the propagation of phages; and pRQ5, a 3.2-Md cryptic plasmid. Tetracycline resistance resides on a conjugative 120-MD plasmid pRQ1, belonging to the incompatibility class H2. Other antibiotic resistance determinants are encoded by a nonconjugative 108-Md plasmid pRQ2. Transfer of multiple-antibiotic resistance to appropriate recipient strains was associated with the appearance of a 230-Md plasmid, pRQ6. It appears that pRQ6 is a stable cointegrate of pRQ1 and pRQ2. This cointegrate plasmid was transferable with the same efficiency as pRQ1. Other conjugative plasmids could mobilize pRQ2, but stable cointegrates were not detected in the transconjugants. Phase type 201 strains carry a prophage, and we show that phage pattern 201 reflects the interference with propagation of typing phages effected by this prophage and plasmid pRQ4 in strains of phage type 201.
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- 1981
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23. Assignment of tra cistrons to EcoRI fragments of F sex factor DNA
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Achtman, M, Skurray, R A, Thompson, R, Helmuth, R, Hall, S, Beutin, L, and Clark, A J
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We describe here the cloning of single EcoRI fragments from the tra region of F DNA using ColE1::Tn3 as vector. These plasmids, as well as the series of Skurray et al. (Proc. Natl. Acad. Sci. U.S.A. 73:64-68, 1976), have been used to refine the map positions of tra cistrons on the F factor as well as to define a new DNA transfer cistron, traM. The current map of the tra cistrons is presented. None of the known tra cistrons, with the exception of traG, straddles an EcoRI site. The EcoRI site at 82 kilobases splits the traG cistron into two portions, an operator-proximal portion necessary for F pilus synthesis and an operator distal portion involved in conjugation itself. The operon structure of the tra cistrons was reevaluated, and we found that traI is at least partially independent of transcription of the traA to traD operon.
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- 1978
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24. Radioimmunotherapy (RIT) with 177 Lutetium-DOTA-Rituximab (177LU-D- R): A Phase I/II - Study in 30 Patients with Relapsing Follicular, Mantle Cell and Other Indolent B-Cell Lymphomas
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Lohri, Andreas, Forrer, Flavio, Campana, Benedetta, Mamot, Christoph, Winterhalder, Ralph, Herrmann, Richard, Maecke, Helmuth R, and Müller-Brand, Jan
- Abstract
RIT in CD 20 positive lymphoma has mainly been studied by using 131Iodine (131I) or 90Yttrium (90Y) labelled antibodies. Lutetium-177 linked to the chimaeric anti CD 20 antibody Rituximab (R) with DOTA (1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid) as chelator emits beta rays (0.497MeV) and a gamma component (113keV 7%, 208keV 11%) suitable for imaging. Its handling is less hazardous than 131I and the beta component may give a more favourable tumour to non-tumour ratio than 90Y. The aim of the study was to determine the maximum tolerated dose (MTD) and to explore clinical response. Non labelled rituximab (250mg/m2) was given on d1 and d8. 177LU-D-R was injected on d8. Pts were hospitalized for five days for sequential imaging and, at higher doses, to fulfil radiation safety requirements. From Feb 02 to Aug 08 we treated 30 pts (m:16, f: 14, median # of preTx: 3) in 7 cohorts (level 1–7) of 2 to 7 pts. Since activity was already seen at the lowest dose (20 mCi/m2), escalation was carried out in steps of only 5 mCi/m2. No Grade III/IV non- hematologic toxicity was observed (2 pts being too early to evaluate). Gr II fatigue and Gr I nausea were reported mainly on the days following treatment (Tx). Hematologic toxicity: Anemia Gr II: 2 in 7 pts (2/7) at level 4, 1/4 at level 5. No Gr III/IV was seen, no transfusions were required. Lc: Gr III was seen at levels 3–6 each (nadir wk 8), no Gr IV was seen. Neutro: Gr III: 1/5 at level 3, 1/6 at level 4, 1/4 at level 5, 3/4 at level 6 no Gr IV was observed. No neutropenic fever was observed. Tc: One brief Gr IV was seen in 1 of 5 pts at level 3, one Gr III each at levels 4–6 (nadir: wk 7), no bleeding occurred and no Tc transfusions were required (2 pts being too early). Response was assessed by [18F]FDG-PET and CT or PET/CT pre Tx, wk 10 and when clinically indicated thereafter. Responses were seen on all dose levels. Six of 12 pts with untransformed follicular lymphoma (FL) (med age: 59 y, 36–82) remain in remission 74, 71, 71, 32, 6 and 4 months after RIT. One pt treated at the lowest dose had a regression of pleural effusions after RIT, received an allogeneic transplant and has been in remission for 70 months. Two pts with FL have died. One pt with transformed FL had a brief response, then received an autologous transplant and has been in remission for 2 yrs. The 14 pts with mantle cell lymphoma (MCL) (med age: 71 y, 46–85) usually had brief responses in parts of their tumour mass. 10 pts have died. Median time to next Tx was 4 months. One pt with localized indolent MCL responded twice to 177LU-D-R, progressed after the 3rd Tx and is alive 60 months after his 1st dose. One pt had a brief response, then received bortezomib and has been in CR for 2 years (2 pts too early). Other indolent histologies had brief responses. With a maximum observation time of 75 months, no MDS or leukemia was seen. According to national radiation safety requirements 177LU-D- R at a dose of 50mCi/m2 requires a hospital stay of 5 days. This dose seems to have a promising therapeutic index mainly in FL and will be tested in a larger patient cohort. (This study was supported by the JP Obrecht Foundation, Arlesheim, Switzerland and the Swiss Cancer League. Day 1 and 8 Rituximab for pts 1 to 25 was provided free of charge by Roche Pharma Schweiz, Reinach, Switzerland. 177LU-D-R was manufactured at the Radiological Chemistry unit, University Hospital, Basel, Switzerland. Lutetium-177 was purchased either from I.D.B. Holland BV or from Perkin Elmer, USA)
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- 2008
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25. Radioimmunotherapy (RIT) with 177Lutetium-DOTA-Rituximab (177LU-D- R): A Phase I/II - Study in 30 Patients with Relapsing Follicular, Mantle Cell and Other Indolent B-Cell Lymphomas
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Lohri, Andreas, Forrer, Flavio, Campana, Benedetta, Mamot, Christoph, Winterhalder, Ralph, Herrmann, Richard, Maecke, Helmuth R, and Müller-Brand, Jan
- Abstract
RIT in CD 20 positive lymphoma has mainly been studied by using 131Iodine (131I) or 90Yttrium (90Y) labelled antibodies. Lutetium-177 linked to the chimaeric anti CD 20 antibody Rituximab (R) with DOTA (1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid) as chelator emits beta rays (0.497MeV) and a gamma component (113keV 7%, 208keV 11%) suitable for imaging. Its handling is less hazardous than 131I and the beta component may give a more favourable tumour to non-tumour ratio than 90Y. The aim of the study was to determine the maximum tolerated dose (MTD) and to explore clinical response. Non labelled rituximab (250mg/m2) was given on d1 and d8. 177LU-D-R was injected on d8. Pts were hospitalized for five days for sequential imaging and, at higher doses, to fulfil radiation safety requirements. From Feb 02 to Aug 08 we treated 30 pts (m:16, f: 14, median # of preTx: 3) in 7 cohorts (level 1–7) of 2 to 7 pts. Since activity was already seen at the lowest dose (20 mCi/m2), escalation was carried out in steps of only 5 mCi/m2. No Grade III/IV non- hematologic toxicity was observed (2 pts being too early to evaluate). Gr II fatigue and Gr I nausea were reported mainly on the days following treatment (Tx). Hematologic toxicity: Anemia Gr II: 2 in 7 pts (2/7) at level 4, 1/4 at level 5. No Gr III/IV was seen, no transfusions were required. Lc: Gr III was seen at levels 3–6 each (nadir wk 8), no Gr IV was seen. Neutro: Gr III: 1/5 at level 3, 1/6 at level 4, 1/4 at level 5, 3/4 at level 6 no Gr IV was observed. No neutropenic fever was observed. Tc: One brief Gr IV was seen in 1 of 5 pts at level 3, one Gr III each at levels 4–6 (nadir: wk 7), no bleeding occurred and no Tc transfusions were required (2 pts being too early). Response was assessed by [18F]FDG-PET and CT or PET/CT pre Tx, wk 10 and when clinically indicated thereafter. Responses were seen on all dose levels. Six of 12 pts with untransformed follicular lymphoma (FL) (med age: 59 y, 36–82) remain in remission 74, 71, 71, 32, 6 and 4 months after RIT. One pt treated at the lowest dose had a regression of pleural effusions after RIT, received an allogeneic transplant and has been in remission for 70 months. Two pts with FL have died. One pt with transformed FL had a brief response, then received an autologous transplant and has been in remission for 2 yrs. The 14 pts with mantle cell lymphoma (MCL) (med age: 71 y, 46–85) usually had brief responses in parts of their tumour mass. 10 pts have died. Median time to next Tx was 4 months. One pt with localized indolent MCL responded twice to 177LU-D-R, progressed after the 3rdTx and is alive 60 months after his 1stdose. One pt had a brief response, then received bortezomib and has been in CR for 2 years (2 pts too early). Other indolent histologies had brief responses. With a maximum observation time of 75 months, no MDS or leukemia was seen. According to national radiation safety requirements 177LU-D- R at a dose of 50mCi/m2requires a hospital stay of 5 days. This dose seems to have a promising therapeutic index mainly in FL and will be tested in a larger patient cohort. (This study was supported by the JP Obrecht Foundation, Arlesheim, Switzerland and the Swiss Cancer League. Day 1 and 8 Rituximab for pts 1 to 25 was provided free of charge by Roche Pharma Schweiz, Reinach, Switzerland. 177LU-D-R was manufactured at the Radiological Chemistry unit, University Hospital, Basel, Switzerland. Lutetium-177 was purchased either from I.D.B. Holland BV or from Perkin Elmer, USA)
- Published
- 2008
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- View/download PDF
26. Detection of the induction of Salmonella enterotoxin gene expression by contact with epithelial cells with RT-PCR
- Author
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Dinjus, Ute, Hänel, Ingrid, Müller, W, Bauerfeind, R, and Helmuth, R
- Abstract
All strains of Salmonella enterica investigated were found to carry the Salmonella enterotoxin gene (stn) as determined by PCR and hybridization studies. However, when using CHO-K1 cells for testing the toxicity of the strains, not all strains showed a toxic effect (cell elongation) on the cells or did so only at a low level. The cultivation of Salmonella in contact with epithelial cells (IEC-6) led to an increase in the production of toxin. The stn gene expression was detectable with the help of the RT-PCR after 3 h of incubation. The RNA of the strains was isolated, transcribed into cDNA (with MMLV-reverse transcriptase) and amplified using PCR. The PCR products were separated electrophoretically using a polyacrylamide gel and detected by silver staining.
- Published
- 1997
- Full Text
- View/download PDF
27. How to Modify Conditions Limiting Resistance in Bacteria in Animals and Other Reservoirs
- Author
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Helmuth, R. and Protz, D.
- Abstract
Antimicrobial agents in veterinary medicine are used for three purposes: therapy, prophylaxis, and nutrition. The major public health risk is that selection pressure leads to an increase in the pool of resistance genes. Since 1987, the nutritional use of antimicrobials in Europe has been regulated by a council directive, which demands special investigations into the potential of antimicrobials to increase rates of drug resistance. However, the prophylactic and therapeutic use of antimicrobials has sometimes led to the emergence of resistant bacteria. For example, the selective effect of the prophylactic use of gentamicin and the therapeutic use of quinolones led to the emergence of resistant salmonellae. To prevent the spread of resistant microorganisms from animals to humans, it should be recognized that antibiotics are not suitable as a compensation for poor hygiene standards or for the eradication of a pathogen from a certain environment. They should be used only by doctors or veterinarians.
- Published
- 1997
- Full Text
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28. Molecular typing methods for S. enteritidis
- Author
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Helmuth, R. and Schroeter, A.
- Published
- 1994
- Full Text
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