Weekly irinotecan in a patient with metastatic colorectal cancer on hemodialysis due to chronic renal failure

Background: The cytotoxic treatment of patients suffering from advanced or metastatic cancer undergoing hemodialysis due to chronic renal failure still remains a problem, since for those patients pharmacokinetic and pharmacodynamic data on most cytotoxic agents are lacking. Case Report: We report a 45-year-old male who suffered from chronic renal failure and was diagnosed with stage-3 colorectal cancer (CRC) in February 2000. After surgical removal of the tumor an adjuvant chemotherapy of dose-reduced i.v. bolus 5-fluorouracil and folinic acid was begun (Mayo protocol). Due to excessive gastrointestinal toxicity, therapy was discontinued after the first cycle. In April 2000 liver metastases were diagnosed. The patient was then put on a weekly schedule of dose-reduced CPT-11 (50 mg/m(2), 80 mg total). No hematological or non-hematological toxicity grade 3/4 was observed. Due to excellent tolerability and lack of severe side effects the dose was increased up to 80 mg/m2 (140 mg total) weekly. A dose escalation to 100 mg/m(2) (180 mg total) resulted in severe diarrhea (grade 4). Within 2 months of treatment the patient achieved a lasting partial remission until April 2001 (12 months). A significant progression of hepatic metastases required an alternative treatment regimen beginning in July 2001 (HAI, hepatic artery infusion). Conclusion: This case report demonstrates the feasibility and efficacy of a weekly treatment with dose-reduced CPT-11 in a patient with metastatic CRC on hemodialysis due to chronic renal failure

Distribution, expression and long range mapping of legiolysin gene (lly) specific DNA sequences in Legionellae

The legiolysin gene (lly) cloned from Legionella pneumophila Philadelphia 1 confers the phenotypes of hemolysis and browning of the culture medium. An internal Uy-specific DNA probe was used in Southern hybridizations for the detection of Uy-specific DNA in the genomes of legioneUae and other gram-negative pathogenic bacteria. Under conditi9ns of high stringency, tlie Uy DNA probe specifically reacted with DNA fragments fr9m L. pneumophiüz isolates; by reducing stringency, hybridization was also observed for all other Legionella strains tested. No hybridization occurred with DNAs isolated from bact~ria of other genera. The Uy genewas mapped by pulsed-field gel electrophoresis to the respective genomic Notl fragments of Legionelltz isolates. By using antilegiolysin monospecific polyclonal antibodies in Western blots (immunoblots), Lly proteins could be detected only in L. pneumophila isolates

Mobilisation and remobilisation of a large archetypal pathogenicity island of uropathogenic Escherichia coli in vitro support the role of conjugation for horizontal transfer of genomic islands

Background: A substantial amount of data has been accumulated supporting the important role of genomic islands (GEIs) - including pathogenicity islands (PAIs) - in bacterial genome plasticity and the evolution of bacterial pathogens. Their instability and the high level sequence similarity of different (partial) islands suggest an exchange of PAIs between strains of the same or even different bacterial species by horizontal gene transfer (HGT). Transfer events of archetypal large genomic islands of enterobacteria which often lack genes required for mobilisation or transfer have been rarely investigated so far. Results: To study mobilisation of such large genomic regions in prototypic uropathogenic E. coli (UPEC) strain 536, PAI II536 was supplemented with the mobRP4 region, an origin of replication (oriVR6K), an origin of transfer (oriTRP4) and a chloramphenicol resistance selection marker. In the presence of helper plasmid RP4, conjugative transfer of the 107-kb PAI II536 construct occured from strain 536 into an E. coli K-12 recipient. In transconjugants, PAI II536 existed either as a cytoplasmic circular intermediate (CI) or integrated site-specifically into the recipient’s chromosome at the leuX tRNA gene. This locus is the chromosomal integration site of PAI II536 in UPEC strain 536. From the E. coli K-12 recipient, the chromosomal PAI II536 construct as well as the CIs could be successfully remobilised and inserted into leuX in a PAI II536 deletion mutant of E. coli 536. Conclusions: Our results corroborate that mobilisation and conjugal transfer may contribute to evolution of bacterial pathogens through horizontal transfer of large chromosomal regions such as PAIs. Stabilisation of these mobile genetic elements in the bacterial chromosome result from selective loss of mobilisation and transfer functions of genomic islands

Neo-Aristotelian Naturalism and the Evolutionary Objection: Rethinking the Relevance of Empirical Science

Neo-Aristotelian metaethical naturalism is a modern attempt at naturalizing ethics using ideas from Aristotle’s teleological metaphysics. Proponents of this view argue that moral virtue in human beings is an instance of natural goodness, a kind of goodness supposedly also found in the realm of non-human living things. Many critics question whether neo-Aristotelian naturalism is tenable in light of modern evolutionary biology. Two influential lines of objection have appealed to an evolutionary understanding of human nature and natural teleology to argue against this view. In this paper, I offer a reconstruction of these two seemingly different lines of objection as raising instances of the same dilemma, giving neo-Aristotelians a choice between contradicting our considered moral judgment and abandoning metaethical naturalism. I argue that resolving the dilemma requires showing a particular kind of continuity between the norms of moral virtue and norms that are necessary for understanding non-human living things. I also argue that in order to show such a continuity, neo-Aristotelians need to revise the relationship they adopt with empirical science and acknowledge that the latter is relevant to assessing their central commitments regarding living things. Finally, I argue that to move this debate forward, both neo-Aristotelians and their critics should pay attention to recent work on the concept of organism in evolutionary and developmental biology

Chiral effective field theories of the strong interactions

Effective field theories of the strong interactions based on the approximate chiral symmetry of QCD provide a model-independent approach to low-energy hadron physics. We give a brief introduction to mesonic and baryonic chiral perturbation theory and discuss a number of applications. We also consider the effective field theory including vector and axial-vector mesons.Comment: 22 pages, 9 figures, proceedings of "Many-Body Structure of Strongly Interacting Systems", Mainz, Germany, Feb. 23-25 201

Land use change suppresses precipitation

Aerosols of natural and anthropogenic origin have important climate effects through interaction with clouds, which are among the main uncertainties in climate models due to the large variability of aerosol sizes, types and 3D-distributions [1]. Experimental investigations are typically restricted to high concentrations in industrial and urban aerosol plumes although in more remote areas already slight changes in the aerosol concentrations can have a large impact. This study reports on investigations of aerosols over a remote natural laboratory, along the ~1500 km long Vermin Proof Fence, also called “State Barrier Fence”, in Western Australia. This Fence, built in the first decade of the 20th century, separates an area of >100.000 square km of homogeneous terrain, converted to arable land (west), from the natural vegetation of inner Australia, conserved as a nature preserve (east). The Fence protects the agriculture from an invasion of animals but also protects the nature preserve from farming pressure and serves as a clear cut between the two types of landscape. Recent satellite images indicate that the Fence also works as a separation line between different meteorological regions. Clouds, for example, develop more often over regions with natural vegetation [2]. Early surveys of aerosols over Australia [3] found generally clean conditions with less than 1000 ultrafine (~ 20 nm) particles / cm3 throughout most of Australia. Local enhancements were occasionally observed in coastal areas, but, for the analysis of particle distributions they were considered to be unimportant. However, higher numbers of ultrafine particles were now also found downwind of tropical eucalyptus forests on the Australian east coast

Baryon polarization in low-energy unpolarized meson-baryon scattering

We compute the polarization of the final-state baryon, in its rest frame, in low-energy meson--baryon scattering with unpolarized initial state, in Unitarized BChPT. Free parameters are determined by fitting total and differential cross-section data (and spin-asymmetry or polarization data if available) for $pK^-$, $pK^+$ and $p\pi^+$ scattering. We also compare our results with those of leading-order BChPT

Preoperative predictors for residual tumor after surgery in patients with ovarian carcinoma

Objectives: Suboptimal debulking (>1 cm residual tumor) results in poor survival rates for patients with an advanced stage of ovarian cancer. The purpose of this study was to develop a prediction model, based on simple preoperative parameters, for patients with an advanced stage of ovarian cancer who are at risk of suboptimal cytoreduction despite maximal surgical effort. Methods: Retrospective analysis of 187 consecutive patients with a suspected clinical diagnosis of advanced-stage ovarian cancer undergoing upfront debulking between January 1998 and December 2003. Preoperative parameters were Karnofsky performance status, ascites and serum concentrations of CA 125, hemoglobin, albumin, LDH and blood platelets. The main outcome parameter was residual tumor >1 cm. Univariate and multivariate logistic regression was employed for testing possible prediction models. A clinically applicable graphic model (nomogram) for this prediction was to be developed. Results: Serum concentrations of CA 125 and blood platelets in the group with residual tumor >1 cm were higher in comparison to the optimally cytoreduced group (p 1 cm based on serum levels of CA 125 and albumin was established. Conclusion: Postoperative residual tumor despite maximal surgical effort can be predicted by preoperative CA 125 and serum albumin levels. With a nomogram based on these two parameters, probability of postoperative residual tumor in each individual patient can be predicted. This proposed nomogram may be valuable in daily routine practice for counseling and to select treatment modality. Copyrigh