Management of Febrile Neutropenia - a German Prospective Hospital Cost Analysis in Lymphoproliferative Disorders, Non-Small Cell Lung Cancer, and Primary Breast Cancer

Background: Febrile neutropenia/leukopenia (FN/FL) is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy, but German data on economic consequences are limited. Patients and Methods: A prospective, multicentre, longitudinal, observational study was carried out to evaluate the occurrence of FN/FL and its impact on health resource utilization and costs in non-small cell lung cancer (NSCLC), lymphoproliferative disorder (LPD), and primary breast cancer (PBC) patients. Costs are presented from a hospital perspective. Results: A total of 325 consecutive patients (47% LPD, 37% NSCLC, 16% PBC; 46% women; 38% age >= 65 years) with 68 FN/FL episodes were evaluated. FN/FL occurred in 22% of the LPD patients, 8% of the NSCLC patients, and 27% of the PBC patients. 55 FN/FL episodes were associated with at least 1 hospital stay (LPD n = 34, NSCLC n = 10, PBC n = 11). Mean (median) cost per FN/FL episode requiring hospital care amounted to (sic) 3,950 ((sic) 2,355) and varied between (sic) 4,808 ((sic) 3,056) for LPD, (sic) 3,627 ((sic) 2,255) for NSCLC, and (sic) 1,827 ((sic) 1,969) for PBC patients. 12 FN/FL episodes (LPD n = 9, NSCLC n = 3) accounted for 60% of the total expenses. Main cost drivers were hospitalization and drugs (60 and 19% of the total costs). Conclusions: FN/FL treatment has economic relevance for hospitals. Costs vary between tumour types, being significantly higher for LPD compared to PBC patients. The impact of clinical characteristics on asymmetrically distributed costs needs further evaluation

Identification of bacterial glycosidases in rat cecal contents

Cecal contents of conventional and germfree rats were examined for glycosidases which may have a role in degrading glycoprotein oligosaccharides. Utilizing p-nitrophenylglycosides as substrates, we identified glycosidases in bacteria-free supernatants from cecal contents which act on β-linkages. These cecal glycosidases appear to be of bacterial origin since: (1) direct comparisons of the enzymes in similar contents from germfree rats showed negligible activities; (2) most of the glycosidase levels in bacterial extracts were at least as high as those of soluble supernatants; and (3) disk gel electrophoresis of contents and bacterial extracts revealed in both preparations a β- N -acetylglucosaminidase band with similar R f s. Also, the blood group B antigenicity of germfree cecal glycoproteins was greatly decreased by conventional cecal contents. These findings indicate that β-galactosidase and β- N -acetylgalactosaminidase in cecal contents are bacterial in origin, and they may have a role in the bacterial catabolism of intestinal glycoproteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44391/1/10620_2005_Article_BF01309607.pd

Molecular Dynamics of Mesophilic-Like Mutants of a Cold-Adapted Enzyme: Insights into Distal Effects Induced by the Mutations

Networks and clusters of intramolecular interactions, as well as their “communication” across the three-dimensional architecture have a prominent role in determining protein stability and function. Special attention has been dedicated to their role in thermal adaptation. In the present contribution, seven previously experimentally characterized mutants of a cold-adapted α-amylase, featuring mesophilic-like behavior, have been investigated by multiple molecular dynamics simulations, essential dynamics and analyses of correlated motions and electrostatic interactions. Our data elucidate the molecular mechanisms underlying the ability of single and multiple mutations to globally modulate dynamic properties of the cold-adapted α-amylase, including both local and complex unpredictable distal effects. Our investigation also shows, in agreement with the experimental data, that the conversion of the cold-adapted enzyme in a warm-adapted variant cannot be completely achieved by the introduction of few mutations, also providing the rationale behind these effects. Moreover, pivotal residues, which are likely to mediate the effects induced by the mutations, have been identified from our analyses, as well as a group of suitable candidates for protein engineering. In fact, a subset of residues here identified (as an isoleucine, or networks of mesophilic-like salt bridges in the proximity of the catalytic site) should be considered, in experimental studies, to get a more efficient modification of the features of the cold-adapted enzyme