bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central nervous system metastases in women with HER‐2 positive metastatic breast cancer after treatment with trastuzumab
Authors: DAWSON Sarah‐Jane , RANIERI Nadia F , SNYDER Raymond D , McLACHLAN Sue‐Anne , BURNS William I , NEWNHAM Genni M , FRANCIS Prudence A , DOWLING Anthony J 
Published: February 2006

Abstract
Background:
Historically, central nervous system (CNS) metastases have been reported to occur in 10–16% of women with metastatic breast cancer (MBC) with a median survival of less than 1 year after diagnosis of CNS disease. A higher rate of CNS metastases has been described in women with metastatic breast cancer (MBC) over‐expressing HER‐2 who receive trastuzumab therapy.
Aims:  The aim of this study was to examine the frequency of and potential risk factors for CNS metastases in these women. Our a priori hypotheses were that in MBC patients treated with trastuzumab, CNS metastases occurred (i) more frequently than historical controls, and (ii) in women with controlled systemic disease.
Methods:  A retrospective cohort study of 28 consecutive patients with MBC over‐expressing HER‐2 and treated with trastuzumab and chemotherapy was performed.
Results:  A total of 22/25 (88%) patients who initially responded to trastuzumab had progressed within a median of 11.2 months after starting trastuzumab therapy. Central nervous system metastases occurred in 11/28 (39%) patients and the remaining 11 patients had progressed elsewhere. At diagnosis of CNS metastases, 9/11 (82%) had controlled systemic disease (CR = 2, PR = 6, SD = 1). There were trends for patients with CNS metastases to have greater than one site of metastatic disease at the commencement of trastuzumab therapy (P = 0.06), and to be hormone receptor negative at initial diagnosis (P = 0.14). The median time to diagnosis of CNS metastases after the commencement of trastuzumab therapy was 12 months (range 6–19 months). The median survival after diagnosis of CNS metastases was 12 months (range 2–22 months).
Conclusions:  This study demonstrates a high rate of CNS metastases (39%) in HER‐2 positive MBC patients treated with trastuzumab. At CNS metastases most patients had controlled systemic disease and the median survival after CNS relapse was 1 year. We suggest aggressive management of CNS disease in this population. Additional strategies to decrease the incidence of CNS metastases in these patients may include prophylactic whole brain irradiation and the development of novel pharmacological agents with successful CNS penetration.
Apoptosis occurs early in the basal layer of the oral mucosa following cancer chemotherapy
Authors: GIBSON Rachel J , CUMMINS Adrian G , BOWEN Joanne M , LOGAN Richard M , HEALEY Tabitha , KEEFE Dorothy M 
Published: February 2006

Abstract
Background: Oral mucositis, a debilitating side‐effect of chemotherapy, is difficult to prevent or treat. The aim of this study was to characterize the histological and ultrastructural change in the human oral mucosa following cytotoxic chemotherapy.
Methods: Oral buccal mucosa biopsies were taken from four volunteers and 20 cancer patients. Each patient had one biopsy prior to chemotherapy and a second biopsy at varying intervals after chemotherapy. Biopsies were assessed histologically and ultrastructurally.
Results: Apoptosis increased in the basal layer in the first 3 days after chemotherapy, began to decline at 6 days, but never returned to levels of volunteers by 11 days after treatment. Ultrastructural changes included increased intercellular fibres in basal layer cells, cytoplasmic vacuolation, loss of membrane contact with neighboring cells, multinucleation of suprabasal cells and loss of cellular cytoplasm. These changes persisted in prechemotherapy biopsies in patients who had prior chemotherapy.
Conclusions: Apoptosis occurs early, and persists in the basal layer of the buccal mucosa after chemotherapy. Ultrastructural changes were present and remained up to 11 days after chemotherapy.
Bone marrow involvement in small cell lung cancer: Prognostic significance and correlation with hematological and biochemical parameters
Authors: OZKAN Metin , ESER Bulent , ER Ozlem , COSKUN H. Senol , OZTURK Ahmet , SARI Ismail , CANOZ Ozlem , ALTINBAS Mustafa 
Published: February 2006

AbstractThe more metastatic sites and bone marrow metastasis in small cell lung cancer (SCLC), the worse the prognosis. Diagnosing the bone marrow invasion at the beginning of the therapy is important for determining of the prognosis and planning the treatment. Abnormalities of some blood parameters may help to estimate the extent of bone marrow invasion by cancer cells. In this retrospective review, the changes in routine laboratory tests that may indicate bone marrow invasion, the predictive values of these tests, and the prognostic importance of bone marrow invasion were evaluated in SCLC patients who were being followed up according to a protocol. One hundred and forty‐four patients with SCLC were enrolled in this study. Retrospectively, it was evaluated that 25 (17.4%) of the patients had bone marrow metastasis. According to univariate analysis, there was a significant difference between hemoglobin, white blood cell count, platelet count, lactate dehydrogenase, alkaline phosphatase and uric acid of the patients with and without bone marrow involvement. Among the biochemical parameters, the elevated LDH and AP had the highest sensitivity and specificity as indicators of bone marrow invasion (0.80–0.82 and 0.84–0.78, respectively). The median overall survival of extensive‐stage disease with and without bone marrow metastasis were 4.0 ± 1.0 months (95% CI 2.2–5.7) and 7.0 ± 1.2 months (95% CI 4.7–9.3), respectively (P = 0.03). Bone marrow metastasis was found to be an indicator of a bad prognosis. Bone marrow biopsy, that is an invasive procedure, can be performed on selected patients who have changes of routine laboratory tests suggesting bone marrow invasion.
A shortcut to seasonal design rainfall estimates in the UK
Authors: Kjeldsen T. R. , Prudhomme C. , Svensson C. , Stewart E. J. 
Published: February 2006

AbstractThe depth–duration–frequency (DDF) model developed as part of the Flood Estimation Handbook (FEH) enables estimates of design rainfall to be made at any location in the UK. This study presents a shortcut method for estimating seasonal design rainfall for a summer and winter season, respectively, using a simple seasonal correction factor in combination with the FEH DDF estimate of design rainfall. The seasonal correction factors were derived for the summer and winter season for a range of durations. The observed correction factors were linked to standard average annual rainfall available from the FEH CD‐ROM, thereby enabling the use of this method at any location in the UK. The results obtained in this study are shown to correspond well to the summary statistics on seasonal rainfall presented in the Flood Studies Report.
Correlation Moment
Analysis and the Time Dependence of Coherence in Systems Described by Nonlinear Partial Differential
Equations
Authors: Belmont M.
R. 
Published: February 2006

Abstract
The work presented introduces correlation moment analysis. This technique can be employed to explore the growth of determinism from stochastic initial conditions in physical systems described by non-linear partial differential equations (PDEs) and is also applicable to wholly deterministic situations. Correlation moment analysis allows the analytic determination of the time dependence of the spatial moments of the solutions of certain types of non-linear partial differential equations. These moments provide measures of the growth of processes defined by the PDE, furthermore the results are obtained without requiring explicit solution of the PDE. The development is presented via case studies of the linear diffusion equation and the non-linear Kortweg de-Vries equation which indicate strategies for exploiting the various properties of correlation moments developed in the text. In addition, a variety of results have been developed which show how various classes of terms in PDEs affect the structure of a sequence of correlation moment equations. This allows results to be obtained about the behavior of the PDE solution, in particular how the presence of certain types of terms affects integral measures of the solution. It is also demonstrated that correlation moments provide a very simple, natural approach to determining certain subsets of conserved quantities associated with the PDEs.
Transient Response of
Transversely Isotropic Composite Plates to a Point
Source
Authors: Mahmoud A. , Shah A.
H. , Dong S.
B. 
Published: February 2006

Abstract
In this paper, transient three-dimensional response of a transversely isotropic composite plate to a time varying point load is efficiently computed by reducing the elastodynamic equation through integral and coordinate transformations to a series of two-dimensional problems, each associated with a plane wave along a given direction in the plate. Discrete equations of a semi-analytical finite element model are solved for the thickness profile eigendata at a given frequency. Three-dimensional steady state responses in the wave number domain are formed by summing contributions from eigenmodes over propagation directions. The transient response is obtained by a numerical integration of inverse Fourier time transform of these steady state responses. Present results showed good agreement with data reported in the literature and confirmed previously observed phenomena.
Size Effects on
Cavitation Instabilities
Authors: Niordson Christian
F. , Tvergaard Viggo 
Published: February 2006

Abstract
In metal-ceramic systems the constraint on plastic flow leads to so high stress triaxialities that cavitation instabilities may occur. If the void radius is on the order of magnitude of a characteristic length for the metal, the rate of void growth is reduced, and the possibility of unstable cavity growth is here analyzed for such cases. A finite strain generalization of a higher order strain gradient plasticity theory is applied for a power-law hardening material, and the numerical analyses are carried out for an axisymmetric unit cell containing a spherical void. In the range of high stress triaxiality, where cavitation instabilities are predicted by conventional plasticity theory, such instabilities are also found for the nonlocal theory, but the effects of gradient hardening delay the onset of the instability. Furthermore, in some cases the cavitation stress reaches a maximum and then decays as the void grows to a size well above the characteristic material length.
Control of Bending
Vibrations Within Subdomains of Thin Plates—Part II: Piezoelectric Actuation and Approximate
Solution
Authors: Krommer Michael , Varadan Vasundara
V. 
Published: February 2006

Abstract
In the first part of this paper, we presented the theoretical basics of a new method to control the bending motion of a subdomain of a thin plate. We used continuously distributed sources of self-stress, applied within the subdomain, to exactly achieve the desired result. From a practical point of view, continuously distributed self-stresses cannot be realized. Therefore, we discuss the application of discretely placed piezoelectric actuators to approximate the continuous distribution in this part. Using piezoelectric patch actuators requires the consideration of electrostatic equations as well. However, if the patches are relatively thin, the electromechanical coupling can be incorporated by means of piezoelastic (instead of elastic) stiffness (piezoelastically stiffended elastic constants). The placement of the patches is based on the discretization of the exact continuous distribution by means of piece-wise constant functions. These are calculated from a convolution integral representing the deviation of the bending motion in the controlled case from the desired one. A proper choice of test loadings allows us to eliminate representative mechanical quantities exactly and to make the resulting bending motion to match the desired one very closely; hence, to find a suboptimal approximate solution. In Part I of this paper we presented exact solutions for the axisymmetric bending of circular plates; it is also considered in Part II. For axisymmetric bending, only the radial coordinate is discretized. Hence, ring-shaped piezoelectric patch actuators are considered in this paper.
Staphylococcal Cassette Chromosome
mec
(SCC
mec
) Typing of Methicillin-Resistant
Staphylococcus aureus
Strains Isolated in 11 Asian Countries: a Proposal for a New Nomenclature for SCC
mec
Elements
Authors: Chongtrakool Piriyaporn , Ito Teruyo , Ma Xiao Xue , Kondo Yoko , Trakulsomboon Suwanna , Tiensasitorn Chuntima , Jamklang Mantana , Chavalit Tavinun , Song Jae-Hoon , Hiramatsu Keiichi 
Published: February 2006

ABSTRACT

A description of staphylococcal cassette chromosome
mec
(SCC
mec
) elements carried by 615 methicillin-resistant
Staphylococcus aureus
(MRSA) strains isolated in 11 Asian countries is reported, and a novel nomenclatural system based on their structures is proposed. The 615 strains were classified as type 3A (370 strains), type 2A (207 strains), type 2B (32 strains), type 1B (1 strain), and nontypeable (5 strains). The previously reported type III SCC
mec
(DDBJ/EMBL/GenBank accession no. AB037671) carried by the MRSA strain 85/2082 was ascertained to be composed of two SCC elements, type 3A SCC
mec
and SCC
mercury
. PCR analysis indicated that 310 of 370 type 3A SCC
mec
strains carried both SCC elements. These strains were prevalent in eight countries: Thailand, Sri Lanka, Indonesia, Vietnam, Philippines, Saudi Arabia, India, and Singapore. The remaining 60 type 3A SCC
mec
strains differed with respect to the left extremity polymorphism or to the presence of
ccrC
. Among these, two were identified as carrying only type 3A SCC
mec
elements, but their left extremities differed. Type 2A SCC
mec
strains predominated in Korea and Japan, although the frequency of the presence of
ant
(
4
′)-1 gene downstream of
mecA
varied (53% for Korean strains; 93% for Japanese strains). Various SCC
mec
elements were identified in the tested strains, and limited numbers were identified by their multilocus sequence typing genotypes. These data suggest that numerous MRSA clones are disseminated in Asian hospitals, and these consist of minor clones that are presumed to have arisen locally and major clones that are presumed to have been introduced from other countries.
Transfer of Vancomycin Resistance Transposon Tn
1549
from
Clostridium symbiosum
to
Enterococcus
spp. in the Gut of Gnotobiotic Mice
Authors: Launay Aline , Ballard Susan A. , Johnson Paul D. R. , Grayson M. Lindsay , Lambert Thierry 
Published: February 2006

ABSTRACT

The vancomycin resistance
vanB2
gene cluster is disseminated worldwide and has been found in phylogenetically remote bacterial genera. The
vanB2
operon is part of conjugative transposons Tn
1549
/Tn
5382
, but conjugative transposition of these elements has not been demonstrated. We have obtained transfer of a Tn
1549
-like element (referred to herein as “Tn
1549
-like”) from
Clostridium symbiosum
MLG101 to
Enterococcus faecium
64/3 and
Enterococcus faecalis
JH2-2 in the digestive tract of gnotobiotic mice and to
E. faecium
64/3 in vitro. Retransfer of Tn
1549
-like from an
E. faecium
transconjugant also containing Tn
916
to
E. faecium
BM77 was obtained in vitro, albeit at a very low frequency. Transfer efficiency was found to be both donor and recipient dependent. Pulsed-field gel electrophoresis analysis of total SmaI-digested DNA of 48 transconjugants indicated in 27 instances the acquisition of ca. 34 kb of DNA. Two transconjugants harbored two copies of the transposon. Sequencing of the flanking regions of Tn
1549
-like in 48 transconjugants revealed 29 integration events in 26 loci in the
E. faecium
genome, and two hot spots for insertion were identified. Integration of the transposon was associated with the acquisition of 5 (
n
= 18) or 6 (
n
= 7) bp of donor DNA or with 5-bp duplications of target DNA in the remaining transconjugants. These data demonstrate functionality of the Tn
1549
-like element and attest that the transfer of the
vanB
operon between enterococci and human commensal anaerobes occurs in the intestinal environment.
Activities of Telithromycin, Erythromycin, Fluoroquinolones, and Doxycycline against
Campylobacter
Strains Isolated from Finnish Subjects
Authors: Schönberg-Norio Daniela , Hänninen Marja-Liisa , Katila Marja-Leena , Kaukoranta Suvi-Sirkku , Koskela Markku , Eerola Erkki , Uksila Jaakko , Pajarre Sini , Rautelin Hilpi 
Published: February 2006

ABSTRACT

The in vitro susceptibilities of 478
Campylobacter jejuni
and
Campylobacter coli
strains isolated from Finnish subjects during 2002 to 2004 were determined. Susceptibility to erythromycin remained high, and telithromycin did not offer any advantage over erythromycin. Reduced susceptibilities to fluoroquinolones and doxycycline were detected almost exclusively among isolates of foreign origin.
Staphylococcus
Efflux
msr
(A) Gene Characterized in
Streptococcus
,
Enterococcus
,
Corynebacterium
, and
Pseudomonas
Isolates
Authors: Ojo Kayode K. , Striplin Megan J. , Ulep Catherine C. , Close Natasha S. , Zittle Jennifer , Luis Henrique , Bernardo Mario , Leitao Jorge , Roberts Marilyn C. 
Published: February 2006

ABSTRACT

The staphylococcal
msr
(A) gene, coding for a macrolide efflux protein, was identified in three new gram-positive genera and one gram-negative genus. These
msr
(A) genes shared 99 to 100% identity with each other and the staphylococcal gene. This study demonstrates that the
msr
(A) gene has a wider host range than previously reported.
In Vitro Activity of Novel Rifamycins against Rifamycin-Resistant
Staphylococcus aureus
Authors: Murphy Christopher K. , Mullin Steve , Osburne Marcia S. , van Duzer John , Siedlecki Jim , Yu Xiang , Kerstein Kathy , Cynamon Michael , Rothstein David M. 
Published: February 2006

ABSTRACT

We describe novel rifamycin derivatives (new chemical entities [NCEs]) that retain significant activity against a comprehensive collection of
Staphylococcus aureus
strains that are resistant to rifamycins. This collection of resistant strains contains 21 of the 26 known single-amino-acid alterations in RpoB, the target of rifamycins. Some NCEs also demonstrated a lower frequency of resistance development than rifampin and rifalazil in
S. aureus
as measured in a resistance emergence test. When assayed for activity against the strongest rifamycin-resistant mutants, several NCEs had MICs of 2 μg/ml, in contrast to MICs of rifampin and rifalazil, which were 512 μg/ml for the same strains. The properties of these NCEs therefore demonstrate a significant improvement over those of earlier rifamycins, which have been limited primarily to combination therapy due to resistance development, and suggest a potential use of these NCEs for monotherapy in several clinical indications.
Pharmacodynamic Evaluation of the Intracellular Activities of Antibiotics against
Staphylococcus aureus
in a Model of THP-1 Macrophages
Authors: Barcia-Macay Maritza , Seral Cristina , Mingeot-Leclercq Marie-Paule , Tulkens Paul M. , Van Bambeke Françoise 
Published: February 2006

ABSTRACT

The pharmacodynamic properties governing the activities of antibiotics against intracellular
Staphylococcus aureus
are still largely undetermined. Sixteen antibiotics of seven different pharmacological classes (azithromycin and telithromycin [macrolides]; gentamicin [an aminoglycoside]; linezolid [an oxazolidinone]; penicillin V, nafcillin, ampicillin, and oxacillin [β-lactams]; teicoplanin, vancomycin, and oritavancin [glycopeptides]; rifampin [an ansamycin]; and ciprofloxacin, levofloxacin, garenoxacin, and moxifloxacin [quinolones]) have been examined for their activities against
S. aureus
(ATCC 25923) in human THP-1 macrophages (intracellular) versus that in culture medium (extracellular) by using a 0- to 24-h exposure time and a wide range of extracellular concentrations (including the range of the MIC to the maximum concentration in serum [
C
max
; total drug] of humans). All molecules except the macrolides caused a net reduction in bacterial counts that was time and concentration/MIC ratio dependent (four molecules tested in detail [gentamicin, oxacillin, moxifloxacin, and oritavancin] showed typical sigmoidal dose-response curves at 24 h). Maximal intracellular activities remained consistently lower than extracellular activities, irrespective of the level of drug accumulation and of the pharmacological class. Relative potencies (50% effective concentration or at a fixed extracellular concentration/MIC ratio) were also decreased, but to different extents. At an extracellular concentration corresponding to their
C
max
s (total drug) in humans, only oxacillin, levofloxacin, garenoxacin, moxifloxacin, and oritavancin had truly intracellular bactericidal effects (2-log decrease or more, as defined by the Clinical and Laboratory Standards Institute guidelines). The intracellular activities of antibiotics against
S. aureus
(i) are critically dependent upon their extracellular concentrations and the duration of cell exposure (within the 0- to 24-h time frame) to antibiotics and (ii) are always lower than those that can be observed extracellularly. This model may help in rationalizing the choice of antibiotic for the treatment of
S. aureus
intracellular infections.
Telavancin versus Standard Therapy for Treatment of Complicated Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: FAST 2 Study
Authors: Stryjewski Martin E. , Chu Vivian H. , O'Riordan William D. , Warren Brian L. , Dunbar Lala M. , Young David M. , Vallée Marc , Fowler Vance G. , Morganroth Joel , Barriere Steven L. , Kitt Michael M. , Corey G. Ralph 
Published: February 2006

ABSTRACT

Telavancin is a bactericidal lipoglycopeptide with a multifunctional mechanism of action. We conducted a randomized, double blind, active-control phase II trial. Patients ≥18 years of age with complicated skin and skin structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin at 10 mg/kg intravenously every 24 h (q24h) or standard therapy (antistaphylococcal penicillin at 2 g q6h or vancomycin at 1 g q12h). A total of 195 patients were randomized and received at least one dose of study medication. Clinical success rates were similar in all analysis populations at test of cure. In microbiologically evaluable patients with
Staphylococcus aureus
at baseline (
n
= 91), 96% of the telavancin group and 90% of the standard-therapy group were cured. Among patients with methicillin-resistant
S. aureus
(MRSA) at baseline (
n
= 45), clinical cure rates were also 96% for telavancin and 90% for standard therapy. Microbiologic eradication in patients with
S. aureus
infection was better with telavancin compared to standard therapy (92% versus 78%,
P
= 0.07) and significantly better in patients with MRSA (92% versus 68%;
P
= 0.04). Therapy was discontinued for an adverse event (AE) in 6% and 3% of the patients receiving telavancin and standard therapy, respectively. Except for two cases of rash in the telavancin group, these AEs were similar in type and severity in the two groups. The overall incidences and severities of AEs and laboratory abnormalities were similar between the two groups. These data support the ongoing studies assessing the efficacy and safety of telavancin in the treatment of serious gram-positive infections, particularly involving MRSA.