bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short versus Long Infusion of Meropenem in Very-Low-Birth-Weight Neonates
Authors: Padari Helgi , Metsvaht Tuuli , Kõrgvee Lenne-Triin , Germovsek Eva , Ilmoja Mari-Liis , Kipper Karin , Herodes Koit , Standing Joseph F. , Oselin Kersti , Lutsar Irja 
Published: June 2012

ABSTRACT

Prolonged infusion of meropenem has been suggested in studies with population pharmacokinetic modeling but has not been tested in neonates. We compared the steady-state pharmacokinetics (PK) of meropenem given as a short (30-min) or prolonged (4-h) infusion to very-low-birth-weight (gestational age, <32 weeks; birth weight, <1,200 g) neonates to define the appropriate dosing regimen for a phase 3 efficacy study. Short (
n
= 9) or prolonged (
n
= 10) infusions of meropenem were given at a dose of 20 mg/kg every 12 h. Immediately before and 0.5, 1.5, 4, 8, and 12 h after the 4th to 7th doses of meropenem, blood samples were collected. Meropenem concentrations were measured by ultrahigh-performance liquid chromatography. PK analysis was performed with WinNonlin software, and modeling was performed with NONMEM software. A short infusion resulted in a higher mean drug concentration in serum (
C
max
) than a prolonged infusion (89 versus 54 mg/liter). In all but two patients in the prolonged-infusion group, the free serum drug concentration was above the MIC (2 mg/liter) 100% of the time. Meropenem clearance (CL) was not influenced by postnatal or postmenstrual age. In population PK analysis, a one-compartment model provided the best fit and the steady-state distribution volume (
V
ss
) was scaled with body weight and CL with a published renal maturation function. The covariates serum creatinine and postnatal and gestational ages did not improve the model fit. The final parameter estimates were a
V
ss
of 0.301 liter/kg and a CL of 0.061 liter/h/kg. Meropenem infusions of 30 min are acceptable as they balance a reasonably high
C
max
with convenience of dosing. In very-low-birth-weight neonates, no dosing adjustment is needed over the first month of life.
Prevalence and Molecular Characterization of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in a Pediatric Patient Population
Authors: Chandramohan Lakshmi , Revell Paula A. 
Published: June 2012

ABSTRACT

Very little is known about the prevalence and composition of various types of extended-spectrum β-lactamases (ESBL) in pediatric patients. The aims of this study were the following: (i) to determine the prevalence of ESBLs among
Enterobacteriaceae
in a tertiary-care pediatric population; (ii) to characterize the genetic composition of the identified ESBL enzymes; and (iii) to determine the relative prevalence of CTX-M enzymes and
Escherichia coli
ST131 strains among ESBL-producing isolates in the same pediatric patient population. Among the 1,430
Enterobacteriaceae
isolates screened for elevated MICs to cefotaxime and/or ceftazidime from pediatric patients during a 1-year period, 94 isolates possessed at least one ESBL gene. CTX-M was the most commonly isolated ESBL type, consisting of 74% of all ESBLs versus 27% TEM and 24% SHV enzymes. Sequence analysis and probe-specific real-time PCR revealed that the majority (80%) of the CTX-M-type ESBLs were CTX-M-15 enzymes, followed by CTX-M-14 (17%) and CTX-M-27(2.8%). Multilocus sequence typing (MLST) and repetitive PCR analyses revealed that the relative prevalence of ST131 among ESBL-producing
E. coli
isolates is 10.2%. This study highlights the growing problem of ESBL resistance in pediatric
Enterobacteriaceae
isolates and demonstrates a transition toward the predominance of CTX-M-type enzymes among ESBL-producing
Enterobacteriaceae
organisms causing pediatric infections.
Novel Mechanism for Fluoroquinolone Resistance in Acinetobacter baumannii
Authors: Saroj Sunil D. , Clemmer Katy M. , Bonomo Robert A. , Rather Philip N. 
Published: June 2012

ABSTRACT

An EZ::TN<R6Kγori/KAN-2>Tnp transposon insertion in an open reading frame of unknown function (
ncr
) in
Acinetobacter baumannii
resulted in an 8-fold increase in ciprofloxacin resistance (Cip
r
). Transposon insertions in an
ncr
mutant that reduced Cip
r
back to wild type mapped to three genes encoding subunits of the RecCBD exonuclease. The
ncr
mutation increased transcription of the
recCBD
genes, and overexpression of the
recCBD
genes in a wild-type background resulted in a 4-fold increase in Cip
r
.
In Vitro Microassay for Biological Activity of Cyclophosphamide Metabolites
Authors: Laux David , Lausch Robert N. 
Published: June 2012

A rapid tissue culture assay for detecting the activated metabolites of cyclophosphamide in serum is described. Serum obtained shortly after drug administration was added to microtest wells containing a known number of previously planted target cells. The presence and amount of drug was directly correlated with the degree of inhibition of target cell replication. Either transformed or untransformed cells could be used as the target cells. No inhibition of cell growth was observed if cyclophosphamide was added directly to target cells without prior in vivo activation.
The appearance and persistence of activated drug in hamster serum was followed by using in vitro microassay. Cyclophosphamide administered intraperitoneally was metabolized to its active form very rapidly, reaching peak activity in 15 min. After 2 h, activity was no longer detectable. Drug given subcutaneously was activated less rapidly and persisted for a longer period of time. The kinetics of drug activation, as determined by tissue culture assay, appeared to be similar to that obtained by chemical assay for other species.
Genome Sequence of Escherichia coli J53, a Reference Strain for Genetic Studies
Authors: Yi Hana , Cho Yong-Joon , Yong Dongeun , Chun Jongsik 
Published: June 2012

ABSTRACT

Escherichia coli
J53 (F
−
met pro
Azi
r
) is a derivative of
E. coli
K-12 which is resistant to sodium azide. This strain has been widely used as a general recipient strain for various conjugation experiments. Here, we report the genome sequence of
E. coli
J53 (=KACC 16628).
Genome Sequence of Enterohemorrhagic Escherichia coli NCCP15658
Authors: Song Ju Yeon , Yoo Ran Hee , Jang Song Yee , Seong Won-Keun , Kim Seon-Young , Jeong Haeyoung , Kang Sung Gyun , Kim Byung Kwon , Kwon Soon-Kyeong , Lee Choong Hoon , Yu Dong Su , Park Mi-Sun , Cho Seung-Hak , Kim Jihyun F. 
Published: June 2012

ABSTRACT

Enterohemorrhagic
Escherichia coli
causes severe food-borne disease in the guts of humans and animals. Here, we report the high-quality draft genome sequence of
E. coli
NCCP15658 isolated from a patient in the Republic of Korea. Its genome size was determined to be 5.46 Mb, and its genomic features, including genes encoding virulence factors, were analyzed.
Draft Genome Sequence of Serratia sp. Strain M24T3, Isolated from Pinewood Disease Nematode Bursaphelenchus xylophilus
Authors: Proença Diogo Neves , Espírito Santo Christophe , Grass Gregor , Morais Paula V. 
Published: June 2012

ABSTRACT

Here we report the draft genome sequence of
Serratia
sp. strain M24T3, which is associated with pinewood nematode
Bursaphelenchus xylophilus
, the causative agent of pine wilt disease.
Serratia
sp. strain M24T3 has been identified as a bionematocide for
B. xylophilus in vitro
, and multiple genes potentially involved in virulence and nematotoxity were identified.
Marathon related cardiac arrest risk differences in men and women
Authors: Roberts William O , Roberts Dana M , Lunos Scott 
Published: June 2012

ObjectiveTo determine the incidence of sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in men and women.DesignRetrospective cohort study.SettingTwo popular urban 42 km marathons.Participants1982 to 2009 finishers.Assessment of risk factorsRace records were assessed for finishers, age distribution and cardiac events by sex.Main outcome measuresThe SCA/SCD incidence for all (total), male and female finishers.ResultsThere were 548 092 finishers with women finishers increasing from 10% to 40% over the first 18 years and remaining near 40% for the last decade. There were 14 SCA events (1 woman, 13 men) with seven successful resuscitations yielding an all finishers SCA rate of 2.6 per 100 000 finishers. The SCA rates (per 100 000) for men and women were 3.4 (95% CI: 1.8 to 5.9) and 0.6 (95% CI: 0.0 to 3.3), respectively (p=0.079). The male SCA rate for the 2000–2009 decade was 4.6 per 100 000 finishers (95% CI: 1.8 to 9.5). Eleven of 13 men were >39 years old. The OR of a man experiencing SCA compared with woman was 5.7.ConclusionsAs the number of women participating in these two marathons has increased, the difference between the men's and total SCA and SCD incidence has increased for men, especially >39 years old, from coronary artery disease with men's incidence for SCA of 1 in 22 000 and SCD at 1 in 50 000 finishers over past decade.
Validity of a computerised five-level emergency triage system for patients with acute ischaemic stroke
Authors: Sung Sheng-Feng , Huang Ying-Chieh , Ong Cheung-Ter , Chen Wei 
Published: June 2012

ObjectivesAn ideal triage system used in the emergency department (ED) should identify patients who need urgent medical care. The purpose of this study was to validate the Taiwan Triage and Acuity Scale (TTAS) for stratifying patients according to their severity, need for thrombolysis, resource utilisation, and outcome.MethodsThe authors retrospectively reviewed all admitted patients with a discharge diagnosis of acute ischaemic stroke from January 2010 to September 2011. Presenting complaints, activation of code stroke protocol, eligibility of intravenous tissue plasminogen activator treatment, time from ED arrival to treatment, and outcome at discharge were compared by the five-level triage system.ResultsOf 706 enrolled patients (level 1, 55; level 2, 455; level 3, 192; level 4, 4; level 5, 0), there were 412 (58.4%) men and 294 women (41.6%), with a mean age of 69.4 years. The initial stroke severity, time from onset to arrival, time from arrival to imaging, proportion of patients for whom code stroke protocol was activated, length of hospital stay, and good functional outcome at discharge correlated with TTAS levels. A total of 84 patients were thrombolysis candidates, and 98.8% of them were designated as either level 1 or level 2. For those treated with thrombolytic therapy (n=47), the time from arrival to thrombolysis was not significantly different between TTAS level 1 and 2.ConclusionAcuity measured by the computerised TTAS demonstrated good validity in facilitating acute care of stroke patients with special regard to thrombolytic therapy.
Dietary and animal‐related factors associated with the rate of urinary oxalate and calcium excretion in dogs and cats
Authors: Dijcker J. C. , Hagen‐Plantinga E. A. , Everts H. , Bosch G. , Kema I. P. , Hendriks W. H. 
Published: June 2012

This paper reports the results of a cohort study and randomised clinical trial (RCT) in cross‐over design. In the cohort study, the range of urinary oxalate (Uox) and calcium (Uca) excretion was determined within a sample of the Dutch population of dogs and cats, and dietary and animal‐related factors associated with these urine parameters were identified. Spot urine samples were collected from privately owned dogs (n=141) and cats (n=50). The RCT determined the effect of a commercial raw meat diet versus a dry diet on Uox and Uca excretion rate in 23 dogs. In the cohort study, Uox excretion ranged from 21.1 to 170.6 mmol oxalate/mol creatinine in dogs and 27.5 to 161.6 in cats. Urinary calcium excretion ranged from 3.4 to 462.8 mmol calcium/mol creatinine in dogs and 10.1 to 128.0 in cats. In dogs, increased Uox and Uca excretion was associated with (1) the intake of a dry diet as the primary source of energy, (2) receiving no snacks and (3) breed. Increased Uox excretion was associated with males as well. In cats, urine collection in anaesthetised subjects was identified as a confounder. In the RCT, feeding the dry diet resulted in higher Uox (P<0.001) and Uca (P=0.021) excretion rates in dogs.
Viral protease inhibitors affect the production of virulence factors inCryptococcus neoformans
Authors: Sidrim J.J.C. , Perdigão-Neto L.V. , Cordeiro R.A. , Brilhante R.S.N. , Leite J.J.G. , Teixeira C.E.C. , Monteiro A.J , Freitas R.M.F. , Ribeiro J.F. , Mesquita J.R.L. , Gonçalves M.V.F. , Rocha M.F.G. 
Published: June 2012

The effects of the protease inhibitors saquinavir, darunavir, ritonavir, and indinavir on growth inhibition, protease and phospholipase activities, as well as capsule thickness of Cryptococcus neoformans were investigated. Viral protease inhibitors did not reduce fungal growth when tested in concentrations ranging from 0.001 to 1.000 mg/L. A tendency toward increasing phospholipase activity was observed with the highest tested drug concentration in a strain-specific pattern. However, these drugs reduced protease activity as well as capsule production. Our results confirm a previous finding that antiretroviral drugs affect the production of important virulence factors of C. neoformans.
BS2-2: Nuclear Receptor Coactivators: Physiology and Disease.
Authors: O'Malley BW 
Published: June 2012

Abstract
Nuclear receptors control gene expression by recruiting transcriptional coactivators (or corepressors). The coactivators are ‘master regulators’ that activate genes to control physiologies such as reproduction, growth and metabolism. Consequently, they are major players in the development of many inherited and acquired endocrine-related pathologies such as fertility/endometriosis, cancers, and disorders of carbohydrate, lipid and protein metabolism. The coactivator proteins provide important insights to polygenic diseases and represent a new class of drug targets for therapeutic interventions.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr BS2-2.
ES1-3: Treatment of Metastatic Breast Cancer – Breast Cancer as a Chronic Disease: Triple Negative Breast Cancer.
Authors: Stearns V 
Published: June 2012

Abstract
Carcinomas of the breast that do not express the estrogen or progesterone receptors (ER/PR) and are not associated with over-expression or amplification of HER2/neu have been designated triple negative breast cancer. These tumors represent approximately 15–20% of all breast cancers, but are more prevalent in younger women, in African Americans, and in BRCA1 mutation carriers. Molecular profiling data suggest that many of triple negative tumors, but not all, are basal-like. The basal-like tumors are more likely to be resistant to standard therapies resulting in disease recurrence and poor prognosis. It is likely that triple negative breast cancer will be further sub classified to several additional distinct subtypes. Regardless of additional sub classification of the entity, the only treatment currently available for women with triple negative breast cancer is chemotherapy-based. In this symposium, I will review current molecular classification, prognosis and predictive markers, treatment options, emerging approaches, and clinical trials.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES1-3.
ES6-1: Oncofertility: Translation in Multiple Dimensions.
Authors: Woodruff TK 
Published: June 2012

Abstract
Cancer is now a disease with a variety of treatment options, which are leading to longer and more productive lives by survivors. Globally, there are 10 million people diagnosed with cancer. 10% of these newly diagnosed men and women are under the age of 45 years old. Infertility can be a consequence of many of the more aggressive chemo- and radiation therapies that prolong and save lives. The ability to easily preserve sperm prior to cancer treatment provides hope at the time of diagnosis and families later in life for male survivors. A notable example is Tour de France winner Lance Armstrong who has three children conceived using sperm frozen days before he underwent the massive chemo- and radiation therapy that saved his life. Unlike sperm, the female germ cell, the oocyte or egg must be retrieved surgically. Moreover, the vast majority of collected oocytes will be immature and cannot be used immediately by a woman who is ready to start a family. The overall hypothesis of the program is that effective fertility-extending options can be provided to young women undergoing life-preserving cancer treatment. The purpose of our work is to bring physicians, medical ethicists, social scientists and basic scientists together to develop new strategies for fertility preservation for female cancer survivors under the new discipline of oncofertility. At the basic science level, complex issues of ovarian function and preservation must be addressed including the problem of follicle growth and development in vitro. Our investigative group has developed a 3-dimensional system that supports follicle development, largely, we believe, because the links between the oocyte and its surrounding cells are maintained. The goal of our program and the broader Oncofertility Consortium is to explore and expand the reproductive options available to young people facing a fertility-threatening but life-preserving cancer treatment.
This work is supported by NIH/NICHD Structure-Function Relationships in Reproductive Science, U54 HD041857; and, the Oncofertility Consortium, UL1DE019587 and RL1HD05829 http://oncofertility.northwestern.edu/
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES6-1.
OT1-02-13: Cardiac Biomarkers on Trastuzumab (Cabot Trial): Determining the Cardiac Biomarker Profile in Breast Cancer Patients Receiving Adjuvant Trastuzumab Therapy.
Authors: Kumar VNC , Kavsak P , Rask S , Mukherjee SD , Ellis P , Dhesy-Thind B 
Published: June 2012

Abstract
Background
Trastuzumab is a humanized anti-HER2 monoclonal antibody that has demonstrated a 50% reduction in the risk of HER2+ breast cancer recurrence. This benefit is at the risk of possible cardiac dysfunction. Detecting trastuzumab-related cardiotoxicity based on physical examination and assessment of left ventricular ejection fraction (LVEF) by serial echocardiography or multi gated acquisition (MUGA) scan, has low diagnostic sensitivity and low predictive power in detecting subclinical myocardial injury. There is interest in developing simple, non-invasive, and cost-effective tools for early identification of trastuzumab-related cardiotoxicity. Use of easily detectible cardiac biomarkers in blood, such as cardiac troponins (cTnT and cTnI) and natriuretic peptides (NPs), are being evaluated. Kavsak et al. have studied a high-sensitivity cTn (hs-cTn) assay that is 10-fold more sensitive, and may be able to identify evolving injury earlier when compared to the conventional cTn assays. B-type natriuretic peptide (BNP) has been established as an indicator for heart failure. Pro-BNP is secreted from the cardiac ventricles in response to increased pressure and volume and is divided into NT-pro-BNP and BNP. The longer half-life of NT-proBNP may make it a more accurate predictor of ventricular stress.
Trial design: This is a pilot single institution, prospective cohort study of 25 patients. Breast cancer patients will be seen at the Juravinski Cancer Centre, Hamilton, Canada. Biomarkers will be collected at baseline, then days 1 and 2 of every 21 day cycle for the first 3 months, then every 42 days for the next 3 months. LVEF will be measured at baseline and then every 3 months while on trastuzumab.
Eligibility criteria: Patients with stage I-III, HER2 positive (3+ by immunohistochemistry or FISH+) breast cancer receiving adjuvant trastuzumab therapy. Patients who have received prior trastuzumab therapy or are unable to provide informed consent will be excluded.
Specific aims: To determine the biological profile of cardiac biomarkers — cTnT, hs-cTn, and NT-proBNP — in patients on adjuvant trastuzumab; and, to determine if elevations in these biomarkers correlate with LVEF.
Statistical methods: A convenient sample size of 25 patients will be entered into this pilot study. The minimum of 20 patients is a requirement by the Clinical Laboratory Standards Institute (CLSI) to formally accept existing reference ranges for the cardiac biomarkers to be used in the HER2 breast cancer population (National Committee for Clinical Laboratory Standards (NCCLS)).
Present accrual and target accrual: 8 patients have enrolled to date.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-13.
OT1-03-02: SAFIR01: A Molecular Screening Trial for Metastatic Breast Cancer Patients.
Authors: Andre F , Peletekian C , Jimenez M , Ferrero JM , Delaloge S , Roman Roman S , Dessen P , Bonnefoi H 
Published: June 2012

Abstract
Background: High number of new drugs are targeting molecular alterations that occur in a few number of patients. Molecular screening that consists in the assessment of single molecular alteration during the screening phase of the therapeutic trial is not suitable. Indeed, this modality of screening is associated with a high rate of screen failure due to the low incidence of the molecular alteration. In order to optimize molecular screening, we have launched a clinical trial that aims at performing array CGH and hot spot mutations in patients with metastatic breast cancer.
Patients and Methods. The trial plans to include 400 patients with metastatic breast cancer and included the first patient in may 2011. This trial is being sponsored by French federation of Cancer centers (UNICANCER) and involves 20 centers. Biopsy is being performed on metastatic site. Both frozen and FFPE samples are obtained. DNA extraction is being performed in the investigation center after control for the % of cancer cells. Array CGH and PIK3CA/AKT mutations (SANGE method) are being performed in four genomic platforms. A pilot study that included 106 patients has shown the feasibility of such technologies in the context of daily practice. Data from array CGH are being sent to a bioinformatician who forward the results on both pre-selected targets, DNA instability and some targets of interest selected based on log2(ratio) and function. Recommendations for trials are then being sent to each investigator. There is no limitation for previous lines and it is recommended to perform biopsy in patients who do not present progressive disease. This trial is being funded by French NCI (750 000 euros)
Conclusion: SAFIR01 is a trial that aims at using high throughput technologies in order to drive patients with molecular alterations to specific therapeutic trials. Further amendments are being planned including implementation of high throughput sequencing and performance of functional testing. Further trial will compare this high throughput approach to standard methods for target identification.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-03-02.