bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Efficacies of Human Simulated Exposures of Tedizolid and Linezolid against Staphylococcus aureus in the Murine Thigh Infection Model
Authors: Keel R. A. , Tessier P. R. , Crandon J. L. , Nicolau D. P. 
Published: June 2012

ABSTRACT

Tedizolid (formally torezolid) is an expanded-spectrum oxazolidinone with enhanced
in vitro
potency against Gram-positive pathogens, including methicillin-susceptible
Staphylococcus aureus
(MSSA) and methicillin-resistant
S. aureus
(MRSA). The efficacies of human simulated exposures of tedizolid and linezolid against
S. aureus
in an immunocompetent mouse thigh model over 3 days were compared. Four strains of MRSA and one of MSSA with tedizolid and linezolid MICs ranging from 0.25 to 0.5 and from 2 to 4 μg/ml, respectively, were utilized. Tedizolid or linezolid was administered in a regimen simulating a human steady-state 24-h area under the free concentration-time curve of 200 mg every 24 h (Q24) or 600 mg Q12, respectively. Thighs were harvested after 4, 8, 12, 24, 36, 48, and 72 h, and efficacy was determined by the change in bacterial density. The mean bacterial density in control mice increased over the 3-day period. After 24 h of treatment, a reduction in bacterial density of ≥1 log CFU was observed for both the tedizolid and linezolid treatments. Antibacterial activity was enhanced for both agents with a reduction of ≥2.6 log CFU after 72 h of treatment. Any statistically significant differences (
P
≤ 0.05) in efficacy between the agents were transient and did not persist throughout the 72-h treatment period. The tedizolid and linezolid regimens demonstrated similar
in vivo
efficacies against the
S. aureus
isolates tested. Both agents were bacteriostatic at 24 h and bactericidal on the third day of treatment. These data support the clinical utility of tedizolid for skin and skin structure infections caused by
S. aureus
, as well as the bactericidal activity of the oxazolidinones after 3 days of treatment.
Impact of Penicillin Nonsusceptibility on Clinical Outcomes of Patients with Nonmeningeal Streptococcus pneumoniae Bacteremia in the Era of the 2008 Clinical and Laboratory Standards Institute Penicillin Breakpoints
Authors: Choi Seong-Ho , Chung Jin-Won , Sung Heungsup , Kim Mi-Na , Kim Sung-Han , Lee Sang-Oh , Kim Yang Soo , Woo Jun Hee , Choi Sang-Ho 
Published: June 2012

ABSTRACT

To investigate the impact of penicillin nonsusceptibility on clinical outcomes of patients with nonmeningeal
Streptococcus pneumoniae
bacteremia (SPB), a retrospective cohort study was performed. The characteristics of 39 patients with penicillin-nonsusceptible SPB (PNSPB) were compared to those of a group of age- and sex-matched patients (
n
= 78) with penicillin-susceptible SPB (PSSPB). Susceptibility to penicillin was redetermined by using the revised Clinical and Laboratory Standards Institute (CLSI) penicillin breakpoints in CLSI document M100-S18. Although the PNSPB group tended to have more serious initial manifestations than the PSSPB group, the two groups did not differ significantly in terms of their 30-day mortality rates (30.8% versus 23.1%;
P
= 0.37) or the duration of hospital stay (median number of days, 14 versus 12;
P
= 0.89). Broad-spectrum antimicrobial agents, such as extended-spectrum cephalosporins, vancomycin, and carbapenem, were frequently used in both the PNSPB and PSSPB groups. Multivariate analysis revealed that ceftriaxone nonsusceptibility (adjusted odds ratio [aOR] = 4.88; 95% confidence interval [CI] = 1.07 to 22.27;
P
= 0.041) was one of the independent risk factors for 30-day mortality. Thus, when the 2008 CLSI penicillin breakpoints are applied and the current clinical practice of using wide-spectrum empirical antimicrobial agents is pursued, fatal outcomes in patients with nonmeningeal SPB that can be attributed to penicillin nonsusceptibility are likely to be rare. Further studies that examine the clinical impact of ceftriaxone nonsusceptibility in nonmningeal SPB may be warranted.
Increase of β-Lactam-Resistant Invasive Haemophilus influenzae in Sweden, 1997 to 2010
Authors: Resman Fredrik , Ristovski Mikael , Forsgren Arne , Kaijser Bertil , Kronvall Göran , Medstrand Patrik , Melander Eva , Odenholt Inga , Riesbeck Kristian 
Published: June 2012

ABSTRACT

The proportions of
Haemophilus influenzae
resistant to ampicillin and other β-lactam antibiotics have been low in Sweden compared to other countries in the Western world. However, a near-doubled proportion of nasopharyngeal Swedish
H. influenzae
isolates with resistance to β-lactams has been observed in the last decade. In the present study, the epidemiology and mechanisms of antimicrobial resistance of
H. influenzae
isolates from blood and cerebrospinal fluid in southern Sweden from 1997 to 2010 (
n
= 465) were studied. Antimicrobial susceptibility testing was performed using disk diffusion, and isolates with resistance to any tested β-lactam were further analyzed in detail. We identified a significantly increased (
P
= 0.03) proportion of β-lactam-resistant invasive
H. influenzae
during the study period, which was mainly attributed to a significant recent increase of β-lactamase-negative β-lactam-resistant isolates (
P
= 0.04). Furthermore, invasive β-lactamase-negative β-lactam-resistant
H. influenzae
isolates from 2007 and onwards were found in higher proportions than the corresponding proportions of nasopharyngeal isolates in a national survey. Multiple-locus sequence typing (MLST) of this group of isolates did not completely separate isolates with different resistance phenotypes. However, one cluster of β-lactamase-negative ampicillin-resistant (BLNAR) isolates was identified, and it included isolates from all geographical areas. A truncated variant of a β-lactamase gene with a promoter deletion,
bla
TEM-1
-PΔ dominated among the β-lactamase-positive
H. influenzae
isolates. Our results show that the proportions of β-lactam-resistant invasive
H. influenzae
have increased in Sweden in the last decade.
Efavirenz Pharmacokinetics in Cerebrospinal Fluid and Plasma over a 24-Hour Dosing Interval
Authors: Yilmaz Aylin , Watson Victoria , Dickinson Laura , Back David 
Published: June 2012

ABSTRACTWe determined the pharmacokinetics of efavirenz in plasma and cerebrospinal fluid (CSF) over a 24-h dosing interval in a patient who had undergone a lumbar drain because of cryptococcal meningitis. Drug concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry in paired CSF (n= 24) and plasma (n= 25) samples. The median plasma efavirenz concentration was 3,718 ng/ml (range, 2,439 to 4,952), and the median CSF concentration was 16.3 ng/ml (range, 7.3 to 22.3). The CSF/plasma area-under-the-curve ratio was 0.0044 corresponding to a CSF penetration of 0.44% of plasma.
Memantine and cholinesterase inhibitor combination therapy for Alzheimer's disease: a systematic review
Authors: Farrimond Lucy E , Roberts Emmert , McShane Rupert 
Published: June 2012

BackgroundMemantine is licensed for moderate-to-severe Alzheimer's disease (AD). National Institute for Clinical Excellence (NICE) guidance does not recommend the use of memantine in combination with cholinesterase inhibitors (acetylcholinesterase inhibitor (AChEI)). The underpinning meta-analysis was disputed by the manufacturer.ObjectivesTo compare the efficacy of AChEI monotherapy with combination memantine and AChEI therapy in patients with moderate-to-severe AD and to examine the impact of including unpublished data on the results.DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesThe Cochrane Dementia Group trial register, ALOIS, searched for the last time on 3 May 2011.Data synthesisData from four domains (clinical global, cognition, function, behaviour and mood) were pooled. Sensitivity analyses examined the impact on the NICE-commissioned meta-analysis of restricting data to patients with moderate-to-severe AD and of including an unpublished trial of an extended release preparation of memantine.ResultsPooled data from the trials, which were included in the NICE-commissioned meta-analysis but which were restricted to moderate-to-severe AD only, showed a small effect of combination therapy on cognition (standardised mean difference (SMD)=−0.29, 95% CI −0.45 to −0.14). Adding data from an unpublished trial of an extended release memantine (total three trials, 1317 participants) showed a small benefit of combination therapy on global scores (SMD=−0.20, 95% CI −0.31 to −0.09), cognition (SMD=−0.25, 95% CI −0.36 to −0.14) and behaviour and mood (SMD=−0.17, 95% CI −0.32 to −0.03) but not on function (SMD=−0.04, 95% CI −0.21 to 0.13) at 6 months. No clinical data have been reported from a 1-year trial, although this found ‘no significant benefit’ on any clinical measures at 1 year.ConclusionsThese results suggest that there may be a small benefit at 6 months of adding memantine to AChEIs. However, the impact on clinical global impression depends on exactly which studies are included, and there is no benefit on function, so its clinical relevance is not robustly demonstrated. Currently available information from randomised controlled trails indicates no benefit of combination therapy over monotherapy at 1 year. Legislation on the form and content of registry posted results is needed in Europe.
Association mapping of height and maturity across five environments using the sorghum mini core collection
Authors: Upadhyaya Hari D. , Wang Yi-Hong , Sharma Shivali , Singh Sube 
Published: June 2012

Sorghum is a potential energy crop thanks to its high biomass productivity and low input. Biomass yield in sorghum is defined by height and maturity. To develop molecular breeding tools for genetic improvement of these two traits, we have identified simple sequence repeat markers linked to height and maturity using a pool-based association mapping technique. The sorghum mini core collection was evaluated across five environments for height and maturity. Seven tall and seven short accessions were selected based on their height in all environments. Likewise, six early- and 10 late-maturing accessions were selected mostly based on their maturity in two post-rainy seasons. Two additional height pools were constructed based on phenotypes in one environment. The three pairs of pools were screened with 703 SSR markers and 39 polymorphic markers were confirmed by individual genotyping. Association mapping of the 39 markers with 242 accessions from the mini core collection identified five markers associated with maturity or height. All were clustered on chromosomes 6, 9, and 10 with previously mapped height and maturity markers or QTLs. One marker associated with both height and maturity was 84 kb from recently cloned Ma1. These markers will lay a foundation for identifying additional height and maturity genes in sorghum.
Coronary blood flow in dogs with contractile dysfunction due to experimental volume overload.
Authors: Carabello B A , Nakano K , Ishihara K , Kanazawa S , Biederman R W , Spann J F 
Published: June 2012

BACKGROUND
Abnormalities in coronary blood flow are responsible for stress-induced reductions in contractile function in pressure overload hypertrophy. Less is known about coronary blood flow in volume overload. In this study, we tested the hypothesis that coronary blood flow abnormalities were responsible for contractile abnormalities in experimental volume overload hypertrophy.

METHODS AND RESULTS
We examined coronary blood flow at rest and during pacing in seven dogs with contractile dysfunction secondary to chronic experimental mitral regurgitation (average regurgitant fraction at 3 months, 0.58 +/- 0.05). After 3 months of mitral regurgitation, left ventricular mass had increased from 92 +/- 8 g at baseline to 118 +/- 10 g (p less than 0.002). The slope of the end-ejection stress-volume relation, one of our indexes used to estimate contractile function, had fallen from 5.4 +/- 0.3 at baseline to 3.0 +/- 0.3 at 3 months of mitral regurgitation (p less than 0.001). In the mitral regurgitation dogs, coronary blood flow at rest was similar to that of control dogs (endocardial blood flow: control dogs, 1.33 +/- 0.12 ml/min/g; mitral regurgitation dogs, 1.16 ml/min/g, p = NS; epicardial blood flow at rest: control dogs, 1.30 +/- 0.16 ml/min/g; mitral regurgitation dogs 1.13 +/- 0.2 ml/min/g, p = NS). With pacing-induced stress, coronary blood flow increased appropriately in control and mitral regurgitation dogs. Ultrasonic dimension gauges placed in the endocardium and epicardium demonstrated no further deterioration in ventricular function during pacing in the mitral regurgitation dogs. In a separate group of five control dogs and five dogs with mitral regurgitation and left ventricular dysfunction, coronary blood flow was examined in the conscious closed-chest state at rest, during adenosine infusion, and during rapid atrial pacing (240 beats/min). Blood flow increased similarly in both groups during pacing and adenosine infusion.

CONCLUSIONS
We conclude that in dogs with mitral regurgitation that have developed contractile dysfunction, abnormalities in coronary blood flow do not explain the resting contractile dysfunction. Furthermore, studies during pacing-induced stress and coronary vasodilation with adenosine demonstrate that substantial coronary blood flow reserve is present in this type of volume overload hypertrophy.
Ten-year incidence of myocardial infarction and prognosis after infarction. Department of Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery.
Authors: Peduzzi P , Detre K , Murphy M L , Thomsen J , Hultgren H , Takaro T 
Published: June 2012

BACKGROUND
The 10-year incidence of myocardial infarction (fatal and nonfatal) and the prognosis after infarction were evaluated in 686 patients with stable angina who were randomly assigned to medical or surgical treatment in the Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery.

METHODS AND RESULTS
Myocardial infarction was defined by either new Q wave findings or clinical symptoms compatible with myocardial infarction accompanied by serum enzyme elevations with or without electrocardiographic findings. Treatment comparisons were made according to original treatment assignment; 35% of the medical cohort had bypass surgery during the 10-year follow-up period. The overall cumulative infarction rate was somewhat higher in patients assigned to surgery (36%) than in medical patients (31%) (p = 0.13) due to perioperative infarctions (13%) and an accelerated infarction rate after the fifth year of follow-up (average, 2.4%/yr in the surgical group versus 1.4%/yr in the medical group). The 10-year cumulative incidence of death or myocardial infarction was also higher in surgical (54%) than in medical (49%) patients (p = 0.20). According to the Cox model, the estimated risk of death after infarction was 59% lower in surgical than in medical patients (p less than 0.0001). The reduction in postinfarction mortality with surgery was most striking in the first month after the event: 99% in the first month (p less than 0.0001) and 49% subsequently (p less than 0.0001). The estimated risk of death in the absence of infarction was nearly identical regardless of treatment (p = 0.75). Exclusion of perioperative infarctions did not alter the findings.

CONCLUSIONS
Although surgery does not reduce the incidence of myocardial infarction overall, it does reduce the risk of mortality after infarction, particularly in the first 30 days after the event (fatal infarctions).
Results and follow-up after percutaneous pulsed laser-assisted balloon angioplasty guided by spectroscopy.
Authors: Geschwind H J , Aptecar E , Boussignac G , Dubois-Randé J L , Zelinsky R , Poirot G , Tomaru T 
Published: June 2012

BACKGROUND
Few data are available on the long-term outcome of patients who undergo laser-assisted balloon angioplasty for recanalization of occluded peripheral arteries. Because the cost of laser angioplasty is high, the value of the method should be carefully analyzed before it can be considered a routine method for recanalization. The purpose of this study was to evaluate the early and late results of laser-assisted balloon angioplasty in patients who could not be recanalized by conventional techniques.

METHODS AND RESULTS
Laser angioplasty was performed in 66 patients with total occlusion of the iliofemoral artery in whom mechanical techniques failed to recanalize the obstructed vessel. The system consisted of a pulsed dye laser operated at 480 nm, 2 microseconds/pulse, 5 Hz, 50 mJ/pulse coupled into a 0.021-in. laser catheter. The treatment laser was connected with a diagnostic laser to induce tissue fluorescence for spectroscopic analysis via the same fiber. The treatment laser was emitted only when atheromatous tissue was recognized. After a pilot hole was created by laser emission, dilatation was performed to enlarge the channel. The mean length of occlusion was 8.8 +/- 6.1 cm. The primary success rate was 82%. It did not depend on the length of occlusion but was greater in non-calcified than in calcified lesions (88% versus 71%, p less than 0.03). Complications included seven early reocclusions that could be recanalized and eight perforations without clinical sequelae. At a mean 18-month follow-up, 64% of the laser-treated arteries remained patent. The rate of patency was related neither to the length of the occlusion nor to calcifications but was lower in patients who had early reocclusion (p less than 0.02).

CONCLUSIONS
Pulsed dye laser-assisted balloon angioplasty is effective for recanalization of totally occluded arteries that cannot be treated by conventional means. The efficacy is limited by calcifications. The long-term patency rate is acceptable given the severity of the lesions.
Concept of maximal flow ratio for immediate evaluation of percutaneous transluminal coronary angioplasty result by videodensitometry.
Authors: Pijls N H , Aengevaeren W R , Uijen G J , Hoevelaken A , Pijnenburg T , van Leeuwen K , van der Werf T 
Published: June 2012

BACKGROUND
In the setting of percutaneous transluminal coronary angioplasty (PTCA), immediate information about the result of the intervention is important, whereas morphological parameters are often less reliable than in diagnostic coronary arteriography. Recently, a new videodensitometric method was introduced and validated in animal experiments, which allows accurate comparison of maximal myocardial perfusion between situations with different degrees of stenosis. This method uses mean transit time (Tmn) of the contrast agent at maximal hyperemia as a parameter for maximal flow and is strictly in accordance with indicated dilation theory.

METHODS AND RESULTS
In 40 patients with angina pectoris, single-vessel disease, and a positive exercise test at the time of acceptance for PTCA, this approach was applied for evaluation of the improvement of maximal flow achieved by the PTCA. Maximal vasodilation was induced immediately before and 15 minutes after PTCA by intracoronary administration of papaverine, and digital angiographic studies were performed. By special breath-holding instruction, almost motionless, triggered image acquisition was possible during 15-20 heartbeats. Excellent subtraction images could be obtained, and reliable determination of Tmn at maximal hyperemia was possible in 33 patients both before and after PTCA. The ratio between maximal flow after and before PTCA, called maximal flow ratio (MFR), was represented by the ratio between Tmn before and after the intervention and compared with the results of exercise testing 24-48 hours before and 7-10 days after the procedure. After correction for pressure changes, MFR was 2.2 +/- 1.5 for the 33 dilated vessels and 1.0 +/- 0.2 for 25 normal vessels serving as a control. In 94% of all patients, an MFR value of more than 1.6 or less than 1.6 discriminated between presence or absence of reversal of exercise test result from positive to negative. If on-line judgment of success was based upon angiographic parameters or measurement of trans-stenotic pressure gradient, the relation with noninvasive functional improvement was present only in 66% and 74% of all patients, respectively. A definite range of what can be called normal Tmn at maximal hyperemia could be distinguished, and post-PTCA values for successfully dilated arteries returned completely to this normal range.

CONCLUSIONS
Accurate comparison of maximal myocardial perfusion before and after PTCA is possible in man, improvement of maximal flow is highly related to functional improvement as indicated by exercise test results, and, therefore, this method provides a straightforward way for on-line evaluation of the result of the intervention.
Heart rate adjustment of exercise-induced ST segment depression. Improved risk stratification in the Framingham Offspring Study.
Authors: Okin P M , Anderson K M , Levy D , Kligfield P 
Published: June 2012

BACKGROUND
Simple heart rate adjustment of ST segment depression during exercise (delta ST/HR index) and the pattern of ST depression as a function of heart rate during exercise and recovery (the rate-recovery loop) have been shown to improve the ability of the exercise electrocardiogram to detect the presence of coronary heart disease (CHD), but the performance of these methods for the prediction of future coronary events remains to be examined.

METHODS AND RESULTS
We compared the delta ST/HR index and the rate-recovery loop with standard electrocardiographic criteria for prediction of CHD events in 3,168 asymptomatic men and women in the Framingham Offspring Study who underwent treadmill exercise electrocardiography and who, at entry, were free of clinical and electrocardiographic evidence of CHD. After a mean follow-up of 4.3 years, there were 65 new CHD events: four sudden deaths, 24 new myocardial infarctions, and 37 incident cases of angina pectoris. When a Cox proportional hazards model with adjustment for age and sex was used, a positive exercise electrocardiogram by standard criteria (greater than or equal to 0.1 mV horizontal or downsloping ST segment depression) was not predictive of new CHD events (chi 2 = 0.40, p = 0.52). In contrast, stratification according to the presence or absence of a positive delta ST/HR index (greater than or equal to 1.6 microV/beat/min) and a positive (counterclockwise) rate-recovery loop was associated with CHD event risk (chi 2 = 9.45, p less than 0.01) and separated subjects into three groups with varying risks of coronary events: high risk, when both tests were positive (relative risk 3.6; 95% confidence interval, 2.4-5.4); intermediate risk, when either the delta ST/HR index or the rate-recovery loop was positive (relative risk, 1.9; 95% confidence interval, 1.3-2.8); and low risk, when both tests were negative. After multivariate adjustment for age, sex, smoking, total cholesterol level, fasting glucose level, diastolic blood pressure, and electrocardiographic evidence of left ventricular hypertrophy, the combined delta ST/HR index and rate-recovery loop criteria remained predictive of coronary events (chi 2 = 5.45, p = 0.02).

CONCLUSIONS
Heart rate adjustment of ST segment depression by the delta ST/HR index and the rate-recovery loop during exercise electrocardiography can improve prediction of future coronary events in asymptomatic men and women.