bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bactericidal Activity of Vancomycin in Cerebrospinal Fluid
Authors: Nagl Markus , Neher Claudia , Hager Josef , Pfausler Bettina , Schmutzhard Erich , Allerberger Franz 
Published: October 2018

ABSTRACT

Intraventricular application of vancomycin is an effective therapeutic regimen for the treatment of shunt-associated staphylococcal ventriculitis. We examined the in vitro activity of vancomycin at high concentrations against
Staphylococcus aureus
ATCC 25923 and
Staphylococcus epidermidis
ATCC 12228 in human cerebrospinal fluid samples. Time-kill curves revealed equal efficacies for concentrations of 10, 100, and 300 μg/ml, and incubation times of 24 to 48 h were needed to achieve a 3 log
10
reduction of viable bacteria. A concentration of 5 μg/ml showed a slightly lower activity, but this difference was not significant. In an infant who was successfully treated for shunt-associated ventriculitis due to
S. epidermidis
by once-daily local administration of vancomycin (3 mg for 2 days and 5 mg for 4 days [0.5 to 0.8 mg/kg of body weight]) the in vivo kill kinetics were similar to those for the in vitro results. These results support time-dose regimens that provide trough vancomycin levels of 5 to 10 μg/ml.
Pharmacokinetics of Enrofloxacin and Danofloxacin in Plasma, Inflammatory Exudate, and Bronchial Secretions of Calves following Subcutaneous Administration
Authors: McKellar Quintin , Gibson Ian , Monteiro Ana , Bregante Miguel 
Published: October 2018

ABSTRACTEnrofloxacin (2.5 mg/kg of body weight) and danofloxacin (1.25 mg/kg) were administered subcutaneously to ruminating calves (n= 8) fitted with subcutaneous tissue cages. Concentrations of enrofloxacin, its metabolite ciprofloxacin, and danofloxacin in blood (plasma), tissue cage exudate (following intracaveal injection of 0.3 ml of 1% [vol/wt] carrageenan), and bronchial secretions were measured by high-performance liquid chromatography (HPLC) and microbiological assay (enrofloxacin plus ciprofloxacin and danofloxacin). Mean maximum concentrations (Cmax) ± standard deviations of enrofloxacin (0.24 ± 0.08 μg/ml), ciprofloxacin (0.11 ± 0.03 [total, 0.34 ± 0.10] μg/ml), and danofloxacin (0.23 ± 0.05 μg/ml) were detected in the plasma of calves by HPLC. TheCmaxwere 0.49 ± 0.17 μg/ml (enrofloxacin equivalents) and 0.24 ± 0.03 μg/ml (danofloxacin) when they were measured by microbiological assay. MeanCmaxin exudate (HPLC) were 0.18 ± 0.07 μg/ml (enrofloxacin), 0.10 ± 0.04 μg/ml (ciprofloxacin), 0.27 ± 0.09 μg/ml (enrofloxacin plus ciprofloxacin), and 0.19 ± 0.05 μg/ml (danofloxacin), and concentrations in exudate exceeded those in plasma from 8 h (enrofloxacin and ciprofloxacin) or 6 h (danofloxacin) after drug administration. TheCmaxwere 0.34 ± 0.09 μg/ml (enrofloxacin equivalents) and 0.22 ± 0.04 μg/ml (danofloxacin) in exudate when they were measured by the microbiological assay. The maximum mean concentration achieved in bronchial secretions (HPLC) were 0.07 ± 0.04 μg/ml (enrofloxacin), 0.04 ± 0.07 μg/ml (ciprofloxacin), 0.10 ± 0.05 μg/ml (enrofloxacin plus ciprofloxacin), and 0.12 ± 0.09 μg/ml (danofloxacin). The maximum mean concentration in bronchial secretions from a limited number of animals from which samples were available for microbiological assay were 0.27 ± 0.11 μg/ml (n= 4 [enrofloxacin equivalents]) and 0.14 ± 0.02 μg/ml (n= 3 [danofloxacin]). With predictive models of efficacy (Cmax/MIC and area under the concentration-time curve/MIC ratios in plasma) forPasteurella multocida(MIC of enrofloxacin, 0.06 μg/ml [24]; MIC of danofloxacin, 0.06 μg/ml [6]), enrofloxacin produced scores of 8.17 and 52.00, respectively, compared to those of danofloxacin, which were 4.02 and 23.05, respectively. With the dosing rates recommended in some markets by manufacturers, enrofloxacin and danofloxacin achieved concentrations above the MICs for important pathogenic organisms in plasma, tissue cage exudate, and bronchial secretion. Since fluoroquinolones display concentration-dependent activities,Cmax/MIC ratios may be critical to efficacy. In the United States enrofloxacin is currently the only fluoroquinolone licensed for food animals and dosages for acute respiratory disease are 2.5 to 5 mg/kg for 3 days or 7.5 to 12.5 mg/kg once. The higher dosages on a single occasion are likely to conferCmax/MIC ratios that are associated with greater clinical efficacy.
Hydroxyurea Enhances the Activities of Didanosine, 9-[2-(Phosphonylmethoxy)ethyl]adenine, and 9-[2-(Phosphonylmethoxy)propyl]adenine against Drug-Susceptible and Drug-Resistant Human Immunodeficiency Virus Isolates
Authors: Palmer Sarah , Shafer Robert W. , Merigan Thomas C. 
Published: October 2018

ABSTRACT
We assessed the effects of hydroxyurea (HU) at a concentration of 50 μM on the in vitro activities of 2′,3′-dideoxyinosine (ddI), 9-[2-(phosphonylmethoxy)ethyl]adenine (PMEA), and 9-[2-(phosphonylmethoxy)propyl]adenine (PMPA) against a wild-type human immunodeficiency virus (HIV) type 1 (HIV-1) laboratory isolate and a panel of five well-characterized drug-resistant HIV isolates. Fifty micromolar HU significantly increased the activities of ddI, PMEA, and PMPA against both the wild-type and the drug-resistant HIV-1 isolates. In fixed combinations, both ddI and PMEA were synergistic with HU against wild-type and drug-resistant viruses.
Penetration of Ciprofloxacin into the Interstitial Space of Inflamed Foot Lesions in Non-Insulin-Dependent Diabetes Mellitus Patients
Authors: Müller Markus , Brunner Martin , Hollenstein Ursula , Joukhadar Christian , Schmid Rainer , Minar Erich , Ehringer Herbert , Eichler Hans Georg 
Published: October 2018

ABSTRACT

Interstitial ciprofloxacin concentrations were measured by microdialysis in inflamed foot lesions of non-insulin-dependent diabetes mellitus patients following intravenous administration of 0.2 g of ciprofloxacin. Interstitial ciprofloxacin concentrations were significantly lower than corresponding serum concentrations. There was no significant difference in the penetration of ciprofloxacin into inflamed and unaffected tissue (area under the concentration-time curve
infection
/area under the concentration-time curve
unaffected tissue
= 0.99 ± 0.15 [mean ± standard error],
n
= 6). Thus, inflammation appears to have little or no effect on the penetration of ciprofloxacin into tissue.
A New Point Mutation (P157S) in the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 Confers Low-Level Resistance to (−)-β-2′,3′-Dideoxy-3′-Thiacytidine
Authors: Smith Robert A. , Klarmann George J. , Stray Kirsten M. , von Schwedler Uta K. , Schinazi Raymond F. , Preston Bradley D. , North Thomas W. 
Published: October 2018

ABSTRACT

A P157S mutation in the reverse transcriptase (RT) of human immunodeficiency virus type 1 conferred fivefold resistance to (−)-β-2′,3′-dideoxy-3′-thiacytidine in cell culture. Interestingly, the P157S mutation resulted in increased sensitivity (two- to threefold) to 3′-azido-3′-deoxythymidine (AZT) and to (
R
)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). A similar increase in susceptibility to AZT and to PMPA was also conferred by the M184V mutation in RT.
Molecular Characterization of the SHV-11 β-Lactamase of
Shigella dysenteriae
Authors: Ahamed Jasimuddin , Kundu Manikuntala 
Published: October 2018

ABSTRACT

A β-lactamase with an
M
r
of 29,000 and a pI of 7.6 was partially purified from a clinical isolate of
Shigella dysenteriae
. The
bla
gene encoded the SHV-11 enzyme carrying the substitution Leu→Gln at position 35 and was linked to a strong promoter. This variant, unlike the prototype SHV-1 enzyme, hydrolyzed oxacillin, cloxacillin, and oxyiminocephalosporins such as cefotaxime.
Characterization and Quantitation of the Pharmacodynamics of Fluconazole in a Neutropenic Murine Disseminated Candidiasis Infection Model
Authors: Andes D. , van Ogtrop M. 
Published: October 2018

ABSTRACT

We determined the pharmacodynamic parameter and the magnitude of that parameter that was predictive of the efficacy of fluconazole in the treatment of disseminated candidiasis. We used a neutropenic murine model of disseminated
Candida albicans
infection to characterize the time course of activity of fluconazole. Quantitation of colony counts in kidneys after 24 h of therapy with a wide range of doses and three dosing intervals was used to determine the dose required to achieve 50% of the maximal effect (ED
50
). The ED
50
was similar for each of the dosing intervals studied, supporting the area under the concentration-time curve (AUC) MIC ratio as the parameter that predicts the efficacy of fluconazole. Similar studies were performed with
C. albicans
strains for which fluconazole MICs are in the susceptible-dose-dependent range (MICs, 16 to 32 mg/liter). We found that the magnitude of the AUC/MIC ratio required to reach the ED
50
was similar for all three organisms studied, ranging from 12 to 25. When the pharmacokinetics of fluconazole in humans are considered, these AUC/MIC ratios would support in vitro susceptibility breakpoints of 8 mg/liter for dosages of 200 mg/day and susceptibility breakpoints of 16 to 32 mg/liter for dosages of 400 to 800 mg/day.
Prevalence and Mechanisms of Macrolide Resistance in Clinical Isolates of Group A Streptococci from Ontario, Canada
Authors: De Azavedo J. C. S. , Yeung R. H. , Bast D. J. , Duncan C. L. , Borgia S. B. , Low D. E. 
Published: October 2018

ABSTRACT

A total of 3,205 group A streptoccal isolates were collected in 1997 through a private laboratory which serves community physicians in southern Ontario and which represents a population base of 6 million people. Nonsusceptibility to erythromycin was detected for 67 (2.1%) isolates both by disk diffusion and by broth microdilution. Of these, 47 (70%) were susceptible to clindamycin and were found by PCR to possess the
mef
gene. Of the other 20 strains, 18 and 2 showed inducible and constitutive resistance, respectively, to clindamycin. Nineteen of these strains were shown by PCR to possess the
ermTR
gene, and a single constitutively resistant strain harbored an
ermB
gene. Sixteen (24%) erythromycin-resistant strains were also resistant to tetracycline. All were susceptible to penicillin and chloramphenicol.
Sulfonamide Resistance in Clinical Isolates of
Campylobacter jejuni
: Mutational Changes in the Chromosomal Dihydropteroate Synthase
Authors: Gibreel Amera , Sköld Ola 
Published: October 2018

ABSTRACT

The characterization of the genetic basis of sulfonamide resistance in
Campylobacter jejuni
was attempted. The resistance determinant from a sulfonamide-resistant strain of
C. jejuni
was cloned and was found to show 42% identity with the
folP
gene (which codes for dihydropteroate synthase, the target of sulfonamides) of the related bacterium
Helicobacter pylori
. The sequences of the areas surrounding the
folP
gene in
C. jejuni
showed similarity to those of the areas surrounding the corresponding gene in
H. pylori
. The
folP
gene of
C. jejuni
, which mediates the resistance, was observed to show particular features when it was compared to other known
folP
genes. One of these features is the presence of two pairs of direct repeats (15 and 27 bp) within the coding sequence of the gene. Comparison of the
C. jejuni folP
genes that mediate susceptibility and resistance revealed the occurrence of mutations that changed four amino acid residues. Resistance of
C. jejuni
to sulfonamides could be associated with one or several of these four mutational substitutions, which all occurred in the five different resistant isolates studied. The codon for one of these changed amino acids was found to be located in the second direct repeat within the coding sequence of the gene. The change made the repeat perfect. The transformation of both the resistance and the susceptibility variants of the gene into an
Escherichia coli folP
knockout mutant was found to complement the dihydropteroate synthase deficiency, confirming that the characterized sulfonamide resistance determinant codes for the
C. jejuni
dihydropteroate synthase enzyme. Kinetic measurements established different affinities of sulfonamide for the dihydropteroate synthase enzyme isolated from the resistant and susceptible strains. In conclusion, sulfonamide resistance in
C. jejuni
was shown to be associated with mutational changes in the chromosomally located gene for dihydropteroate synthase, the target of sulfonamides.
Activities of Clinafloxacin, Alone and in Combination with Other Compounds, against 45 Gram-Positive and -Negative Organisms for Which Clinafloxacin MICs Are High
Authors: Clark Catherine L. , Jacobs Michael R. , Appelbaum Peter C. 
Published: October 2018

ABSTRACT
Time-kill studies indicated that clinafloxacin showed synergy after 24 h with ceftazidime, amikacin, and imipenem against 12, 8, and 10 of 33 gram-negative rods, respectively; with vancomycin, teicoplanin, cefotaxime, and amikacin against 3, 3, 1, and 1 of 9 staphylococci and enterococci, respectively; and with vancomycin, penicillin, and cefotaxime against 0, 2, and 2 of 3 pneumococci, respectively. The MICs of clinafloxacin alone for most strains were ≥1 μg/ml.
Topical glyceryl trinitrate for the treatment of tendinopathies: a systematic review
Authors: Challoumas Dimitris , Kirwan Paul D , Borysov Dmytro , Clifford Christopher , McLean Michael , Millar Neal L 
Published: October 2018

ObjectiveTo produce a best evidence synthesis of the clinical effects of topical glyceryl trinitrate (GTN) in the treatment of tendinopathies.DesignA systematic review of published randomised controlled trials (RCTs) of the use of GTN in patients with tendinopathy.Data sourcesMEDLINE, Embase, Scopus and CINAHL from database inception to January 2018.MethodsWe examined RCTs comparing the effects of topical GTN with either placebo or other treatments on tendinopathy. Overall quality of each eligible study was determined based on a combined assessment of internal validity, external validity and precision. The level of evidence for each assessed parameter was rated based on the system by van Tulderet al.ResultsA total of 10 eligible RCTs were identified including patients with tendinopathy of the rotator cuff (n=4), wrist extensors (n=3), Achilles (n=2) and patellar (n=1) tendons. For all tendinopathies, improvements in pain were significant when comparing GTN versus placebo in the short term (<8 weeks; poor evidence). Significant improvements in midterm outcomes for treatment with GTN versus placebo included the following: patient satisfaction (strong evidence); chances of being asymptomatic with activities of daily living (strong evidence); range of movement (moderate evidence); strength (moderate evidence); pain (at night and with activity; poor evidence) and local tenderness (poor evidence). Patients treated with topical GTN reported a higher incidence of headaches than those who received placebo (moderate evidence).Conclusions and relevanceTreatment of tendinopathies with topical GTN for up to 6 months appears to be superior to placebo and may therefore be a useful adjunct to the treating healthcare professions.
Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial
Authors: Ackerman Kathryn E , Singhal Vibha , Baskaran Charumathi , Slattery Meghan , Campoverde Reyes Karen Joanie , Toth Alexander , Eddy Kamryn T , Bouxsein Mary L , Lee Hang , Klibanski Anne , Misra Madhusmita 
Published: October 2018

ObjectiveNormal-weight oligo-amenorrhoeic athletes (OAA) are at risk for low bone mineral density (BMD). Data are lacking regarding the impact of oestrogen administration on bone outcomes in OAA. Our objective was to determine the effects of transdermal versus oral oestrogen administration on bone in OAA engaged in weight-bearing activity.Methods121 patients with OAA aged 14–25 years were randomised to receive: (1) a 17β-estradiol transdermal patch continuously with cyclic oral micronised progesterone (PATCH), (2) a combined ethinyl estradiol and desogestrel pill (PILL) or (3) no oestrogen/progesterone (NONE). All participants received calcium and vitamin D supplementation. Areal BMD was assessed at the lumbar spine, femoral neck, total hip and total body less head using dual-energy X-ray absorptiometry at baseline, 6 and 12 months. Intention-to-treat (ITT) and completers analyses were performed.ResultsRandomised groups did not differ for age, body mass index or BMD Z-scores at baseline. For ITT analysis, spine and femoral neck BMD Z-scores significantly increased in the PATCH versus PILL (p=0.011 and p=0.021, respectively) and NONE (p=0.021 and p=0.033, respectively) groups, and hip BMD Z-scores significantly increased in the PATCH versus PILL group (p=0.018). Similar findings were noted in completers analysis.ConclusionTransdermal estradiol over 12 months improves BMD in young OAA, particularly compared with an ethinyl estradiol-containing contraceptive pill/oral contraceptives.Trial registration numberNCT00946192; Pre-results
Sociodemographic correlates of eating disorder subtypes among men and women in France, with a focus on age
Authors: Andreeva Valentina A , Tavolacci Marie-Pierre , Galan Pilar , Ladner Joel , Buscail Camille , Péneau Sandrine , Galmiche Marie , Hercberg Serge , Déchelotte Pierre , Julia Chantal 
Published: October 2018

BackgroundOn the population level, the association of age and other sociodemographic factors with eating disorders (ED) is unclear.MethodsWe used cross-sectional data from the French general population-based NutriNet-Santé e-cohort (n=49 603 adults; 76.3% women; mean age=50.4±14.6 years). ED were evaluated in 2014 with the 5-item SCOFF screening questionnaire and the Expali algorithmic tool. Likely cases of restrictive, bulimic, hyperphagic and other ED were the dependent variables. Age, marital status, education, occupation, physical activity and smoking were the independent variables. Associations were estimated via gender-stratified multivariable polytomous logistic regression.ResultsAmong women, age displayed inverse linear associations with both restrictive and bulimic ED, underscoring 18–25 years as the most vulnerable period (adjusted OR=3.37, 95% CI: 2.24 to 5.08 for restrictive ED; adjusted OR=2.98, 95% CI: 2.37 to 3.74 for bulimic ED, respectively). A similar association was observed in men regarding bulimic ED. In women, age was not associated with hyperphagic ED for which living alone, low education, low physical activity, being a homemaker/disabled/unemployed/retired, a manual worker or a former/current smoker had increased importance. In men, 18–39 years emerged as the least vulnerable period regarding hyperphagic ED (adjusted OR=0.74, 95% CI: 0.56 to 0.99). Across gender, having postsecondary education had significant inverse associations with all except restrictive ED, whereas being a student had a significant positive association with restrictive ED.ConclusionsThe findings support gender-specific associations of age with four ED subtypes and could inform future prevention initiatives targeting specific ED among specific age groups.Trial registration numberNCT03335644; Pre-results.
10q23.31 microduplication encompassing PTEN decreases mTOR signalling activity and is associated with autosomal dominant primary microcephaly
Authors: Oliveira Danyllo , Leal Gabriela Ferraz , Sertié Andréa L , Caires Jr Luiz Carlos , Goulart Ernesto , Musso Camila Manso , Oliveira João Ricardo Mendes de , Krepischi Ana Cristina Victorino , Vianna-Morgante Angela Maria , Zatz Mayana 
Published: October 2018

BackgroundHereditary primary microcephaly (MCPH) is mainly characterised by decreased occipitofrontal circumference and variable degree of intellectual disability. MCPH with a dominant pattern of inheritance is a rare condition, so far causally linked to pathogenic variants in the ALFY, DPP6, KIF11 and DYRK1A genes.ObjectiveThis study aimed at identifying the causative variant of the autosomal dominant form of MCPH in a Brazilian family with three affected members.MethodsFollowing clinical evaluation of two sibs and their mother presenting with autosomal dominant MCPH, array comparative genome hybridisation was performed using genomic DNA from peripheral blood of the family members. Gene and protein expression studies were carried out in cultured skin fibroblasts.ResultsA 382 kb microduplication at 10q23.31 was detected, encompassing the entire PTEN, KLLN and ATAD1 genes. PTEN haploinsufficiency has been causally associated with macrocephaly and autism spectrum disorder and, therefore, was considered the most likely candidate gene to be involved in this autosomal dominant form of MCPH. In the patients’ fibroblasts, PTEN mRNA and protein were found to be overexpressed, and the phosphorylation patterns of upstream and downstream components of the mammalian target of rapamycin (mTOR) signalling pathway were dysregulated.ConclusionsTaken together, our results demonstrate that the identified submicroscopic 10q23.31 duplication in a family with MCPH leads to markedly increased expression of PTEN and reduced activity of the mTOR signalling pathway. These results suggest that the most probable pathomechanism underlying the microcephaly phenotype in this family involves downregulation of the mTOR pathway through overexpression of PTEN.
Engineering geological considerations for the ‘Old’ Beacon Hill Railway Tunnel, Hong Kong Special Administrative Region
Authors: Mackay Alexander D. 
Published: October 2018

Abstract
The ‘Old’ Beacon Hill Tunnel was constructed through granite from 1906 to 1910 as part of the Kowloon Canton Railway in the then British colony of Hong Kong. It was the first railway tunnel to be constructed in this region and, at 2.2 km long, longer than any Chinese railway tunnel. Prior to Japanese occupation in December 1941, the British detonated charges to collapse the tunnel to deny its use as an invasion route. Following Japanese defeat in 1945 and return to British government, the tunnel was re-excavated and the damaged sections were supported using steel arches based on Terzaghi's rock mass classification system, which uses geological descriptions to classify loading onto arched tunnel supports. The railway was subsequently realigned during the 1980s and placed in a new tunnel running alongside and west of the ‘Old’ Beacon Hill Tunnel, which was converted to accommodate a pipeline connecting gas supplies. Ground investigations implemented after return of the territory to Chinese sovereignty in July 1997 established that groundwater flow and tunnel stability were influenced by a dyke within the granite, joint set orientation, faulting and weathering as well as the wartime detonations.