bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Ginkgo Biloba on the Pharmacokinetics of Raltegravir in Healthy Volunteers
Authors: Blonk Maren , Colbers Angela , Poirters Anne , Schouwenberg Bas , Burger David 
Published: July 2012

ABSTRACT

Medicinal herbs may cause clinically relevant drug interactions with antiretroviral agents. Ginkgo biloba extract is a popular herbal product among HIV-infected patients because of its positive effects on cognitive function. Raltegravir, an HIV integrase inhibitor, is increasingly being used as part of combined antiretroviral therapy. Clinical data on the potential inhibitory or inductive effect of ginkgo biloba on the pharmacokinetics of raltegravir were lacking, and concomitant use was not recommended. We studied the effect of ginkgo biloba extract on the pharmacokinetics of raltegravir in an open-label, randomized, two-period, crossover phase I trial in 18 healthy volunteers. Subjects were randomly assigned to a regimen of 120 mg of ginkgo biloba twice daily for 15 days plus a single dose of raltegravir (400 mg) on day 15, a washout period, and 400 mg of raltegravir on day 36 or the test and reference treatments in reverse order. Pharmacokinetic sampling of raltegravir was performed up to 12 h after intake on an empty stomach. All subjects (9 male) completed the trial, and no serious adverse events were reported. Geometric mean ratios (90% confidence intervals) of the area under the plasma concentration-time curve from dosing to infinity (AUC
0-∞
) and the maximum plasma concentration (
C
max
) of raltegravir with ginkgo biloba versus raltegravir alone were 1.21 (0.93 to 1.58) and 1.44 (1.03 to 2.02). Ginkgo biloba did not reduce raltegravir exposure. The potential increase in the
C
max
of raltegravir is probably of minor importance, given the large intersubject variability of raltegravir pharmacokinetics and its reported safety profile.
Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects
Authors: Rodvold Keith A. , Gotfried Mark H. , Still J. Gordon , Clark Kay , Fernandes Prabhavathi 
Published: July 2012

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.
The Combination of Colistin and Doripenem Is Synergistic against Klebsiella pneumoniae at Multiple Inocula and Suppresses Colistin Resistance in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model
Authors: Deris Zakuan Z. , Yu Heidi H. , Davis Kathryn , Soon Rachel L. , Jacob Jovan , Ku Caron K. , Poudyal Anima , Bergen Phillip J. , Tsuji Brian T. , Bulitta Jurgen B. , Forrest Alan , Paterson David L. , Velkov Tony , Li Jian , Nation Roger L. 
Published: July 2012

ABSTRACT

Multidrug-resistant (MDR)
Klebsiella pneumoniae
may require combination therapy. We systematically investigated bacterial killing with colistin and doripenem mono- and combination therapy against MDR
K. pneumoniae
and emergence of colistin resistance. A one-compartment
in vitro
pharmacokinetic/pharmacodynamic model was employed over a 72-h period with two inocula (∼10
6
and ∼10
8
CFU/ml); a colistin-heteroresistant reference strain (ATCC 13883) and three clinical isolates (colistin-susceptible FADDI-KP032 [doripenem resistant], colistin-heteroresistant FADDI-KP033, and colistin-resistant FADDI-KP035) were included. Four combinations utilizing clinically achievable concentrations were investigated. Microbiological responses were examined by determining log changes and population analysis profiles (for emergence of colistin resistance) over 72 h. Against colistin-susceptible and -heteroresistant isolates, combinations of colistin (constant concentration regimens of 0.5 or 2 mg/liter) plus doripenem (steady-state peak concentration [
C
max
] of 2.5 or 25 mg/liter over 8 h; half-life, 1.5 h) generally resulted in substantial improvements in bacterial killing at both inocula. Combinations were additive or synergistic against ATCC 13883, FADDI-KP032, and FADDI-KP033 in 9, 9, and 14 of 16 cases (4 combinations at 6, 24, 48, and 72 h) at the 10
6
-CFU/ml inoculum and 14, 11, and 12 of 16 cases at the 10
8
-CFU/ml inoculum, respectively. Combinations at the highest dosage regimens resulted in undetectable bacterial counts at 72 h in 5 of 8 cases (4 isolates at 2 inocula). Emergence of colistin-resistant subpopulations in colistin-susceptible and -heteroresistant isolates was virtually eliminated with combination therapy. Against the colistin-resistant isolate, colistin at 2 mg/liter plus doripenem (
C
max
, 25 mg/liter) at the low inoculum improved bacterial killing. This investigation provides important information for optimization of colistin-doripenem combinations.
Vaccination with SesC Decreases Staphylococcus epidermidis Biofilm Formation
Authors: Shahrooei Mohammad , Hira Vishal , Khodaparast Laleh , Khodaparast Ladan , Stijlemans Benoit , Kucharíková Soňa , Burghout Peter , Hermans Peter W. M. , Van Eldere Johan 
Published: July 2012

ABSTRACT

The increased use of medical implants has resulted in a concomitant rise in device-related infections. The majority of these infections are caused by
Staphylococcus epidermidis
biofilms. Immunoprophylaxis and immunotherapy targeting
in vivo
-expressed, biofilm-associated, bacterial cell surface-exposed proteins are promising new approaches to prevent and treat biofilm-related infections, respectively. Using an
in silico
procedure, we identified 64 proteins that are predicted to be

S
.
e
pidermidis

s
urface exposed (Ses), of which 36 were annotated as (conserved) hypothetical. Of these 36 proteins, 5 proteins—3 LPXTG motif-containing proteins (SesL, SesB, and SesC) and 2 of the largest ABC transporters (SesK and SesM)—were selected for evaluation as vaccine candidates. This choice was based on protein size, number of antigenic determinants, or the established role in
S. epidermidis
biofilm formation of the protein family to which the candidate protein belongs. Anti-SesC antibodies exhibited the greatest inhibitory effect on
S. epidermidis
biofilm formation
in vitro
and on colonization and infection in a mouse jugular vein catheter infection model that includes biofilms and organ infections. Active vaccination with a recombinant truncated SesC inhibited
S. epidermidis
biofilm formation in a rat model of subcutaneous foreign body infection. Antibodies to SesC were shown to be opsonic by an
in vitro
opsonophagocytosis assay. We conclude that SesC is a promising target for antibody mediated strategies against
S. epidermidis
biofilm formation.
A Ferritin Mutant of Mycobacterium tuberculosis Is Highly Susceptible to Killing by Antibiotics and Is Unable To Establish a Chronic Infection in Mice
Authors: Pandey Ruchi , Rodriguez G. Marcela 
Published: July 2012

ABSTRACT

Iron is an essential, elusive, and potentially toxic nutrient for most pathogens, including
Mycobacterium tuberculosis
. Due to the poor solubility of ferric iron under aerobic conditions, free iron is not found in the host.
M. tuberculosis
requires specialized iron acquisition systems to replicate and cause disease. It also depends on a strict control of iron metabolism and intracellular iron levels to prevent iron-mediated toxicity. Under conditions of iron sufficiency,
M. tuberculosis
represses iron acquisition and induces iron storage, suggesting an important role for iron storage proteins in iron homeostasis.
M. tuberculosis
synthesizes two iron storage proteins, a ferritin (BfrB) and a bacterioferritin (BfrA). The individual contributions of these proteins to the adaptive response of
M. tuberculosis
to changes in iron availability are not clear. By generating individual knockout strains of
bfrA
and
bfrB
, the contribution of each one of these proteins to the maintenance of iron homeostasis was determined. The effect of altered iron homeostasis, resulting from impaired iron storage, on the resistance of
M. tuberculosis
to
in vitro
and
in vivo
stresses was examined. The results show that ferritin is required to maintain iron homeostasis, whereas bacterioferritin seems to be dispensable for this function.
M. tuberculosis
lacking ferritin suffers from iron-mediated toxicity, is unable to persist in mice, and, most importantly, is highly susceptible to killing by antibiotics, showing that endogenous oxidative stress can enhance the antibiotic killing of this important pathogen. These results are relevant for the design of new therapeutic strategies against
M. tuberculosis
.
Helicobacter pylori Requires TlpD-Driven Chemotaxis To Proliferate in the Antrum
Authors: Rolig Annah S. , Shanks James , Carter J. Elliot , Ottemann Karen M. 
Published: July 2012

ABSTRACT

Different disease outcomes of
Helicobacter pylori
infection correlate with distinct inflammation patterns. These different inflammatory distributions may be initiated by differences in bacterial localization. One
H. pylori
property known to affect murine stomach localization is chemotaxis, the ability to move in response to chemical cues. In this report, we used nonchemotactic mutants (Che
−
) to analyze whether chemotaxis is required for initial colonization of particular stomach regions or for subsequent growth therein. We found that
H. pylori
behaves differently in the corpus, antrum, and corpus-antrum transition zone subregions of the stomach. This outcome suggests that these regions contain unique chemotactic signals. In the corpus,
H. pylori
utilizes chemotaxis for initial localization but not for subsequent growth. In contrast, in the antrum and the corpus-antrum transition zone, chemotaxis does not help initial colonization but does promote subsequent proliferation. To determine which chemoreceptor is responsible for the corpus-antrum phenotypes, we infected mice with strains lacking each chemoreceptor. Strains lacking TlpA, TlpB, or TlpC displayed only modest deviations from the wild-type phenotype, while strains lacking TlpD resembled the Che
−
mutant in their antral colonization defect and fared even worse than the Che
−
mutant in the corpus. Additional analysis showed that inflammation is worse in the antrum than in the corpus in both wild-type and Che
−
mutant infections. These results suggest that chemotaxis, specifically, that controlled by TlpD, is necessary for
H. pylori
to survive or grow in the environment of increased inflammation in the antrum.
Abscess Formation and Alpha-Hemolysin Induced Toxicity in a Mouse Model of Staphylococcus aureus Peritoneal Infection
Authors: Rauch Sabine , DeDent Andrea C. , Kim Hwan Keun , Bubeck Wardenburg Juliane , Missiakas Dominique M. , Schneewind Olaf 
Published: July 2012

ABSTRACT

Staphylococcus aureus
is a frequent cause of skin infection and sepsis in humans. Preclinical vaccine studies with
S. aureus
have used a mouse model with intraperitoneal challenge and survival determination as a measure for efficacy. To appreciate the selection of protective antigens in this model, we sought to characterize the pathological attributes of
S. aureus
infection in the peritoneal cavity. Testing C57BL/6J and BALB/c mice, >10
9
CFU of
S. aureus
Newman were needed to produce a lethal outcome in 90% of animals infected via intraperitoneal injection. Both necropsy and histopathology revealed the presence of intraperitoneal abscesses in the vicinity of inoculation sites. Abscesses were comprised of fibrin as well as collagen deposits and immune cells with staphylococci replicating at the center of these lesions. Animals that succumbed to challenge harbored staphylococci in abscess lesions and in blood. The establishment of lethal infections, but not the development of intraperitoneal abscesses, was dependent on
S. aureus
expression of alpha-hemolysin (Hla). Active immunization with nontoxigenic Hla
H35L
or passive immunization with neutralizing monoclonal antibodies protected mice against early lethal events associated with intraperitoneal
S. aureus
infection but did not affect the establishment of abscess lesions. These results characterize a mouse model for the study of intraperitoneal abscess formation by
S. aureus
, a disease that occurs frequently in humans undergoing continuous ambulatory peritoneal dialysis for end-stage renal disease.
A longitudinal qualitative exploration of healthcare and informal support needs among survivors of critical illness: the RELINQUISH protocol
Authors: Ramsay Pam , Huby Guro , Rattray Janice , Salisbury Lisa G , Walsh Timothy Simon , Kean Susanne 
Published: July 2012

Introduction and backgroundSurvival following critical illness is associated with a significant burden of physical, emotional and psychosocial morbidity. Recovery can be protracted and incomplete, with important and sustained effects upon everyday life, including family life, social participation and return to work. In stark contrast with other critically ill patient groups (eg, those following cardiothoracic surgery), there are comparatively few interventional studies of rehabilitation among the general intensive care unit patient population. This paper outlines the protocol for a sub study of the RECOVER study: a randomised controlled trial evaluating a complex intervention of enhanced ward-based rehabilitation for patients following discharge from intensive care.Methods and analysisThe RELINQUISH study is a nested longitudinal, qualitative study of family support and perceived healthcare needs among RECOVER participants at key stages of the recovery process and at up to 1 year following hospital discharge. Its central premise is that recovery is a dynamic process wherein patients' needs evolve over time. RELINQUISH is novel in that we will incorporate two parallel strategies into our data analysis: (1) a pragmatic health services-oriented approach, using an a priori analytical construct, the ‘Timing it Right’ framework and (2) a constructivist grounded theory approach which allows the emergence of new themes and theoretical understandings from the data. We will subsequently use Qualitative Health Needs Assessment methodology to inform the development of timely and responsive healthcare interventions throughout the recovery process.Ethics and disseminationThe protocol has been approved by the Lothian Research Ethics Committee (protocol number HSRU011). The study has been added to the UK Clinical Research Network Database (study ID. 9986). The authors will disseminate the findings in peer reviewed publications and to relevant critical care stakeholder groups.
Simultaneous retinal and cortical visually evoked electrophysiological responses in between migraine attacks
Authors: Nguyen Bao N , McKendrick Allison M , Vingrys Algis J 
Published: July 2012

Purpose: People with migraine often report aversion to flickering lights and show abnormal results on behavioural tasks that require the processing of temporal visual information. Studies have reported that the cortically evoked electrophysiological response to a flickering visual stimulus is abnormal; however, none have considered whether there is an underlying pre-cortical abnormality. In this cross-sectional study, we consider whether people with migraine have retinal and cortical electrophysiological abnormalities to flickering stimuli. Methods: Monocular transient (1 Hz) and steady-state (8.3 Hz) pattern reversal electroretinograms (PERGs) and pattern visual evoked responses (PVERs) were measured simultaneously in 45 people with migraine (26 without aura, 19 with aura) and 30 non-headache controls at a time between migraine attacks. Results: PERG amplitude and timing did not differ significantly between groups. Transient PVER amplitude was significantly reduced (28%) in the migraine with aura group compared to the controls F(2,72) = 3.6, p = 0.03). Both migraine groups showed significant reductions (32%, 39%) in steady-state PVER amplitude relative to controls (F(2,70) = 4.3, p = 0.02). Conclusions: This study finds normal retinal processing of flickering stimuli in the presence of abnormal cortical function between migraine attacks.
Fixation of the Achilles Tendon Insertion Using Suture Button Technology
Authors: Fanter Nathan J. , Davis Edward W. , Baker Champ L. 
Published: July 2012

Background: In the operative treatment of Achilles insertional tendinopathy, no guidelines exist concerning which form of fixation of the Achilles tendon insertion is superior. Hypothesis: Transcalcaneal drill pin passage does not place any major plantar structures at risk, and the addition of a Krackow stitch and suture button to the fixation technique provides a significant increase in ultimate load to failure in Achilles tendon insertional repairs. Study Design: Controlled laboratory study. Methods: The Achilles tendon insertions in 6 fresh-frozen cadaveric ankles were detached, and transcalcaneal drill pins were passed. Plantar dissection took place to evaluate the drill pin relationship to the plantar fascia, lateral plantar nerve and artery, flexor digitorum longus tendon, and master knot of Henry. The Achilles tendons were then repaired with a double-row suture anchor construct alone or with a suture button and Krackow stitch added to the double-row suture anchor construct. The repairs were then tested to maximum load to failure at 20 mm/min. The mode of failure was recorded, and the mean maximum load to failure was assessed using the Student t test for distributions with equal variance. Results: Transcalcaneal drill pin passage did not place any selected anatomic structures at risk. The mean maximum load to failure for the suture bridge group was 239.2 N; it was 391.4 N for the group with the suture button ( P = .014). The lateral plantar artery was the structure placed at greatest risk from drill pin placement, with a mean distance of 22.7 mm (range, 16.5-29.2 mm) between the pin and artery. Conclusion: In this laboratory study, transcalcaneal drill pin passage appeared to be anatomically safe, and the use of suture button technology with a Krackow stitch for Achilles tendon insertional repair significantly increased repair strength. Clinical Relevance: Achilles tendon insertional repair with suture button fixation and a Krackow stitch may facilitate the earlier institution of postoperative rehabilitation and improve clinical outcomes.
A Pilot Study of Home-Based Videoconferencing for Breastfeeding Support
Authors: Rojjanasrirat Wilaiporn , Nelson Eve-Lynn , Wambach Karen A. 
Published: July 2012

Background: Research on using videoconferencing for breastfeeding support is limited. Purpose: Although European case reports have described videoconferencing for providing lactation support, this was the first study to assess the reliability and feasibility of home videoconferencing for breastfeeding assessment and support in the United States. Method: The study used 4 real-time, secure videoconferencing sessions to deliver lactation support to 10 mothers in the home. To assess interrater reliability, percentage agreement was calculated on LATCH assessment scores from telehealth and home-visit International Board Certified Lactation Consultants (IBCLCs) during the first 2 visits. Participants’ perceptions of satisfaction and the overall experiences were documented. Results: The percentage agreement on the 5 LATCH score dimensions ranged between 40% to 100% during the first visit and 80% to 100% during the second visit. To assess feasibility, participants reported their satisfaction with the technology and their perceptions of the videoconference consultation. All participants “strongly agreed” that they were comfortable talking about breastfeeding concerns using home videoconferencing. Conclusion: The findings suggest videoconferencing can potentially be used to support breastfeeding mothers in their homes.
Factors Considered in End-of-Life Care Decision Making by Health Care Professionals
Authors: Foo Wei Ting , Zheng Yiliang , Kwee Ann K. , Yang Grace M. , Krishna Lalit 
Published: July 2012

Aim: To explore the importance of factors influencing the end-of-life care decision making of health care professionals (HCPs) in Singapore. Methods: This cross-sectional survey encompassed facets of patient, family, and HCP-related care considerations. In total, 187 questionnaires were distributed to physicians and nurses and had a response rate of 78.6%. Results: The respondents rated patients’ wishes (96.6%), their clinical symptoms (93.9%), and patients’ beliefs (91.1%) very high. In all, 94.6% of the HCPs would respect a competent patient’s wishes over the family’s wishes when goals conflict. However, 59.9% of HCPs would abide by the family’s wishes when the patient loses capacity even if the patient’s previously expressed wishes are known. Conclusion: End-of-life care decision making by HCPs appears largely patient centered, although familial determination still wields significant influence with implications for advance care planning.