bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significantly higher frequency of Helicobacter suis in patients with idiopathic parkinsonism than in control patients
Authors: Blaecher C. , Smet A. , Flahou B. , Pasmans F. , Ducatelle R. , Taylor D. , Weller C. , Bjarnason I. , Charlett A. , Lawson A. J. , Dobbs R. J. , Dobbs S. M. , Haesebrouck F. 
Published: October 2013

SummaryBackgroundThere is increased proportional mortality from Parkinson's disease amongst livestock farmers. The hypokinesia of Parkinson's disease has been linked to Helicobacter pylori. H. suis is the most common zoonotic helicobacter in man.AimTo compare the frequency of H. suis, relative to H. pylori, in gastric biopsies of patients with idiopathic parkinsonism (IP) and controls from gastroenterology services.MethodsDNA extracts, archived at a Helicobacter Reference Laboratory, from IP patient and gastroenterology service biopsies were examined anonymously for H. suis, using species‐specific RT‐PCR.ResultsRelative risk of having H. suis in 60 IP patients compared with 256 controls was 10 times greater than that of having H. pylori. In patients with IP and controls, respectively, frequencies of H. suis were 27 (exact binomial 95% C.I. 15, 38) and 2 (0, 3)%, and of H. pylori, 28 (17, 40) and 16 (12, 21)%. Excess of H. suis in IP held when only the antral or corporal biopsy was considered. Of 16 IP patients with H. suis, 11 were from 19 with proven H. pylori eradication, 3 from 17 pre‐H. pylori eradication, 2 from 24 H. pylori culture/PCR‐negative. Frequency was different between groups (P = 0.001), greatest where H. pylori had been eradicated. Even without known exposure to anti‐H. pylori therapy, H. suis was more frequent in IP patients (5/41) than in controls (1/155) (P = 0.002). Partial multilocus sequence typing confirmed that strains from IP patients (6) and control (1) differed from RT‐PCR standard strain.ConclusionsGreater frequency of H. suis in idiopathic parkinsonism appears exaggerated following H. pylori eradication. Multilocus sequence testing comparison with porcine strains may clarify whether transmission is from pigs/porcine products or of human‐adapted, H. suis‐like, bacteria.
Formation of the prismatic layer in the freshwater bivalveHyriopsis cumingii: the feedback of crystal growth on organic matrix
Authors: Liu Xiaojun , Li Jiale 
Published: October 2013

AbstractThe squeezing hypothesis and the organic frameworks preformation hypothesis propose two different mechanisms to explain the interaction between organic frameworks and crystals during biomineralization of the prismatic layer of the mollusk shell. In this study, we began to studyHyriopsis cumingiishell formation and discover that this species seemed to follow the squeezing hypothesis. During the formation of the aragonite prismatic layer in the freshwater bivalveH. cumingii, we found that crystal growth was involved in controlling initiation of formation of the interprismatic organic membranes. First, newly formed crystals were embedded in the periostracum. Next, the interprismatic organic membranes of the prismatic layer were produced via squeezing between neighboring crystals. The organic matrix secreted by the mantle continuously self‐assembled into the interprismatic organic membranes as the crystals grew. In the mature stage, the interprismatic organic membranes were shaped by crystal growth. These findings provide evidence to support the squeezing hypothesis and add to the existing knowledge about interactions that occur at the organic–inorganic interfaces during mollusk shell biomineralization.
Effectiveness of pharmaceutical care for patients with chronic obstructive pulmonary disease (PHARMACOP): a randomized controlled trial
Authors: Tommelein Eline , Mehuys Els , Van Hees Thierry , Adriaens Els , Van Bortel Luc , Christiaens Thierry , Van Tongelen Inge , Remon Jean‐Paul , Boussery Koen , Brusselle Guy 
Published: October 2013

AimsFew well‐designed randomized controlled trials have been conducted regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of a pharmaceutical care programme for patients with COPD.MethodsThe pharmaceutical care for patients with COPD (PHARMACOP) trial is a single‐blind 3 month randomized controlled trial, conducted in 170 community pharmacies in Belgium, enrolling patients prescribed daily COPD medication, aged ≥50 years and with a smoking history of ≥10 pack‐years. A computer‐generated randomization sequence allocated patients to an intervention group (n = 371), receiving protocol‐defined pharmacist care, or a control group (n = 363), receiving usual pharmacist care (1:1 ratio, stratified by centre). Interventions focusing on inhalation technique and adherence to maintenance therapy were carried out at start of the trial and at 1 month follow‐up. Primary outcomes were inhalation technique and medication adherence. Secondary outcomes were exacerbation rate, dyspnoea, COPD‐specific and generic health status and smoking behaviour.ResultsFrom December 2010 to April 2011, 734 patients were enrolled. Forty‐two patients (5.7%) were lost to follow‐up. At the end of the trial, inhalation score [mean estimated difference (Δ),13.5%; 95% confidence interval (CI), 10.8–16.1; P < 0.0001] and medication adherence (Δ, 8.51%; 95% CI, 4.63–12.4; P < 0.0001) were significantly higher in the intervention group compared with the control group. In the intervention group, a significantly lower hospitalization rate was observed (9 vs. 35; rate ratio, 0.28; 95% CI, 0.12–0.64; P = 0.003). No other significant between‐group differences were observed.ConclusionsPragmatic pharmacist care programmes improve the pharmacotherapeutic regimen in patients with COPD and could reduce hospitalization rates.
A model‐based approach for the evaluation of once daily dosing of lamivudine in HIV‐infected children
Authors: Piana Chiara , Zhao Wei , Adkison Kimberly , Burger David , Jacqz‐Aigrain Evelyne , Danhof Meindert , Della Pasqua Oscar 
Published: October 2013

AimLittle attention has been paid to the effects of compliance and prescription practice on treatment outcome in HIV‐infected children. In this context, an evaluation of the role of covariates on pharmacokinetics is required to establish the impact of differences in dosing regimens. Here we investigate whether a once daily dosing regimen of lamivudine provides comparable exposure to the currently approved paediatric regimen.MethodsA hypothetical group of 180 patients between 3 months and 12 years old was used to evaluate the impact of body weight on systemic exposure to lamivudine. Simulation scenarios were evaluated using AUC and Cmax as parameters of interest. The analysis was performed using a population pharmacokinetic model previously implemented in nonmem v.6.2.ResultsThe simulations show that once daily dosing of lamivudine yields comparable exposure to historical values observed in children and adults, both for liquid and solid dosage forms. Simulated steady‐state AUC(0–24 h) and Cmax values after once daily doses ranged respectively from 9.95 mg l−1 h and 1.9 mg l−1 for children lighter than 14 kg to 13.75 mg l−1 h and 3.0 mg l−1 for children heavier than 30 kg. These values are comparable or higher than historical values observed after once daily dosing in children and adults.ConclusionsOur findings illustrate how dosing regimens can be evaluated taking into account the effects of developmental growth on drug disposition. Most importantly, they suggest that the reduction in dosing frequency to once daily leads to comparable lamivudine exposure, as observed after administration of a twice daily dosing regimen.
Relationship between plasma, atrial and ventricular perhexiline concentrations in humans: insights into factors affecting myocardial uptake
Authors: Drury Nigel E. , Licari Giovanni , Chong Cher‐Rin , Howell Neil J. , Frenneaux Michael P. , Horowitz John D. , Pagano Domenico , Sallustio Benedetta C. 
Published: October 2013

AimLittle is known regarding the steady‐state uptake of drugs into the human myocardium. Perhexiline is a prophylactic anti‐anginal drug which is increasingly also used in the treatment of heart failure and hypertrophic cardiomyopathy. We explored the relationship between plasma perhexiline concentrations and its uptake into the myocardium.MethodsBlood, right atrium ± left ventricle biopsies were obtained from patients treated with perhexiline for a median of 8.5 days before undergoing coronary surgery in the perhexiline arm of a randomized controlled trial. Perhexiline concentrations in plasma and heart tissue were determined by HPLC.ResultsAtrial biopsies were obtained from 94 patients and ventricular biopsies from 28 patients. The median plasma perhexiline concentration was within the therapeutic range at 0.24 mg l−1 (IQR 0.12–0.44), the median atrial concentration was 6.02 mg kg–1 (IQR 2.70–9.06) and median ventricular concentration was 10.0 mg kg–1 (IQR 5.76–13.1). Atrial (r2 = 0.76) and ventricular (r2 = 0.73) perhexiline concentrations were closely and directly correlated with plasma concentrations (both P < 0.001). The median atrial : plasma ratio was 21.5 (IQR 18.1–27.1), ventricular : plasma ratio was 34.9 (IQR 24.5–55.2) and ventricular : atrial ratio was 1.67 (IQR 1.39–2.22). Using multiple regression, the best model for predicting steady‐state atrial concentration included plasma perhexiline, heart rate and age (r2 = 0.83). Ventricular concentrations were directly correlated with plasma perhexiline concentration and length of therapy (r2 = 0.84).ConclusionsThis study demonstrates that plasma perhexiline concentrations are predictive of myocardial drug concentrations, a major determinant of drug effect. However, net myocardial perhexiline uptake is significantly modulated by patient age, potentially via alteration of myocardial:extracardiac drug uptake.
Cumulative Mitoxantrone‐Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study
Authors: Rossato Luciana G. , Costa Vera M. , Dallegrave Eliane , Arbo Marcelo , Dinis‐Oliveira Ricardo J. , Santos‐Silva Alice , Duarte José A. , de Lourdes Bastos Maria , Palmeira Carlos , Remião Fernando 
Published: October 2013

AbstractMitoxantrone (MTX) is an antineoplastic agent that can induce hepato‐ and haematotoxicity. This work aimed to investigate the occurrence of cumulative early and late MTX‐induced hepatic and haematological disturbances in an vivo model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 (MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the IgG levels was observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato‐ and direct hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury.
Nilotinib Interferes with the Signalling Pathways Implicated in Acetaminophen Hepatotoxicity
Authors: Shaker Mohamed E. 
Published: October 2013

AbstractNilotinib, a second‐generation tyrosine kinase inhibitor, has been recently approved for the treatment for chronic myeloid leukaemia. The objective of this study was to explore the potential effects of clinically relevant doses of nilotinib against acetaminophen (APAP)‐induced hepatotoxicity in mice. To simulate the clinical application in human beings, nilotinib (25 and 50 mg/kg) was administered to mice 2 hr after APAP intoxication (500 mg/kg). The results indicated that nilotinib (25 mg/kg) (i) abolished APAP‐induced liver injury and necro‐inflammation, (ii) increased hepatic‐reduced glutathione (GSH) and its related enzymes synthesis, (iii) suppressed hepatic oxidative/nitrosative stress cascades, (iv) decreased neutrophil accumulation in the liver, and (v) prevented the over‐expression of B‐cell lymphoma‐2 (bcl‐2), cyclin‐D1 and stem cell factor receptor (c‐Kit) proteins in the liver. Although nilotinib (50 mg/kg) acted through the same mechanisms, there was severe depletion in hepatic GSH content by nilotinib itself at that dose level, rather than the potent stimulation observed by using a dose of 25 mg/kg. Consequently, the mortality rate after 18 hr was 100% for nilotinib (50 mg/kg) + APAP (750 mg/kg) versus 60% for APAP (750 mg/kg) and 40% for nilotinib (25 mg/kg) + APAP (750 mg/kg) in the survival analysis experiment. In conclusion, nilotinib can counteract the hepatotoxicity produced by a non‐lethal dose of APAP. However, there is a risk of aggravating the mortality for a lethal dose of APAP when nilotinib is co‐administered at doses relatively high, or near to the clinical range because of hepatic GSH depletion and c‐kit inhibition.
Microdialysis as a Tool for Drug Quantification in the Bronchioles of Anaesthetized Pigs
Authors: Rottbøll Lisa A. H. , Friis Christian 
Published: October 2013

AbstractTarget site drug determinations are crucial for optimizing treatment of infectious diseases. There is limited knowledge of antibiotic drug penetration into the pulmonary epithelial lining fluid (PELF) and a lack of easily performed methods for continuous drug sampling hereof. The aim of this study was to develop a readily accessible microdialysis (MD) method for antibiotic drug quantification inPELFof pigs. The fluoroquinolone danofloxacin was administered to anaesthetized pigs allocated to three groups: intravenous injection, intravenous infusion and intramuscular injection.MDprobes were guided through a tracheostomy into the distal bronchioles using an insertion tube. Intravenously administered inulin served as a marker of extracellular fluid contamination ofPELF. Concentrations of free drug inMDfractions were compared to total and non‐protein‐bound drug concentrations in plasma. Rising and declining danofloxacin plasma concentrations were rapidly reflected inPELF, suggesting an efficient drug transport across the blood bronchial barrier. TheAUCFREE DRUG PELF/AUCFREE DRUG PLASMAratio was 1.8 (S.D. 0.4, 95%CL1.4–2.3). Although the probes were placed without fiberscopic or other special equipment, the danofloxacin concentrations inPELFwere consistent within the different administration groups. The describedMDmethod for drug quantification inPELFis easily accessible and provides repeatable results. However, trace amount of inulin was detected in theMDfractions, suggesting a local tissue reaction induced by theMDmembrane. The significance of this finding needs to be clarified in future studies.
Antiproliferative Activity of King Cobra (Ophiophagus hannah) Venom l‐Amino Acid Oxidase
Authors: Li Lee Mui , Chung Ivy , Yee Fung Shin , Kanthimathi M.S. , Hong Tan Nget 
Published: October 2013

AbstractKing cobra (Ophiophagus hannah) venom l‐amino acid oxidase (LAAO), a heat‐stable enzyme, is an extremely potent antiproliferative agent against cancer cells when compared with LAAO isolated from other snake venoms. King cobra venom LAAO was shown to exhibit very strong antiproliferative activities against MCF‐7 (human breast adenocarcinoma) and A549 (human lung adenocarcinoma) cells, with an IC50 value of 0.04 ± 0.00 and 0.05 ± 0.00 μg/mL, respectively, after 72‐hr treatment. In comparison, its cytotoxicity was about 3–4 times lower when tested against human non‐tumourigenic breast (184B5) and lung (NL 20) cells, suggesting selective antitumour activity. Furthermore, its potency in MCF‐7 and A549 cell lines was greater than the effects of doxorubicin, a clinically established cancer chemotherapeutic agent, which showed an IC50 value of 0.18 ± 0.03 and 0.63 ± 0.21 μg/mL, respectively, against the two cell lines. The selective cytotoxic action of the LAAO was confirmed by phycoerythrin (PE) annexin V/7‐amino‐actinomycin (AAD) apoptotic assay, in which a significant increase in apoptotic cells was observed in LAAO‐treated tumour cells than in their non‐tumourigenic counterparts. The ability of LAAO to induce apoptosis in tumour cells was further demonstrated using caspase‐3/7 and DNA fragmentation assays. We also determined that this enzyme may target oxidative stress in its killing of tumour cells, as its cytotoxicity was significantly reduced in the presence of catalase (a H2O2 scavenger). In view of its heat stability and selective and potent cytotoxic action on cancer cells, king cobra venom LAAO can be potentially developed for treating solid tumours.
Am I My Profession's Keeper?
Authors: Kolers Avery 
Published: October 2013

AbstractConscientious refusal is distinguished by its peculiar attitude towards the obligations that the objector refuses: the objector accepts the authority of the institution in general, but claims a right of conscience to refuse some particular directive. An adequate ethics of conscientious objection will, then, require an account of the institutional obligations that the objector claims a right to refuse. Yet such an account must avoid two extremes: ‘anarchism,’ where obligations apply only insofar as they match individual conscience; and ‘totalitarianism,’ where even immoral obligations bind us. The challenge is to explain institutional obligations in such a way that an agent can be obligated to act against conscience, yet can object if the institution's orders go too far. Standard accounts of institutional obligations rely on individual autonomy, expressed through consent. This paper rejects the Consent model; a better understanding of institutional obligations emerges from reflecting on the intersecting goods produced by institutions and the intersecting autonomy of numerous distinct agents rather than only one. The paper defends ‘Professionalism’ as a grounding of professional obligations. The professional context can justify acting against conscience but more often that context partly shapes the professional conscience. Yet Professionalism avoids totalitarianism by distinguishing between (mere) injustice and abuse. When institutions are – or we conscientiously believe them to be – merely unjust, their directives still obligate us; when they are abusive, however, they do not. Finally, the paper applies these results to the problem of conscientious refusal in general and specifically to controversial reproduction cases.
Welcome to the Wild, Wild North: Conscientious Objection Policies Governing Canada's Medical, Nursing, Pharmacy, and Dental Professions
Authors: Shaw Jacquelyn , Downie Jocelyn 
Published: October 2013

AbstractIn Canada, as in many developed countries, healthcare conscientious objection is growing in visibility, if not in incidence. Yet the country's health professional policies on conscientious objection are in disarray. The article reports the results of a comprehensive review of policies relevant to conscientious objection for four Canadian health professions: medicine, nursing, pharmacy and dentistry. Where relevant policies exist in many Canadian provinces, there is much controversy and potential for confusion, due to policy inconsistencies and terminological vagueness. Meanwhile, in Canada's three most northerly territories with significant Aboriginal populations, whose already precarious health is influenced by funding and practitioner shortages, there are major policy gaps applicable to conscientious objection. In many parts of the country, as a result of health professionals' conscientious refusals, access to some legal health services – including but not limited to reproductive health services such as abortion – has been seriously impeded. Although policy reform on conscientious conflicts may be difficult, and may generate strenuous opposition from some professional groups, for the sake of both patients and providers, such policy change must become an urgent priority.
Conscientious Refusal and Health Professionals: Does Religion Make a Difference?
Authors: Weinstock Daniel 
Published: October 2013

AbstractFreedom of Conscience and Freedom of Religion should be taken to protect two distinct sets of moral considerations. The former protects the ability of the agent to reflect critically upon the moral and political issues that arise in her society generally, and in her professional life more specifically. The latter protects the individual's ability to achieve secure membership in a set of practices and rituals that have as a moral function to inscribe her life in a temporally extended narrative. Once these grounds are distinguished, it becomes more difficult to grant healthcare professionals' claims to religious exemptions on the basis of the latter than it is on the basis of the former. While both sets of considerations generate ‘internal reasons’ for rights to accommodation, the relevant ‘external’ reasons present in the case of claims of moral conscience do not possess analogues in the case of claims of religious conscience. However, the argument applies only to ‘irreducibly religious’ claims, that is to claims that cannot be translated into moral vocabulary. What's more, there may be reasons to grant the claims of religious persons to exemptions that have to do not with the nature of the claims, but with the beneficial effects that the presence of religious persons may have in the context of the healthcare institutions of multi‐faith societies.
Two-Stage Hierarchical Group Testing for Multiple Infections with Application to the Infertility Prevention Project
Authors: Tebbs Joshua M. , McMahan Christopher S. , Bilder Christopher R. 
Published: October 2013

SummaryScreening for sexually transmitted diseases (STDs) has benefited greatly from the use of group testing (pooled testing) to lower costs. With the development of assays that detect multiple infections, screening practices now involve testing pools of individuals for multiple infections simultaneously. Building on the research for single infection group testing procedures, we examine the performance of group testing for multiple infections. Our work is motivated by chlamydia and gonorrhea testing for the infertility prevention project (IPP), a national program in the United States. We consider a two-stage pooling algorithm currently used to perform testing for the IPP. We first derive the operating characteristics of this algorithm for classification purposes (e.g., expected number of tests, misclassification probabilities, etc.) and identify pool sizes that minimize the expected number of tests. We then develop an expectation–maximization (EM) algorithm to estimate probabilities of infection using both group and individual retest responses. Our research shows that group testing can offer large cost savings when classifying individuals for multiple infections and can provide prevalence estimates that are actually more efficient than those from individual testing.