bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double‐blind, placebo‐controlled trials
Authors: Schoenfeld P. , Pimentel M. , Chang L. , Lembo A. , Chey W. D. , Yu J. , Paterson C. , Bortey E. , Forbes W. P. 
Published: April 2014

SummaryBackgroundThe efficacy of rifaximin, a nonsystemic, gut‐targeted antibiotic for reducing non–constipation‐predominant irritable bowel syndrome (non‐C IBS) symptoms, has been demonstrated in one phase 2b and two phase 3 randomised, double‐blind, placebo‐controlled trials, but detailed data about rifaximin safety and tolerability during treatment and subsequent follow‐up periods are lacking.AimTo assess and determine the frequency of rifaximin and placebo adverse events (AEs) in phase 2b and phase 3 non‐C IBS trials.MethodsA post hoc pooled safety analysis of the phase 2b (rifaximin 275, 550, and 1100 mg twice daily for 2 weeks; 550 mg twice daily for 4 weeks) and phase 3 (rifaximin 550 mg three times daily for 2 weeks) studies was performed. Data on treatment and post‐treatment AEs were collected. Patients were followed up for 12 weeks and 10 weeks post‐treatment in the phase 2b and phase 3 trials, respectively.ResultsPatients receiving rifaximin (n = 1103) and placebo (n = 829) had a similar incidence of drug‐related AEs (12.1% vs. 10.7%), serious AEs (1.5% vs. 2.2%), drug‐related AEs resulting in study discontinuation (0.8% vs. 0.8%), gastrointestinal‐associated AEs (12.2% vs. 12.2%) and infection‐associated AEs (8.5% vs. 9.5%). There were no cases of Clostridium difficile colitis or deaths.ConclusionsThe safety and tolerability profile of rifaximin during treatment and post‐treatment was comparable to placebo. Future research should define the safety and tolerability profile, including risk of C. difficile colitis and microbial antibiotic resistance, with repeated courses of rifaximin in patients with non—constipation‐predominant irritable bowel syndrome (ClinicalTrials.gov: NCT00269412, NCT00731679, and NCT00724126).
Influence of UGT2B7,OPRM1 and ABCB1 Gene Polymorphisms on Postoperative Morphine Consumption
Authors: Bastami Salumeh , Gupta Anil , Zackrisson Anna‐Lena , Ahlner Johan , Osman Abdimajid , Uppugunduri Srinivas 
Published: April 2014

AbstractTherapeutic modulation of pain with morphine and other opioids is associated with significant variation in both effects and adverse effects in individual patients. Many factors including gene polymorphisms have been shown to contribute to the interindividual variability in the response to opioids. The aim of this study was to investigate the significance of UGT2B7, OPRM1 and ABCB1 polymorphisms for interindividual variability in morphine‐induced analgesia in patients undergoing hysterectomy. The frequency of these polymorphisms was also investigated in forensic autopsies as morphine is also a very commonly abused drug. Blood samples were collected from 40 patients following abdominal hysterectomy, 24 hr after initiation of analgesia through a patient‐controlled analgesia (PCA) pump. Samples were genotyped and analysed for morphine and its metabolites. We also genotyped approximately 200 autopsies found positive for morphine in routine forensic analysis. Patients homozygous for UGT2B7 802C needed significantly lower dose of morphine for pain relief. The same trend was observed for patients homozygous for ABCB1 1236T and 3435T, as well as to OPRM1 118A. The dose of morphine in patients included in this study was significantly related to variation in UGT2B7 T802C. Age was significantly related to both dose and concentration of morphine in blood. Regression analysis showed that 30% of differences in variation in morphine dose could be explained by SNPs in these genes. The genotype distribution was similar between the forensic cases and the patients. However, the mean concentration of morphine was higher in forensic cases compared to patients. We conclude that gene polymorphisms contribute significantly to the variation in morphine concentrations observed in individual patients.
Charts for Weight Loss to Detect Hypernatremic Dehydration and Prevent Formula Supplementing
Authors: van Dommelen Paula , Boer Suzanne , Unal Sevim , van Wouwe Jacobus P. 
Published: April 2014

AbstractBackgroundMost breast‐fed newborns get the milk they need. However, very rarely milk intake is insufficient mostly as a result of poor breastfeeding techniques. Dramatic weight loss and hypernatremic dehydration may occur. Our aim was to construct charts for weight loss.MethodsA case–control study was performed. Charts with standard deviation score (SDS) lines for weight loss in the first month were constructed for 2,359 healthy breast‐fed term newborns and 271 cases with breastfeeding‐associated hypernatremic dehydration with serum sodium level > 149 mEq/L. Day 0 was defined as the day of birth.ResultsMany cases with (or who will develop) hypernatremic dehydration (84%; +1 SDS line) fell below the −1 SDS line at day 3, the −2 SDS line at day 4, and the −2.5 SDS line at day 5 in the chart of the healthy breast‐fed newborns. Weight loss of cases with permanent residual symptoms was far below the −2.5 SDS.ConclusionsAlready at an early age, weight loss differs between healthy breast‐fed newborns and those with hypernatremic dehydration. Charts for weight loss are, therefore, useful tools to detect early, or prevent newborns from developing, breastfeeding‐associated hypernatremic dehydration, and also to prevent unnecessary formula supplementing.
Sex differences in animal models of psychiatric disorders
Authors: Kokras N , Dalla C 
Published: April 2014

Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender‐oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post‐traumatic stress disorder, substance‐related disorders, obsessive–compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment‐sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories.Linked ArticlesThis article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20
Activation of P2Y6 receptors increases the voiding frequency in anaesthetized rats by releasing ATP from the bladder urothelium
Authors: Carneiro Inês , Timóteo M Alexandrina , Silva Isabel , Vieira Cátia , Baldaia Catarina , Ferreirinha Fátima , Silva‐Ramos Miguel , Correia‐de‐Sá Paulo 
Published: April 2014

Background and purposeDespite the abundant expression of the UDP‐sensitive P2Y6 receptor in urothelial cells and sub‐urothelial myofibroblasts its role in the control of bladder function is not well understood.Experimental approachWe compared the effects of UDP and of the selective P2Y6 receptor agonist, PSB0474, on bladder urodynamics in anaesthetized rats; the voided fluid was tested for ATP bioluminescence. The isolated urinary bladder was used for in vitro myographic recordings and [3H]‐ACh overflow experiments.Key resultsInstillation of UDP or PSB0474 into the bladder increased the voiding frequency (VF) without affecting the amplitude (A) and the duration (Δt) of bladder contractions; an effect blocked by the P2Y6 receptor antagonist, MRS2578. Effects mediated by urothelial P2Y6 receptors required extrinsic neuronal circuitry as they were not detected in the isolated bladder. UDP‐induced bladder hyperactvity was also prevented by blocking P2X3 and P2Y1 receptors, respectively, with A317491 and MRS2179 applied i.v.. UDP decreased [3H]‐ACh release from stimulated bladder strips with urothelium, but not in its absence. Inhibitory effects of UDP were converted into facilitation by the P2Y1 receptor antagonist, MRS2179. The P2Y6 receptor agonist increased threefold ATP levels in the voided fluid.Conclusions and ImplicationsActivation of P2Y6 receptors increased the voiding frequency indirectly by releasing ATP from the urothelium and activation of P2X3 receptors on sub‐urothelial nerve afferents. Bladder hyperactivity may be partly reversed following ATP hydrolysis to ADP by E‐NTPDases, thereby decreasing ACh release from cholinergic nerves expressing P2Y1 receptors.
Does PKC activation increase the homologous desensitization of μ opioid receptors?
Authors: Arttamangkul Seksiri , Birdsong William , Williams John T 
Published: April 2014

Background and PurposeThis study examined the role of agents known to activate PKC on morphine‐induced desensitization of μ‐opioid receptors (MOP receptors) in brain slices containing locus coeruleus neurons.Experimental ApproachIntracellular recordings were obtained from rat locus coeruleus neurons. Two measurements were used to characterize desensitization, the decline in hyperpolarization induced by application of a saturating concentration of agonist (acute desensitization) and the decrease in hyperpolarization induced by a subsaturating concentration of [Met]5enkephalin (ME) following washout of the saturating concentration (sustained desensitization). Internalization of MOP receptors was studied in brain slices prepared from transgenic mice expressing Flag‐MOP receptors. The subcellular distribution of activated PKC was examined using a novel fluorescent sensor of PKC in HEK293 cells.Key ResultsThe phorbol esters (PMA and PDBu) and muscarine increased acute desensitization induced by a saturating concentration of morphine and ME. These effects were not sensitive to staurosporine. Staurosporine did not block the decline in hyperpolarization induced by muscarine. PDBu and muscarine did not affect sustained desensitization induced by ME nor did phorbol esters or muscarine change the trafficking of MOP receptors induced by morphine or ME. The distribution of activated PKC measured in HEK293 cells differed depending on which phorbol ester was applied.Conclusions and ImplicationsThis study demonstrates a distinct difference in two measurements that are often used to evaluate desensitization. The measure of decline correlated well with the reduction in peak amplitudes caused by PKC activators implicating the modification of other factors rather than MOP receptors.Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Maresin 1 mitigatesLPS‐induced acute lung injury in mice
Authors: Gong Jie , Wu Zhou‐yang , Qi Hong , Chen Lin , Li Hong‐bin , Li Bo , Yao Cheng‐ye , Wang Ya‐xin , Wu Jing , Yuan Shi‐ying , Yao Shang‐long , Shang You 
Published: April 2014

Background and PurposeAcute lung injury (ALI) is a severe illness with a high rate of mortality.Maresin 1 (MaR1) was recently reported to regulate inflammatory responses. We used aLPS‐inducedALImodel to determine whetherMaR1can mitigate lung injury.Experimental ApproachMaleBALB/c mice were injected, intratracheally, with eitherLPS(3 mg·kg−1) or normal saline (1.5 mL·kg−1). After this, normal saline, a low dose ofMaR1(0.1 ng per mouse) or a high dose ofMaR1(1 ng per mouse) was given i.v. Lung injury was evaluated by detecting arterial blood gas, pathohistological examination, pulmonary oedema, inflammatory cell infiltration, inflammatory cytokines in the bronchoalveolar lavage fluid and neutrophil–platelet interactions.Key ResultsThe high dose ofMaR1significantly inhibitedLPS‐inducedALIby restoring oxygenation, attenuating pulmonary oedema and mitigating pathohistological changes. A combination ofelisaand immunohistochemistry showed that high‐doseMaR1attenuatedLPS‐induced increases in pro‐inflammatory cytokines (TNF‐α,IL‐1β andIL‐6), chemokines [keratinocyte chemokine, monocyte chemoattractant protein‐5, macrophage inflammatory protein (MIP)‐1α andMIP‐1γ], pulmonary myeloperoxidase activity and neutrophil infiltration in the lung tissues. Consistent with these observations, flow cytometry and Western blotting indicated thatMaR1down‐regulatedLPS‐induced neutrophil adhesions and suppressed the expression of intercellular adhesion molecule (ICAM)‐1,P‐selection andCD24.Conclusions and ImplicationsHigh‐doseMaR1mitigatedLPS‐induced lung injury in mice by inhibiting neutrophil adhesions and decreasing the levels of pro‐inflammatory cytokines.
Ecological restoration of rich fens in Europe and North America: from trial and error to an evidence‐based approach
Authors: Lamers Leon P. M. , Vile Melanie A. , Grootjans Ab P. , Acreman Mike C. , van Diggelen Rudy , Evans Martin G. , Richardson Curtis J. , Rochefort Line , Kooijman Annemieke M. , Roelofs Jan G. M. , Smolders Alfons J. P. 
Published: April 2014

ABSTRACTFens represent a large array of ecosystem services, including the highest biodiversity found among wetlands, hydrological services, water purification and carbon sequestration. Land‐use change and drainage has severely damaged or annihilated these services in many parts of North America and Europe; restoration plans are urgently needed at the landscape level. We review the major constraints on the restoration of rich fens and fen water bodies in agricultural areas in Europe and disturbed landscapes in North America: (i) habitat quality problems: drought, eutrophication, acidification, and toxicity, and (ii) recolonization problems: species pools, ecosystem fragmentation and connectivity, genetic variability, and invasive species; and here provide possible solutions. We discuss both positive and negative consequences of restoration measures, and their causes. The restoration of wetland ecosystem functioning and services has, for a long time, been based on a trial‐and‐error approach. By presenting research and practice on the restoration of rich fen ecosystems within agricultural areas, we demonstrate the importance of biogeochemical and ecological knowledge at different spatial scales for the management and restoration of biodiversity, water quality, carbon sequestration and other ecosystem services, especially in a changing climate. We define target processes that enable scientists, nature managers, water managers and policy makers to choose between different measures and to predict restoration prospects for different types of deteriorated fens and their starting conditions.
Effect of topical diclofenac on postoperative photorefractive keratectomy pain: a randomized, controlled trial
Authors: Eslampoor Alireza , Ehsaei Asieh , Abrishami Mojtaba 
Published: April 2014

AbstractBackgroundA major disadvantage of photorefractive keratectomy is postoperative pain and discomfort. This study aims to evaluate whether topical diclofenac 0.1% therapy adds any extra benefit to systemic diclofenac in controlling pain after photorefractive keratectomy.DesignProspective randomized, double‐masked clinical trial applied in the Khatam‐al‐Anbia Eye Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.ParticipantsSixty‐eight individuals (age range, 18–35 years) having bilateral photorefractive keratectomy for myopic correction with or without astigmatism.MethodsAll patients received 100 mg of extended‐release oral diclofenac two times (12‐h interval) before photorefractive keratectomy surgery. Postoperatively, patients were randomized into the case and control groups. Case group was administered the diclofenac 0.1% drop, one drop 2 h preoperatively and four times daily postoperatively for 3 days, whereas the control group was given artificial tears instead.Main Outcome MeasuresPain level, photophobia and functional activity were evaluated by the patient after operation.ResultsTwo days after surgery, no statistically significant difference in pain level was noted between both groups. In addition, photophobia and functional activity was not different between the case and control groups. Eyelid oedema and conjunctival injection levels were significantly higher in the control group (P < 0.001).ConclusionsAdministration of topical diclofenac to a standardized postoperative pain regime did not alleviate post‐photorefractive keratectomy pain, although it is effective in local signs like eyelid oedema and conjunctival injection. It can be concluded that oral diclofenac is sufficient in the management of post‐photorefractive keratectomy pain and addition of the topical diclofenac is unnecessary.
Agreement between ultrasound and dual‐energy X‐ray absorptiometry in assessing percentage body fat in college‐aged adults
Authors: Johnson Kelly E. , Miller Brian , Juvancic‐Heltzel Judith A. , Agnor Sarah E. , Kiger Dana L. , Kappler Rachele M. , Otterstetter Ronald 
Published: April 2014

SummaryBackgroundThe BodyMetrix® BX‐2000 Ultrasound device (ULTRA) shows prowess in being an effective alternative to the expense and technicality of dual‐energy X‐ray absorptiometry (DXA). However, this technique has not been investigated using a seven‐site methodology.Subject/ObjectiveTo employ a cross‐over design to investigate the agreement between ULTRA using a seven‐site methodology and DXA in assessing body fat (%BF) in a normal‐weight sample of college‐age men and women. Methods: Subjects (n = 84, BMI = 23·6 ± 3·6 kg m−², age = 23·0 ± 4·7 years) participated in this study with %BF measurements following the manufacturer's specifications.ResultsSignificant differences were observed between methods with ULTRA less than DXA (difference = 4·4 ± 0·8%, t‐statistic = 7·27, P<0·001) with no difference between men and women.ConclusionThe current study showed that ULTRA using a seven‐site methodology did not agree with DXA in measuring %BF. Thus, this investigational ULTRA methodology might not be appropriate in estimating %BF in this population.
Pallidotomy for medically refractory status dystonicus in childhood
Authors: Marras Carlo Efisio , Rizzi Michele , Cantonetti Laura , Rebessi Erika , De Benedictis Alessandro , Portaluri Francesco , Randi Franco , Savioli Alessandra , Castelli Enrico , Vigevano Federico 
Published: April 2014

AimStatus dystonicus is a rare and potentially fatal condition of continuous and generalized muscle contraction that can complicate dystonia. As status dystonicus is usually refractory to traditional pharmacological therapy, alternative and invasive strategies have been developed, but so far there are no guidelines on status dystonicus management. Pallidotomy has shown good results in status dystonicus treatment.MethodWe report indications, surgical strategy, and outcome of bilateral pallidotomy in four pediatric patients (four males; mean age at surgery 11y 5mo) with secondary dystonia, who developed refractory status dystonicus. Pallidotomy was performed in the area corresponding to the mid portion of the globus pallidus internus.ResultsThis procedure allowed patients to recover the pre‐status dystonicus condition, controlling dystonic postures and movements of trunk and limbs. Moreover oromandibular dystonia, which is resistant to conservative approaches and deep brain stimulation, was significantly reduced. No postoperative complications were registered.InterpretationOur study suggests pallidotomy as a feasible treatment in patients with secondary dystonia complicated by status dystonicus.
Intracardiac Echocardiography of Ebstein's Anomaly
Authors: Dauphin Claire , Chalard Aurélie , Lusson Jean‐René 
Published: April 2014

Mini‐AbstractWe report the case of a 9‐year‐old girl with a severe form of Ebstein's anomaly. Intracardiac echocardiography used for guidance in closure of the atrial septal defect (ASD) showed a clear picture of nondelamination of the septal and posterior leaflets of the tricuspid valve.
Ia Diastolic Dysfunction: An Echocardiographic Grade
Authors: Pandit Anil , Mookadam Farouk , Hakim Fayaz A. , Mulroy Eoin , Saadiq Rayya , Doherty Mairead , Cha Stephen , Seward James , Wilansky Susan 
Published: April 2014

ObjectiveTo demonstrate that a distinct group of patients with Grade Ia diastolic dysfunction who do not conform to present ASE/ESE diastolic grading exists.Method and ResultsEchocardiographic and demographic data of the Grade Ia diastolic dysfunction were extracted and compared with that of Grades I and II in 515 patients. The mean of age of the cohort was 75 ± 9 years and body mass index did not differ significantly between the 3 groups (P = 0.45). Measurements of left atrial volume index (28.58 ± 7 mL/m2 in I, 33 ± 10 mL/m2 in Ia, and 39 ± 12 mL/m2 in II P < 0.001), isovolumic relaxation time (IVRT) (100 ± 17 msec in I, 103 ± 21 msec in Ia, and 79 ± 15 msec in II P < 0.001), deceleration time (248 ± 52 msec in I, 263 ± 58 msec in Ia, and 217 ± 57 msec in II P < 0.001), medial E/e′ (10 ± 3 in I, 18 ± 5.00 in Ia, and 22 ± 8 in II), and lateral E/e′ (8 ± 3 in I, 15 ± 6 in Ia, and 18 ± 9 in II P < 0.001) were significantly different in grade Ia compared with I and II. These findings remained significant even after adjusting for age, gender, diabetes, and smoking.ConclusionPatients with echocardiographic characteristics of relaxation abnormality (E/A ratio of <0.8) and elevated filling pressures (septal E/e′ ≥15, lateral E/e′ ≥12, average E/e′ ≥13) should be graded as a separate Grade Ia group.
Determinants of an Abnormal Septal Curvature in Chronic Pulmonary Hypertension
Authors: López‐Candales Angel 
Published: April 2014

BackgroundEven though systolic eccentricity index has been traditionally categorized based on right ventricular (RV) pressure overload, which hemodynamic component is particularly responsible for modulating leftward ventricular septal bowing (LVSB) in chronic pulmonary arterial hypertension (PAH) is less well‐known.MethodsTherefore, currently used echocardiographic variables, as suggested by the American Society of Echocardiography, for evaluation of RV performance were evaluated in 60 patients to determine which of these commonly used parameters best determine an abnormal LVSB in chronic PAH patients.ResultsIn a stepwise multiple regression analysis of the echocardiographic variables used in this study, elevated pulmonary artery systolic pressures was the best discriminatory variable to identify an abnormal LVSB at any level along the interventricular septum in chronic PAH patients followed by smaller left ventricular end‐diastolic volumes and larger RV end‐systolic areas.ConclusionProgressive RV failure in chronic PAH not only is associated with a decline in longitudinal base to apical motion of the annulus; but also with reduced inward displacement of the RV free wall. Additional reduction in RV systolic function also occurs as a result of progressive displacement of the interventricular septum toward the left ventricle. Therefore, as measures of LVSB along the interventricular septum not only are easily obtained and related to RV systolic performance in chronic PAH patients, routine use of these parameters might be helpful in monitoring decline of RV function as well as progression of end‐stage PAH.