bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy, safety and tolerability of topical terbinafine nail solution in patients with mild‐to‐moderate toenail onychomycosis: results from three randomized studies using double‐blind vehicle‐controlled and open‐label active‐controlled designs
Authors: Elewski B.E. , Ghannoum M.A. , Mayser P. , Gupta A.K. , Korting H.‐C. , Shouey R.J. , Baker D.R. , Rich P.A. , Ling M. , Hugot S. , Damaj B. , Nyirady J. , Thangavelu K. , Notter M. , Parneix‐Spake A. , Sigurgeirsson B. 
Published: December 2011

AbstractBackground  Terbinafine nail solution (TNS) was developed for the treatment of onychomycosis.Objective  To assess the efficacy of TNS vs. vehicle and amorolfine 5% nail lacquer.Methods  Subjects with mild‐to‐moderate toe onychomycosis (25% to ≤75% nail‐involvement, matrix uninvolved) were randomized to receive either TNS or vehicle in two double‐blind studies, and to TNS or amorolfine in an active‐controlled, open‐label study. Primary endpoint was complete cure (no residual clinical involvement and negative mycology) at week 52. Secondary endpoints were mycological cure (negative mycology defined as negative KOH microscopy and negative culture) and clinical effectiveness (≤10% residual‐involvement and negative mycology) at week 52.Results  Complete cure was not different between TNS vs. vehicle and amorolfine. Mycological cure was higher with TNS vs. vehicle, as was clinical effectiveness with TNS vs. vehicle, and TNS and amorolfine were not different for secondary efficacy endpoints. Patients achieving mycological cure had a better clinical outcome, and efficacy was improved in subjects with milder disease. Post hoc analysis suggests that nail thickness is an important prognostic factor. Moreover, mycological cure may require 6 months of treatment regimen while complete cure and clinical effectiveness may be achievable only after 10 months. A simulation study suggests that longer treatment duration would have resulted in higher complete cure with TNS vs. vehicle. Study treatments were well‐tolerated.Conclusion  Primary efficacy objectives were not met in the studies reported herein. Possible reasons for failure to achieve significant outcomes include insufficient length of treatment; stringency of primary endpoint and severity of nail involvement of study population.
Lack of association between filaggrin gene mutations and onset of psoriasis in childhood
Authors: Winge M.C.G. , Suneson J. , Lysell J. , Nikamo P. , Liedén A. , Nordenskjöld M. , Wahlgren C.F. , Bradley M. , Ståhle M. 
Published: December 2011

AbstractBackground  Atopic dermatitis (AD; OMIM#603165) and psoriasis (OMIM#177900) are two common inflammatory skin disorders. Both are genetically complex, multifactorial and do not follow a Mendelian pattern of inheritance. Both diseases share several genetic susceptibility loci such as the epidermal differentiation complex (EDC) on chromosome 1q21. Within the EDC, mutations in the filaggrin (FLG) gene are strongly associated with AD whereas no association has been replicated with psoriasis. However, reduced levels of filaggrin have been reported in psoriatic skin. Further, filaggrin deficiency was shown to be a modifying factor for the phenotype in another epidermal skin disorder, X‐linked recessive ichthyosis. Altogether, this raises the question if FLG mutations may modify the disease course in other epidermal skin diseases such as psoriasis. Psoriasis is a highly heterogeneous disease and so far genetic studies have not taken the distinct sub‐phenotype childhood onset into account.Objective  To determine if FLG mutations modify the onset of psoriasis.Materials and methods  A total of 241 children with onset of psoriasis below 15 years of age and 314 healthy controls were identified at the Dermatology clinic, Karolinska University Hospital and diagnosed by the same dermatologist (JL). Blood samples were taken and medical history was recorded. FLG was genotyped in all patients and controls using allelic discrimination (n = 555) and sequencing (n = 20).Results and conclusions  No association between FLG mutations and early onset of psoriasis was demonstrated (P = 0.57) and no novel mutations were detected, indicating that FLG loss‐of‐function variants do not have a strong effect on the onset of psoriasis in childhood.
Oral etoposide as first‐line therapy in the treatment of patients with advanced classic Kaposi’s sarcoma (CKS): a single‐arm trial (oral etoposide in CKS)
Authors: Tas F. , Sen F. , Keskin S. , Kilic L. 
Published: December 2011

AbstractBackground  Classic Kaposi’s sarcoma (CKS) affects an elderly population; it is important to have effective treatment options with high activity and relatively low toxicity, and availability to be used for long periods.Objective  We investigated the activity and safety of single‐agent etoposide with an oral administration schedule in patients with advanced CKS.Methods  Histologically confirmed, CKS patients were eligible for study. All had a negative test for HIV and good performance status. All patients received oral etoposide 50 mg twice daily for 10 days every 3 weeks.Results  Thirty patients (median age 66 and 22 males) were enrolled into the study. The majority of them had non‐metastatic, local advanced disease and symptoms in nearly half of patients. Complete and partial responses were observed in 10% and 77% of patients, respectively, giving an overall response rate of 87%. Stable disease occurred in the other 13% of patients. Treatment was well tolerated. Grade IV toxicity was not observed. Haematological toxicity was the principal dose‐limiting side effect. Severe leucopaenia and neutropaenia were observed in 7% and 10% of patients respectively. No patient was complicated by febrile neutropaenia. Mild‐moderate anaemia observed frequently, but only 3% of patients had severe anaemia and severe thrombocytopaenia was not observed. The 5‐year overall survival rate was 92%.Conclusions  Single‐agent oral etoposide is an effective treatment option and is acceptably toxic and easily administered. Therefore, we recommend the single agent of oral etoposide as the first‐line chemotherapy for advanced CKS.
Lost in translation: preclinical studies on 3,4‐methylenedioxymethamphetamine provide information on mechanisms of action, but do not allow accurate prediction of adverse events in humans
Authors: Green AR , King MV , Shortall SE , Fone KCF 
Published: December 2011

3,4‐Methylenedioxymethamphetamine (MDMA) induces both acute adverse effects and long‐term neurotoxic loss of brain 5‐HT neurones in laboratory animals. However, when choosing doses, most preclinical studies have paid little attention to the pharmacokinetics of the drug in humans or animals. The recreational use of MDMA and current clinical investigations of the drug for therapeutic purposes demand better translational pharmacology to allow accurate risk assessment of its ability to induce adverse events. Recent pharmacokinetic studies on MDMA in animals and humans are reviewed and indicate that the risks following MDMA ingestion should be re‐evaluated. Acute behavioural and body temperature changes result from rapid MDMA‐induced monoamine release, whereas long‐term neurotoxicity is primarily caused by metabolites of the drug. Therefore acute physiological changes in humans are fairly accurately mimicked in animals by appropriate dosing, although allometric dosing calculations have little value. Long‐term changes require MDMA to be metabolized in a similar manner in experimental animals and humans. However, the rate of metabolism of MDMA and its major metabolites is slower in humans than rats or monkeys, potentially allowing endogenous neuroprotective mechanisms to function in a species specific manner. Furthermore acute hyperthermia in humans probably limits the chance of recreational users ingesting sufficient MDMA to produce neurotoxicity, unlike in the rat. MDMA also inhibits the major enzyme responsible for its metabolism in humans thereby also assisting in preventing neurotoxicity. These observations question whether MDMA alone produces long‐term 5‐HT neurotoxicity in human brain, although when taken in combination with other recreational drugs it may induce neurotoxicity.LINKED ARTICLESThis article is commented on by Parrott, pp. 1518–1520 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2012.01941.x and to view the the rebuttal by the authors (Green et al., pp. 1521–1522 of this issue) visit http://dx.doi.org/10.1111/j.1476‐5381.2012.01940.x
Concomitant facilitation of GABAA receptors and KV7 channels by the non‐opioid analgesic flupirtine
Authors: Klinger Felicia , Geier Petra , Dorostkar Mario M , Chandaka Giri K , Yousuf Arsalan , Salzer Isabella , Kubista Helmut , Boehm Stefan 
Published: December 2011

BACKGROUND AND PURPOSEFlupirtine is a non‐opioid analgesic that has been in clinical use for more than 20 years. It is characterized as a selective neuronal potassium channel opener (SNEPCO). Nevertheless, its mechanisms of action remain controversial and are the purpose of this study.EXPERIMENTAL APPROACHEffects of flupirtine on native and recombinant voltage‐ and ligand‐gated ion channels were explored in patch‐clamp experiments using the following experimental systems: recombinant KIR3 and KV7 channels and α3β4 nicotinic acetylcholine receptors expressed in tsA 201 cells; native voltage‐gated Na+, Ca2+, inward rectifier K+, KV7 K+, and TRPV1 channels, as well as GABAA, glycine, and ionotropic glutamate receptors expressed in rat dorsal root ganglion, dorsal horn and hippocampal neurons.KEY RESULTSTherapeutic flupirtine concentrations (≤10 µM) did not affect voltage‐gated Na+ or Ca2+ channels, inward rectifier K+ channels, nicotinic acetylcholine receptors, glycine or ionotropic glutamate receptors. Flupirtine shifted the gating of KV7 K+ channels to more negative potentials and the gating of GABAA receptors to lower GABA concentrations. These latter effects were more pronounced in dorsal root ganglion and dorsal horn neurons than in hippocampal neurons. In dorsal root ganglion and dorsal horn neurons, the facilitatory effect of therapeutic flupirtine concentrations on KV7 channels and GABAA receptors was comparable, whereas in hippocampal neurons the effects on KV7 channels were more pronounced.CONCLUSIONS AND IMPLICATIONSThese results indicate that flupirtine exerts its analgesic action by acting on both GABAA receptors and KV7 channels.
A Web‐Based Personal Health Information System for Homeless Youth and Young Adults
Authors: Dang Michelle T. , Whitney Kimberley D. , Virata Maria Catrina D. , Binger Melissa M. , Miller Elizabeth 
Published: December 2011

AbstractRunaway and homeless youth face multiple challenges to their health and experience inadequate access to health care services. This article describes a Web‐based Personal Health Information System (PHIS) called Healthshack that was specifically designed to improve health care access and health outcomes for runaway and homeless youth at a community‐based agency that served homeless youth and young adults up to age 24. The program was developed in partnership with homeless youth and piloted by public health nurses. Preliminary findings from the program indicate that a PHIS is acceptable to runaway and homeless youth and feasible to incorporate into the flow of a youth agency. Thus, a PHIS may be an innovative model of service delivery for other marginalized populations.
Palpation and Dorsal Acetabular Rim Radiographic Projection for Early Detection of Canine Hip Dysplasia: A Prospective Study
Authors: Gatineau Matthieu , Dupuis Jacques , Beauregard Guy , Charette Benoît , Breton Luc , Beauchamp Guy , d'Anjou Marc‐André 
Published: December 2011

ObjectiveTo determine the value of 2 diagnostic methods: (1) the reduction angle (RA) using theOrtolani maneuver and (2) the dorsal acetabular slope (DAS) from the dorsal acetabular rim (DAR) radiographic projection, to predict osteoarthritis (OA) in dogs with hip dysplasia.Study DesignProspective study.Sample PopulationDogs (n = 73).MethodsHip‐extended ventrodorsal (VD) radiographic projections,RA, andDASwere evaluated when dogs were 6, 12, and 24 months of age.VDprojections were qualitatively scored forOA.RAwas determined using theOrtolani maneuver in dorsal recumbency andDASusing theDARprojection. Distraction index (DI) measurements from the compression–distraction radiographic projections (PennHIPmethod) were also performed at 6 months of age. Statistical analyses were used to establish the range of values of normal and abnormalRAandDAS, to document the temporal variation inRAandDAS, to compare the ability of the different methods to predict coxofemoralOA, to determine the influence of pure passive laxity and of theDASon the occurrence of anOrtolani sign and on the magnitude of theRA, to establish the relationship between theDASand subsequent development of passive laxity and coxofemoralOA, and to evaluate the influence of theDASandRAon the occurrence of coxofemoralOAwith severe, moderate, and minimal coxofemoral passive joint laxity, respectively.ResultsVD,RA,DAS, andDImethods of coxofemoral joint evaluation correlated significantly with the status of the coxofemoral joints at 2 years of age. The risk of occurrence of coxofemoralOAincreased, as theRA,DAS, orDIincreased. There was a significant positive linear relationship betweenRAandDI(P= .015, r2= 0.32),RAandDAS(P= .0078, r2= 0.38), andDASandDI(P= .015, r2= 0.33). A negativeOrtolani sign was at all times significantly predictive of absence of coxofemoralOAat 2 years of age.DASbest predicted coxofemoralOAforDI≥ 0.7, whereasRAbest predicted coxofemoralOAfor 0.3 <DI< 0.7; however,RAproved to be the best overall predictor of coxofemoralOA.ConclusionRAmeasured at 6 months of age in dorsal recumbency was the best predictor of coxofemoralOAat 2 years of age.
Radiographic Evaluation of Early Periprosthetic Femoral Bone Contrast and Prosthetic Stem Alignment after Uncemented and Cemented Total Hip Replacement in Dogs
Authors: Mostafa Ayman A. , Drüen Svenja , Nolte Ingo , Wefstaedt Patrick 
Published: December 2011

ObjectiveTo radiographically evaluate periprosthetic femoral bone contrast and assess alignment of the prosthetic stem after uncemented and cemented total hip replacement (THR).Study DesignProspective clinical study.AnimalsDogs (n = 15).MethodsDogs were classified into uncemented (n = 8) and cemented (n = 7)THRgroups. Radiographs were analyzed using image processing software to evaluate femoral bone contrast (gray scale value,GV) for each and combined modifiedGruen zone(s) immediately and 4 months afterTHR. ModifiedGruen zones were classified into 5 zones to analyze retrospectively the regional radiographicGVof the femur around uncemented and cemented prosthetic stem. Alignment of prosthetic stem was assessed immediately and 4 months postoperatively. Variables were compared by use of 2‐tailed t‐test, withP< .05 considered significant.ResultsZone 1 showed significant decrease in the mean boneGV4 months after uncementedTHR. No differences in zones 1–5 after 4 months of cementedTHR. Combined zones showed significant decrease in overall mean boneGV4 months after uncementedTHR. No changes were observed 4 months after cementedTHR. Number of limbs with varus‐aligned femoral stem markedly increased after 4 months of uncementedTHR.ConclusionsRegional bone contrast and prosthetic stem alignment vary with the design ofTHR.
Pelvic Limb Kinematics and Surface Electromyography of the Vastus Lateralis, Biceps Femoris, and Gluteus Medius Muscle in Dogs with Hip Osteoarthritis
Authors: Bockstahler Barbara , Kräutler Cordula , Holler Peter , Kotschwar Alexander , Vobornik Angela , Peham Christian 
Published: December 2011

ObjectiveTo measure the activity patterns of the vastus lateralis (VL), biceps femoris, and gluteus medius (GM) muscle at a walk in sound dogs and dogs with hip osteoarthritis (OA).AnimalsDogs (n = 10) with hipOAand 7 clinically sound dogs.MethodsSelf‐reflective markers and a high‐speed camera system were used for kinematic measurements and surface electrodes were used for the electromyography (EMG). All measurements were performed on walking dogs. Maximal, minimal, and mean values of the joint angles were evaluated, together with the surfaceEMGdata.ResultsIn all muscles investigated, mean activity was significantly decreased during the early swing phase in dogs with hipOA. TheVLandGMmuscle of the clinically worse pelvic limb had significantly higher activity than the contralateral pelvic limb during early stance.ConclusionThe muscles investigated were significantly affected by hipOA. This finding suggests that there is a more distinct resting phase of the muscles during swing and a higher activity during early stance.
Risk Factors and Clinical Relevance of Positive Intraoperative Bacterial Cultures in Dogs with Total Hip Replacement
Authors: Ireifej Shadi , Marino Dominic J. , Loughin Catherine A. , Lesser Martin L. , Akerman Meredith 
Published: December 2011

ObjectiveTo report incidence and relevance of positive intraoperative total hip replacement (THR) bacterial cultures taken at the time of surgical closure in dogs having unilateralTHR.Study designRetrospective case series.AnimalsDogs (n = 100) with cemented (CFX), cementless (BFX), or hybridTHR.MethodsMedical records (January 2007–March 2010) of dogs that hadTHRwere reviewed. Signalment, type and side ofTHR, concurrent surgery, operative and anesthetic times, intraoperative coxofemoral closing (CC) bacterial culture results, organism cultured, duration of postoperative antibiotic administration, physical examination findings at 3 weeks, 3 months, and at 6 months to 1 year after surgery, radiographic findings at 3 months and between 6 months and 1 year after surgery, and incidence of complications were retrieved.ResultsThere was a significant difference in duration of surgery betweenCCculture negative andCCculture positive groups (103.27 minutes versus 122.50 minutes, respectively,P< .038) and in total anesthetic time betweenCCculture negative and culture positive groups (165.20 minutes versus 189.50 minutes, respectively,P< .038). There was no significant difference betweenCCculture negative and culture positive groups for median age (30 months versus 39 months, respectively,P< .75), median weight (36.91 kg versus 35.68 kg, respectively,P< .61), median clinical signs (4 months versus 3.5 months, respectively,P< .65), sex (males 44.32% versus females 25.00%, respectively,P< .20), laterality (left 55.68% versus right 50.00%, respectively,P< .71), concurrent surgery (extracapsular lateral imbrication/medial patella luxation/lateral patella luxation [ECLI/MPL/LPL] 22.73% versus none 25.00%, respectively,P< 1.00), andTHRtype (hybrid 17.05% versus 25.00% respectively;CFX60.23% versus 75.0%;BFX22.73% versus 0.0%;Fisher's exact testP< .17).ConclusionsSurgical and anesthetic duration were significantly associated with positiveCCculture results. PositiveCCculture results were not associated with adverse results at 3 months and at 6‐month to 1‐year follow‐up evaluation.
Two Different Days of Transcranial Doppler Examinations Should Be Performed for Detection of Right‐to‐Left Shunt in Acute Stroke Patients
Authors: Aoki Junya , Kimura Kazumi , Iguchi Yasuyuki , Sakai Kenichiro , Sakamoto Yuki , Terasawa Yuka , Shibazaki Kensaku , Kobayashi Kazuto 
Published: December 2011

ABSTRACTBACKGROUNDWe investigated how many contrast‐transcranial Doppler (c‐TCD) examinations should be performed on different days in patients with acute stroke.METHODSConsecutive acute stroke patients within 24 hours of onset were enrolled. Presence of RLS was examined using c‐TCD examinations on days 1, 7, and 14. Each c‐TCD examination used one test without Valsalva maneuver (VM) and three tests with VM. Patients were diagnosed with RLS when TCD detected ≥1 microembolic signal on ≥1 c‐TCD examination on any of the days 1, 7, or 14.RESULTSOne hundred seventy patients (105 men [62%]; median age, 74 [IQR, 66–81] years) were enrolled. RLS was diagnosed in 45 patients (26%). RLS was identified on day 1 in 30 patients (18%), on day 7 in 28 patients (16%), and on day 14 in 23 patients (14%; P= .143). Detection rate of RLS by combining day 1 and 7 examinations was significantly higher than that of day 1 alone (25% vs 18%, P < .001). However, the rate did not increase when results of day 14 were added (25% vs 26%, P= .250).CONCLUSIONSc‐TCD examinations should be performed on at least two different days to assess the prevalence of RLS.
Acute myocardial infarction elevates serine protease activity in saliva of patients with periodontitis
Authors: Mäntylä P. , Buduneli E. , Emingil G. , Tervahartiala T. , Pussinen P. J. , Barış N. , Akıllı A. , Atilla G. , Sorsa T. 
Published: December 2011

Mäntylä P, Buduneli E, Emingil G, Tervahartiala T, Pussinen PJ, Barış N, Akıllı A, Atilla G, Sorsa T. Acute myocardial infarction elevates serine protease activity in saliva of patients with periodontitis. J Periodont Res 2012; 47: 345–353. © 2011 John Wiley & Sons A/SBackground and Objective:  There are indications that acute myocardial infarction (AMI) may have an effect on the oral environment, which is reflected in the expression of salivary and gingival proteinases. According to our knowledge, no studies have been carried out to investigate the effect of AMI on the activities of two major tissue‐destructive serine protease and microbial effectors, elastase and cathepsin G, produced by oral fluid polymorphonuclear granulocytes (PMN). Therefore, we compared the activities of elastase and cathepsin G in saliva from patients with AMI and from systemically healthy subjects (non‐AMI) with similar periodontal conditions.Material and Methods:  A total of 92 patients (47 AMI and 28 non‐AMI patients with gingivitis or periodontitis, and 17 systemically and periodontally healthy subjects as a control group) were recruited. Clinical periodontal measurements were recorded, and stimulated whole‐saliva samples were collected. The patients with AMI were clinically examined within 3–4 d after admission to the coronary care unit. The activities of saliva neutrophil elastase and cathepsin G were measured after collection, at specific time‐points during incubation (from baseline to 23 h) by specific synthetic peptide substrate assays.Results:  The saliva of patients with AMI and periodontitis had a significant trend for the highest elastase activities among the study groups. Elastase and cathepsin G activities correlated significantly with each other in the AMI periodontitis group (r = 0.8, p < 0.01). In a logistic regression analysis, the level of salivary elastase activity associated significantly with periodontitis.Conclusion:  AMI may be reflected in PMN serine protease elastase activity in saliva, despite its strong association with periodontitis.
National prevalence of oral HPV infection and related risk factors in the U.S. adult population
Authors: Sanders AE , Slade GD , Patton LL 
Published: December 2011

Oral Diseases (2012) 18, 430–441This article reviews the rapidly growing evidence that oral human papilloma viruses (HPV) infection contributes to the risk of oral squamous cell carcinoma. It also reports the first nationally representative estimates of oral HPV prevalence in the United States adult population. An estimated 7.3% (95% CI: 6.0, 8.9) of the U.S. population had one or more oral HPV types detected in oral rinse; 3.1% (95%CI: 2.4, 3.9) of the U.S. population had one or more oncogenic HPV types. A substantial excess risk of HPV infection in men is not explained by education, smoking, age of sexual debut, or number of lifetime sex partners. Based on the published finding from a case–control study, where there was an odds ratio of 2.6 (95% CI: 1.5, 4.2) for the association of head and neck cancer oncogenic oral HPV infection, the estimated population attributable risk for head and neck cancer in the U.S. population was 4.7%. In other words, there would be a 4.7% reduction in incidence rate of head and neck cancer in the United States if oncogenic HPV infection could be prevented. The results also provide population data that help evaluate the likely public health benefits of prophylactic vaccination against oral HPV acquisition.