bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic exposure of topical erythromycin in comparison to oral administration and the effect on cytochrome P450 3A4 activity
Authors: Carls Alexandra , Jedamzik Julia , Witt Lukas , Hohmann Nicolas , Burhenne Juergen , Mikus Gerd 
Published: August 2014

AimsErythromycin is a macrolide antibiotic, which is frequently used as a topical formulation for the treatment of acne. It is also known as an inhibitor of the cytochrome P450 (CYP) isoenzyme 3A4. In this study, the systemic availability of topical erythromycin, hence the influence on the activity of CYP3A, is evaluated in comparison to orally administered erythromycin.MethodsSixteen healthy volunteers received consecutively topical (two applications of 800 mg) and oral erythromycin (two dose groups, 250 and 1000 mg, with n = 8) to assess erythromycin pharmacokinetics. A microdose of midazolam (3 μg orally) was used to determine the effect on CYP3A activity.ResultsAfter topical administration, erythromycin was detected in the plasma of every participant without causing a statistically significant alteration of CYP3A activity. After oral administration, the dose‐normalized erythromycin exposure (AUC∞) was 1335 h ng ml−1 after 250 mg and 3‐fold higher after the 1000 mg dose (4051 h ng ml−1; P < 0.01), suggesting nonlinear pharmacokinetics of erythromycin. Both oral doses inhibited CYP3A activity; midazolam clearance was decreased to 61% (250 mg) and 21% (1000 mg). The relationship between erythromycin exposure and CYP3A activity (Hill equation) revealed a 50% reduction of CYP3A activity by an erythromycin AUC∞ of 2106 h ng ml−1.ConclusionsTopical erythromycin did not cause clinically relevant CYP3A alterations, although low systemic availability of erythromycin was observed. This supports the assumption that treatment with topical erythromycin is not critical in terms of CYP3A inhibition. Furthermore, substantial nonlinearity of erythromycin pharmacokinetics after two different oral doses was observed, possibly due to autoinhibition.
Next‐generation sequencing is a credible strategy for blood group genotyping
Authors: Fichou Yann , Audrézet Marie‐Pierre , Guéguen Paul , Le Maréchal Cédric , Férec Claude 
Published: August 2014

SummaryAlthough several medium/high‐throughput tools have been engineered for molecular analysis of blood group genes, they usually rely on the targeting of single nucleotide polymorphisms, while other variants remain unidentified. To circumvent this limitation a strategy for genotyping blood group genes by next‐generation sequencing (NGS) was set up. Libraries consisting of exons, flanking introns and untranslated regions of 18 genes involved in 15 blood systems were generated by the Ion AmpliSeq™ Library Kit 2.0 and by fragmenting polymerase chain reaction products, normalized by two different approaches, mixed and sequenced by the Ion Torrent Personal Genome Machine (PGM™) Sequencer. In our conditions, defined to limit both intra‐ and inter‐sample variability, sequences from mixed libraries were read in a single run for a total coverage of 86·03% of the coding DNA sequences, including all loci defining the most clinically relevant antigens in all genes, except ABO. Importantly, the challenging attempt to generate gene‐specific data for the homologous genes was successful. This work, which combines two complementary approaches to generate libraries, defines technical conditions for genotyping blood group genes, illustrates that NGS is suitable for such an application and suggests that, after automation, this novel tool could be used for molecular typing at the laboratory level.
Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies
Authors: Latrofa F , Ricci D , Montanelli L , Piaggi P , Mazzi B , Bianchi F , Brozzi F , Santini P , Fiore E , Marinò M , Tonacchera M , Vitti P 
Published: August 2014

SummaryThe subclass distribution of thyroglobulin autoantibodies (TgAb) is debated, whereas their epitope pattern is restricted. Radioidine (131 I) treatment for Graves' disease (GD) induces a rise in TgAb levels, but it is unknown whether it modifies subclass distribution and epitope pattern of TgAb as well. We collected sera from GD patients before 131 I treatment and 3 and 6 months thereafter. We measured total TgAb, TgAb light chains and TgAb subclasses by enzyme-linked immunosorbent assay (ELISA) in 25 patients. We characterized the TgAb epitope pattern in 30 patients by inhibiting their binding to 125-ITg by a pool of four TgAb-Fab (recognizing Tg epitope regions A, B, C and D) and to Tg in ELISA by each TgAb-Fab. Total TgAb immunoglobulin (Ig)G rose significantly (P = 0·024). TgAb κ chains did not change (P = 0·052), whereas TgAb λ chains increased significantly (P = 0·001) and persistently. We observed a significant rise in IgG1 and IgG3 levels after 131 I (P = 0·008 and P = 0·006, respectively), while IgG2 and IgG4 levels did not change. The rise of IgG1 was persistent, that of IgG3 transient. The levels of inhibition of TgAb binding to Tg by the TgAb-Fab pool were comparable. A slight, non-significant reduction of the inhibition by the immune-dominant TgAb-Fab A was observed 3 and 6 months after 131 I. We conclude that 131 I treatment for GD increases the levels of the complement-activating IgG1 and IgG3 subclasses and does not influence significantly the epitope pattern of TgAb. In autoimmune thyroid disease subclass distribution of autoantibodies is dynamic in spite of a stable epitope pattern.
Ultrasound scoring in combination with ultrasound elastography for differentiating benign and malignant thyroid nodules
Authors: Shao Jun , Shen Ye , Lü Jieqiong , Wang Jianming 
Published: August 2014

SummaryObjectiveThe aim of this study was to evaluate the value of ultrasound scores obtained by conventional ultrasonography and ultrasound elastography in the differentiation of benign and malignant thyroid nodules in Chinese patients.MethodsThis study included 297 patients who were referred for surgery for compressive symptoms or suspicion of malignancy. Five hundred and twelve thyroid nodules were examined by ultrasonography. The final diagnosis was based on histological findings. A seven‐point ultrasound scoring system based on conventional ultrasonography and a five‐point scoring system based on ultrasound elastography were applied independently or in combination. The receiver operating characteristic (ROC) curves were graphed, and the areas under the curves (AUCs) were compared using the χ2‐test.ResultsSolid composition, hypo‐echoic appearance, an irregular or blurred margin, an aspect ratio ≥1, intranodular blood flow and presence of microcalcifications were significant predictors of malignant thyroid nodules. The AUC (95% CI) was 0·9067 (0·8817–0·9318) for the ultrasound scores based on conventional ultrasonography and 0·9080 (0·8842–0·9317) for the elasticity scores. The combination of these two scoring systems provided good accuracy with an AUC (95% CI) of 0·9415 (0·9223–0·9606), which was significantly higher than that obtained with the conventional ultrasound scores (χ2 = 36·03, P < 0·001) or the elasticity scores (χ2 = 12·80, P < 0·001) individually. When we set the cut‐point to ≥5, the sensitivity and specificity were 85·22% and 87·38%, respectively.ConclusionsElastography in combination with conventional ultrasonography is a promising imaging‐based approach that can assist in the differential diagnosis of thyroid cancer.
Pilot study to assess measures to be used in the prospective audit of the management of foot ulcers in people with diabetes
Authors: Holman N. , Young B. , Stephens H. , Jeffcoate W. ,   the members of the National Foot Care Audit Steering Group
Published: August 2014

AbstractAimTo design and test a methodology for assessing aspects of the management of foot disease in diabetes.MethodsA national working group devised pilot datasets that may be used to document the process of management of active ulceration. Participating volunteer specialist units throughout England were required to characterize newly presenting people with diabetic foot ulcers using a standard questionnaire comprising the dataset and to document outcomes at 6 and 12 months. Semi‐structured interviews were later conducted with the volunteers at the units.ResultsA total of 23 units recorded baseline data on 652 people with incident foot ulcers; valid outcome data were available for 541 people (83.0%). Of the 541 index ulcers, 351 (64.9%) healed within 24 weeks, with a median time to healing of 63 days. Ulcer site and depth and peripheral arterial disease were associated with differing ulcer healing rates. By contrast, baseline demographic characteristics were not independently associated with healing. These were used to calculate a standardized case‐mix adjusted healing ratio. In most units data collection took < 10 min per person, but participants reported that the burden of local data collection was still excessive.ConclusionThis study confirmed the feasibility of routine multi‐unit comparative assessment of care of the foot in diabetes, including the generation of meaningful service reports, but for general use the burden of local data collection will need to be reduced (e.g. by using linkage to existing national data collections).
Congenital oesophageal stricture in anArabian filly treated by balloon dilation
Authors: Berlin D. , Shaabon K. , Peery D. 
Published: August 2014

SummaryCongenital oesophageal stricture was diagnosed via endoscopy in a 3‐day‐oldArabian filly suffering from nasal milk regurgitation. Vascular ring anomaly or other extramural, intramural or intraluminal causes were not identified on radiographs or on a computed tomography scan; thus a functional abnormality was suspected. The filly was treated with antibiotics for aspiration pneumonia and was fed milk through an indwelling nasoesophageal tube. Two sessions of balloon bougienage at the stenotic site, under sedation, resulted in marked clinical improvement and thereafter the filly was gradually reintroduced to suckling from the mare. The filly was discharged from the hospital after 17 days and on follow‐up there were no reports of food regurgitation even after the introduction of solid food. The filly was still doing well in the latest follow‐up at age 11 months.
Caudal lumbar vertebral fractures inCaliforniaQuarterHorse andThoroughbred racehorses
Authors: Collar E. M. , Zavodovskaya R. , Spriet M. , Hitchens P. L. , Wisner T. , Uzal F. A. , Stover S. M. 
Published: August 2014

SummaryReasons for performing studyTo gain insight into the pathophysiology of equine lumbar vertebral fractures in racehorses.ObjectivesTo characterise equine lumbar vertebral fractures inCalifornia racehorses.Study designRetrospective case series and prospective case–control study.MethodsRacehorsepost mortemreports and jockey injury reports were retrospectively reviewed. Vertebral specimens from 6 racehorses affected with lumbar vertebral fractures and 4 control racehorses subjected to euthanasia for nonspinal fracture were assessed using visual, radiographic, computed tomography and histological examinations.ResultsLumbar vertebral fractures occurred in 38QuarterHorse and 29Thoroughbred racehorses over a 22 year period, primarily involving the 5th and/or 6th lumbar vertebrae (L5–L6; 87% ofQuarterHorses and 48% ofThoroughbreds). Lumbar vertebral fractures were the third most common musculoskeletal cause of death inQuarterHorses and frequently involved a jockey injury. Lumbar vertebral specimens contained anatomical variations in the number of vertebrae, dorsal spinous processes and intertransverse articulations. Lumbar vertebral fractures examined in 6 racehorse specimens (5QuarterHorses and oneThoroughbred) coursed obliquely in a cranioventral to caudodorsal direction across the adjacentL5–L6vertebral endplates and intervertebral disc, although one case involved only one endplate. All cases had evidence of abnormalities on the ventral aspect of the vertebral bodies consistent with pre‐existing, maladaptive pathology.ConclusionsLumbar vertebral fractures occur in racehorses with pre‐existing pathology at theL5–L6vertebral junction that is likely predisposes horses to catastrophic fracture. Knowledge of these findings should encourage assessment of the lumbar vertebrae, therefore increasing detection of mild vertebral injuries and preventing catastrophic racehorse and associated jockey injuries.
Faunal response to benthic and hyporheic sedimentation varies with direction of vertical hydrological exchange
Authors: Mathers Kate L. , Millett Jonathan , Robertson Anne L. , Stubbington Rachel , Wood Paul J. 
Published: August 2014

Summary

Sedimentation and clogging of benthic and hyporheic zone substrata is increasingly being recognised as one of the greatest threats to the ecological integrity of riverine ecosystems globally. This ex situ study examined the influence of sedimentation (surface and subsurface) and pattern of hydrological exchange on the vertical distribution of the freshwater shrimp Gammarus pulex within the experimental substrata of running water mesocosms.

Six sediment treatments representing a continuum from a clean gravel substratum to heavy sediment loading of both surface (benthic) and subsurface (hyporheic) substrata were used to examine the distribution of G. pulex in relation to the direction of hydrological exchange (downwelling, upwelling and no exchange).

The distribution of G. pulex between the sediment layers was dependent on the pattern of hydrological exchange, sediment treatment and the interaction between these two factors.

Sedimentation of the surface layer under no‐exchange conditions resulted in a lower proportion of G. pulex being recorded in the benthic sediments, whilst there were no significant differences under downwelling and upwelling flow conditions.

Sedimentation of multiple layers of the column (benthic and subsurface) reduced the ability of individuals to utilise the subsurface layers of the substratum (i.e. the hyporheic zone) under no‐exchange and upwelling conditions. However, with downwelling conditions, the abundance of G. pulex declined with depth regardless of the fine sediment distribution or volume.

This study demonstrates that faunal movement, and use of benthic and hyporheic substrata, may be influenced by sedimentation and modified by the pattern of vertical hydrological exchange. Severe sedimentation (colmation) has the potential to prevent benthic fauna from accessing the hyporheic zone and its resources which may ultimately lead to a reduction in stream diversity and metabolism, thereby limiting overall productivity and lotic ecosystem resilience.
Neonatal lethality of neural crest cell‐specific Rest knockout mice is associated with gastrointestinal distension caused by aberrations of myenteric plexus
Authors: Aoki Hitomi , Hara Akira , Oomori Yoshiyuki , Shimizu Yasutake , Yamada Yasuhiro , Kunisada Takahiro 
Published: August 2014

RE1‐silencing transcription factor (REST), also known as NRSF (neuron‐restrictive silencer factor), is a well‐known transcriptional repressor of neural genes. Rest null mice have embryonic lethality which prevents further investigations of the functions of the Rest gene in vivo. We studied neonatal but not embryonic lethality that was characterized by gastrointestinal tract dilation in the neural crest cell (NCC)‐specific Rest conditional knockout (CKO) mice. While no histological abnormalities except the thinning of the digestive tract as a consequence of the gas accumulation were found in the digestive tract of the mutant mice, they do not have proper gastric retention after oral dye administration and the reduction of acetylcholinesterase (AChE) activity in NCC‐derived myenteric plexus in the stomach was detected. High CO2 concentration in the dilated digestive tract of the Rest CKO mice indicates a failure of gut function by underdeveloped cholinergic transmission in the enteric nervous system. The observed gastrointestinal distension phenotype provides a model for understanding the genetic and molecular basis of NCC defects in humans.
Exploration of shared decision‐making processes among dieticians and patients during a consultation for the nutritional treatment of dyslipidaemia
Authors: Vaillancourt Hugues , Légaré France , Gagnon Marie‐Pierre , Lapointe Annie , Deschênes Sarah‐Maude , Desroches Sophie 
Published: August 2014

AbstractBackgroundShared decision making (SDM) holds great potential for improving the therapeutic efficiency and quality of nutritional treatment of dyslipidaemia by promoting patient involvement in decision making. Adoption of specific behaviours fostering SDM during consultations has yet to be studied in routine dietetic practice.ObjectiveUsing a cross‐sectional study design, we aimed to explore both dieticians' and patients' adoption of SDM behaviours in dietetic consultations regarding the nutritional treatment of dyslipidaemia.MethodsTwenty‐six dieticians working in local health clinics in the Quebec City metropolitan area were each asked to identify one dyslipidaemic patient they would see in an upcoming consultation. Based on the Theory of Planned Behaviour (TPB), questionnaires were designed to study two targeted SDM behaviours: ‘to discuss nutritional treatment options for dyslipidaemia’ and ‘to discuss patients’ values and preferences about nutritional treatment options for dyslipidaemia'. These questionnaires were administered to the dietician–patient dyad individually before the consultation. Associations between TPB constructs (attitude, subjective norm and perceived behavioural control) towards behavioural intentions were analysed using Spearman's partial correlations.ResultsThirteen unique patient‐dietician dyads completed the study. Perceived behavioural control was the only TPB construct significantly associated with both dieticians' and patients' intentions to adopt the targeted SDM behaviours (P < 0.05).ConclusionsAs perceived behavioural control seems to determine dieticians' and patients' adoption of SDM behaviours, interventions addressing barriers and reinforcing enablers of these behaviours are indicated. This exploratory study highlights issues that could be addressed in future research endeavours to expand the knowledge base relating to SDM adoption in dietetic practice.
Extracavitary primary effusion lymphoma: clinical, morphological, phenotypic and cytogenetic characterization using nuclei enrichment technique
Authors: Juskevicius Darius , Dietsche Tanja , Lorber Thomas , Rufle Alexander , Ruiz Christian , Mickys Ugnius , Krasniqi Fatime , Dirnhofer Stephan , Tzankov Alexandar 
Published: August 2014

Abstract AimsPrimary effusion lymphoma (PEL) is a rare form of aggressive B‐cell lymphoma, which typically manifests as malignant effusion in the body cavities. However, extracavitary solid variants are also described. The aim of this study was to investigate copy number aberrations in two cases of solid PEL at their first occurrences and relapse by applying a newly developed methodology of tumour nuclei enrichment.Methods and resultsUsing histological and genetic techniques, a novel protocol for tumour nuclei enrichment by flow sorting and array‐comparative genomic hybridization, we characterized two cases of extracavitary PEL, one of which later relapsed as effusion. Both primary tumours were positive for HHV8 and EBV, confined to lymph nodes, and aberrantly expressed CD3, yet displaying clonal immunoglobulin gene rearrangements indicating B‐cell origin. Cytogenetic characterization of primary tumours revealed modest number of aberrations, partially overlapping with previously reported affected loci. The effusional relapse in case 1 was cytogenetically related to the primary tumour but showed dramatic increase of chromosomal instability.ConclusionsWe for the first time demonstrate a cytogenetic relationship between solid and effusional presentations of PEL. Moreover, we provide an indirect evidence of multiple malignant clones, which gave rise to clonally‐related, yet karyotypically different relapsing lymphoma manifestations.
Bone marrow involvement of Langerhans cell histiocytosis: immunohistochemical evaluation of bone marrow for CD1a, Langerin, and S100 expression
Authors: Kim Hyun‐Ki , Park Chan‐Jeoung , Jang Seongsoo , Cho Young‐Uk , Park Sang Hyuk , Koh Kyung Nam , Im Ho Joon , Seo Jong Jin 
Published: August 2014

AimsAlthough bone marrow (BM) involvement in Langerhans cell histiocytosis (LCH) is a negative prognostic indicator, there are no widely accepted criteria to define BM involvement in LCH. We evaluated the BM of LCH patients at diagnosis by immunohistochemical (IHC) staining for S100, CD1a and Langerin, along with other features.Methods and resultsWe retrospectively reviewed the records of 75 patients diagnosed as LCH at our center. IHC stains of Langerin, CD1a and S100 were done using paraffin‐embedded tissue sections. Only three cases showed massive involvement of clustered Langerhans cells. There were linear associations between positive cell count and disease extent. Some discordant results between Langerin and CD1a IHC stains were noted. Among cases showing positive results for all three IHC stains, six patients (54.5%) were in the multisystem group, and three patients (27.3%) had cytopenias. The reactivation‐free survival rates did not differ between the group positive for CD1a or Langerin, and the group negative for Langerin and CD1a.ConclusionsLangerin and CD1a seem to be useful markers of Langerhans cells, and S100 might be a nonspecific marker for these cells, in the BM. Both Langerin and CD1a IHC staining is needed to evaluate the BM involvement of LCH.
Childhood florid follicular hyperplasia with immunoglobulin light‐chain restriction in the gastrointestinal tract
Authors: Martinez‐Lopez Azahara , Montes‐Moreno Santiago , Ramos Rafael , Afonso‐Martin Juan Luis , Mazorra Francisco , Gonzalez de Villambrosia Sonia , Batlle Ana , Grogan Thomas M , Piris Miguel Angel 
Published: August 2014

AimsImmunoglobulin light‐chain expression is used routinely as an indirect marker of clonality for recognizing B cell lymphoproliferative disorders.Methods and resultsHere we describe four floral follicular hyperplasia cases in the gastrointestinal tract (appendix and rectum) of children (4 to 6 years). Immunohistochemical studies revealed lambda light‐chain restriction that was associated with polyclonal IgH pattern. Clinical features and follow‐up of the patients did not reveal any other systemic symptoms, laboratory abnormalities or organ alterations.ConclusionsRecognition of this phenomenon is useful in the diagnosis of nodular lymphoid hyperplasia of the gastrointestinal tract, for avoiding overdiagnosis of lymphoid malignancies, and raises concerns that the identification of light‐chain restriction is not necessarily a marker of monoclonality.