bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technical Limitations in Detection of Gastroesophageal Reflux in Neonates
Authors: Di Fiore Juliann M , Arko Marina , Churbock Kim , Hibbs Anna Maria , Martin Richard J 
Published: July 2009

ABSTRACTObjective:Characterize the incidence and possible etiologies of acid reflux events detected by pH and not identified by multiple intraluminal impedance (MII) monitoring.Materials and Methods:Acid reflux events detected by pH but not identified by MII (pH‐only) were documented in 80 preterm and 39 term infants. Reasons for failure of MII to detect these events were classified as failure to meet MII scoring criteria, presence of an air bolus, technical artifact, and no change in impedance. Events with no change in impedance were stratified to low impedance throughout the study (possible esophageal inflammation), transient decrease in pre‐event impedance (presence of refluxate), occurrence <30 seconds of a preceding event, and no explanation.Results:A total of 2572 events were detected by pH, with 59% of events not identified by MII. A higher incidence of pH‐only events occurred in preterm versus term infants (54 ± 27% versus 42 ± 23%, P = .025, respectively). Thirteen percent of pH‐only events were missed due to MII scoring criteria, 12% due to technical artifact, 11% due to an air bolus, and 64% had no change in impedance. Of the 978 events with no change in impedance, 154 were associated with low impedance throughout the study, 430 with a transient decrease in pre‐event impedance, and 175 were preceded by a reflux episode within 30 seconds.Conclusions:There was a high incidence of acid reflux events detected by pH but not identified by MII. This occurred more often in the least mature infants, and we speculate that delayed esophageal fluid clearance is the major underlying mechanism.
Association Between Genotypes and Phenotypes in Coeliac Disease
Authors: Gudjónsdóttir Audur H , Nilsson Staffan , Naluai Åsa Torinsson , Ek Johan , Amundsen Silja S , Wahlström Jan , Ascher Henry 
Published: July 2009

ABSTRACTBackground:Coeliac disease (CD) is a genetically driven immunological intolerance to dietary gluten with a wide range of clinical presentations. The aim of this study was to investigate the heritability of the phenotype in CD and the influence on the phenotype of different genes associated with the disease.Patients and Methods:One hundred and seven families with at least 2 siblings with CD were collected. The patients were grouped in symptom grades on the basis of the clinical presentation, the age at diagnosis, and sex. Stratification analyses of the human leucocyte antigen‐DQA1 and human leucocyte antigen‐DQB1 genotypes, the CTLA4 +49A/G polymorphism, the CTLA4 haplotype MH30*G:−1147*T:+49*A:CT60*G:CT61*A, and the 5q31‐33 loci were done.Results:The heritability of the phenotype was estimated to be 0.45. Significant association and linkage was found between the clinical presentation and the CTLA4 +49A/G polymorphism but not for the other genotypes. No correlation was found between genotypes and age at diagnosis or sex.Conclusions:Our results indicate that the heritability is determiner of the phenotype in CD. The CTLA4 +49A/G polymorphism is correlated to the clinical presentation: the AA genotype is associated with clinically silent disease.
Partial External Biliary Diversion in Children With Progressive Familial Intrahepatic Cholestasis and Alagille Disease
Authors: Yang Huiqi , Porte Robert J , Verkade Henkjan J , De Langen Zacharias J , Hulscher Jan BF 
Published: July 2009

ABSTRACTBackground:Partial external biliary diversion (PEBD) is a promising treatment for children with progressive familial intrahepatic cholestasis (PFIC) and Alagille disease. Little is known about long‐term outcomes.Patients and Methods:A retrospective chart review of all patients undergoing PEBD in the University Medical Centre of Groningen (UMCG).Results:Between 2000 and 2005, PEBD was performed on 14 children with severe pruritus (PFIC 11, mean age 5.3 ± 4.4 years; Alagille 3, mean age 7.4 ± 4.2 years). Stature was <−2 standard deviation score (SDS) in 50%. Median preoperative serum bile salt concentration was 318 μmol/L (range 23–527 μmol/L). Twenty‐nine percent had severe liver fibrosis and 71% had mild or moderate fibrosis. Median follow‐up was 3.1 years (range 2.0–5.7 years). One patient (7%) underwent a liver transplantation at 3.2 years post‐PEBD. Two years postoperatively, 50% were without pruritus and 21% had mild pruritus. In 29%, pruritus had not diminished; 3 of them had severe fibrosis preoperatively. In patients with mild or moderate fibrosis, PEBD decreased serum bile salts (105 μmol/L [range 8–269 μmol/L] 2 years postoperatively). Bile salts did not decrease in the patients with severe fibrosis. Two years after PEBD, 27% had a stature below −2 SDS.Conclusions:At median follow‐up of 3.1 years after PEBD, pruritus has been relieved in 75%. Bile salts level and growth are improved in most patients. Longer follow‐up is needed to determine whether PEBD can postpone or avoid the demand for liver transplantation.
Autoimmune Hepatitis
Authors: Mieli‐Vergani Giorgina , Heller Solange , Jara Paloma , Vergani Diego , Chang Mei‐Hwei , Fujisawa Tomoo , González‐Peralta Regino P , Kelly Deirdre , Mohan Neelam , Shah Uzma , Murray Karen F 
Published: July 2009

ABSTRACTAutoimmune hepatitis is characterized by inflammatory liver histology, circulating nonorgan‐specific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of juvenile autoimmune hepatitis (AIH) are recognized according to seropositivity for smooth muscle and/or anti‐nuclear antibody (AIH type 1) or liver kidney microsomal antibody (AIH type 2). There is a female predominance in both. AIH type 2 presents more acutely, at a younger age and commonly with immunoglobulin A deficiency, whereas duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long‐term prognosis are similar in the 2 groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long‐term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. Differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. In this article we review the state of the art of diagnosis, monitoring, and treatment for children with AIH.
Phase 2 study of weekly bortezomib in mantle cell and follicular lymphoma
Authors: Gerecitano John , Portlock Carol , Moskowitz Craig , Hamlin Paul , Straus David , Zelenetz Andrew D. , Zhang Zhigang , Dumitrescu Otilia , Sarasohn Debra , Lin Dorothy , Pappanicholaou Jennifer , Cortelli Barbara M. , Neylon Ellen , Hamelers Rachel , Wright John , O’Connor Owen A. 
Published: July 2009

SummaryTwice‐weekly bortezomib has proven activity in mantle cell (MCL) and indolent lymphomas. This study explored a weekly schedule of bortezomib in follicular lymphoma (FL) and MCL. Although weekly bortezomib was better tolerated, the overall response rate (ORR) was inferior (18% vs. 50%, P = 0·02) with no complete remissions (CR) (compared with 18% CR for the twice‐weekly schedule). Progression‐free survival (PFS) was not different. The weekly schedule of bortezomib was less toxic, but yielded fewer and lower quality responses than twice‐weekly bortezomib. Given the similar PFS, the weekly schedule may still be appropriate for some patients.
RQ‐PCR based WT1 expression in comparison to BCR‐ABL quantification can predict Philadelphia negative clonal evolution in patients with imatinib‐treated chronic myeloid leukaemia
Authors: Schnittger Susanne , Bacher Ulrike , Kern Wolfgang , Tschulik Claudia , Weiss Tamara , Haferlach Claudia , Haferlach Torsten 
Published: July 2009

SummaryA retrospective comparison of WT1 and BCR‐ABL1 expression was performed in 40 imatinib‐treated chronic myeloid leukaemia patients. The overall correlation of WT1 and BCR‐ABL1 was low. In two patients WT1 expression was increasing despite very low BCR‐ABL1 levels. As both revealed Ph‐negative aberrant clones, a second independent cohort of 20 cases, all with Ph‐negative clonal evolution, was analysed. High WT1 expression (5·0–177·0%) was detected in a case with +11 and in four of eight cases with +8, but not in cases with del(20q) or −Y. Thus, increasing WT1 levels in molecular responders may indicate Ph‐negative clonal cytogenetic evolution during imatinib treatment.
The non‐specific lipid transfer protein, Ara h 9, is an important allergen in peanut
Authors: Lauer I. , Dueringer N. , Pokoj S. , Rehm S. , Zoccatelli G. , Reese G. , Miguel‐Moncin M. S. , Cistero‐Bahima A. , Enrique E. , Lidholm J. , Vieths S. , Scheurer S. 
Published: July 2009

SummaryBackground
Plant food allergy in the Mediterranean area is mainly caused by non‐specific lipid transfer proteins (nsLTP). The aim of this study was to characterize peanut nsLTP in comparison with peach nsLTP, Pru p 3, and assess its importance in peanut allergy.Methods
Peanut‐allergic patients from Spain (n=32) were included on the basis of a positive case history and either a positive skin prick test or specific IgE to peanut. For comparison, sera of 41 peanut‐allergic subjects from outside the Mediterranean area were used. Natural Ara h 9 and two isoforms of recombinant Ara h 9, expressed in Pichia pastoris, were purified using a two‐step chromatographic procedure. Allergen characterization was carried out by N‐terminal sequencing, circular dichroism (CD) spectroscopy, immunoblotting, IgE inhibition tests and basophil histamine release assays.Results
Compared with natural peanut nsLTP, the recombinant proteins could be purified in high amounts from yeast supernatant (45 mg/L). The identity of the proteins was verified by N‐terminal amino acid sequencing and with rabbit nsLTP‐specific antibodies. CD spectroscopy revealed similar secondary structures for all preparations and Pru p 3. The Ara h 9 isoforms showed 62–68% amino acid sequence identity with Pru p 3. IgE antibody reactivity to rAra h 9 was present in 29/32 Spanish and 6/41 non‐Mediterranean subjects. Recombinant Ara h 9 showed strong cross‐reactivity to nPru p 3 and similar IgE‐binding capacity as nAra h 9. The two Ara h 9 isoforms displayed similar IgE reactivity. In peanut‐allergic patients with concomitant peach allergy, Ara h 9 showed a weaker allergenic potency than Pru p 3 in histamine release assays.Conclusions
Ara h 9 is a major allergen in peanut‐allergic patients from the Mediterranean area. Ara h 9 is capable of inducing histamine release from basophils, but to a lesser extent than Pru p 3.
CD4+CD25+ T cell depletion impairs tolerance induction in a murine model of asthma
Authors: Boudousquié C. , Pellaton C. , Barbier N. , Spertini F. 
Published: July 2009

SummaryBackground
Regulatory T cells (Tregs) are key players in controlling the development of airway inflammation. However, their role in the mechanisms leading to tolerance in established allergic asthma is unclear.Objective
To examine the role of Tregs in tolerance induction in a murine model of asthma.Methods
Ovalbumin (OVA) sensitized asthmatic mice were depleted or not of CD25+ T cells by anti‐CD25 PC61 monoclonal antibody (mAb) before intranasal treatment (INT) with OVA, then challenged with OVA aerosol. To further evaluate the respective regulatory activity of CD4+CD25+ and CD4+CD25− T cells, both T cell subsets were transferred from tolerized or non‐tolerized animals to asthmatic recipients. Bronchoalveolar lavage fluid (BALF), T cell proliferation and cytokine secretion were examined.Results
Intranasal treatment with OVA led to increased levels of IL‐10, TGF‐β and IL‐17 in lung homogenates, inhibition of eosinophil recruitment into the BALF and antigen specific T cell hyporesponsiveness. CD4+CD25+Foxp3+ T cells were markedly upregulated in lungs and suppressed in vitro and in vivo OVA‐specific T cell responses. Depletion of CD25+ cells before OVA INT severely hampered tolerance induction as indicated by a strong recruitment of eosinophils into BALF and a vigorous T cell response to OVA upon challenge. However, the transfer of CD4+CD25− T cells not only suppressed antigen specific T cell responsiveness but also significantly reduced eosinophil recruitment as opposed to CD4+CD25+ T cells. As compared with control mice, a significantly higher proportion of CD4+CD25− T cells from OVA treated mice expressed mTGF‐β.Conclusion
Both CD4+CD25+ and CD4+CD25− T cells appear to be essential to tolerance induction. The relationship between both subsets and the mechanisms of their regulatory activity will have to be further analyzed.
High‐risk HPV detection in specimens collected in SurePath preservative fluid: comparison of ambient and refrigerated storage
Authors: Hardie A. , Moore C. , Patnick J. , Cuschieri K. , Graham C. , Beadling C. , Ellis K. , Frew V. , Cubie H. A. 
Published: July 2009

Objective:  With moves to introduce human papillomavirus (HPV) triage at sentinel sites in England, it is essential that optimal storage and transport conditions are determined for efficient HPV detection using residual liquid‐based cytology specimens.Methods:  Two cytology laboratories with comparable workloads sent residual cervical cytology specimens collected in BD Surepath™ Preservative Fluid to the Specialist Virology Centre for HPV testing. Storage and transport of specimens was at ambient (site A) or refrigerated (site R) temperatures. The effect of temperature on the ability to detect high‐risk human papillomavirus (HR‐HPV) using Digene Hybrid Capture® 2 High‐Risk HPV DNA Test (hc2) and Roche AMPLICOR® HPV Test (AMPLICOR) was assessed. All specimens with discordant results were tested using Roche Linear Array HPV Genotyping test.Results:  A total of 796 residual cytology specimens, with cytology ranging from normal to severe dyskaryosis, were provided (399 from site A and 397 from site R). Ambient storage and transit of cervical specimens in SurePath medium did not appear to affect significantly the suitability of the specimen for HPV testing, as measured by the concordance of the HR‐HPV screening assays for ambient versus refrigerated specimens and by the proportion of specimens which tested invalid.Conclusion:  Residual cytology specimens in SurePath medium, stored and transported at ambient temperature, appear suitable for HR‐HPV detection by AMPLICOR beyond the manufacturer’s recommended time and potentially up to four weeks.
A compact STED microscope providing 3D nanoscale resolution
Authors: WILDANGER D. , MEDDA R. , KASTRUP L. , HELL S.W. 
Published: July 2009

SummaryThe advent of supercontinuum laser sources has enabled the implementation of compact and tunable stimulated emission depletion fluorescence microscopes for imaging far below the diffraction barrier. Here we report on an enhanced version of this approach displaying an all‐physics based resolution down to (19 ± 3) nm in the focal plane. Alternatively, this single objective lens system can be configured for 3D imaging with resolution down to 45 × 45 × 108 nm in a cell. The obtained results can be further improved by mathematical restoration algorithms. The far‐field optical nanoscale resolution is attained in a variety of biological samples featuring strong variations in the local density of features.
Light‐emitting diode flashlights as effective and inexpensive light sources for fluorescence microscopy
Authors: ROBERTSON J.B. , ZHANG Y. , JOHNSON C.H. 
Published: July 2009

SummaryLight‐emitting diodes (LEDs) are becoming more commonly used as light sources for fluorescence microscopy. We describe the adaptation of a commercially available light‐emitting diode flashlight for use as a source for fluorescence excitation. This light source is long‐lived, inexpensive and is effective for excitation in the range of 440–600 nm.
Re‐examination of a proposed case of stasipatric speciation: phylogeography of the Australian morabine grasshoppers (Vandiemenella viatica species group)
Authors: KAWAKAMI TAKESHI , BUTLIN ROGER K. , ADAMS MARK , SAINT KATHLEEN M. , PAULL DAVID J. , COOPER STEVEN J. B. 
Published: July 2009

AbstractKaryotypic differences have been used for delimiting populations or species, although whether these mutations provide strong barriers to gene flow between populations and promote speciation remains contentious. In this study, we assessed whether 11 chromosomal races of Australian morabine grasshoppers (Vandiemenella viatica species group) represent genetically distinct populations by analyses of cytological and allozyme (35 loci) data and DNA sequences of the elongation factor‐1 alpha (EF‐1α), anonymous Mvia11, and mitochondrial cytochrome c oxidase subunit I (COI) loci. While the Vandiemenella chromosomal taxa generally represent genetically distinct units, a substantial portion of the total genetic variation in our samples was not explained by the chromosomal variation. Mantel tests indicated that Vandiemenella populations were spatially structured and have maintained gene flow at a local scale within each of the taxa. The group was subdivided into 13 genetic clusters; four chromosomal taxa comprised single exclusive clusters, while others comprised more than one cluster or clusters shared with other taxa. Boundaries of these cryptic population subdivisions correspond with several biogeographical barriers, such as straits, gulfs, the Murray River, and an ancient mega‐lake, Lake Bungunnia. The viatica species group was previously proposed to have diversified without major geographical separation based on the stasipatric speciation model; however, the present study suggests the involvement of allopatric fragmentation. Given extensive nonmonophyly of chromosomal taxa and incomplete barriers to gene flow among taxa, all Vandiemenella chromosomal taxa and genetically distinct populations within chromosomal taxa, except Vandiemenella pichirichi, should be regarded as populations of one species: Vandiemenella viatica.
Quantification of collider‐stratification bias and the birthweight paradox
Authors: Whitcomb Brian W. , Schisterman Enrique F. , Perkins Neil J. , Platt Robert W. 
Published: July 2009

SummaryThe ‘birthweight paradox’ describes the phenomenon whereby birthweight‐specific mortality curves cross when stratified on other exposures, most notably cigarette smoking. The paradox has been noted widely in the literature and numerous explanations and corrections have been suggested. Recently, causal diagrams have been used to illustrate the possibility for collider‐stratification bias in models adjusting for birthweight. When two variables share a common effect, stratification on the variable representing that effect induces a statistical relation between otherwise independent factors. This bias has been proposed to explain the birthweight paradox.Causal diagrams may illustrate sources of bias, but are limited to describing qualitative effects. In this paper, we provide causal diagrams that illustrate the birthweight paradox and use a simulation study to quantify the collider‐stratification bias under a range of circumstances. Considered circumstances include exposures with and without direct effects on neonatal mortality, as well as with and without indirect effects acting through birthweight on neonatal mortality. The results of these simulations illustrate that when the birthweight–mortality relation is subject to substantial uncontrolled confounding, the bias on estimates of effect adjusted for birthweight may be sufficient to yield opposite causal conclusions, i.e. a factor that poses increased risk appears protective. Effects on stratum‐specific birthweight–mortality curves were considered to illustrate the connection between collider‐stratification bias and the crossing of the curves. The simulations demonstrate the conditions necessary to give rise to empirical evidence of the paradox.
Neuromuscular features in Marfan syndrome
Authors: Voermans NC , Timmermans J , Van Alfen N , Pillen S , Op Den Akker J , Lammens M , Zwarts MJ , Van Rooij IALM , Hamel BC , Van Engelen BG 
Published: July 2009

Marfan syndrome is a clinically and allelic heterogeneous, heritable connective tissue disorder with infrequently reported neuromuscular features. This study is the first to delineate these symptoms in a non‐selected population. Neuromuscular involvement was evaluated in 10 Marfan patients through a standardized questionnaire, physical examination, nerve conduction study (NCS), needle electromyography (EMG), muscle ultrasound, laboratory investigation, and muscle biopsy. Existing neuroimages were screened for dural ectasia and spinal meningeal cysts. Twenty healthy controls with similar age distribution completed the questionnaire.The results showed that various neuromuscular symptoms occur more frequently in the patients. Four older patients reported muscle weakness, five patients had a mild‐to‐moderate reduction in vibration sense, and all older patients mentioned mild functional impairments. NCS showed axonal polyneuropathy in four and EMG myopathic and neurogenic changes in all patients. Increased echo intensity and atrophy on muscle ultrasound was found in more than half of the patients. Muscle biopsies obtained in two patients showed myopathic changes in the older, female patient.In conclusion, the majority of Marfan patients exhibited neuromuscular symptoms characterized as myopathy or polyneuropathy or both, and signs of lumbosacral radiculopathy, with symptoms being most pronounced in the older patients. Although meriting corroboration, these findings indicate a need to further the awareness of neuromuscular involvement in this population.