bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time course of the increase in 4β‐hydroxycholesterol concentration during carbamazepine treatment of paediatric patients with epilepsy
Authors: Wide Katarina , Larsson Hanna , Bertilsson Leif , Diczfalusy Ulf 
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • CYP3A4 converts cholesterol into 4β‐hydroxycholesterol.• We have suggested that 4β‐hydroxycholesterol could be used as a clinical marker for CYP3A4 activity aiding in dose adjustments.• The kinetics of 4β‐hydroxycholesterol formation is not known, however, and must be determined in order to establish under what conditions 4β‐hydroxycholesterol can be used as a CYP3A marker. WHAT THIS STUDY ADDS • The concentration of 4β‐hydroxycholesterol increases very slowly during CYP3A4/5 induction in paediatric patients.• Whereas induction of CYP3A4/5 was apparently complete within 1–2 weeks of carbamazepine treatment, plasma 4β‐hydroxycholesterol levels continued to increase until at least 8 weeks of treatment.AIMS To investigate the time course of the increase in 4β‐hydroxycholesterol and carbamazepine plasma concentrations during treatment of paediatric patients with epilepsy.METHODS Eight paediatric patients with newly diagnosed epilepsy were studied. Blood samples were drawn before and after about 1, 2, 4, 8 and 16 weeks of carbamazepine treatment. The plasma concentrations of 4β‐hydroxycholesterol were determined by gas chromatography–mass spectrometry and carbamazepine and its epoxide metabolite by high‐performance liquid chromatography.RESULTS The basal plasma concentrations of 4β‐hydroxycholesterol showed a large range of observed values between 18 and 99 ng ml−1. Carbamazepine treatment increased mean plasma 4β‐hydroxycholesterol significantly already after 1 week of treatment (from 43 to 80 ng ml−1, P < 0.001). 4β‐Hydroxycholesterol concentrations continued to increase until at least 8 weeks of treatment and the concentrations in the final samples (8–23 weeks of treatment) varied between 122 and 494 ng ml−1. Plasma concentrations of carbamazepine and its epoxide metabolite reached steady state at 1–2 weeks after last dose change.CONCLUSIONS Carbamazepine treatment of paediatric patients with epilepsy resulted in an induction of CYP3A4/5 and a concomitant increase in plasma 4β‐hydroxycholesterol. Whereas the induction of CYP3A4/5 was apparently complete after 1–2 weeks, the increase in 4β‐hydroxycholesterol continued for several weeks. Thus CYP3A4 activity is not the only determinant of the circulating level of 4β‐hydroxycholesterol. Additional factors such as transport and storage or presence of another enzyme may thus be of importance.
Ten renin‐angiotensin system‐related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure
Authors: Zakrzewski‐Jakubiak Marcin , De Denus Simon , Dubé Marie‐Pierre , Bélanger François , White Michel , Turgeon Jacques 
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The progression and pharmacological response of heart failure‐affected patients are subject to interindividual variability.• It is also acknowledged that the genotype frequency of certain gene polymorphisms varies across different ethnic groups and that a difference in gene polymorphism frequencies between healthy and heart failure patients seems to exist. WHAT THIS STUDY ADDS • This study investigated associations between 10 gene polymorphisms of RAAS‐related genes with an individual's susceptibility to heart failure.• Our data suggest that the angiotensinogen (AGT) 235 single nucleotide polymorphism (SNP) may be associated with heart failure in our population and that the AGT(M174)‐AGT(T235) haplotype, as well as the AGT/angiotensin‐converting enzyme (ACE) gene combination, may play an important role in disease predisposition.AIMS Racial differences in survival outcomes point towards a genetic role in the pathophysiology of heart failure. Furthermore, contemporary evidence links genetics to heart failure (HF) predisposition. We tested for a difference in prevalence of 10 renin‐angiotensin‐aldosterone system (RAAS)‐related gene polymorphisms between a homogenous population of HF patients and healthy controls.METHODS One hundred and eleven healthy volunteers and 58 HF patients were included in this study. The healthy control group consisted of males aged between 18 and 35 years old. The HF group consisted of patients (89.7% male) who were 63.8 ± 7.9 years old, were in New York Heart Association (NYHA) class II‐III and had a documented left ventricular ejection fraction (LVEF) ≤ 40% within the previous 6 months. Despite being treated maximally for their condition with angiotensin‐converting‐enzyme (ACE)‐inhibitors and β‐adrenoceptor blockers, they continued to be symptomatic and, as such, were a highly specialized and homogeneous patient population. Both groups were composed of Canadian Caucasians. The analyzed polymorphisms were: ACE (I/D), angiotensin‐II‐receptor‐type‐1 (AGTR1)(A1166C), angiotensinogen (AGT)(M235T and T174M), endothelial‐nitric‐oxide‐synthase (eNOS)(T‐786C and Glu298Asp), adrenergic‐receptor‐â2 (ADRB2)(Gln27Glu), bradykinin‐receptor‐β2 (BDKRB2)(+9/−9), aldosterone‐synthase (CYP11B2)(T‐344C) and adducin‐1 (ADD1)(Gly460Trp).RESULTS The AGT (T235) allele (P = 0.0025, OR 2.02, 95% CI 1.24, 3.30) was found to be more prevalent in our HF group. The AGT (174M)‐AGT (235T) haplotype was also associated with the HF phenotype (P = 0.0069). Exploratory evaluation of gene‐gene combinations revealed an indicative association of the AGT (T235)/ACE(D) combined polymorphisms in the HF group (P = 0.02, OR 2.12, 95% CI 1.11, 4.06).CONCLUSIONS This study demonstrates that the SNPs of AGT may be associated with HF in our population and that the AGT/ACE gene combination may play an important role in disease predisposition.
A human anti‐D monoclonal antibody selected for enhanced FcγRIII engagement clears RhD+ autologous red cells in human volunteers as efficiently as polyclonal anti‐D antibodies
Authors: Beliard Roland , Waegemans Tony , Notelet Dominique , Massad Léna , Dhainaut Frédéric , Romeuf Christophe de , Guemas Eric , Haazen Wouter , Bourel Dominique , Teillaud Jean‐Luc , Prost Jean‐François 
Published: February 2008

SummaryA human anti‐RhD immunoglobulin G1 monoclonal antibody (mAb), R297, was tested in a phase I study to assess its ability to induce the clearance of antibody‐coated autologous RhD+ red blood cells (RBCs) in healthy male volunteers. The clearance potency of R297 was compared with that of a marketed human polyclonal anti‐D product (Rhophylac®). This mAb has been selected for its ability to strongly engage Fc‐gamma receptor IIIA and to mediate a potent antibody‐dependent cell cytotoxicity (ADCC) against RhD+ RBCs. Autologous RhD+ RBCs were sensitized with either Rhophylac® or R297 at three different coating percentages (25, 12·5 and 6·25%), before re‐infusion. This phase I study showed that the human R297 mAb promoted rapid and complete clearance of RBCs, and showed activity that was at least as potent as the human polyclonal anti‐D antibody preparation. Clearance of RBCs could still be observed when the percentage of R297 used to coat the RBCs was reduced to 6·25%. Finally, none of the adverse events was severe or considered to be related to R297. Thus, R297 is a promising candidate for the prevention of allo‐immunization and represents a new generation of Fc‐modified monoclonal antibodies with increased FcγRIII binding and increased ADCC.
Managing relapsed and refractory Hodgkin lymphoma
Authors: Brice Pauline 
Published: February 2008

SummaryDespite a high curability rate, some patients with Hodgkin lymphoma (HL) fail to respond to, or relapse after, primary conventional treatment. This review aims to identify prognostic factors at relapse and guidelines for treatment in relapsed HL. Patients with relapsed HL should be identified according to their prognostic factors at relapse (duration of remission and extranodal disease or stage). This enables relapsing patients to be separated in to three different prognostic groups; primary refractory patients should be included in the unfavourable group because of their poor prognosis. All relapsed HL should receive second‐line chemotherapy and the response to this chemotherapy is crucial for the outcome. Benefit of autologous stem‐cell transplantation (ASCT) has been shown in a large randomized study and, although is often proposed in relapsed HL, it may be not necessary in the rare group of patients with stage I/II and late relapse who can receive additional radiotherapy after response to chemotherapy. Patients with intermediate and unfavourable relapse should receive high‐dose chemotherapy and ASCT when chemosensitive; the first goal is to achieve this chemosensitivity. For patients in the unfavourable group, including refractory patients, the role of tandem HDT or allogeneic SCT will be discussed and should be proposed for patients not in complete remission at the time of HDT.
Toll‐like receptor 4 ligand can differentially modulate the release of cytokines by human platelets
Authors: Cognasse Fabrice , Hamzeh‐Cognasse Hind , Lafarge Sandrine , Delezay Olivier , Pozzetto Bruno , McNicol Archie , Garraud Olivier 
Published: February 2008

SummaryBlood platelets link the processes of haemostasis and inflammation. This study examined the immunomodulatory factors released by platelets after Toll‐Like Receptor 4 (TLR4) engagement on their surfaces. Monoclonal anti‐human FcγRII Ab (IV.3)‐treated human platelets were cultured with TLR4 ligands in the presence or absence of blocking monoclonal antibody to human TLR4. The release of sCD62p, epidermal growth factor (EGF), transforming growth factor β (TGFβ), interleukin (IL)‐8, platelet activating factor 4 (PAF4), platelet‐derived growth factor, α, β polypeptide (PDGF‐AB), Angiogenin, RANTES (regulated upon activation, normal T‐cell expressed, and presumably secreted) and sCD40L were measured by specific enzyme‐linked immunosorbent assay. TLR4 ligand [Escherichia coli lipopolysaccharide (LPS)] bound platelet TLR4, which differentially modulates the release of cytokines by platelets. It was noted that (i) sCD62p, IL‐8, EGF and TGFβ release were each independent of platelet activation after TLR4 engagement; (ii) RANTES, Angiogenin and PDGF‐AB concentration were weaker in platelet supernatant after TLR4 engagement; (iii) sCD40L and PAF4 are present in large concentration in the releaseate of platelets stimulated by TLR4 ligand. The effects of LPS from E. coli on the modulation of secretory factors were attenuated by preincubation of platelets with an anti‐TLR4 monoclonal antibody, consistent with the immunomodulation being specifically mediated by the TLR4 receptor. We propose that platelets adapt the subsequent responses, with polarized cytokine secretion, after TLR4 involvement.
Frequency and characteristics of TBII‐seronegative patients in a population with untreated Graves’ hyperthyroidism: a prospective study
Authors: Vos Xander G. , Smit Natalie , Endert Erik , Tijssen Jan G. P. , Wiersinga Wilmar M. 
Published: February 2008

SummaryObjective  It is claimed that second generation thyrotropin‐binding inhibitory immunoglobulin (TBII) assays have a very high sensitivity for the diagnosis of Graves’ hyperthyroidism (GH). However, studies evaluating the accuracy of TBII have been retrospective in nature and/or GH had not been diagnosed independently of TBII. The aim of the present study, therefore, was to prospectively evaluate the frequency and characteristics of TBII‐seronegative patients in a population of untreated GH diagnosed independent of serum TBII.Design  Prospective multicentre observational study.Patients  A total of 259 consecutive untreated patients with a first episode of GH, diagnosed independent of serum TBII. TBII levels were measured by second generation assay and correlated to thyroid function, clinical characteristics and exposure to environmental factors.Results  Serum TBII was positive in 245 (94·6%) patients and negative (< 2 IU/l) in 14 (5·4%) patients. TBII‐seronegative patients had lower fT4 (median 42·5 vs. 53·9 pmol/l, P = 0·02), T3 (median 3·55 vs. 4·90 nmol/l, P < 0·01) and fT3‐index (median 4·30 vs. 6·27, P < 0·01) compared to TBII‐seropositive patients. None of the TBII‐seronegative patients had TSH‐receptor activating mutations, Graves’ orbitopathy or pretibial myxedema. Serum TBII was positively correlated to free T3 (fT3)‐index and free T4 (fT4)‐index (P < 0·01), goitre size (P < 0·01) and the prevalence of Graves’ orbitopathy (P < 0·01). There were no significant differences between TBII‐seropositive and TBII‐seronegative patients in environmental factors.Conclusion  The prevalence of TBII‐seronegativity in untreated patients with GH is 5·4% using a second generation assay. TBII‐seronegative patients have biochemically less severe thyrotoxicosis and no Graves’ orbitopathy. TBII‐seronegative and TBII‐seropositive patients apparently belong to the same population of GH, albeit the severity of the autoimmune attack is less in TBII‐seronegative patients.
High prevalence of biochemical acromegaly in primary care patients with elevated IGF‐1 levels
Authors: Schneider H. J. , Sievers C. , Saller B. , Wittchen H. U. , Stalla G. K. 
Published: February 2008

SummaryObjective  The estimated prevalence of acromegaly is 40–125 per million. The diagnosis of acromegaly is often delayed due to deficits in recognizing the signs of the disease. It is not known how many subjects with increased IGF‐1 levels have acromegaly. We aimed to assess the prevalence of acromegaly in primary care by screening for elevated IGF‐1 levels.Design  A cross‐sectional, epidemiological study (the DETECT study).Patients  A total of 6773 unselected adult primary care patients were included.Measurements  We measured IGF‐1 in all patients and recommended further endocrine evaluation in all patients with elevated IGF‐1 levels (> 2 age‐dependent SDS).Results  Of 125 patients with elevated IGF‐1 levels, 76 patients had indeterminate results and acromegaly could be excluded in 42 patients. One patient had known florid acromegaly. Two patients had newly diagnosed acromegaly and pituitary adenomas. Four patients had biochemical acromegaly but refused further diagnostics. This corresponds to a prevalence of 1034 per million patients.Conclusions  Our study shows a high prevalence of undiagnosed acromegaly in primary care. These results imply that acromegaly is underdiagnosed and stress the importance of detecting acromegaly.
On the classification of surface geoelectric arrays
Authors: Szalai Sándor , Szarka László 
Published: February 2008

ABSTRACTWe collected approximately one hundred independent geoelectric arrays from published geophysical literature. We have presented them in a systematic way and with a unified notation. The classification of arrays is based on three divalent parameters: “superposition” of measurements, “focusing” of currents and “colinearity” of the array, creating 8 classes of geoelectric arrays.Among the 102 independent arrays we found in the geophysical literature, we managed to classify 92 arrays in the aforementioned way. Ten further techniques fell beyond the proposed classification.The classification we propose may open the way to new geoelectric arrays, hopefully providing improving responses to the infinite variety of field problems we may face. It may bring to daylight, exclusively in a logical way, currently unused arrays. In searching new geoelectric arrays this paper helps to avoid rediscovering the discovered. Although it might be thought that the modern multielectrode systems will supersede all former arrays, such systematization is not only for historical and tutorial interests: some of the “old” arrays can be perhaps built into new multielectode systems, further enhancing their effectivity in the future. Finally, this collection of arrays establishes the possibility of systematic intercomparisons of arrays on the basis of various theoretical or practical aspects.
An algorithm to calculate the gravity anomaly of sedimentary basins with exponential density‐depth relationships
Authors: Chappell Alex , Kusznir Nick 
Published: February 2008

ABSTRACTWe derive wavenumber domain expressions to calculate the gravity anomaly of a body with irregular bounding surfaces and an exponential density‐depth relationship. We apply the method to sedimentary basins, which commonly have this type of geometry and density distribution. The mathematical formulation also allows the exponential density‐depth relationship to be measured from an arbitrary irregular surface rather than the top surface. Using this arrangement, the gravity anomaly of exhumed sedimentary basins can be predicted if the amount of eroded section can be estimated. The corresponding inverse algorithms are also derived. Examples of the use of the forward algorithms, from the Galicia Interior Basin and the Central Irish Sea Basin, are used to illustrate these methods.
Inversion of magnetotelluric data in the presence of strong bathymetry/topography
Authors: Li Shenghui , Booker John R. , Aprea Claudia 
Published: February 2008

ABSTRACTWe describe an algorithm for inverting magnetotelluric (MT) data in the presence of strong bathymetry or topography. Instead of correcting distortions due to bathymetry or topography we incorporate them directly into the inversion. To achieve a high accuracy in computing MT responses we use finite‐difference approximations that permit sloping discrete boundaries inside model elements. The same approach is applicable to any seafloor electromagnetic calculation and can also be used to incorporate steep topography on land. We test our approach on various topographic features and compare our results to that of a finite element approach. Finally, we present inversion examples that illustrate the effectiveness of our inversion algorithm in recovering true subsurface structures in the presence of strong bathymetry and topography.
When should we extract deciduous teeth and place implants in young individuals with tooth agenesis?
Authors: BERGENDAL B. 
Published: February 2008

Summary  The aim was to systematically review and find evidence to determine when to extract deciduous teeth and place implants in young individuals with tooth agenesis. A search was made in MEDLINE on combinations of the terms ‘tooth agenesis’, ‘deciduous teeth’ and ‘dental implants’. Publications with an abstract and written in the English language only were included. To give a background to the clinical management of young individuals with agenesis of teeth, publications on epidemiology of tooth agenesis, persistence of deciduous teeth, treatment outcomes after multi‐disciplinary treatment planning and experiences of treatment with dental implants in young individuals were also reviewed.A search on the terms ‘tooth agenesis’, ‘deciduous teeth’ and ‘dental implants’ resulted in nine references and a search on ‘dental implants’ and ‘tooth agenesis’ gave 132 references; 46 met the inclusion criteria. Only two were prospective studies on treatment with implants in young individuals.A vast majority of publications on the clinical management of young individuals with tooth agenesis are reflections of clinical experiences and single case reports. Deciduous teeth are extracted for different reasons and at different ages in an optimal plan for a good treatment result from aesthetic and functional point of view. For ethical reasons, randomized clinical trials on when to extract deciduous teeth and place implants cannot be made in young individuals. There was only limited, low level evidence on when to extract deciduous teeth and place implants. Recommendations on treatment are based mainly on clinical experience.
Comparative pharmacokinetics of two intravenous administration regimens of tiludronate in healthy adult horses and effects on the bone resorption marker CTX‐1
Authors: DELGUSTE C. , AMORY H. , GUYONNET J. , THIBAUD D. , GARNERO P. , DETILLEUX J. , LEPAGE O. M. , DOUCET M. 
Published: February 2008

Bioavailability and pharmacological effects of tiludronate were compared when administered as an intravenous (i.v.) bolus at a dosage of 0.1 mg/kg body weight (b.w.) once daily for 10 consecutive days (group 1, n = 6) and as a single constant rate infusion (CRI) at a total dose of 1 mg/kg b.w. (group 2, n = 6) in healthy adult horses.Tiludronate and carboxy‐terminal cross‐linking telopeptide of type I collagen (CTX‐1) were measured in plasma and urine.There was no statistically significant difference in area under the curve (AUC) and clearance (Cl) between the two groups. Bioavailability of the CRI was 103% (not significantly different) that of the 10 daily i.v. bolus doses. Cumulative urine tiludronate excretion could not be compared between groups because of poor sensitivity of the assay in urine. Plasma and urine CTX‐1 levels were not different between groups throughout the study. However, interindividual variations were greater in group 1 than in group 2. A significant decrease in CTX‐1 levels was observed in plasma after the first administration in group 1, but not in urine; while in group 2, a significant decrease in CTX‐1 concentrations was observed after treatment in both plasma and urine.In conclusion, both dosage regimens of tiludronate produced similar plasma exposure and pharmacological effects in adult healthy horses.
Patterns of differentiation in a colour polymorphism and in neutral markers reveal rapid genetic changes in natural damselfly populations
Authors: ABBOTT J. K. , BENSCH S. , GOSDEN T. P. , SVENSSON E. I. 
Published: February 2008

AbstractThe existence and mode of selection operating on heritable adaptive traits can be inferred by comparing population differentiation in neutral genetic variation between populations (often using FST values) with the corresponding estimates for adaptive traits. Such comparisons indicate if selection acts in a diversifying way between populations, in which case differentiation in selected traits is expected to exceed differentiation in neutral markers [FST (selected) > FST (neutral)], or if negative frequency‐dependent selection maintains genetic polymorphisms and pulls populations towards a common stable equilibrium [FST (selected) < FST (neutral)]. Here, we compared FST values for putatively neutral data (obtained using amplified fragment length polymorphism) with estimates of differentiation in morph frequencies in the colour‐polymorphic damselfly Ischnura elegans. We found that in the first year (2000), population differentiation in morph frequencies was significantly greater than differentiation in neutral loci, while in 2002 (only 2 years and 2 generations later), population differentiation in morph frequencies had decreased to a level significantly lower than differentiation in neutral loci. Genetic drift as an explanation for population differentiation in morph frequencies could thus be rejected in both years. These results indicate that the type and/or strength of selection on morph frequencies in this system can change substantially between years. We suggest that an approach to a common equilibrium morph frequency across all populations, driven by negative frequency‐dependent selection, is the cause of these temporal changes. We conclude that inferences about selection obtained by comparing FST values from neutral and adaptive genetic variation are most useful when spatial and temporal data are available from several populations and time points and when such information is combined with other ecological sources of data.