bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limited influence of UGT1A1*28 and no effect of UGT2B7*2 polymorphisms on UGT1A1 or UGT2B7 activities and protein expression in human liver microsomes
Authors: Peterkin Vincent C. , Bauman Jonathan N. , Goosen Theunis C. , Menning Lee , Man Michael Z. , Paulauskis Joseph D. , Williams J. Andrew , Myrand Scott P. 
Published: June 2007

What is already known about this subject • The UGT1A1*28 polymorphism is known to reduce UGT1A1 enzyme activities, via an extra TA repeat in the promoter.• However, a gap exists with regard to a comprehensive assessment of the influence of this genotype on variability in enzyme activity.• There is equivocal evidence on the functional relevance of the UGT2B7*2 polymorphism on UGT2B7 enzyme activities. What this study adds • Using comprehensive approaches to measure enzyme activities and protein expression levels, the UGT1A1*28 polymorphism is shown to contribute to only 40% of the variability in enzyme activities for UGT1A1.• A novel, nonproprietary method for genotyping UGT1A1*28 is provided.• Definitive evidence is provided to conclude there is no effect of the UGT2B7*2 polymorphism on zidovudine glucuronidation activity.AimsUGT1A1 and UGT2B7 are enzymes that commonly contribute to drug glucuronidation. Since genetic factors have been suggested to contribute to variability in activities and expression levels of these enzymes, a quantitative assessment of the influence of the major genotypes (UGT1A1*28 or UGT2B7*2) on enzyme activities was conducted.MethodsUsing a bank of microsomal samples from 59 human livers, the effect of UGT1A1*28 or UGT2B7*2 polymorphisms were investigated on rates of estradiol 3‐glucuronidation (a marker of UGT1A1 enzyme activity) or zidovudine glucuronidation (a marker of UGT2B7 enzyme activity) and levels of immunoreactive protein for each enzyme. Glucuronidation rates for both enzymes were measured at Km/S50 and 10 times Km/S50 concentrations.ResultsUGT1A1 and UGT2B7 enzyme activities varied up to 16‐fold and sixfold, respectively. Rates at Km/S50 concentration closely correlated with rates at 10 times Km/S50 concentration for both enzymes (but not at 1/10th Km for UGT2B7). Enzyme activities correlated with relative levels of immunoreactive protein for UGT1A1 and UGT2B7. Furthermore, rates of zidovudine glucuronidation correlated well with rates of glucuronidation of the UGT2B7 substrate gemcabene, but did not correlate with UGT1A1 enzyme activities. For the UGT1A1*28 polymorphism, consistent with levels of UGT1A1 immunoreactive protein, mean UGT1A1 activity was 2.5‐ and 3.2‐fold lower for TA6/TA7 (P < 0.05) and TA7/TA7 (P < 0.001) genotypes in comparison with the TA6/TA6 genotype.ConclusionsRelative to the observed 16‐fold variability in UGT1A1 activity, these data indicate only a partial (approximately 40%) contribution of the UGT1A1*28 polymorphism to variability of interindividual differences in UGT1A1 enzyme activity. For the UGT2B7*2 polymorphism, genotype had no influence on immunoreactive UGT2B7 protein or the rate of 3'‐azido‐3'‐deoxythymidine glucuronidation.
Pharmacokinetics, safety, and efficacy of mycophenolate mofetil in combination with sirolimus or ciclosporin in renal transplant patients
Authors: Pescovitz Mark D. , Vincenti Flavio , Hart Marquis , Melton Larry , Whelchel John , Mulgaonkar Shamkant , McKay Diane , Leung Mimi , Calleja Elizabeth , Bouw M. René 
Published: June 2007

AimsTo compare the pharmacokinetics of mycophenolic acid (MPA) and its metabolite (MPAG) when mycophenolate mofetil (MMF) is administered in combination with sirolimus or ciclosporin (CsA) in renal allograft recipients. Safety and efficacy (biopsy‐proven acute rejection (BPAR)) were also assessed.MethodsPatients (n = 45) were randomized 2 : 1 to receive treatment with sirolimus (n = 30; dosed to maintain trough concentrations of 10–25 ng ml−1 until week 8, and then 8–15 ng ml−1 thereafter) or CsA (n = 15; administered as per centre practice) both in combination with daclizumab, oral MMF and corticosteroids. Pharmacokinetic assessments were performed at day 7, week 4, and months 3 and 6 post‐transplant. The primary endpoint was the AUC(0,12 h) for MPA and MPAG. The pharmacokinetics of sirolimus were also assessed.ResultsMPA exposure was 39–50% lower (month 6 mean AUC(0,12 h) (95%CI): 40.4 (33.8, 47.0) vs. 68.5 (54.9, 82.0) µg ml−1 h) and MPAG exposure was 25–52% higher (722 (607, 838) vs. 485 (402, 569) µg ml−1 h at month 6) in the presence of CsA compared with sirolimus across visits. BPAR was 40.0% with sirolimus and 13.3% with CsA. The incidence of hypertension, tremors and hirsutism was higher with CsA than with sirolimus, while the incidence of diarrhoea, hyperlipidaemia and impaired wound closure was higher with sirolimus. No deaths, malignancies or graft losses were reported.ConclusionsCo‐administration of sirolimus with MMF led to greater MPA exposure, but lower MPAG exposure, than co‐administration with CsA. As rejection rates were higher in the absence of CsA, further study of calcineurin inhibitor‐free regimens is required before general recommendations can be made.
Recent advances in the understanding of mastocytosis: the role of KIT mutations*
Authors: Orfao Alberto , Garcia‐Montero Andrés C. , Sanchez Laura , Escribano Luis 
Published: June 2007

AbstractMastocytosis is a heterogeneous disorder characterised by the expansion and accumulation of mast cells in different organs and tissues. Mast cell physiology is closely dependent on activation of the stem cell factor/Kit signalling pathways and accumulating evidences confirm the physiopathological key role of activating KIT mutations (typically D816V) in mastocytosis and their relationship with the clinical manifestations of the disease. This paper reviews the most recent advances in the understanding of the molecular mechanisms associated with KIT mutations in mastocytosis, including recent data about the use of new therapies targeting the Kit molecule and its associated downstream signalling pathways.
High risk of pregnancy‐related venous thromboembolism in women with multiple thrombophilic defects
Authors: Folkeringa Nienke , Brouwer Jan Leendert P. , Korteweg Fleurisca J. , Veeger Nic J.G.M. , Erwich Jan Jaap H.M. , Van Der Meer Jan 
Published: June 2007

SummaryPregnancy is associated with an increased risk of venous thromboembolism, which probably varies according to the presence of single or multiple thrombophilic defects. This retrospective family cohort study assessed the risk of venous thromboembolism during pregnancy and puerperium, and the contribution of concomitant thrombophilic defects in families with hereditary antithrombin, protein C or protein S deficiencies. Probands were excluded. Of 222 female relatives, 101 were deficient and 121 non‐deficient. Annual incidences of venous thromboembolism were 1·76% in deficient women versus 0·19% in non‐deficient women [adjusted relative risk (RR) 11·9; 95% confidence interval (CI), 3·9–36·2]. Other single and multiple thrombophilic defects increased the risk in deficient women from 1·55% to 2·14% and 2·92%, and in non‐deficient women from 0·16% to 0·09% and 0·54% respectively. Deficient women were at lower risk (1·37%; 0·80–2·19) than deficient women that had never been pregnant (2·96%; 1·53–5·18); RR 0·5 (0·2–0·99). This difference was due to the predominance of events related to oral contraceptives in deficient women that had never been pregnant (75%), while 71% of events in deficient women that had had at least one pregnancy were pregnancy‐related. In conclusion, women with hereditary deficiencies of antithrombin, protein C or protein S are at high risk of pregnancy‐related venous thromboembolism. This risk is increased by multiple additional thrombophilic defects.
Decreased TCR ζ‐chain expression in T cells from patients with acquired aplastic anaemia
Authors: Solomou Elena E. , Wong Susan , Visconte Valeria , Gibellini Federica , Young Neal S. 
Published: June 2007

SummaryIn aplastic anaemia, T cells have a central role in the pathophysiology of bone marrow destruction. This study showed that T cells from patients with aplastic anaemia expressed decreased T‐cell receptor (TCR) ζ‐chain protein and mRNA levels compared to healthy controls. Patients with decreased TCR ζ‐chain showed an abnormal response in intracellular calcium following stimulation through the TCR. We also observed an altered pattern of the transcription factors CREMα and Elf‐1 that are implicated in ζ‐chain transcription. We concluded that TCR ζ‐chain expression was decreased in the majority of patients with aplastic anaemia, regardless of disease activity or treatment status.
Treatment of acromegaly improves quality of life, measured by AcroQol
Authors: Paisley Angela N. , Rowles Susannah V. , Roberts Margaret E. , Webb Susan M. , Badia X. , Prieto L. , Shalet Stephen M. , Trainer Peter J. 
Published: June 2007

SummaryBackground   AcroQol is a disease‐generated questionnaire, developed to assess quality of life (QOL) in patients with acromegaly. We have previously demonstrated severely impaired QOL in patients with acromegaly and the value of AcroQol in measuring QOL in a cross‐sectional study compared with the non‐disease‐specific generic tools ‘Psychological general wellbeing schedule’ (PGWBS) and EuroQol (EQ‐5D), and the disease‐specific signs and symptoms score (SSS).Aim, subjects and methods   We re‐evaluated these tools in a longitudinal study of 56 of the previously reported patients (33 male, mean age 55 ± 15 years), in order to determine change in QOL over time and the effect of different treatment modalities. Data were analysed using Spearman's correlation tests.Results   Baseline median IGF‐I was 354 ng/ml (range 48–899) and at re‐evaluation 217 ng/ml (60–594) (P < 0·001) [median time interval 608 days (113–1136)]. Analysis of change in IGF‐I levels and AcroQol scores demonstrated a significant negative correlation (i.e. a reduction in IGF‐I being associated with improved overall QOL (r = –0·36, P = 0·006). Significant negative correlations were also seen in the physical (r = –0·33, P = 0·01), psychological (r = –0·37, P = 0·005) and appearance (r = –0·42, P = 0·001) AcroQol subdomains. No correlations were seen between change in IGF‐I and change in overall PGWBS score or subdomains, SSS or EQ‐5D.Conclusions   In summary, of the tools studied we have demonstrated AcroQol to be uniquely capable of detecting changes in QOL associated with treatment‐induced improvement in the main biochemical marker of disease activity in patients with acromegaly. Further studies are required to evaluate the long‐term biological significance of the changes seen in AcroQol.
Derevator: a soft tissue elevator for maxillary sinus in Endoscopic sinus surgery
Authors: Dere H. , Ozcan K.M. , Ozcan I. 
Published: June 2007

Keypoints• Removal of the soft tissue lesions from the maxillary sinus is sometimes difficult and time consuming in endoscopic sinus surgery.• Failure of endoscopic removal may necessitate combination of canine fossa approach and endoscopic approach.• Our new instrument, ‘Derevator’, is designed for easy removal of the pathological soft tissue lesions from the maxillary sinus through middle meatal antrostomy.• Derevators are available for both adults and children. Suction‐tipped ones are also available.
Lesson plans in surgical training
Authors: Lester S.E. , Robson A.K.R. 
Published: June 2007

Keypoints• Lesson plans in surgery enable trainers and trainees to agree on goals that balance training needs with service commitments.• Lesson plans are individualised to the trainee and encourage ownership of learning.• They are based on SMART criteria and therefore have a sound educational footing.• Most of the work in creating a lesson plan falls to the trainee. The total time for creation of each plan is approximately 20 min.• Our use of lesson plans for surgical training has been met with favourable response from both trainer and trainees.
Photodynamic therapy in the treatment of multiple primary tumours in the head and neck, located to the oral cavity and oropharynx
Authors: Copper M.P. , Triesscheijn M. , Tan I.B. , Ruevekamp M.C. , Stewart F.A. 
Published: June 2007

Objectives:  Multiple primary tumours are a common problem in the head and neck cancer patients. Curative surgery or radiotherapy of these tumours can be very mutilating or even impossible. This study aims at evaluating meta‐tetrahydroxy‐phenyl chlorin‐mediated photodynamic therapy for second or multiple primary tumours in the head and neck.Design:  Retrospective study of all patients with second or multiple primary tumours treated by photodynamic therapy over a 10‐year period.Setting:  All patients were treated in the Netherlands Cancer Institute, a tertiary referral centre for the head and neck cancer patients.Participants:  A total of 27 patients with 42 the second or the multiple primary head and neck tumours were treated by photodynamic therapy (0.15 mg/kg meta‐tetrahydroxy‐phenyl chlorin).Main outcomes measures:  Cure rates.Results:  Twenty‐eight of 42 tumours were cured (67%). Cure rates for stage I or in situ disease were 85%versus 38% for stage II/III.Conclusions:  Cure rates for photodynamic therapy of the multiple primary head and neck tumours were lower than previously described for first primaries, but were still very encouraging for this difficult patient population. The high cure rate obtained in stage I multiple primaries emphasises the importance of a meticulous follow‐up of patients treated for the head and neck cancer to detect new tumours at a curable stage.
Dentine‐bonded resin composite (Retroplast) for root‐end filling: a prospective clinical and radiographic study with a mean follow‐up period of 8 years
Authors: Yazdi P. M. , Schou S. , Jensen S. S. , Stoltze K. , Kenrad B. , Sewerin I. 
Published: June 2007

AbstractAim  To evaluate treatment outcome after using a resin composite (Retroplast, RP) in combination with a dentine‐bonding agent (GLUMA) as root‐end filling material after 1 year as well as after more than 5 years (final examination). Also, the influence of various pre‐, intra‐ and postoperative factors on the treatment outcome was studied.Methodology  All patients (87) undergoing root‐end resection consecutively treated by root‐end filling with RP on an incisor, canine, pre‐molar, or first molar (87 teeth, 118 roots) were initially enrolled in the study. RP was applied on the entire resected surface that was prepared to a slightly concave shape and after conditioning with EDTA and GLUMA. The treatment outcome involving subjective, clinical and radiographic parameters was evaluated after 1 year and at the final examination. A total of 27 patients (36 roots) were excluded from the study because of unavailability of follow‐up (19) and extraction of the operated tooth for reasons other than failed surgery (8). Consequently, 60 patients (82 roots) were included in the final material. The mean follow‐up period at the final examination was 8 years (range: 6.5–9 years).Results  The radiographic evaluation at the final examination revealed that 77%, 5%, 7% and 11% of the treated roots were characterized by complete, incomplete, uncertain and unsatisfactory healing, respectively. A total of 95% of the roots classified as completely healed at the 1‐year control were also completely healed at the final examination. Two roots (5%) showing complete healing at the 1‐year control revealed unsatisfactory healing at the final examination because of displaced or lost RP‐filling. Moreover, 60% of the roots with uncertain healing at the 1‐year control demonstrated complete or incomplete healing at the final examination. The classification according to subjective, clinical and radiographic parameters revealed that 78% of the teeth were characterized by a successful treatment outcome at the final examination. Evaluation of the influence of various pre‐, intra‐ and postoperative factors on the treatment outcome revealed that the radiographic classification at the final examination was exclusively influenced by the radiographic classification at the 1‐year control (P < 0.001).Conclusions  The present long‐term study indicates that RP can be used for root‐end filling with a successful treatment outcome.
Capacity building in nursing and midwifery research and development: an old priority with a new perspective
Authors: McCance Tanya V. , Fitzsimons Donna , Keeney Sinead , Hasson Felicity , McKenna Hugh P. 
Published: June 2007

Abstract Title. Capacity building in nursing and midwifery research and development: an old priority with a new perspective. Aim.  This paper is a report of a study to identify strategic priorities to inform the development of a regional strategy for nursing and midwifery research and development.Background.  Research capacity has been highlighted internationally as a crucial element in the advancement of nursing and midwifery research and development. Research capacity has been defined as that which relates to the ability to conduct research. In a strategic context, however, there is a broader perspective that encompasses activities related both to ‘using’ and ‘doing’ research.Methods.  A modified nominal group technique was employed. Three rounds were used to identify the main strategic priorities for nursing and midwifery research and development. Round one was based on the Delphi Technique and further rounds were based on the nominal group technique approach. Data were collected during February 2005. Participants (n = 105) were those involved in the research and development agenda for nursing and midwifery in Northern Ireland.Findings.  Capacity building was highlighted as a central component from the final 12 priorities, with three key areas identified: (1) the importance of strong and visible leadership; (2) developing research expertise that will enable the profession to deliver programmes of research and (3) increasing the capacity of individuals and organizations to engage in development activity.Conclusion.  The 12 priorities identified emphasize the need for a broad perspective on building capacity that reflects involvement in a range of activities that span ‘research’ and ‘development’. This has important implications globally if nurses and midwives are to develop the knowledge and skills required to engage in research and development as an integral part of their practice. Embracing this broader perspective has the potential to enhance performance that will contribute to continuous quality improvement.
A geometric morphometric approach to the study of ecogeographical and clinal variation in vervet monkeys
Authors: Cardini Andrea , Jansson Anna‐Ulla , Elton Sarah 
Published: June 2007

AbstractAim  To examine and visualize clines in size and shape of Cercopithecus aethiops Linneus, 1758 (Primate, Cercopithecidae) skulls, and to investigate environmental factors which might best explain the observed variation.Location  Sub‐Saharan Africa.Methods  Eighty‐six three‐dimensional anatomical landmarks were used to describe 306 skulls of adult C. aethiops sampled over its entire distribution. Geometric morphometric methods for the quantitative analysis of form variation were applied. Size and shape variables were computed and regressed onto geographical coordinates and environmental variables (elevation, temperature, rainfall, moisture and Shannon rainfall diversity index) using both linear and curvilinear models. Components (geographical, environmental, spatially structured environmental and residual) of ecogeographical variation in skull form were partitioned using partial regression. A novel approach for summarizing and visualizing nonlinear patterns of clinal variation using surface rendering of three‐dimensional shapes is presented.Results  Clinal variation in size and shape was highly significant, and was best described by curvilinear models. There were strong similarities between females and males. The cline in size was especially pronounced, explaining up to about 40% of observed variation, and was mainly longitudinal rather than latitudinal. A major trend of clinal shape variation also occurred from west to east, and corresponded to an expansion of the face relative to the neurocranium in the west. In the east, skulls also tended to be deeper and with narrower zygomatic arches. Geography and the spatially structured environmental component were the major contributors to the explained variance in size in both sexes, but the proportion of variance explained by the latter was smaller in females. In contrast, geography and environment explained similar amounts of variation in shape and their contribution was about twice that of the spatially structured environmental component. About 60–80% of variation in skull form was not explained by any variable in the analysis. The main factors influencing skull size differed in females and males, with rainfall being very influential in males. Both female and male skull shapes were strongly affected by average annual rainfall.Main conclusions  A strong spatial and environmental basis to variations in African vervet monkey skull form was evident. However, the observed pattern did not conform to predictions based on Bergmann's rule. Rainfall consistently emerged as an important predictor, which may contribute to intraspecific variation in the size and shape of vervet monkey skulls through its effect on habitat productivity.
Decay of similarity of gamasid mite assemblages parasitic on Palaearctic small mammals: geographic distance, host‐species composition or environment
Authors: Vinarski Maxim V. , Korallo Natalia P. , Krasnov Boris R. , Shenbrot Georgy I. , Poulin Robert 
Published: June 2007

AbstractAim  The similarity between parasite assemblages should decrease with increasing geographic distance between them, increasing dissimilarity in environmental conditions, and/or increasing dissimilarity of the local host fauna, depending on the dispersal abilities of the parasites and the intimacy of their associations with the host. We tested for a decay in the similarity of gamasid mite assemblages parasitic on small mammals with increasing geographic, ‘environmental’ and ‘host faunal’ (= ‘host’) distances.Location  We used data on assemblages of haematophagous gamasid mites (superfamily Dermanyssoidea) parasitic on small mammals (Insectivora, Lagomorpha and Rodentia) from 26 different regions of the northern Palaearctic.Methods  Similarity in mite assemblages was investigated at the compound community level across all regions, and at the component community level, across populations of the same host species for each of 11 common host species. Similarity between pairs of mite communities was estimated using both the Jaccard and the Sorensen indices. Environmental distance was estimated as the dissimilarity between locations in a composite measure of climatic variables, and host faunal distance was simply taken as the reciprocal of indices of similarity between the composition of host faunas in different locations. Generalized Linear Models (GLM) and Akaike's Information Criterion were used to select the best model of decay in similarity as a function of geographic, ‘environmental’ and ‘host faunal’ distances.Results  Overall, despite slight differences among host species, the similarity in mite assemblages decreased with both increasing ‘environmental’ distance and increasing ‘host faunal’ distance, but was generally unaffected by geographic distance between regions. The similarity of component communities of gamasid mites among host populations was determined mainly by similarity in the physical environment, whereas that of compound communities varied mainly with host‐species composition.Main conclusions  Our results indicate that the general decay in community similarity with increasing geographic distances does not apply to assemblages of gamasid mites; it is possible that they can overcome great distances by means of passive dispersal (either by phoresy or wind‐borne), or more likely they occur wherever their hosts are found as a result of tight cospeciation in the past. Mite assemblages on small mammalian hosts seem to be affected mainly by local environmental conditions, and, to a much lesser extent, by the species composition of local host communities.