bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antihypertensive drug prescribing in Grampian
Authors: Ross Sarah , Macleod Mary Joan 
Published: August 2005

AimsTo assess the cost implications of changing prescribing patterns for antihypertensive drugs and to analyse adherence to guidelines and formulary in Grampian region over a 1 year period.MethodsData on all prescriptions for antihypertensive medicines between November 2001 and October 2002 were obtained from Grampian Health Board. The total quantity and cost of each drug prescribed was calculated and compared with November 1998 to October 1999. Adherence to the local formulary and 1999 British Hypertension Society guidelines for first line agents and prescribing of generic drug names were analyzed for each practice.ResultsThere was an increase in the total number of prescriptions for antihypertensive drugs from 504929 in 1998/99 to 741620 in 2001/02, and a corresponding increase in total cost from £4.52 million to £6.79 million. Increases were seen in all drug classes, particularly angiotensin II antagonists (246.27%). Adherence to the local formulary was good, with an average of 91.25% (SD 5.94%) of prescribing consistent with recommended agents. This fell to 71.70% (SD 23.10%) for angiotensin II antagonists. Prescription using generic name was related to whether the practice dispensed medication or not: the mean level of generic prescribing in dispensing practices was 75.25% and in nondispensing practices was 89.02% (mean difference 13.76 (9.27, 18.26), P < 0.001).ConclusionsThere was a substantial increase in prescribing volume and cost of antihypertensives between 1998/99 and 2001/02. This trend is likely to have continued, given changing targets and indications for therapy. Although practices generally showed high concordance with formulary recommendations, newer agents such as angiotensin II antagonists were less consistent, possibly related to pharmaceutical influences on prescribing. Dispensing practices were more likely to prescribe branded drugs which may reflect current reimbursement policies. Changing prescribing practices by encouraging formulary based prescribing and prescribing of generic agents may help offset the cost implications of guideline driven increases in antihypertensive drug prescribing. Education, and reviewing payment practices in dispensing and smaller practices, may also have a role.
Population pharmacokinetics and association between A77 1726 plasma concentrations and disease activity measures following administration of leflunomide to people with rheumatoid arthritis
Authors: Chan Vivien , Charles Bruce G. , Tett Susan E. 
Published: August 2005

AimsTo investigate the concentration‐effect relationship and pharmacokinetics of leflunomide in patients with rheumatoid arthritis (RA).MethodsData were collected from 23 RA patients on leflunomide therapy (as sole disease modifying antirheumatic drug (DMARD)) for at least 3 months. Main measures were A77 1726 (active metabolite of leflunomide) plasma concentrations and disease activity measures including pain, duration/intensity of morning stiffness, and SF‐36 survey. A population estimate was sought for apparent clearance (CL/F ) and volume of distribution was fixed (0.155 l kg−1). Factors screened for influence on CL/F were weight, age, gender and estimated creatinine clearance.ResultsSignificantly higher A77 1726 concentrations were seen in patients with less swollen joints and with higher SF‐36 mental summary scores than in those with measures indicating more active disease (P < 0.05); concentration‐effect trends were seen with five other disease activity measures. Statistical analysis of all disease activity measures showed that mean A77 1726 concentrations in groups with greater control of disease activity were significantly higher than those in whom the measures indicated less desirable control (P < 0.05). There was large between subject variability in the dose‐concentration relationship. A steady‐state infusion model best described the pharmacokinetic data. Inclusion of age as a covariate decreased interindividual variability (P < 0.01), but this would not be clinically important in terms of dosage changes. Final parameter estimate (% CV interindividual variability) for CL/F was 0.0184 l h−1 (50%) (95% CI 0.0146, 0.0222). Residual (unexplained) variability (% CV) was 8.5%.ConclusionsThis study of leflunomide in patients using the drug clinically indicated a concentration‐effect relationship. From our data, a plasma A77 1726 concentration of 50 mg l−1 is more likely to indicate someone with less active disease than is a concentration around 30 mg l−1. The marked variability in pharmacokinetics suggests a place for individualized dosing of leflunomide in RA therapy.
Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation
Authors: Mulla Hussain , Pooboni Suneel 
Published: August 2005

AimsExtracorporeal membrane oxygenation (ECMO) is a life support system used during severe respiratory or cardiorespiratory failure. The objective of this study was to characterize the population pharmacokinetics of vancomycin during ECMO.MethodsA population model was developed using WinNonMix (Version 2.0.1) from a total of 366 plasma observations in 45 patients, including term neonates, older children and adults. The study utilized both rich prospective and sparse retrospective data. Prospective samples were drawn at baseline and then 30, 60,90, 120, 180, 240, 300, 360 and 420 min postinfusion. Steady state concentrations were obtained retrospectively from an assay database, cross‐referencing with the patients’ medical records.ResultsData were examined using a two‐compartment model with an additive and proportional residual error. Model fit improved substantially when clearance, CL (l kg−1 h−1) was modelled as a nonlinear function of serum creatinine (Cr) µmol l−1. There was a linear relationship between CL and age up to 1000 days: CL (Age < 1000 days) = [2.4 + 0.0018 × Age (days)]/Cr; CL (Age > 1000 days) = 4.3/Cr. Age also influenced central volume (V1) when included in the model as a dichotomous variable: V1 (Age < 4000 days) = 0.45 l kg−1; V1 (Age > 4000 days) = 0.36 l kg−1. Intercompartmental clearance and tissue volume were estimated to be 0.09 l kg−1 h−1 and 0.25 l kg−1, respectively. Model validation in a separate group of 20 patients revealed a bias of −7.7% and a precision of 26.7%.ConclusionsThe clearance of vancomycin was decreased and its volume of distribution increased in patients receiving ECMO, suggesting altered drug disposition during this treatment.
Cyclin D1 overexpression in thyroid papillary microcarcinoma: its association with tumour size and aberrant β‐catenin expression
Authors: Lantsov D , Meirmanov S , Nakashima M , Kondo H , Saenko V , Naruke Y , Namba H , Ito M , Abrosimov A , Lushnikov E , Sekine I , Yamashita Sh 
Published: August 2005

Aims : Cyclin D1 is a target molecule transcriptionally activated by aberrant β‐catenin in Wnt signalling. Thyroid papillary microcarcinoma (PMC) may be considered a precursor of papillary thyroid cancer (PTC). Ki67 is widely used as a proliferation marker. The aim of this study was to determine whether cyclin D1 overexpression is involved in early thyroid carcinogenesis.Methods and results : Thirty‐five cases of PMC were examined immunohistochemically, including 11 cases less than 5 mm (PMC < 5) and 24 cases more than 5 mm (PMC > 5), and 18 PTC cases (size 11–15 mm). Cyclin D1 expression was significantly lower in PMC < 5 than in PMC > 5, while there was no significant difference between PMC > 5 and PTC. Statistical analysis revealed significant correlations between cyclin D1 labelling index (LI) and Ki67 LI (P = 0.0272)/cytoplasmic β‐catenin expression (P < 0.001) in PMC and PTC. Four of five PMC > 5 cases with lymph node (LN) metastases displayed a high cyclin D1 LI and strong cytoplasmic β‐catenin expression.Conclusions : Cyclin D1 overexpression and correlation with aberrant β‐catenin expression were demonstrated in PMC. Cyclin D1 expression was significantly associated with tumour size and LN metastases in PMC. Cyclin D1 may be up‐regulated at an early stage of thyroid carcinogenesis and promote tumour growth and metastatic potency in PMC through activation of the Wnt/β‐catenin pathway.
Expression and prognostic implications of cell cycle regulatory molecules, p16, p21, p27, p14 and p53 in germinal centre and non‐germinal centre B‐like diffuse large B‐cell lymphomas
Authors: Paik J H , Jeon Y K , Park S S , Kim Y A , Kim J E , Huh J , Lee S‐S , Kim W H , Kim C W 
Published: August 2005

Aims : To evaluate the different expression patterns and the prognostic significance of cell cycle regulatory molecules in diffuse large B‐cell lymphomas (DLBCLs) of germinal centre (GC) and non‐GC phenotypes.Methods and results : Tissue microarray slides composed of 126 extranodal and 88 nodal DLBCLs were immunostained for p16, p21, p27, p14 and p53. DLBCLs were classified into GC and non‐GC phenotype according to the immunohistochemical expression of bcl‐6, CD10, and MUM1. Aberrant expression of p53 was more frequent in the GC phenotype in nodal cases (P = 0.038), and the loss of p16, p21 and p14 expression was significantly more common in the non‐GC phenotype (P = 0.004, P = 0.001, P < 0.001). Concurrent disruptions of the p16‐Rb and p14‐p53 pathways as represented by the immunoprofile of p16/p14/p53 (–/–/+) were associated with a poor prognosis in the GC phenotype [mean survival 31 months in the p16/p14/p53 (–/–/+) group versus 62 months in the other groups, P =0.0485].Conclusions : The expression and prognostic implications of cell cycle regulatory molecules differ between GC and non‐GC phenotypes in DLBCLs. The immunoprofile of p16/p14/p53 (–/–/+) within the GC phenotype of DLBCLs can be defined as a poor prognostic subgroup.
Expression of type V secretory phospholipase A2 in myocardial remodelling after infarction
Authors: Ishikawa Y , Komiyama K , Masuda S , Murakami M , Akasaka Y , Ito K , Akishima‐Fukasawa Y , Kimura M , Fujimoto A , Kudo I , Ishii T 
Published: August 2005

Aims : Secretory phospholipase A2 is associated with ischaemic injury in the human heart, but the distribution of type V secretory phospholipase A2 (sPLA2‐V) remains unknown. The significance of sPLA2‐V in myocardial infarction was investigated histopathologically.Methods : Sequential changes in the localization of sPLA2‐V and its mRNA in myocardial tissues obtained from 30 autopsied hearts were examined by immunohistochemistry and in situ hybridization and compared with those of fibronectin, vascular endothelial growth factor (VEGF), interleukin (IL)‐1β, tumour necrosis factor (TNF)‐α, and cyclooxygenase‐2 (COX‐2).Results : No expression of sPLA2‐V was observed in normal heart, but it was promptly expressed in wavy myofibres positive for fibronectin just after the onset of infarction. sPLA2‐V was subsequently expressed in ischaemic cardiomyocytes around the lesion. The expression decreased at the granulation tissue and disappeared at the chronic stage with scar formation. The distribution of the signal for sPLA2‐V mRNA paralleled that of the protein. Ischaemic myocytes around the lesion expressed VEGF, IL‐1β, TNF‐α and COX‐2 at all stages.Conclusions : sPLA2‐V production in myocardium is limited to the acute phase of infarction. sPLA2‐V may play a dual role, acting both to remove degraded cell‐membrane through cooperative activity with COX‐2 in necrotic areas and to attack ischaemic myocytes around the lesion via degradation of membrane phospholipids.
Phytogeography of the bryophyte floras of oak forests and páramo of the Cordillera de Talamanca, Costa Rica
Authors: Holz Ingo , Robbert Gradstein S. 
Published: August 2005

AbstractAim  Central America is a biogeographically interesting area because of its location between the rich and very different biota of North and South America. We aim to assess phytogeographical patterns in the bryophyte floras of oak forests and páramo of the Cordillera de Talamanca, Costa Rica.Location  Tropical America, in particular the montane area of Cordillera de Talamanca, Costa Rica.Methods  The analysis is based on a new critical inventory of the montane bryophyte flora of Cordillera de Talamanca. All species were assigned to phytogeographical elements on the basis of their currently known distribution. Absolute and percentage similarities were employed to evaluate floristic affinities.Results  A total of 401 species [191 hepatics (liverworts), one hornwort, 209 mosses] are recorded; of these, 251 species (128 hepatics, one hornwort, 122 mosses) occur in oak forests. Ninety‐three per cent of all oak forest species are tropical in distribution, the remaining 7% are temperate (4%) and cosmopolitan (3%) species. The neotropical element includes almost 74% of the species, the wide tropical element (pantropical, amphi‐atlantic, amphi‐pacific) only 19%. A significant part of the neotropical species from oak forests are species with tropical Andean‐centred ranges (27%). As compared with bryophyte species, vascular plant genera in the study region are represented by fewer neotropical, more temperate and more amphi‐pacific taxa. Bryophyte floras of different microhabitats within the oak forest and epiphytic bryophyte floras on Quercus copeyensis in primary, early secondary and late secondary oak forest show a similar phytogeographical make‐up to the total oak forest bryophyte flora. Comparison of oak forest and páramo reveals a greater affinity of the páramo bryophyte flora to temperate regions and the great importance of the páramo element in páramo. Surprisingly, oak forests have more Central American endemics than páramo.Main conclusions  (1) Providing first insights into the phytogeographical patterns of the bryophyte flora of oak forests and páramo, we are able to confirm general phytogeographical trends recorded from vascular plant genera of the study area although the latter were more rich in temperate taxa. (2) Andean‐centred species are a conspicuous element in the bryophyte flora of Cordillera de Talamanca, reflecting the close historical connection between the montane bryophyte floras of Costa Rica and South America. (3) High percentages of Central American endemics in the bryophyte flora of the oak forests suggest the importance of climatic changes associated with Pleistocene glaciations for allopatric speciation.
FAREAST: a forest gap model to simulate dynamics and patterns of eastern Eurasian forests
Authors: Xiaodong Yan , Shugart H. H. 
Published: August 2005

AbstractAim  This paper describes the forest gap model, FAREAST, its testing and its application to simulating the distribution, composition and dynamics of forests in eastern Eurasia.Location  The FAREAST model is tested in north‐eastern China, initially for forests on the elevational gradient of Changbai Mountain, which is located on the border of the People's Republic of China and the Democratic People's Republic of Korea. Subsequently, the model is inspected regionally for other northern Chinese mountains and, finally, it is applied to predict subcontinental forest communities in the Russian Far East. Boreal larch (Larix spp.) forests cover much of the 6 million km2 of eastern Eurasia. Mixed broad‐leaved tree species/Korean pine (Pinus koraiensis) forests and spruce/fir (Picea/Abies) forests also occupy considerable areas.Methods  The model is tested using three types of information: (1) direct species composition comparisons between simulated and observed mature forests at the same locations; (2) forest type comparisons between simulated and observed forests along altitudinal gradients of several different mountains; and (3) comparison with forest stands in different succession stages of simulated forests.Results  Model comparisons with independent data indicate that the FAREAST model is capable of representing many of the broad features of the forests of north‐eastern China. After regional model validation in the north‐eastern region of China, geographical model applications were developed for the forests of the Russian Far East. In simulations at 31 different sites distributed across the entire Russian Far East and including a wide variety of natural forests, the model demonstrates an ability to reproduce observed vegetation pattern. The model simulations are correct with respect to our criteria for 23 of the 31 sites, and there are close results for three other sites. Among the five sites that are incorrectly predicted, four simulations can be corrected by adding a simple assumption to the model for permafrost effects on water balance.Main conclusions  Continental‐scale forest cover can be simulated using a forest gap model to represent individual–plant interactions with one another, and their environment, and with parameters that describe the biology of each tree species. It appears that such a model, validated relatively locally (in this case, in north‐eastern China), can then be applied over a much larger region. These results further imply that the Russian Far East forests can be regarded as a natural geographical expansion of north‐eastern Chinese forests. In both regions, forests share not only similar species compositions, but also similar underlying causes of forest successional dynamics.
Biogeography of mammals on tropical Pacific islands
Authors: Carvajal Alejandra , Adler Gregory H. 
Published: August 2005

AbstractAim  We examine the influence of geography on species richness and endemism of mammals on tropical Pacific archipelagos to determine the importance of intra‐ and inter‐archipelago speciation in promoting local and regional species richness.Location  Thirty tropical Pacific archipelagos.Methods  A distributional list of mammals on 30 archipelagos was compiled, and values for 10 geographical variables were estimated for each archipelago. Mammal species were placed in three different categories (continental, Pacific and endemic) based on their distribution. The total number of species and numbers of species within each category were related to the geographical variables using Poisson regression analysis.Results  Species richness was related positively to variables describing land area, numbers of large islands and elevation; and negatively to variables describing isolation. Levels of endemism did not differ between volant and non‐volant species, but differed between mega‐ and microchiropterans.Main conclusions  Variation in species richness of mammals in the tropical Pacific region can be accounted for by a combination of intra‐archipelago speciation within archipelagos composed of large islands, and inter‐archipelago speciation, particularly among more isolated archipelagos. Mammals were less widely distributed throughout the study area than previously found for butterflies, skinks or birds. However, the level of endemism was similar to that of skinks and birds on the same archipelagos, and was higher than that of butterflies.
The distribution of the ectoparasite fauna of Sebastes capensis from the southern hemisphere does not correspond with zoogeographical provinces of free‐living marine animals
Authors: González M. T. , Moreno C. A. 
Published: August 2005

AbstractAim  We examined the ectoparasite fauna of Sebastes capensis over almost all its geographical distribution range (Chilean, Argentinean and South African coasts) to determine (1) whether the ectoparasites of this host show a zoogeographical pattern and, if so, (2) how this pattern is related to known zoogeographical patterns for free‐living organisms.Location  Fish were captured from 20, 24, 30, 33, 36, 40, 45 and 52° S along the Chilean coast; 11° S on the Peruvian coast; 43° S on the Argentina coast; and 34° S on the South African coast.Methods  From April to September 2003 and from April to August 2004, 626 fish were captured. The parasites were collected using standard parasitological techniques. At the component community level, zoogeographical distribution patterns were evaluated using cluster analysis. At the infra‐community level, patterns of similarity in parasite composition among localities were investigated with multivariate discriminant analyses.Results  The ectoparasite fauna of S. capensis consists of six species distributed along the whole of the Chilean coast. Four other species are distributed only within the transitional zone between the northern warm temperate region (Peruvian faunistic province), extending from Peru to the northern Chilean coast up to c. 30° S, and the cold temperate region (Magellanic faunistic province). The component communities from latitudes 30 to 40° S showed higher ectoparasite species richness, while localities on the margins of the geographical range showed lower species richness. Cluster analysis indicated a grouping of localities consistent with the transitional zone. Argentina and South Africa always emerged as separate localities.Main conclusions  The ectoparasite communities of S. capensis do not follow a distributional pattern concordant with the known biogeographical zones for invertebrates and/or fish along the south‐eastern Pacific. Therefore their ectoparasite fauna is not useful as a zoogeographical indicator, although it does allow us to distinguish the transitional zone of the south‐eastern Pacific. On a more extended geographical scale, it is possible to distinguish the ectoparasite communities of S. capensis in the south‐eastern Pacific (as a whole) from those of Argentina and South Africa.
Self‐reported smoking, cotinine levels, and patterns of smoking in pregnancy
Authors: Pickett Kate E. , Rathouz Paul J. , Kasza Kristen , Wakschlag Lauren S. , Wright Rosalind 
Published: August 2005

SummaryNon‐pregnant adult smokers generally exhibit fairly stable smoking behaviour over time. In studies of this population, cotinine assays are considered a ‘gold standard’ measure of exposure to cigarette smoke; current smoking status can be validated with high sensitivity and specificity. In contrast, there is substantial within‐person fluctuation in pregnancy smoking, as women try repeatedly to quit or cut down. As a result, cotinine measures may be of limited use for validation of amount smoked, as they are informative only about recent exposure, vary with individual smoking topography and are dependent on time lapsed since the last cigarette smoked. Thus, in reproductive epidemiology, where timing, intensity and duration of exposure are critical, self‐reported history of cigarette consumption may be a more relevant fetal exposure than current smoking status. If there were substantial within‐person variation over the course of pregnancy, numerous measures of cotinine would be needed to characterise patterns of fetal exposure and would not be feasible in many studies.We examined self‐reported smoking patterns and compared them to patterns of urinary cotinine levels in a prospective study of 998 pregnant women, recruited 1988–92. Fluctuations in smoking were considerable and, while cotinine measures and self‐reported number of cigarettes were highly correlated at any given time point across women (r = 0.70), the within‐person correlation between the patterns of self‐reported number of cigarettes and cotinine levels was weaker (r = 0.33). For researchers interested in fetal outcomes in which intensity and timing of exposure are critical, we conclude that self‐reported variations in smoking during pregnancy may be a valid way to characterise detailed patterns of fetal exposure in epidemiological studies.