bluuebunny/crossref_metadata_2025_split huggingface dataset:
A critical review of the causes of death among post‐mortem toxicological investigations: analysis of 34 buprenorphine‐associated and 35 methadone‐associated deaths
Authors: Pirnay S. , Borron S. W. , Giudicelli C. P. , Tourneau J. , Baud F. J. , Ricordel I. 
Published: July 2004

ABSTRACTAims  To assess the trends in the number, mortality and the nature of forensic cases involving toxicological detection of buprenorphine or methadone among toxicological investigations performed in Paris from June 1997 to June 2002.Design  Retrospective, 5 year study with review of premortem data, autopsy, police reports, hospital data, and post‐mortem toxicological analyses.Setting and participants  34 forensic cases of buprenorphine and 35 forensic cases of methadone detection among 1600 toxicological investigations performed at the Laboratory of Toxicology in the Medical Examiner's Office in Paris.Measurements and results  Therapeutic, toxic or lethal drug concentrations were defined based upon the results of blood analyses and the published literature. Drug concentrations were cross‐referenced with other available ante‐ and post‐mortem data. Subsequently, we classified a ‘clear responsibility’, ‘possible responsibility’ or ‘not causative’ role for buprenorphine or methadone in the death process, or ‘no explanation of death’. Buprenorphine and methadone can be regarded as being directly implicated in, respectively, four of 34 death cases (12%) and three of 35 death cases (9%), and their participation in the lethal process is strongly plausible in eight (buprenorphine) and 11 (methadone) additional deaths.Conclusions  Analysis of causes of death reveals the difficulties in determining the role of substitution drugs in the death process, as many other factors may be involved, including circumstances surrounding death, past history, differential selection of subjectsinto either substitution modality and concomitant intake of other drugs (especially benzodiazepines and neuroleptics). The potential for synergistic or additive actions by other isolated molecules—particularly opioids, benzodiazepines, other psychotropes and alcohol—must be also considered.
Under‐reporting of alcohol consumption in household surveys: a comparison of quantity–frequency, graduated–frequency and recent recall
Authors: Stockwell Tim , Donath Susan , Cooper‐Stanbury Mark , Chikritzhs Tanya , Catalano Paul , Mateo Cid 
Published: July 2004

ABSTRACTAim  To compare alternative survey methods for estimating (a) levels of at risk alcohol consumption and (b) total volume of alcohol consumed per capita in comparison with estimates from sales data and to investigate reasons for under‐reporting.Setting  The homes of respondents who were eligible and willing to participate.Participants  A total of 21 674 Australians aged 14 years and older.Design  A 2001 national household survey of drug use, experiences and attitudes with weights applied for age, sex, geographic location and day of week of interview.Measures  Self‐completion questionnaire using quantity–frequency (QF) and graduated–frequency (GF) methods plus two questions about consumption ‘yesterday’: one in standard drinks, another with empirically based estimates of drink size and strength.Results  The highest estimate of age 14 + per capita consumption of 7.00 l of alcohol derived from recall of consumption ‘yesterday’ or 76.8% of the official estimate. The lowest was QF with 49.8%. When amount consumed ‘yesterday’ was recalled in standard drinks this estimate was 5.27 l. GF questions yielded higher estimates than did QF questions both for total volume (5.25 versus 4.54 l) and also for the proportion of the population at risk of long‐term alcohol‐related harm (10.6%versus 8.1%). With the detailed ‘yesterday’ method 61% of all consumption was on high risk drinking days.Conclusions  Questions about typical quantities of alcohol consumed can lead to underestimates, as do questions about drinking ‘standard drinks’ of alcohol. Recent recall methods encourage fuller reporting of volumes plus more accurate estimates of unrecorded consumption and the proportion of total alcohol consumption that places drinkers at risk of harm. However, they do not capture longer‐term drinking patterns. It is recommended that both recent recall and measures of longer‐term drinking patterns are included in national surveys.
An expanded comparative map of bovine chromosome 27 targeting dairy form QTL regions*
Authors: Connor E. E. , Sonstegard T. S. , Ashwell M. S. , Bennett G. L. , Williams J. L. 
Published: July 2004

SummaryAt present, the density of genes on the bovine maps is extremely limited and current resolution of the human–bovine comparative map is insufficient for selection of candidate genes controlling many economic traits of interest in dairy cattle. This study describes the chromosomal mapping of 10 selected gene‐associated markers to bovine linkage and radiation hybrid maps to improve the breakpoint resolution in the human–bovine comparative map near two previously identified quantitative trait loci for the linear type trait, dairy form. Two regions of conserved synteny not previously described are reported between the telomeric region of bovine chromosome 27 (BTA27) and human chromosome 3 (HSA3) p24 region and between the HSA4q34.1 region and BTA8. These data increase the number of genes positioned on the bovine gene maps, refine the human–bovine comparative map, and should improve the efficiency of candidate gene selection for the dairy form trait in cattle.
Impact of the ESR gene on litter size and production traits in Czech Large White pigs
Authors: Goliášová E. , Wolf J. 
Published: July 2004

SummaryTo evaluate the effect of the PvuII polymorphism of the oestrogen receptor gene on litter size and production traits in Czech Large White swine, data from 1250 sows and 3600 litters were analysed with two four‐trait animal models. The traits in the first model were number of piglets born alive in a sow's first litter, number of piglets born alive in second and subsequent litters, lifetime daily gain and lean meat percentage. The second model included number of piglets born, number of piglets born alive, number of piglets weaned and litter weight at weaning from first and subsequent litters. The oestrogen receptor (ESR) locus significantly affected prolicacy in the first parity and averaged over all parities (P < 0.05), with allele A superior to allele B. In the first parity, AA sows produced approximately 0.5 more live piglets per litter than BB sows. Averaged over all parities, this difference was c. 0.25 piglets. Results for total number of piglets born and number of piglets weaned were similar to results for numbers born alive. No significant dominance effect was found for prolificacy traits. For litter weight at weaning, no significant additive effect was observed at the ESR locus, but a significant negative dominance effect (−1.5 kg) was estimated averaged across parities (litters of AB sows were similar to litters of BB sows for this trait). No pleiotropic effect of the ESR polymorphism on average daily gain or lean meat percentage was found.
Identification of an ovulation rate QTL in cattle on BTA14 using selective DNA pooling and interval mapping1
Authors: Gonda M. G. , Arias J. A. , Shook G. E. , Kirkpatrick B. W. 
Published: July 2004

SummaryIncreased twinning incidence in beef cattle has the potential to improve production efficiency. However, phenotypic selection for twinning rate is difficult because of the trait's low heritability and the long time interval necessary to collect phenotypic records. Therefore, this trait and the correlated trait of ovulation rate are ideal candidates for marker‐assisted selection. The objective of this study was to complete a genome‐wide search for ovulation rate quantitative trait loci (QTL) in two related sire families. The families (paternal halfsib sires 839802 and 839803) were from a population of cattle selected for ovulation rate at the USDA Meat Animal Research Center, Clay Center, Nebraska. Putative ovulation rate QTL have previously been identified in the 839802 family on chromosomes 7 and 19; however, marker coverage in the original scan was not complete. This study fills the gaps in marker coverage of the earlier study by adding approximately 60 informative microsatellites to each sire family. Each family was genotyped using selective DNA pooling. Sons and daughters were included in either the high or low pool based on their estimated breeding value deviations from the mid‐parent average (EBVMD) for ovulation rate. Approximately 40% (839802) and 26% (839803) of available progeny comprised the high and low pools combined. Pooled typing revealed possible associations (nominal P < 0.05) between ovulation rate and marker genotype for 11 and 15 microsatellites in the 839802 and 839803 families, respectively. Subsequent interval mapping strengthened support for the presence of an ovulation rate QTL on BTA14 (chromosome‐wise P < 0.02).
A new single nucleotide polymorphism in the chicken pituitary‐specific transcription factor (POU1F1) gene associated with growth rate
Authors: Jiang R. , Li J. , Qu L. , Li H. , Yang N. 
Published: July 2004

SummaryThe pituitary‐specific transcription factor (POU1F1) is a protein which binds to and transactivates promoters of growth hormone (GH), prolactin (PRL) and thyroid‐stimulating hormone chain (TSHB)‐encoding genes. Ten chicken populations (n = 662), including six Chinese indigenous breeds, White Leghorn, paternal/maternal lines of brown egg layer and a paternal line of broiler, were used to detect single nucleotide polymorphisms in the pituitary‐specific transcription factor gene (PIT1) by means of PCR‐SSCP. A nucleotide transversion from adenine (A) to thymidine (T) at position 980 of the open reading frame of the PIT1 cDNA (GenBank accession no. AF029892) was identified. This nucleotide transversion results in an alteration of codon 299 from AAC to ATC, which leads to a change from asparagine (Asn) to isoleucine (Ile) in the POU domain of POU1F1. The distribution of allele and genotype frequencies differed significantly between meat‐type chickens (higher frequencies of A and A/A) and layer‐type chickens (P < 0.01). Another experimental population with growth records was used to evaluate the relationship between this polymorphism and growth rate. The results revealed a positive relationship between genotype A/A and body weight at 8 weeks of age, indicating that the SNP in PIT1 gene is a potential molecular marker for early growth rate in chicken.
The genes encoding bovine SP‐A, SP‐D, MBL‐A, conglutinin, CL‐43 and CL‐46 form a distinct collectin locus on Bos taurus chromosome 28 (BTA28) at position q.1.8–1.9
Authors: Gjerstorff M. , Hansen S. , Jensen B. , Dueholm B. , Horn P. , Bendixen C. , Holmskov U. 
Published: July 2004

SummaryCollectins are a group of C‐type lectins involved in the innate immune system, where they mediate and modulate clearance of pathogens. The health status of cattle is of major economical and ethical concern; therefore, the study of bovine collectins is of importance. The collectins conglutinin, CL‐43 and CL‐46 are only present in Bovidae and the characterization of their genes indicates that they are structural descendants of another collectin, lung surfactant protein D (SP‐D). In this study, we assembled BAC clones into a contig spanning 330–1150 kb, which includes the bovine genes encoding the collectins SP‐A (SFTPA), SP‐D (SFTPD), mannan‐binding lectin A (MBL1), CL‐43 (COLEC9), CL‐46 (COLEC13) and conglutinin (COLEC8). In the same contig, we also identified a gene that potentially encodes a novel conglutinin‐like collectin (COLEC14). The arrangement of STFPA, SFTPD and MBL1 is homologous to the organization found in humans and mice, whereas the Bovidae‐specific collectin genes, COLEC8, COLEC9 and COLEC13, extend from SFTPD. Proximal to the collectin locus at BTA28q1.8–1.9, and included in the contig, we found the microsatellite IDVGA8, which may be a valuable marker for tracking polymorphisms in the linked collectin genes.
Contributions of Portuguese cattle breeds to genetic diversity using marker‐estimated kinships
Authors: Mateus J. C. , Eding H. , Penedo M. C. T. , Rangel‐Figueiredo M. T. 
Published: July 2004

SummaryThe quantitative assessment of genetic diversity within and between populations is important for decision‐making in genetic conservation plans. In our study, we applied the livestock core set method to define the contribution of 15 cattle breeds, 11 of which are Portuguese indigenous cattle breeds, to genetic diversity. In livestock core set theory genetic diversity is defined as the maximum genetic variance that can be obtained in a random‐mating population that is bred from the populations present in that core set. Two methods to estimate marker‐estimated kinships to obtain the contributions to the core set were used in this study: the weighted log‐linear model (WLM) and the weighted log‐linear mixed model (WLMM). The breeds that contributed most to diversity in the core set were Holstein‐Friesian followed by the Portuguese Mertolenga and Cachena for both WLM and WLMM methods. The ranking of relative contributions of cattle breeds was maintained when we considered only the Portuguese cattle breeds. Furthermore, we were able to identify the marginal contributions and respective losses of diversity for each of the 11 Portuguese cattle breeds when we considered a subset of populations that are not threatened of being lost (the Safe set composed of the four exotic breeds present in this study). When WLM was used losses in genetic diversity ranged from 2.68 to 0.65% while the loss in founder genome equivalents ranged from 37.37 to 8.43% for Mertolenga and Brava de Lide breeds respectively. When WLMM was used losses in genetic diversity and founder genome equivalents were less extreme than for the WLM method, ranging from 1.27 to 0.69 and 26.8 to 12.99 respectively.
Antipsychotic polypharmacy in patients with schizophrenia: a multicentre comparative study in East Asia
Authors: Sim Kang , Su Alex , Fujii Senta , Yang Shu‐yu , Chong Mian‐Yoon , Ungvari Gabor S. , Si Tianmei , Chung Eun K. , Tsang Hin‐Yeung , Chan Yiong H. , Heckers Stephan , Shinfuku Naotaka , Tan Chay H. 
Published: July 2004

AimsPrevious studies of the prescription patterns of psychotropic medications in patients with schizophrenia have highlighted a high rate of antipsychotic polypharmacy, but data in Asia are sparse. This study seeks to examine the prevalence of antipsychotic polypharmacy in patients with schizophrenia and compare the differences between patients receiving one vs. those receiving more than one antipsychotic.MethodsAntipsychotic prescription for a sample of 2399 patients with schizophrenia from six countries and territories was evaluated. Daily doses of antipsychotic medications were converted to standard chlorpromazine equivalents (CPZ).ResultsAntipsychotic polypharmacy was found in 45.7% (n = 1097) of the patients with wide intercountry variations. Polypharmacy was associated with male gender [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.06, 1.46, P < 0.01], advanced age (t = −7.81, d.f. = 2396, P < 0.001), psychiatric hospital setting (OR 1.34, 95% CI 1.11, 1.62) as well as higher daily CPZeq doses (411.47 vs. 983.10 CPZeq day−1, z = −25.94, P < 0.001), anticholinergic use (OR 3.17, 95% CI 2.65, 3.79, P < 0.001) and less use of an atypical antipsychotic drug (OR 0.83, 95% CI 0.71, 0.98, P < 0.05). On multivariate analysis, country, age and duration of illness were significantly associated with antipsychotic polypharmacy.ConclusionThis study highlighted the wide intercountry variations of antipsychotic polypharmacy which are likely to be influenced by a complex combination of clinical, setting, cultural and personal practice factors, requiring more research.
In vitro fertilization and childhood retinoblastoma
Authors: Bradbury Brian D. , Jick Hershel 
Published: July 2004

AimsTo estimate the frequency of childhood retinoblastoma among children conceived by in vitro fertilization (IVF).MethodsUsing the United Kingdom‐based General Practice Research Database (GPRD), we identified all live births, cases of retinoblastoma and IVF procedures occurring between January 1989 and December 2001.ResultsWe identified 0 cases of retinoblastoma among 176 children conceived by IVF (Risk = 0/176, one‐sided 97.5% CI 0, 0.02) and 24 cases of retinoblastoma diagnosed before age 5 years among 358 094 children not conceived by IVF (6.7 cases per 100 000 births [95% CI 4.5, 10]).ConclusionsThese data provide some reassurance that children born as a result of IVF are not at markedly increased risk of retinoblastoma.
In vitro blood distribution and plasma protein binding of the tyrosine kinase inhibitor imatinib and its active metabolite, CGP74588, in rat, mouse, dog, monkey, healthy humans and patients with acute lymphatic leukaemia
Authors: Kretz Olivier , Weiss H Markus , Schumacher Martin M , Gross Gerhard 
Published: July 2004

AimsTo determine blood binding parameters of imatinib and its metabolite CGP74588 in humans and non‐human species.MethodsThe blood distribution and protein binding of imatinib and CGP74588 were determined in vitro using 14C labelled compounds.ResultsThe mean fraction of imatinib in plasma (fp) was 45% in dog, 50% in mouse, 65% in rat, 70% in healthy humans and up to 92% in acute lymphatic leukaemia (AML) patients. Similarly, fp for CGP74588 was low in dog and monkey (30%), higher in rat, mouse and humans (70%) and highest in some AML patients (90%). The unbound fraction of imatinib and CGP74588 in plasma was lower in rat, mouse, healthy humans and AML patients (2.3–6.5% at concentrations ≤ 5000 ng ml−1) compared to monkey and dog (7.6–19%). Both compounds displayed high binding to human α1‐acid glycoprotein. AML patients had a reduced haematocrit and showed greatest variability in their blood binding parameters.ConclusionImatinib and CGP74588 displayed very similar blood binding parameters within all species/groups investigated. The five species clustered into two distinct groups with rat, mouse and humans being clearly different from dog and monkey. For both compounds, higher protein binding was associated with a decreased partitioning into blood cells.
Plasma concentrations during naltrexone implant treatment of opiate‐dependent patients
Authors: Olsen Linda , Christophersen Asbjørg S. , Frogopsahl Grete , Waal Helge , Mørland Jørg 
Published: July 2004

AimsTo evaluate individual variations in plasma concentrations over time in patients with naltrexone implants.MethodsTen opioid‐dependent patients received up to four implants. Plasma samples were collected regularly for the analyses of naltrexone and the metabolite β‐naltrexol.ResultsThe median naltrexone Cmax was 12.3 (range 5.8–22.1) ng ml−1, the median Tmax was 1 day (range 3 h to 35 days), and the median length of time that plasma concentrations were above 1 ng ml−1 was 55 (range 30–80) days. Two patients reported heroin use without experiencing any effect. Tissue reactions were recorded in two patients after repeated implantation.ConclusionMarked individual and intraindividual variations in naltrexone concentrations were observed. Further studies should be performed to evaluate the need for therapeutic drug monitoring during naltrexone implant treatment.
Leflunomide in active rheumatoid arthritis: a prospective study in daily practice
Authors: Van Roon E. N. , Jansen T. L. TH. A. , Mourad L. , Houtman P. M. , Bruyn G. A. W. , Griep E. N. , Wilffert B. , Tobi H. , Brouwers J. R. B. J. 
Published: July 2004

Aims  We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care‐as‐usual.Methods  In this prospective case series study, a standard dataset was collected from outpatient medical records, including patient and disease characteristics, data on leflunomide use and adverse drug reactions.Results  During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow‐up duration was 317 (11–911) days. Sixty‐five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow‐up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS28) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow‐up, respectively. Within a 12‐month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS28 response criteria.Conclusions  In the setting of care‐as‐usual rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within 1 year of starting leflunomide treatment, mainly because of adverse drug reactions.
Robustness of chlorzoxazone as an in vivo measure of cytochrome P450 2E1 activity
Authors: Ernstgård Lena , Warholm Margareta , Johanson Gunnar 
Published: July 2004

AimsChlorzoxazone is metabolized by cytochrome P450 2E1 (CYP2E1) to a single oxidized metabolite, 6‐hydroxychlorzoxazone. The aim of the study was to test the robustness of chlorzoxazone as an in vivo probe of CYP2E1 activity in humans, with emphasis on investigating short‐term and long‐term intra‐individual variabilities and effects of different doses of the drug. In addition, the influences of body build, drug metabolizing enzyme genotype, blood sampling time, and moderate recent ethanol intake were investigated.MethodsThe 6‐hydroxychlorzoxazone : chlorzoxazone (metabolic) ratio in plasma was measured at 2 h in 28 male and nine female volunteers following a single oral dose of 500 mg chlorzoxazone. Similarly, the metabolic ratios at 4 h and 6 h were measured in 20 of the males. The metabolic ratio at 2 h was also determined 1.5 and 2.5 years later in 13 and seven males, respectively, and weekly for 3 weeks in seven males, after a dose of 500 mg, once at higher (750 mg) and lower (250 mg) doses, and once (500 mg) following moderate ethanol intake (0.5 g kg−1 body weight) the preceding evening. Genotypes were determined for CYP2E1 as well as for N‐acetyltransferase 2 and glutathione transferase M1.ResultsExcluding an outlier (ratio = 1.6) the metabolic ratio at 2 h ranged from 0.12 to 0.61 (n = 36). A positive correlation with body weight (r = 0.61, P < 0.001) suggested dose‐dependent metabolism of chlorzoxazone. The metabolic ratio decreased with increasing chlorzoxazone dose (P = 0.01), again suggesting dose‐dependent metabolism. Long‐term (yearly intervals) and short‐term (weekly intervals) intra‐ and interindividual variabilities in metabolic ratio were similar (30% and 63%vs 28% and 54%, respectively). Both inter‐ and intra‐individual variabilities tended to decrease with increasing dose of chlorzoxazone. There was no significant influence of moderate ethanol intake the preceding evening, or of CYP2E1 genotype on the metabolic ratio.ConclusionsThe relatively low intra‐individual variability in the metabolism of chlorzoxazone suggests that a single‐sample procedure may suffice to assess CYP2E1 activity in vivo. However, chlorzoxazone metabolism is dose‐dependent at commonly used doses and it is therefore advisable to adjust the dose for body weight. Moderate intake of ethanol the preceding evening did not significantly affect the chlorzoxazone metabolic ratio.