bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pharmacological treatment of schizophrenia in Chinese patients: a comparison of prescription patterns between 1996 and 1999
Authors: Ungvari Gabor S , Chung Yiu Gar , Chee Yip Ka , Fung‐Shing Ng , Kwong Tang Wai , Chiu Helen F. K. 
Published: March 2003

Aims
In 1996 a Hong Kong‐wide survey of pharmacological treatment for schizophrenic inpatients identified a few idiosyncratic prescription patterns that were not consistent with international standards. In the context of continuous quality assurance, the survey was repeated in 1999 to monitor trends in the pharmacotherapy of schizophrenia and to identify changes in prescribing practices. It was expected that the widespread introduction of novel antipsychotic drugs coupled with continuing medical education would favourably alter prescribing habits.
Methods
A representative random sample of 1202 schizophrenic patients from all inpatient settings in Hong Kong was surveyed. Basic socio‐demographic data and a list of all psychotropic medication taken on census day were collected.
Results
Significant  improvement  was  noted  in  several  aspects  of  pharmacotherapy in   1999   as   compared   with   1996.   The   total   daily   dosage   of   antipsychotic   drugs decreased from 716 ± 627 to 561 ± 482 mg day−1 chlorpromazine equivalent (CPZeq) (Mann–Whitney U‐test; Z = −3.906, P = 0.000; 95% confidence interval [CI] = 70.0, 240.2 mg day−1 CPZeq), for acute patients and from 923 ± 809 to 675 ± 545 mg day−1 CPZeq (Mann–Whitney U‐test; Z=−5.036, P = 0.000; 95% CI = 175.57, 321.63 mg day−1 CPZeq) for chronic patients. The percentage of patients coprescribed antipsychotics and an antiparkinson drug significantly decreased from 67.8% to 61.8% (χ2 = 5.558, P = 0.018) in the chronic schizophrenia group. The percentage of patients taking atypical antipsychotic medication increased significantly from 5.5% to 19.2% (χ2 = 27.14, P = 0.000) in the acute and 3.4% to 12.3% (χ2 = 27.76, P = 0.000) in the chronic group.
Conclusions
Repeated surveys of prescribing practices proved to be a useful tool to demonstrate trends in the pharmacological treatment of schizophrenia. Our findings suggest that the widespread use of atypical antipsychotic drugs contributed to a more rational pharmacotherapy for schizophrenia.
St John's wort (Hypericum perforatum): drug interactions and clinical outcomes
Authors: Henderson L. , Yue Q. Y. , Bergquist C. , Gerden B. , Arlett P. 
Published: March 2003

Aims
The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible.
Methods
A systematic review of all the available evidence, including worldwide published literature and spontaneous case reports provided by healthcare professionals and regulatory authorities within Europe has been undertaken.
Results
A number of clinically significant interactions have been identified with prescribed medicines including warfarin, phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and oral contraceptives resulting in a decrease in concentration or effect of the medicines. These interactions are probably due to the induction of cytochrome P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P‐glycoprotein by constituent(s) in SJW. The degree of induction is unpredictable due to factors such as the variable quality and quantity of constituent(s) in SJW preparations. In addition, possible pharmacodynamic interactions with selective serotonin re‐uptake inhibitors and serotonin (5‐HT1d) receptor‐agonists such as triptans used to treat migraine were identified. These interactions are associated with an increased risk of adverse reactions.
Conclusions
In Sweden and the UK the potential risks to patients were judged to be significant and therefore information about the interactions was provided to health care professionals and patients. The product information of the licensed medicines involved has been amended to reflect these newly identified interactions and SJW preparations have been voluntarily labelled with appropriate warnings.
Pharmacokinetic modelling of morphine, morphine‐3‐glucuronide and morphine‐6‐glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short‐term infusion of morphine
Authors: Meineke Ingolf , Freudenthaler Stefan , Hofmann Ute , Schaeffeler Elke , Mikus Gerd , Schwab Matthias , Prange Hilmar W. , Gleiter Christoph H. , Brockmöller J. 
Published: March 2003

Aims Concentrations in the cerebrospinal fluid (CSF) are a useful approximation to the effect site for drugs like morphine. However, CSF samples, are available only in rare circumstances. If they can be obtained they may provide important insights into the pharmacokinetics/pharmacodynamics of opioids.Methods Nine neurological and neurosurgical patients (age 19–69 years) received 0.5 mg kg−1 morphine sulphate pentahydrate as an intravenous infusion over 30 min. Plasma and CSF were collected for up to 48 h. Concentration time‐course and interindividual variability of morphine (M), morphine‐3‐glucuronide (M3G) and morphine‐6 glucuronide (M6G) were analysed using population pharmacokinetic modelling.Results While morphine was rapidly cleared from plasma (total clearance = 1838 ml min−1 (95% CI 1668, 2001 ml min−1)) the glucuronide metabolites were eliminated more slowly (clearance M3G = 44.5 ml min−1 (35.1, 53.9 ml min−1), clearance M6G = 42.1 ml min−1 (36.4, 47.7 ml min−1)) and their clearance could be described as a function of creatinine clearance. The central volumes of distribution were estimated to be 12.7 l (11.1, 14.3 l) for morphine. Transfer from the central compartment into the CSF was also rapid for M and considerably slower for both glucuronide metabolites. Maximum concentrations were achieved after 102 min (M), 417 min (M3G) and 443 min (M6G). A P‐glycoprotein exon 26 polymorphism previously found to be linked with transport activity could be involved in CSF accessibility, since the homozygous mutant genotype was associated (P < 0.001) with high maximum CSF concentrations of M but not M3G or M6G.Conclusions From the population pharmacokinetic model presented, CSF concentration profiles can be derived for M, M3G and M6G on the basis of dosing information and creatinine clearance without collecting CSF samples. Such profiles may then serve as the link between dose regimen and effect measurements in future clinical effect studies.
Quantification of heparin‐induced TFPI release: a maximum release at low heparin dose
Authors: Kemme Michiel J. B. , Burggraaf Jacobus , Schoemaker Rik C. , Kluft Cornelis , Cohen Adam F. 
Published: March 2003

Aims Heparin releases tissue factor pathway inhibitor (TFPI) from the endothelium and this release may decrease after repeated high dose heparin administration. The primary aim was to investigate and quantify this phenomenon during a short low dose heparin infusion. Also, the effects of heparin on tissue plasminogen activator (t‐PA) were studied.Methods Nine healthy, nonsmoking, male volunteers (range 19–23 years) received a continuous heparin infusion (2000 IU) over 40 min. The endothelial TFPI release rate was estimated from the total TFPI concentration profile using a pharmacokinetic model.Results   Mean  ± s.d.  total  and  free  TFPI  increased  from  62.9 ± 9.4/8.3 ± 2.1 ng ml−1 at baseline to 237.2 ± 40.9/111.0 ± 19.9 ng ml−1 after 40 min infusion. The relationship between heparin concentration (anti‐IIa activity) and TFPI concentration followed a maximum effect model and a clockwise loop (proteresis) was observed. The TFPI release rate rapidly increased to maximum of 200 ± 45 µg min−1 after 17.5 min heparin infusion but did not increase further although heparin concentrations further doubled. In contrast to TFPI, t‐PA antigen decreased from 5.6 ± 1.0 at baseline to 4.5 ± 1.0 ng ml−1 at the end of infusion (t = 40 min) (difference of 1.1 ng ml−1 (95% confidence interval; 0.9, 1.3).Conclusions Our application of concentration‐effect models and pharmacokinetic principles to these haemostatic variables showed that endothelial TFPI release has a maximum that is already reached at low heparin dose, corresponding with an anti‐IIa activity of 0.08 IU ml−1. The relationship between anti‐IIa activity and TFPI release rate showed signs of acute tolerance (clockwise loop) indicating exhaustion of endothelial TFPI pools. These findings may be of importance for the heparin dose used in conditions such as unstable angina, in which the favourable effects of heparin have been ascribed to its ability to release TFPI.
Lack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects
Authors: Cooper Kelvin J. , Martin Paul D. , Dane Aaron L. , Warwick Mike J. , Raza Ali , Schneck Dennis W. 
Published: March 2003

Aims  To examine in vivo the effect of ketoconazole on the pharmacokinetics of rosuvastatin, a 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor.Methods  This was a randomized, double‐blind, two‐way crossover, placebo‐controlled trial. Healthy male volunteers (n = 14) received ketoconazole 200 mg or placebo twice daily for 7 days, and rosuvastatin 80 mg was coadministered on day 4 of dosing. Plasma concentrations of rosuvastatin, and active and total HMG‐CoA reductase inhibitors were measured up to 96 h postdose.Results  Following coadministration with ketoconazole, rosuvastatin geometric least square mean AUC(0,t) and Cmax were unchanged compared with placebo (treatment ratios (90% confidence intervals): 1.016 (0.839, 1.230), 0.954 (0.722, 1.260), respectively). Rosuvastatin accounted for essentially all of the circulating active HMG‐CoA reductase inhibitors and most (> 85%) of the total inhibitors. Ketoconazole did not affect the proportion of circulating active or total inhibitors accounted for by circulating rosuvastatin.Conclusions  Ketoconazole did not produce any change in rosuvastatin pharmacokinetics in healthy subjects. The data suggest that neither cytochrome P450 3A4 nor P‐gp‐mediated transport contributes to the elimination of rosuvastatin.
Pharmacokinetic interaction between amprenavir and delavirdine after multiple‐dose administration in healthy volunteers
Authors: Justesen Ulrik S. , Klitgaard Niels A. , Brosen Kim , Pedersen Court 
Published: March 2003

Aims  To evaluate the safety and the pharmacokinetic interaction between amprenavir and delavirdine after multiple dose administration in healthy volunteers.Methods  This was a prospective, open‐label, randomized, controlled, two‐sequence, two‐period multiple dose study with 18 healthy subjects. Volunteers were randomly assigned to amprenavir, 600 mg twice a day, or delavirdine, 600 mg twice a day, for 10 days, followed by both drugs for another 10 days with pharmacokinetic evaluation on day 10 and day 20. Adverse events were recorded throughout the study.Results  Amprenavir decreased all the delavirdine pharmacokinetic parameters apart from tmax. Delavirdine C12h dropped from 7916 to 933 ng ml−1 (median decrease 5930 ng ml−1, 95% CI 3013, 8955 ng ml−1). A decrease in amprenavir t½ was also seen leading to almost identical median amprenavir C24h values. No serious clinical adverse events were observed during the study. The most frequently reported effects were gastrointestinal symptoms, headache, fatigue and rash.Conclusions  Amprenavir is an effective inducer of delavirdine metabolism, probably through its effect on hepatic CYP3A4. This could have consequences in other drug‐drug interaction situations. Delavirdine is an inhibitor of amprenavir metabolism. The regimen of amprenavir 600 mg and delavirdine 600 mg twice a day is not recommended when an antiretroviral effect from delavirdine is required.
Pharmacokinetics, food intake requirements and tolerability of once‐daily combinations of nelfinavir and low‐dose ritonavir in healthy volunteers
Authors: Aarnoutse R. E. , Droste J. A. H. , Van Oosterhout J. J. G. , Koopmans P. P. , Popescu M. , Reiss P. , Hekster Y. A. , Burger D. M. 
Published: March 2003

Aims This study was performed to evaluate the steady‐state pharmacokinetics, food intake requirements and short‐term tolerability of once‐daily combinations of nelfinavir and low‐dose ritonavir.Methods Twenty‐seven healthy volunteers were randomized over three groups to receive a once‐daily regimen of nelfinavir/ritonavir 2000/200 mg (group 1), 2000/400 mg (group 2) or 2500/200 mg (group 3) with food for 14 days. Pharmacokinetic parameters for nelfinavir and its active metabolite M8 were assessed on study days 15 and 16, after administration of the regimens with a full (610 kcal) or light (271 kcal) breakfast, respectively.Results Pharmacokinetic data were evaluable for eight volunteers in group 1, eight in group 2 and four in group 3. Administration of nelfinavir/ritonavir with a full breakfast resulted in geometric mean (GM) nelfinavir AUC24h values of 76.8, 51.3, and 61.9 h*mg/l in group 1, 2 and 3, respectively. GM 24‐h Cmin concentrations of nelfinavir were 0.76 mg l−1, 0.43 mg l−1 and 0.47 mg l−1, respectively. Co‐administration of ritonavir increased M8 concentrations more than nelfinavir concentrations, resulting in GM AUC24h and Cmin values for nelfinavir plus M8 that were higher than or comparable to reference values for the approved regimen of nelfinavir (1250 mg BID without ritonavir). In the 2000/200 mg group, seven out of eight subjects had a Cmin value of nelfinavir plus M8 above a threshold of 1.0 mg l−1. Administration of the combinations with a light breakfast resulted in significant decreases in the AUC24h and Cmin of nelfinavir and nelfinavir plus M8, compared with intake with a full breakfast. For the Cmin of nelfinavir plus M8, the GM ratio (light/full breakfast) was 0.76 (90% confidence interval 0.67–0.86, participants from all groups combined). Short‐term tolerability was satisfactory, apart from a higher than expected incidence of mild rash (12%).Conclusions Administration of nelfinavir in a once‐daily regimen appears feasible. A nelfinavir/ritonavir 2000/200 mg combination appears appropriate for further evaluation. Once‐daily nelfinavir/ritonavir should be taken with a meal containing at least 600 kcal.
Apocrine acrosyringeal keratosis in association with syringocystoadenoma papilliferum
Authors: Kishimoto S. , Wakabayashi S. , Yamamoto M. , Noda Y. , Takenaka H. , Yasuno H. 
Published: March 2003

AbstractWe report the clinical and histopathological features of a keratosis that developed in association with syringocystadenoma papilliferum. This tumour shows a pinkish, pedunculated, spherical nodule with a cerebriform surface and visible keratinous plugs. In addition to the typical features of syringocystadenoma papilliferum, the tumour shows many hyperkeratotic columns surrounded by acanthotic epidermis with the characteristics of trichilemmal keratinization and keratohyalin granules. This keratosis seems to be derived from the middle to lower portion of the apocrine acrosyringium, based on the distribution of keratohyalin granules and the direct connection with the apocrine acrosyringium in an early lesion. Accordingly, we propose to identify this rare keratosis as apocrine acrosyringeal keratosis.
A1,2BO1,2 genotyping by multiplexed allele‐specific PCR
Authors: Pearson Steven L. , Hessner Martin J. 
Published: March 2003

The ABO blood group is the most clinically important human alloantigen system in transfusion medicine. The system involves three antigens A, B and H. H antigen is converted to either A or B by the activity of α1 → 3‐ n‐acetyl‐galactosaminyl transferase (A transferase) or α1 → 3 galactosyl transferase (B transferase). The O phenotype is the result of an inactive glycosyltransferase, which is unable to glycosylate the H antigen.The immunological properties of the ABO system were identified at the turn of the century; however, the genetic basis of the ABO system has only recently been characterized. This has enabled the development of a number of molecular ABO typing methods. Described here is a two‐reaction multiplex allele‐specific PCR (ASPCR) genotyping assay for the A1, A2, B, O1 and O2 subtypes. 11 different allele‐specific oligonucleotide primers were selected to detect the presence or absence of the O1 associated G →  (−) deletion at base 261, the O2 associated G → A substitution at base 802, the B associated G → A substitution at base 803, and finally the A2 associated C → (−) deletion at base 1059.A total of 122 peripheral blood samples were genotyped and serologically forward and reverse typed. A concordance rate of 98.4% (120/122 samples) was observed between the actual genotype and the serologically‐based predicted genotype. These results indicate that this assay provides a rapid, accurate, and simple method for A1,2BO1,2 genotyping that serves as a useful supplement to standard serological ABO typing.
Protein A immunoadsorption in chronic refractory ITP reverses increased platelet activation but fails to achieve sustained clinical benefit
Authors: Cahill  , Macey  , Cavenagh  , Newland  
Published: March 2003

Adults with chronic relapsing ITP present a difficult therapeutic challenge. The ongoing antibody‐ mediated platelet destruction in this group might be expected to be associated with increased expression of platelet surface membrane activation antigens.We have studied a group of 10 patients with refractory ITP and 35 healthy controls. Using an immediate, sensitive, unfixed, whole blood, flow cytometric method to detect platelet surface P‐selectin and GP53, we have detected markedly increased platelet activation in the ITP group compared with the controls (P‐selectin; patient median 24.5% v control median 2.0%, GP53 median 6.5% v 2.1%, P < 0.01 for both).Five patients underwent protein A immunoadsorption therapy. The effect of protein A immunoadsorption on platelet activation before, during and after 18 treatments in these patients was studied and patients were followed‐up to assess clinical outcome. Platelet‐associated immunoglobulin measurements were made before and at the end of six treatments.Platelet activation decreased after immunoadsorption. P‐selectin expression fell significantly; pre‐ and post‐treatment median values differed by 15.5%, P < 0.01, for GP53 the difference was 2.5.%, P = NS. A reduction in both platelet‐associated IgG (median reduction of 11.8 ng/106 platelets, P = 0.08) and IgM (7.6 ng/106 platelets, P = 0.06) was recorded.
Cytomegalovirus infection in recipients of related and unrelated donor bone marrow transplants: no evidence of increased incidence in patients receiving unrelated donor grafts
Authors: Foot  , Pamphilon  , Caul  , Roome  , Hunt  , Cornish  , Oakhill  
Published: March 2003

Recent reports suggest an increased incidence of cytomegalovirus (CMV) infection in recipients of unrelated donor (UD) bone marrow transplantation (BMT).In this study we have collated the incidence of CMV infection and disease in sequential UD (n = 119) and related donor (RD; n = 79) BMT performed in a single institution over a 7‐year period. Low‐risk patients (CMV seronegative recipient and donor) accounted for 51% of UD BMT (n = 61) and 62% of RD BMT (n = 49), with CMV excretion documented in one RD BMT only. The remaining high‐risk patients received identical prophylaxis regimens with aciclovir and intravenous immunoglobulin (IVIG). Two groups consisting of 58 UD BMT (median age 9.0 years, range 0.7–45.3 years) and 30 RD BMT (median age 13.6 years, range 1.6–47.6 years) were analysed. CMV reactivation/re‐infection was documented in 15 UD BMT (26%) and 10 RD BMT (33%) (P = 0.72), and CMV disease in four UD BMT (8%) and four RD BMT (13%) (P = 0.533). In this series the risk of CMV excretion and disease following UD BMT was similar to that following RD BMT.
VLA‐4 is involved in the engraftment of the human pre‐B acute lymphoblastic leukaemia cell line NALM‐6 in SCID mice
Authors: Filshie Robin , Gottlieb David , Bradstock Kenneth 
Published: March 2003

Attachment of human pre‐B leukaemic cells to human or murine bone marrow stromal cells in vitro is largely mediated by the β1 integrin VLA‐4 binding to VCAM‐1. Cells subsequently migrate within the stroma, a process also involving VLA‐4.	A variant of the pre‐B acute lymphoblastic leukaemia cell line NALM‐6, designated 4A1, lacking expression of VLA‐4, was generated by radiation‐induced mutagenesis followed by several rounds of negative selection with immunomagnetic beads, fluorescence activated cell sorting and clonal expansion. In vitro assays using 4A1 cells showed reduced binding to, and migration under, the murine stromal line M2‐10B4.	Sublethally irradiated mice (n = 19) with severe combined immunodeficiency were injected intravenously with NALM‐6 cells. Animals developed signs of leukaemia with hind‐limb paralysis at a median of 30 d (95% confidence interval 28–30). Although there were no gross abnormal findings at autopsy, histological analysis revealed extensive marrow replacement and focal liver infiltration with leukaemic blasts, which were confirmed to be of human origin by flow cytometry. 12 mice were injected with a similar number of cells from the VLA‐4‐negative variant cell line 4A1. Six mice developed signs of leukaemia after 43–74 d, with the remaining six being free of signs of disease after > 100 d (P < 0.001). Mice in this group with leukaemia had a lower incidence of hind‐limb paralysis and less leukaemic infiltration in the marrow, but in some cases had large tumour nodules elsewhere. After a single 500 μg intraperitoneal injection of anti‐murine VCAM‐1 monoclonal antibody (MK2.7), five additional mice were injected with an identical number of wild‐type (VLA‐4+) NALM‐6. All animals developed signs of leukaemia after a similar period to those injected with wild‐type NALM‐6 only.	These results demonstrate that the β1 integrin VLA‐4 is involved in the engraftment of the pre‐B‐cell leukaemic cell line NALM‐6 in SCID mice, although the interaction with VCAM‐1 is unlikely to be the sole explanation.
Effect of 1‐β‐ D‐arabino‐furanosyl‐cytosine (ara‐C) induction of K562 cells on expression of Rh and other blood group active proteins
Authors: Wiener Edith , Shiels Allan , Wickramasinghe  , Avent  
Published: March 2003

K562 cells undergoing differentiation induced by 1‐β‐ D‐arabino‐furanosyl‐cytosine (ara‐C) were examined as a model for studying the biosynthesis and regulation of Rh and other blood group active membrane proteins. Untreated and ara‐C‐induced K562 cells were analysed for the expression of these proteins using monoclonal antibodies in combination with flow cytometry. The major membrane proteins glycophorins A and C remained unaltered upon induction by ara‐C. The display of LFA‐3 (CD58) and DAF (CD55) by uninduced K562 was one order of magnitude lower than that of the glycophorins; following ara‐C treatment there was a 50% rise in LFA‐3 but a modest decrease in the level of DAF expression. The expression by untreated K562 cells of Rh, Lutheran and Kell proteins as well as the Rh D antigen was low, whereas that of CD44 and band 3 protein was negligible. Following induction by ara‐C the levels of Rh and Kell proteins rose up to 7‐ and 3.5‐fold respectively, and there was an increase in RhD‐antigen expression. In contrast, ara‐C induction of K562 cells failed to augment their display of Lutheran, CD44 and band 3 proteins.Analysis of Rh transcripts following the purification and RT‐PCR analysis of K562 mRNA showed that uninduced K562 cells contain two distinct mRNAs corresponding to Rh Ce (1.8 kb) and Rh D (3.5 kb). The apparent concentration of each mRNA increased following induction with ara‐C. K562 plasma membranes also contained Rh polypeptides as determined by immunoblot analysis using anti‐Rh polypeptide rabbit polyclonal sera raised to Rh synthetic peptides. A novel hybrid Rh transcript corresponding to exons 1–4 of RHD and exons 5–10 of RHCE has been cloned and sequenced from ara‐C induced K562 cells, and may have arisen by general recombination between the RHD and RHCE genes.