bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the CYP2C19 oxidation polymorphism on fluoxetine metabolism in Chinese healthy subjects
Authors: Liu Zhao‐Qian , Cheng Ze‐Neng , Huang Song‐Lin , Chen Xiao‐Ping , Ou‐Yang Dong‐Sheng , Jiang Chang‐Hong , Zhou Hong‐Hao 
Published: March 2003

Aims  The study was designed to investigate whether genetically determined CYP2C19 activity affects the metabolism of fluoxetine in healthy subjects.Methods  A single oral dose of fluoxetine (40 mg) was administrated successively to 14 healthy young men with high (extensive metabolizers, n=8) and low (poor metabolizers, n = 6) CYP2C19 activity. Blood samples were collected for 5–7 half‐lives and fluoxetine, and norfluoxetine were determined by reversed‐phase high performance liquid chromatography.Results  Poor metabolizers (PMs) showed a mean 46% increase in fluoxetine peak plasma concentrations (Cmax, P < 0.001), 128% increase in area under the concentration vs time curve (AUC(0,∞), P < 0.001), 113% increase in terminal elimination half‐life (t½) (P < 0.001), and 55% decrease in CLo (P < 0.001) compared with extensive metabolizers (EMs). Mean ± (s.d) norfluoxetine AUC(0,192 h) was significantly lower in PMs than that in EMs (1343 ± 277 vs 2935 ± 311, P < 0.001). Mean fluoxetine Cmax and AUC(0,∞) in wild‐type homozygotes (CYP2C19*1/CYP2C19*1) were significantly lower than that in PMs (22.4 ± 3.9 vs 36.7 ± 8.9, P < 0.001; 732 ± 42 vs 2152 ± 492, P < 0.001, respectively). Mean oral clearance in individuals with the wild type homozygous genotype was significantly higher than that in heterozygotes and that in PMs (54.7 ± 3.4 vs 36.0 ± 8.7, P < 0.01; 54.7 ± 3.4 vs 20.6 ± 6.2, P < 0.001, respectively). Mean norfluoxetine AUC(0,192 h) in PMs was significantly lower than that in wild type homozygotes (1343 ± 277 vs 3163 ± 121, P < 0.05) and that in heterozygotes (1343 ± 277 vs 2706 ± 273, P < 0.001), respectively.Conclusions  The results indicated that CYP2C19 appears to play a major role in the metabolism of fluoxetine, and in particular its N‐demethylation among Chinese healthy subjects.
Plasma concentrations of haloperidol are related to CYP2D6 genotype at low, but not high doses of haloperidol in Korean schizophrenic patients
Authors: Roh Hyung‐Keun , Chung Jea‐Yon , Oh Dong‐Yul , Park Chang‐Shin , Svensson Jan‐Olof , Dahl Marja‐Liisa , Bertilsson Leif 
Published: March 2003

Aims  This study was carried out to evaluate the influence of CYP2D6 genotype on the steady state plasma concentrations of haloperidol and reduced haloperidol in Korean schizophrenic patients.Methods  One hundred and twenty Korean schizophrenic patients treated with various, clinically determined, doses of haloperidol (range 3–60, median 20 mg day−1) during monotherapy were recruited. CYP2D6 genotypes were determined by analysis of the CYP2D6*10 allele using allele‐specific PCR and the CYP2D6*5 allele by long‐PCR. Steady state plasma concentrations of haloperidol and reduced haloperidol were analysed by h.p.l.c.Results  Twenty‐three (19.2%), 60 (50.0%), 1 (0.8%), 33 (27.5%) and 3 patients (2.5%) possessed the CYP2D6 genotypes *1/*1, *1/*10, *1/*5, *10/*10 and *10/*5, respectively. The allele frequencies of CYP2D6*1, *10 and *5 were 44.6%, 53.8% and 1.7%, respectively. Significant relationships between dose and plasma concentrations of haloperidol (linear; r2 = 0.60, P < 0.0001) and reduced haloperidol (quadratic equation; r2 = 0.67) were observed. Overall, the concentrations normalized for dose (C/D) of haloperidol were significantly different between the CYP2D6*1/*1, *1/*10 and*10/*10 genotype groups (one‐way anova; P = 0.028). No significant differences between the genotype groups were found with respect to the C/D of reduced haloperidol (P = 0.755). However, in patients with daily doses less than 20 mg, significant differences in the C/D of haloperidol (P = 0.003), but not of reduced haloperidol, were found between the three major genotype groups. In patients with doses higher than 20 mg, no differences were found between the genotype groups for either haloperidol or reduced haloperidol. 68 patients (57%) used benztropine, an antimuscarinic agent. All four patients with a *5 allele (one together with *1 and three with *10) were found to use benztropine. The patients homozygous for the *1 allele seemed to need less benztropine than the patients with one or two mutated alleles (Fisher's exact test; P = 0.036).Conclusions  The dose‐corrected steady state plasma concentrations of haloperidol, but not of reduced haloperidol, were significantly different between the CYP2D6*1/*1, *1/*10 and *10/*10 genotype groups when doses lower than 20 mg haloperidol were given. No differences were found at higher doses. These results suggest the involvement of CYP2D6 in the metabolism of haloperidol at low doses of haloperidol (< 20 mg daily), while another enzyme, probably CYP3A4, contributes at higher doses.
Curtailing unnecessary vancomycin usage in a hospital with high rates of methicillin resistant Staphylococcus aureus infections
Authors: Kumana Cyrus R. , Ching Tai Yin , Kong Yvonne , Ma Evelyn C. W. , Kou Maybelle , Lee Rodney A. , Cheng Vincent C. C. , Chiu Susan S. , Seto Wing‐Hong 
Published: March 2003

Aims  To implement and monitor the effectiveness of a strategy to curb unnecessary use of vancomycin and teicoplanin for inpatients in a teaching hospital/tertiary referral centre where 33% of S. aureus isolates (72% from ICU patients) were methicillin resistant.Methods  A sample of 182 vancomycin/teicoplanin inpatient prescriptions surveyed, revealed that only 31 (17%) conformed with Centre for Disease Control (CDC) guidelines. Following education (ward‐rounds, bulletins) on appropriate CDC based guidelines for prescribing glycopeptides directed at relevant clinicians, ‘Immediate Concurrent Feedback’ (ICF) was gradually deployed throughout the hospital. This entailed review of respective inpatient records on the next working day. If the indication was deemed not to conform with our guidelines, the prescriber was issued a memo (copied to the supervising doctor). Each memo detailed the ‘errant’ incident, listed appropriate indications and explicitly advised desisting from such prescribing and suggested alternative therapy if necessary. Corresponding glycopeptide usage data for our hospital and others in Hong Kong were retrieved and analysed as were samples of records of our inpatients with staphylococcal septicaemia (pre and during ICF).Results  Compared with baseline values, during 2 years of ICF, inpatient prescribing of vancomycin and teicoplanin deemed to conform increased to 71% (773/1086); difference 54% (P < 0.0001, 95% CIs 47–62%). Corresponding average monthly usage (DDDs/1000 admissions) decreased from 76 (pre‐ICF) to 45; mean difference 31 (P < 0.0001, 95% CIs 24, 38). Mortality from staphylococcal bacteraemia remained unchanged. No comparable changes in glycopeptide usage ensued in comparator hospitals.Conclusions  ICF can be used safely to curb irrational overuse of vancomycin and teicoplanin in a hospital with high methicillin resistant S. aureus infection rates.
Population pharmacokinetics and pharmacodynamics of oral etoposide
Authors: Toffoli Giuseppe , Corona Giuseppe , Sorio Roberto , Robieux Isabelle , Basso Barbara , Colussi Anna Maria , Boiocchi Mauro 
Published: March 2003

Aims  To study the population pharmacokinetics and pharmacodynamics of oral etoposide in patients with solid tumours.Methods  A prospective, open label, cross‐over, bioavailability study was performed in 50 adult patients with miscellaneous, advanced stage solid tumours, who were receiving oral (100 mg capsules) etoposide for 14 days and i.v. (50 mg) etoposide on day 1 or day 7 in randomised order during the first cycle treatment. Total and unbound etoposide concentration were assayed by h.p.l.c. Population PK parameters estimation was done by using the P‐Pharm software (Simed). Haematological toxicity and tumour response were the main pharmacodynamic endpoints.Results  Mean clearance was 1.14 l h−1 (CV 25%). Creatinine clearance was the only covariable to significantly reduce clearance variability (residual CV 18%). (CL = 0.74 + 0.0057 CLCR; r2 = 0.32). Mean bioavailability was 45% (CV 22%) and mean protein binding 91.5% (CV 5%). Exposure to free, pharmacologically active etoposide (free AUC p.o.) was highly variable (mean value 2.8 mg l−1 h; CV 64%; range 0.4–9.5). It decreased with increased creatinine clearance and increased with age which accounted for 9% of the CV. Mean free AUC p.o. was the best predictor of neutropenia. Free AUC50 (exposure producing a 50% reduction in absolute neutrophil count) was 1.80 mg l−1 h. In patients with lung cancer, the free AUC p.o. was higher in the two patients with responsive tumour (5.9 mg l−1 h) than in patients with stable (2.1 mg l−1 h) or progressive disease (2.3 mg l−1 h) (P = 0.01).Conclusions  Exposure to free etoposide during prolonged oral treatment is highly variable and is the main determinant of pharmacodynamic effects. The population PK model based on creatinine clearance is poorly predictive of exposure. Therapeutic drug monitoring would be necessary for dose individualization or to study the relationship between exposure and antitumour effect.
A rapid screening method for a single nucleotide polymorphism (SNP) in the human MOR gene
Authors: Grösch Sabine , Niederberger Ellen , Lötsch Jörn , Skarke Carsten , Geisslinger Gerd 
Published: March 2003

Aims  Genetic association studies have suggested that the single nucleotide polymorphism (SNP) at position 118 of the human µ‐opioid receptor (MOR) gene could be a potential risk factor for drug treatment variability in patients. Therefore, we wanted to develop a fast and reliable detection method for this SNP which is applicable in a clinical setting.Methods  To detect the polymorphism at position A118→G in the human MOR gene we used the fluorescence resonance energy transfer (FRET)‐PCR technique with subsequent melting curve analysis.Results  The polymorphism at position A118→G in the human MOR gene could be clearly discriminated with melting peak temperatures of 69.8 ° C and 63.8 ° C, corresponding to the wild type and mutated MOR allele, respectively. The results from FRET‐PCR were validated by sequencing and restriction‐fragment length polymorphism (RFLP). Screening of blood samples from 100 subjects showed an allelic distribution for the human MOR alleles of 79% (homozygous wild type), 20% (heterozygous) and 0.9% (homozygous mutated).Conclusions  The FRET‐PCR protocol for detection of the human MOR gene polymorphism at position 118 offers a rapid and reliable method which could be used for population screening of this and other genes.
Activated charcoal alone or after gastric lavage: a simulated large paracetamol intoxication
Authors: Christophersen A. B. , Levin D. , Hoegberg L. C. G. , Angelo H. R. , Kampmann J. P. 
Published: March 2003

Aims  Activated charcoal is now being recommended for patients who have ingested potentially toxic amounts of a poison, where the ingested substance adsorbs to charcoal. Combination therapy with gastric lavage and activated charcoal is widely used, although clinical studies to date have not provided evidence of additional efficacy compared with the use of activated charcoal alone. There are also doubts regarding the efficacy of activated charcoal, when administered more than 1 h after the overdose. The aim of this study was to examine if there was a difference in the effect of the two interventions 1 h post ingestion, and to determine if activated charcoal was effective in reducing the systemic absorption of a drug, when administered 2 h post ingestion.Methods  We performed a four‐limbed randomized cross‐over study in 12 volunteers, who 1 h after a standard meal ingested paracetamol 50 mg kg−1 in 125 mg tablets to mimic real‐life, where several factors, such as food, interfere with gastric emptying and thus treatment. The interventions were activated charcoal after 1 h, combination therapy of gastric lavage followed by activated charcoal after 1 h, or activated charcoal after 2 h. Serum paracetamol concentrations were determined by h.p.l.c. Percentage reductions in the area under the curve (AUC) were used to estimate the efficacy of each intervention (paired observations).Results  There was a significant (P<0.005) reduction in the paracetamol AUC with activated charcoal at 1 h (median reduction 66%, 95% confidence intervals 49, 76) compared with controls, and a significant (P<0.01) reduction for gastric lavage followed by activated charcoal at 1 h (median reduction 48.2%, 95% confidence interval 32.4, 63.7) compared with controls. There was no significant difference between the two interventions (95% confidence interval for the difference −3.8, 34.0). Furthermore, we found a significant (P<0.01) reduction in the paracetamol AUC when activated charcoal was administered 2 h after tablet ingestion when compared with controls (median 22.7%, 95% confidence intervals 13.6–34.4).Conclusions  These results suggest that combination treatment may be no better than activated charcoal alone in patients presenting early after large overdoses. The effect of activated charcoal given 2 h post ingestion is substantially less than at 1 h, emphasizing the importance of early intervention.
Chronic Tension-Type Headache in Children and Adolescents
Authors: Abu-Arafeh Ishaq 
Published: March 2003

In this study, the causes, predisposing factors and clinical features of chronic daily headache in children and adolescents were studied within the population of patients attending a specialist headache. The International Headache Society's (IHS) criteria for the diagnosis of chronic tension type headache (CTTH) were assessed for their applicability in the paediatric age group. Over a period of three years, demographic and clinical data were collected prospectively on all children who attended the clinic and suffered from daily attacks of headache. One hundred and fifteen children and adolescents (32% of all clinic population) had chronic daily headache, of whom 93 patients (81%) fulfilled the IHS criteria for the diagnosis of CTTH. They were between 3-15 years of age (mean: 11.1, SD: 2.3) and their female to male ratio was 1.2: 1. Around one third of the patients also suffered from migraine (mainly migraine without aura). The headache was described as mild in 60.9%, moderate 36.5% and severe 2.6%. Headache was located at the forehead in 53% or over the whole of the head in 29.6%. Pain was described as ‘just sore’ or dull by 73.9%. During attacks of headache, at least half the patients reported light intolerance, noise intolerance, anorexia or nausea. Thirty-two percent of patients had at least one underlying chronic disease that may have contributed to the pathogenesis of the CTTH. Eleven percent had serious stressful events related to family illnesses and in four patients headaches were triggered by family bereavement. Fourteen percent were investigated with neuroimaging and 22% were referred for clinical psychology assessment and management. In conclusion, CTTH is a common cause of headache in children attending a specialist headache clinic. The clinical features closely match those of adult population and the IHS criteria for the diagnosis of CTTH can be adapted for use in children. Predisposing stressful risk factors, physical or emotional, are present in a large proportion.
Global motion integration in the cat's lateral posterior‐pulvinar complex
Authors: Dumbrava Daniela , Faubert Jocelyn , Casanova Christian 
Published: March 2003

AbstractOur laboratory previously showed that thalamic neurons in an extrageniculate nucleus, the lateral posterior‐pulvinar complex (LP‐pulvinar) could perform higher‐order neuronal operations that had until then only been attributed to higher‐level cortical areas. To further assess the role of the thalamus in the analysis of complex percepts, we have investigated whether neurons in the LP‐pulvinar complex can signal the direction of motion of random‐dot kinematograms wherein the individual elements of the pattern do not provide coherent motion cues. Our results indicate that a subset of LP‐pulvinar cells can integrate the displacement of individual elements into a global motion percept and that their large receptive fields permit the integration of motion for elements separated by large spatial intervals. We also found that almost all of the global motion‐sensitive neurons were not systematically pattern‐motion‐selective when tested with plaid patterns. The results indicate that LP‐pulvinar cells can perform the higher‐level spatio‐temporal integration required to detect the global displacement of objects in a complex visual scene, further supporting the notion that extrageniculate thalamic cells are involved in higher‐order motion processing. Furthermore, these results provide some evidence that there may be specialized mechanisms for processing different types of complex motion within the LP‐pulvinar complex.
Feeding suppression by fibroblast growth factor‐1 is accompanied by selective induction of heat shock protein 27 in hypothalamic astrocytes
Authors: Suzuki Seigo , Li Ai‐Jun , Ishisaki Akira , Hou Xiaogang , Hasegawa Mamoru , Fukumura Masayuki , Akaike Toshihiro , Imamura Toru 
Published: March 2003

AbstractIt has been suggested that fibroblast growth factor (FGF)‐1 serves as a physiological satiety factor in the hypothalamus, although the molecular mechanism underlying such a function is poorly understood. To gain additional insight into this issue, we used a Sendai virus (SeV) gene expression system in rats to explore genes differentially expressed subsequent to expression of FGF‐1. Using cDNA arrays, we determined that infusion of FGF‐1/SeV into one lateral ventricle induced selective expression of heat shock protein (HSP) 27 in the hypothalamus. Whereas FGF‐1 expression was restricted to the ependymal cell layer of the cerebral ventricles, HSP27 was more widely expressed in astrocytes residing in the surrounding periventricular region. Similarly, infusion of FGF‐1 polypeptide into a lateral ventricle induced dose‐dependent HSP27 expression in periventricular astrocytes surrounding the third ventricle, with maximum mRNA levels being attained 6 h after infusion. This induction of HSP27 was accompanied by a significant suppression of feeding behaviour. Interestingly, suppression of feeding caused by intracerebro ventricular infusion of ciliary neurotrophic factor was also accompanied by induction of HSP27 in periventricular astrocytes, but suppression of feeding caused by infusion of leptin was not. It therefore appears that suppression of feeding by FGF‐1 is accompanied by selective induction of HSP27 expression in hypothalamic astrocytes surrounding the third ventricle, and that this response may be a key component of the mechanism by which appetite is regulated by FGF‐1.
Survival from out‐of‐hospital cardiac arrest in the Geelong region of Victoria, Australia
Authors: Jennings Paul , Pasco John 
Published: March 2003

AbstractObjective:To study the outcome from prehospital cardiac arrest managed by ambulance personnel, and to examine overall survival rates from successful resuscitation.Methods:A retrospective analysis was made of 115 patient care records of prehospital cardiac arrests with attempted resuscitation between July 1996 and September 1999. All cases had a presumed primary cardiac cause for their cardiac arrest.Results:Overall survival, defined as admitted to hospital alive, was 22 subjects (19.1%), with five subjects (4.3%) being discharged from hospital neurologically intact. Of the patients who survived to the emergency department, six (5%) had initially presented in pulseless electrical activity and 16 (14%) presented with ventricular fibrillation. No patients prsented with ventricular tachycardia and no survivors presented in asystole. Median response interval from time of call to arrival of initial crew at patient’s side was 9 min. No patients survived when response interval was greater than 14 min. Bystander cardiopulmonary resuscitation was being performed on 55 patients (48%) on arrival of initial ambulance crew; 68.2% of patients surviving to hospital having had bystander cardiopulmonary resuscitation.Conclusion:Decreasing time delays in accessing the patient is crucial to improving outcome in out‐of‐hospital cardiac arrest.
Ethical relationships in paediatric emergency medicine: Moving beyond the dyad
Authors: Bridges John , Hanson Ralph , Little Miles , Flannigan Alison Choy , Fairley Michael , Haywood Leigh 
Published: March 2003

AbstractMost areas of health‐services research concentrate on a dyadic relationship between doctor and patient. In paediatric emergency medicine it may be necessary to focus on a more complicated relationship because the parents of the child play an important role in the delivery of medical services. This paper discusses the ethical principles in paediatric emergency medicine from the perspective of five disciplines: health economics, paediatrics, medical ethics, law and mental health. The general consensus is that the traditional dyadic model is inadequate and that a more complicated relationship is needed for the paediatric emergency setting, such as triadic, multiple‐dyadic or polyadic. Such models allow the inclusion of the parents and possibly other family members, medical providers and community members. If the paediatric setting is considered in such a framework, it may be possible to deliver a more socially beneficial medical service.
Acute opioid withdrawal in the emergency department: Inadvertent naltrexone abuse?
Authors: Bristow Katherine , Meek Robert , Clark Nicholas 
Published: March 2003

AbstractFrom July 1999 it became evident that a rising number of heroin users were presenting to the Dandenong Hospital Emergency Department with a rapid onset, florid opioid withdrawal syndrome following the intravenous injection of what they had believed to be heroin. We suspect that the injected substance was in fact naltrexone. This paper describes two such cases and reviews the literature on naltrexone. Recommendations regarding the management of the acute opioid withdrawal syndrome are made.
Effects of intravenous injection of Salmonella antigen on the distribution of major histocompatibility complex class II positive cells in the ovarian follicles of hens
Authors: YOSHIMURA Yukinori , TAKATA Tomomasa 
Published: March 2003

ABSTRACTThe goal of this study was to determine whether the distribution of major histocompatibility complex class II positive (MHC class II+) cells was affected by foreign agents in the blood circulation. White Leghorn layers were injected intravenously with or without formalin fixed Salmonella paratyphi, and the area of MHC class II+ cells in the ovarian follicles, which included the largest (F1) and third largest follicles (F3), white follicles (WF) and cortical follicles, was examined by immunocytochemistry. The immunoreaction products for MHC class II were observed in cells of the thecal layer of all follicles in both treated and control birds. Salmonella paratyphi antigen caused a significant increase in the area of MHC class II+ cells in the theca of the F1, F3 and WF, but not in the cortical follicles. The results suggest that the MHC class II+ cells in the theca increase in response to circulating foreign agents, and play a significant role in ovarian local immunity.
Comparison of the antioxidant activities of 22 commonly used culinary herbs and spices on the lipid oxidation of pork meat
Authors: TANABE Hisako , YOSHIDA Masami , TOMITA Nanae 
Published: March 2003

ABSTRACTThe antioxidant activities of 22 selected culinary herbs and spices (i.e. ginger, cinnamon, clove, bay, sage, rosemary, thyme, savory, oregano, sweet basil, parsley, coriander, tarragon, sansho, allspice, cumin, black and white peppercorns, nutmeg, caraway, dill and fennel) when they were added to pork homogenate were measured and expressed as a thiobarbituric acid (TBA) value. The addition of liquid extracts of all the herbs and spices significantly suppressed lipid oxidation of the pork, especially the extracts of sansho, sage and ginger, which showed the strongest inhibition of lipid oxidation.