bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consultant child and adolescent psychiatrists' knowledge of and attitude to the use of legislation concerning young people with psychiatric disorder
Authors: Mears Alex , White Richard , Lelliott Paul 
Published: September 2003

Aims and MethodThis study aimed to examine in-patient child and adolescent consultant psychiatrists' knowledge of and attitude to the Mental Health Act 1983 (MHA), the Children Act 1989 and issues around consent. A questionnaire form was sent to all in-patient consultants in England and Wales.ResultsThe consultants who responded (n=51, 67%) reported a desire for more training in legal issues. Knowledge of the MHA was better than for the Children Act 1989; those who used the MHA at least once every 6 months scored more correct answers to questions about the MHA than did those who used it less frequently or never.Clinical ImplicationsAlthough the study indicates specific gaps in knowledge, the main message is that training should consider the legal framework as a whole, with an emphasis on practical issues about its application in the in-patient setting.
Setting up clinical audit in a psychodynamic psychotherapy service: a pilot study
Authors: Adelman Simon , Ward Anne , Davison Sue 
Published: September 2003

Aims and MethodClinical governance implies a need to engage in a demonstrable form of clinical audit. We decided to pilot a pre–post-therapy questionnaire study, involving both therapists and patients, with the aim of assessing its feasibility as a routine measure of outcome in our service. Questionnaires were chosen to reflect both the symptom profile Clinical Outcomes in Routine Evaluation (CORE) and the general level of functioning Global Assessment of Functioning Scale (GAF). The patients were also questioned about their satisfaction with the therapy.ResultsOf 53 eligible patient–therapist pairs, 26 patients and 19 therapists responded pre-treatment (overall 51% response rate). The mean (s.d.) CORE score per item was 1.93 (0.78), whereas the GAF score was 55 (15.2), somewhat belying the idea that psychotherapists only treat the ‘worried well’. The post-therapy response rate was poorer, rendering statistical analysis of change difficult to perform. The trend, however, was towards an improvement in both symptoms and level of functioning over the course of therapy.Clinical ImplicationsOur patient group presents with a considerable degree of impairment. Although the response rates in this pilot study were poor, the data trend suggests that patients do benefit from the treatment offered. The aims of the study were met in that implementation of a clinical audit process within our department is feasible and the data are obtainable. The main interest, however, lies in what we learned from the process. We offer a dynamic and practical assessment of the impediments encountered, with implications for how these might be confronted.
Clinical activity within a specialist mental health service for deaf people: comparison with a general psychiatric service
Authors: Appleford Jim 
Published: September 2003

Aims and MethodThis paper compares the case mix and clinical activity in a specialist mental health service for deaf people within a general psychiatric population, using ICD–10 diagnostic criteria.ResultsOut-patient and in-patient caseloads differ between the two services: 27% of the deaf out-patient caseload have schizophrenia, schizotypal and delusional disorders (compared with 19% of hearing patients) and 19% have neurotic, stress-related and somatoform disorders (compared with 8% of hearing patients). The general psychiatric service out-patient case-load had rates of 8% and 43% for bipolar affective disorder and unipolar depression, respectively, compared with 3% and 17% in the deaf group. Deaf patients have a mean length of stay of 59 days, compared with 30 days for the hearing group. In-patient treatment accounts for 89% of the annual treatment cost for the deaf patient population.Clinical ImplicationsExpansion of community services for deaf people as recommended by a recent Health Advisory Service report could reduce admission rates for deaf patients, delivering treatment benefits and cost savings.
Out-of-area placements: implications of psychiatric services in learning disability
Authors: Mitra Ipsita , Alexander Regi 
Published: September 2003

Aims and MethodWith an absence of appropriate residential services, people with learning disabilities are often placed outside their local areas and there is regularly no dialogue between the relevant health authorities prior to a placement being made. This survey from Leicestershire explored this issue by focusing on the catchment area covered by one consultant psychiatrist. Practice standards were formulated and compliance with these was examined.ResultsA total of 29 patients were identified as ‘out-of-area’ placements. They had high psychiatric morbidity, exhibited significant degrees of aggression and needed a high level of professional input. The suggested practice standards were met by less than 10%.Clinical ImplicationsIn parts of the country where a large number of ‘specialist’ residential homes have opened, there has been an unplanned increase in the workload of local learning disability/ mental health services. This can compromise patient care and there is an urgent need for health authorities to address this issue.
The new MRCPsych Part II exam – golden tips on how to pass
Authors: Naeem Asim , Rutherford Joan , Kenn Chris 
Published: September 2003

“Examinations are formidable even to the best prepared, for the greatest fool may ask more than the wisest man can answer!” (Charles Kaleb Cotton)The MRCPsych Part II examination remains an important milestone (or barrier) for those wishing to pursue higher specialist training in psychiatry. There have been significant changes to the structure of this complex exam, with modification of the multiple choice question (MCQ) and essay papers and the introduction of the critical review paper. With pass rates varying from 39–49% over recent years, it clearly represents a significant hurdle for psychiatric trainees. This article aims to provide specific advice on how best to approach and tackle each of the components of the exam.
High-Dose Therapy Improves Progression-Free Survival and Survival in Relapsed Follicular Non-Hodgkin’s Lymphoma: Results From the Randomized European CUP Trial
Authors: Schouten Harry C. , Qian Wendi , Kvaloy Stein , Porcellini Adolfo , Hagberg Hans , Johnsen Hans Erik , Doorduijn Jeanette K. , Sydes Matthew R. , Kvalheim Gunnar 
Published: September 2003

Purpose: To determine, in a randomized clinical trial, whether high-dose therapy (HDT) followed by autologous stem-cell transplantation is more effective than standard treatment with regard to progression-free survival (PFS) and overall survival (OS) in patients with relapsed follicular non-Hodgkin’s lymphoma; and to assess the additional value of B-cell purging of the stem-cell graft with regards to PFS and OS. Patients and Methods: Patients received three cycles of chemotherapy. Responding patients with limited bone marrow infiltration were eligible for random assignment to three further cycles of chemotherapy (C), unpurged HDT (U), or purged HDT (P). Results: Between August 1993 and April 1997, 140 patients were registered from 36 centers internationally, and 89 were randomly assigned. Reasons for not randomizing included patient refusal, early progression, or death on induction therapy. With a 69-month median follow-up, the log-rank P value for PFS and OS were .0037 and .079, respectively. For PFS, the hazard ratios (95% CIs) for U versus C, P versus C, and P versus U were 0.33 (0.16 to 0.70), 0.38 (0.19 to 0.79), and 1.02 (0.51 to 2.05), respectively. The hazard ratio (95% CI) for C versus U + P was 0.30 (0.15 to 0.61). Hazard ratios (95% CIs) for OS were 0.43 (0.18 to 1.06), 0.43 (0.18 to 1.02), and 0.72 (0.32 to 1.63). For C versus U + P, the hazard ratio (95% CI) was 0.40 (0.18 to 0.89). Kaplan-Meier estimates (95% CIs) of 2-year PFS for C, U, and P were 26% (8% to 44%), 58% (37% to 79%), and 55% (34% to 75%), respectively. OS at 4 years for C, U, and P are 46% (25% to 67%), 71% (52% to 91%), and 77% (60% to 95%) respectively. Conclusion: HDT significantly improves PFS and OS. There is no clear evidence of benefit through purging.
Pharmacokinetics, Safety, and Efficacy of Trastuzumab Administered Every Three Weeks in Combination With Paclitaxel
Authors: Leyland-Jones Brian , Gelmon Karen , Ayoub Jean-Pierre , Arnold Andrew , Verma Shail , Dias Reg , Ghahramani Parviz 
Published: September 2003

Purpose: This phase II study evaluated the pharmacokinetics and safety of trastuzumab and paclitaxel given every 3 weeks to women with human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic breast cancer. Patients and Methods: Thirty-two patients received a loading dose of trastuzumab 8 mg/kg intravenously (day 1) and paclitaxel 175 mg/m2 (day 0). Thereafter, trastuzumab 6 mg/kg was administered on the same day as paclitaxel 175 mg/m2 every 3 weeks for seven cycles. In responding patients, trastuzumab monotherapy every 3 weeks was then continued until disease progression or patient withdrawal. Results: Trastuzumab trough levels were more than 20 μg/mL by the end of cycle 1. The half-life of trastuzumab was estimated to be 18 to 27 days, although this may be an underestimate. The combination of paclitaxel and trastuzumab was generally well tolerated, with no unexpected toxicities and no pharmacokinetic interaction. The most common adverse events were myalgia, paresthesias, alopecia, arthralgia, and fatigue. Events associated with trastuzumab included infusion-related reactions and cardiac dysfunction. Ten patients had a ≥ 15% decrease in ejection fraction, but only one had symptomatic heart failure. The investigator-assessed objective response rate was 59% (four complete and 15 partial responses) and seven patients (22%) had stable disease. The median duration of response was 10.5 months and median time to progression was 12.2 months. Conclusion: Additional investigation of trastuzumab administered every 3 weeks is warranted. In combination with paclitaxel, it is generally well tolerated. Plasma trastuzumab trough levels and clinical response rates compare favorably with those achieved with the standard weekly trastuzumab regimen plus chemotherapy. The presence of trastuzumab does not alter exposure to paclitaxel.
Membrane Estrogen Receptor-Dependent Extracellular Signal-Regulated Kinase Pathway Mediates Acute Activation of Endothelial Nitric Oxide Synthase by Estrogen in Uterine Artery Endothelial Cells
Authors: Chen Dong-bao , Bird Ian M. , Zheng Jing , Magness Ronald R. 
Published: September 2003

Abstract
Rapid uterine vasodilatation after estrogen administration is believed to be mediated by endothelial production of nitric oxide (NO) via endothelial NO synthase (eNOS). However, the mechanism(s) by which estrogen activates eNOS in uterine artery endothelial cells (UAEC) is unknown. In this study, we observed that estradiol-17β (E2) and E2-BSA rapidly (&lt;2 min) increased total NOx production in UAEC in vitro. This was associated with rapid eNOS phosphorylation and activation but was unaltered by pretreatment with actinomycin-D. estrogen receptor-α protein was detectable in isolated plasma membrane proteins by immunoblotting, and E2-BSA-fluorescein isothiocyanate binding was evident on the plasma membrane of UAEC. E2 did not mobilize intracellular Ca2+, but E2 and ionomycin in combination induced greater eNOS phosphorylation than either E2 or ionomycin alone. E2 did not stimulate rapid Akt phosphorylation. E2 stimulated rapid ERK2/1 activation in a time- and dose-dependent manner, with maximal responses observed at 5–10 min with E2 (10 nm to 1 μm) treatment. Acute activation of eNOS and NOx production by E2 could be inhibited by PD98059 but not by LY294002. When E2-BSA was applied, similar responses in NOx production, eNOS, and ERK2/1 activation to those of E2 were achieved. In addition, E2 and E2-BSA-induced ERK2/1 activation and ICI 182,780 could inhibit NOx production by E2. Thus, acute activation of eNOS to produce NO in UAEC by estrogen is at least partially through an ERK pathway, possibly via estrogen receptor localized on the plasma membrane. This pathway may provide a novel mechanism for NO-mediated rapid uterine vasodilatation by estrogen.
Hypothalamic-Pituitary Cytokine Network
Authors: Kariagina Anastasia , Romanenko Dmitry , Ren Song-Guang , Chesnokova Vera 
Published: September 2003

Abstract
Cytokines expressed in the brain and involved in regulating the hypothalamus-pituitary-adrenal (HPA) axis contribute to the neuroendocrine interface. Leukemia inhibitory factor (LIF) and LIF receptors are expressed in human pituitary cells and murine hypothalamus and pituitary. LIF potently induces pituitary proopiomelanocortin (POMC) gene transcription and ACTH secretion and potentiates CRH induction of POMC. In vivo, LIF, along with CRH, enhances POMC expression and ACTH secretion in response to emotional and inflammatory stress. To further elucidate specific roles for both CRH and LIF in activating the inflammatory HPA response, double-knockout mice (CRH/LIFKO) were generated by breeding the null mutants for each respective single gene. Inflammation produced by ip injection of lipopolysaccharide (1 μg/mouse) to double CRH and LIF-deficient mice elicited pituitary POMC induction similar to wild type and markedly higher than in single null animals (P &lt; 0.0.01). Double-knockout mice also demonstrated robust corticosterone response to inflammation. High pituitary POMC mRNA levels may reflect abundant TNFα, IL-1β, and IL-6 activation observed in the hypothalamus and pituitary of these animals. Our results suggest that increased central proinflammatory cytokine expression can compensate for the impaired HPA axis function and activates inflammatory ACTH and corticosterone responses in mice-deficient in both CRH and LIF.
Influence of traditional Chinese anti-inflammatory medicinal plants on leukocyte and platelet functions
Authors: Prieto J M , Recio M C , Giner R M , Máñez S , Giner-Larza E M , Ríos J L 
Published: September 2003

Abstract
The enzymes 5-lipoxygenase and elastase are therapeutic targets in dermatological disorders such as psoriasis. Fifteen extracts from traditional Chinese medicinal plants used to treat topical inflammations were screened for their inhibitory effect on lipoxygenase, cyclooxygenase and elastase activity in intact leukocytes and platelets. Astragalus membranaceus, Forsythia suspensa and Poria cocos inhibited 5-lipoxygenase, with IC50 values of 141, 80 and 141 μg mL−1, respectively. The latter two species, along with Angelica dahurica and Angelica pubescens, also inhibited elastase (IC50 values of 80, 123, 68 and 93 μg mL−1, respectively), while A. pubescens, Atractylodes macrocephala, Lentinus edodes, Rehmannia glutinosa and Paeonia lactiflora selectively inhibited 12-(S)-HHTrE production, a valid marker of cyclooxygenase activity. The inhibition of phospholipase A2 activity by P. cocos is discussed. Dehydrotumulosic and pachymic acids, which have been isolated from P. cocos, were shown to inhibit leukotriene B4 release. The results indicate that both P. cocos and F. suspensa are potentially valuable species in the management of skin pathologies involving chronic inflammation.
Pharmacokinetic interaction between oltipraz and dimethyl-4,4‘-dimethoxy-5,6,5′,6’-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB) after single intravenous and oral administration to rats
Authors: Bae Soo Kyung , Kim Eun Jung , Chung Suk Jae , Kim Sang Geon , Lee Myung Gull 
Published: September 2003

Abstract
The aim of this study was to report the pharmacokinetic interaction between oltipraz (50 mg kg−1) and dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB, 10 mg kg−1) after single intravenous and oral administration to rats. After intravenous administration of oltipraz plus DDB, the area under the plasma concentration–time curve from time zero to time infinity (AUC) of oltipraz was significantly greater (1440 vs 1740 μg min mL−1) than that after oltipraz alone. This was not due to slower clearances of oltipraz after oltipraz plus DDB since the total body, renal and nonrenal clearances were comparable between the two groups of rats. It could be due to a decrease in tissue binding of oltipraz by DDB. The apparent volume of distribution at steady state (Vdss) of DDB was significantly smaller (7060 vs 4650 mL kg−1) than after oltipraz alone. After oral administration of oltipraz plus DDB, the AUC of olitpraz was also significantly greater (479 vs 583 μg min mL−1) than that after oltipraz alone. This was not due to increased absorption of oltipraz from the rat gastrointestinal tract after oltipraz plus DDB but again could be due to a decrease in Vdss of oltipraz by DDB. However, after both intravenous and oral administration, the pharmacokinetic parameters of DDB were comparable between DDB alone and DDB plus oltipraz, indicating that oltipraz did not greatly affect the pharmacokinetics of DDB in rats.
Effect of bupropion on CYP2B6 and CYP3A4 catalytic activity, immunoreactive protein and mRNA levels in primary human hepatocytes: comparison with rifampicin
Authors: Hesse Leah M , Sakai Yumiko , Vishnuvardhan Daesety , Li Albert P , von Moltke Lisa L , Greenblatt David J 
Published: September 2003

Abstract
Animals treated with multiple doses of bupropion have had increased bupropion clearance or increased liver weight, suggesting induction of drug-metabolizing activity. The possibility of cytochrome p450 (CYP) induction by bupropion (10 μM) was evaluated in-vitro by comparing catalytic activity, immunoreactive protein and CYP mRNA levels from human hepatocytes in primary culture versus cells treated with vehicle (0.5% methanol) and with rifampicin (rifampin) as a positive control. mRNA levels were analysed using a branched DNA luminescent assay. CYP2B6 activity, protein and mRNA levels were increased by 2.5, 1.5 and 2.1 fold, respectively, by 20 μM rifampicin. However, 10 μM bupropion minimally altered CYP2B6 (1.4, 1.1, 0.8 fold). Although CYP3A4 activity, protein, and mRNA levels were increased by 4.0, 2.3, and 14.0 fold, respectively, by 20 μM rifampicin, 10 μM bupropion minimally altered CYP3A4 (1.4, 1.0, 0.8 fold). Rifampicin (20 μM) increased CYP2E1 protein by 2.1 fold, while 10 μM bupropion minimally altered CYP2E1 protein (1.2 fold). Overall, results of this study suggest that multiple doses of bupropion are not likely to induce CYP2B6, 3A4 or 2E1 in-vivo in man.
Quantitative evaluation of isothiocyanates as substrates and inhibitors of P-glycoprotein
Authors: Barecki-Roach Mary , Wang Er-jia , Johnson William W 
Published: September 2003

Abstract
The ATP-binding cassette transporter P-glycoprotein (P-gp) exerts a critical role in the systemic disposition of, and exposure to, lipophilic and amphipathic drugs, carcinogens, toxins and other xenobiotics. The ability of P-gp to transfer a wide variety of structurally unrelated compounds from the cell interior across the membrane bilayer remains intriguing. Since dietary chemicals in cruciferous and several other foods appear to exert anticarcinogenic effects by inducing phase II enzymes and inhibiting some phase I enzymes, the isothiocyanate constituents are frequently studied for interactions with various biomacromolecules as well as cytotoxins or isolated cells. Several prominent dietary isothiocyanates were characterized for their interaction with P-gp and their specific effects on the P-gp export activity of several marker substrates. Some of these compounds inhibit the active P-gp-mediated efflux of the fluorescent markers LDS-751 and daunorubicin with low potency, with the most potent among them, phenethyl isothiocyanate, inhibiting transport of the LDS-751 substrate with an IC50 of ˜240 μM. Overall, these isothiocyanates are unlikely to impede the xenobiotic defence function of P-gp even in the intestine where the concentrations are potentially high.
Quantification of crystalline forms in active pharmaceutical ingredient and tablets by X-ray powder diffraction
Authors: Cooper V Brett , Pearce Gareth E S , Petts Catherine R 
Published: September 2003

Abstract
A Merck development compound was known to exist in several polymorphic forms, hydrates and solvates. The polymorphic forms were characterized and the most thermodynamically stable form at room temperature was identified and taken into development. During routine stability analysis it became apparent that the crystalline form of the compound was converting from one form to another in tablets that were stored at 40° C/75% relative humidity in open containers. This form conversion did not occur when the active pharmaceutical ingredient (API) alone was stored under these conditions. This paper describes the development and application of an X-ray powder diffraction method for the determination of the relative content of the two crystalline forms in API and within the final formulation. Results of monitoring the crystalline form conversion are reported and a possible mechanism of conversion is postulated.
Effects of surface roughness and chrome plating of punch tips on the sticking tendencies of model ibuprofen formulations
Authors: Roberts Matthew , Ford James L , MacLeod Graeme S , Fell John T , Smith George W , Rowe Philip H 
Published: September 2003

Abstract
The sticking of three model ibuprofen–lactose formulations with respect to compaction force and the surface quality of the upper punch were assessed. Compaction was performed at 10, 25 or 40 kN using an instrumented single-punch tablet press. Two sets of 12.5-mm flat-faced punches were used to evaluate the influence of surface quality. A third set of chrome-plated tooling was also used. Surface profiles (Taylor Hobson Talysurf 120) of the normal tooling upper punches indicated a large difference in quality. The punches were subsequently classified as old (Ra = 0.33 μm) or new (Ra = 0.04 μm) where Ra is the mean of all positive deviations from zero. Surface profiles of sample tablets were also obtained. Following compaction, ibuprofen attached to the face was quantified by spectroscopy. Punch surface roughness, compaction force and the blend composition were all significant factors contributing to sticking. Chrome plating of punch faces increased sticking at a low compaction force but decreased sticking at higher forces. Surface roughness of the tablets did not correlate with the corresponding data for sticking, indicating that this is not a suitable method of quantifying sticking.
Comparative study of eight well-known polyphenolic antioxidants
Authors: Cos P , Hermans N , Calomme M , Maes L , De Bruyne T , Pieters L , Vlietinck A J , Berghe D Vanden 
Published: September 2003

Abstract
Eight antioxidants from five different polyphenolic classes (cinnamic acids, benzoic acids, flavonoids, proanthocyanidins and stilbenes), and the water-soluble vitamin E derivative trolox were examined for their antioxidant activity in-vitro. In addition, the compounds were tested for their cytotoxicity on growing fibroblasts and their inhibition of the classical pathway of the complement system. Procyanidin C1 was shown to be a good scavenger of both DPPH* and HO*, and a strong inhibitor of lipid peroxidation and the classical pathway of the complement system. Consequently, procyanidin C1 was classified as the most promising antioxidant in-vitro of all compounds tested. In contrast, genistein exhibited a very low antioxidant activity in both the lipid peroxidation and the DPPH* scavenging assay, a high cytotoxicity and a low complement-inhibiting activity.