bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials
Authors: Adams Clive Elliott , Rathbone John , Thornley Ben , Clarke Mike , Borrill Jo , Wahlbeck Kristian , Awad A George 
Published: October 2005

Abstract

Background
Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo.

Methods
We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated.

Results
Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth.

Conclusion
It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations.
Phase III Study Comparing Standard Radiotherapy With or Without Weekly Oxaliplatin in Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma: Preliminary Results
Authors: Zhang Li , Zhao Chong , Peng Pei-Jian , Lu Li-Xia , Huang Pei-Yu , Han Fei , Wu Shao-Xiong 
Published: October 2005

Purpose A prospective, randomized, phase III study was performed to evaluate the feasibility and efficacy of concurrent weekly oxaliplatin with radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Patients and Methods From January 2001 to January 2003, 115 patients with locoregionally advanced NPC were randomly assigned to either radiotherapy (RT) alone (56 patients) or concurrent chemoradiotherapy (CCRT; 59 patients). All patient characteristics were well balanced in both arms. CCRT with oxaliplatin 70 mg/m2 weekly was administered for six doses from the first day of RT. Results All patients were eligible for toxicity and response analysis. Compliance with the protocol treatment was excellent, with 97% of patients completing all planned doses of oxaliplatin, and a lack of high-grade toxicity was observed. After a median follow-up time of 24 months, there was a significant difference in overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS) in favor of the CCRT arm. The 2-year OS rates were 100% for the CCRT arm and 77% for the RT arm (P = .01). The 2-year MFS rates were 92% for the CCRT arm and 80% for the RT arm (P = .02). The 2-year RFS rates were 96% for the CCRT arm and 83% for the RT arm (P = .02). Conclusion CCRT with weekly oxaliplatin is feasible and improves OS, MFS, and RFS rates in patients with locoregionally advanced NPC. Therefore, further randomized trials including oxaliplatin are warranted.
Feasibility of Withholding Antibiotics in Selected Febrile Neutropenic Cancer Patients
Authors: Nijhuis Claudi Oude , Kamps Willem A. , Daenen Simon M.G. , Gietema Jourik A. , van der Graaf Winette T.A. , Groen Harrie J.M. , Vellenga Edo , ten Vergert Els M. , Vermeulen Karin M. , de Vries-Hospers Hillie G. , de Bont Eveline S.J.M. 
Published: October 2005

Purpose To investigate the feasibility of withholding antibiotics and early discharge for patients with chemotherapy-induced neutropenia and fever at low risk of bacterial infection by a new risk assessment model. Patients and Methods Outpatients with febrile neutropenia were allocated to one of three groups by a risk assessment model combining objective clinical parameters and plasma interleukin 8 level. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk. Based on their interleukin-8 level, remaining patients were allocated to low or medium risk for bacterial infection. Medium-risk and high-risk patients received standard antibiotic therapy, whereas low-risk patients did not receive antibiotics and were discharged from hospital after 12 hours of a febrile observation. End points were the feasibility of the treatment protocol. Results Of 196 assessable episodes, 76 (39%) were classified as high risk, 84 (43%) as medium risk, and 36 (18%) as low risk. There were no treatment failures in the low-risk group (95% CI, 0% to 10%). Therefore, sensitivity of our risk assessment model was 100% (95% CI, 90% to 100%), the specificity, positive, and negative predictive values were 21%, 13%, and 100%, respectively. Median duration of hospitalization was 3 days in the low-risk group versus 7 days in the medium- and high-risk groups (P < .0001). The incremental costs of the experimental treatment protocol amounted to a saving of €471 (US $572) for every potentially low-risk patient. Conclusion This risk assessment model appears to identify febrile neutropenic patients at low risk for bacterial infection. Antibiotics can be withheld in well-defined neutropenic patients with fever.
Sustained Complete Molecular Remissions After Treatment With Imatinib-Mesylate in Patients With Failure After Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia: Results of a Prospective Phase II Open-Label Multicenter Study
Authors: Hess Georg , Bunjes Donald , Siegert Wolfgang , Schwerdtfeger Rainer , Ledderose Georg , Wassmann Barbara , Kobbe Guido , Bornhäuser Martin , Hochhaus Andreas , Ullmann Andrew J. , Kindler Thomas , Haus Ulrike , Gschaidmeier Harald , Huber Christoph , Fischer Thomas 
Published: October 2005

Purpose In the era of molecular therapy of chronic myelogenous leukemia (CML) applying BCR-ABL tyrosine kinase inhibitors, the usefulness of molecular end points, in particular, quantitative polymerase chain reaction (PCR) for BCR-ABL in monitoring responses has been broadly accepted. Therefore, we have designed a prospective phase II trial in CML, which, for the first time, evaluated the feasibility and safety of molecular end points as surrogate markers to guide through a stratified treatment algorithm within a multicenter trial. Patients and Methods As a clinical model, we adopted minimal residual disease (MRD) found in relapse after allogeneic stem cell transplantation (SCT) in CML. Forty-four patients were enrolled and received the BCR-ABL tyrosine kinase inhibitor imatinib (IM) at a starting dose of 400 mg/d. The quality of molecular responses achieved then decided on discontinuation of IM or dose escalation up to 800 mg/d, and finally, on application of donor lymphocyte infusions. Results Seventy percent of patients achieved a complete molecular response (CMR), defined as nested PCR-negativity for BCR-ABL in three consecutive samples. Interestingly, in four out of 10 patients who discontinued IM, CMR was durable even after cessation of IM with a median follow-up of 494 days. This suggests the possibility of long-term tumor control in a subset of patients. Conclusion The treatment strategy showed that IM treatment was well-tolerated and highly efficacious in MRD after allogeneic SCT. Moreover, this study demonstrated that evaluation of a molecular end point within a multicenter trial can be a safe and effective tool for clinical decision making.
Treatment With All-Trans Retinoic Acid and Anthracycline Monochemotherapy for Children With Acute Promyelocytic Leukemia: A Multicenter Study by the PETHEMA Group
Authors: Ortega Juan J. , Madero Luis , Martín Guillermo , Verdeguer Amparo , García Purificación , Parody Ricardo , Fuster José , Molines Antonio , Novo Andrés , Debén Guillermo , Rodríguez Antonia , Conde Eulogio , de la Serna Javier , Allegue María J. , Capote Francisco J. , González José D. , Bolufer Pascual , González Marcos , Sanz Miguel A. 
Published: October 2005

Purpose To analyze the simultaneous combination of all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for children with acute promyelocytic leukemia (APL). Patients and Methods Since November 1996, 66 children (younger than 18 years) with genetically proven APL received induction therapy with ATRA and idarubicin. Consolidation therapy consisted of three courses of anthracycline monochemotherapy. After November 1999, patients with intermediate and high risk of relapse received consolidation therapy with ATRA and slightly reinforced doses of idarubicin. Maintenance therapy consisted of ATRA and low-dose mercaptopurine and methotrexate. Results Thirty-nine girls (59%) and 27 boys (41%) were included in this study. The WBC count at presentation was more than 10 × 109/L in 26 patients (39%). Sixty-one children (92%) achieved complete remission (CR). Early deaths from hemorrhage and retinoic acid syndrome occurred in three patients and two patients, respectively. Toxicity was manageable during consolidation and maintenance therapy. No deaths in CR, clinical cardiomyotoxicity, or secondary malignancy occurred. Two patients had molecular persistence at the end of consolidation. Three clinical relapses and two molecular relapses were also observed. Apart from one molecular relapse, all these events occurred among children with hyperleukocytosis. The 5-year cumulative incidence of relapse was 17%, whereas disease-free and overall survival rates were 82% and 87%, respectively. Conclusion A high incidence of hyperleukocytosis in children with APL was confirmed. Besides low toxicity and a high degree of compliance, a risk-adapted therapy combining ATRA and anthracycline monochemotherapy showed an antileukemic efficacy comparable to those previously reported with other chemotherapy combinations in children.
Retrospective Analysis of Time to Recurrence in the ATAC Trial According to Hormone Receptor Status: An Hypothesis-Generating Study
Authors: Dowsett Mitch , Cuzick Jack , Wale Chris , Howell Tony , Houghton Joan , Baum Michael 
Published: October 2005

Purpose Arimidex, tamoxifen alone, or in combination (ATAC) trial of anastrozole (Arimidex) versus tamoxifen or a combination of the two in 9,366 postmenopausal patients with primary breast cancer found a significant improvement in disease-free survival and time to recurrence (TTR) for anastrozole compared with tamoxifen, that was restricted to patients with hormone receptor-positive (ie, estrogen receptor–positive [ER+] and/or progesterone receptor-positive [PgR+]) disease, the target population for these therapies. We retrospectively tested the hypothesis that this benefit might differ according to PgR status. Patients and Methods TTR was compared between the three treatment groups for subgroups defined by ER and PgR status using Cox's proportional hazards model, with and without adjustment for baseline variables. Results The unadjusted hazard ratio (HR) for anastrozole versus tamoxifen for TTR was 0.74 (95% CI, 0.64 to 0.87) for women with either ER+ or PgR+ tumors. In the ER+/PgR+ subgroup (n = 3,834) the HR was 0.84 (95% CI, 0.69 to 1.02) compared with 0.43 (95% CI, 0.31 to 0.61) in the ER+/PgR-negative (PgR–) subgroup (n = 880). In the adjusted model the HRs were 0.83 and 0.45, respectively. Conclusion Time to recurrence was longer for anastrozole- than tamoxifen-treated patients in both ER+/PgR+ and ER+/PgR– subgroups, but the benefit was substantially greater in the PgR– subgroup. As this was an “exploratory” analysis, this effect should be considered as hypothesis generating and assessed prospectively in other trials comparing the adjuvant use of an aromatase inhibitor with tamoxifen.
Retrospective Analysis of Topoisomerase IIa Amplifications and Deletions As Predictive Markers in Primary Breast Cancer Patients Randomly Assigned to Cyclophosphamide, Methotrexate, and Fluorouracil or Cyclophosphamide, Epirubicin, and Fluorouracil: Danish Breast Cancer Cooperative Group
Authors: Knoop Ann S. , Knudsen Helle , Balslev Eva , Rasmussen Birgitte B. , Overgaard Jens , Nielsen Kirsten V. , Schonau Andreas , Gunnarsdóttir Katrín , Olsen Karen E. , Mouridsen Henning , Ejlertsen Bent 
Published: October 2005

Purpose The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIα gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients. Patients and Methods In the Danish Breast Cancer Cooperative Group trial 89D, 980 pre- and postmenopausal primary patients were randomly allocated to either CMF (cyclophosphamide, methotrexate, and fluorouracil; n = 500) or CEF (cyclophosphamide, epirubicin, and fluorouracil; n = 480) times 9, between January 1990 and November 1999. Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions. Results HER2-positivity was found in 33% of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity. TOP2A changes were identified in 23% of the 773 investigated tumors: 12% had TOP2A amplifications and 11% had TOP2A deletions. We found that patients with TOP2A amplification had an increased recurrence-free (RFS; hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.78) and overall survival (OS; HR, 0.57; 95% CI, 0.29 to 1.13), respectively if treated with CEF compared with CMF, and that patients with TOP2A deletions had an almost identical hazard ratio (RFS: HR, 0.63; 95% CI, 0.36 to 1.11; OS: HR, 0.56; 95% CI, 0.30 to 1.04). This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms (RFS: HR, 0.90; 95% CI, 0.70 to 1.17; OS: HR, 0.88; 95% CI, 0.66 to 1.17). Conclusion TOP2A amplification—and possibly deletion—seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer, but a final conclusion has to await a confirmative study or a meta-analysis.
Chemical design of materials: A case study of inorganic open-framework materials
Authors: Rao C. N. R. , Dan Meenakshi , Behera J. N. 
Published: October 2005

Abstract
Inorganic open-framework materials are discussed as a case study in the chemical design of materials. Investigations of open-framework zinc phosphates have demonstrated that the formation of the complex 3D architectures may involve a process wherein 1D ladders or chains, and possibly 0D monomers comprising four-membered rings, transform to the higher-dimensional structures. The 1D ladder and the four-membered rings appear to be important building units of these structures. At one stage of the building-up process, spontaneous self-assembly of a low-dimensional structure such as the ladder could occur, followed by the crystallization of a 3D structure. Accordingly, many of the higher-dimensional structures retain structural features of the 0D or 1D structure. It is significant that a four-membered ring zinc phosphate spontaneously yields a linear chain phosphate at room temperature, on addition of piperazine, the chain transforming to a sodalite-type 3D structure under mild conditions. The occurrence of a hierarchy of structures from 0-3 dimensions is found in open-framework metal oxalates as well. Interestingly, the 3D sodalite structure is generated readily by the assembly of metal squarates, possessing the four-membered ring motif. It is noteworthy that open-framework structures are also formed by oxyanions such as sulfate, selenite, and selenate. Transformations of molecules to complex architectures are a worthy area of study, defining a new direction in the chemistry of materials.
Carbon-based materials: From fullerene nanostructures to functionalized carbon nanotubes
Authors: Tagmatarchis Nikos , Prato Maurizio 
Published: October 2005

Abstract
Self-assembly in morphological organization of various fullerene derivatives affords different supramolecular architectures. Nanospheres, tubules, and bundles of nanorods are formed depending on the nature of the organic group in the fullerene unit. The current work highlights an efficient method to fabricate almost perfect and uniformly shaped nanocrystals in a novel connection between spherical fullerene-based materials and fibrous nanotubes. In a parallel research line, carbon nanotubes (CNTs) have been functionalized using 1,3-dipolar cycloaddition of azomethine ylides. The organically functionalized CNTs, having improved solubility and potential for applications, are characterized by standard analytical methods as well as microscopy techniques.
Synthesis and single-crystal structure analysis of a new layered zinc phosphate
Authors: Zabukovec Logar Natasa , Rajic Nevenka , Stojakovic Djordje , Golobic Amalija , Kaucic Venceslav 
Published: October 2005

Abstract
A new 2D zinc phosphate [H3NCH(CH3)CH2NH3]2+
0.75[COOH(CH2)COOH]0.25(Zn3P3O11OH)2-
* 0.5NH4
+ consists of zinc phosphate layers, which are intercalated by diprotonated 1,2-diaminopropane, malonic acid, and NH4
+ ions. The inorganic layers are composed of alternating ZnO4 and PO4 (PO3OH) tetrahedra that form 8-membered ring apertures. The intercalated species strongly interact with the zinc phosphate layers through hydrogen bonds, which is a key factor in stabilizing the structure. Crystal data: monoclinic, P21/a, a = 8.3457(1) Å, b = 16.8953(3) Å, c = 10.1817(2) Å, β = 95.3121(8)°, Z = 4, R = 0.0423.
Direct synthesis of N-methylurethanes from primary amines with dimethyl carbonate
Authors: Tundo Pietro , Bressanello Salima , Loris Alessandro , Sathicq Gabriel 
Published: October 2005

Abstract
The mechanism of the reaction between amines with dimethyl carbonate (DMC) has been investigated. Whereas in the absence of bases, they give methylation and carboxymethylation reactions without selectivity (BAl2 and BAc2 mechanisms, respectively), in the presence of bases, the BAc2 mechanism prevails. The carbamate already formed reacts further with DMC via the BAl2 mechanism to give the corresponding N-methyl derivative. Such pronounced double selectivity has been explained in terms of Pearson's Hard-Soft Acid-Base (HSAB) theory.
Accordingly, N-methylcarbamates have been prepared from primary aliphatic and aromatic amines, either at reflux temperature of DMC (90 °C) or at 230 °C in autoclave. The reaction can be carried out in one step or through the isolation of the carbamate and the subsequent methylation reaction with DMC. This method is the direct synthesis, in high yield and selectivity, of secondary N-methylamines from the corresponding primary amines.
Ten-Year Follow-up of Children Born at &lt;30 Weeks’ Gestational Age Supplemented With Thyroxine in the Neonatal Period in a Randomized, Controlled Trial
Authors: van Wassenaer Aleid G. , Westera Jolanda , Houtzager Bregje A. , Kok Joke H. 
Published: October 2005

Background. Thyroid hormones are essential for brain development. We conducted a randomized, controlled trial with thyroxine (T4) supplementation in infants &lt;30 weeks’ gestation and with the last neurodevelopmental follow-up moment at the age of 5.5 years. T4 supplementation was associated with improved outcome of infants &lt;28 weeks’ gestation and worse outcome of infants of 29 weeks’ gestation. We studied gestational age–dependent effects of T4 supplementation at the mean age of 10.5 years in children participating in our randomized, controlled trial.
Methods. Questionnaires regarding school outcome, behavior, quality of life, motor problems, and parental stress were sent to the parents and children and their teachers at the same time point for all surviving children (9–12 years of age).
Results. Seventy-two percent of the families responded to our questionnaires. Nonrespondents had more sociodemographic risk factors and worse development until 5.5 years. At the mean age of 10.5 years, T4 supplementation was associated with better school outcome in those who were &lt;27 weeks’ gestation and better motor outcome in those who were &lt;28 weeks’ gestation, whereas the reverse was true for those who were born at 29 weeks’ gestation. No other gestational age–dependent outcomes were found.
Conclusions. Gestation-dependent effects of T4 supplementation remain stable over time. These effects do not prove beneficial effects of T4 in infants &lt;28 weeks but should be the background for a new randomized, controlled trial with thyroid hormone in this age group.
Targeting of Sebocytes by Aminolevulinic Acid‐dependent Photosensitization
Authors: Kosaka Sachiko , Kawana Seiji , Zouboulis Christos C. , Hasan Tayyaba , Ortel Bernhard 
Published: October 2005

ABSTRACTPhotodynamic therapy using 5‐aminolevulinic acid‐induced protoporphyrin IX has been developed as a very useful therapeutic modality. Recently, several authors have reported on the efficacy of this procedure for acne. This approach is based on the fact that 5‐aminolevulinic acid‐induced protoporphyrin IX has strong selectivity for sebaceous glands. We used the immortalized human sebaceous gland cell line SZ95 to investigate cellular mechanisms of photodynamic therapy using 5‐aminolevulinic acid‐induced protoporphyrin IX. Quantification of induced protoporphyrin IX production showed dependence on the applied 5‐aminolevulinic acid dose. When SZ95 sebocytes were differentiated by arachidonic acid treatment, there was no difference between them and the control cells with respect to both the amount of 5‐aminolevulinic acid‐induced protoporphyrin IX and the phototoxic effects. We altered protoporphyrin IX formation rates by growing cells scattered as single cells in the culture dishes. Single cells produced significantly lower protoporphyrin IX levels than those grown with intercellular contacts. Intracellular localization of protoporphyrin IX was imaged using confocal laser scanning microscopy. The differentiation‐specific lipid droplets were virtually excluded from protoporphyrin IX fluorescence. In addition to weak mitochondrial and strong membrane fluorescence, distinctive spots with strong fluorescence were observed. These did not colocalize with fluorescent probes for mitochondria, lysosomes or the Golgi apparati.