bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective, Multicenter, Randomized Phase II Trial of the Herbal Supplement, PC-SPES, and Diethylstilbestrol in Patients With Androgen-Independent Prostate Cancer
Authors: Oh William K. , Kantoff Philip W. , Weinberg Vivian , Jones Graham , Rini Brian I. , Derynck Mika K. , Bok Robert , Smith Matthew R. , Bubley Glenn J. , Rosen Robert T. , DiPaola Robert S. , Small Eric J. 
Published: August 2004

Purpose To evaluate the herbal combination, PC-SPES, and diethylstilbestrol (DES) in patients with androgen independent prostate cancer (AIPC). Patients and Methods A randomized phase II study was conducted with cross-over design. Patients were randomly assigned to receive either three PC-SPES capsules orally three times a day or DES 3 mg orally once a day. Prophylactic warfarin was administered. At clinical or prostate-specific antigen progression, patients received the other therapy. The study closed prematurely after PC-SPES was withdrawn from the market. Chemical analyses were performed on multiple lots of PC-SPES. Results Ninety patients were enrolled, of whom 85 were assessable for response. Prostate-specific antigen declines ≥ 50% were noted in 40% (95% CI, 25% to 56%) with PC-SPES, and 24% (95% CI, 12% to 39%) with DES. Median response duration was not reached with PC-SPES, and was 3.8 months with DES. Median time to progression for randomly assigned patients was 5.5 months for PC-SPES and 2.9 months for DES. Common toxicities included mild fatigue, gynecomastia, and mastodynia. Five thromboembolic events occurred (one PC-SPES, four DES). Responses in the cross-over phase were inconclusive. Four lots of PC-SPES had measurable quantities of DES, ranging from 0.01% to 3.1% of the dose used in the DES arm. Ethinyl estradiol was also detected in PC-SPES lots. Conclusion PC-SPES and DES demonstrate activity in AIPC and are well tolerated. However, the synthetic estrogens, DES and ethinyl estradiol, were detected in various lots of PC-SPES, including those used in this trial. Clinical trials that utilize herbal therapies must account for issues of purity and consistency.
Thin Primary Cutaneous Malignant Melanoma: A Prognostic Tree for 10-Year Metastasis Is More Accurate Than American Joint Committee on Cancer Staging
Authors: Gimotty Phyllis A. , Guerry DuPont , Ming Michael E. , Elenitsas Rosalie , Xu Xiaowei , Czerniecki Brian , Spitz Francis , Schuchter Lynn , Elder David 
Published: August 2004

PurposeThe majority of invasive primary melanomas are thin (≤ 1.00 mm). Since the current staging system imperfectly predicts outcome in patients with such lesions, we sought to develop a more effective classification scheme to better identify both patients at high risk of metastasis who are candidates for further staging and therapy and those with little risk.Patients and MethodsThis prospective cohort study included 884 patients who had thin invasive melanomas. A tree-structured analysis of 10-year metastasis was used to develop a new classification scheme.ResultsThe overall 10-year metastasis rate was 6.5% (95% CI, 4.8% to 8.1%). The prognostic tree defined four risk groups: high-risk: men with vertical growth phase (VGP) lesions that had mitotic rates (MRs) greater than 0, and for whom the 10-year metastasis rate was 31% (22% to 42%; n = 90); moderate-risk: women with VGP lesions that had MRs greater than 0 and for whom the rate was 13% (9% to 18%; n = 136); low-risk: patients with VGP lesions that had MR of 0 for whom the rate was 4% (2% to 7%; n = 247); and minimal-risk: patients with invasive lesions without VGP for whom the rate was 0.5% (0% to 1.2%; n = 411). Survival curves differed significantly among the four groups (P < .001).ConclusionGrowth phase, mitotic rate, and sex are important prognostic factors for patients with thin melanomas, and they identify subgroups at substantial risk for metastasis. After validation in other populations, the proposed prognostic tree will be useful in the design of clinical trials and clinical management.
A novel test method for evaluation of the abrasive wear behaviour of total hip stems at the interface between implant surface and bone cement
Authors: Bader R , Steinhauser E , Holzwarth U , Schmitt M , Mittelmeier W 
Published: August 2004

After total hip replacement, some cemented titanium stems show above-average early loosening rates. Increased release of wear particles and resulting reaction of the peri-prosthetic tissue were considered responsible. The objective was to develop a test method for analysing the abrasive wear behaviour of cemented stems and for generating wear particles at the interface with the bone cement. By means of the novel test device, cemented hip stems with different designs, surface topographies and material compositions using various bone cements could be investigated. Before testing, the cemented stems were disconnected from the cement mantle to simulate the situation of stem loosening (debonding). Subsequently, constant radial contact pressures were applied on to the stem surface by a force-controlled hydraulic cylinder. Oscillating micromotions of the stem (± 250 μm; 3 × 106cycles; 5 Hz) were carried out at the cement interface initiating the wear process. The usability of the method was demonstrated by testing geometrically identical Ti-6A1-7Nb and Co-28Cr-6Mo hip stems ( n = 12) with definite rough and smooth surfaces, combined with commercially available bone cement containing zirconium oxide particles. Under identical frictional conditions with the rough shot-blasted stems, clearly more wear particles were generated than with the smooth stems, whereas the material composition of the hip stems had less impact on the wear behaviour.
An investigation of using various diesel-type fuels in homogeneous charge compression ignition engines and their effects on operational and controlling issues
Authors: Milovanovic N , Chen R , Dowden R , Turner J 
Published: August 2004

Homogeneous charge compression ignition (HCCI) engines appear to be a future alternative to diesel and spark-ignited engines. The HCCI engine has the potential to deliver high efficiency and very low NOx and particulate matter emissions. There are, however, problems with the control of ignition and heat release range over the entire load and speed range which limits the practical application of this technology. The aim of this paper is to analyse the use of different types of diesel fuels in an HCCI engine and hence to find the most suitable with respect to operational and control issues. The single-zone combustion model with convective heat transfer loss is used to simulate the HCCI engine environment. n-Heptane, dimethyl ether and bio-diesel (methyl butanoate and methyl formate) fuels are investigated. Methyl butanoate and methyl formate represent surrogates of heavy and light bio-diesel fuel respectively. The effects of different engine parameters such as equivalence ratio and engine speed on the ignition timing are investigated. The use of internal exhaust gas recirculation is investigated as a potential strategy for controlling the ignition timing. The results indicate that the use of bio-diesel fuels will result in lower sensitivity of ignition timing to changes in operational parameters and in a better control of the ignition process when compared with the use of n-heptane and dimethyl ether.
Excitation Wavelength Dependence of Solvation Dynamics in a Water Pool of a Reversed Micelle
Authors: Satoh Taku , Okuno Hiroaki , Tominaga Keisuke , Bhattacharyya Kankan 
Published: August 2004

Abstract
We have investigated the excitation wavelength dependence of solvation dynamics in the water pool of a reversed micelle using dynamic Stokes shift method. The solvation dynamics displays nanosecond and subnanosecond components, which are almost independent of the excitation wavelength. On the other hand, the total dynamics Stoke shift decreases with increasing the excitation wavelength.
Novel Silver(I) and Copper(II) Complexes of Tetrakis(2-pyridyl)methane
Authors: Matsumoto Kouzou , Kannami Masaki , Oda Masaji 
Published: August 2004

Abstract
Tetrakis(2-pyridyl)methane forms a novel one dimensional coordination polymer complex with Ag(I) ion and two kinds of complexes different in coordination modes with Cu(II) ion, indicating its versatile ability as a symmetric tetradentate ligand.
Molecular Design and Crystal Structures of Chiral Macrotricyclic Cage Amines
Authors: Yoshida Haruki , Izumi Mitsunori , Ito Naohito , Ichikawa Kazuhiko , Shiro Motoo 
Published: August 2004

Abstract
Chiral macrotricyclic cage amines have been synthesized; their X-ray structures have revealed that the asymmetric framework has been formed by adding a single chiral carbon into methylene skeleton of cage amine. The 1H NMR spectra have shown the stable and rigid conformation in solution.
Preparation of H2Ti4O9 with High Specific Surface Area
Authors: Wang Jinshu , Yin Shu , Sato Tsugio 
Published: August 2004

Abstract
H2Ti4O9 nanocrystals with high specific surface areas were prepared by exfoliation and reassembly process through a novel way of ball milling and ion-exchange reaction. The specific surface area of H2Ti4O9 nanocrystals depends on solution pH value and ball milling time. H2Ti4O9 nanocrystals precipitated by milling K2Ti4O9 for 2 h and exfoliating in 1 M HCl followed by adjusting solution pH at 8 has the specific surface area of 328.2 m2/g.
Thiopurine methyltransferase: should it be measured before commencing thiopurine drug therapy?
Authors: Sanderson Jeremy , Ansari Azhar , Marinaki Tony , Duley John 
Published: August 2004

Thiopurines [azathioprine (AZA), 6-mercaptopurine (6-MP) and thioguanine (6-TG)] have a well-established role as immunosuppressive agents in a variety of chronic inflammatory conditions, haematological neoplasia and in transplant rejection. Despite good overall clinical response rates, particularly when used as steroid sparing agents, adverse effects are a limiting problem leading to withdrawal in up to a quarter of patients. Severe myelosuppression is the most serious toxicity occurring early or occasionally later during treatment. An understanding of the competing pathways involved in the metabolism of thiopurines has important implications for predicting some of the more severe toxicity seen with these drugs. Thiopurine methyl transferase (TPMT) is an enzyme catalysing the methylation of 6-MP, competing with xanthine oxidase (XO) and hypoxanthine guanine phosphoribosyl transferase (HGPRT) to determine the amount of 6-MP metabolised to cytotoxic thioguanine nucleotides. Allelic polymorphisms in the TPMT gene predict the activity of the enzyme such that 1 in 10 of the population are heterozygous and have approximately 50% of normal activity, whilst 1 in 300 are completely deficient. As a result, these individuals are at high risk of severe myelosuppression. Conversely, individuals with very high levels of TPMT activity are hyper-methylators in whom clinical response is less likely. Prior knowledge of TPMT status avoids exposure of individuals with zero TPMT to potentially fatal treatment with AZA or 6-MP and provides one of the best examples of predictive pharmacogenetics in therapeutics. This article reviews literature on the role of TPMT measurement prior to treatment with thiopurines and provides some guidance to the use of TPMT as a guide to tailoring thiopurine therapy.
The measurement of vitamin D: analytical aspects
Authors: Zerwekh Joseph E 
Published: August 2004

In the past quarter of a century, our understanding of the metabolism and mechanism of action of vitamin D has been elucidated. During this period, many metabolites of vitamin D have been identified and a small proportion of these assayed in blood. The ability to assay these vitamin D metabolites has led to a better appreciation of the pathological role that altered vitamin D metabolism plays in the development of diseases of calcium homeostasis. However, for many physicians it is not clear which vitamin D metabolites should be quantitated and what the information gained tells us. Of the four major circulating vitamin D metabolites in blood, only two, namely 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25(OH)2D], have warranted measurement. Of these, the need for assessing serum 1,25(OH)2D is actually quite limited and should therefore not be considered as part of the standard vitamin D testing regimen. 25OHD, on the other hand, provides us with the single best assessment of vitamin D nutritional status and should be the only vitamin D assay typically ordered for this reason. Which of the many methods that are available should a laboratory use for quantitating either of these vitamin D metabolites? Early methods required large volumes of blood, organic solvent extractions, and extensive purification of the vitamin D metabolites prior to assay. Today, these time-consuming and costly methods have given way to a range of radioimmunoassays and enzyme-linked immunosorbent assays that can accurately and conveniently provide important information concerning an individual's vitamin D status. This review will consider when vitamin D measurements should be undertaken and how best to perform such assays.
The response of serum apolipoprotein H to an oral fat load
Authors: Zahedi RG , Summers LKM , Lumb P , Chik G , Crook MA 
Published: August 2004

Background: We tested the hypothesis that serum apolipoprotein H (apo H) concentration increases after an oral fat load. Such a study would give valuable insight into whether apo H was influenced by the postprandial state. Methods: Ten male subjects aged 24-48 years were fed 62.5 g of total fat (saturates 12 g, monounsaturates 35.3 g, polyunsaturates 12.5 g). Venous blood was sampled hourly for 5 h post-oral fat load. Results: No significant change in serum apo H concentration occurred following the oral fat load. However, serum apo H in the baseline samples correlated significantly with subject body mass index ( r = 0.683, P < 0.05), body fat mass ( r = 0.778, P < 0.01), lean body mass ( r = 0.693, P < 0.05), serum triglyceride ( r = 0.732, P < 0.02), serum insulin ( r = 0.808, P < 0.01) and insulin resistance index ( r = 0.794, P < 0.01). In stepwise multiple linear regression model, with serum apo A1, apo B, lipoprotein(a), total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, plasma glucose and insulin and apo H as the dependent variable, insulin remained in the model ( r = 0.81, P < 0.01). Conversely, with body mass index, body fat mass, lean body mass and waist/hip ratio in the model and apo H as dependent variable, only body fat mass remained in the model ( r = 0.78, P < 0.01). Conclusions: Serum apo H may be involved in insulin resistance and relates to various indices of adipose tissue, including body fat mass. However, serum apo H concentrations do not significantly change postprandially.
Characterization of the epitopes specific for the monoclonal antibody 9F5-3a and quantification of oxidized HDL in human plasma
Authors: Nakajima Takanori , Matsunaga Toshiyuki , Kawai Shin-Ichiroh , Hokari Shigeru , Inoue Ikuo , Katayama Shigehiro , Nagata Atsuo , Komoda Tsugikazu 
Published: August 2004

Background: We previously isolated a monoclonal antibody, 9F5-3a, that is specific for HDL oxidized by CuSO4. Methods: We examined the characteristics of the 9F5-3a epitope by Western blot and measured the concentration of oxidized HDL in human plasma by enzyme-linked immunosorbent assay using this antibody. Results: The monoclonal antibody specifically reacted with oxidized HDL in a mixture of HDL, LDL and modified lipoproteins. Oxidation of the HDL particles accelerated cross-linkage of apolipoproteins caused by lipid peroxidation, and the cross-linked apolipoprotein AI selectively reacted with the 9F5-3a antibody. Mean (standard deviation) plasma concentrations of oxidized HDL were 127 (50) μg/L in 23 healthy controls, 191 (65) μg/L in 30 patients with non-insulin-dependent diabetes mellitus ( P < 0.01 versus healthy controls) and 200 (87) μg/L in 25 patients with coronary artery disease ( P < 0.01 versus healthy controls). The concentrations of oxidized HDL did not correlate with the concentrations of thiobarbituric acid-reactive substances. Conclusions: The results indicate that determination of oxidized HDL concentration may be useful for identifying patients with atherosclerotic disease.
Urinary 6β-hydroxycortisol/17-hydroxycorticosteroids ratio as a measure of hepatic CYP3A4 capacity after enzyme induction
Authors: Konishi Hiroki , Tanaka Kazuhiko , Minouchi Tokuzo , Yamaji Akira 
Published: August 2004

Background: The correlation between the urinary 6 β-hydroxycortisol/17-hydroxycorticosteroids (6 β-OHF/17-OHCS) ratio and the metabolic capacity of the most abundant form of hepatic cytochrome P450 (CYP3A4) after induction remains unclear. Methods: Concentrations of 6 β-OHF and 17-OHCS in spot urine specimens obtained from 61 epileptic children receiving continuous carbamazepine therapy were measured by high-performance liquid chromatography. The relationship between the urinary 6 β-OHF/17-OHCS ratio and the serum carbamazepine concentration, corrected for dose and body weight, was examined. Results: Serum carbamazepine was inversely associated with the urinary 6 β-OHF/17-OHCS ratio, and the hyperbolic relationship between the two parameters was statistically significant ( P < 0.01). Discussion: Carbamazepine is well known as a potent inducer and a substrate of hepatic CYP3A4. The present results suggest that measurement of the urinary 6 βOHF/17-OHCS ratio is helpful for assessing individuals' hepatic CYP3A4 capacity after enzyme induction.
Establishment of paediatric biochemical reference intervals
Authors: Brinkworth Russell SA , Whitham Elaine , Nazeran Homer 
Published: August 2004

Background: The standard method for the determination of reference values in a population by testing a number of healthy volunteers is difficult within the paediatric age group; this study explores an alternative approach. Methods: Biochemical blood test results collected by the Woman's and Children's Hospital over a 1 year period were used and the data selected to ensure, as far as possible, that the results were from patients who were 'healthy'. This was achieved using various selection criteria, such as the exclusion of patients with more than one test episode. Some of the data were skewed, making standard statistical approaches difficult. In such cases, transformations were used to ensure that the resulting information had a distribution that was approximately Gaussian. Results: Data from different biochemical tests covering both genders and ages in the range 0-18 years were collected; this included more than 250 000 laboratory test results. After elimination of non-representative data and tests with insufficient results, there were approximately 23 500 results covering almost 3000 individuals and 16 different biochemical tests. There were no results from very young children (< 1 year) after the data selection process; hence the derivation of reference values from that age group was not possible. Conclusions: This approach permitted better delineation of reference intervals for common biochemical tests performed on paediatric patients than is currently readily available. In addition, some important benchmarks for transformation of medical data have been found.
Reference intervals for thiopurine S-methyltransferase activity in red blood cells using 6-thioguanine as substrate and rapid non-extraction liquid chromatography
Authors: Ford Loretta T , Cooper Sheldon C , Lewis Matthew Jv , Berg Jonathan D 
Published: August 2004

Background: Although widely used, thiopurine drugs have a narrow therapeutic index and treatment can result in life-threatening toxicity, the basis being pharmacogenetic variation in thiopurine metabolism by thiopurine S-methyltransferase (TPMT). We recently developed a modified phenotyping assay to determine TPMT activity in red blood cells. Here we describe improvements to the method and establish reference intervals in a large prospective study. Methods: A modified enzyme assay for TPMT activity is reported. It uses 6-thioguanine as substrate with heat treatment of the incubate to stop the reaction and precipitate protein prior to high-performance liquid chromatographic (HPLC) analysis. Measurement of the reaction product, 6-methylthioguanine (6-MTG), uses HPLC with fluorimetric detection. Results: The assay shows excellent characteristics, with clear discrimination of patients who are deficient in TPMT activity (< 5 nmol 6-MTG per g Hb per h) from heterozygotes (5-24 nmol 6-MTG per g Hb per h) and patients with normal activity (>25 nmol 6-MTG per g Hb per h). Conclusion: A modified TPMT assay is described which is suited for routine analysis in a regional centre. The method overcomes the need for extraction and has speeded up the chromatographic determination of 6-MTG, enabling large numbers of samples to be analysed. A prospective study of 1000 individuals has established the distribution of TPMT activity using the assay.
Paracetamol-associated interference in an HPLC-ECD assay for urinary free metadrenalines and catecholamines
Authors: Davidson Fraser D 
Published: August 2004

Background: Some high-performance liquid chromatography techniques with electrochemical detection for urinary catecholamines and their metabolites can be subject to interference from drugs and their metabolites. Prime amongst these interferences are those due to paracetamol ingestion. Methods: The prevalence of paracetamol contamination was determined by measuring the drug in all patient specimens submitted for catecholamine analysis over a 2-month period. These findings were then related to the proportion of unreportable results at each range of specimen paracetamol concentration. The apparent results from a small representative sample of the paracetamol-positive specimens are illustrated. Results: Approximately one-third of urine specimens were found to contain paracetamol. Low-level contamination can produce apparent patterns of results which may easily be confused with those found in predominantly adrenaline-, or metadrenaline-secreting phaeochromocytomas. Conclusion: Despite the fact that significantly less than 5% of an oral dose of paracetamol is excreted as the free drug, its analysis provides a good surrogate marker for the likelihood of spurious results. It is useful to know prior to urinary free metadrenaline or catecholamine analysis which urine specimens are likely to contain potentially interfering paracetamol metabolites.
Concurrent Crashing and Overlapping in Product Development
Authors: Roemer Thomas A. , Ahmadi Reza 
Published: August 2004

This research addresses two common tools for reducing product development lead times: overlapping of development stages and crashing of development times. For the first time in the product development literature, a formal model addresses both tools concurrently, thus facilitating analysis of the interdependencies between overlapping and crashing. The results exhibit the necessity of addressing overlapping and crashing concurrently, and exhibit general characteristics of optimal overlapping/crashing policies. The impact of different evolution/sensitivity constellations on optimal policies is investigated, and comprehensive guidelines for structuring development processes are provided. For the special case of linear costs, an efficient procedure is presented that generates the efficient time-cost trade-off curves and determines the corresponding optimal overlapping/crashing policies. The impact of key parameters and the robustness regarding their estimates is illustrated with a simple two-stage example.