bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bevacizumab Plus Interferon Alfa Compared With Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: CALGB 90206
Authors: Rini Brian I. , Halabi Susan , Rosenberg Jonathan E. , Stadler Walter M. , Vaena Daniel A. , Ou San-San , Archer Laura , Atkins James N. , Picus Joel , Czaykowski Piotr , Dutcher Janice , Small Eric J. 
Published: October 2008

Purpose Bevacizumab is an antibody that binds to vascular endothelial growth factor (VEGF) and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN) is a historic standard first-line treatment for RCC. A prospective, randomized phase III trial of bevacizumab plus IFN versus IFN monotherapy was conducted. Patients and Methods Patients with previously untreated, metastatic clear-cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN (9 million U subcutaneously three times weekly) or the same dose and schedule of IFN monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate (ORR), and safety. Results Between October 2003 and July 2005, 732 patients were enrolled. The prespecified stopping rule for OS has not yet been reached. The median PFS was 8.5 months in patients receiving bevacizumab plus IFN (95% CI, 7.5 to 9.7 months) versus 5.2 months (95% CI, 3.1 to 5.6 months) in patients receiving IFN monotherapy (log-rank P < .0001). The adjusted hazard ratio was 0.71 (95% CI, 0.61 to 0.83; P < .0001). Bevacizumab plus IFN had a higher ORR as compared with IFN (25.5% [95% CI, 20.9% to 30.6%] v 13.1% [95% CI, 9.5% to 17.3%]; P < .0001). Overall toxicity was greater for bevacizumab plus IFN, including significantly more grade 3 hypertension (9% v 0%), anorexia (17% v 8%), fatigue (35% v 28%), and proteinuria (13% v 0%). Conclusion Bevacizumab plus IFN produces a superior PFS and ORR in untreated patients with metastatic RCC as compared with IFN monotherapy. Toxicity is greater in the combination therapy arm.
Randomized Phase II Study of Vandetanib Alone or With Paclitaxel and Carboplatin as First-Line Treatment for Advanced Non–Small-Cell Lung Cancer
Authors: Heymach John V. , Paz-Ares Luis , De Braud Filippo , Sebastian Martin , Stewart David J. , Eberhardt Wilfried E.E. , Ranade Anantbhushan A. , Cohen Graham , Trigo Jose Manuel , Sandler Alan B. , Bonomi Philip D. , Herbst Roy S. , Krebs Annetta D. , Vasselli James , Johnson Bruce E. 
Published: October 2008

Purpose Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non–small-cell lung cancer (NSCLC). Patients and Methods All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P < .2) and to demonstrate noninferiority for vandetanib versus PC. Overall survival was a secondary assessment. Results The risk of progression was reduced for patients receiving VPC (n = 56) versus PC (n = 52; hazard ratio = 0.76, one-sided P = .098); median PFS was 24 weeks (VPC) and 23 weeks (PC). The vandetanib monotherapy arm (n = 73) was discontinued after a planned interim PFS analysis met the criterion for discontinuation (hazard ratio > 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention. Conclusion VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.
Circulating 25-Hydroxyvitamin D, VDR Polymorphisms, and Survival in Advanced Non–Small-Cell Lung Cancer
Authors: Heist Rebecca Suk , Zhou Wei , Wang Zhaoxi , Liu Geoffrey , Neuberg Donna , Su Li , Asomaning Kofi , Hollis Bruce W. , Lynch Thomas J. , Wain John C. , Giovannucci Edward , Christiani David C. 
Published: October 2008

Purpose We showed previously that in early-stage non–small-cell lung cancer (NSCLC), serum vitamin D levels and VDR polymorphisms were associated with survival. We hypothesized that vitamin D levels and VDR polymorphisms may also affect survival among patients with advanced NSCLC. Patients and Methods We evaluated the relationship between circulating 25-hydroxyvitamin D levels; VDR polymorphisms, including Cdx-2 G>A (rs11568820), FokI C>T (rs10735810), and BsmI C>T ( rs144410 ); and overall survival among patients with advanced NSCLC. Analyses of survival outcomes were performed using the log-rank test and Cox proportional hazards models, adjusting for sex, stage, and performance status. Results There were 294 patients and 233 deaths, with median follow-up of 42 months. We found no difference in survival by circulating vitamin D level. The C/C genotype of the FokI polymorphism was associated with improved survival: median survival for C/C was 21.4 months, for C/T was 12.1 months, and for T/T was 15.6 months (log-rank P = .005). There were no significant effects on survival by the Cdx-2 or BsMI polymorphism. However, having increasing numbers of protective alleles was associated with improved survival (adjusted hazard ratio for two or more v zero to one protective alleles, 0.57; 95% CI, 0.41 to 0.79; P = .0008). On haplotype analysis, the G-T-C (Cdx-2-FokI-BsmI) haplotype was associated with worse survival compared with the most common haplotype of G-C-T (adjusted hazard ratio, 1.61; 95% CI, 1.21 to 2.14; P = .001). Conclusion There was no main effect of vitamin D level on overall survival in the advanced NSCLC population. The T allele of the VDR FokI>T polymorphism and the G-T-C (Cdx-2-FokI-BsmI) haplotype were associated with worse survival.
Strain-Specific Effects of Rosiglitazone on Bone Mass, Body Composition, and Serum Insulin-Like Growth Factor-I
Authors: Ackert-Bicknell Cheryl L. , Shockley Keith R. , Horton Lindsay G. , Lecka-Czernik Beata , Churchill Gary A. , Rosen Clifford J. 
Published: October 2008

Activation of peroxisome proliferator activated receptor-γ (PPARG) is required for the differentiation of marrow mesenchymal stem cell into adipocytes and is associated with the development of age-related marrow adiposity in mice. Thiazolidinediones are agonists for PPARG and have a heterogeneous effect on bone mineral density (BMD). We postulated that genetic determinants influence the skeletal response to thiazolidinediones. We examined the effects of rosiglitazone (3 mg/kg · d for 8 wk) on BMD, body composition, and serum IGF-I in adult female mice from four inbred strains. C3H/HeJ mice showed the most significant response to treatment, exhibiting decreased femoral and vertebral BMD, reduced distal femoral bone volume fraction and a decrease in serum IGF-I. In DBA/2J, there were no changes in femoral BMD or bone volume fraction, but there was a decrease in vertebral BMD. C57BL/6J mice showed increases in marrow adiposity, without associated changes in trabecular bone volume; the skeletal effects from rosiglitazone in A/J mice were minimal. No association between trabecular bone volume and marrow adiposity was found. The effect of rosiglitazone on gene expression in the femur was then examined in the C3H/HeJ and C57BL/6J strains by microarray. Increased gene expression was observed in the PPARG signaling pathway and fatty acid metabolism in both C3H/HeJ and C57BL/6J, but a significant down-regulation of genes associated with cell cycle was noted only in the C3H/HeJ strain. The divergent skeletal responses to rosiglitazone in this study suggest the existence of a strong genetic background effect.Treatment of four inbred strains of mice with rosiglitazone results in very distinct skeletal and metabolic responses, suggesting an important genotype by drug interaction.
Identification of proSAAS Homologs in Lower Vertebrates: Conservation of Hydrophobic Helices and Convertase-Inhibiting Sequences
Authors: Kudo H. , Liu J. , Jansen E. J. R. , Ozawa A. , Panula P. , Martens G. J. M. , Lindberg I. 
Published: October 2008

The prohormone convertases (PCs) 1/3 and 2 accomplish the major proteolytic cleavage events in neuroendocrine tissues; each of these convertases has a small associated binding protein that inhibits convertase action in the secretory pathway. The proSAAS protein binds to PC1/3, whereas the 7B2 protein binds to PC2. However, both convertase-binding proteins are more widely expressed than their cognate enzymes, suggesting that they may perform other functions as well. All known mammalian proSAASs are over 85% conserved; thus, identifying functionally important segments has been impossible. Here, we report the first identification of nonmammalian proSAAS molecules, from Xenopus and zebrafish (Danio rerio). Although these two proteins show an overall amino acid sequence identity of only 29 and 30% with mouse proSAAS, two 14–16 residue hydrophobic segments (predicted to form α-helices) and two, nine through 11 residue sequences containing basic convertase cleavage sites are highly conserved; therefore, these sequences may be of functional importance. Confidence that these nonmammalian molecules represent authentic proSAAS is supported by the finding that both inhibit mouse PC1/3 with nanomolar inhibition constants; human furin was not inhibited. In vitro, the two proteins were cleaved by PC2 and furin to three or more peptide products. Both zebrafish and Xenopus proSAAS exhibited neural and endocrine distributions, as assessed by in situ and PCR experiments, respectively. In summary, the identification of proSAAS molecules in lower vertebrates provides clues as to functional regions within this widely expressed neuroendocrine protein.The identification of two proSAAS molecules in lower vertebrates provides clues as to functional regions within this widely-expressed neuroendocrine protein.
Development and validation of criteria to identify medication-monitoring errors in care home residents
Authors: Alldred David P , Standage Claire , Zermansky Arnold G , Jesson Barbara , Savage Imogen , Franklin Bryony Dean , Barber Nick , Raynor David K 
Published: October 2008

Abstract

Aim
The identification of medication-monitoring errors requires a validated definition. This paper describes the development and validation of a definition which includes criteria for specific medicines to determine whether a medication-monitoring error has occurred in the care home setting.

Setting
Criteria were developed for older people (aged 65 years or older) living in care homes.

Methods
Criteria were developed by two clinical pharmacists using published guidelines. The criteria were divided into those relating to initiation of therapy and maintenance monitoring. The study steering group, made up of clinical pharmacists, a general practitioner (GP) and pharmacy academics, then reviewed the criteria and a consensus was achieved. The criteria were then reviewed by a sample of 21 GPs and 11 clinical pharmacists. The threshold for acceptance for each criterion was set at 70% by agreement of all participants.

Key findings
The definition of a medication-monitoring error was accepted as ‘when a prescribed medicine is not monitored in the way which would be considered acceptable in routine general practice. It includes the absence of tests being carried out at the frequency listed in the criteria for each medicine, with tolerance of +50%’. Seventy per cent agreement was reached on all criteria for the initiation of therapy, except warfarin (69%), and on all criteria for maintenance monitoring, except penicillamine (63%) and potassium (63%).

Conclusions
To our knowledge, this is the first study to define a medication-monitoring error, and to determine and validate specific criteria to identify such errors in older people living in care homes.
Spurious hyperkalaemia due to EDTA contamination: common and not always easy to identify
Authors: Cornes Michael P , Ford Clare , Gama Rousseau 
Published: October 2008

Background To study the detection and prevalence of spurious hyperkalaemia due to potassium ethylenediaminetetra-acetic acid (kEDTA) contamination. Methods In a one-month prospective study, serum EDTA, zinc, calcium, magnesium concentrations and alkaline phosphatase activity were measured in samples with serum potassium ≥6.0 mmol/L. Results Twenty-eight out of 117 hyperkalaemic samples were contaminated with EDTA. Only serum zinc values below the reference range had 100% sensitivity for indicating EDTA contamination, but even at an optimal specificity of 89% at least 12 potentially genuine hyperkalaemic samples would be rejected. Conclusion Spurious hyperkalaemia due to kEDTA contamination is common. Gross kEDTA contamination is obvious by marked unexpected hyperkalaemia, hypocalcaemia, hypomagnesaemia and hypozincaemia. Spurious hyperkalaemia due to low concentrations of kEDTA contamination can only be confidently detected by measurement of serum EDTA.
Measurement of cholesterol concentrations of major serum lipoprotein classes in haemodialysis patients by anion-exchange chromatography
Authors: Hirowatari Yuji , Yoshida Hiroshi , Fueki Yuriko , Ito Masayuki , Ogura Yutaka , Sakurai Nobuyuki , Miida Takashi 
Published: October 2008

Background Increased triglyceride (TG)-rich lipoproteins and decreased HDL that are implicated in the progression of atherosclerotic vascular diseases, are present in serum samples of patients undergoing haemodialysis (HD) therapy. Therefore, it is important to measure serum TG-rich lipoprotein concentrations to prevent the diseases. Methods The cholesterol concentrations of lipoprotein classes in serum samples from the HD patients ( n = 18) and healthy subjects ( n = 18) were analysed by our recently developed method of high-performance liquid chromatography (HPLC), in which the lipoprotein classes were separated using an anion-exchange column, and the cholesterol concentrations of each of those were measured enzymatically using a post-column reaction. The ability of fractionated lipoprotein cholesterol determination by this HPLC method is mostly equivalent to the determination ability of an ultracentrifugation (UC). Results HDL, LDL, and TG-rich lipoproteins, i.e. IDL, VLDL and chylomicrons, were well separated in the chromatograms. HDL cholesterol concentrations in the HD patients were significantly lower than in the healthy subjects ( P < 0.0001), and IDL cholesterol concentrations and VLDL cholesterol concentrations in the HD patients were significantly higher than in the healthy subjects ( P < 0.05). Profiles of these measured lipoprotein values were consistent with the previously reported lipoprotein values, measured ultracentrifugally characteristic of HD patients. Conclusion These results suggest that the HPLC method may be sufficiently applied to the assessment of serum lipoprotein profile in HD patients in place of the other method including an UC.
Effect of delay in sampling on haemoglobin determined by faecal immunochemical tests
Authors: Brown Louise F , Fraser Callum G 
Published: October 2008

Background Faeces must be sampled directly onto guaiac-based faecal occult blood test (FOBT) cards since analysis of specimens collected in traditional faeces containers is inappropriate because degradation of haemoglobin continues after faeces have been passed. Newer faecal immunochemical tests (FIT) are replacing FOBT, but it is likely that the practice of obtaining specimens in traditional faeces collection containers for later analysis will continue. The aim of this study was to assess the effect of delay in stool sampling on FIT. Methods Five specimens of faeces from healthy volunteers, all qualitatively FIT negative, were supplemented with whole blood haemolysate to three different FIT positive concentrations. Each sample was analysed daily after 1–14 days delay using a quantitative latex immunoturbidimetric-based FIT and also after five and ten days delay using a qualitative FIT. Results Haemoglobin concentrations fell each day, the rate being generally proportional to the original haemoglobin concentration. After eight days delay, no sample had a haemoglobin concentration >100 ng/mL and, after nine days, no sample had a haemoglobin concentration >50 ng/mL. After five days delay, five of the 15 supplemented faeces with initially positive qualitative FIT had negative FIT; after 10 days, none had positive FIT. Conclusion False-negative results will occur if sampling of fresh faeces into or onto FIT collection devices is delayed. Laboratories that undertake FIT analyses on faeces collected into traditional containers are likely to miss significant neoplasia. FIT collection devices must be used for sampling fresh faeces.
A rapid rise in circulating pancreastatin in response to somatostatin analogue therapy is associated with poor survival in patients with neuroendocrine tumours
Authors: Stronge R L , Turner G B , Johnston B T , McCance D R , McGinty A , Patterson C C , Ardill J E S 
Published: October 2008

Aim To assess the value of pancreastatin as a predictive factor for identifying patients with neuroendocrine tumours (NETs) who respond poorly to somatostatin analogues. Methods A retrospective study of patients with NETs. Patient records from the Northern Ireland Neuroendocrine Tumour Register were interrogated. Those who had pancreastatin concentrations measured on two or more occasions, before and during somatostatin analogue therapy (within the set time-limits) were selected. Data relating to diagnosis, surgery, somatostatin analogue therapy and survival outcome were noted. Data were subjected to univariate and multivariate analysis using Cox proportional hazard model. Results Fifty-nine patients with gastroenteropancreatic NETs fulfilled the inclusion criteria. Factors associated with a poor survival outcome on univariate analysis were primary tumour site ( P = 0.006) and rapid rise in pancreastatin during somatostatin analogue treatment ( P < 0.001). In multivariate analysis, highly significant clinical prognostic indicators were: tumour location ( P < 0.001), pre-treatment pancreastatin ( P < 0.001) and pancreastatin change ( P < 0.001). Conclusions This study endorses the finding that pancreastatin is a useful prognostic indicator of neuroendocrine disease. On commencement of treatment, one-third of the subjects showed an immediate negative pancreastatin response to somatostatin analogues, which was associated with poor survival. This is the first study to document such an association. These findings have significant therapeutic consequences. In the presence of a rapidly rising pancreastatin alternative, treatment modalities should be sought.
Determination of the reference range of endogenous plasma carnitines in healthy adults
Authors: Reuter Stephanie E , Evans Allan M , Chace Donald H , Fornasini Gianfranco 
Published: October 2008

Background l-carnitine is an endogenous substance, vital in the transport of fatty acids across the inner mitochondrial membrane for oxidation. Disturbances in carnitine homeostasis can have a significant impact on human health; therefore, it is critical to define normal endogenous concentrations for l-carnitine and its esters to facilitate the diagnosis of carnitine deficiency disorders. This study was conducted to determine the normal concentrations of a number of carnitines in healthy adults using three analytical methods. The impact of age and gender on carnitine concentrations was also examined. Methods Blood samples were collected from 60 healthy subjects of both genders and various ages. Plasma samples were analysed for endogenous carnitine concentrations by radioenzymatic assay, high-performance liquid chromatography and electrospray tandem mass spectrometry. Results Precision and accuracy of results obtained for each assay were within acceptable limits. Average endogenous concentrations obtained from the three analytical methods in this study were in the range of 38–44, 6–7 and 49–50 μmol/L for l-carnitine, acetyl-l-carnitine and total carnitine, respectively. Comparison of results between the genders indicated that males had significantly higher endogenous plasma l-carnitine and total carnitine concentrations than females. Age was found to have no impact on plasma carnitine concentrations. Conclusion These results are useful in the evaluation of biochemical or metabolic disturbances and in the diagnosis and treatment of patients with carnitine deficiency.
Standardization of the IMMULITE systems growth hormone assay with the recombinant IS 98/574
Authors: Barth Julian H , Sibley Paul E C 
Published: October 2008

Background The diagnosis of disorders of growth hormone (GH) secretion is based on the measurement of GH before and after dynamic stimulation or suppression tests. Over the years, specific cut-off values have been proposed without taking account of the considerable variation in results obtained using different methods for analysing GH. Recent publications have recommended the standardization of GH assays using IS 98/574, which is calibrated in mass and units (U). The IMMULITE range of GH assays have been recalibrated using this standard. Methods We analysed 745 samples using the current and the restandardized GH assay kits. This series of samples contained 90 stimulation tests and seven suppression tests. Results The data comparing the current and restandardized assays show a similar relationship for both basal and stimulated GH values for all IMMULITE platforms. There is a negative bias by the restandardized assay above approximately 20 μg/L. A conversion can be derived from this study which would mean that patient GH results expressed in milliunits per litre of IMMULITE in-house derived standard will be approximately three-fold of that expressed in micrograms per litre of IS 98/574. Conclusion Use of IS 98/574 offers standardized reporting in microgram per litre IS 98/574. This will permit compliance with the consensus recommendations and the development of a firm evidence base for defining decision-making GH values.