bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical utility of serum holotranscobalamin as a marker of cobalamin status in elderly patients with neuropsychiatric symptoms
Authors: Nilsson Karin , Isaksson Anders , Gustafson Lars , Hultberg Björn 
Published: August 2004

AbstractEarly diagnosis of cobalamin deficiency is crucial, owing to the latent nature of this disorder and the resulting possible irreversible neurological damage. A normal serum cobalamin concentration does not reliably rule out a functional cobalamin deficiency and there does not at present seem to be any single diagnostic approach to achieve this diagnosis. A new marker for cobalamin status is the serum concentration of cobalamin bound to transcobalamin II (holoTC). Because methods suitable for routine use have been unavailable until recently, the clinical value of lowholoTC is still uncertain. Furthermore, there is at the moment no gold standard or true reference method to diagnose subtle cobalamin deficiency, which makes evaluation of the clinical usefulness of holoTC and the estimation of sensitivity and specificity problematic. In this study, we aimed to assess whether low holoTC concentrations are congruent with other biochemical signs of cobalamin deficiency in a group of psychogeriatric patients. The findings in the present study showthat holoTC is strongly related to serum cobalamin (0.68; p<0.001 in both patients and controls). Distribution of the different markers for cobalamin/folate status in the 33 patients with low levels of serum holoTC (below40 pmol/l) showed that 17 patients had normal levels of the other markers for cobalamin status. This may indicate poor specificity of lowholoTC for cobalamin deficiency. In 23 out of 176 patients with normal levels of holoTC we observed pathological levels of other markers for cobalamin deficiency. The use of holoTC in the present study group did not give significant additional information other than that given by serum cobalamin and therefore cannot be recommended in this clinical setting.
Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3)
Authors: Elmlinger Martin W. , Kühnel Werner , Weber Matthias M. , Ranke Michael B. 
Published: August 2004

AbstractAssays for insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) have become essential tools in the diagnostic work-up of disorders of the somatotropic axis in children and adults. The aim of this study was to evaluate the automated IMMULITE
First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay – Lp(a) SRM 2B
Authors: Dati Francesco , Tate Jillian R. , Marcovina Santica M. , Steinmetz Armin 
Published: August 2004

AbstractLipoprotein(a) is an important predictor of cardiovascular disease risk. The lack of internationally accepted standardization has impeded the broad application of this lipoprotein in laboratory medicine. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), through its Working Group on Lipoprotein(a) and together with research institutions and several diagnostic companies, have succeeded in developing an international reference material that is intended for the transfer of a lipoprotein(a) concentration to manufacturers' master calibrators. IFCC SRM 2B has recently been accepted by the WHO Expert Committee on Biological Standardization as the ‘First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay’. The assigned unitage of 0.1071 nanomoles of lipoprotein(a) per vial is traceable to the consensus reference method for lipoprotein( a) and will enable conformity by diagnostic companies to the European Union's Directive on In vitro Diagnostic Medical Devices for the metrological traceability of calibrator materials.
Selecting clinically relevant populations for reference intervals
Authors: Ritchie Robert F. , Palomaki Glenn 
Published: August 2004

AbstractThe selection of individuals to represent a group for any purpose can commit the effort to success or failure from the very outset. The description of this group must reflect what is, in reality, the purpose for which the group is being studied. Considering that reference intervals are designed to assist clinicians during diagnostic triage, criteria must reflect the nature of the subjects entering the system for care. The majority of people seeking care have non-life-threatening, yet troublesome complaints. In other words, persons who are in aCompounding this awkward situation has been the conviction that by increasing laboratory precision and accuracy, the utility of laboratory data, reference intervals in particular, will improve clinical understanding. This has, after many years, not proven to be the case. What has become very evident, however, is that unsustainably large sums of money are being devoted to improving laboratory performance. To what end, when we are unable to grasp the significance of what is available now including published reference intervals for common test values?A realistic perspective on the value of prevailing laboratory performance, as illustrated by reference intervals, must be adopted. The obligation of laboratories, its regulators and professional groups is to create a sustainable mechanism to provide clinically usable information, in a timely and affordable manner, to our population and to those legions of less fortunate humans.
Creation of a low-risk reference group and referenceinterval of fasting venous plasma glucose
Authors: Jørgensen Lone G. M. , Brandslund Ivan , Petersen Per Hyltoft , Stahl Marta , Olivarius Niels de Fine 
Published: August 2004

AbstractReference intervals are recommended for naturally occurring quantities and required in the evaluation of new components in order to provide clinically useful information.The aim of the present study is to present a method for selecting reference individuals for the determination of fasting venous plasma glucose (f-vPG) reference intervals and ways to determine if disease groups can share reference intervals with an ideal reference population.Reference subjects were randomly selected, eligibility was judged according to predetermined inclusion and exclusion criteria. Using the literature we selected risk indicators for diabetes mellitus (DM) and used these indicators to rule out high-risk individuals in order to obtain a reference distribution of f-vPG determined using individuals with low risk of DM. The distributions of f-vPG in the high-risk individuals was compared with that determined for the low-risk group. We then estimated the ability of the high-risk individuals to share the reference interval of the low risk individuals, and calculated the fraction that was outside this interval. Distributions were also investigated for linearity in the cumulated frequency rankit distribution of ln-values. The allowable difference between two reference limits could not exceed 0.375 times the population biological variation.Most risk indicators were powerful predictors of high f-vPG values. Subgroups with these risk indicators should not be included in the homogeneous ln-normally distributed reference distribution. Distributions of f-vPG concentrations in individuals with risk factors were not homogeneous and varying percentages of individuals were outside the reference distribution, having f-vPG greater than 7.0 mmol/l.We conclude that randomisation is only useful to recruit candidate reference subjects. To rule out subjects according to clinical risk factors for diabetes, it is necessary to identify a reference population with low risk of exhibiting increased f-vPG concentrations. This method may be used to validate a reference interval for a particular analyte with respect to an investigated disease, and to stratify risk factors of importance.
Metrological traceability of calibration in the estimation and use of common medical decision-making criteria
Authors: Thienpont Linda M. , Uytfanghe Katleen Van , Cabaleiro Diego Rodríguez 
Published: August 2004

AbstractThis manuscript explains the establishment andvalidation of metrological traceability of calibration for routine measurement procedures using common medical decision-making criteria. Metrological traceability is considered the basis for achieving comparability of measurement results in laboratory medicine. This concept is supported by European legislation, which demands that manufacturers provide assurance andd emonstrate metrological traceability of in vitro Diagnostic Medical Devices. The guidance to comply with these legislative requirements is available in different CEN/ISO standards and is used as a basis of this manuscript. The goals andaccomplishments in metrological traceability of SI- and non-SI analytes is considered. Specific problems, such as non-availability of primary reference materials and measurement procedures, lack of official endorsement, andnon-commutability of certain reference materials are discussed. With respect to non-commutability, the use of split-sample measurements is advocated. Also, the expression of measurement uncertainty associatedwith the application of the metrological traceability chain is discussed. In addition, the needfor post-market vigilance assessment of traceable performance is considered. Finally, laboratory medicine scientific and professional societies, diagnostics manufacturers, and clinicians are urged to share responsibilities for understanding the implications of metrological traceability of routine measurements.
High Doses of Corticosteroid Suppress Resistance to Ichthyophonus in Starry Flounder
Authors: Perry J. A. , Kocan R. M. , Winton J. R. , Hershberger P. K. 
Published: August 2004

Abstract
Application of pharmacological doses of the corticosteroid dexamethasone phosphate to starry flounder Platichthys stellatus resulted in a predisposition to clinical ichthyophoniasis and a progression from latent Ichthyophonus infections to patent, histologically identifiable infections. Among Ichthyophonus-challenged starry flounder, the prevalences of clinical infections and histologically identifiable infections were significantly greater in two groups that received dexamethasone (100% and 31%, respectively) than in the respective control groups (8% and 0%). Proliferation of Ichthyophonus infections in corticosteroid-treated groups may have resulted from suppression of the cellular immune response that typically follows corticosteroid application; however, further studies are needed to determine whether these effects occur at lower, physiological concentrations of corticosteroids.
Gastric Polyp in a Wild-Caught Blue Shark
Authors: Borucinska Joanna D. , Bogicevic Tanja 
Published: August 2004

Abstract
An adult male blue shark Prionace glauca was caught in June 2002 by recreational fisherman off Long Island, New York. The shark was necropsied dockside and all major tissues were collected into elasmobranch formalin and processed for light microscopy. Macroscopic lesions included a polyp arising from the mucosa of the gastric body and numerous larval cestodes Hepatoxylon trichiuri attached to the hepatic capsule. The gastric polyp was a slender, pedunculated growth with a mucosa similar to the remaining gastric lining except for a few pinpoint areas of erosion and hemorrhage. Microscopically, the growth was classified as a well-differentiated adenomatous polyp. Histological evidence suggested minimal chronic gastritis, but special stains failed to reveal intralesional microorganisms, and no histological evidence of viral infection was detected. No other significant microscopic lesions were detected. This is the first literature report of a gastric polyp in a shark and in fishes in the class Chondrichthyes.
Antiangiogenic Strategies and Agents in Clinical Trials
Authors: Rosen Lee 
Published: August 2004

AbstractThe understanding that the growth of tumors depends on the acquisition of a blood supply has led to the development of new therapies for cancer and other angiogenic diseases based on inhibition of neovascularization. This review examines the role of angiogenesis in cancer progression and describes various strategies for interfering with this process. The developmental status of angiogenesis inhibitors in human clinical trials is presented, including their proposed mechanisms of action. Standard chemotherapeutic agents and angiogenesis inhibitors are compared, noting that different end points might need to be considered in clinical trials and that drug resistance may be less of a problem with antiangiogenic therapy than with conventional chemotherapy regimens. The suggestion is made that cytotoxic chemotherapy and angiogenesis inhibitors used in combination may produce complementary therapeutic benefits in the treatment of cancer.
The Role of Vascular Endothelial Growth Factor (VEGF) in AIDS-Related Kaposi's Sarcoma
Authors: Arastéh Keikawus , Hannah Alison 
Published: August 2004

AbstractKaposi's sarcoma (KS) is the most common neoplasm associated with human immunodeficiency virus-1 (HIV-1) infection. KS involves the skin and mucous membranes as well as other organs and can lead to tumor-associated edema and ulcerations. Despite therapy with highly active antiviral agents, most patients with HIV-1-related KS eventually develop disseminated disease. In the treatment of KS, a strong rationale exists for the use of agents that inhibit vascular endothelial growth factor (VEGF). Angiogenesis appears to be an important feature of this disease, and recent experimental studies have demonstrated the role of VEGF and its receptors in the pathogenesis of KS. Thus, therapeutic agents that target the VEGF pathway may be an effective strategy in reducing the tumor growth and edema associated with KS. Phase I study results with SU5416, a synthetic low molecular-weight inhibitor of the VEGF-Flk-1/KDR receptor tyrosine kinase, demonstrate that this agent is well tolerated.Preliminary results show that in a majority of patients with autoimmune deficiency syndrome (AIDS)-related disease, SU5416 clearly has biological activity (it flattens, shrinks, or dissolves lesions and reduces or resolves edema) or stabilizes the disease. Angiogenesis inhibition with SU5416 is a promising therapeutic approach in treating patients with KS, and further clinical evaluation is currently under way.
Options in Advanced Non-Small Cell Lung Cancer: A Review and Report on a Phase II Study of Vinorelbine Plus Gemcitabine
Authors: Lilenbaum Rogerio 
Published: August 2004

Abstract
Although platinum-containing regimens prolong survival in advanced non-small cell lung cancer (NSCLC), toxicity remains substantial. There is a clear need for a nonplatinum-based regimen which is active, well tolerated, and suitable for outpatient administration. Vinorelbine and gemcitabine have different mechanisms of action and are both active in NSCLC. A phase II trial was undertaken to evaluate activity and tolerability when the two drugs were administered as a first-line combination regimen in 32 patients with stage IIIB/IV disease. Gemcitabine was administered at a dose of 1,000-1,250 mg/m2 together with vinorelbine 25 mg/m2 on days 1 and 8 of a 21-day cycle. The overall response rate was 25%, median survival 8.3 months and one-year survival rate 38% (48% in patients of performance status 0-1). Grade 3/4 neutropenia was observed in 38% of 148 treatment cycles, however, thrombocytopenia was infrequent and there was no grade 3/4 anemia. Nonhematological toxicity was minimal. The response and survival rates experienced were comparable with standard platinum-based combinations. Ongoing randomized trials will further define the role of the vinorelbine/gemcitabine combination in advanced NSCLC.
Carboplatin/Paclitaxel or Carboplatin/Vinorelbine Followed by Accelerated Hyperfractionated Conformal Radiation Therapy: A Preliminary Report of a Phase I Dose Escalation Trial from the Carolina Conformal Therapy Consortium
Authors: Socinski M. A. , Marks L.B. , Garst J. , Sibley G.S. , Blackstock W. , Turrisi A. , Herndon J. , Zhou S. , Anscher M. , Crawford J. , Shafman T. , Rosenman J. 
Published: August 2004

Abstract
The maximum tolerated dose of conformal radiation therapy delivered at 1.6 Gy bid is being assessed in patients with unresectable stage IIB-IIIB non-small cell lung cancer who have been treated with induction regimens consisting of carboplatin plus paclitaxel or carboplatin plus vinorelbine. Data from the early stages of this parallel phase I study show that the two induction regimens are similar in toxicity and that both induce partial responses in 45% of patients. Both regimens can be followed by conformal radiotherapy using an accelerated hyperfractionated schedule to a dose of at least 80 Gy without experiencing unacceptable toxicity. Key morbidity observed thus far has involved the esophagus. Further cohorts of patients will receive higher doses of conformal radiotherapy (in 6.4 Gy increments) until the maximum tolerated dose is reached.
Long Term Analysis of Survival in the European Randomized Trial Comparing Vinorelbine/Cisplatin to Vindesine/Cisplatin and Vinorelbine Alone in Advanced Non-Small Cell Lung Cancer
Authors: Le Chevalier T. , Brisgand D. , Soria J.C. , Douillard J.Y. , Pujol J.L. , Ruffie P. , Aberola V. , Cigolari S. 
Published: August 2004

Abstract
In the period 1989-1991, 612 patients with inoperable stage IIIA/B and IV non-small cell lung cancer (NSCLC) were randomized in a phase III trial comparing three chemotherapy regimens. Survival data at five and six years of follow-up confirm the overall benefit of treatment with a combination of vinorelbine and cisplatin compared to vindesine plus cisplatin or vinorelbine alone. Of the 612 patients randomized at the start of the study, 17 have survived beyond five years. Of these patients, eight had entered the trial with metastatic disease. Multivariate analysis to detect prognostic factors suggested a possible interaction between the effect of having cisplatin in the chemotherapy received and baseline performance status. Subgroup analysis subsequently confirmed that the survival benefit of the vinorelbine plus chemotherapy regimen is evident only in patients with initial World Health Organization performance status (PS) of 0-1. Among these patients, the one-year survival rate is 38% for the vinorelbine/cisplatin arm, 29% for vindesine/cisplatin and 34% for vinorelbine alone. The corresponding figures for median survival are 43, 33 and 36 weeks. Among inoperable NSCLC patients with a PS of 2, who appear from this trial not to have benefited from the presence of cisplatin in their chemotherapy, use of single agent vinorelbine is an appropriate treatment option.
Clinical Experience of Arsenic Trioxide in Relapsed Acute Promyelocytic Leukemia
Authors: Soignet Steven L. 
Published: August 2004

Abstract
Acute promyelocytic leukemia (APL) has unique clinical, cytogenetic, and molecular features and is one of the most potentially curable human malignancies. The current standard treatment given to patients with newly diagnosed APL con-sists of all-trans retinoic acid and anthracycline-based cytotoxic chemotherapy, which is highly effective for remission induction. However, despite the potential for cure with existing treatments, approximately 20%-30% of patients relapse and require salvage therapy. Reports of the safety and efficacy of arsenic trioxide from centers in China led to a pivotal trial of this agent in the United States for patients with relapsed APL. In an initial pilot study, 11 of 12 patients experienced a complete response, and a subsequent multicenter trial confirmed the efficacy and safety of arsenic trioxide for remission induction in this patient population. Additional trials are under way to evaluate the use of this agent alone or as part of a chemotherapy regimen for consolidation and maintenance of patients with APL.
Nonanthracycline Containing Docetaxel-Based Combinations in Metastatic Breast Cancer
Authors: Crown John 
Published: August 2004

Abstract
Many active nonanthracycline-containing regimens are emerging from clinical trials and may offer the option of treating metastatic breast cancer without resorting to doxorubicin or analogues. When used first-line in metastatic breast cancer, both cisplatin and carboplatin are active agents and hence candidates for combination therapy. In a dose-finding study in patients with no prior chemotherapy for metastatic disease, docetaxel administered together with cisplatin produced a promising response rate (RR) of 60% (73% in patients without prior adjuvant chemotherapy). The combination is feasible, although adequate hydration and antiemetic medication must be given. There is also an early indication that it may be possible to dramatically cytoreduce disease in patients with locally advanced breast cancer who are treated with docetaxel plus cisplatin. Given its lower toxicity, carboplatin may also have a role in combination with the taxanes. Of the nonplatinum agents, vinorelbine appears to hold promise; its combination with docetaxel produced an RR of 59% in a group of anthracycline-pretreated patients with progressive disease. Forty-two percent of the patients studied also had prior exposure to a taxane. Weekly gemcitabine plus monthly docetaxel is feasible and active, as is the combination of docetaxel q 3 weeks with daily oral capecitabine.
Neoadjuvant Therapy in Breast Cancer: Can We Define Its Role?
Authors: Aapro Matti S. 
Published: August 2004

Abstract
It remains unclear whether neoadjuvant therapy increases disease-free survival when compared with an approach in which chemotherapy is delayed until after surgery. However, the current rationale for neoadjuvant therapy is based on its usefulness in quickly evaluating the likely benefit of new approaches to treatment and tailoring therapy to the biological characteristics of the individual tumor. In the primary therapy of breast cancer, the Aberdeen study shows that patients unresponsive to an anthracycline-based neoadjuvant regimen may achieve a response when switched to docetaxel. Further, patients with an initial clinical response to CVAP were more likely to show a pathological complete response (pCR) at final assessment when four cycles of CVAP were followed by four of docetaxel than when CVAP was maintained for eight cycles (pCR rate 34% versus 16%). Early data suggest that this difference translates into significantly lengthened progression-free survival. As in other disease settings, it may be possible to devise nonanthracycline-containing neoadjuvant regimens which are at least as effective as those in current use.