bluuebunny/crossref_metadata_2025_split huggingface dataset:
Problems with GH assays and strategies toward standardization
Authors: Bidlingmaier Martin 
Published: September 2008

Disorders affecting GH secretion – either GH deficiency or GH excess (acromegaly) – are biochemically defined through peak or nadir concentrations of human GH in response to dynamic tests. Immunoassays employing polyclonal or monoclonal antibodies are routinely used for the analysis of GH concentrations, and many different assays are available on the market today. Unfortunately, the actual value reported for the GH concentration in a specific patient's sample to a large extent depends on the assay method used by the respective laboratory. Variability between assay results exceeds 200%, limiting the applicability of consensus guidelines in clinical practice. Reasons for the heterogeneity in GH assay results include the heterogeneity of the analyte itself, the availability of different preparations for calibration, and the interference from matrix components such as GH-binding protein. Furthermore, the reporting of results in mass units or international units together with the application of variable conversion factors led to confusion.International collaborations proposed measures to improve the comparability of assay results, recommending the use of a single, recombinant calibrator for all assays and reporting only in mass units as first steps. However, because of the differences in epitope specificity of antibodies used in different assays, method-specific cut-off levels for dynamic tests might remain necessary to correctly interpret and compare results from different laboratories.
Mortality from thyroid cancer in patients with hyperthyroidism: the Theagenion Cancer Hospital experience
Authors: Pazaitou-Panayiotou Kalliopi , Perros Petros , Boudina Maria , Siardos George , Drimonitis Apostolos , Patakiouta Frideriki , Vainas Iraklis 
Published: September 2008

BackgroundThyroid carcinoma has been reported in patients operated for different types of hyperthyroidism and the probability of a hot nodule being malignant seems to be low. The aim of the present study was to explore the relationship between thyroid cancer, hyperthyroidism and outcome in a large cohort of patients who presented to a tertiary cancer centre in Northern Greece.PatientsAmong 720 patients treated for thyroid cancer, 60 had a concomitant diagnosis of hyperthyroidism due to Graves' disease (n=14), solitary autonomous adenoma (n=17), or multinodular goiter (n=29). Adverse prognostic factors were common in patients with a previous history of hyperthyroidism at the time of diagnosis of thyroid cancer, including cases where the cancer was discovered coincidentally after thyroid surgery for hyperthyroidism and cases where tumor size was more than 10 mm.ResultsIn 10 out of 17 patients with hyperthyroidism due to solitary autonomous adenomas, the tumor was located within the hot nodule and two of these patients developed local and distant metastases and died from the disease 4 and 15 years after thyroidectomy.ConclusionClinicians managing patients with hyperthyroidism need to be aware of the possible increased risk of thyroid cancer in this patient group.
Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children
Authors: Shaikh M Guftar , Grundy Richard G , Kirk Jeremy M W 
Published: September 2008

BackgroundObesity following hypothalamic damage is often severe and resistant to lifestyle changes. Disruption of hypothalamic feedback mechanisms that maintain energy homeostasis may be responsible for this intractable obesity. Adipocytokines including insulin and leptin are also known to be important regulators of appetite and weight.ObjectiveTo investigate the role of insulin, leptin, adiponectin and resistin in the aetiology of hypothalamic obesity (HO).DesignThis was a cross-sectional study of three groups of children, those with HO, congenital hypopituitarism (CH) and simple obesity (SO).ResultsA total of 69 children (HO=28, CH=18, SO=23) had leptin, resistin, adiponectin and insulin measured. Although fasting hyperinsulinaemia and insulin resistance were demonstrated, no differences in insulin or insulin resistance were seen between the groups. The HO group, however, had higher levels of leptin, adiponectin and resistin, which persisted even after adjusting for fat mass, compared with the other groups (P<0.05).ConclusionNo differences in fasting hyperinsulinaemia or insulin resistance were seen between the groups; however, leptin levels are elevated, even after adjusting for fat mass, suggesting that an element of leptin resistance is associated with HO. This is consistent with the inability of leptin to act on the hypothalamus, either due to transport across the blood–brain barrier or dysfunctional receptors. The lack of response to leptin may be more important in the development of obesity in these individuals, and the fasting hyperinsulinaemia is a result of the increased adipose tissue rather than the cause of the weight gain.
Impaired subjective health status in chronic adrenal insufficiency: impact of different glucocorticoid replacement regimens
Authors: Bleicken Benjamin , Hahner Stefanie , Loeffler Melanie , Ventz Manfred , Allolio Bruno , Quinkler Marcus 
Published: September 2008

ContextRecent studies have suggested that current glucocorticoid replacement therapies fail to fully restore well-being in patients with adrenal insufficiency (AI).ObjectiveTo investigate the effect of different glucocorticoid preparations used for replacement therapy on subjective health status (SHS) in AI.Design and patientsIn a cross-sectional study, primary and secondary AI patients were contacted by mail. Individual glucocorticoid replacement regimens, underlying diagnoses and comorbidities were verified by questionnaires and review of medical records. Patients were asked to complete three validated self-assessment questionnaires (Short Form 36 (SF-36), Giessen Complaint List (GBB-24), and Hospital Anxiety and Depression Scale). Results were compared with sex- and age-matched controls drawn from the questionnaire-specific reference cohort.ResultsOf the 883 patients identified, 526 agreed to participate in the study. Completed questionnaire sets were available from 427 patients (primary AI n=232; secondary AI n=195). AI patients showed significantly impaired SHS compared with controls irrespective of the glucocorticoid used for replacement. The only difference in SHS between patients on prednisolone (PR) and hydrocortisone (all patients and sub-analysis for primary AI) was significant higher bodily pain (lower Z-score in SF-36) in patients on PR (P<0.05, P<0.01 respectively). In patients with secondary AI, the PR group showed significantly (P<0.05) less heart complaints (lower Z-score) in the GBB questionnaire compared with the cortisone acetate group.ConclusionsGlucocorticoid replacement therapy with PR seems to be equivalent to hydrocortisone regarding SHS in patients with AI. However, SHS remains impaired in all patient groups suggesting a need for further improved glucocorticoid replacement strategies.
Pharmacokinetics of Oral Posaconazole in Neutropenic Patients Receiving Chemotherapy for Acute Myelogenous Leukemia or Myelodysplastic Syndrome
Authors: Krishna Gopal , AbuTarif Malaz , Xuan Fengjuan , Martinho Monika , Angulo David , Cornely Oliver A. 
Published: September 2008

Study Objective. To analyze the pharmacokinetics of posaconazole administered as prophylaxis for invasive fungal infection (IFI) in neutropenic patients receiving chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS).Design. Pharmacokinetic subanalysis of a phase III, prospective, randomized, multicenter, evaluator‐blinded trial comparing posaconazole with standard azoles (fluconazole and itraconazole).Patients. One hundred ninety‐four patients with AML or MDS who received posaconazole oral suspension 200 mg 3 times/day with meals or a nutritional supplement for a minimum of 7 days to achieve steady state and for a maximum of 12 weeks.Intervention. For the first 20 patients, blood samples were collected before the first dose on day 8 and at 2, 4, 6, and 24 hours after that first dose; for all other patients, blood samples were collected at 1 and 3 hours after the first dose on day 8 and during the first episode of evaluation for a possible IFI.Measurements and Main Results. The effects of the following covariates on average (Cav) and maximum (Cmax) posaconazole plasma concentrations at steady state were explored: age, sex, and race‐ethnicity; proven or probable IFI; baseline body weight and body surface area; and baseline (on or before day 7) increases in liver enzyme levels, mucositis, neutropenia, diarrhea, vomiting, or use of an H2‐receptor antagonist or proton pump inhibitor. Diarrhea, proton pump inhibitor use, γ‐glutamyl transferase level of 2 or more times the upper limit of normal, and race‐ethnicity reduced Cav. Although statistically significant, these results were not considered clinically significant and did not necessitate posaconazole dosage adjustments. Mean Cav and Cmax values did not appear different in the six patients with IFIs (three with proven IFIs, three with probable IFIs) compared with the entire sample of 194 patients; however, a definitive conclusion cannot be made due to the small sample size of patients with IFI. No factor found to affect posaconazole concentrations predominated in patients with IFIs.Conclusion. Oral posaconazole 200 mg 3 times/day provided plasma concentrations adequate for preventing IFIs. No dosage adjustments are recommended based on any covariate tested.
The Asymmetric Effect of Diffusion Processes: Risk Sharing and Contagion
Authors: Gallegati Mauro , Greenwald Bruce , Richiardi Matteo G. , Stiglitz Joseph E. 
Published: September 2008

In this paper we provide a general characterization of diffusion processes, allowing us to analyze both risk-sharing and contagion effects at the same time. We illustrate the relevance of our theory with reference to the subprime mortgage crisis and more in general to the processes of securitization and interbank linkages. We show that interdependencies in real and financial assets are beneficial from a social point of view when the economic environment is favorable and detrimental when the economic environment deteriorates. In the latter case, private incentives are such that too many linkages are formed, with respect to what is socially desirable. The risk of contagion increases the volatility of the outcome and thus reduces the ability of the financial networks to provide risk-sharing. Our analysis suggests that a likely major explanation of the subprime mortgage crisis is the process of securitization itself, in addition to the absence of transparency about the characteristics of the underlying assets that the multiple layers of financial intermediation fostered, as commonly claimed. This may call for a different emphasis on the role of public intervention. While a goal to stabilize the economy in good times should be to disrupt the channels that bring contagion, that is a positive correlation in the returns, in a period of worsening economic conditions our analysis suggests regulatory intervention aimed at disconnecting the economy at crucial nodes. Moreover, we show that policy interventions should be aimed at rescuing institutions, but not their managers. Diminishing the cost of default actually increases the inefficiency due to the divergence between the social and the individual optimum.
Versatile Nanocomposite Coatings with Tunable Cell Adhesion and Bactericidity
Authors: Es‐Souni Martha , Fischer‐Brandies Helge , Es‐Souni Mohammed 
Published: September 2008

AbstractTiO2‐Ag nanocomposites are known for their bactericidal effect during exposure to appropriate UV radiation. While involving hazardous radiation, and limited to accessible areas, the bactericidity of these coatings is not persistent in the absence of UV light, which impedes their commercial application. Herein it is shown that TiO2‐Ag nanocomposites can be made highly bactericidal without the need of irradiation. Beyond this, bactericidity can even be mitigated in the presence of pre‐irradiated coatings. Biocompatibility and cell adhesion are also negligibly small for the as‐processed, non‐irradiated coatings, and become fairly high when the coatings are irradiated prior to testing. This opens the possibility to pattern the coatings into areas with high and low cell adhesion properties. Indeed by irradiating the coating through a mechanical mask it is shown that fibroblast cell adherence is sharply confined to the irradiated area. These properties are achieved using TiO2‐Ag thin films with high silver loadings of 50 wt%. The films are processed on stainless steel substrates using solution deposition. Microstructural characterization by means of X‐ray diffraction, Raman, and X‐ray photoelectron spectroscopy, high‐resolution scanning electron microscopy, and atomic force microscopy show a highly amorphous TiO2‐AgxO nanocomposite matrix with scattered silver nanoparticles. UV irradiation of the films results in the precipitation of a high density of silver nanoparticles at the film surface. Bactericidal properties of the films are tested on α‐haemolyzing streptococci and in‐vitro biocompatibility is assessed on primary human fibroblast cultures. The results mentioned above as to the tunable bactericidity and biocompatibility of the TiO2‐Ag coatings developed herein, are amenable to silver ion release, to catalytic effects of silver nanoparticles, and to specific wettabilities of the surfaces.
Self‐assembly of Protein Nanoarrays on Block Copolymer Templates
Authors: Lau K. H. Aaron , Bang Joona , Kim Dong Ha , Knoll Wolfgang 
Published: September 2008

AbstractThere is considerable interest in developing functional protein arrays on the nanoscale for high‐throughput protein‐based array technology, and for the study of biomolecular and cell interactions at the physical scale of the biomolecules. To these ends, self‐assembly based techniques may be desirable for the nanopatterning of proteins on large sample areas without the use of lithography equipment. We present a fast, general approach for patterning proteins (and potentially other biomolecules) on the nanoscale, which takes advantage of the ability of block copolymers to self‐assemble into ordered surface nanopatterns with defined chemical heterogeneity. We demonstrate nanoarrays of immunoglobulin and bovine serum albumin on polystyrene‐block‐poly(methyl methacrylate) templates, and illustrate the applicability of our technique through immunoassays and DNA sensing performed on the protein nanoarrays. Furthermore, we show that the pattern formation mechanism is a nanoscale effect originating from a combination of fluid flow forces and geometric restrictions templated by an underlying nanopattern with a difference in protein adsorption behavior on adjacent, chemically distinct surfaces. This understanding may provide a framework for extending the patterning approach to other proteins and material systems.
Multiple system atrophy: A primary oligodendrogliopathy
Authors: Wenning Gregor K. , Stefanova Nadia , Jellinger Kurt A. , Poewe Werner , Schlossmacher Michael G. 
Published: September 2008

AbstractTo this day, the cause of multiple system atrophy (MSA) remains stubbornly enigmatic. A growing body of observations regarding the clinical, morphological, and biochemical phenotypes of MSA has been published, but the interested student is still left without a clue as to its underlying cause. MSA has long been considered a rare cousin of Parkinson's disease and cerebellar degeneration; it is rich in acronyms but poor in genetic and environmental leads. Because of the worldwide research efforts conducted over the last two decades and the discovery of the α‐synuclein–encodingSNCAgene as a cause of rare familial Parkinson's disease, the MSA field has seen advances on three fronts: the identification of its principal cellular target, that is, oligodendrocytes; the characterization of α‐synuclein–rich glial cytoplasmic inclusions as a suitable marker at autopsy; and improved diagnostic accuracy in living patients resulting from detailed clinicopathological studies. The working model of MSA as a primary glial disorder was recently strengthened by the finding of dysregulation in the metabolism of myelin basic protein and p25α, a central nervous system–specific phosphoprotein (also called tubulin polymerization promoting protein, TPPP). Intriguingly, in early cases of MSA, the oligodendrocytic changes in myelin basic protein and p25α processing were recorded even before formation of glial cytoplasmic inclusions became detectable. Here, we review the evolving concept that MSA may not just be related to Parkinson's disease but also share traits with the family of demyelinating disorders. Although these syndromes vary in their respective cause of oligodendrogliopathy, they have in common myelin disruption that is often followed by axonal dysfunction. Ann Neurol 2008;64:239–246
Axonal loss and myelin in early ON loss in postacute optic neuritis
Authors: Klistorner Alexander , Arvind Hemamalini , Nguyen Than , Garrick Raymond , Paine Mark , Graham Stuart , O'Day Justin , Grigg John , Billson Francis , Yiannikas Con 
Published: September 2008

AbstractObjectiveTo investigate the relation between retinal nerve fiber layer (RNFL) thickness and latency and amplitude of multifocal visual‐evoked potentials (mfVEPs) in the postacute stage of optic neuritis in patients with early or possible multiple sclerosis.MethodThirty‐two patients with clinical diagnosis of unilateral optic neuritis and magnetic resonance imaging lesions typical of demyelination and 25 control subjects underwent mfVEP and optical coherence tomography imaging.ResultsAlthough there was significant reduction of RNFL thickness in the affected eyes (18.7%), a considerably larger decrease was observed for the amplitude of the mfVEPs (39.8%). Latency of the mfVEPs was also significantly delayed in optic neuritis eyes. In fellow eyes, the amplitude of mfVEPs was significantly reduced and the latency prolonged, but RNFL thickness remained unaltered. RNFL thickness correlated highly with the mfVEP amplitude (r = 0.90). There was also strong correlation between optical coherence tomography measure of axonal loss and mfVEP latency (r = −0.66).InterpretationAlthough our findings demonstrate strong associations between structural and functional measures of optic nerve integrity, the functional loss was more marked. This fact, together with amplitude and latency changes of the mfVEPs observed in clinically normal fellow eyes, may indicate greater sensitivity of mfVEPs in detecting optic nerve abnormality or the presence of widespread inflammation in the central nervous system, or both. The significant correlation of the mfVEP latency with RNFL thickness suggests a role for demyelination in promoting axonal loss. Ann Neurol 2008
MRI‐Kontrastmittel mit hoher Relaxivität: Komplexchemie im Dienste medizinischer Bildgebung
Authors: Werner Eric J. , Datta Ankona , Jocher Christoph J. , Raymond Kenneth N. 
Published: September 2008

AbstractUm die klinischen Anwendungsmöglichkeiten der Kernspintomographie (MRI) zu verbessern, wird intensiv nach effizienteren Kontrastmitteln gesucht. Dazu müssen die Koordinationschemie von Gadolinium(III) und die Parameter, die seine Wirksamkeit als Protonenrelaxationsagens beeinflussen, berücksichtigt werden. Will man jeden Parameter optimieren, so sind auch Eigenschaften wie Löslichkeit und In‐vivo‐Toxizität zu beachten, was die Entwicklung sicherer und starker Relaxationsagentien zu einem anspruchsvollen Ziel macht. Dieser Kurzaufsatz stellt die neuesten Fortschritte auf diesem Gebiet vor, wobei ein besonderes Augenmerk auf Gadolinium(III)‐Hydroxypyridinon‐Chelatkomplexen liegt.
Percent true calcium absorption, mineral metabolism, and bone mass in children with arthritis: Effect of supplementation with vitamin D3 and calcium
Authors: Hillman Laura S. , Cassidy James T. , Chanetsa Fungai , Hewett John E. , Higgins Barry J. , Robertson John D. 
Published: September 2008

AbstractObjectiveTo assess whether percent true calcium absorption (α) is normal and whether supplementation with placebo, vitamin D3 (2,000 IU/day), calcium (1,000 mg/day), or vitamin D3 plus calcium improves α, mineral metabolism, or bone mass accrual in children with arthritis.MethodsEighteen children received all 4 treatments, each for 6 months, in 4 different, randomly assigned orders. Changes in levels of 25‐hydroxyvitamin D (25[OH]D), 1,25‐dihydroxyvitamin D (1,25[OH]2D), parathyroid hormone, bone turnover markers, and minerals and in bone mineral content were measured. Calcium absorption was determined with a dual stable isotope method using 48Ca administered intravenously and 46Ca administered orally, and measuring 48Ca, 46Ca, and 42Ca in a 24‐hour urine specimen by high‐resolution inductively coupled plasma mass spectroscopy. Wilcoxon's signed rank test was used both to identify significant change over the treatment period with a given regimen and to compare change with an experimental treatment versus change with placebo.ResultsPercent true calcium absorption was in the lower‐normal range and did not differ by treatment (mean ± SD 28.3 ± 20.2% with placebo, 26.1 ± 12.1% with calcium, 19.2 ± 11.7% with vitamin D3, and 27.1 ± 16.5% with vitamin D3 plus calcium). With vitamin D3 and vitamin D3 plus calcium treatment, 25(OH)D levels were increased and 1,25(OH)2D levels were maintained. Serum calcium levels were increased only with vitamin D3 and vitamin D3 plus calcium treatment. Levels of bone turnover markers and increases in bone mineral content did not differ by treatment.ConclusionThe findings of this study indicate that percent true calcium absorption is low‐normal in children with arthritis. Vitamin D3 at 2,000 IU/day increases serum 25(OH)D and calcium levels but does not improve bone mass accretion. Calcium at 1,000 mg/day also failed to improve bone mass.
Initiation of the alternative pathway of murine complement by immune complexes is dependent on N‐glycans in IgG antibodies
Authors: Banda Nirmal K. , Wood Allyson K. , Takahashi Kazue , Levitt Brandt , Rudd Pauline M. , Royle Louise , Abrahams Jodie L. , Stahl Gregory L. , Holers V. Michael , Arend William P. 
Published: September 2008

AbstractObjectiveCollagen antibody–induced arthritis in mice exhibits a requirement for amplification by the alternative pathway of complement. Although the alternative pathway is activated by spontaneous hydrolysis, it is not known whether this pathway can also be initiated directly by IgG antibodies in immune complexes (ICs). IgG lacking terminal sialic acid and galactose (G0 IgG) can activate the lectin pathway of complement, but it is not known if G0 IgG can also activate the classical or alternative pathway. The purpose of this study was to examine the mechanism of initiation of the alternative pathway of complement by ICs.MethodsWe used adherent ICs containing bovine type II collagen (CII) and 4 monoclonal antibodies (mAb) to CII (adCII‐IC). C3 activation was measured in the presence of sera from wild‐type C57BL/6 mice or from mice deficient in informative complement components. The mAb were used intact or after enzyme digestion to create G0 IgG or to completely remove the N‐glycan.ResultsBoth the classical and alternative pathways, but not the lectin pathway, mediated C3 activation induced by the adCII‐IC. Mannose inhibited the alternative pathway–mediated C3 activation but had no effect on the classical pathway, and N‐glycans in IgG were required by the alternative pathway but not the classical pathway. Both the classical and alternative pathways mediated C3 activation induced by G0 IgG. Mannose‐binding lectin bound avidly to G0 IgG, but lectin pathway–mediated C3 activation was only slightly increased by G0 IgG.ConclusionThe alternative pathway of complement is capable of initiating C3 activation induced by adCII‐IC and requires the presence of N‐glycans on the IgG. G0 IgG activates both the classical and alternative pathways more strongly than the lectin pathway.