bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability of mental capacity assessments in psychiatric in-patients
Authors: Cairns Ruth , Maddock Clementine , Buchanan Alec , David Anthony S. , Hayward Peter , Richardson Genevra , Szmukler George , Hotopf Matthew 
Published: September 2005

BackgroundPrevious work on the reliability of mental capacity assessments in patients with psychiatric illness has been limited.AimsTo describe the interrater reliability of two independent assessments of capacity to consent to treatment, as well as assessments made by a panel of clinicians based on the same interview.MethodFifty-five patients were interviewed by two interviewers 1–7 days apart and a binary (yes/no) capacity judgement was made, guided by the MacArthur Competence Assessment Tool for Treatment (MacCAT-T). Four senior clinicians used transcripts of the interviews to judge capacity.ResultsThere was excellent agreement between the two interviewers for capacity judgements made at separate interviews (kappa=0.82). A high level of agreement was seen between senior clinicians for capacity judgements of the same interview (mean kappa=0.84)ConclusionsIn combination with a clinical interview, the MacCAT–T can be used to produce highly reliable judgements of capacity.
Antipsychotic drugs – information and choice: a patient survey
Authors: Olofinjana Banke , Taylor David 
Published: September 2005

Aims and MethodThe National Institute for Clinical Excellence (NICE) has issued guidance on the use of atypical antipsychotic drugs and recommended that patients be involved in a discussion about the antipsychotic prescribed to them. We undertook a study to evaluate information provision and patient choice subsequent to the publication of this guidance. Patients were recruited from the South London and Maudsley Trust and interviewed. Case notes were examined for documentation of informed discussions.ResultsThirty patients were interviewed, of whom 15 claimed to have received no information. Twenty-seven patients felt that they had had no choice in regard to antipsychotic prescribed. None of the patients had documentation in their notes to suggest that they were involved in informed discussions about the antipsychotic they were prescribed.Clinical ImplicationsPatients were not involved in decisions regarding the antipsychotic medication prescribed. Practice did not follow the NICE guidance.
Clozapine prescribing in adolescent psychiatry: survey of prescribing practice in in-patient units
Authors: Cirulli Giovanni 
Published: September 2005

Aims and MethodClozapine is an effective drug in treatment-resistant schizophrenia, but it seems to be prescribed for few patients under the age of 18 years. This study reports a survey of consultant psychiatrists working in adolescent units in the UK, looking at their use of clozapine and experience with it.ResultsOut of 83 clinicians, 59 responded (71%). More than 40% of respondents do not use clozapine, and those who do may not always be following best practice recommendations. Reasons for not using clozapine, beliefs about its effectiveness and problems encountered in its use are described.Clinical ImplicationsClozapine may not always be made available to young people with treatment-resistant schizophrenia. There is a need for more education, guidance and debate on clozapine use in child and adolescent psychiatry.
Early Enhanced Expression of Interferon-Inducible Protein-10 (CXCL-10) and Other Chemokines Predicts Adverse Outcome in Severe Acute Respiratory Syndrome
Authors: Tang Nelson Leung-Sang , Chan Paul Kay-Sheung , Wong Chun-Kwok , To Ka-Fai , Wu Alan Ka-Lun , Sung Ying-Man , Hui David Shu-Cheong , Sung Joseph Jao-Yiu , Lam Christopher Wai-Kei 
Published: September 2005

AbstractBackground: Exaggerated activation of cytokines/chemokines has been proposed as a factor in adverse outcome of severe acute respiratory syndrome (SARS). Previous studies on chemokines have included only small numbers of patients, and the utility of plasma chemokines as prognostic indicators is unclear.Methods: We studied 255 archival plasma samples collected during the first or second week after disease onset. The chemokines interferon-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and regulated upon activation normal T cell expressed and secreted (RANTES) were measured by cytometric bead array with a 4-color FACSCalibur flow cytometer. Reverse transcription and real-time quantitative PCR and immunohistochemical staining were performed to analyze the production of IP-10 in lung tissue at autopsy. Conditional logistic regression was used to identify independent predictors for adverse disease outcome.Results: Increases in IP-10, MIG, and IL-8 during the first week after onset of fever were associated with adverse outcome (intensive care unit admission or death) in the univariate analysis. During the second week, only MIG concentration was associated with prognosis. After adjusting for other risk factors, plasma IP-10 concentration at the first week remained as an independent prognostic factor, with an odds ratio for adverse outcome of 1.52 (95% confidence interval, 1.05–2.55) per fold increase in plasma IP-10 concentration above the median. During the second week, chemokines provided little independent prognostic information. IP-10 was increased in lung tissue from patients who died of SARS.Conclusions: Increased plasma IP-10 during the first week of SARS symptoms is an independent predictor of outcome. Chemokine activation may be an early event in SARS, and an exaggerated host response may produce complications.
Hyperhomocysteinemia and arteriosclerosis: historical perspectives
Authors: McCully Kilmer S. 
Published: September 2005

AbstractEarly concepts of the origin of arteriosclerosis were introduced in the 19th century by Rokitansky and Virchow, who described mural thrombosis, inflammatory damage to arterial intima, increased intimal permeability to plasma, mucoid degeneration of arterial wall, deposition of plasma lipids in plaques, and fibrosis and calcification of plaques. Experimental production of arteriosclerosis by feeding animal foods to rabbits was attributed to protein intoxication by Ignatowsky in 1908 and to dietary cholesterol by Anitschkow in 1913. Newburgh confirmed the protein hypothesis in 1915–1925 but failed to identify which amino acid produced plaques because methionine (1922) and homocysteine (1932) had not yet been discovered. Cases of homocystinuria from inherited deficiency of cystathionine synthase were found to be associated with thrombosis and vascular disease in 1964. The index case of methionine synthase deficiency (cobalamin C disease) was found by McCully in 1969 to be associated with arteriosclerosis, leading to the homocysteine theory of arteriosclerosis. The theory explains experimental arteriosclerosis by deficiency of vitamin B
Homocysteine and vascular disease in diabetes: a double hit?
Authors: Huijberts Maya S. P. , Becker Annemarie , Stehouwer Coen D. A. 
Published: September 2005

AbstractCardiovascular disease is a major problem in diabetes, and risk factors presumably unrelated to diabetes, such as hyperhomocysteinaemia, may be related to the development of cardiovascular complications in diabetic individuals. Plasma homocysteine levels are usually normal in diabetes, although both lower and higher levels have been reported. Homocysteine levels in diabetes are modulated by hyperfiltration and renal dysfunction, as well as low folate status. Insulin resistance does not appear to be a major determinant of plasma homocysteine level. Hyperhomocysteinaemia has been associated with microalbuminuria and retinopathy in type 1 and type 2 diabetes. In patients with type 2 diabetes, plasma homocysteine concentration is a significant predictor of cardiovascular events and death. This relation seems to be stronger in subjects with diabetes than without. The underlying pathophysiological mechanism of this increased vascular risk remains unexplained, but may be related to worsening of endothelial dysfunction and/or structural vessel properties induced by oxidative stress. Because homocysteine and diabetes have apparent synergistic detrimental vascular effects, patients with diabetes are candidates for screening and treatment with folic acid until the results of ongoing clinical trials are available.
Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
Authors: van Guldener Coen , Stam Frank , Stehouwer Coen D. A. 
Published: September 2005

AbstractHyperhomocysteinaemia almost invariably occurs in patients with end-stage renal disease (ESRD), but there is debate whether, within the group of ESRD patients, higher or lower plasma homocysteine concentrations are related to an increased risk of vascular disease. Homocysteine is thought to be vasculotoxic in high concentrations, but it may also lead to elevated levels of its precursor, S-adenosylhomocysteine (AdoHcy), which is a potent inhibitor of the transmethylation pathway, in which S-adenosylmethionine (AdoMet) donates its methyl group to a variety of acceptors. Impairment of this transmethylation pathway in ESRD patients has been suggested by high AdoHcy levels, decreased AdoMet/AdoHcy ratios, decreased protein repair requiring methyltransferases, and by DNA hypomethylation. Stable isotope techniques using labelled methionine have indeed demonstrated a decreased whole body transmethylation flux in ESRD patients. These studies have also shown that folic acid treatment is capable of restoring transmethylation rates to normal values. The remaining hyperhomocysteinaemia after folic acid treatment in ESRD is probably due to a persistent impairment of homocysteine clearance through transsulphuration. DNA hypomethylation with its concurrent alterations in gene expression is largely improved by folate treatment. The adverse effects of hyperhomocysteinaemia in ESRD may thus be related to impaired transmethylation. Normalisation of plasma homocysteine does not seem to be required to restore transmethylation to normal levels in ESRD patients.
Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
Authors: Morkbak Anne L. , Heimdal Randi M. , Emmens Kathleen , Molloy Anne , Hvas Anne-Mette , Schneede Joern , Clarke Robert , Scott John M. , Ueland Per M. , Nexo Ebba 
Published: September 2005

AbstractA commercially available holotranscobalamin (holo-TC) radioimmunoassay (RIA) (Axis-Shield, Dundee, Scotland) was evaluated in four laboratories and compared with a holoTC ELISA run in one laboratory. The performance of the holoTC RIA assay was comparable in three of the four participating laboratories. The results from these three laboratories, involving at least 20 initial runs of “low”, “medium” and “high” serum-based controls (mean holoTC concentrations 34, 60 and 110pmol/L, respectively) yielded an intra-laboratory imprecision of 6–10%. No systematic inter-laboratory deviations were observed on runs involving 72 patient samples (holoTC concentration range 10–160pmol/L). A fourth laboratory demonstrated higher assay imprecision for control samples and systematic deviation of results for the patient samples. Measurement of holoTC by ELISA showed an imprecision of 4–5%, and slightly higher mean values for the controls (mean holoTC concentrations 40, 70 and 114pmol/L, respectively). Comparable results were obtained for the patient samples. The long-term intra-laboratory imprecision was 12% for the holoTC RIA and 6% for the ELISA. In conclusion, it would be prudent to check the calibration and precision prior to starting to use these holoTC assays in research or clinical practice. The results obtained using the holoTC RIA were similar to those obtained using the holoTC ELISA assay.
Betaine: a key modulator of one-carbon metabolism and homocysteine status
Authors: Ueland Per Magne , Holm Pål I. , Hustad Steinar 
Published: September 2005

AbstractBetaine serves as a methyl donor in a reaction converting homocysteine to methionine, catalysed by the enzyme betaine-homocysteine methyltransferase. It has been used for years to lower the concentration of plasma total homocysteine (tHcy) in patients with homocystinuria, and has recently been shown to reduce fasting and in particular post-methionine load (PML) tHcy in healthy subjects.Betaine exists in plasma at concentrations of about 30μmol/L; it varies 10-fold (from 9 to 90μmol/L) between individuals, but the intra-individual variability is small. Major determinants are choline, dimethylglycine and folate in plasma, folic acid intake and gender.Recent studies have demonstrated that plasma betaine is a stronger determinant of PML tHcy than are vitamin BTo conclude, betaine status is a component of an individual's biochemical make-up with ramifications to one-carbon metabolism. Betaine status should be investigated in pathologies related to altered metabolism of homocysteine and folate, including cardiovascular disease, cancer and neural tube defects.
Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
Authors: Jacobsen Donald W. , Catanescu Otilia , DiBello Patricia M. , Barbato John C. 
Published: September 2005

AbstractHyperhomocysteinemia is an independent risk factor for cardiovascular disease. Although there is a growing body of evidence that homocysteine plays a causal role in atherogenesis, specific mechanisms to explain the underlying pathology have remained elusive. This review focuses on chemistry unique to the homocysteine molecule to explain its inherent cytotoxicity. Thus, the high pKa of the sulfhydryl group (pKa=10.0) of homocysteine underlies its ability to form stable disulfide bonds with protein cysteine residues, and in the process, alters or impairs the function of the protein. Albumin, fibronectin, transthyretin, annexin II, and factor V have now been identified as molecular targets for homocysteine, and in the case of albumin, the mechanism of targeting has been elucidated.
Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
Authors: Schroecksnadel Katharina , Winkler Christiana , Wirleitner Barbara , Schennach Harald , Weiss Günter , Fuchs Dietmar 
Published: September 2005

AbstractInflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process. Resveratrol, a phenolic antioxidant synthesized in grapes and vegetables and present in wine, has also been supposed to be beneficial for the prevention of cardiovascular events. Apart from its strong antioxidant properties, resveratrol has also been demonstrated to act as an anti-inflammatory agent. In this study the influence of resveratrol on the production of homocysteine by stimulated human peripheral blood mononuclear cells (PBMCs) was investigated. Results were compared to earlier described effects of the anti-inflammatory compounds aspirin and salicylic acid and of the lipid-lowering drug atorvastatin. Stimulation of PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significantly higher homocysteine accumulation in supernatants compared with unstimulated cells. Treatment with 10–100μM resveratrol suppressed homocysteine formation in a dose-dependent manner. Resveratrol did not influence the release of homocysteine from resting PBMCs. The data suggest that resveratrol may prevent homocysteine accumulation in the blood by suppressing immune activation cascades and the proliferation of mitogen-driven T-cells. The effect of resveratrol to down-regulate the release of homo-cysteine was comparable to the decline of neopterin concentrations in the same experiments. The suppressive effect of resveratrol was very similar to results obtained earlier with aspirin, salicylic acid and atorvastatin; however, it appeared that doses of compounds needed to reduce homocysteine levels to 50% of stimulated cells were always slightly lower than those necessary to achieve the same effect on neopterin concentrations. The influence of resveratrol and of all the other compounds on homocysteine production appears to be independent of any direct effect on homocysteine biochemistry.
Homocysteine and B vitamins in mild cognitive impairment and dementia
Authors: Quadri Pierluigi , Fragiacomo Claudia , Pezzati Rita , Zanda Enrica , Tettamanti Mauro , Lucca Ugo 
Published: September 2005

AbstractElderly subjects with mild cognitive impairment have a high risk for conversion to Alzheimer's disease or are already in a preclinical dementia stage. By cross-sectionally comparing subjects in prodromal and early phases of dementia with non-demented controls, we tested the hypothesis whether low serum vitamin B
Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
Authors: Robbins Michael A. , Elias Merrill F. , Budge Marc M. , Brennan Suzanne L. , Elias Penelope K. 
Published: September 2005

AbstractType 2 diabetes mellitus and higher total plasma homocysteine concentrations are each associated with an increased incidence of cardiovascular disease and with diminished cognitive performance. Relations between homocysteine concentrations and cardiovascular disease incidence are stronger in the presence of type 2 diabetes mellitus. Therefore, we hypothesized that relations between homocysteine concentrations and cognitive performance would be stronger in the presence of type 2 diabetes. We related homocysteine concentrations and cognitive performance on the Mini-Mental State Examination in 817 dementia- and stroke-free participants of the Maine-Syracuse Study, 90 of whom were classified with type 2 diabetes mellitus. Regardless of statistical adjustment for age, sex, gender, vitamin co-factors (folate, vitamin B
Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
Authors: Teerlink Tom 
Published: September 2005

AbstractAsymmetric dimethylarginine (ADMA) is a potent inhibitor of nitric oxide synthase and is regarded as a novel risk factor for cardiovascular disease. The metabolic pathways of ADMA and homocysteine are strongly intertwined. First, during synthesis of ADMA, two equivalents of homocysteine are formed. Second, homocysteine has been shown to inhibit the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase. Finally, homocysteine, either directly or by increasing oxidative stress, may promote release of free ADMA by accelerating protein degradation. Currently used techniques for the quantification of ADMA in plasma are mostly based on liquid chromatography with fluorimetric or mass spectrometric detection. Plasma ADMA has a very narrow concentration distribution, with an inter-individual coefficient of variation of approximately 12%, and even slightly elevated ADMA concentrations are associated with increased cardiovascular disease risk. Therefore, to generate useful results in clinical research, high precision of the assay used for the quantification of ADMA assay is a matter of prime importance. Assays with a high coefficient of variation may lead to low statistical power in clinical trials and to a severe underestimation of the strength of associations in epidemiological studies.
Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
Authors: Herrmann Wolfgang , Isber Sonia , Obeid Rima , Herrmann Markus , Jouma Muhidien 
Published: September 2005

AbstractBackground: Hyperhomocysteinemia, a proxy measure for the nutritional status of the B vitamins, may be involved in the etiology of preeclampsia via inducing endothelial dysfunction. Asymmetric dimethylarginine (ADMA) is an inhibitor of NO-synthase that may adversely affect the endothelium.Materials and methods: We investigated serum concentrations of folate, vitamin BResults: Higher concentrations of Hcy, cystathionine and methylmalonic acid (MMA) were closely linked to a lower status of the B vitamins. Higher concentrations of Hcy and cystathionine were observed in the preeclamptic group than in the matched controls (median Hcy 9.3 vs. 6.0μmol/L; median cystathionine 284 vs. 232nmol/L). Serum folate was significantly lower in patients than in controls (16.4 vs. 36.0nmol/L). Folate supplementation was less likely to be used in preeclamptic women. Concentrations of MMA were elevated in patients and controls and did not differ significantly between the two groups. Median plasma concentrations of ADMA were significantly lower in asymptomatic women than in those who developed preeclampsia before the 37th week of gestation (0.61 vs. 0.68μmol/L).Conclusions: Elevated serum concentrations of Hcy, cystathionine and MMA indicate poor status of the B vitamins during pregnancy. The adverse effect of Hcy on endothelial function might be related to ADMA in early-onset preeclampsia. More emphasis should be placed on increasing the intake of B vitamins in pregnant women from developing countries.
Interactions between folate and aging for carcinogenesis
Authors: Choi Sang-Woon , Friso Simonetta 
Published: September 2005

AbstractInadequate folate intake and aging are each strongly implicated as important risk factors for certain cancers. Since both folate depletion and aging are strongly associated with hyperhomocysteinemia, genomic DNA hypomethylation, and increased uracil misincorporation into DNA, it appears that each of them enhances carcinogenesis by inducing a derangement of one-carbon metabolism that supplies one-carbons to biological methylation reactions and nucleotide synthesis. Recent studies have demonstrated that inadequate dietary folate and aging may interact and synergistically disturb the normal homeostasis of one-carbon metabolism, thereby provoking subsequent biochemical and molecular aberrations, including alterations in critical gene expression related to carcinogenesis. These studies have further indicated that modest folate supplementation may reverse or partially ameliorate those adverse effects induced by folate depletion and aging.