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High Plasma Levels (high + plasma_level)
Selected AbstractsHigh plasma levels of factor VIII and risk of recurrence of venous thromboembolismBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2004Legnani Cristina Summary The aim of this study was to evaluate the relationship between factor VIII (FVIII) levels, measured by chromogenic and clotting assays, and risk of venous thromboembolism (VTE) recurrence. A total of 564 patients underwent clinical follow-up after oral anticoagulant withdrawal (total follow-up = 924·4 years). Recurrent VTE developed in 39 of 309 (12·6%) patients with a first idiopathic VTE and in 14 of 255 (5·5%) patients whose first event was secondary. In patients with a first idiopathic VTE, the risk of recurrence was more than fivefold higher in patients with FVIII levels exceeding the 90th percentile [chromogenic FVIII: relative risk (RR) 5·43 (95% CI 1·76,16·8); clotting FVIII: RR 6·21 (95% CI 1·57,24·5)] after adjustment for all possible confounding variables. In patients with a first secondary VTE, the risk of recurrence was slightly higher in patients with high FVIII levels [chromogenic FVIII: RR 2·62 (95% CI 0·34,19·9); clotting FVIII: RR 1·74 (95% CI 0·25,12·1)], but, given the low number of recurrences, the 95% CI were very large. In conclusion, this study shows that high FVIII levels are associated with increased risk of VTE recurrence in patients with a first idiopathic VTE. Although the measurement of FVIII levels by a specific chromogenic assay might, in principle, be preferred to avoid the risk of aspecific clotting effects, no significant differences in results obtained by chromogenic or clotting methods were found. [source] Type 2 diabetes mellitus in UK children , an emerging problemDIABETIC MEDICINE, Issue 12 2000S. Ehtisham SUMMARY Aims Type 2 diabetes mellitus has never previously been described in UK children, although an increasing incidence in childhood is recognized in international studies. The prevalence of obesity in UK children is increasing and is a recognized risk factor for the development of diabetes. The aim of this study was to identify and characterize children with Type 2 diabetes in the West Midlands and Leicester. Methods Children were identified by contacting paediatricians responsible for diabetes in five hospitals. Details were collected on demographics, mode of presentation, investigations and treatment on a standard proforma. Results Eight girls were identified with Type 2 diabetes, aged 9,16 years and who were of Pakistani, Indian or Arabic origin. They were all overweight (percentage weight for height 141,209%) and had a family history of diabetes in at least two generations. They presented insidiously with hyperglycaemia and glycosuria without ketosis and five were asymptomatic. Islet cell antibodies measured in seven patients were negative. Four had acanthosis nigricans which is a cutaneous marker of insulin resistance and the other four had high plasma levels of insulin and/or C peptide. These patients are distinct from those with maturity-onset diabetes of the young (MODY). All were initially managed with dietary measures, seven have been treated with oral anti-diabetic agents of whom two have subsequently required insulin. Conclusions These are the first UK case reports of Type 2 diabetes in children. Paediatricians need to be aware of the risk of Type 2 diabetes developing in childhood in high-risk ethnic groups, particularly in association with obesity and a positive family history. [source] Ventricular tachycardia during hyperthermic intraperitoneal chemotherapyANAESTHESIA, Issue 10 2009C. A. Thix Summary Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is used for selected gastrointestinal carcinomas. We report a case of ventricular tachycardia during HIPEC with cisplatin that persisted as long as the chemotherapy solution remained in the intra-abdominal cavity. We hypothesise that high plasma levels of cisplatin with concomitant low magnesium levels caused the arrhythmia. [source] Effects of glucose and amino acids on ghrelin secretion in sheepANIMAL SCIENCE JOURNAL, Issue 2 2010Toshihisa SUGINO ABSTRACT Two experiments were conducted to elucidate the effects of post-ruminal administration of starch and casein (Exp. 1), plasma amino acids concentrations (Exp. 2), and plasma glucose and insulin concentrations (Exp. 2) on plasma ghrelin concentrations in sheep. In Exp. 1, plasma ghrelin concentrations were determined by four infusion treatments (water, cornstarch, casein and cornstarch plus casein) in four wethers. Abomasal infusion of casein increased plasma ,-amino N (AAN) concentrations. Infusion of starch or casein alone did not affect plasma ghrelin concentrations, but starch plus casein infusion increased plasma levels of ghrelin, glucose and AAN. In Exp 2, we investigated the effects of saline or amino acids on ghrelin secretion in four wethers. Two hours after the initiation of saline or amino acid infusion into the jugular vein, glucose was also continuously infused to investigate the effects of blood glucose and insulin by hyper-glycemic clump on plasma ghrelin concentrations. Infusion of amino acids alone raised plasma levels of ghrelin, but the higher plasma glucose and insulin concentrations had no effect on plasma ghrelin concentrations. These results suggest that high plasma levels of amino acids can stimulate ghrelin secretion, but glucose and insulin do not affect ghrelin secretion in sheep. [source] Defective phosphorylation of interleukin-18 receptor , causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 9 2009Wilco de Jager Objective Systemic-onset juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by arthritis and systemic features. Its pathogenesis is still largely unknown. It is characterized immunologically by natural killer (NK) cell dysfunction and cytokine signatures that predominantly feature interleukin-1 (IL-1), IL-6, and IL-18. Since IL-18 can drive NK cell function, we examined how the high plasma levels of this cytokine are related to the documented NK cell failure in these patients. Methods The phenotype and function of NK cells from 10 healthy control subjects, 15 patients with polyarticular JIA, and 15 patients with systemic-onset JIA were characterized by staining and functional assays in vitro. IL-18 ligand binding was visualized by fluorescence microscopy. Phosphorylation of several MAP kinases and the IL-18 receptor , (IL-18R,) were visualized by Western blotting. Results IL-18 from the plasma of systemic-onset JIA patients stimulated the activation of NK cells from healthy controls and bound its cognate receptor. However, NK cells from systemic-onset JIA patients failed to up-regulate cell-mediated killing molecules, such as perforin and interferon-,, after IL-18 stimulation. Furthermore, treatment with IL-18 did not induce the phosphorylation of receptor-activated MAP kinases in NK cells. Alternate activation of NK cells by IL-12 induced NK cell cytotoxicity. We observed no additive effect of IL-18 in combination with IL-12 in systemic-onset JIA patients. Immunoprecipitation of IL-18R, showed that NK cells from systemic-onset JIA could not phosphorylate this receptor after IL-18 stimulation. Conclusion The mechanism of the impaired NK cell function in systemic-onset JIA involves a defect in IL-18R, phosphorylation. This observation has major implications for the understanding and, ultimately, the treatment of systemic-onset JIA. [source] Generalized Wegener's granulomatosis in an immunocompetent adult after cytomegalovirus mononucleosis and bacterial urinary tract infectionARTHRITIS & RHEUMATISM, Issue 5 2009Stefania Varani Human cytomegalovirus (HCMV) is frequently detected in autoimmune diseases, but its role in such disorders is poorly understood. Herein we describe the case of a young woman who developed generalized Wegener's granulomatosis (WG) after HCMV mononucleosis and urinary tract infection. During mononucleosis, the patient had extraordinarily high plasma levels of proinflammatory cytokines such as interleukin-5 and lymphotoxin ,, autoantibodies, and a higher blood level of viral DNA than were found in other immunocompetent patients infected with HCMV or healthy controls. Active HCMV replication was detected after the onset of vasculitis, and HCMV genomes or antigens were found in blood, urine, and inflammatory lesions on the kidney. Thus, HCMV may have triggered or exacerbated inflammation and autoimmunity in this case of WG. [source] Metabolism of Desipramine in Japanese Psychiatric Patients: The Impact of CYP2D6 Genotype on the Hydroxylation of DesipramineBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2000Kazutaka Shimoda We investigated the impact of the genotype of CYP2D6 on the hydroxylation of desipramine in eighteen patients who were administered desipramine hydrochloride per os. Significantly higher plasma concentration of desipramine/daily dose of desipramine/body weight was observed in the subjects with two mutated alleles than in the subjects with either no mutated alleles or one mutated allele (two mutated alleles versus no mutated alleles=530.4±215.2 versus 118.1±63.9 ng/ml/mg/kg, t=5.68, P<0.001; two mutated alleles versus one mutated allele=530.4±215.2 versus 176.2±62.3 ng/ml/mg/kg, P<0.001; One-way analysis of variance followed by Bonferroni's multiple comparison test, respectively). Significantly higher ratio of desipramine/2-hydroxy-desipramine was observed in the subjects with two mutated alleles compared to subjects with no mutated alleles or the subjects with one mutated allele (two mutated alleles versus one mutated allele=4.39±0.36 versus 2.00±0.64, t=5.12, P<0.001; two mutated alleles versus no mutated alleles=4.39±0.36 versus 2.02±0.59, t=4.42, P<0.01). The genotyping of CYP2D6 only grossly predicts the steady state concentration of desipramine, mainly predicts the risk of getting very high plasma levels. Within each genotype there is marked interindividual variability. [source] | ||||||||||