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  1. Article ; Online: Effect of acute variations of insulin and glucose on plasma concentrations of asymmetric dimethylarginine in young people with Type 1 diabetes.

    Marcovecchio, M Loredana / Widmer, Barry / Dunger, David B / Dalton, R Neil

    Clinical science (London, England : 1979)

    2008  Volume 115, Issue 12, Page(s) 361–369

    Abstract: ADMA (asymmetric dimethylarginine), an endogenous inhibitor of nitric oxide synthase, is considered a major risk factor for cardiovascular disease and progression of renal disease. In the present study we aim to investigate the effect of acute variations ...

    Abstract ADMA (asymmetric dimethylarginine), an endogenous inhibitor of nitric oxide synthase, is considered a major risk factor for cardiovascular disease and progression of renal disease. In the present study we aim to investigate the effect of acute variations in plasma glucose and insulin on plasma ADMA levels in young people with T1D (Type 1 diabetes). Fifteen young patients (ten males) with T1D, median age 18.3 (13.2-24.4) years, HbA(1c) (glycated haemoglobin) 9% (6.4-13.6%), underwent an overnight (18:00-08:00 hours) variable insulin infusion for euglycaemia, followed by a hyperinsulinaemic-euglycaemic clamp (08:00-12:00 hours). Blood samples were collected every 15 min for determination of ADMA, SDMA (symmetric dimethylarginine), valine, phenylalanine, arginine, creatinine and glucose. Insulin levels were assessed every 30 min. During the overnight period, glucose levels increased following the evening meal. In response to the protein intake there was a significant increase in ADMA, arginine, valine, phenylalanine and creatinine. For the remaining part of the night, glucose levels progressively decreased reaching 5 mmol/l by 04:00 hours. ADMA and SDMA did not change significantly. During the hyperinsulinaemic clamp, a significant fall in ADMA was observed, from 0.468+/-0.056 to 0.364+/-0.050 micromol/l (P<0.001). A significant fall was also found in SDMA, valine, phenylalanine, arginine and the ADMA/SDMA ratio (all P<0.001), but not in creatinine levels. No correlation was found between insulin sensitivity and ADMA. We conclude that acute changes in glycaemia do not significantly affect plasma ADMA levels whereas infusion of insulin significantly reduces ADMA, suggesting an important role for insulin in the regulation of this cardiovascular risk factor.
    MeSH term(s) Adolescent ; Arginine/analogs & derivatives ; Arginine/blood ; Biomarkers/blood ; Blood Glucose/metabolism ; Creatinine/blood ; Diabetes Mellitus, Type 1/blood ; Drug Administration Schedule ; Female ; Glucose Clamp Technique ; Humans ; Insulin/administration & dosage ; Insulin/blood ; Male ; Phenylalanine/blood ; Valine/blood ; Young Adult
    Chemical Substances Biomarkers ; Blood Glucose ; Insulin ; Phenylalanine (47E5O17Y3R) ; N,N-dimethylarginine (63CV1GEK3Y) ; Arginine (94ZLA3W45F) ; Creatinine (AYI8EX34EU) ; Valine (HG18B9YRS7)
    Language English
    Publishing date 2008-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 206835-7
    ISSN 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
    ISSN (online) 1470-8736
    ISSN 0301-0538 ; 0009-0360 ; 0143-5221
    DOI 10.1042/CS20080079
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  2. Article ; Online: Cognitive-behavioural therapy and short-term psychoanalytic psychotherapy versus brief psychosocial intervention in adolescents with unipolar major depression (IMPACT): a multicentre, pragmatic, observer-blind, randomised controlled trial.

    Goodyer, Ian M / Reynolds, Shirley / Barrett, Barbara / Byford, Sarah / Dubicka, Bernadka / Hill, Jonathan / Holland, Fiona / Kelvin, Raphael / Midgley, Nick / Roberts, Chris / Senior, Rob / Target, Mary / Widmer, Barry / Wilkinson, Paul / Fonagy, Peter

    Health technology assessment (Winchester, England)

    2017  Volume 21, Issue 12, Page(s) 1–94

    Abstract: Background: Although there are effective psychological treatments for unipolar major depression in adolescents, whether or not one or more of the available therapies maintain reduced depressive symptoms 1 year after the end of treatment is not known. ... ...

    Abstract Background: Although there are effective psychological treatments for unipolar major depression in adolescents, whether or not one or more of the available therapies maintain reduced depressive symptoms 1 year after the end of treatment is not known. This is a non-trivial issue because maintaining lowered depressive symptoms below a clinical threshold level reduces the risk for diagnostic relapse into the adult years.
    Objective: To determine whether or not either of two specialist psychological treatments, cognitive-behavioural therapy (CBT) or short-term psychoanalytic psychotherapy (STPP), is more effective than a reference brief psychosocial intervention (BPI) in maintaining reduction of depression symptoms in the year after treatment.
    Design: Observer-blind, parallel-group, pragmatic superiority randomised controlled trial.
    Setting: A total of 15 outpatient NHS clinics in the UK from East Anglia, north-west England and North London.
    Participants: Adolescents aged 11-17 years with
    Interventions: In total, 154 adolescents received CBT, 156 received STPP and 155 received BPI. The trial lasted 86 weeks and study treatments were delivered in the first 36 weeks, with 52 weeks of follow-up.
    Main outcome measures: Mean sum score on self-reported depressive symptoms (primary outcome) at final study assessment (nominally 86 weeks, at least 52 weeks after end of treatment). Secondary measures were change in mean sum scores on self-reported anxiety symptoms and researcher-rated Health of the Nation scales for children and adolescents measuring psychosocial function. Following baseline assessment, there were a further five planned follow-up reassessments at nominal time points of 6, 12, 52 and 86 weeks post randomisation.
    Results: There were non-inferiority effects of CBT compared with STPP [treatment effect by final follow-up = -0.578, 95% confidence interval (CI) -2.948 to 4.104;
    Conclusions: The three psychological treatments differed markedly in theoretical and clinical approach and are associated with a similar degree of clinical improvement, cost-effectiveness and subsequent maintenance of lowered depressive symptoms. Both STPP and BPI offer an additional patient treatment choice, alongside CBT, for depressed adolescents attending specialist Child and Adolescent Mental Health Services. Further research should focus on psychological mechanisms that are associated with treatment response, the maintenance of positive effects, determinants of non-response and whether or not brief psychotherapies are of use in primary care and community settings.
    Limitations: Neither reason for SSRI prescribing or monitoring of medication compliance was controlled for over the course of the study, and the economic results were limited by missing data.
    Trial registration: Current Controlled Trials ISRCTN83033550.
    Funding: This project was funded by the National Institute for Heath Research Health Technology Assessment programme and will be published in full in
    MeSH term(s) Adolescent ; Child ; Cognitive Behavioral Therapy/economics ; Cognitive Behavioral Therapy/methods ; Cost-Benefit Analysis ; Depressive Disorder, Major/therapy ; Female ; Humans ; Male ; Psychotherapy/economics ; Psychotherapy/methods ; Single-Blind Method ; State Medicine ; United Kingdom
    Language English
    Publishing date 2017-05-05
    Publishing country England
    Document type Journal Article ; Observational Study ; Randomized Controlled Trial
    ZDB-ID 2006765-3
    ISSN 2046-4924 ; 1366-5278
    ISSN (online) 2046-4924
    ISSN 1366-5278
    DOI 10.3310/hta21120
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  3. Article ; Online: Cognitive behavioural therapy and short-term psychoanalytical psychotherapy versus a brief psychosocial intervention in adolescents with unipolar major depressive disorder (IMPACT): a multicentre, pragmatic, observer-blind, randomised controlled superiority trial.

    Goodyer, Ian M / Reynolds, Shirley / Barrett, Barbara / Byford, Sarah / Dubicka, Bernadka / Hill, Jonathan / Holland, Fiona / Kelvin, Raphael / Midgley, Nick / Roberts, Chris / Senior, Rob / Target, Mary / Widmer, Barry / Wilkinson, Paul / Fonagy, Peter

    The lancet. Psychiatry

    2016  Volume 4, Issue 2, Page(s) 109–119

    Abstract: Background: Psychological treatments for adolescents with unipolar major depressive disorder are associated with diagnostic remission within 28 weeks in 65-70% of patients. We aimed to assess the medium-term effects and costs of psychological therapies ... ...

    Abstract Background: Psychological treatments for adolescents with unipolar major depressive disorder are associated with diagnostic remission within 28 weeks in 65-70% of patients. We aimed to assess the medium-term effects and costs of psychological therapies on maintenance of reduced depression symptoms 12 months after treatment.
    Methods: We did this multicentre, pragmatic, observer-blind, randomised controlled superiority trial (IMPACT) at 15 National Health Service child and adolescent mental health service (CAMHS) clinics in three regions in England. Adolescent patients (aged 11-17 years) with a diagnosis of DSM IV major depressive disorder were randomly assigned (1:1:1), via a web-based randomisation service, to receive cognitive behavioural therapy (CBT) or short-term psychoanalytical therapy versus a reference brief psychological intervention. Randomisation was stochastically minimised by age, sex, self-reported depression sum score, and region. Patients and clinicians were aware of group allocation, but allocation was concealed from outcome assessors. Patients were followed up and reassessed at weeks 6, 12, 36, 52, and 86 post-randomisation. The primary outcome was self-reported depression symptoms at weeks 36, 52, and 86, as measured with the self-reported Mood and Feelings Questionnaire (MFQ). Because our aim was to compare the two psychological therapies with the brief psychosocial intervention, we first established whether CBT was inferior to short-term psychoanalytical psychotherapy for the same outcome. Primary analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN83033550.
    Findings: Between June 29, 2010, and Jan 17, 2013, we randomly assigned 470 patients to receive the brief psychosocial intervention (n=158), CBT (n=155), or short-term psychoanalytical therapy (n=157); 465 patients comprised the intention-to-treat population. 392 (84%) patients had available data for primary analysis by the end of follow-up. Treatment fidelity and differentiation were established between the three interventions. The median number of treatment sessions differed significantly between patients in the brief psychosocial intervention group (n=6 [IQR 4-11]), CBT group (n=9 [5-14]), and short-term psychoanalytical therapy group (n=11 [5-23]; p<0·0001), but there was no difference between groups in the average duration of treatment (27·5 [SD 21·5], 24·9 [17·7], 27·9 [16·8] weeks, respectively; Kruskal-Wallis p=0·238). Self-reported depression symptoms did not differ significantly between patients given CBT and those given short-term psychoanalytical therapy at weeks 36 (treatment effect 0·179, 95% CI -3·731 to 4·088; p=0·929), 52 (0·307, -3·161 to 3·774; p=0·862), or 86 (0·578, -2·948 to 4·104; p=0·748). These two psychological treatments had no superiority effect compared with brief psychosocial intervention at weeks 36 (treatment effect -3·234, 95% CI -6·611 to 0·143; p=0·061), 52 (-2·806, -5·790 to 0·177; p=0·065), or 86 (-1·898, -4·922 to 1·126; p=0·219). Physical adverse events (self-reported breathing problems, sleep disturbances, drowsiness or tiredness, nausea, sweating, and being restless or overactive) did not differ between the groups. Total costs of the trial interventions did not differ significantly between treatment groups.
    Interpretation: We found no evidence for the superiority of CBT or short-term psychoanalytical therapy compared with a brief psychosocial intervention in maintenance of reduced depression symptoms 12 months after treatment. Short-term psychoanalytical therapy was as effective as CBT and, together with brief psychosocial intervention, offers additional patient choice for psychological therapy, alongside CBT, for adolescents with moderate to severe depression who are attending routine specialist CAMHS clinics.
    Funding: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and the Department of Health.
    MeSH term(s) Adolescent ; Child ; Cognitive Behavioral Therapy/methods ; Cost-Benefit Analysis ; Depressive Disorder, Major/psychology ; Depressive Disorder, Major/therapy ; England ; Female ; Humans ; Linear Models ; Male ; Psychiatric Status Rating Scales ; Self Report ; State Medicine/economics ; Treatment Outcome
    Language English
    Publishing date 2016-12-01
    Publishing country England
    Document type Equivalence Trial ; Journal Article ; Multicenter Study ; Pragmatic Clinical Trial ; Research Support, Non-U.S. Gov't
    ISSN 2215-0374
    ISSN (online) 2215-0374
    DOI 10.1016/S2215-0366(16)30378-9
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  4. Article ; Online: Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus.

    Hagan, Cindy C / Graham, Julia M E / Tait, Roger / Widmer, Barry / van Nieuwenhuizen, Adrienne O / Ooi, Cinly / Whitaker, Kirstie J / Simas, Tiago / Bullmore, Edward T / Lennox, Belinda R / Sahakian, Barbara J / Goodyer, Ian M / Suckling, John

    NeuroImage. Clinical

    2015  Volume 7, Page(s) 391–399

    Abstract: Objective: There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group ... ...

    Abstract Objective: There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity.
    Method: Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects.
    Results: Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms.
    Conclusions: The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain.
    MeSH term(s) Adolescent ; Child ; Cross-Sectional Studies ; Depressive Disorder, Major/pathology ; Female ; Gray Matter/pathology ; Gyrus Cinguli/pathology ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Thalamus/pathology
    Language English
    Publishing date 2015-01-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701571-3
    ISSN 2213-1582 ; 2213-1582
    ISSN (online) 2213-1582
    ISSN 2213-1582
    DOI 10.1016/j.nicl.2014.12.019
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  5. Article: C-Reactive Protein in Relation to the Development of Microalbuminuria in Type 1 Diabetes: The Oxford Regional Prospective Study

    Marcovecchio, M. Loredana / Giannini, Cosimo / Widmer, Barry / Dalton, R. Neil / Martinotti, Stefano / Chiarelli, Francesco / Dunger, David B

    Diabetes care. 2008 May, v. 31, no. 5

    2008  

    Abstract: OBJECTIVE:S--To perform a longitudinal evaluation of high-sensitivity C-reactive protein (hs-CRP) in young people with type 1 diabetes in relation to the development of microalbuminuria (MA). RESEARCH DESIGN AND METHODS--hs-CRP was measured in 329 blood ... ...

    Abstract OBJECTIVE:S--To perform a longitudinal evaluation of high-sensitivity C-reactive protein (hs-CRP) in young people with type 1 diabetes in relation to the development of microalbuminuria (MA). RESEARCH DESIGN AND METHODS--hs-CRP was measured in 329 blood samples collected from 49 subjects with type 1 diabetes with MA and 49 normoalbuminuric subjects matched for age, sex, and duration of diabetes. RESULTS:--In subjects developing MA, a progressive rise in hs-CRP was detected with levels significantly higher in the years after the onset of MA when compared with levels before MA onset (P = 0.003; age-adjusted P = 0.06). After the onset of MA, hs-CRP levels were significantly higher in subjects with MA when compared with normoalbuminuric subjects (median 1.9 mg/l [range 0.2-9.8] vs. 1.1 mg/l [0.2-6.4]; P = 0.02; adjusted P = 0.036). CONCLUSIONS:--In this population of young subjects with type 1 diabetes, there was a significant increase in hs-CRP levels after the onset of MA, likely reflecting a general state of inflammation.
    Keywords C-reactive protein ; blood ; inflammation ; insulin-dependent diabetes mellitus ; people ; prospective studies
    Language English
    Size p. 974-976.
    Publishing place American Diabetes Association
    Document type Article
    ZDB-ID 441231-x
    ISSN 1935-5548 ; 0149-5992
    ISSN (online) 1935-5548
    ISSN 0149-5992
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  6. Article ; Online: Clinical characteristics associated with the prescribing of SSRI medication in adolescents with major unipolar depression.

    Cousins, Lesley / Whitaker, Kirstie J / Widmer, Barry / Midgley, Nick / Byford, Sarah / Dubicka, Bernadka / Kelvin, Raphael / Reynolds, Shirley / Roberts, Christopher / Holland, Fiona / Barrett, Barbara / Senior, Robert / Wilkinson, Paul / Target, Mary / Fonagy, Peter / Goodyer, Ian M

    European child & adolescent psychiatry

    2016  Volume 25, Issue 12, Page(s) 1287–1295

    Abstract: Unipolar major depressions (MD) emerge markedly during adolescence. National Institute for Health and Care Excellence (NICE) UK recommends psychological therapies, with accompanying selective serotonin reuptake inhibitors (SSRIs) prescribed in severe ... ...

    Abstract Unipolar major depressions (MD) emerge markedly during adolescence. National Institute for Health and Care Excellence (NICE) UK recommends psychological therapies, with accompanying selective serotonin reuptake inhibitors (SSRIs) prescribed in severe cases only. Here, we seek to determine the extent and rationale of SSRI prescribing in adolescent MD before entering a randomised clinical trial. SSRI prescribing, together with their clinical characteristics was determined in 465 adolescent patients with MD prior to receiving a standardised psychological therapy as part of the Improving mood with psychoanalytic and cognitive therapies (IMPACT) clinical trial. Overall, 88 (19 %) had been prescribed antidepressants prior to psychological treatment. The clinical correlates varied by gender: respectively, depression severity in boys and self-harming behaviours in girls. Prescribing also differed between clinical research centres. Medical practitioners consider severity of depression in boys as an indicator for antidepressant prescribing. Self-injury in girls appears to be utilised as a prescribing aid which is inconsistent with past and current revised UK NICE guidelines.
    MeSH term(s) Adolescent ; Antidepressive Agents/therapeutic use ; Depressive Disorder, Major/diagnosis ; Depressive Disorder, Major/drug therapy ; Depressive Disorder, Major/psychology ; Drug Prescriptions ; Female ; Humans ; Male ; Self-Injurious Behavior/diagnosis ; Self-Injurious Behavior/drug therapy ; Self-Injurious Behavior/psychology ; Serotonin Uptake Inhibitors/therapeutic use ; Severity of Illness Index ; Sex Characteristics ; Surveys and Questionnaires
    Chemical Substances Antidepressive Agents ; Serotonin Uptake Inhibitors
    Language English
    Publishing date 2016-04-28
    Publishing country Germany
    Document type Journal Article ; Multicenter Study ; Randomized Controlled Trial
    ZDB-ID 1118299-4
    ISSN 1435-165X ; 1018-8827 ; 1433-5719
    ISSN (online) 1435-165X
    ISSN 1018-8827 ; 1433-5719
    DOI 10.1007/s00787-016-0849-y
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  7. Article ; Online: Symmetric dimethylarginine, an endogenous marker of glomerular filtration rate, and the risk for microalbuminuria in young people with type 1 diabetes.

    Marcovecchio, M Loredana / Dalton, R Neil / Turner, Charles / Prevost, A Toby / Widmer, Barry / Amin, Rakesh / Dunger, David B

    Archives of disease in childhood

    2010  Volume 95, Issue 2, Page(s) 119–124

    Abstract: Objectives: To perform a cross-sectional comparison of endogenous markers of glomerular filtration rate (GFR) (plasma symmetric dimethylarginine (SDMA) and estimated GFR (eGFR)) with a direct measure of GFR (using the plasma clearance of Inutest (In-GFR) ...

    Abstract Objectives: To perform a cross-sectional comparison of endogenous markers of glomerular filtration rate (GFR) (plasma symmetric dimethylarginine (SDMA) and estimated GFR (eGFR)) with a direct measure of GFR (using the plasma clearance of Inutest (In-GFR)), and a longitudinal evaluation of these markers in relation to the development of microalbuminuria, in young people with type 1 diabetes (T1D).
    Methods: Longitudinal stored blood samples (n=1105) were available from 417 young people from the Oxford Regional Prospective Study (an inception cohort of 527 children followed for a median of 10.3 (interquartile range 7.1-12.3) years), for measurement of SDMA and creatinine. Additional annually collected data on anthropometric parameters, HbA1c, insulin dose and three early morning albumin:creatinine ratios were available. In-GFR was measured in a representative subgroup of 183 subjects.
    Main outcome measures: SDMA and eGFR.
    Results: SDMA and eGFR were significantly and similarly associated with In-GFR (r=-0.38 and r=0.36, p<0.001). Overall SDMA levels were lower in microalbuminuric (n=116) than normoalbuminuric subjects (n=301) (0.385 + or - 0.063 vs 0.412 + or - 0.059 micromol/l, p<0.001), probably reflecting hyperfiltration. The pattern of change in SDMA levels with age differed between microalbuminuric and normoalbuminuric subjects. Whereas SDMA levels declined in both groups until the age of 16 years, thereafter they tended to rise only in microalbuminuric subjects, probably reflecting a decline in renal function.
    Conclusions: In this longitudinal study of young people with T1D, measurement of SDMA, in contrast to eGFR, proved to be a reliable marker in identifying changes in filtration rates associated with the development of microalbuminuria (MA).
    MeSH term(s) Adolescent ; Age of Onset ; Albuminuria/blood ; Albuminuria/epidemiology ; Albuminuria/etiology ; Albuminuria/physiopathology ; Arginine/analogs & derivatives ; Arginine/blood ; Biomarkers/blood ; Child ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/epidemiology ; Diabetes Mellitus, Type 1/physiopathology ; Diabetic Nephropathies/blood ; Diabetic Nephropathies/epidemiology ; Diabetic Nephropathies/physiopathology ; Disease Progression ; England/epidemiology ; Epidemiologic Methods ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Prognosis
    Chemical Substances Biomarkers ; symmetric dimethylarginine (49787G1ULV) ; Arginine (94ZLA3W45F)
    Language English
    Publishing date 2010-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 524-1
    ISSN 1468-2044 ; 0003-9888 ; 1359-2998
    ISSN (online) 1468-2044
    ISSN 0003-9888 ; 1359-2998
    DOI 10.1136/adc.2009.158394
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  8. Article: Maternal but Not Paternal Association of Ambulatory Blood Pressure With Albumin Excretion in Young Offspring With Type 1 Diabetes

    Marcovecchio, M. Loredana / Tossavainen, Paivi H / Acerini, Carlo L / Barrett, Timothy G / Edge, Julie / Neil, Andrew / Shield, Julian / Widmer, Barry / Dalton, R. Neil / Dunger, David B

    Diabetes care. 2010 Feb., v. 33, no. 2

    2010  

    Abstract: OBJECTIVE: Familial predisposition to hypertension has been associated with the development of diabetic nephropathy in adults, but there are limited data in adolescents. Our aim was to assess whether parental ambulatory blood pressure (ABP) was ... ...

    Abstract OBJECTIVE: Familial predisposition to hypertension has been associated with the development of diabetic nephropathy in adults, but there are limited data in adolescents. Our aim was to assess whether parental ambulatory blood pressure (ABP) was associated with ABP and albumin excretion in young offspring with type 1 diabetes. RESEARCH DESIGN AND METHODS: Twenty-four-hour ABP monitoring was performed in 509 young offspring (mean ± SD age 15.8 ± 2.3 years) with type 1 diabetes, 311 fathers, and 444 mothers. Systolic (SBP) and diastolic blood pressure (DBP) measurements during 24 h, daytime, and nighttime were calculated. Three early morning urinary albumin-to-creatinine ratios (ACRs), A1C, and anthropometric parameters were available for the offspring. RESULTS: All paternal ABP parameters, except for nighttime SBP, were independently related to the offspring's ABP (24-h SBP β = 0.18, 24-h DBP β = 0.22, daytime SBP β = 0.25, daytime DBP β = 0.23, and nighttime DBP β = 0.18; all P < 0.01). Maternal 24-h DBP (β = 0.19, P = 0.004), daytime DBP (β = 0.09, P = 0.04), and nighttime SBP (β = 0.24 P = 0.001) were related to the corresponding ABP parameter in the offspring. Significant associations were found between the offspring's logACR and maternal ABP. The association with 24-h DBP (β = 0.16, P = 0.02), daytime DBP (β = 0.16 P = 0.02), and nighttime DBP (β = 0.15 P = 0.03) persisted even after adjustment for the offspring's ABP. Mothers of offspring with microalbuminuria had higher ABP than mothers of offspring without microalbuminuria (all P < 0.05). CONCLUSIONS: In this cohort, parental ABP significantly influenced offspring blood pressure, therefore confirming familial influences on this trait. In addition, maternal ABP, particularly DBP, was closely related to ACR in the offspring, suggesting a dominant effect of maternal genes or an effect of the intrauterine environment on microalbuminuria risk.
    Keywords adolescents ; adults ; albumins ; diabetic nephropathy ; diastolic blood pressure ; excretion ; fathers ; genes ; hypertension ; insulin-dependent diabetes mellitus ; maternal effect ; monitoring ; mothers ; progeny ; risk
    Language English
    Size p. 366-371.
    Publishing place American Diabetes Association
    Document type Article
    ZDB-ID 441231-x
    ISSN 1935-5548 ; 0149-5992
    ISSN (online) 1935-5548
    ISSN 0149-5992
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  9. Article ; Online: C-reactive protein in relation to the development of microalbuminuria in type 1 diabetes: the Oxford Regional Prospective Study.

    Marcovecchio, M Loredana / Giannini, Cosimo / Widmer, Barry / Dalton, R Neil / Martinotti, Stefano / Chiarelli, Francesco / Dunger, David B

    Diabetes care

    2008  Volume 31, Issue 5, Page(s) 974–976

    Abstract: Objectives: To perform a longitudinal evaluation of high-sensitivity C-reactive protein (hs-CRP) in young people with type 1 diabetes in relation to the development of microalbuminuria (MA).: Research design and methods: hs-CRP was measured in 329 ... ...

    Abstract Objectives: To perform a longitudinal evaluation of high-sensitivity C-reactive protein (hs-CRP) in young people with type 1 diabetes in relation to the development of microalbuminuria (MA).
    Research design and methods: hs-CRP was measured in 329 blood samples collected from 49 subjects with type 1 diabetes with MA and 49 normoalbuminuric subjects matched for age, sex, and duration of diabetes.
    Results: In subjects developing MA, a progressive rise in hs-CRP was detected with levels significantly higher in the years after the onset of MA when compared with levels before MA onset (P = 0.003; age-adjusted P = 0.06). After the onset of MA, hs-CRP levels were significantly higher in subjects with MA when compared with normoalbuminuric subjects (median 1.9 mg/l [range 0.2-9.8] vs. 1.1 mg/l [0.2-6.4]; P = 0.02; adjusted P = 0.036).
    Conclusions: In this population of young subjects with type 1 diabetes, there was a significant increase in hs-CRP levels after the onset of MA, likely reflecting a general state of inflammation.
    MeSH term(s) Adolescent ; Albuminuria/blood ; Albuminuria/diagnosis ; C-Reactive Protein/analysis ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/complications ; Female ; Glycated Hemoglobin A/metabolism ; Humans ; Male ; Reference Values
    Chemical Substances Glycated Hemoglobin A ; C-Reactive Protein (9007-41-4)
    Language English
    Publishing date 2008-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 441231-x
    ISSN 1935-5548 ; 0149-5992
    ISSN (online) 1935-5548
    ISSN 0149-5992
    DOI 10.2337/dc07-2101
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance-Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT).

    Hagan, Cindy C / Graham, Julia Me / Widmer, Barry / Holt, Rosemary J / Ooi, Cinly / van Nieuwenhuizen, Adrienne O / Fonagy, Peter / Reynolds, Shirley / Target, Mary / Kelvin, Raphael / Wilkinson, Paul O / Bullmore, Edward T / Lennox, Belinda R / Sahakian, Barbara J / Goodyer, Ian / Suckling, John

    BMC psychiatry

    2013  Volume 13, Page(s) 247

    Abstract: Background: Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients ... ...

    Abstract Background: Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making.
    Methods/design: Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550).
    Discussion: MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response.
    Trial registration: Adjunctive study to IMPACT trial (Current Controlled Trials: ISRCTN83033550).
    MeSH term(s) Adolescent ; Affect ; Clinical Protocols ; Cognitive Behavioral Therapy/methods ; Depressive Disorder/psychology ; Depressive Disorder/therapy ; Humans ; Magnetic Resonance Imaging ; Research Design ; Treatment Outcome
    Language English
    Publishing date 2013-10-05
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2050438-X
    ISSN 1471-244X ; 1471-244X
    ISSN (online) 1471-244X
    ISSN 1471-244X
    DOI 10.1186/1471-244X-13-247
    Database MEDical Literature Analysis and Retrieval System OnLINE

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