A case of refractory Sézary syndrome with large-cell transformation responsive to brentuximab vedotin.

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A case of refractory Sézary syndrome with large-cell transformation responsive to brentuximab vedotin.

JAMA Dermatol. 2014 Feb;150(2):210-2

Authors: Corey K, Cook D, Bekker J, Mugnaini E, Lin JH

PMID: 24352253 [PubMed - indexed for MEDLINE]

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Using spatial analysis to predict health care use at the local level: a case study of type 2 diabetes medication use and its association with demographic change and socioeconomic status.

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Using spatial analysis to predict health care use at the local level: a case study of type 2 diabetes medication use and its association with demographic change and socioeconomic status.

PLoS One. 2013;8(8):e72730

Authors: Dijkstra A, Janssen F, De Bakker M, Bos J, Lub R, Van Wissen LJ, Hak E

Abstract

Local health status and health care use may be negatively influenced by low local socio-economic profile, population decline and population ageing. To support the need for targeted local health care, we explored spatial patterns of type 2 diabetes mellitus (T2DM) drug use at local level and determined its association with local demographic, socio-economic and access to care variables. We assessed spatial variability in these associations. We estimated the five-year prevalence of T2DM drug use (2005-2009) in persons aged 45 years and older at four-digit postal code level using the University of Groningen pharmacy database IADB.nl. Statistics Netherlands supplied data on potential predictor variables. We assessed spatial clustering, correlations and estimated a multiple linear regression model and a geographically weighted regression (GWR) model. Prevalence of T2DM medicine use ranged from 2.0% to 25.4%. The regression model included the extent of population ageing, proportion of social welfare/benefits, proportion of low incomes and proportion of pensioners, all significant positive predictors of local T2DM drug use. The GWR model demonstrated considerable spatial variability in the association between T2DM drug use and above predictors and was more accurate. The findings demonstrate the added value of spatial analysis in predicting health care use at local level.

PMID: 24023636 [PubMed - indexed for MEDLINE]

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Metformin protects rat hepatocytes against bile acid-induced apoptosis.

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Metformin protects rat hepatocytes against bile acid-induced apoptosis.

PLoS One. 2013;8(8):e71773

Authors: Woudenberg-Vrenken TE, Conde de la Rosa L, Buist-Homan M, Faber KN, Moshage H

Abstract

BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD). Metformin activates AMP-activated protein kinase (AMPK), the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR). Both AMPK and mTOR are able to modulate cell death.

AIM: To evaluate the effects of metformin on hepatocyte cell death.

METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA) or TNFα in combination with actinomycin D (actD). AMPK, mTOR and phosphoinositide-3 kinase (PI3K)/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively.

RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation.

CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

PMID: 23951244 [PubMed - indexed for MEDLINE]

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Economic evaluation of a problem solving intervention to prevent recurrent sickness absence in workers with common mental disorders.

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Economic evaluation of a problem solving intervention to prevent recurrent sickness absence in workers with common mental disorders.

PLoS One. 2013;8(8):e71937

Authors: Arends I, Bültmann U, van Rhenen W, Groen H, van der Klink JJ

Abstract

OBJECTIVES: Workers with common mental disorders (CMDs) frequently experience recurrent sickness absence but scientifically evaluated interventions to prevent recurrences are lacking. The objectives of this study are to evaluate the cost-effectiveness and cost-benefit of a problem solving intervention aimed at preventing recurrent sickness absence in workers with CMDs compared to care as usual.

METHODS: An economic evaluation was conducted alongside a cluster-randomised controlled trial with 12 months follow-up. Treatment providers were randomised to either a 2-day training in the SHARP-at work intervention, i.e. a problem solving intervention, or care as usual. Effect outcomes were the incidence of recurrent sickness absence and time to recurrent sickness absence. Self-reported health care utilisation was measured by questionnaires. A cost-effectiveness analysis (CEA) from the societal perspective and a cost-benefit analysis (CBA) from the employer’s perspective were conducted.

RESULTS: The CEA showed that the SHARP-at work intervention was more effective but also more expensive than care as usual. The CBA revealed that employer’s occupational health care costs were significantly higher in the intervention group compared to care as usual. Overall, the SHARP-at work intervention showed no economic benefit compared to care as usual.

CONCLUSIONS: As implementation of the SHARP-at work intervention might require additional investments, health care policy makers need to decide if these investments are worthwhile considering the results that can be accomplished in reducing recurrent sickness absence.

PMID: 23951270 [PubMed - indexed for MEDLINE]

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Upregulation of endogenous ICAM-1 reduces ovarian cancer cell growth in the absence of immune cells.

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Upregulation of endogenous ICAM-1 reduces ovarian cancer cell growth in the absence of immune cells.

Int J Cancer. 2014 Jan 15;134(2):280-90

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Impaired long-term expansion and self-renewal potential of pediatric acute myeloid leukemia-initiating cells by PTK787/ZK 222584.

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Impaired long-term expansion and self-renewal potential of pediatric acute myeloid leukemia-initiating cells by PTK787/ZK 222584.

Mol Cancer Res. 2013…

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Are renin-angiotensin-aldosterone system inhibitors lifesaving in chronic kidney disease?

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Are renin-angiotensin-aldosterone system inhibitors lifesaving in chronic kidney disease?

J Am Coll Cardiol. 2014 Feb 25;63(7):659-60

Authors: …

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Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter.

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Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter.

Nucleic Acids Res. 2014 Feb;42(3):1563-74

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The impact of organisational external peer review on colorectal cancer treatment and survival in the Netherlands.

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The impact of organisational external peer review on colorectal cancer treatment and survival in the Netherlands.

Br J Cancer. 2014 Feb 18;110(4):850-8

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Prevalence of self-reported skin complaints and avoidance of common daily life consumer products in selected European Regions.

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Prevalence of self-reported skin complaints and avoidance of common daily life consumer products in selected European Regions.

JAMA Dermatol. 2014…

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Estimated albumin excretion rate versus urine albumin-creatinine ratio for the assessment of albuminuria: a diagnostic test study from the Prevention of Renal and Vascular Endstage Disease (PREVEND) Study.

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Estimated albumin excretion rate versus urine albumin-creatinine ratio for the assessment of albuminuria: a diagnostic test study from the Prevention of Renal and Vascular…

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Rationale and design of the DIPAK 1 study: a randomized controlled clinical trial assessing the efficacy of lanreotide to Halt disease progression in autosomal dominant polycystic kidney disease.

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Rationale and design of the DIPAK 1 study: a randomized controlled clinical trial assessing the efficacy of lanreotide to Halt disease progression in autosomal dominant…

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Fast LC-MS/MS analysis of tacrolimus, sirolimus, everolimus and cyclosporin A in dried blood spots and the influence of the hematocrit and immunosuppressant concentration on recovery.

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Fast LC-MS/MS analysis of tacrolimus, sirolimus, everolimus and cyclosporin A in dried blood spots and the influence of the hematocrit and immunosuppressant concentration on recovery.

Talanta. 2013 Oct 15;115:47-54

Authors: Koster RA, Alffenaar JW, Greijdanus B, Uges DR

Abstract

We developed a method for the analysis of four immunosuppressants in dried blood spot (DBS) samples to facilitate therapeutic drug monitoring for transplant patients outside the hospital. An 8mm disc from the central part of the DBS was punched, extracted and followed by LC-MS/MS analysis. The method was validated with ranges from 1.00-50.0 µg/L for tacrolimus, sirolimus and everolimus, and from 20.0-2000 µg/L for cyclosporin A. The validation showed a maximum overall bias of 13.0% for the sirolimus LLOQ, while the maximum overall CV was 15.7% for the everolimus LLOQ. All four immunosuppressants showed to be stable in DBS for at least 7 days at 22°C. The volume of the blood spot showed to have minor effect on measured concentrations. A cross-validation test between the 31 ET CHR paper and the Whatman FTA DMPK-C cards showed no significant difference between the two types of paper. During validation the hematocrit (HT) showed to have significant influence on the analytical results. When the measured concentrations were corrected for the effect of the HT, biases improved significantly. Additional recovery tests proved that the combination of especially low HT and high concentration does not only affect the spot size but can also affect the extraction recoveries of sirolimus and especially everolimus. Although the tested parameters like HT and concentrations are extreme and unlikely for routine analysis of outpatients, the fundamental effect of the combination of these parameters on extraction recoveries are proven with this research. The protein binding in the blood and hydrogen binding to the cellulose of the paper is suggested to influence extractions and gives new insights in the extraction methodology of DBS samples. The observed HT effect during the validation appeared to be negligible during the correlation study as no concentration corrections for the HT values were needed. Nevertheless, results from DBS samples with extremely high concentrations combined with extremely low HT values should be interpreted with caution. The patient correlation study showed good correlations with R(2) values higher than 0.87 between venous whole blood and venous DBS samples were observed for all four immunosuppressants. The Passing & Bablok plots showed positive biases of the slopes of 18% for tacrolimus and less than 12% for sirolimus, everolimus and cyclosporin A. The validated method, proved stability of the immunosuppressants in DBS, and the correlation study showed the capability of the DBS method to be used as an alternative for whole blood analysis in therapeutic drug monitoring.

PMID: 24054560 [PubMed - indexed for MEDLINE]

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Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants.

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Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants.

Gut. 2014 Mar;63(3):415-22

Authors: Romanos J, Rosén A, Kumar V, Trynka G, Franke L, Szperl A, Gutierrez-Achury J, van Diemen CC, Kanninga R, Jankipersadsing SA, Steck A, Eisenbarth G, van Heel DA, Cukrowska B, Bruno V, Mazzilli MC, Núñez C, Bilbao JR, Mearin ML, Barisani D, Rewers M, Norris JM, Ivarsson A, Boezen HM, Liu E, Wijmenga C, PreventCD Group

Abstract

BACKGROUND: The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD.

OBJECTIVE: We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing.

DESIGN: We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case-control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals.

RESULTS: Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations.

CONCLUSIONS: Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD.

PMID: 23704318 [PubMed - indexed for MEDLINE]

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Stump sensibility in children with upper limb reduction deficiency.

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Stump sensibility in children with upper limb reduction deficiency.

J Rehabil Med. 2014 Jan;46(1):51-8

Authors: Reinkingh M, Reinders-Messelink HA, Dijkstra PU, Maathuis KG, van der Sluis CK

Abstract

OBJECTIVES: To compare stump sensibility in children with upper limb reduction deficiency with sensibility of the unaffected arm and hand. In addition, to evaluate the associations between stump sensibility, stump length and activity level.

DESIGN: Cross-sectional study.

SUBJECTS: Children and young adults aged 6-25 years with upper limb reduction deficiency.

METHODS: Threshold of touch was measured with Semmes-Weinstein monofilaments, stereognosis was measured with the Shape-Texture Identification test and kinaesthesia and activity level was measured with the Child Amputee Prosthetics Project – Functional Status Inventory and the Prosthetic Upper Extremity Functional Index.

RESULTS: A total of 31 children with upper limb reduction deficiency (mean age 15 years, 3 prosthesis wearers) were investigated. The threshold of touch of the stump circumference was lower (indicating higher sensibility) than of the unaffected arm (p = 0.006), hand (p = 0.004) and stump end-point (p = < 0.001). Long stumps had higher threshold of touch (indicating lower sensibility) than short stumps (p = 0.046). Twenty-nine children recognized 1 or more shapes or textures with the stump. Kinaesthesia in the affected and unaffected sides was comparable. Sensibility was not correlated with activity level.

CONCLUSION: Threshold of touch, stereognosis and kinaesthesia of the affected sides were excellent. Threshold of touch of the stump circumference was lower (indicating higher sensibility) than of the unaffected arm and hand. High stump sensibility may clarify good functioning in the children without prostheses and contribute to prosthesis rejection.

PMID: 24036887 [PubMed - indexed for MEDLINE]

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Normothermic machine perfusion of discarded liver grafts.

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Normothermic machine perfusion of discarded liver grafts.

Am J Transplant. 2013 Sep;13(9):2504

Authors: Op den Dries S, Karimian N, Porte RJ

PMID: 23919300 [PubMed - indexed for MEDLINE]

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Changes in teachers’ involvement versus rejection and links with academic motivation during the first year of secondary education: a multilevel growth curve analysis.

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Changes in teachers’ involvement versus rejection and links with academic motivation during the first year of secondary education: a multilevel growth curve analysis. …

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The use of PET/CT in the radiotherapy treatment planning for esophageal cancer

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Association of intraoperative tissue oxygenation with suspected risk factors for tissue hypoxia.

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Association of intraoperative tissue oxygenation with suspected risk factors for tissue hypoxia.

J Clin Monit Comput. 2013 Oct;27(5):541-50

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Adolescent social stress does not necessarily lead to a compromised adaptive capacity during adulthood: a study on the consequences of social stress in rats.

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Adolescent social stress does not necessarily lead to a compromised adaptive capacity during adulthood: a study on the consequences of social stress in rats.

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