Diagnostische und prognostische Bedeutung der HLA-Genotypisierung bei Rheutmatoider Arthritis

Gegenstand der vorgelegten Arbeit ist die Untersuchung des HLA DR4-Status hinsichtlich seiner diagnostischen und prognostischen Aussagefähigkeit bei Patienten aus der rheumatologischen Ambulanz mit früher RA. Zur Untersuchung dieses Zusammenhanges wurde bei 247 Patienten bei der Erstvorstellung das HLA-DR-Differenzialbild mittels FACS-Methode bestimmt. Es erfolgte bei 227 Patienten eine definitive Diagnosestellung anhand der geltenden ACR-Kriterien und eine Progredienzerfassung mittels konventioneller Röntgentechnik und Bestimmung des Larsenscores bei gesicherten RA-Fällen und Vorliegen von radiologischen Verlaufskontrollen. Es konnte eine deutliche Korrelation des Shared Epitope mit der RA gezeigt werden (r=0,434). Die Effizienzmaße erfüllen jedoch nicht die Gütekriterien wie sie für einen diagnostischen Test zu fordern wären. Zwar zeigt sich deutlich eine Assoziation mit der RA, zur Diagnosestellung allein ist das Shared Epitope ungenügend. Ein Zusammenhang zwischen dem Shared Epitope und einer stärkeren radiologischen Progredienz der RA war nur schwach erkennbar und lässt sich auf statistisch signifikantem Niveau nicht nachweisen. Unsere Daten können einen signifikanten Einfluss der HLA-DR4 Allele auf den radiologischen Verlauf der RA nicht belegen. Somit ist der HLA-Status als Einzelparameter für eine Prognosestratifizierung und Therapieplanung der RA ungeeignet und es kann die kostenintensive HLA DR4-Bestimmung für die breite Anwendung in der klinischen Praxis nicht empfohlen werden

Human NK Cell Subset Functions Are Differentially Affected by Adipokines

Background: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines). Since natural killer (NK) cells are the host’s primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM) affects functions of two distinct human NK cell subsets. Methods: Isolated human peripheral blood mononuclear cells (PBMCs) were cultured with various concentrations of human and murine ACM harvested on two different days during adipogenesis and analyzed by fluorescent-activated cell sorting (FACS). Results: FACS analyses showed that the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), granzyme A (GzmA) and interferon (IFN)-γ in NK cells was regulated in a subset-specific manner. ACM treatment altered IFN-γ expression in CD56dim NK cells. The production of GzmA in CD56bright NK cells was differentially affected by the distinct adipokine compositions harvested at different states of adipogenesis. Comparison of the treatment with either human or murine ACM revealed that adipokine-induced effects on NK cell expression of the leptin receptor (Ob-R), TRAIL and IFN-γ were species-specific. Conclusion: Considering the growing prevalence of obesity and the various disorders related to it, the present study provides further insights into the roles human NK cell subsets play in the obesity-associated state of chronic low-grade inflammation

Antibiotic Dosing in Critically Ill Patients Receiving CRRT : Underdosing is Overprevalent

Published CRRT drug dosing algorithms and other dosing guidelines appear to result in underdosed antibiotics, leading to failure to attain pharmacodynamic targets. High mortality rates persist with inadequate antibiotic therapy as the most important risk factor for death. Reasons for unintended antibiotic underdosing in patients receiving CRRT are many. Underdosing may result from lack of the recognition that better hepatic function in AKI patients yields higher nonrenal antibiotic clearance compared to ESRD patients. Other factors include the variability in body size and fluid composition of patients, the serious consequence of delayed achievement of antibiotic pharmacodynamic targets in septic patients, potential subtherapeutic antibiotic concentrations at the infection site, and the influence of RRT intensity on antibiotic concentrations. Too often, clinicians weigh the benefits of overcautious antibiotic dosing to avoid antibiotic toxicity too heavily against the benefits of rapid attainment of therapeutic antibiotic concentrations in critically ill patients receiving CRRT . We urge clinicians to prescribe antibiotics aggressively for these vulnerable patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108650/1/sdi12203.pd

Adipokines Regulate the Expression of Tumor-Relevant MicroRNAs

Background: Increasing prevalence of obesity requires the investigation of respective comorbidities, including tumor diseases like colorectal, renal, post-menopausal breast, prostate cancer, and leukemia. To date, molecular mechanisms of the malignant transformation of these peripheral tissues induced by obesity remain unclear. Adipose tissue secretes factors with hormone-like functions, the adipokines, and is therefore categorized as an endocrine organ. Current research demonstrates the ability of adipose tissue to alter DNA methylation and gene expression in peripheral tissues, probably affecting microRNA (miR) expression. Methods: Literature was analyzed for adipokine-regulated miRs. Many of these adipokine upregulated or downregulated miRs exert either oncogenic or anti-tumoral potential. Results: The three selected and analyzed adipokines, adiponectin, leptin, and resistin, induce more strongly oncogenic miRs and simultaneously reduce anti-tumoral miRs than vice versa. This effect is not only true for the pure number of regulated miRs, it is also the case by consideration of the abundance of the respective miR expression based on actual data sets derived from next-generation sequencing. Conclusion: The link of obesity and cancer is analyzed under the aspect of adipokine-regulated miRs. At the same time the impact of miR abundance is considered as a regulatory variable. This context offers new strategies for tumor therapy and diagnostics

Biopsy proven acute interstitial nephritis after treatment with moxifloxacin

<p>Abstract</p> <p>Background</p> <p>Acute interstitial nephritis (AIN) is an important cause of reversible acute kidney injury. At least 70% of AIN is caused by various drugs, mainly penicillines and non-steroidal anti-inflammatory drugs. Quinolones are only rarely known to cause AIN and so far cases have been mainly described with older fluoroquinolones.</p> <p>Case Presentation</p> <p>Here we describe a case of biopsy proven interstitial nephritis after moxifloxacin treatment. The patient presented with fever, rigors and dialysis dependent acute kidney injury, just a few days after treatment of a respiratory tract infection with moxifloxacin. The renal biopsy revealed dense infiltrates mainly composed of eosinophils and severe interstitial edema. A course of oral prednisolone (1 mg/kg/day) was commenced and rapidly tapered to zero within three weeks. The renal function improved, and the patient was discharged with a creatinine of 107 μmol/l.</p> <p>Conclusion</p> <p>This case illustrates that pharmacovigilance is important to early detect rare side effects, such as AIN, even in drugs with a favourable risk/benefit ratio such as moxifloxacin.</p

Serum Concentrations of Symmetric Dimethylarginine and Creatinine in Dogs with Naturally Occurring Chronic Kidney Disease

Citation: Hall, J. A., Yerramilli, M., Obare, E., Yerramilli, M., Almes, K., & Jewell, D. E. (2016). Serum Concentrations of Symmetric Dimethylarginine and Creatinine in Dogs with Naturally Occurring Chronic Kidney Disease. Journal of Veterinary Internal Medicine, 30(3), 794-802. doi:10.1111/jvim.13942Background: Serum concentrations of symmetric dimethylarginine (SDMA) detected chronic kidney disease (CKD) in cats an average of 17.0 months before serum creatinine (Cr) concentrations increased above the reference interval. Objectives: To report on the utility of measuring serum SDMA concentrations in dogs for detection of CKD before diagnosis by measurement of serum Cr. Animals: CKD dogs (n = 19) included those persistently azotemic for ?3 months (n = 5), dogs that were azotemic at the time of death (n = 4), and nonazotemic dogs (n = 10). CKD dogs were compared with healthy control dogs (n = 20). Methods: Retrospective study, whereby serum Cr concentrations were determined by enzymatic colorimetry and serum SDMA concentrations were determined by liquid chromatography-mass spectrometry in dogs with necropsy confirmed CKD. Results: Serum SDMA increased before serum Cr in 17 of 19 dogs (mean, 9.8 months; range, 2.2-27.0 months). Duration of elevations in serum SDMA concentrations before the dog developed azotemia (N = 1) or before the dog died (N = 1) was not determined. Serum SDMA and Cr concentrations were linearly related (r = 0.84; P < .001). Serum SDMA (r = -0.80) and serum Cr (r = -0.89) concentrations were significantly related to glomerular filtration rate (both P < .001). Conclusion and Clinical Importance: Using serum SDMA as a biomarker for CKD allows earlier detection of kidney dysfunction in dogs than does measurement of serum Cr. Earlier detection might be desirable for initiating renoprotective interventions that slow progression of kidney disease. © 2016 American College of Veterinary Internal Medicine