[Mild behavioral impairment checklist : English-German translation and feasibility study assessing its use in clinical practice]. / "Mild-behavioral-impairment"-Checkliste : Englisch-deutsche Übersetzung und Beurteilung der Anwendbarkeit in klinischer Praxis.

BACKGROUND: The mild behavioral impairment (MBI) syndrome is defined by the emergence in later life of persistent neuropsychiatric symptoms. The MBI checklist (MBI-C) can be used for systematic detection and documentation of such symptoms. OBJECTIVE: Development of a German version of the MBI­C and assessment of its application in a clinical setting. MATERIAL AND METHODS: The MBI­C was translated from English into German in collaboration with the main author of the original version, and its practical application was then tested on a study population (n = 21) in a gerontopsychiatric inpatient clinic. Patient compliance, understanding of questions, time effort, evaluation procedure and possible discrepancy between patient and family member evaluations were assessed. RESULTS: The German translation of the original MBI­C obtained certification as an official version and can be downloaded at https://mbitest.org . All 34 questions were fully completed by the study population, the level of understanding of questions was good, with the mean time effort being 16 min. In some cases, significant differences between patients' and family members' responses were found. DISCUSSION: The presence of MBI may indicate the development of an otherwise presymptomatic neurodegenerative dementia syndrome. Hence, the MBI­C could aid in the early detection of neurodegenerative dementia. By means of the translated version of the MBI­C presented in this study, this hypothesis can now be tested in German-speaking countries.

[Adverse Drug Reactions in Geriatric Psychiatric Patients - Influence of Potentially Inappropriate Drugs]. / Unerwünschte Arzneimittelwirkungen in der Gerontopsychiatrie.

OBJECTIVE: The purpose of this study was to examine the extent to which "potentially inappropriate drugs" (PID) are associated with an increased risk for adverse drug reactions (ADR). METHODS: Data from 304 geriatric psychiatric inpatients was collected. Medical documentation was used to find indications of ADRs. Causal relationship between the ADR and the prescribed drugs was assessed by experts. RESULTS: Almost 30 % of patients received ≥ 1 PID before admission to hospital, in comparison to 22 % at discharge. Increasing number of total prescriptions and the diagnosis of schizophrenia resulted in an increased risk for receiving ≥ 1 PID. Higher age and dementia were protective factors. Patients receiving ≥ 1 PID had a 5-fold increased risk of experiencing ≥ 1 ADR. Risk for an ADR increased with number of PID prescriptions. Patients treated with ≥ 1 PID had a 4-fold increased risk of experiencing severe ADRs. Risk for severe ADRs was 10-fold higher in patients treated with ≥ 2 PIDs. CONCLUSION: The PRISCUS list predicts significant risk factors for the occurrence of ADRs in the geriatric psychiatric setting.

ß3-integrin Leu33Pro gain of function variant does not modulate inflammatory activity in human derived macrophages in diabetes.

Objective: We aimed to investigate the association between the Leu33Pro (rs5918) polymorphism in ß3-integrin with diabetic complications and inflammatory function of macrophages depending on the genotype in subjects with diabetes mellitus. Material and methods: We determined the Leu33Pro polymorphism in 186 diabetic subjects and collected laboratory data. Monocytes from 24 patients were collected for macrophage differentiation to determine the inflammatory activity by treating with different stimulants. Results: We could demonstrate that human derived differentiated macrophages expressed ß3­integrin. Their secretory capacity upon inflammatory stimulation did not reveal any differences depending on the Leu33Pro variant. We found trends for an association of the polymorphism with the presence of diabetic nephropathy (p = 0.071), as well as with creatinine [1.32 mg/dL (1) vs. 0.98 mg/dL (0)] (p = 0.029 in recessive model) and glomerular filtration rate [75.6 ml/min ± 22 vs. 62.3 ml/min ± 25] (p = 0.076 in recessive model) as quantitative markers of kidney function. Conclusion: Despite the expression of ß3­integrin in human macrophages, the Leu33Pro polymorphism in ß3­integrin does not modify the inflammatory response upon stimulation but might play a role in the progression of diabetic nephropathy. Further studies are necessary to substantiate such a hypothesis.

Increased Alexithymia But No Profound Emotion Processing Disorder in Burnout Syndrome.

Our objectives were to investigate alexithymia in burnout patients while controlling for depression and anxiety, as well as to evaluate whether alexithymia may be part of a profound emotional processing disorder or of a mentalization deficit. Alexithymia, depressive, and anxious feelings were compared in patients with burnout, depression, and healthy controls using an age-, sex-, and education-matched cross-sectional design (n = 60). A facial emotion recognition task and an emotional mentalizing performance test as well as physical and emotional violation experiences were conducted. Alexithymia was significantly increased in burnout patients, mediated by negative affect in this group. No impairment of facial emotion recognition or mental attribution could be shown. Burnout patients demonstrated slightly increased emotional abuse experiences in early childhood. The present results corroborate the supposition that alexithymia in burnout primarily depends on affect and may rise due to current strain and overload experience, rather than based on a profound developmental disorder in emotion processing.

The effect of alexithymia and depressive feelings on pain perception in somatoform pain disorder.

OBJECTIVE: To investigate the relationship between alexithymia and depression and their influence on the subjective versus experimental pain perception in somatoform pain disorder. METHODS: Three groups consisting of 40 patients with somatoform pain disorder, 40 patients with depression, and 40 healthy controls were matched. They completed questionnaires regarding alexithymia (TAS26) and depressive feelings (BDI-II). In addition, pain patients rated their subjective pain intensity (NRS). Quantitative sensory testings were conducted in all participants examining temperature (CPT, HPT) and mechanical (MPT, PPT) thresholds. RESULTS: Analysis of variance showed that alexithymia was significantly increased in both patient groups compared to healthy controls, but with the highest amount in somatoform pain. Regression analyses confirmed that this finding was in part due to a high comorbidity of depressive feelings in both patient groups. We found a discrepancy between increased clinical pain ratings and elevated pressure pain thresholds, indicating a less intense mechanical pain perception in somatoform pain. Correlation analyses demonstrated a significant connection of subjective pain ratings and pressure pain thresholds with depressive feelings. CONCLUSION: Contrary to the results of other experimental pain studies on chronic muskuloskeletal pain syndromes, we could not confirm central sensitization in somatoform pain disorder. Our findings place the somatoform pain disorder more in the direction of affective disorder such as depression. These findings may improve a better understanding of the disease and also have direct therapeutic implications. The high occurrence of alexithymia and depressive feelings in somatoform pain should be considered in diagnostic and therapeutic regimens of these patients.

Immunological Alterations due to Hemodialysis Might Interfere with Early Complications in Renal Transplantation.

BACKGROUND: Chronic or intercurrent alterations of the immune system in patients with end-stage renal disease (CKD) and intermittent hemodialysis (CKD5D, HD) have been attributed to an acute rejection of renal allograft. METHODS: Leukocyte subsets in flow cytometry, complement activation, and concentrations of TGFß, sCD30 (ELISA), and interleukins (CBA) of fifteen patients eligible for renal transplantation were analyzed before, during, and after a regular HD. RESULTS: Before HD, the median proportion of CD8+ effector cells, CD8+ CCR5+ effector cells, and HLA-DR+ regulatory T cells as well as the median concentration of soluble CD30 increased and naive CD8+ T cells decreased. During HD, there was a significant decrease in CD4- CD8- T cells (p < 0.001) and an increase in CD25+ T cells (p = 0.026), sCD30 (p < 0.001), HLA-DR+ regulatory T cells (p = 0.005), and regulatory T cells (p = 0.003). TGFß and sCD30 increased significantly over time. The activity of the classical complement pathway started to slightly increase after the first hour of HD and lasted until fifteen minutes after finishing dialysis. The decrease in the functional activity of the alternative pathway was only transient and was followed by a significant increase within 15 minutes after finishing the treatment. CONCLUSION: HD might interact with the allograft outcome by influencing T cell subsets and activation of the complement system in a biphasic course.

Early Flow Disturbances of Tunnelled Haemodialysis Catheters and Topographic Landmarks in Chest X-Ray.

BACKGROUND/AIMS: The position of the tip of tunnelled haemodialysis (HD) catheters (THC) might influence flow characteristics during HD. In chest X-ray (CXR), carina-related landmarks may be practicable to verify the THC position, and tip-carina distance (TCD) might be useful to predict early-flow dysfunctions. METHODS: In this single-centre, retrospective study, the TCD and the angle between the distal catheter and the body vertical axis (tip-body vertical-angle [TVA]) was measured in 115 THC by post-procedure CXR with 2 investigators. The parameters were proved to be feasible by interrater-reliability and correlated with the incidence of flow-dysfunction within 10 days after insertion. RESULTS: Steep-aligned (TVA <40°, p < 0.01) and deep-ending catheters (TCD: right-sighted >1.5 cm or left-sighted >4.5 cm below the carina; p < 0.01) showed a significantly less dysfunction with a good interrater-reliability (R[TVA] = 0.8, R[TCD] = 0.9). CONCLUSIONS: Carina-related landmarks in CXR might be helpful to predict early-flow dysfunctions. However, randomized studies will be necessary to confirm this in fluoroscopic-guided placement during the insertion of THC.

The Pituitary-Thyroid Axis and Prolactin Secretion in Hemodialysis Patients in Two Endemic Regions of Eastern Germany.

INTRODUCTION: Endocrine disorders of the pituitary axes are frequent in patients with hemodialysis (CKD5D). The aim of this multicenter study (Leipzig (L), Quedlinburg and Blankenburg in the Harz region (Hz)) in CKD5D patients was to evaluate influences of CKD5D related factors, morphological and biochemical parameters, and serum iodine and prolactin concentrations on the pituitary-thyroid axis. PATIENTS AND METHODS: 170 patients (L n=58; Hz n=112) were included in this prospective, non-interventional, cross-sectional study. Mann-Whitney-U-test and bivariate correlation analyses with Spearman-Rho test (r correlation coefficient) were used in statistical analysis. RESULTS: TSH was higher in patients with prolactin concentrations>370 mIU/l (p=0.013), in patients with high flux membranes (p=0.0013) and in patients with longer dialysis vintage (p=0.04). Median iodine serum concentrations were slightly elevated in the Leipzig cohort (p=0.001) and correlated with fT4 (p<0.001, r=0.43) and albumin (p=0.001, r=0.245) but not with morphological signs. Albumin was correlated with fT3 (p<0.001, r=0.339) and fT4 (p<0.001, r=0.421). Prolactin was correlated with residual excretion rate (p=0.001, r=- 0.303) and thyroid volume (p=0.027, r=0.217). CONCLUSIONS: In the assessment of the thyroid status in CKD5D patients, the synopsis of the clinical and nutritional status, comorbidities, ultrasound of the thyroid gland and laboratory results is necessary for further intervention with hormone replacement. Standardized reference values of the pituitary-thyroid axis should be critically evaluated and are still lacking in CKD5D.

Dual RAAS Blockade with Aliskiren in Patients with Severely Impaired Chronic Kidney Disease.

Dual renin-angiotensin-aldosterone blockade (dRAASb) is purposed in the prevention of the cardiorenal syndrome (CRS). However, all attempts with dRAASb even in patients with moderate impaired chronic kidney disease (CKD) were terminated due to the typical severe adverse events (SAE), e. g., hyperkalemia and rise of serum creatinine. The aim of our study with the direct renin inhibitor aliskiren was to evaluate the effect of dRAASb with a washout phase in patients with severely advanced CKD. We have studied 45 patients (G3b to 4, A2 and >A3; median glomerular filtration rate (GFR) CKD-EPI 31 (23-40) ml/min per 1.73 m² BSA (body surface area), albumin-creatinine-ratio in urine (UACR) (0.413 (0.164 to 1.39) g/g) and proteinuria (0.5 (0.2 to 0.9) g/l) before, with and without aliskiren (150 respectively 300 mg per day) added to an angiotensin-converting enzyme inhibitor (ACEi) or an AT1-receptor blocker (ARB) over 4 ½ years. The dRAASb with aliskiren showed a significant decrease of proteinuria (0.5 to 0.38 g/l), especially in patients with an UACR≥350 mg/g and in the subgroup analysis e. g., in patients with diabetes, but proteinuria increased in the washout phase again. The blood pressure (130/80 mm Hg), serum potassium (4.9 to 5.0 mmol/l) and GFR remained nearly constant (31 to 29.5 ml/min per 1.73 m2 BSA). A more than 30% increase in serum creatinine was associated with an UACR>300 mg/g. The dRAASb has beneficial effects on proteinuria and is safe in patients with severely advanced CKD. However, in patients with high UACR (>300 mg/g) raise of creatinine and potassium have to be controlled.

Endemic influences of political regimes, healthcare systems, and preferences on the frequencies and incidences of nephropathies in eastern Saxony, Germany
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INTRODUCTION: The possible confounding influence of investigator-related preferences, available histological techniques, and healthcare systems on the frequencies and incidences of primary and secondary nephropathies was evaluated in this long-term observation. MATERIALS AND METHODS: The observation time from 1983 to 2010 was divided in regard to the political regimes: a) prior to and after German reunification: German Democratic Republic (GDR, period 1 from 1983 to 1990)/Federal Republic of Germany (FRG, period 2 from 1990 to 2010); and the two heads of the division of nephrology, b) conductor 1 (1983 - 2006) and conductor 2 (2006 - 2010). 467 kidney biopsies at the University Hospital of Leipzig were included in our analysis. RESULTS: In period 1, due to the unavailability of immunofluorescence methods, mesangioproliferative glomerulonephritis (MesP) was the most dominating nephropathy. In period 2, IgA nephropathy (IgAN) was the most common nephropathy (17%). IgAN was followed by crescentic glomerulonephritis (13%), hypertensive nephropathy (10%), minimal-change disease, and membranous glomerulonephritis (each 9%). From period 1 to period 2, MesP/IgAN (62% to 16%), membranoproliferative glomerulonephritis and postinfectious glomerulonephritis decreased significantly (p < 0.05). IgAN decreased significantly (p < 0.05) from conductor 1 to conductor 2 (21% to 6%), while diabetic nephropathy significantly increased. Focal-segmental glomerulosclerosis (FSGS) had the highest incidence rate with 1.0, followed by IgAN with 0.8 (per 100,000 per year). CONCLUSION: In a nearly ethnically identical cohort, we have demonstrated that confounding factors, e.g., healthcare systems and preferences of conductors, have a strong influence - more than 10-fold variance - on frequency and incidence on the spectrum of nephropathies.
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Modern peptide biomarkers and echocardiography in cardiac healthy haemodialysis patients.

BACKGROUND: In this prospective study, we aimed to assess the haemodynamic changes before and after haemodialysis (HD) in cardiac healthy subjects on chronic HD by imaging methods and endocrine markers of fluid balance. METHODS: Mid-regional pro-atrial natriuretic peptide (MR-proANP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), vasopressin (AVP) and copeptin (CT-proAVP), metanephrines and normetanephrines, renin and aldosterone, standard transthoracic echocardiography and diameter of vena cava inferior (VCID) were performed in 20 patients with end stage renal disease (CKD5D) before and after HD and were stratified in residual excretion (RE, less or more 0.5 l) and ultrafiltration rate (UF, less or more 2 l). RESULTS: Copeptin was significantly higher in patients before HD. Copeptin was inversely correlated with haemodialysis treatment adequacy (KT/v), RE and UF, but was not significantly influenced by age, gender and body mass index (BMI). MR-proANP was significantly reduced by haemodialysis by 27% and was inversely correlated with KT/v, but there was a significant influence by UF, RE, age, gender and BMI. NT-proBNP was significantly higher in patients before HD and was not influenced by RE and UF. Renin, aldosterone, metanephrines and normetanephrines did not demonstrate significant differences. Echocardiographic parameters and VCID were significantly correlated with RE, UF and copeptin. CONCLUSION: Modern biomarkers will provide cardiovascular risk assessment, but elimination (UF), RE and other factors may influence the serum concentrations, e.g. in patients with renal impairment. The interpretation will be limited by altered reference ranges, and will be restricted to individual courses combined with clinical and echocardiographic data.

The Proline 7 Substitution in the Preproneuropeptide Y Is Associated with Higher Hepatic Lipase Activity In Vivo.

Hepatic lipase (HL) functions as a lipolytic enzyme that hydrolyzes triglycerides and phospholipids present in circulating plasma lipoproteins. Plasma HL activity is known to be regulated by hormonal and metabolic factors, but HL responsiveness to insulin as well as its role in modulating atherosclerotic risk is still controversial. We investigated on the influence of a known polymorphism in the neurotransmitter neuropeptide Y (NPY) on HL activity in two different cohorts consisting of diabetic and nondiabetic patients. HL activity was 24% and 34% higher on nondiabetic and diabetic subjects in the presence of the 7Pro allele in NPY, respectively. The presence of the 7Pro allele was an independent predictor of HL activity in multivariate analyses in both cohorts. These data suggest a regulatory effect of NPY on HL activity. Among carriers of the 7Pro allele, we also found a statistically significant lower absolute number of infarctions compared to noncarriers (p < 0.05) and a nonsignificant trend towards less myocardial infarction in the 7Pro allele diabetic carriers (p = 0.085). In conclusion, the common 7Pro allele in NPY was associated with higher HL activity in nondiabetic and diabetic subjects and its presence seems to coincide with a lower frequency of certain cardiovascular events.

Influence of Erythropoiesis-Stimulating Agents on HbA1c and Fructosamine in Patients with Haemodialysis.

HbA1c is the most accepted laboratory parameter for the long term observation of glucose control. There is still much of a debate about the use of HbA1c as a metabolic indicator in diabetic patients (DM) on haemodialysis (HD) and erythropoiesis-stimulating agent (ESA) therapy because of the altered erythrocyte turn over in patients with chronic kidney disease and haemodialysis (CKD5D). In 102 CKD5 patients with and without diabetes mellitus, we examined the dose dependent variability in HbA1c and fructosamine levels under haemodialysis and treated with epoetin α (n=48) and a new generation agent with continuous stimulation of methoxy polyethylene glycol epoetin beta (C.E.R.A.; n=54). HbA1c levels were affected by therapy with ESA treatments. ESA dose was inversely correlated with HbA1c and an escalation of 10.000 IU per week induced an estimated decrease of HbA1c of 0.6 percent. In addition, the increase of reticulocyte number as a marker for erythropoiesis was significantly inversely correlated with the increase of ΔHbA1c. ESA treatments had no such effect on the alternative metabolic parameter fructosamine. When compared, both therapeutic agents had comparable success in attaining haemoglobin (Hb) target values. C.E.R.A. showed better correlation and was more effective over a longer dose interval. Our results show that HbA1c levels in patients should be carefully interpreted based on interfering factors. Nevertheless, HbA1c is currently the most consistent parameter for use ascertaining metabolic status of patients suffering from diabetes mellitus.

Autochthonous Dobrava-Belgrade virus infection in Eastern Germany.

A 21-year-old male patient from Borna, Saxony, in Eastern Germany, suffered from acute kidney injury (AKI) and symptoms typical for a hantavirus infection. These symptoms included nausea, vomiting, abdominal pain, diarrhea, and acute renal failure. Serological investigations by indirect IgM and IgG in-house ELISAs, commercial immunofluorescence and line assays, as well as chemiluminescence focus reduction neutralization assay confirmed an acute Dobrava-Belgrade virus (DOBV) infection of the patient. Serological and RT-PCR analyses of striped field mouse (Apodemus agrarius) trapped in a neighboring region of the residence of the patient identified an infection by DOBV, genotype Kurkino. This is the first report of an autochthonous DOBV infection in a German patient living far from the known endemic region in the north of the country. This finding has implications for the awareness of physicians in areas which are not recognized as hantavirus endemic regions but where the reservoir host of the virus is present.

No-reflow phenomenon: pathophysiology, diagnosis, prevention, and treatment. A review of the current literature and future perspectives.

No-reflow is responsible for 40% of the primary percutaneous coronary intervention without complete myocardial reperfusion despite successful reopening of the infarct-related artery. This review describes the main pathophysiological mechanisms of no-reflow, its clinical manifestation, including the strong association with increased in-hospital mortality, malignant arrhythmias, and cardiac failure as well as the diagnostic methods. The latter ranges from simple angiographic thrombolysis in myocardial infarction grade score to more complex angiographic indexes, imaging techniques such as myocardial contrast echo or cardiac magnetic resonance, and surrogate clinical end points such as ST-segment resolution. This review also summarizes the strategies of prevention and treatment of no-reflow, considering the most recent studies results regarding medical therapy and devices.

Association between a gene variant near ataxia telangiectasia mutated and coronary artery disease in men.

OBJECTIVE: Type 2 diabetes is accompanied by increased mortality from coronary artery disease (CAD), but the mechanisms linking these conditions remain elusive. Hence, treatment of hyperglycaemia alone is not sufficient to avoid CAD in diabetes. Alternative views suggest that metabolic and vascular diseases share unifying cellular defects that could serve as targets for novel therapeutic strategies. Recently, a variant [single-nucleotide polymorphism (SNP); rs11212617] near the gene for ataxia telangiectasia mutated (ATM) has been associated with glycaemic response to metformin. MATERIALS AND METHODS: We determined rs11212617 in 240 male patients who underwent elective coronary angiography. RESULTS: While the variant was not associated with glucose concentrations, the A allele was significantly associated with the presence of CAD (chi-square, p = 0.003), as well as with logarithmically transformed quantitative CAD indices [severe score (SS): 0.5 (0.4-0.6) vs 0.3 (0.2-0.5); extent score (ES): 2.63 (2.4-2.9) vs 1.94 (1.4-2.4), both p < 0.05, respectively]. Multivariate analysis revealed an independent association between the A allele with ES (ß = 0.17, p < 0.01). CONCLUSION: Our data suggest that ATM-dependent signalling might play a role in the development of atherosclerotic vascular disease, but larger studies are necessary to substantiate such a hypothesis.

Short-term akt activation in cardiac muscle cells improves contractile function in failing hearts.

Akt is a serine/threonine protein kinase that is activated by a variety of growth factors or cytokines in a phosphatidylinositol 3-kinase-dependent manner. By using a conditional transgenic system in which Akt signaling can be turned on or off in the adult heart, we previously showed that short-term Akt activation induces a physiological form of cardiac hypertrophy with enhanced coronary angiogenesis and maintained contractility. Here we tested the hypothesis that induction of physiological hypertrophy by short-term Akt activation might improve contractile function in failing hearts. When Akt signaling transiently was activated in murine hearts with impaired contractility, induced by pressure overload or doxorubicin treatment, contractile dysfunction was attenuated in both cases. Importantly, improvement of contractility was observed before the development of cardiac hypertrophy, indicating that Akt activation improves contractile function independently of its growth-promoting effects. To gain mechanistic insights into Akt-mediated positive inotropic effects, transcriptional profiles in the heart were determined in a pressure overload-induced heart failure model. Biological network analysis of differentially expressed transcripts revealed significant alterations in the expression of genes associated with cell death, and these alterations were reversed by short-term Akt activation. Thus, short-term Akt activation improves contractile function in failing hearts. This beneficial effect of Akt on contractility is hypertrophy-independent and may be mediated in part by inhibition of cell death associated with heart failure.

Cathepsin G is differentially expressed in primary human antigen-presenting cells.

Cathepsins are required for the processing of antigens in order to make them suitable for loading on major histocompatibility complex (MHC) class II molecules, for subsequent presentation to CD4(+) T cells. It was shown that antigen processing in monocyte-derived dendritic cells (DC), a commonly used DC model, is different from that of primary human DC. Here, we report that the two subsets of human myeloid DC (mDC) and plasmacytoid DC (pDC) differ in their cathepsin distribution. The serine protease cathepsin G (CatG) was detected in mDC1, mDC2, pDC, cortical thymic epithelial cells (cTEC) and high levels of CatG were determined in pDC. To address the role of CatG in the processing and presentation of a Multiple Sclerosis-associated autoantigen myelin basic protein (MBP), we used a non-CatG expressing fibroblast cell line and fibroblasts, which were preloaded with purified CatG. We find that preloading fibroblasts with CatG results in a decrease of MBP84-98-specific T cell proliferation, when compared to control cells. Our data suggest a different processing signature in primary human antigen-presenting cells and CatG may be of functional importance.