Etiologies and predictors of mortality in an all-comer population of patients with non-ischemic heart failure.

BACKGROUND: Despite progress in diagnosis and therapy of heart failure (HF), etiology and risk stratification remain elusive in many patients. METHODS: The My Biopsy HF Study (German clinical trials register number: DRKS22178) is a retrospective monocentric study investigating an all-comer population of patients with unexplained HF based on a thorough workup including endomyocardial biopsy (EMB). RESULTS: 655 patients (70.9% men, median age 55 [45/66] years) with non-ischemic, non-valvular HF were included in the analyses. 489 patients were diagnosed with HF with reduced ejection fraction (HFrEF), 52 patients with HF with mildly reduced ejection fraction (HFmrEF) and 114 patients with HF with preserved ejection fraction (HFpEF). After a median follow-up of 4.6 (2.5/6.6) years, 94 deaths were enumerated (HFrEF: 68; HFmrEF: 8; HFpEF: 18), equating to mortality rates of 3.3% and 11.6% for patients with HFrEF, 7.7% and 15.4% for patients with HFmrEF and 5.3% and 11.4% for patients with HFpEF after 1 and 5 years, respectively. In EMB, we detected a variety of putative etiologies of HF, including incidental cardiac amyloidosis (CA, 5.8%). In multivariate logistic regression analysis adjusting for age, sex and comorbidities only CA, age and NYHA functional class III + IV remained independently associated with all-cause mortality (CA: HRperui 3.13, 95% CI 1.5-6.51; p = 0.002). CONCLUSIONS: In an all-comer population of patients presenting with HF of unknown etiology, incidental finding of CA stands out to be independently associated with all-cause mortality. Our findings suggest that prospective trials would be helpful to test the added value of a systematic and holistic work-up of HF of unknown etiology.

Increased C reactive protein, cardiac troponin I and GLS are associated with myocardial inflammation in patients with non-ischemic heart failure.

Inflammatory cardiomyopathy diagnosed by endomyocardial biopsy (EMB) is common in non-ischemic heart failure (HF) and might be associated with adverse outcome. We aimed to identify markers predicting myocardial inflammation in HF. We screened 517 patients with symptomatic non-ischemic HF who underwent EMB; 397 patients (median age 54 [IQR 43/64], 28.7% females) were included in this study. 230 patients were diagnosed with myocardial inflammation, defined as ≥ 7.0 CD3+ lymphocytes/mm2 and/or ≥ 35.0 Mac1 macrophages/mm2 and were compared to 167 inflammation negative patients. Patients with myocardial inflammation were more often smokers (52.4% vs. 39.8%, p = 0.013) and had higher C-reactive protein (CRP) levels (5.4 mg/dl vs. 3.7 mg/dl, p = 0.003). In logistic regression models CRP ≥ 8.15 mg/dl (OR 1.985 [95%CI 1.160-3.397]; p = 0.012) and Troponin I (TnI) ≥ 136.5 pg/ml (OR 3.011 [1.215-7.464]; p = 0.017) were independently associated with myocardial inflammation, whereas no association was found for elevated brain natriuretic peptide (OR 1.811 [0.873-3.757]; p = 0.111). In prognostic performance calculation the highest positive predictive value (90%) was detected for the combination of Global longitudinal strain (GLS) ≥ -13.95% and TnI ≥ 136.5 pg/ml (0.90 (0.74-0.96)). Elevated CRP, TnI and GLS in combination with TnI can be useful to detect myocardial inflammation. Smoking seems to predispose for myocardial inflammation.

The structural organization of the septate and gap junctions of Hydra.

The septate junctions and gap junctions of Hydra were studied utilizing the extracellular tracers lanthanum hydroxide and ruthenium red. Analysis of the septate junction from four perspectives has shown that each septum consists of a single row of hexagons sharing common sides of 50-60 A. Each hexagon is folded into chair configuration. Two sets of projections emanate from the corners of the hexagons. One set (A projections) attaches the hexagons to the cell membranes at 80-100-A intervals, while the other set (V projections) joins some adjacent septa to each other. The septate junctions generally contain a few large interseptal spaces and a few septa which do not extend the full length of the junction. Basal to the septate junctions the cells in each layer are joined by numerous gap junctions. Gap junctions also join the muscular processes in each layer as well as those which connect the layers across the mesoglea. The gap junctions of Hydra are composed of rounded plaques 0.15-0.5 micro in diameter which contain 85-A hexagonally packed subunits. Each plaque is delimited from the surrounding intercellular space by a single 40-A band. Large numbers of these plaques are tightly packed, often lying about 20 A apart. This en plaque configuration of the gap junctions of Hydra contrasts with their sparser, more widely separated distribution in many vertebrate tissues. These studies conclude that the septate junction may possess some barrier properties and that both junctions are important in intercellular adhesion. On a morphological basis, the gap junction appears to be more suitable for intercellular coupling than the septate junction.

e-Health-based management of patients receiving oral anticoagulation therapy: results from the observational thrombEVAL study.

Essentials e-Health based health care by an expert centre may advance management of oral anticoagulation. Outcome of patients was compared between an e-health based coagulation service and regular care. Patients in the coagulation service cohort experienced a significantly better clinical outcome. Lower risk for adverse events was related to anticoagulation-specific and non-specific outcome. SUMMARY: Background Management of oral anticoagulation (OAC) therapy is essential to minimize adverse events in patients receiving vitamin K-antagonists (VKAs). Data on the effect of e-health-based anticoagulation management systems on the clinical outcome of OAC patients are limited. Objectives To compare the clinical outcome of OAC patients managed by an e-health-based coagulation service (CS) with that of patients receiving regular medical care (RMC). Methods The prospective multicenter cohort study thrombEVAL (NCT01809015) comprised 1558 individuals receiving RMC and 760 individuals managed by a CS. Independent study monitoring and adjudication of endpoints by an independent review panel were implemented. Results The primary study endpoint (composite of thromboembolism, clinically relevant bleeding and death) occurred in 15.7 per 100 patient-years (py) with RMC and in 7.0 per 100 py with the CS (rate ratio [RR], 2.3; 95% confidence interval [CI], 1.7-3.1). Rates for major and clinically relevant bleeding were higher with RMC than with the CS: 6.8 vs. 2.6 and 10.1 vs. 3.6 per 100 py, respectively. Thromboembolic events showed an RR of 1.5 (95% CI, 0.8-2.6) comparing RMC with the CS. Hospitalization (RR, 2.6; 95% CI, 2.3-3.0) and all-cause mortality (RR, 4.6; 95% CI, 2.8-7.7) were markedly more frequent with RMC. In Cox regression analysis with adjustment for age, sex, cardiovascular risk factors, comorbidities, treatment characteristics and sociodemographic status, hazard ratios (HR) for the primary endpoint (HR, 2.2; 95% CI, 1.5-3.4), clinically relevant bleeding (HR, 3.1; 95% CI, 1.7-5.5), hospitalization (HR, 2.2; 95% CI, 1.8-2.8) and all-cause mortality (HR, 5.6; 95% CI, 2.9-11.0) favored CS treatment. Conclusions In this study, e-health-based management of OAC therapy was associated with a lower frequency of OAC-specific and non-specific adverse events.

[Gracilis tendon augmented reconstruction of the medial patellofemoral ligament with soft tissue fixation at the patellar insertion site]. / Ersatz des medialen patellofemoralen Ligaments durch autologe Gracilissehne mit implantat- und bohrkanalfreier patellarer Fixation.

OBJECTIVE: Reconstruction of the medial patellofemoral ligament with autologous tendon augmentation and soft tissue fixation at the patellar insertion with resorbable suture material. INDICATIONS: Patellofemoral instability due to insufficiency of the medial passive stabilizers and dysplastic trochlea. CONTRAINDICATIONS: Primary traumatic dislocation of the patella without risk factors for patellar redislocation, severe osteoarthritis of the patellofemoral joint, infection. SURGICAL TECHNIQUE: Diagnostic arthroscopy to evaluate cartilage and shape of trochlea and to treat associated injuries. Harvesting of the gracilis tendon and arming with resorbable suture material. Transfer of the tendon through the medial capsule in the anatomical layer of the MPFL and weaving in u-shape through the capsule and periosteum near the patella. Soft tissue fixation with resorbable suture material. Anatomical reconstruction of the femoral insertion site. Femoral fixation with interference screw. POSTOPERATIVE TREATMENT: For 4 weeks, partial (20 kg) weight bearing with crutches; cast with physiotherapy (limited ROM extension, flexion 0-0-90°). Thereafter free range of motion and full weight bearing. RESULTS: 27 patients (age 12-45 years) with patellofemoral instability underwent reconstruction of the medial patellofemoral ligament. Clinical follow-up was assessed up to 12 months postoperatively. After 1 year, the Kujala and Flandry scores increased from preoperatively 72 points to 95 points and 65.7 points to 89.9 points, respectively. One redislocation was observed. Patient satisfaction was significantly increased at 6 months postoperatively. Reconstruction of the medial patellofemoral ligament shows good clinical results after 12 months.

Golgi studies in the substantia gelatinosa neurons in the spinal trigeminal nucleus.

This Golgi study identifies three neuronal cell types in the substantia gelatinosa (SG) layer of the spinal trigeminal nucleus. The SG neurons are distinguished from each other based on: (1) dendritic branching pattern, (2) denritic spine distribution, (3) geometric shape of the denritic tree, (4) laminar distribution of the dendrites, (5) axonal branching pattern and (6) laminar distribution of the axonal arbor. The islet cell is found in small clusters and its dendrites and axonal arbor are confined within the SG layer. Its dendrites span the full width of the SG layer and extend up to 500 mum in the long axis of the layer. Dendritic spines are generally sparse with small clusters of spines found on the higher order dendritic branches. The islet cell axon extends for at least 1 mm in the long axis of the layer. Each of its collaterals divide every 50-100 mum with one branch doubling back in the direction of the cell body and the other branch continuing on in the direction of its parent. In this manner each islet cell generates a profuse axonal plexus in the SG layer. The stalked cell is found individually within the SG layer. Its cell body is usually found in the inner half of the SG layer and its sinuous dendrites cross the SG layer and enter the marginal layer. The stalked cell dendrites emit numerous fine stalk-like branches and dentritic spines. Its axon emits branches in the SG and marginal layers. The spiny cell is found singly between groups of islet cells. Its extensive dendritic tree spans up to 500 mum rostrocaudally and mediolaterally crossing into both the marginal and magnocellular layers. Spiny cells have evenly distributed dendritic spines along their dendrites in the SG layer. The spiny cell axon sends branches into all three layers of nucleus caudalis. Numerous branches enter the outer 300 mum of the magnocellular layer where they undergo further branching with some branches returning in recurrent fashion toward the SG layer. The three neuronal cell types of the SG layer satisfy all of the morphological criteria for Golgi type II interneurons. Their highly branched axons generate many collaterals within the confines of their dendritic trees and do not project out of nucleus caudalis. The SG neurons are considered to be inhibitory interneurons interposed between V nerve primary afferent axons which arborize in the SG layer and second order neurons of nucleus caudalis.

Golgi studies of the neurons in layer II of the dorsal horn of the medulla (trigeminal nucleus caudalis).

The translucent band which lies just beneath the spinal V tract at the lower end of the spinal trigeminal nucleus (nucleus caudalis) can be divided into three layers. These three layers are distinguished by textural differences in their neuropil and by the morphology and laminar distribution of the axons and dendrites of their neurons. Layer II contains four different kinds of interneurons. Stalked cells are named after their short, stalk-like branches. Their cell bodies are found in greatest numbers in the outer half of layer II. Their coneshaped dendritic arbors extend medially across layers II and III and sometimes extend into layer IV. Their axons form extensive, canopy-like arborizations in layer I. Stalked cells are considered to be excitatory interneurons receiving input on their dendritic spines from primary axonal endings in the layers II and III glomeruli and transferring it to the dendrites of the layer I projection neurons. Layer II contains three kinds of Golgi type II inteneurons, i.e, neurons whose axons branch repeatedly within the confimes of their dendritic arbors. Islet cells similar to those found in layer III (Gobel), '75a), are found in small clusters in layer II. Their dendrites and axons are largely confined in layer II. The dendrites of the arboreal cell burst, in tree-like fashion, into highly focal dendritic arbors confined largely in layer II while the extensive rostral and caudal dendritic arbors of the II-III border cell lie largely in layers II and III with a few branches extending into layer I. The axons of both of these interneurons arborize in layers II and III with a few collaterals extending into layer I. Islet cells, arboreal cells and II-III border cells are considered to be inhibitory interneurons. They are strategically situated to interrupt transmission between primary axonal endings in layers II and III and the layer I projection neurons by altering the output of the stalked cells.

Golgi and EM studies of the formation of dendritic and axonal arbors: the interneurons of the substantia gelatinosa of Rolando in newborn kittens.

Golgi studies in newborn kittens show that the two most prevalent interneurons in Rexed's lamina II of the dorsal horn of the medulla, the stalked cell and islet cell (Gobel, '75a,b, '78b) form their dendritic arbors in a similar fashion. At birth, both cell types are present in forms ranging from immature, in which numerous short dendrites radiate from the cell body in all directions, to relatively mature in which their dendritic arbors have elongated in specific directions and the adult branching pattern is already evident. During postnatal maturation, many dendrites are lost while only a few go on to lengthen. The unmyelinated axons of both cells are first recognized in forms in which lengthening dendrites have taken on their preferred direction of orientation. The two parts of Rexed's lamina II, i.e., layers IIa and IIb have already reached their adult mediolateral width at birth and the neuropil has nearly achieved its adult compactness. Space in the compact neuropil for elongating neuronal and astrocytic processes becomes available through the disintegration of many existing dendrites and by an overall fourfold increase in the rostrocaudal length of the dorsal horn of the medulla during postnatal maturation. At birth, the lengthening of the plasma membranes of elongating neuronal and astrocytic processes proceeds as vesicles (addition vesicles) found in aggregates throughout dendrites, unmyelinated axons and astrocytic processes fuse with and become incorporated into the existing plasma membranes. In addition, many dendrites in layers IIa and IIb are beading up and disintegrating. Within the beads, neurotubules are lost and addition vesicles fuse with each other to form small cavities. These cavities continue to enlarge, hollowing out the beads. The cavities ultimately open to the intercellular space as their membranes fuse with the plasma membrane of the beads. Finally, the beads disintegrate and their plasma membranes fragment. The thread-like segments between adjacent disintegrating beads shrivel until they ultimately disappear. Disintegration of beaded dendrites results in very little debris and does not provoke a phagocytic glial reaction. The disintegration of a dendritic branch takes place in spite of synaptic input from non-primary axons and is thought to occur from a failure to establish synaptic connections with primary axonal endings.

An HRP study of the central projections of primary trigeminal neurons which innervate tooth pulps in the cat.

Trigeminal ganglia and brain stem of adult cats were studied following HRP injections into tooth pulps or after exposure of the cut end of the inferior alveolar nerve to HRP. Ipsilateral ganglion cells within a wide range of sizes were labeled in both experimental situations, whereas no labeled cells were observed in the contralateral ganglion in any animal. Labeled central branches of tooth pulp and inferior alveolar neurons were observed in all subdivisions of the ipsilateral trigeminal sensory complex. Terminal labeling in the tooth pulp experiments was confined to the dorsomedial parts of the main sensory nucleus and subnuclei oralis and interpolaris. Caudal to the obex terminal labeling was restricted to the medial halves of laminae I, IIa and V of the medullary dorsal horn. In the inferior alveolar nerve experiments dense terminal labeling was observed in the dorsal parts of the main sensory nucleus and subnuclei oralis and interpolaris. Caudal to the obex terminal labeling was located throughout laminae I to V in contrast to the tooth pulp experiments. Neither of the two experimental situations offers any evidence for a bilateral or contralateral brain stem projection of primary trigeminal neurons.

Dendritic changes in the spinal dorsal horn following transection of a peripheral nerve.

In an attempt to examine the morphologic changes which take place in the spinal dorsal horn as a consequence of peripheral nerve injury, the superficial radial nerve was cut and prevented from regenerating in adult cats. In laminae I-V of the 7th cervical segment of spinal dorsal horn at 2 weeks, 1 and 2 months following transection, small and medium-sized dendritic shafts developed membrane-bounded cavities. These cavities varied in number and size in each dendrite and were sometimes connected to the agranular reticulum. Large cavities often hollowed out a dendrite, leaving little remaining cytoplasm between the cavity membrane and the plasma membrane. Small and large cavities were frequently found open to the intercellular space. Synaptic glomeruli showed a loss of small dendrites with empty scalloped depressions in the central axonal endings of these structures left exposed to enlarged intercellular spaces. In addition, clusters of many enlarged oval or irregular intercellular spaces were found in the neuropil where many cavitated dendrites were observed. At least some of these intercellular spaces were thought to be derived from the loss of dendrites. From these observations we conclude that small and medium-sized dendrites involute through cavitation and eventually disappear from the spinal dorsal horn when primary input is disturbed by transection of peripheral sensory nerves.

An anatomical demonstration of projections to the medullary dorsal horn (trigeminal nucleus caudalis) from rostral trigeminal nuclei and the contralateral caudal medulla.

This study demonstrates that the medullary dorsal horn (MDH), the most caudal subdivision of the spinal trigeminal nucleus, receives input from neurons located in the trigeminal main sensory nucleus, the more rostral subdivisions of the spinal trigeminal nucleus, and the contralateral MDH. Using the retrograde transport of horseradish peroxidase (HRP), we show here that the MDH receives ipsilateral projections from rostral trigeminal nuclei but not from adjacent areas of the retricular formation. The rostral pole of spinal trigeminal nucleus oralis (nucleus oralis, pars beta) contains the highest density of MDH projection neurons. In addition, the MDH on one side receives projections from contralateral MDH neurons located in layers I, III, IV, V, VII and VIII but not from neurons in layers II and VI. We conclude that: (1) specific subdivisions of rostral trigeminal nuclei send projections to the MDH that could modulate the activity of MDH neurons; (2) projections from trigeminal nuclei to layers V and VI of the MDH, but not from adjacent areas of the reticular formation, provide further evidence that these deeper layers are related functionally to the MDH and trigeminal sensory processes; and (3) several populations of MDH neurons send axons across the midline into the contralateral MDH and may mediate contralateral inhibitory effects.

Ultrastructural characterization of axonal endings in the substantia gelatinosa which take up [3H]serotonin.

Serotonergic axonal endings in layers I and II of the dorsal horn of the medulla were identified by autoradiography. In adult cats, pretreated with a monoamine oxidase inhibitor, tritiated serotonin ([3H]5-HT) was topically applied onto the surface of the caudal medulla. Light autoradiographs from 1 micrometer sections demonstrated silver grains in both layers I and II. In EM autoradiographs, two categories of axonal endings were labeled by [3H]5-HT uptake: dome-shaped endings which form a single synapse and scalloped endings which form multiple synapses. Each category was further divided into several types based on morphological criteria. The [3H]5-HT-labeled endings synapse primarily on small caliber dendritic shafts and spines, with the dome-shaped endings forming both symmetrical and asymmetrical synapses and the scalloped endings forming only asymmetrical synapses. Dome-shaped endings were most common and two types were found in layers I and II while a third type was found only in layer II. Layer I contained a single type of scalloped ending while layer II contained three types of scalloped endings. In a series of experiments designed to provide another approach to identifying serotonergic endings, 5,6-dihydroxytryptamine, a serotonin neurotoxin, was either topically applied onto the caudal medulla or injected into the fourth ventricle. Following treatment with the neurotoxin, blackened degenerating dome-shaped and scalloped endings similar to those labeled in the [3H]5-HT uptake experiments were found in layers I and II. The presence of serotonergic endings in layer I suggests that some of these endings synapse on the dendrites of layer I projection neurons where they may inhibit the output of the projection neuron directly. Serotonergic endings in layer II may modulate the activity of layer II interneurons by synapsing directly on these interneurons. The interneurons in layer II may function by mediating the transfer of inputs from primary endings in these layers to layer I projection neurons.

Ultrastructural analysis of medial brain stem afferents to the superficial dorsal horn.

Axonal projections of medial brain stem areas rich in serotonin-containing neurons were identified in layers I and II of cat medullary dorsal horn using EM autoradiography. Following [3H]amino acid injections into the brain stem, labeled axonal endings were found throughout layers I and II but were most numerous in layer I. Three different morphological types of endings could be distinguished. Each type resembled serotonergic axonal endings identified in previous experiments. The labeled endings formed both symmetrical and asymmetrical synapses on dendritic shafts and spines and occasionally on a neuronal soma suggesting that the major site of action of the descending serotonergic afferents is on the neurons in layers I and II.

Enkephalin immunoreactive stalked cells and lamina IIb islet cells in cat substantia gelatinosa.

Neurons in lamina II of the lumbar spinal cords of colchicine-pretreated cats were stained immunocytochemically for enkephalin. Two morphological types were found. The most common type had the light microscopic characteristics of stalked cell. The other type was found in the deep part of the lamina and had the light and electron microscopic characteristics of the lamina IIb islet cell.

Effect of n-3 and n-6 fatty acids on 7,12 dimethylbenz (a) anthracene-induced mammary tumorigenesis.

Numerous studies have consistently shown that vegetable oils containing linoleic acid enhance mammary tumorigenesis more effectively than fish oils containing eicosapentaenoic and docohexaenoic acids. The purpose of this investigation was to study these and additional n-3 and n-6 PUFA, e.g., a-linolenic (a-LN) (18:3 n-3) and gamma-linolenic (GLA) (18:3 n-6) acid. Different oils were used as dietary sources of fatty acids: corn (CO) (61% LA); blackcurrant (BCO) (44% LA, 18% GLA and 16% a-LN); fish oil (FO) (mixed with corn oil, 12% LA and 24% EPA + DPA + DHA). Thirty-five-day-old female Sprague-Dawley rats were divided into 5 dietary treatment groups and were allowed to feed ab libitum on one of the test diets: I. BCO (23.5%); II. CO (23.5%); III. BCO (15.5%) + FO (8%); IV. FO (20.5%) + CO (3%); and V. BCO (20.5%) + FO (3%). From 48 to 52 days of age, rats in all five groups were fed rat chow. At 50 days of age, all rats were given 5 mg DMBA by oral intubation, and 2 days later the test diets were resumed until termination of the experiment. Analysis of tumor incidence, and multiplicity data for 5 diet groups indicated that rats fed 23.5% CO (II) exhibited enhanced mammary tumor yields when compared to animals on the remaining 4 diets in the order II greater than I, III, V greater than IV. Since the level of fat (23.5% w/w) was similar in all 5 diets, and body weight gain was in the order IV greater than II greater than I, the results of this study indicate that differences in tumor yields were related to fatty acid composition of diets. In support of this conclusion, fatty acid profiles of RBC and tumor phosphoglycerides reflected dietary fatty acid composition. In groups I and II, even though tumor levels of LA were similar, the levels of GLA, DHLA (20:3 n-6) and a-LN were higher in I compared to II, suggesting that these differences may be associated with lower yields of DMBA-induced mammary tumors in group I. Incorporation of marine type n-3 PUFA (EPA, DPA and DHA) in tumor PL was greater in Group IV compared to plant type n-3 PUFA (a-LN) in Groups I, III, and V. Since tumor yields were the lowest in Group IV, these results suggest that incorporation of marine type n-3 PUFA into cell membranes does not favor development of DMBA-induced mammary tumors.

Application of capillary zone electrophoresis for analyzing biotin in pharmaceutical formulations--a comparative study.

The detection limit and reproducibility of capillary zone electrophoresis (CZE) measurement of biotin were compared to those of a spectrophotometric method and those of the determination of the sulphur content by combustion of the biotin sample followed by coulometric titration of the formed SO2. Drug analysis showed that all three methods gave consistent results and were suitable for the determination of biotin. CZE was found to be the best method for the determination of pharmaceutical formulations containing biotin because of its high separation efficiency, short analysis time, ease of instrumentation and sample preconditioning, and good precision.

[Various mechanisms of disorders of carbohydrate metabolism in myocardial infarct]. / Nekotorye mekhanizmy narushenií uglevodnogo obmena u bol'nykh infarktom miokarda.

A group of 112 patients with acute myocardial infarction was studied. Methods for determining the content of immunoreactive insulin, uric acid, triglycerides, and sugar in blood on a fasting stomach and under conditions of carbohydrate load in dynamics were used. The data obtained show that patients, mainly those with uncomplicated myocardial infarction, are marked by relative insulin insufficiency as well as by a high level of triglycerides and uric acid in the acute period of the disease. The causal relationship between hyperuricemia, hypertriglyceridemia, and carbohydrate metabolism disorders is discussed.

[Aggression, inanimate objects and fantasy of invulnerability]. / Aggression, unbelebte Objekte und die Phantasie der Unzerstörbarkeit.

Some highly aggressive children prefer to symbolize and express their inner experiences by toys, which represent "things" and not living creatures. The special function of this preference represents a defense structure of deanimation after traumatization. It implicates the phantasy, that inanimated objects are not part of the vivid dialogue and can "survive" every attack. Thus in the transferential relationship the deanimation can slowly be reanimated by borrowing the undestroyable aspects of a thing in combination with the suffering feelings of the therapist.

Relevance of depression for anticoagulation management in a routine medical care setting: results from the ThrombEVAL study program.

BACKGROUND: Depressive symptoms have detrimental effects on quality of life and mortality. Poor adherence to a treatment regimen is a potential mechanism for the increased risk of adverse medical events associated with depression. Regarding oral anticoagulation with vitamin K antagonists, adherence is crucial for the outcome. Little is known about the clinical relevance of current depressiveness for anticoagulation treatment. OBJECTIVES: To examine the impact of current depressiveness on anticoagulation treatment in regular medical care. PATIENTS/METHODS: We examined the association between clinically significant depressiveness as assessed by the Patient Health Questionnaire-2 ≥ 2 (PHQ-2 ≥ 2) with the percentage of time in the therapeutic range (TTR), self-rated compliance, several aspects of health literacy, anticoagulation side-effects and treatment satisfaction in a cross-sectional study of 1790 oral anticoagulation outpatients. RESULTS: Seven hundred and sixteen participants (40.0%) had clinically significant depressive symptoms. Depressed persons reported lower compliance with intake of prescribed medication and regular visits for control of anticoagulation, more unspecific side-effects (e.g. pruritus) and lower satisfaction with the anticoagulation treatment and their doctors' expertise and empathy. Depressed as compared with non-depressed individuals had a lower TTR (-4.67; 95% CI, -8.39 to -0.95). Increasing severity of depressiveness was related with decreasing TTR. However, depressiveness lost its significant impact on TTR after multivariable adjustment (-3.11; 95% CI, -6.88 to 0.66). CONCLUSIONS: Clinically significant depressiveness was highly prevalent and impaired several aspects of anticoagulation treatment. Depressiveness should be regarded as a clinically significant condition that needs to be addressed in the management of anticoagulation patients.