Circulating soluble fibroblast activation protein (FAP) levels are independent of cardiac and extra-cardiac FAP expression determined by targeted molecular imaging in patients with myocardial FAP activation.

INTRODUCTION: Tissue Fibroblast Activation Protein alpha (FAP) is overexpressed in various types of acute and chronic cardiovascular disease. A soluble form of FAP has been detected in human plasma, and low circulating FAP concentrations are associated with increased risk of death in patients with acute coronary syndrome. However, little is known about the regulation and release of FAP from fibroblasts, and whether circulating FAP concentration is associated with tissue FAP expression. This study characterizes the release of FAP in human cardiac fibroblasts (CF) and analyzes the association of circulating FAP concentrations with in vivo tissue FAP expression in patients with acute (ST-segment elevation myocardial infarction, STEMI) and chronic (severe aortic stenosis, AS) myocardial FAP expression. METHODS AND RESULTS: FAP was released from CF in a time- and concentration-dependent manner. FAP concentration was higher in supernatant of TGFß-stimulated CF, and correlated with cellular FAP concentration. Inhibition of metallo- and serine-proteases diminished FAP release in vitro. Median FAP concentrations of patients with acute (77 ng/mL) and chronic (75 ng/mL, p = 0.50 vs. STEMI) myocardial FAP expression did not correlate with myocardial nor extra-myocardial nor total FAP volume (P ≥ 0.61 in all cases) measured by whole-body FAP-targeted positron emission tomography. CONCLUSION: We describe a time- and concentration dependent, protease-mediated release of FAP from cardiac fibroblasts. Circulating FAP concentrations were not associated with increased in vivo tissue FAP expression determined by molecular imaging in patients with both chronic and acute myocardial FAP expression. These data suggest that circulating FAP and tissue FAP expression provide complementary, non-interchangeable information.

microRNA-206 correlates with left ventricular function after transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is the method of choice in patients with high risk or contraindications for conventional aortic valve replacement. However, it is not well understood which parameters predict the overall cardiac function postprocedurally. miRNAs are small noncoding RNA molecules that repress gene expression by different mechanisms and can also be detected in the blood. Recent studies have shown that miRNAs detected in the blood may serve as sensitive and specific biomarkers in various diseases; therefore, we examined the levels of different microRNAs in the serum of patients undergoing TAVI. We thereby intended to find potential predictors for cardiac function after TAVI. Serum from patients with aortic valve disease was obtained at five different points: before the TAVI procedure, at days 1 and 3 after the TAVI procedure, and the day of dischargement and after a period of 3 mo. We next performed quantitative real-time PCRs to examine the samples for changes in the level of miRNAs previously described as cardiac enriched. Our results show that the level of miR-206 in the serum of patients after TAVI correlated negatively with the left ventricular ejection fraction of individual patients. We found left ventricular function to be better in patients with lower levels of miR-206 after implantation of the new valve. A decrease in the serum level of miR-206 may be linked to changes in cardiac function of patients after TAVI. Further studies are necessary to test the miRNA for its potential value as a prognostic marker. NEW & NOTEWORTHY This study is the first to investigate novel miRNA-based biomarkers within the context of transcatheter aortic valve implantation. miRNA-206 proved to correlate inversely with the postprocedural left ventricular ejection fraction of patients.

[Medical education in the dilemma between theory and praxis. The reforms in medical studies make an impact]. / Die ärztliche Ausbildung im Spannungsfeld von Theorie und Praxis. Die Reform des Medizinstudiums zeigt Wirkung.

The 2002 German medical licensing regulations for physicians represent an interim end point of a development that demands stronger orientation of medical education towards practical skills training. Meanwhile the responsible institutions have implemented the regulations. The article portrays the history of this reform of medical studies and critically discusses the value of an early practical orientation during the course of medical education. The article stresses the value of medical knowledge, which must receive priority in order to sustain the high quality of medical practice.

[Validation of an observer-based rating set compared to a standardized written psychological test for the diagnosis of depression and anxiety in a university preadmission test center]. / Vergleich der Einschätzung von Depressivität und Angstlichkeit durch einen standardisierten Fragebogen oder Fremdbeobachtung in einer universitären Prämedikationsambulanz.

INTRODUCTION: Depression and anxiety can be a major factor of perioperative stress and might contribute to patients dissatisfaction with medical care if they remain unrecognized. There are several methods to diagnose depression and anxiety like standardized written psychological tests or self report scales. Because these tests are not always suitable for routine use in a busy preadmission test center we evaluated an observer-based rating set for the diagnosis of depression and anxiety. MATERIAL AND METHODS: 70 patients of a university hospital preadmission test center were tested with the HADS-D-Test and the observer-based rating set after approval of the institutional review board and written informed consent. Test-data were compared using a logistic regression model and demographic variables were analyzed using t-Test. ANOVA and Pearson correlation. RESULTS: The prevalence of depression in our study population was 11.11% (14.75% in male, 9.76% in female) and the prevalence of anxiety was 7.14% (6.9% in male and 7.32% in female). The correlation between the observer-based rating items and the HADS-D-diagnosis was statistically highly significant. The observer based items "unsteady eye movements" and "general worrisome mood" proved to be especially sensitive for anxiety and the items "sorrowful mood" and "impression of resignation" were sensitive for depression without any influence of the experience of the anesthesiologist. A higher prevalence of depression and anxiety was found in patients with ASA-class III compared to those with ASA-classes I and II while age and type of surgery had no significant influence. CONCLUSIONS: Based on our observations depression and anxiety are a relevant factor of preoperative morbidity assessment. Observer-based items are a reliable tool to detect those patients which might need special assistance and therapy in the perioperative period to reduce stress associated with high preexisting levels of depression and anxiety.

[Perceived threat related to dental amalgam fillings]. / Wahrgenommene Bedrohung durch Amalgamfüllungen der Zähne.

Amalgam carriers without somatic complaints and patients who attribute symptoms to amalgam fillings of their teeth do not differ with respect to toxicologic or allergologic parameters. Somatic complaints of amalgam carriers usually are explained as misattributions of unspecific complaints. Perceived threat is a relevant factor within the theoretical models. For the explanation of health related behavior perceived threat is also an important variable. In the present study perceived threat was a relevant factor for complaints associated with dental material, but not for health related behavior in the sense of caries prophylaxis.

Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation.

BACKGROUND: Neurodevelopmental outcome after neonatal arterial switch operation for complete transposition of the great arteries is an important topic needing prospective assessment. METHODS: A group of 33 unselected children (3.0 to 4.6 years) operated on as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass and a control group of 32 age-matched healthy children (3.0 to 4.8 years) underwent evaluation of socioeconomic and clinical neurological status and a standardized test comprising all areas of child development. Results of patients were related to those of the control group, to population norms, and to preoperative, perioperative, and postoperative cerebral risk factors. RESULTS: Clinical neurological status was normal in 26 patients (78.8%) and reduced in 7 (21.2%). Complete developmental score and the subscores for motor function, visual perception, learning and memory, cognitive function, language, and socioemotional functions were not different compared to population norms. Compared to the patients, the children of the control group scored higher on tests of complete development, cognition, and language, but also on socioeconomic status. Complete developmental score and the scores for motor, cognitive, and language functions were weakly inversely related to the duration of circulatory arrest, but not to the duration of bypass. Cerebral risk factors such as serum levels of the neuron-specific enolase, perinatal acidosis, perinatal asphyxia, peri- and postoperative cardiocirculatory insufficiency, or clinical seizures were not correlated to the test results. CONCLUSIONS: Neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with neurological impairment, but not with reduced development as assessed by formal testing of motor, cognitive, language, and behavioral functions. Perioperative serum level of the neuron-specific enolase is not a valid marker for later developmental impairment.

[Neuropsychological effects of preventive CNS irradiation in adult tumor patients]. / Neuropsychologische Effekte der prophylaktischen ZNS-Bestrahlung bei erwachsenen Tumorpatienten.

Prophylactic cranial irradiation (PCI) has led to marked prolongation of survival, but also to intellectual and neuropsychological retardation in children with ALL. PCI has also been conducted in adult patients with small-cell bronchial carcinoma in the stage of minimal disease or with breast cancer. There are no studies assessing cognitive or other neuropsychological consequences of PCI in adult cancer patients. We report on a longitudinal prospective study of the effects of PCI on five major neuropsychological domains (intelligence, concentration, attention, memory and psychomotor performance). We report on our ongoing study, in which up to now 11 patients with small-cell lung cancer undergoing PCI have been investigated. Patients are assessed immediately before therapy started as well as 4 weeks and 3 months after onset of PCI. The used instruments are Standard Progressive Matrices (SPM), d2 Concentration Test, Minimental State, Verbal Learning Test and Psychomotor Tests (Steadiness, Aiming, Tapping, Tracking, Pursuit Rotor Test). Although our sample is small, results indicate that there is no evidence for a decrease in neuropsychological abilities in adults after three months. This is in contrast to the observed results after PCI in children. As compared to baseline measures, differences in memory, intelligence, concentration and attention were marginal over time. Moreover the progress of motor performance skills showed no clear tendency.

[Prevention of smoking from the psychological medicine perspective]. / Prävention des Rauchens aus medizinpsychologischer Perspektive.

Smoking is a complex socio-psycho-biological behavior with high prevalence and high risk for several diseases. Referring to a widely accepted concept of prevention, the review presents recent psychological and pharmacological strategies to cease smoking with respect to theory, application, and evaluation. Primary prevention, which includes appropriate settings in schools, families, and social groups, seems adequate in preventing people from health problems associated with tobacco-smoke. Although evaluations are rarely found, curricula starting at childhood and intensive training programs for adolescents can be presently recommended. These programs have to take into account specific group characteristics and should focus on active and self-controlled behavior without smoking. Additionally, negative short-term effects of smoking should be emphasized more clearly instead of longterm risks of smoking. The broad diversity of secondary prevention programs for smoking cessation and relapse prevention includes well established and efficient psychological and pharmacological treatments. Flexible combinations of psychotherapeutic and pharmacological strategies (e.g. behavioral skill training programs and nicotine replacement therapy), which also consider the strength of nicotine dependence and withdrawal symptoms, are most promising. For smokers, who continue to smoke despite of health damages (e.g. cardiovascular diseases, cancer), intensive psychotherapeutic regimens (tertiary prevention) are suggested. However, evaluation on this issue is almost missing. In summary, smoking prevention programs can be considered to be cost-effective. Nevertheless, 1 year abstinence rates range only between 20-30%. Furthermore, there is a strong need for psychobiological research on the development of smoking behavior, on long-term follow-up of prevention programs, and on outcome prediction.

[Psychosomatic research on stress in bone marrow transplantation]. / Psychosomatische Forschung zur Belastung unter Knochenmarktransplantation.

Bone marrow transplantation (BMT) offers a therapeutic chance for a number of hematologic diseases, but BMT is associated with a number of stressful situations. Prospective longitudinal studies on 30 BMT patients suffering from acute leukemia or CML are reported. The studies refer to stress reactions of patients, stressful situational characteristics of the BMT procedure and psychological features (personality, coping, social support), which potentially modify distress reactions.

Personality and survival time after bone marrow transplantation.

Personality was assessed by means of the Personality Research Form (PRF) in 35 patients with acute leukaemia, Chronic Myelogenous Leukaemia, or Severe Aplastic Anemia at hospital admission for bone marrow transplantation (BMT). The sample was split into two groups of patients with high or low scores, respectively, in four PRF second order factors and survival curves of these groups were compared by means of Kaplan-Meier Analyses. Longest observation time lasted for more than two years. Patients scoring high in 'Strive for recognition and help' had a higher survival probability after about one year post BMT. It is suggested that compliance behaviour is the pathway mediating between personality and survival probability.

Associations of personality variables with smoking behavior and pulmonary function.

Interindividual variability of lung function responses to smoking is unexplained. The aim of the present study is to inquire about a possible role of personality factors for an explanation of interindividual differences of lung function responses in smokers of both sexes. The results of canonical correlation analyses showed that there are no substantial correlations of personality with smoking behavior and also no significant associations of smoking behavior with pulmonary function in a healthy sample of smokers. In males only, personality factors were related to breathing frequency, but not to static and dynamic lung volumes.

Sudden idiopathic hearing loss: psychopathology and antecedent stressful life-events.

Otologists repeatedly state that patients suffering from Sudden Idiopathic Hearing Loss (SIHL) often have significant emotional problems or stressful living conditions. The study described here compared males and females suffering from SIHL with controls without any impairment of the inner ear. Personality data were gathered by means of Faschingbauer's Abbreviated MMPI (FAM). Stress factors were assessed by an Inventory of Stressful Life-Events (ILE). SIHL patients reported more stressful life-events, whose distressing effects lasted until onset of symptoms, than controls. There was no significant influence of personality upon report of stress. Stress factors and inability to cope with these seem to be important psychological factors in SIHL patients, while psychopathological disturbances may be important for some but not for the majority of cases.

[Methodology of geriatric research]. / Zur Methodologie der Altersforschung.

Starting from the basic equation of research on aging [behaviour = f (age)], various issues involved in defining the subject-matter of that research are discussed. Advantages and disadvantages of aging research methods (i.e. cross-sectional, longitudinal, and time-lag study, cohort analysis), evolved by extension of the basic equation, are put forth and are critically discussed in terms of the relevancy of the findings obtained.

[Uses and disturbing effect of videodocumentation of diagnostic interviews]. / Nutzen und Störeffekte der Videodokumentation diagnostischer Gespräche.

Videorecording of diagnostic interviews is reviewed with respect to its effects upon patient behaviour. If this behaviour is to be a model of the behaviour outside the diagnostic situation, videorecording should not essentially alter behaviour. It can be derived from psychological findings that due to the patient's necessary consent to videorecording, but also by the recording situation itself, patient behaviour is modified. The advantage of audiovision compared to audiorecording to reach a more objective judgement is limited by the very few possibilities of evaluation of nonverbal behaviour. Empirical studies comparing the relative effects of video- and audiorecording have shown that videorecording has more disturbing effects on patients. If these disturbances do have differential effects at certain problems and personality structures of patients using the artifacts of videorecording should be a possibility for the efficient employment of videorecording diagnostic interviews.