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According to a growing body of neurobiological evidence, the core symptoms of borderline personality disorder (BPD) may be linked to an opioidergic imbalance between the hedonic and stimulatory activity of mu opioid receptors (MOR) and the reward system inhibiting effects of kappa opioid receptors (KOR). Childhood trauma (CT), which is etiologically relevant to BPD, is also likely to lead to epigenetic and neurobiological adaptations by extensive activation of the stress and endogenous opioid systems. In this study, we investigated the methylation differences in the promoter of the KOR gene (OPRK1) in subjects with BPD (N = 47) and healthy controls (N = 48). Comparing the average methylation rates of regulatorily relevant subregions (specified regions CGI-1, CGI-2, EH1), we found no differences between BPD and HC. Analyzing individual CG nucleotides (N = 175), we found eight differentially methylated CG sites, all of which were less methylated in BPD, with five showing highly interrelated methylation rates. This differentially methylated region (DMR) was found on the falling slope (5') of the promoter methylation gap, whose effect is enhanced by the DMR hypomethylation in BPD. A dimensional assessment of the correlation between disease severity and DMR methylation rate revealed DMR hypomethylation to be negatively associated with BPD symptom severity (measured by BSL-23). Finally, analyzing the influence of CT on DMR methylation, we found DMR hypomethylation to correlate with physical and emotional neglect in childhood (quantified by CTQ). Thus, the newly identified DMR may be a biomarker of the risks caused by CT, which likely epigenetically contribute to the development of BPD., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: Major Depression (MDD) and anxiety disorders are stress-related disorders that share pathophysiological mechanisms. There is evidence for alterations of glutamate-glutamine, N-acetylaspartate (NAA) and GABA in the anterior cingulate cortex (ACC), a stress-sensitive region affected by hypothalamic-pituitary-adrenal axis (HPA). The aim was to investigate metabolic alterations in the ACC and whether hair cortisol, current stress or early life adversity predict them., Methods: We investigated 22 patients with MDD and comorbid anxiety disorder and 23 healthy controls. Proton magnetic resonance spectroscopy was performed with voxels placed in pregenual (pg) and dorsal (d) ACC in 3 T. Analysis of hair cortisol was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS)., Results: The N-acetylaspartate/Creatin ratio (NAA/Cr) was reduced in patients in both pgACC ( p  = .040) and dACC ( p  = .016). A significant interactive effect of diagnosis and cortisol on both pg-NAA/Cr (F = 5.00, p  = .033) and d-NAA/Cr (F = 7.86, p  = .009) was detected, whereby in controls cortisol was positively correlated with d-NAA/Cr (r = 0.61, p  = .004)., Conclusions: Our results suggest a relationship between NAA metabolism in ACC and HPA axis activity as represented by long-term cortisol output.

Background: The global pandemic of the coronavirus disease 2019 (COVID-19) has presented many unique challenges to health systems. The hidden impact of COVID-19 and its associated lockdown have been an increased prevalence of domestic violence., Objective: To increase our understanding of the connection between COVID-19 containment measures, domestic violence, and mental health in Germany, we conducted an online self-assessment survey of 98 domestic violence victims and 276 controls. All participants answered questions concerning domestic violence, emotional regulation skills, limitations due to and acceptance of containment measures, and quality of their contact experiences., Results: There was no significant effect of "gender" x "domestic violence." Among victims of domestic violence, the number of women was considerably higher than the number of men. In addition, the factors "negative contact quality," "emotional regulation," and "resilience" differed significantly between the victims of domestic violence and the control group., Conclusions: The COVID-19 outbreak and associated containment and quarantine measures resulted in a "hidden pandemic" of domestic violence for which prevention programs and early victim assistance through the expansion of digital technologies are urgently needed. Prospective studies should expand empirical data to focus on the long-term psychological effects of domestic violence and biomarkers that can serve as warning signs of stress-related disorders., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objectives: This study aims to find out whether volatile organic compounds (VOCs) from exhaled breath differ significantly between patients with schizophrenia and healthy controls and whether it might be possible to create an algorithm that can predict the likelihood of suffering from schizophrenia., Methods: To test this theory, a group of patients with clinically diagnosed acute schizophrenia as well as a healthy comparison group has been investigated, which have given breath samples during awakening response right after awakening, after 30 min and after 60 min. The VOCs were measured using Proton-Transfer-Reaction Mass Spectrometry., Results: By applying bootstrap with mixed model analysis (n = 1000), we detected 10 signatures (m/z 39, 40, 59, 60, 69, 70, 74, 85, 88 and 90) showing reduced concentration in patients with schizophrenia compared to healthy controls. These could safely discriminate patients and controls and were not influenced by smoking. Logistic regression forward method achieved an area under the receiver operating characteristic curve (AUC) of 0.91 and an accuracy of 82% and a machine learning approach with bartMachine an AUC of 0.96 and an accuracy of 91%., Conclusion: Breath gas analysis is easy to apply, well tolerated and seems to be a promising candidate for further studies on diagnostic and predictive clinical utility.

Background: Several studies in major depressive disorder (MDD) have found inflammation, especially C-reactive protein (CRP), to be consistently associated with MDD and network dysfunction. The aim was to investigate whether CRP is linked to a distinct set of resting-state functional connectivity (RSFC) alterations., Methods: For this reason, we investigated the effects of diagnosis and elevated blood plasma CRP levels on the RSFC in 63 participants (40 females, mean age 31.4 years) of which were 27 patients with a primary diagnosis of MDD and 36 healthy control-subjects (HC), utilizing a seed-based approach within five well-established RSFC networks obtained using fMRI., Results: Of the ten network pairs examined, five showed increased between-network RSFC-values unambiguously connected either to a diagnosis of MDD or elevated CRP levels. For elevated CRP levels, increased RSFC between DMN and AN was found. Patients showed increased RSFC within DMN areas and between the DMN and ECN and VAN, ECN and AN and AN and DAN., Conclusions: The results of this study show dysregulated neural circuits specifically connected to elevated plasma CRP levels and independent of other alterations of RSFC in MDD. This dysfunction in neural circuits might in turn result in a certain immune-inflammatory subtype of MDD., (Copyright © 2022. Published by Elsevier B.V.)

Background: Borderline Personality Disorder (BPD) is characterized by emotional instability, impulsivity, disturbed cognition, sleeplessness and states of high inner tension. Altered arousal regulation which is regarded as a higher domain of functioning according to the research domain criteria of the NIMH and which has previously been reported in several psychiatric disorders, such as mania or major depression could be involved in these features of BPD., Methods: 40 unmedicated patients with BPD and 42 matched healthy volunteers participated in a twenty minute resting-state EEG measurement with closed eyes. EEG-vigilance regulation was assessed with VIGALL2.0 (Vigilance Algorithm Leipzig), which allows a classification of consecutive 1-s segments in different vigilance stages ranging from high alertness/relaxed wakefulness (stages 0, A1, A2, A3) to drowsiness (B1, B2/3) and sleep onset (C)., Results: Across 20 min, both groups showed a similar decline from higher to lower vigilance stages, but patients with BPD remained in higher stages of vigilance compared to healthy volunteers across the whole measurement (p = .013). Contrary to this, pre-experimental ratings indicated enhanced subjective sleepiness but no differences in self-reported sleep quantity in the previous night in patients with BPD compared to healthy volunteers., Conclusions: The results of an elevated arousal regulation (in combination with increased subjective sleepiness) might reflect several symptoms, such as aversive inner tension and impoverished sense of self in patients with BPD. As arousal is linked to the noradrenergic system, further investigations in this field seem to be promising., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Epigenetic mechanisms have been described in several mental disorders, such as mood disorders, anxiety disorders and schizophrenia. However, less is known about the influence of epigenetic mechanisms with regard to personality disorders (PD). Therefore, we conducted a literature review on existing original data with regards to epigenetic peculiarities in connection with personality disorders. Methods: Systematic literature review using PRISMA guidelines. Search was performed via NCBI PubMed by keywords and their combinations. Used search terms included "epigenetic," "methylation," "acetylation" plus designations of specified personality traits and disorders according to DSM-IV. Results: Search yielded in total 345 publications, 257 thereof with psychiatric topic, 72 on personality disorder or traits, 43 of which were in humans and epigenetic, 23 thereof were original studies. Lastly, 23 original publications fulfilled the intended search criteria and were included. Those are 13 studies on gene methylation pattern with aggressive, antisocial and impulsive traits, 9 with borderline personality disorder (BPD), and 2 with antisocial personality disorder (ASPD). The results of these studies showed significant associations of PD with methylation aberrances in system-wide genes and suggest evidence for epigenetic processes in the development of personality traits and personality disorders. Environmental factors, of which childhood trauma showed a high impact, interfered with many neurofunctional genes. Methylation alterations in ASPD and BPD repeatedly affected HTR2A, HTR3A, NR3C1 , and MAOA genes. Summary: Epigenetic studies in PD seem to be a useful approach to elucidate the interaction of co-working risk factors in the pathogenesis of personality traits and disorders. However, the complexity of pathogenesis leads to divergent results and impedes an explicit interpretation. Differing methylation patterns within the selected PD could indicate subgroups which would benefit from patient-oriented therapeutic adjustments. They might play a major role in the future design and observation of early therapeutic intervention and thus could help to prevent severe dysfunctional conduct or full-blown personality disorder in risk subjects.

Persistent loneliness is often reported by patients with borderline personality disorder (BPD). However, empirical studies investigating this aspect of BPD psychopathology are sparse. Studies from social psychology revealed that social isolation and low social functioning contribute to loneliness, that is, the subjective feeling of being alone. The aim of the present study was to contribute to the understanding of loneliness in BPD by investigating its relation to social isolation and functioning in different domains of life. Subjective experience of loneliness was measured in 80 women (40 BPD patients, 40 healthy controls) with the UCLA Loneliness Scale. Social isolation and social functioning were assessed with the Social Network Inventory and the Social Functioning Scale. In addition, we assessed global functioning with the Global Assessment of Functioning. BPD patients reported stronger feelings of loneliness compared to healthy participants. In general, the level of loneliness was linked to network size, social engagement, and prosocial behavior. Diversity of social networks and functioning in the domain of interpersonal communication were associated with the level of loneliness only in BPD. A reduced variety of roles in social life together with impairments in interpersonal communication were particularly relevant for the experience of loneliness in BPD, suggesting an indirect path to target this psychopathological feature in therapeutic interventions. However, both social isolation and social functioning were not sufficient to explain the severely increased loneliness experienced by these patients, stressing the need for further investigation of determinants of loneliness in this clinical population. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Introduction: Patients with borderline personality disorder (BPD) often report an unstable sense of self, which is further enhanced in dissociative states. As one consequence, BPD patients show a labile body percept, which might result in a higher degree of body plasticity. However, experimental data on body plasticity in BPD are not yet available., Materials and Methods: The rubber hand illusion (RHI) probes the plasticity of one's body by inducing the feeling of ownership for an artificial limb. We tested the proneness to perceive the RHI in female patients with current and remitted BPD compared to healthy controls, and related their perceptions to state and trait dissociation., Results: Participants with current BPD, compared to healthy controls, reported higher proneness to perceive the RHI (p<.05, with an effect size [Cohen's d] of 0.68). Remission was associated with a stabilization of perceptions. RHI vividness was positively related to state and trait dissociation across the groups, and specifically in current BPD when controlling for symptom severity (all Pearson's r≥.30, p<.05)., Discussion: These results indicate enhanced body plasticity related to dissociation in BPD, point to shared neurobiological mechanisms, and might help to elucidate the body-related perceptual disturbances associated with BPD., Conclusion: The results provide initial empirical evidence for significant alterations in body ownership processing associated with a current BPD diagnosis, resulting in enhanced body plasticity. Dissociation significantly correlated with illusory limb ownership experiences, making body plasticity a marker for BPD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Importance: The ability to perceive and regulate one's own emotions has been tightly linked to the processing of afferent bodily signals (interoception). Thus, disturbed interoception might contribute to the core feature of emotional dysregulation in borderline personality disorder (BPD), as increased levels of depersonalization, body image disturbances, and reduced sensitivity to physical pain suggest poor body awareness in BPD., Objective: To determine neural correlates of disturbed body awareness in BPD and its associations with emotional dysregulation and to explore improvements in body awareness with BPD symptom remission., Design, Setting, and Participants: Case-control study performed at Heidelberg University Hospital, Heidelberg, Germany. Heartbeat evoked potentials (HEPs), an indicator of the cortical representation of afferent signals from the cardiovascular system, were investigated in 34 medication-free patients with BPD, 31 healthy volunteers, and 17 medication-free patients with BPD in remission. The HEPs were assessed using 5-minute resting-state electroencephalograms and parallel electrocardiograms. Core BPD symptoms, history of childhood traumatization, and psychiatric disorders were assessed by means of self-reports and structured interviews. To measure neural correlates of disturbed body awareness, high-resolution T1-weighted structural magnetic resonance imaging scans were collected and analyzed using voxel-based morphometry and region-of-interest-based approaches. The study was performed between 2012 and 2014, and data analysis was performed in 2014., Main Outcomes and Measures: Mean HEP amplitudes in resting-state electroencephalograms and their correlation with self-reported emotional dysregulation, as well as with gray matter volume., Results: Patients with BPD had significantly reduced mean HEP amplitudes compared with healthy volunteers (F1,61 = 11.32, P = .001), whereas the mean HEP amplitudes of patients with BDP in remission lie somewhere in between these 2 groups of participants (P > .05). The HEP amplitudes were negatively correlated with emotional dysregulation (R = -0.30, P = .01) and positively associated with gray matter volume in the left anterior insula (R = 0.53, P < .05) and the bilateral dorsal anterior cingulate cortex (R = 0.47, P < .05), 2 structures that have been identified as core regions for interoception., Conclusions and Relevance: The results indicate state-dependent deficits in the cortical processing of bodily signals in patients with BPD, which appear to be associated with core features of BPD. The analysis of patients with BPD in remission suggests an improvement in cortical representation of bodily signals with symptom remission. Results recommend the integration of techniques to strengthen bodily awareness in psychotherapeutic interventions of BPD.

Background: Borderline personality disorder (BPD) is characterized by a profound instability of identity, by stress and affect dysregulation and impulsivity, and by cognitive-perceptual disturbances. These deficits seriously impair interpersonal experiences and social interaction. The typical impulsive style and psychosocial malfunctioning of these patients lead to grave disturbances in their everyday areas of life with numerous break-ups in all relevant areas of life and entail inadequate vocational placement. Despite vast demands on the health care system, BPD attracts little attention of care process research and reintegration measures as, for instance, exist for schizophrenia. At the LVR-Klinikum Düsseldorf as representative of a large clinic in North Rhein-Westphalia, we analysed socio-demographic characteristics of BPD inpatients. The aims of the study were to substantiate the high impact of the disease on patient's social and vocational integration and to sensitize for significant aspects of disease-specific therapy and care., Methods: A retrospective analysis of DGPPN-BADO of all patients (n = 9,425) who were admitted between January 2004 and December 2009 to the LVR-Klinikum Düsseldorf, department of psychiatry and psychotherapy, Heinrich Heine University Hospital, Germany. Data analysis involved the divisions general psychiatry and addictive disorders and covered 999 patients with BPD (ICD-10: F60.3) and 1,937 patients with schizophrenia (ICD-10: F20). The defined characteristics of DGPPN-BADO that depict psychosocial integration were "living situation at admission", "highest academic/professional degree achieved", "working situation" und "livelihood". Besides descriptive statistics of the elected variables, comparative analysis of the diagnoses BPD and schizophrenia involved calculating group differences after adjusting the groups for sex and age. Statistical analysis was performed by the χ2-test., Results: The comparative analysis of psychosocially relevant BADO characteristics reveals a significantly stronger impairment of patients with BPD concerning their academic and professional qualification than patients with schizophrenia. Nevertheless they more often hold a job or cover their living expenses without subsidy, respectively., Conclusion: The data suggest a lack of general awareness in the significance of social and vocational disturbances in BPD. The interactional deficits of patients with BPD affect all areas of life but their illness-related nature seems to be disregarded in relevant life areas, such as educational processes and the vocational situation. Furthermore, the impact of BPD on earning capacity is not given adequate consideration in the assessment of pensions or subsidies. Consistent with the recent literature, our socio-demographic data indicate significant deficits of the present health system in handling BPD.

Depressive disorder is a serious and frequent complication in borderline personality disorder (BPD), however, its severity tends to be neglected particularly if symptoms are short-lived or inconsistent as is common in patients with BPD. Yet the high frequency in these patients requires especially rapid and effective therapy to reduce the risks of vital endangerment, chronification and psychosocial impairment. Efficient crisis intervention is essential for continuity of the disease-specific multimodal therapy enabling lasting remission and social and vocational rehabilitation in BPD. In particular with regard to the high incidence of poor or failed pharmacological responses in patients with BPD, electroconvulsive therapy (ECT) is of significant relevance among antidepressant treatment options. Despite the wide consensus on its efficacy, there are only few selected trials on ECT for major depression (MD) in BPD. This review summarises the published original studies on this issue, and critically scrutinises indication, benefits and risks of ECT for MD in BPD. It contributes to a focused, discriminating view on ECT and thus enables an optimised patient-oriented, efficient indication for MD in BPD., (© Georg Thieme Verlag KG Stuttgart · New York.)

Infective endocarditis is a rare but life-threatening disease associated with high mortality. Early diagnosis of the causative microorganism is critical to patient outcome. However, conventional diagnostic methods are often unsatisfactory in achieving this goal. As a proof of concept, we applied fluorescence in situ hybridization (FISH) for detection and identification of bacteria in histological sections of heart valves. Biopsy specimens from 54 suspected endocarditis patients were obtained during valve surgery and analysed via FISH. Specimens were screened with a probe panel that identifies the most common bacteria implicated in endocarditis. Results were compared with those of culture-based diagnostics and clinical data. Discrepant results were subjected to comparative sequence analysis of PCR-amplified 16S rRNA genes. FISH detected bacteria in 26 of the 54 heart valves. FISH allowed successful diagnosis of infective endocarditis in five of 13 blood culture-negative cases and in 11 of 37 valve culture-negative cases, showing the bacteria within their histological context. This technique allows the simultaneous detection and identification of microorganisms at the species or genus level directly from heart valves and might be a valuable tool for diagnosis of endocarditis.

Borderline Personality Disorder (BPD) constitutes a profound instability with dysfunction in three psychopathological dimensions as cognitive-perceptual symptoms, affective dysregulation and behavioral impulsivity. Psychopharmacotherapy has a crucial role in the treatment of this complex disorder and targets the respective core symptoms. It comprises basically atypical antipsychotics, antidepressant agents and moodstabilizers, often requiring a combination of these substances in case of complex, multidimensional symptoms. Regarding the predominantly young and female patients the teratogenic risk demands critical consideration. This study focuses on the use of moodstabilizers in the treatment of BPD and gives an overview of the currently available studies on this substance class, in particular on lithium, carbamazepine, divalproex sodium, topiramate and lamotrigine. Results show significant effects on core features of BPD, but nevertheless, there are considerable limits in comparability and validity among the studies because of heterogeneities in the patient groups, study design, additive medication and outcome measures. Disregarding the off-label use in this indication the data reflect however an established clinical practice of use for these substances and underline the pivotal impact of moodstabilizers in the treatment of core symptoms of BPD.

Sepsis is a life-threatening disease with a high mortality rate. Rapid identification of blood culture isolates plays a crucial role in adequate antimicrobial therapy in sepsis patients. To accelerate microbiological diagnosis, a comprehensive panel of oligonucleotide probes for fluorescence in situ hybridisation (FISH) targeting Gram-positive cocci was compiled and evaluated on 428 positive blood culture specimens. By combining genus-specific and species-specific probes, the assay allowed discrimination of staphylococci, streptococci and enterococci as well as differentiation of therapy-relevant pathogens such as Staphylococcus aureus and Enterococcus faecium/durans. Furthermore, the newly designed FISH probes STREP2, ENCO and GRANU targeted Streptococcus pneumoniae/mitis, Enterococcus spp. (except E. faecalis) and Granulicatella adiacens group, respectively. The FISH assay achieved an overall sensitivity of 98.65% and a specificity of 99.0% and therefore allowed rapid and reliable molecular identification of Gram-positive cocci in blood culture specimens.

Digital dermatitis (DD) of cattle leads to lameness and a decrease of milk production and is responsible for major economic losses worldwide. Although a bacterial aetiology is generally accepted, it still is unclear which microorganisms cause and/or maintain the disease. Recently, a previously undiscovered bacterial species, Guggenheimella bovis, has been isolated from the front of two DD lesions in Swiss cattle and suggested as a potential pathogen. The aims of the present study were to determine the prevalence of G. bovis in 58 German cows suffering from DD via dot blot hybridization, and to analyse the spatial distribution of G. bovis within the affected tissue by fluorescence in situ hybridization (FISH). A species-specific probe, GUBO1, was designed and evaluated. In none of the 58 samples Guggenheimella could be detected, while cultured G. bovis was reliably identified by GUBO1. Further FISH experiments were carried out on two additional biopsies of Swiss cattle tested positive for G. bovis by quantitative PCR and permitted visualization of the newly discovered bacteria in situ. In these biopsies G. bovis proved to be tissue invasive forming characteristic spherical microcolonies not only within the bacterial biofilm but also in seemingly unaffected parts of the tissue not yet reached by the advancing bacterial front. Although the presence of G. bovis does not constitute an essential premise for DD, it seems likely that the bacterial species involved in DD vary, and that in some cases G. bovis is crucial for the development of DD lesions.

Culture-negative endocarditis is a frequent problem in cardiology, especially if caused by fastidious organisms. Among these, the diagnostic tools for the detection of Bartonella quintana are still unsatisfactory. In a culture-negative case of suspected endocarditis undergoing aortic valve replacement, polymerase chain reaction amplification and sequencing of the 16S rRNA gene indicated B. quintana infection. To develop a new diagnostic tool, independent from culture and amplification techniques, we designed and optimized an oligonucleotide fluorescence in situ hybridization (FISH) probe specific for B. quintana and suitable for FISH. FISH succeeded in simultaneous visualization and identification of vital microorganisms directly within the aortic valve tissue and in fast and univocal diagnosis of B. quintana endocarditis.

Oral infection of susceptible mice with Toxoplasma gondii results in Th1-type immunopathology in the ileum. We investigated gut flora changes during ileitis and determined contributions of gut bacteria to intestinal inflammation. Analysis of the intestinal microflora revealed that ileitis was accompanied by increasing bacterial load, decreasing species diversity, and bacterial translocation. Gram-negative bacteria identified as Escherichia coli and Bacteroides/Prevotella spp. accumulated in inflamed ileum at high concentrations. Prophylactic or therapeutic administration of ciprofloxacin and/or metronidazole ameliorated ileal immunopathology and reduced intestinal NO and IFN-gamma levels. Most strikingly, gnotobiotic mice in which cultivable gut bacteria were removed by quintuple antibiotic treatment did not develop ileitis after Toxoplasma gondii infection. A reduction in total numbers of lymphocytes was observed in the lamina propria of specific pathogen-free (SPF), but not gnotobiotic, mice upon development of ileitis. Relative numbers of CD4(+) T cells did not differ in naive vs infected gnotobiotic or SPF mice, but infected SPF mice showed a significant increase in the frequencies of activated CD4(+) T cells compared with gnotobiotic mice. Furthermore, recolonization with total gut flora, E. coli, or Bacteroides/Prevotella spp., but not Lactobacillus johnsonii, induced immunopathology in gnotobiotic mice. Animals recolonized with E. coli and/or total gut flora, but not L. johnsonii, showed elevated ileal NO and/or IFN-gamma levels. In conclusion, Gram-negative bacteria, i.e., E. coli, aggravate pathogen-induced intestinal Th1-type immunopathology. Thus, pathogen-induced acute ileitis may prove useful to study bacteria-host interactions in small intestinal inflammation and to test novel therapies based on modulation of gut flora.

Progestational hormones may have anxiolytic properties. CCK-4 (cholecystokinin tetrapeptide) can be used pharmacologically to induce panic attacks both in normal controls and patients suffering from panic disorder. In this study we compared the effects of pretreatment with the progestational hormone megestrol and placebo on CCK-4-induced panic attacks and stress hormone release in healthy male controls. Using a double-blind balanced design, we pretreated 10 medically and psychiatrically healthy male controls with placebo or megestrol 160 mg at 11 p.m. and 8 a.m. (sigma=320 mg) prior to the experiment. Following 1 h of rest, 12 blood samples were drawn between 1,000 h and 1,300 h and analyzed for ACTH and cortisol levels. At 1,100 h, subjects received an intravenous injection of 50 microg CCK-4. Clinical ratings were performed at 1,045 h and 1,110 h, and included the Acute Panic Inventory (API), International Diagnostic Checklist (IDCL), as well as a visual analog scale (VAS) for anxiety and tension. CCK-4 significantly increased anxiety and tension. Pretreatment with megestrol showed no significant effect on clinical ratings. Baseline ACTH and cortisol levels, as well as ACTH and cortisol levels after administration of CCK-4, were significantly reduced after pretreatment with megestrol. In a sample of healthy male controls, pretreatment with megestrol had a profound effect on the hypothalamic-pituitary-adrenal (HPA) axis, whereas the clinical effects on panic attacks were weak. Further studies in a larger sample of subjects, including both females and patients suffering from panic disorder, seem warranted.

Background: In endometriosis, angiogenesis is a crucial step for implantation of the exfoliates. A priori potential to induce angiogenesis by vascular endothelial growth factor (VEGF) expression was compared in eutopic endometrium of patients with and without endometriosis to discriminate the pivotal pathogenic step that differs in endometriosis., Methods: In an experimental prospective study, endometrium samples were obtained from endometriosis patients (n=10) and from healthy, ovulating women as controls (n=6) undergoing curettage and laparoscopy for benign gynaecological conditions at the Aachen University Hospital, Aachen, Germany. Endometrial fragments were transplanted to the chicken chorioallantoic membrane (CAM) and re-explanted after 0, 24, 48, 72 and 96 h of cultivation for analysis. The main outcome measure was VEGF mRNA expression and protein localisation in endometrial fragments as parameters of angiogenic induction that was quantified by the vessel index., Results: VEGF mRNA expression increased significantly in endometrial fragments of endometriosis and control patients (p<0.05). Protein is expressed in the glands and endometrial stroma. The vessel index is significantly elevated compared with native CAM controls. Endometrial fragments of endometriosis and control patients showed no significant differences in VEGF expression or angiogenic induction., Conclusions: Eutopic endometrial fragments of patients with and without endometriosis do not differ in their VEGF expression or angiogenic activity in the CAM assay. Implantation is obviously decided by external regulating influences on the exfoliates.

Background: Although silicone breast implants are well tolerated, local complications such as capsular contracture occur because of insufficient integration with surrounding tissues. In this study, cell behaviour on hydrophilized silicone breast implant foils was analysed qualitatively and quantitatively under in vitro conditions in order to provoke the desired responses in a defined environment., Methods: Silicone breast implant foils with different surface modifications were tested after 24 hours, 5 days and 7 days. The following modifications of silicone implant foils were tested: Unmodified silicone, silicone after-graft polymerisation for polyacrylic acid (pAAc), silicone-pAAc-fibronectin adsorptive, silicone-pAAC-fibronectin covalent, positive and negative controls. Experiments were conducted using cell culture with murine mouse fibroblasts L-929. Cytotoxicity assays were carried out in direct and indirect contact with cells grown on the material. For the viability test and qualitative analysis of cell proliferation on different foils, both fluoresceine-diacetate and ethidiumbromide were used and in addition the morphologic description of hemalaun-stained cells were used. Quantitative cell analysis was carried out using XTT after resuspension., Results: Toxic influence on cell cultures could be excluded for coated and uncoated surfaces in contact with dissolved biomaterials. Unmodified silicone surfaces showed poor cell growth in direct contact. We found a gradual improvement of cell morphology, with the spread and proliferation depending on the type of surface modification. Better results were achieved with covalently coupled fibronectin and GRGDS than with pAAc., Conclusion: Covalent immobilisation of hydrophobic silicone rubber can improve the initial cell-biomaterial interactions that are required to aid the successful development of tissue-like structures.

Objective: To investigate the role of angiopoietin 1 and 2 (ANGPT1/ANGPT2) in angiogenesis of the ectopic endometrium as a crucial step in the development of an endometriotic lesion, we analyzed their expression patterns in an experimental model of endometriosis., Design: Experimental prospective study., Setting: University hospital., Patient(s): Endometrium samples obtained from healthy, ovulating women undergoing hysterectomy for benign gynecologic conditions., Intervention(s): Endometrial fragments were transplanted to the chicken chorioallantoic membrane (CAM) and cultivated for 0, 24, 48, and 72 hours., Main Outcome Measure(s): Expression of ANGPT1 and ANGPT2 mRNA was quantified by competitive reverse transcriptase polymerase chain reaction (RT-PCR) and normalized to expression of the housekeeping gene human glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA. The expression of ANGPT1 and ANGPT2 protein was analyzed by immunohistochemical staining., Result(s): All grafts expressed ANGPT1 and ANGPT2 mRNA. The mRNA concentration of both factors decreased after cultivation, but the ANGPT2/ANGPT1 ratio increased considerably during the first 24 hours of cultivation. The immunohistochemical investigation for ANGPT1 and ANGPT2 revealed presence of both proteins at all the times but no obvious correlation with the duration of cultivation., Conclusion(s): The ratio of ANGPT2/ANGPT1 mRNA in endometrial grafts increased after 24 hours of cultivation on the chicken chorioallantoic membrane and shows a shift toward a more dominant role of ANGPT2. This agrees with the current model of angiopoietin action in angiogenesis and might indicate angiogenic activity in the endometrial graft. The angiopoietins are likely to play an important role in the pathogenesis of endometriosis.

Objective: To analyze the expression of angiopoietin 1 (ANGPT1) in pigmented and nonpigmented endometriosis implants and specify its role in the interaction of angiogenic factors., Design: Experimental retrospective study., Setting: University hospital., Patient(s): Eighty-two sections from 201 laparoscopic tissue samples of 43 female patients., Intervention(s): Biopsies of peritoneal endometriotic lesions of macroscopically different forms., Main Outcome Measure(s): Angiopoietin 1 expression and location pattern in endothelial cells, periendothelial cells, glandular epithelium, and stromal structures., Result(s): Angiopoietin 1 is immunohistochemically detectable in endothelial cells, periendothelial cells, in the glandular epithelium, and in the stroma. Differences in the expression of pigmented and nonpigmented lesions are not statistically significant., Conclusion(s): Pigmented and nonpigmented endometriotic lesions differ according to their clinical activity and angiogenic potential. Angiopoietin 1 is an important representative of the angiogenic factors and is involved in the angiogenic processes of these lesions. There were no significant differences in the expression and location within different lesion types for ANGPT1. Thus, it is not a direct activity marker of a lesion.

Background: Clinical observations suggest that prolonged treatment with megestrol can lead to Cushing-like symptoms, while withdrawal of prolonged treatment with megestrol may result in adrenal insufficiency. However, only little is known about the acute effects of megestrol on the hypothalamic-pituitary-adrenal (HPA) axis. As part of an endocrine study, we evaluated the acute effects of megestrol, hydrocortisone and placebo on morning cortisol and ACTH levels., Method: . Using a balanced double-blind design, ten healthy male subjects were treated at 11:00 p.m. and 8:00 a.m. with megestrol (total dose 320 mg), hydrocortisone (total dose 30 mg) or placebo. After 1 h of rest, blood was drawn at 10:00 a.m. and 10:30 a.m. for determination of cortisol and ACTH levels., Results: . Compared to placebo, acute administration of megestrol resulted in a significant decrease in morning ACTH and cortisol levels. The suppression of ACTH after pretreatment with megestrol was less pronounced than after pretreatment with hydrocortisone., Conclusions: Our results suggest that megestrol exerts glucocorticoid-like effects and has an acute depressing effect on the HPA axis. Therefore alterations in the steroid system should be included in the differential diagnosis of all subjects under treatment with megestrol.

The pathogenesis of endometriosis is dependent on implantation. Therefore, angiogenesis of the ectopic endometrium is discussed as a crucial step in the development of an endometriotic lesion. It is not only the main condition for implantation, but also a parameter for the clinical activity of endometriosis. Pigmented and non-pigmented endometriotic lesions differ according to their clinical activity and angiogenic potential. Using a model system of endometriosis, the chorioallantoic membrane assay, mRNA expression of VEGF and matrix metalloproteinases 1 and 2 was analysed. As the most representative angiogenic factors, they were correlated to the angiogenic reaction on the CAM by the vessel index. We assume that angiogenic activity of ectopic endometrium is a condition sine qua non for the pathogenesis of endometriosis, but is regulated by different other factors.