Improvements of complex post-traumatic stress disorder symptoms during a multimodal psychodynamic inpatient rehabilitation treatment - results of an observational single-centre pilot study.

Background: Complex post-traumatic stress disorder (CPTSD) describes chronic disturbances in self-organization (i.e. affect dysregulation; negative self-concept; severe difficulties in relationships) which are frequently observed in survivors of prolonged, repeated or multiple traumatic stressors. So far, evidence of psychodynamic treatment approaches for CPTSD is scarce.Methods: In this single-centre observational pilot study, symptom change during a 6-week psychodynamic inpatient treatment in a multimodal psychosomatic rehabilitation centre was evaluated using repeated measures analyses of variance (ANOVAs). Patients completed questionnaires on PTSD and CPTSD symptoms (ITQ), anxiety, depression and somatization (BSI-18), functional impairment (WHODAS) and epistemic trust, mistrust and credulity (ETMCQ) before (T1) and at the end of treatment (T2). A hierarchical linear regression analysis was calculated to identify factors associated with improved CPTSD symptoms.Results: A total of n = 50 patients with CPTSD were included in the study, of whom n = 40 (80%) completed treatment. Patients reported a significant reduction of CPTSD symptoms during treatment with a large effect size (-3.9 points; p < .001; η2 = .36), as well as a significant reduction of psychological distress (p < .001; η2 = .55) and functional impairment (p < .001; η2 = .59). At the end of treatment, 41.0% of patients no longer fulfilled the diagnostic criteria for CPTSD. Changes in epistemic stance included improved epistemic trust (ß = -.34, p = .026) and decreased epistemic credulity (ß = .37, p = .017), which together with lower age (ß = .43, p = .012) and lower depression levels at baseline (ß = .35, p = .054) were significantly associated with baseline adjusted mean change of CPTSD symptoms during therapy and explained 48% of its variance.Discussion: In our study, patients reported a significant reduction of CPTSD symptoms and comorbid symptoms during a multimodal psychodynamic inpatient rehabilitation treatment. Improved epistemic trust may facilitate the establishment of a trusting therapeutic relationship, thus fostering an environment of openness for knowledge transfer (i.e. social learning) and the exploration of diverse viewpoints and perspectives in the therapeutic process.

Complex post-traumatic stress disorder (CPTSD) is a condition often found in individuals who have experienced severe trauma, such as childhood abuse or torture.A study involving 50 patients with CPTSD showed significant improvements in symptoms and overall quality of life after undergoing a 6-week integrative multimodal psychodynamic inpatient rehabilitation treatment.The study also highlighted that improvement in epistemic trust could be a potential mechanism of change contributing to the positive therapeutic outcomes.

Mentalization and dissociation after adverse childhood experiences.

.Impairment of mentalization may impact coping strategies, regulation of affect and stress. The influence of impaired mentalization on dissociation in patients with adverse childhood experiences (ACEs) could be important for treatment strategies. The aim of this study is to assess the relationship between ACEs, mentalizing and dissociation in adult individuals. Sixty-seven patients with ACEs completed the Mentalization Questionnaire (MZQ), the Essener Trauma Inventory (ETI) and the Brief Symptom Inventory-18 (BSI-18). The SPSS PROCESS macro tool was applied to test if mentalization mediated the relationship of ACEs and dissociation. ACEs were significantly associated with higher dissociation (ß = 0.42, p < 0.001) and lower mentalization (ß = - 0.49, p < 0.001). When mentalization was added to the model as a predictor, the association of ACEs with dissociation was no longer significant (ß = 0.11, p = 0.31) and a statistically significant indirect effect was found (ß = 0.32, 95% CI 0.16-0.47). The overall explained variance of dissociation notably improved after inclusion of mentalization (17.5% to 49.1%). Thus, the results indicated that the association of ACEs on dissociation was fully mediated by mentalization. Our results suggest that ACEs are associated with lower mentalization and higher dissociation. Lower mentalization was also associated with worse depression, anxiety, somatization and PTSD symptoms. These findings underline the increasing importance of early treatment of individuals affected by ACEs with a focus to foster the development of mentalization.

Worlds apart or two sides of the same coin? Attitudes, meanings, and motives of potential oocyte and sperm donors in Austria.

PURPOSE: Gamete donors and recipients of such donations have been explored by previous studies, which mostly focus on post-donation scenarios. Our study analyses the general willingness to donate oocytes or sperm and focuses on differences between potential female and male donors in attitudes, meanings, and motives in a pre-donation setting. METHODS: An electronic survey (n = 555 students) was used in this anonymous observational study. To enable comparisons between men and women regarding their attitudes, meanings, and motives and their willingness to donate gametes, we designed two separate questionnaires. RESULTS: The sample was divided into three groups based on the willingness to donate: potential donors (n = 133; women: 48.1%, men: 51.9%); doubtful donors (n = 207; women: 75.8%, men: 24.2%); and non-donors (n = 215; women: 68.3%, men: 31.7%). The group of potential male donors (39.2%) was significantly larger than the group of potential female donors (16.9%). Significant differences regarding altruism, the meaning of one's self-worth, and passing on the own genes were found between doubtful and potential donors. Potential donors attached less value to altruism but more value to the enhancement of one's self-worth and passing on one's genes than doubtful donors. The motive of passing on one's genes and altruistic motives were more important to men than to women. CONCLUSION: This study helps to create a better understanding of potential donors in the existing donation framework and supports the evaluation of the given regimes in the context of designing an improved framework.

Paediatric referral and attendance rates for the clinical genetics service in south-east Scotland--a comparison of a regional clinic with satellite clinics.

BACKGROUND AND AIMS: In some studies the establishment of specialist satellite clinics nearer to the homes of patients has resulted in increased referral and attendance rates, particularly amongst populations in lower socio-economic groups. We investigated the effect on these rates of establishing satellite genetic counselling clinics for families with paediatric conditions in South East Scotland. METHODS AND RESULTS: Families offered appointments at a clinic at the regional paediatric hospital were compared with those offered appointments at a satellite clinic at a local district general hospital. Both groups of families were more socially deprived than the general population (regional clinic p < 0.001, satellite clinics p < 0.05), and in both groups attendance rate at first appointment was 88% and inversely related to social deprivation. There was no evidence of greater attendance amongst more deprived patients at the satellite clinics compared to the regional clinic. CONCLUSION: Our study found no evidence that the establishment of satellite clinics for genetic counselling in South East Scotland increases attendance by families with paediatric conditions in lower socio-economic groups. This suggests that factors other than clinic location determine referral and attendance rates, and these may include understanding of the reason for referral and the advantage of attendance.

Cyclosporine A treatment for Ullrich congenital muscular dystrophy: a cellular study of mitochondrial dysfunction and its rescue.

Mutations in COL6A1, COL6A2 and COL6A3, the genes which encode the extra-cellular matrix component collagen VI, lead to Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD). Although the Col6a1(-/-) null mouse has an extremely mild neuromuscular phenotype, a mitochondrial defect has been demonstrated, linked to dysregulation of the mitochondrial permeability transition pore (PTP) opening. This finding has been replicated in UCMD muscle cells in culture, providing justification for a clinical trial using cyclosporine A, an inhibitor of PTP opening. We investigated whether PTP dysregulation could be detected in UCMD fibroblasts (the predominant source of muscle collagen VI), in myoblast cells from patients with other diseases and its response to rescue agents other than collagen VI. Although we confirm the presence of PTP dysregulation in muscle-derived cultures from two UCMD patients, fibroblasts from the same patients and the majority of fibroblasts from other well-characterized UCMD patients behave normally. PTP dysregulation is found in limb girdle muscular dystrophy (LGMD) type 2B myoblasts but not in myoblasts from patients with Bethlem myopathy, merosin-deficient congenital muscular dystrophy, LGMD2A, Duchenne muscular dystrophy and Leigh syndrome. In addition to rescue by cyclosporine A and collagen VI, this cellular phenotype was also rescued by other extra-cellular matrix constituents (laminin and collagen I). As the muscle derived cultures demonstrating PTP dysregulation shared poor growth in culture and lack of desmin labelling, we believe that PTP dysregulation may be a particular characteristic of the state of these cells in culture and is not specific to the collagen VI defect, and can in any case be rescued by a range of extra-cellular matrix components. Further work is needed on the relationship of PTP dysregulation with UCMD pathology.

[Endocarditis due to Aggregatibacter (formerly: Actinobacillus) actinomycetemcomitans, a bacterium that grows in characteristic star-shaped colonies]. / Endocarditis door Aggregatibacter (voorheen: Actinobacillus) actinomycetemcomitans, een bacterie met karakteristieke stervormige kolonies.

A 72-year-old man, having had an artificial valve for almost 20 years now, presented with tiredness that had persisted for several weeks and reported weight loss of 5 kg. In more recent days he experienced fever and cold shivers, and an associated dry cough. Bearing in mind the potential for endocarditis, blood cultures were grown. In this, we identified a small, Gram-negative rod with a small, smooth, raised colony that grew slowly. We considered a micro-organism from the 'HACEK group', which is a group of micro-organisms including Haemophilus aphrophilus, Haemophilus paraphrophilus, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae and Aggregatibacter (formerly: Actinobacillus) actinomycetemcomitans. More careful observation revealed that the bacteria formed star-shaped colonies, proving that A. actinomycetemcomitans was the cause of this non-acute endocarditis. The patient received antibiotic treatment. Because non-acute endocarditis is often caused by hidden abnormalities in the mouth or teeth and A. actinomycetemcomitans plays an important role in severe cases of peridontitis, a dental surgeon was consulted. The dental surgeon diagnosed multifocal peridontitis and treated the patient, who was able to leave the hospital after 6 weeks of antibiotic treatment.

A refined diagnostic algorithm for Bethlem myopathy.

OBJECTIVE: Mutations in COL6A1, COL6A2, and COL6A3, the genes that encode the extracellular matrix component collagen VI, lead to Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). Unlike UCMD, BM is difficult to diagnose because of its clinical overlap with other contractural phenotypes and the lack of sensitivity of standard muscle biopsy immunohistochemical diagnostic techniques. METHODS: We appraised two potential techniques for the diagnosis of BM: dual immunofluorescence (IF) for collagen VI and basal lamina-located perlecan in muscle, and immunofluorescent labeling of collagen VI in skin biopsy-derived fibroblast cultures, which was conducted in 40 patients by blinded investigators and correlated with genetic findings. RESULTS: Dual IF was indistinguishable from normal controls in most BM patients. However, abnormalities in the IF labeling pattern of collagen VI were detected in more than 78% of genetically confirmed BM patient fibroblast cell lines. In addition, in a group of patients with unknown diagnosis studied prospectively, the fibroblast IF technique was highly predictive of the presence of a COL6A mutation, providing a positive predictive value of 75%, a sensitivity and negative predictive value of 100%, and a specificity of 63%. CONCLUSIONS: Immunofluorescent labeling of collagen VI in fibroblast cultures is a useful addition to current diagnostic services for Bethlem myopathy (BM). It can be used to guide molecular genetic testing, the gold standard diagnostic technique for BM, in a cost-effective and time-saving manner.

Exon skipping mutations in collagen VI are common and are predictive for severity and inheritance.

Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), two related conditions of differing severity. BM is a relatively mild dominantly inherited disorder characterized by proximal weakness and distal joint contractures. UCMD was originally regarded as an exclusively autosomal recessive condition causing severe muscle weakness with proximal joint contractures and distal hyperlaxity. We and others have subsequently modified this model when we described UCMD patients with heterozygous in-frame deletions acting in a dominant-negative way. Here we report 10 unrelated patients with a UCMD clinical phenotype and de novo dominant negative heterozygous splice mutations in COL6A1, COL6A2, and COL6A3 and contrast our findings with four UCMD patients with recessively acting splice mutations and two BM patients with heterozygous splice mutations. We find that the location of the skipped exon relative to the molecular structure of the collagen chain strongly correlates with the clinical phenotype. Analysis by immunohistochemical staining of muscle biopsies and dermal fibroblast cultures, as well as immunoprecipitation to study protein biosynthesis and assembly, suggests different mechanisms each for exon skipping mutations underlying dominant UCMD, dominant BM, and recessive UCMD. We provide further evidence that de novo dominant mutations in severe UCMD occur relatively frequently in all three collagen VI chains and offer biochemical insight into genotype-phenotype correlations within the collagen VI-related disorders by showing that severity of the phenotype depends on the ability of mutant chains to be incorporated in the multimeric structure of collagen VI.

A comparative analysis of collagen VI production in muscle, skin and fibroblasts from 14 Ullrich congenital muscular dystrophy patients with dominant and recessive COL6A mutations.

Ullrich congenital muscular dystrophy (UCMD) is caused by recessive and dominant mutations in COL6A genes. We have analysed collagen VI expression in 14 UCMD patients. Sequencing of COL6A genes had identified homozygous and heterozygous mutations in 12 cases. Analysis of collagen VI in fibroblast cultures derived from eight of these patients showed reduced extracellular deposition in all cases and intracellular collagen VI staining in seven cases. This was observed even in cases that showed normal collagen VI labelling in skin biopsies. Collagen VI immunolabelling was reduced in all the available muscle biopsies. When comparisons were possible no correlation was seen between the extent of the reduction in the muscle and fibroblast cultures, the mode of inheritance or the severity of the clinical phenotype. Mutations affecting glycine substitutions in the conserved triple helical domain were common and all resulted in reduced collagen VI. This study expands the spectrum of collagen VI defects and shows that analysis of skin fibroblasts may be a useful technique for the detection of collagen VI abnormalities. In contrast, immunohistochemical analysis of skin biopsies may not always reveal an underlying collagen VI defect.

Collagen VI related muscle disorders.

Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), two conditions which were previously believed to be completely separate entities. BM is a relatively mild dominantly inherited disorder characterised by proximal weakness and distal joint contractures. UCMD was originally described as an autosomal recessive condition causing severe muscle weakness with proximal joint contractures and distal hyperlaxity. Here we review the clinical phenotypes of BM and UCMD and their diagnosis and management, and provide an overview of the current knowledge of the pathogenesis of collagen VI related disorders.

Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy.

INTRODUCTION: Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). BM is a relatively mild dominantly inherited disorder with proximal weakness and distal joint contractures. UCMD is an autosomal recessive condition causing severe muscle weakness with proximal joint contractures and distal hyperlaxity. METHODS: We developed a method for rapid direct sequence analysis of all 107 coding exons of the COL6 genes using single condition amplification/internal primer (SCAIP) sequencing. We have sequenced all three COL6 genes from genomic DNA in 79 patients with UCMD or BM. RESULTS: We found putative mutations in one of the COL6 genes in 62% of patients. This more than doubles the number of identified COL6 mutations. Most of these changes are consistent with straightforward autosomal dominant or recessive inheritance. However, some patients showed changes in more than one of the COL6 genes, and our results suggest that some UCMD patients may have dominantly acting mutations rather than recessive disease. DISCUSSION: Our findings may explain some or all of the cases of UCMD that are unlinked to the COL6 loci under a recessive model. The large number of single nucleotide polymorphisms which we generated in the course of this work may be of importance in determining the major phenotypic variability seen in this group of disorders.

Congenital muscular dystrophy with short stature, proximal contractures and distal laxity.

We report 5 cases (2 familial and 3 sporadic) who share a diagnosis of congenital muscular dystrophy (CMD) in association with short stature, proximal contractures, rigidity of the spine and distal joint laxity as well as early respiratory failure and mild to moderate mental retardation. The expression of collagen VI was confirmed to be normal on muscle biopsies of all 5 patients and in the informative family linkage to any of the three COL6 A loci was excluded. These findings extend the phenotypes within the CMD classification.

The clinical picture of the Börjeson-Forssman-Lehmann syndrome in males and heterozygous females with PHF6 mutations.

The usual description of the Börjeson-Forssman-Lehmann syndrome (BFLS) is that of a rare, X-linked, partially dominant condition with severe intellectual disability, epilepsy, microcephaly, coarse facial features, long ears, short stature, obesity, gynecomastia, tapering fingers, and shortened toes. Recently, mutations have been identified in the PHF6 gene in nine families with this syndrome. The clinical history and physical findings in the affected males reveal that the phenotype is milder and more variable than previously described and evolves with age. Generally, in the first year, the babies are floppy, with failure to thrive, big ears, and small external genitalia. As schoolboys, the picture is one of learning problems, moderate short stature, with emerging truncal obesity and gynecomastia. Head circumferences are usually normal, and macrocephaly may be seen. Big ears and small genitalia remain. The toes are short and fingers tapered and malleable. In late adolescence and adult life, the classically described heavy facial appearance emerges. Some heterozygous females show milder clinical features such as tapering fingers and shortened toes. Twenty percent have significant learning problems, and 95% have skewed X inactivation. We conclude that this syndrome may be underdiagnosed in males in their early years and missed altogether in isolated heterozygous females.

Daily psychosocial stressors and cyclic response patterns in urine cortisol and neopterin in a patient with systemic lupus erythematosus.

This study investigated the complex biochemical responses to personally meaningful everyday stressors in a patient with systemic lupus erythematosus (SLE). For this purpose, a 52 year-old woman with SLE collected her entire urine for 56 days on a 12-h basis for the determination of cortisol as well as neopterin, a cellular immune parameter. Additionally, using questionnaires, daily notes and interviews, extensive psychosocial and psychological time-series data were collected every 12 h. Cross-correlational analyses of the resulting time-series revealed that stressful incidents were associated with cyclic fluctuations in both urine cortisol and urine neopterin. Specifically, whenever the patient anticipated a moderately stressful incident, urine cortisol initially increased 24 h before the incident and then decreased 12 h before the incident. Moderate stressors not anticipated by the patient were associated with an initial increase 24 h following the incident and then with a decrease after a total of 36 h. Moreover, stressors having to do with the patient's extramarital relationship were followed initially by a decrease in urine neopterin after 36 h and then by an increase after a total of 60 h. Our findings indicate that when investigating the relationship between psychosocial stressors and biochemical activity in SLE, appropriate consideration of the data's dynamic nature may be necessary to avoid flawed conclusions.

Borjeson-Forssman-Lehmann syndrome and multiple pituitary hormone deficiency.

We describe two brothers with Borjeson-Forssman-Lehmann syndrome and the 22A-->T (Lys8X) PHF6 mutation, who presented with the symptoms and signs of multiple pituitary hormone deficiency. Biochemical investigations and radiology confirmed growth hormone (GH), thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH) as well as gonadotrophin deficiency. They were also found to have optic nerve hypoplasia. This family suggests that the BFL gene product may play an important role in midline neuro-development including the hypothalamo-pituitary axis.

[Quality criteria for psychosomatic consultation-liaison service]. / Qualitätskriterien für den psychosomatischen Konsiliar-Liaison-Dienst.

Besides the integrated psychosomatic models in various medical specialities (e.g. Internal medicine, Obstetrics and Gynaecology or Paediatrics), specific models of cooperation in the form of consultation-liaison (C-L) service between specialised psychosomatic-psychotherapeutic departments and other medical departments play a crucial role in providing psychosomatic care to patients. The concept 'liaison' expresses a particularly close form of cooperative activity, going far beyond the classical model of consultation services. In this context, the psychosomatic consultant has not only a fixed organised presence in the provision of patient care, he/she also participates in case discussions, hospital rounds, ward discussions and continuing education programmes of the 'partner' department. Thus, the liaison service is not only patient-centred, but also team-centred. Such consultation-liaison services, in Austria, were first established at the University Hospitals. As a consequence of laws regulating psychotherapeutic care, according to which such care is to be offered in general hospitals, increasingly C-L services are becoming part of regular care provision in more and more hospitals. Consensus groups, international as well as in German-speaking countries, are currently working on establishing quality standards in the area of psychosomatic C-L services. A working group of the scientific medical representatives has recently published guidelines for the structure, process and results of quality control. A second group, of the European Association of Consultation Liaison Psychiatry and Psychosomatics, is currently working on guidelines for training consultation-liaison service providers. In the present article, an overview of these projects will be presented and the results discussed against the background of the specific health policy situation in Austria.

Familial neurofibromatosis microdeletion syndrome complicated by rhabdomyosarcoma.

Neurofibromatosis type 1 with dysmorphism and developmental delay is reported in a mother and two children. The son required treatment for a prostatic rhabdomyosarcoma. His sister has an optic pathway glioma. Fluorescence in situ hybridisation confirmed a submicroscopic deletion at 17q11.2. New evidence suggests an increased malignancy frequency in microdeletion cases.

[The influence of daily psychosocial stressors and associated emotions on the dynamic course of urine cortisol and urine neopterin in systemic lupus erythematosus: Experience taken from two "integrative single-case studies"]. / Der Einfluss von Alltagsbelastungen und assoziierten Emotionen auf den dynamischen Verlauf von Cortisol und Neopterin bei Patientinnen mit systemischem Lupus Erythematodes: Ergebnisse aus zwei "integrativen Fallstudien"

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by flare-ups, the cause of which is unknown. According to new stress concepts, two "integrative single-case studies" have been conducted in order to gather evidence about whether daily stressful incidents and associated emotions interfere with the dynamics of urine cortisol and urine neopterin in SLE. Patients under study collected their urine at home, for a period of at least 50 days, on a daily basis, divided into day and night urine. Additionally, patients filled out questionnaires twice a day to determine their emotional state, life style and disease activity. Each week, patients were examined clinically and interviewed to identify the past week's stressors using the Incidents and Hassles Inventory (IHI, Brown and Harris). Statistical analysis of the serial data was performed using time-series analysis according to Box and Jenkins. In both "integrative single-case studies" we were able to demonstrate that stressful incidents predicted an increase in urine neopterin 36 hours (Case 1) to 60 hours (Case 2) later (p < 0.05). Additionally, in Case 1 the neopterin levels were highly associated with stress resulting from the weekly examinations and interviews. Furthermore, in Case 2 it turned out that depending on their predictability stressful incidents were preceded by a decrease in urine cortisol 12 hours earlier or were followed by a decrease in urine cortisol 36 hours later. And finally, emotional irritation was highly correlated with the course of urine-neopterin. In Case 2 irritation led to an increase in urine neopterin 84 hours later. There were no clinical signs of SLE during both prospective studies. In conclusion, our results validate the idea of "integrative single-case studies" as a new "bio-psycho-social" approach in psychoneuroimmunology. Further studies with SLE patients as well as with healthy probands will be necessary in order to both strengthen and generalize these results.