The interplay of chronic stress and genetic traits discriminates between patients suffering from multisomatoform disorder with pain as the leading symptom and matched controls.

OBJECTIVE: Somatoform disorders and functional somatic syndromes (FSS) with symptoms that are not sufficiently explained by physical or technical examination are among the most challenging underlying causes. Many different somatoform disorders and FSS have overlapping symptoms, often with pain as the most prevalent one, leading to a high burden of disease. The concept of multisomatoform disorder (MSD) has been developed to acknowledge that fact. We analyzed a group of 151 patients and 149 matched controls to identify interactions of genetic and environmental factors with a possible influence on the development of MSD. DESIGN: In a retrospective case-control study, we performed a statistical analysis on 151 patients and 149 matched controls using logistic regression and a Classification and Regression Tree (CART) analysis. RESULTS: The logistic regression analysis of genes and environmental factors demonstrated significant differences in the results of the Trier Inventory of Chronic Stress (TICS) questionnaire, the single nucleotide polymorphism rs1800955 of the dopamine receptor D4 and the single nucleotide polymorphism rs4818 of the enzyme catechol-O-methyltransferase between patients with MSD and healthy controls. The resulting decision tree of the CART analysis determined that the TICS questionnaire was able to differentiate patients and controls most accurately, followed by certain genotypes of the 5-hydroxytryptamine receptor 2A and a single nucleotide polymorphism of the enzyme catechol-O-methyltransferase. CONCLUSIONS: The results of the statistical analysis identified a gene-environmental interaction possibly leading to MSD. The resulting identifiers could be used as a reference to inform diagnostic algorithms to easier identify patients suffering from MSD.

Distal muscle weakness and optic atrophy without central nervous system involvement in a patient with a homozygous missense mutation in the C19ORF12-gene.

Variants of the C19ORF12-gene have been described in patients with spastic paraplegia type 43 and in patients with mitochondrial membrane protein-associated neurodegeneration (MPAN), a subtype of neurodegeneration associated with brain iron accumulation (NBIA). In both subtypes optic atrophy and neuropathy have been frequently described. This case report describes a patient with bilateral optic atrophy and severe distal muscle weakness based on motor neuropathy without involvement of the central nervous system. Exome sequencing revealed a homozygous pathogenic missense variant (c.187G>C;p.Ala63Pro) of the C19ORF12-gene while iron deposits were absent on repeat MR-imaging of the brain, thus showing that peripheral neuropathy and optic neuropathy can be the sole manifestations of the C19ORF12-related disease spectrum whereby iron accumulation in the brain may be absent.

KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia.

Variants in the KIF1A gene can cause autosomal recessive spastic paraplegia 30, autosomal recessive hereditary sensory neuropathy, or autosomal (de novo) dominant mental retardation type 9. More recently, variants in KIF1A have also been described in a few cases with autosomal dominant spastic paraplegia. Here, we describe 20 KIF1A variants in 24 patients from a clinical exome sequencing cohort of 347 individuals with a mostly 'pure' spastic paraplegia. In these patients, spastic paraplegia was slowly progressive and mostly pure, but with a highly variable disease onset (0-57 years). Segregation analyses showed a de novo occurrence in seven cases, and a dominant inheritance pattern in 11 families. The motor domain of KIF1A is a hotspot for disease causing variants in autosomal dominant spastic paraplegia, similar to mental retardation type 9 and recessive spastic paraplegia type 30. However, unlike these allelic disorders, dominant spastic paraplegia was also caused by loss-of-function variants outside this domain in six families. Finally, three missense variants were outside the motor domain and need further characterization. In conclusion, KIF1A variants are a frequent cause of autosomal dominant spastic paraplegia in our cohort (6-7%). The identification of KIF1A loss-of-function variants suggests haploinsufficiency as a possible mechanism in autosomal dominant spastic paraplegia.

The HER2 phenotype of circulating tumor cells in HER2-positive early breast cancer: A translational research project of a prospective randomized phase III trial.

BACKGROUND: HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy. METHODS: The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining. RESULTS: 258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1-1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC. CONCLUSION: This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.

Predicting the functional states of human iPSC-derived neurons with single-cell RNA-seq and electrophysiology.

Human neural progenitors derived from pluripotent stem cells develop into electrophysiologically active neurons at heterogeneous rates, which can confound disease-relevant discoveries in neurology and psychiatry. By combining patch clamping, morphological and transcriptome analysis on single-human neurons in vitro, we defined a continuum of poor to highly functional electrophysiological states of differentiated neurons. The strong correlations between action potentials, synaptic activity, dendritic complexity and gene expression highlight the importance of methods for isolating functionally comparable neurons for in vitro investigations of brain disorders. Although whole-cell electrophysiology is the gold standard for functional evaluation, it often lacks the scalability required for disease modeling studies. Here, we demonstrate a multimodal machine-learning strategy to identify new molecular features that predict the physiological states of single neurons, independently of the time spent in vitro. As further proof of concept, we selected one of the potential neurophysiological biomarkers identified in this study-GDAP1L1-to isolate highly functional live human neurons in vitro.

Pyridoxine responsive epilepsy caused by a novel homozygous PNPO mutation.

We report a patient with anti-epileptic treatment refractory neonatal seizures responsive to pyridoxine. Biochemical analysis revealed normal markers for antiquitin deficiency and also mutation analysis of the ALDH7A1 (Antiquitin) gene was negative. Mutation analysis of the PNPO gene revealed a novel, homozygous, presumed pathogenic mutation (c.481C > T; p.(Arg161Cys)). Measurements of B6 vitamers in a CSF sample after pyridoxine administration revealed elevated pyridoxamine as the only metabolic marker for PNPO deficiency. With pyridoxine monotherapy the patient is seizure free and neurodevelopmental outcome at the age of 14 months is normal.

First on-line survey of an international multidisciplinary working group (MightyMedic) on current practice in diagnosis, therapy and follow-up of dyslipidemias.

The MightyMedic (Multidisciplinary International Group for Hemapheresis TherapY and MEtabolic DIsturbances Contrast) Working Group has been founded in 2013. The leading idea was to establish an international network of interdisciplinary nature aimed at working to cross national borders research projects, clinical trials, educational initiatives (meetings, workshops, summer schools) in the field of metabolic diseases, namely hyperlipidemias, and diabetes, preventive cardiology, and atherosclerosis. Therapeutic apheresis, its indications and techniques, is a parallel field of investigation. The first on-line survey of the Group has been completed in the first half of 2014. The survey included # 24 Centers in Italy, Germany, Greece, UK, Sweden, Japan and USA. Relevant data have been collected on current practice in diagnosis, therapy and follow-up of dyslipidemias. 240 subjects with hyperlipidemia and treated with lipoprotein apheresis have been reported in the survey, but a large percentage of patients (35%) who could benefit from this therapeutic option are still treated by conventional drug approach. Genetic molecular diagnosis is performed in only 33% of patients while Lipoprotein(a) (Lp(a)) is included in cardiovascular disease risk assessment in 71% of participating Centers. New detailed investigations and prospective multicenter studies are needed to evaluate changes induced by the impact of updated indications and strategies, as well as new treatment options, targeting standardization of therapeutic and diagnostic approaches.

Adjuvant therapeutic decisions in elderly breast cancer patients: the role of chemotherapy in a retrospective analysis.

PURPOSE: Decisions on the type of adjuvant treatment in older breast cancer patients are challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty on the basis of studies usually excluding patients over 69 years. To aid this decision, we analyzed a database of 6000 unselected patients and of those evaluated elderly primary breast cancer patients with hormone receptor-negative tumors from 1963 until 2003 in respect of survival data depending on adjuvant treatment. METHODS: A total of 131 elderly (i.e., >65 years) patients were observed retrospectively for a median of 72 months. Patients received breast-conserving therapy or mastectomy and adjuvant radiotherapy, chemotherapy, and endocrine therapy. Data were collected from a hospital-intern database. RESULTS: Median age at diagnosis was 72 years. Mostly, tumors were small (81 % T1, 17 % T2) but of unfavorable grading (40 % G2, 35 % G3). Lymph nodes were positive in 42 %. Mastectomy was performed in 65 %. While 42 % of patients received radiotherapy, only 10 % were treated with chemotherapy. Patients with G2 and G3 tumors (p = 0.027), younger women (p = 0.012), and patients with positive lymph node status (p < 0.0001) more likely received chemotherapy. Recurrence-free survival was longer in patients without chemotherapy (37 vs. 29 months, p = 0.234). Overall survival was non-significantly shorter in patients who received chemotherapy (59 vs. 81 months, p = 0.131). CONCLUSIONS: In this analysis, adjuvant chemotherapy was not associated with improved survival, presumably caused by an a priori poor prognosis of these patients. For an aging society more data are urgently needed to help selecting and personalizing adjuvant treatment within subgroups of breast cancer in older women.

Evaluation of two different analytical methods for circulating tumor cell detection in peripheral blood of patients with primary breast cancer.

BACKGROUND: Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. MATERIAL AND METHODS: We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. RESULTS: The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). CONCLUSION: Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.

Knowledge about post-anoxic somatosensory evoked potentials--present or not?

BACKGROUND AND PURPOSE: Median nerve somatosensory evoked potential (SEP) recordings play an important role in outcome algorithms in comatose patients after cardiopulmonary resuscitation. Knowledge of technical difficulties, clinical implications and uniform interpretation of SEP recordings is crucial. The aim of this study was to evaluate the skills of neurologists to interpret SEP recordings in post-anoxic patients. METHODS: Nationwide Dutch clinical neurophysiology examinations from 2007, 2008 and 2011, containing SEP related questions, were analysed. Participants were classified as neurology residents, neurologists with less than 10 years of experience, neurologists with more than 10 years of experience and clinical neurophysiologists. End-points were the knowledge of all participants about SEP recordings per year as well as improvement in knowledge over the years, as reflected by the test scores. RESULTS: A total of 194 participants completed the examination in 2007, 200 in 2008 and 263 in 2011. Between 2007 and 2008, all groups of respondents showed a significant increase in percentage of correct answers to SEP questions. Sixty-six participants completed all three examinations. The SEP score of this group improved in 2008 [75%, interquartile range (IQR) 50-75, P < 0.001] compared with 2007 (38%, IQR 38-50); there was no further improvement in 2011 (69%, IQR 54-77). CONCLUSION: Continuing education about technical knowledge, possible pitfalls and interpretation of SEP recordings remains of utmost importance.

Early prediction of cardiac allograft vasculopathy and heart transplant failure.

Early risk-prediction is essential to prevent cardiac allograft vasculopathy (CAV) and graft failure in heart transplant patients. We developed multivariate models to identify patients likely to experience CAV, severe CAV, and failure due to CAV, at 1, 5 and 10 years. A cohort of 172 patients was followed prospectively for 6.7 ± 3.9 years. Logistic regression models were developed and cross-validated using bootstrap resampling. Predictive markers of atherothrombosis (myocardial fibrin deposition, and loss of vascular antithrombin and tissue plasminogen activator) and arterial endothelial activation (intercellular adhesion molecule-1 expression) were measured in serial biopsies obtained within 3 months posttransplant. Most markers were univariately associated with outcome. Multivariate models showed that loss of tissue plasminogen activator was the dominant and, in most cases, only predictor of long-term CAV (p < 0.001), severe CAV (p < 0.001), and graft failure due to CAV (p < 0.001). The models discriminated patients having adverse outcomes, had particularly high negative predictive values (graft failure due to CAV: 99%, 99% and 95% at 1, 5 and 10 years) and predicted event incidence and time to event. Early absence of atherothrombotic risk identifies a patient subgroup that rarely develops CAV or graft failure, implying that this low-risk subgroup could possibly be followed with fewer invasive procedures.

Immunological effects of stress in psoriasis.

BACKGROUND: Psychological stress causes phenotypic changes in circulating lymphocytes and is regarded as an important trigger of the Th1-polarized inflammatory skin disease psoriasis. OBJECTIVE: To study the effects of psychological stress on immunological parameters, i.e. membrane molecules relevant to the pathophysiology of psoriasis, especially cutaneous lymphocyte-associated antigens (CLA) involved in T and natural killer (NK) cells homing in on the skin. METHODS: The severity of psoriasis was assessed in patients using the Psoriasis Area and Severity Index. Patients with psoriasis (n=15) and healthy volunteers (n=15) were exposed to brief psychological stress in the laboratory. In vitro analyses were conducted 1 h before, immediately following and 1 h after stress exposure. Peripheral T- and NK-cell subsets including CD8+ T lymphocytes, CLA+ lymphocytes and lymphocyte function-associated antigen type 1 (LFA-1)+ lymphocytes were analysed by flow cytometry. RESULTS: We found a significant stress-induced increase of CD3+ T lymphocytes in patients with psoriasis only. Analyses of T-cell subsets revealed that this increase was observable for cytotoxic CD8+ T lymphocytes and CLA+ CD3+ lymphocytes. The total number of circulating NK cells (CD16+, CD56+) increased immediately after stress in both groups whereas only patients with psoriasis showed a significant increase in CLA+ NK cells. CONCLUSIONS: A higher stress-induced increase of CLA+ T and CLA+ NK cells in the circulation of patients with psoriasis might point to an increased ability of T and NK cells in the presence of psoriasis to home in on the skin during mental stress. Further studies are needed to verify these relationships in more detail and to investigate the time point at which these cells accumulate within lesional skin, and whether or not psychotherapy improves the quality of life of patients with psoriasis and influences stress-dependent parameters.

Potential renoprotective effects of the angiotensin receptor blocker eprosartan: a review of preliminary renal studies.

The importance of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of hypertension and in renal disease, particularly in patients with diabetes, has become increasingly evident. Pharmacological blockade of the RAAS offers potential for the therapeutic management of these pathologies. Angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AII) receptor blockers have been shown to exhibit effectiveness in the treatment of hypertension. AII receptor blockers have a renal protective effect owing to their ability to reduce systemic blood and intraglomerular pressures. Eprosartan is a chemically distinct AII blocker, which displays a dual mode of action whereby it blocks both pre- and postsynaptic AT(1) receptors, potentially benefiting patients with hypertension and renal disease. In addition, evidence suggests that eprosartan is well tolerated by both healthy subjects and patients with varying degree of renal impairment, such that the dose does not need to be modified in patients with mild to moderate renal impairment. Results from preliminary studies demonstrates that eprosartan doses will below those required for blood pressure control have a pronounced effect on the kidney and do not compromise renal autoregulatory mechanisms. Therefore, eprosartan may have a benefit in the prevention or delay of renal damage in hypertensive patients with renal impairment, although this remains to be determined in a clinical setting.

Molecular identification and differentiation of Staphylococcus species and strains of cheese origin.

Amplified Ribosomal-DNA Restriction Analysis (ARDRA) was used to differentiate among 12 species and 4 subspecies of the genus Staphylococcus. With a universal primer pair a 2.4 kbp PCR-product was amplified, including the 16S rDNA, the 16S-23S rDNA interspacer region, and about 500 bp of the 23S rDNA. Species-specific restriction patterns were found using the restriction enzymes HindIII and XmnI separately. Cheese related staphylococci were clearly differentiated. ARDRA results were in good agreement with results of partial sequencing of the 16S rDNA. ARDRA could fully replace the biochemical identification with ID32 Staph (BioMerieux) which was less reliable when staphylococci of cheese origin were analysed. Genomic restriction digests of cheese-related S. equorum strains by SmaI and SacI gave unique strain-specific restriction patterns which can be used to identify starter staphylococci in a complex microbial environment such as the surface of Red-Smear cheeses.

[Prevention of early graft occlusion after coronary bypass grafting by post-operative reduction of plasma fibrinogen by H.E.L.P. apheresis. First evaluation of 12 patients treated during our study (44 bypasses)]. / Verhinderung von Frühverschlüssen nach koronarer Bypassoperation durch postoperative Reduktion des Plasmafibrinogens mittels H.E.L.P.-Apherese. Erste Auswertung von 12 im Rahmen dieser Studie behandelten Patienten (44 Bypässen).

BACKGROUND: Early graft occlusion is a known complication after CABG (Coronary Artery Bypass Grafting). The thromboembolic closure of the bypass occurs at a frequency of 5-15%, depending on the implemented vessel (arterial or venous graft). Fibrinogen as a substrate of thrombus formation plays a major role in both primary and secondary haemostasis. The operative trauma triggers the acute phase-response and also activates the clotting process. This leads to high fibrinogen levels of up to 600 mg/dl postoperatively, providing an impaired haemorrheological pattern which promotes thrombus formation. In a prospective pilot-study we examined whether drastic postoperative lowering of fibrinogen by H.E.L.P.-(Heparin-mediated Extracorporeal LDL-/Fibrinogen Precipitation) apheresis can prevent early graft vessel closure in patients undergoing CABG. METHODS: For the purpose of this study 12 male patients (mean age 60+/-5.8 years) who underwent multivessel CABG were recruited between 12/2000 and 2/2002 according to a GCP approved protocol. The postoperative fibrinogen levels of the patients were monitored and H.E.L.P. apheresis was applied when plasma fibrinogen levels exceeded >350 mg/dl on day 1 and >250 mg/dl every following day up to day 8 after the operation. Pre- and post apheresis blood samples were obtained and reduction of plasma fibrinogen, LDL-Cholesterol and CRP were determined. Coronary angiography was performed within the 9th-16th postoperative day. To investigate the long term outcome a second coronary angiography was performed half a year after the operation. RESULTS: A total of 44 bypass grafts (23 arterial; 21 vein grafts) were implemented in 12 patients (mean 3.6/patient) and a total of 66 H.E.L.P.-Apherses from day 1-8 were postoperatively applied (mean 5.5/patient). Fibrinogen levels were lowered from a maximum on day 2 of 447+/-112.2 mg/dl (pre-apheresis) to a minimum on day 8 of 228+/-46.2 mg/dl (pre-apheresis) demonstrating a reduction of 50%. Per single treatment the fibrinogen was lowered from 357+/-93 mg/dl (pre-apheresis) to 157+/-46 mg/dl (post apheresis); reduction: 55%. Coronary angiography revealed graft patency in 43 of 44 grafts (97.7% patency). The one occluded bypass was an Y-graft to a diagonal branch less than 1mm in diameter. No bleeding or H.E.L.P. related complications were observed.Up to now 7 of 12 patients underwent the second coronary angiography according to the study protocol. Apart from the already immediately postoperatively occluded Y-graft no new bypass-occlusion was revealed. CONCLUSIONS: Early and extensive reduction of postoperatively elevated plasma fibrinogen levels by H.E.L.P. apheresis seems to be an efficient and safe therapeutic approach for preventing early graft occlusion in patients undergoing multivessel CABG.

[Treatment of sudden hearing loss through Fibrinogen/LDL-apheresis. A prospective, randomized multicenter trial]. / Behandlung des Hörsturzes durch Fibrinogen-LDL-Apherese. Eine prospektive randomisierte Multizenterstudie.

INTRODUCTION: Sudden sensorineural hearing loss (SSHL) is thought to be of various origins. Disturbances of microcirculation, autoimmune pathology and viral infection are among the most likely causes. Acute reduction of plasma fibrinogen and serum LDL positively influences hemorheology and endothelial function and might thus be an effective therapy for SSHL. OBJECTIVE: To test the hypothesis that fibrinogen/LDL-apheresis is as effective or superior to conventional therapy with plasma expanders and prednisolone in the treatment of SSHL. DESIGN: controlled, prospective, randomized, multicenter trial. SETTING AND PATIENTS: 201 patients were recruited from 01/2000 to 6/2001 at the University Clinics of Munich, Berlin, Hamburg and Bochum. Inclusion criteria was sudden sensorineural hearing loss of unknown origin within 6 days of onset. INTERVENTIONS: Single fibrinogen/ LDL-apheresis infusion of prednisolone (250 mg, tapered by 25 mg daily), hydroxyethyl starch (500 ml, 6%) and pentoxifylin (400 mg/day). MAIN OUTCOMES: Improvement of pure tone thresholds 48 h after onset of therapy. RESULTS: Over all improvement of pure tone thresholds in the fibrinogen/ LDL-apheresis treated patients is slightly but not significantly better than in the standard therapy group. After 48 h, 50% speech perception in the fibrinogen/ LDL-apheresis group (21.6+/-20.1 dB) is significantly (p<0.034) better than in the standard group (29.3+/-29.4 dB). Patients with plasma fibrinogen levels of more than 295 mg/dl have a substantial and significantly (p<0.005) better improvement of speech perception (15.3+/-17.3 dB) than standard treated patients (6.1+/-10.4 dB). CONCLUSIONS: Fibrinogen/LDLapheresis is at least equally effective compared to prednisolone treatment in sudden hearing loss. Selected patients with plasma fibrinogen of more than 295 mg/dl improve significantly better when treated with fibrinogen/LDLapheresis.

Identification and differentiation of species and strains of Arthrobacter and Microbacterium barkeri isolated from smear cheeses with Amplified Ribosmal DNA Restriction Analysis (ARDRA) and pulsed field gel electrophoresis (PFGE).

ARDRA (Amplified Ribosomal-DNA Restriction Analysis) was used to differentiate among species and genera of Arthrobacter and Microbacteria. Species-specific restriction patterns of PCR-products were obtained with NciI for Arthrobacter citreus (DSM 20133T), A. sulfureus (DSM 20167T), A. globiformis (DSM 20124T) and A. nicotianae strains (DSM 20123T, MGE 10D, CA13, CA14, isolate 95293, 95294, and 95299), A. rhombi CCUG 38813T, and CCUG 38812, and Microbacterium barkeri strains (DSM 30123T, MGE 10D, CA12 and CA15, isolate 95292, and isolate 95207). All yellow pigmented coryneforme bacteria isolated from the smear of surface ripened cheeses were identified as either A. nicotianae or M. barkeri strains. Using pulsed field gel electrophoresis (PFGE) strain specific restriction pattern for all Arthrobacter species and Microbacteria tested were obtained with restriction enzymes AscI and SpeI.

[Atopic dermatitis and psychological stress]. / Atopische Dermatitis und psychischer Stress.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. Its main features are eczematous skin lesions with a typical distribution and severe pruritus. Allergens, skin irritants, systemic or local infections, environmental pollutants and hormonal changes have a role in the pathophysiology of AD. A further important trigger factor for both intrinsic and extrinsic AD is emotional stress. Recently published observations point to direct psychoneuroimmunological and -endocrinological mechanisms: Psychological stress causes a transient increase of peripheral blood eosinophil count and an increase in both CD8+/CD11b+ and CLA+ T-cells. In addition, stress changes the cytokine and the hormone profile with increased levels of IFN-gamma and IL-5, and decreased levels of cortisol in AD patients in contrast to healthy controls. These findings underline the role of immunological changes and a possible suppressed hypothalamic-pituitary-adrenal (HPA) axis closing the loop for the final aggravation of AD.

[Coronary heart disease in childhood in familial hypercholesteremia. Maximum therapy with LDL apheresis]. / Koronare Herzkrankheit im Kindesalter bei familiärer Hypercholesterinämie. Maximaltherapie unter Einsatz der LDL-Apherese.

In children with familial hypercholesterolemia, coronary heart disease requires both medical theraphy and LDL apheresis. We report a case of verified occlusion of the anterior descending branch of the left coronary artery in a 10-year-old patient. The pathological findings revealed by ergometry established the diagnosis. The goal was to achieve the greatest possible reduction of lipid parameters and fibrinogen by lowering plasma viscosity employing LDL apheresis. It is astonishing that this treatment is also well tolerated by children. The basic vascular approaches suffice and shunt operations are not absolutely necessary. The efficacy of this method became vividly apparent by the changes in the skin lesions. Additional angiographic follow-up and further clinical course wil provide information on the usefulness of this treatment strategy with maximum lipid theraphy and the expected improvement in prognosis.

Body dissatisfaction and its interrelations with other risk factors for bulimia nervosa in 12 countries.

BACKGROUND: It is widely accepted that risk factors for bulimia nervosa, mainly body dissatisfaction, are dependent on cultural factors. However, to date few studies have compared data from different cultures with an appropriate methodology. Therefore we aimed to gather reliable information on body dissatisfaction and other risk factors for bulimia from different nations and to reveal their functional interrelations. METHODS: A series of 10 silhouettes, designed to be as far as possible free from cultural and other detailed aspects, was shown to 1,751 medical and nursing students in 12 nations. A functional model was applied to each sample and tested by structural equation methodology. RESULTS: The most extreme body dissatisfaction was found in northern Mediterranean countries, followed by northern European countries. Countries currently undergoing a process of westernization show an intermediate amount of body dissatisfaction, and non-western countries demonstrate rather low values. Body dissatisfaction is the most important influence on dieting behaviour in most countries. CONCLUSIONS: Despite ongoing adoption of western values worldwide, we observe remarkable differences in body dissatisfaction between different cultures. That body dissatisfaction seems disturbingly partly detached from the actual BMI, i.e. possible overweight, as well as from feelings of low self-esteem in some western countries, raises new questions about the possible origin of the pressure to be thin.