Medizin - Open Access LMU - Teil 14/22

Es wird der Fall einer Patientin mit Dissoziativer Identitätsstörung vorgestellt, die nach 15-jähriger, als kortikal diagnostizierter Blindheit im Laufe einer psychotherapeutischen Behandlung schrittweise wieder zu sehen begann. Zunächst konnten nur einige wenige Persönlichkeitsanteile wieder sehen, während andere weiterhin blind waren. Dies konn-te durch elektrophysiologische Untersuchungen bestätigt werden, in denen die noch blinden Persönlichkeitsanteile ausbleibende, die sehenden Persönlichkeitsanteile hin-gegen völlig unauffällige, reguläre evozierte Potentiale aufwiesen. Das Umschalten zwi-schen sehenden und blinden Anteilen konnte übergangslos geschehen. Als neuronale Grundlage der psychogenen Blindheit kommt eine „top-down“ Modulation der Aktivität der primären Sehbahn, auf Ebene des Thalamus oder primären visuellen Kortex, in Be-tracht. Mittels VEP-Untersuchungen kann daher eine psychogene Blindheit nicht von organischen Ursachen einer Unterbrechung der Sehbahn abgegrenzt werden. Zusam-menfassend scheint psychogene Blindheit den Zufluß visueller Information auf früher Stufe zu blockieren.

Mon, 1 Jan 2007 12:00:00 +0100 http://gut.bmj.com/content/56/9/1310.short https://epub.ub.uni-muenchen.de/14956/1/Diagnosis_prevention_and_treatment_of_hepatorenal.pdf Arroyo, Vicente; Wong, Florence; Ginès, Pere; Gerbes, Alexander L.; Salerno, Francesco ddc:610, Med

As a luminogram, coronary angiography provides a good overview of the coronary artery tree. Using quantitative coronary measurements, the degree of coronary obstruction can be determined. The limitation of coronary angiography is that it does not provide information on the arterial wall structure and therefore cannot assess the extent of atherosclerosis. Knowledge about adaptive coronary remodelling processes as compensatory enlargement of the coronary artery has focused diagnostic interest on the non-stenotic lesions of the coronary tree. Intravascular ultrasound (IVUS) can reveal discrepancies between the extent of coronary atherosclerosis and angiography imaging by in vivo plaque imaging. Spectrum analysis of IVUS-derived radiofrequency (RF) data enables a more detailed analysis of plaque composition and morphology. Preliminary in vitro studies correlated four histological plaque components with a specific spectrum analysis of the RF data. The different components (fibrous, fibrofatty, necrotic core and dense calcium) are colour coded. Coronary tissue maps were reconstructed from RF data using IVUS–Virtual Histology (VH IVUS) software (Real-Time VH, Volcano Corporation, Rancho Cordova, California, USA). VH IVUS has the potential to detect high-risk lesions and can provide new insights into the pathophysiology of coronary artery disease. VH IVUS allows the differentiation of different lesion types based on information derived from histopathology. The in vivo specific histological analysis of coronary atherosclerosis may allow better stratification of treatment of patients with coronary artery disease.

Background: The pulsed electron avalanche knife (PEAK-fc) is a new pulsed electrosurgical device that allows for precise, ``cold'' and traction-free tissue dissection.Aim: To evaluate the surgical applicability, safety and potential complications of PEAK-fc in complicated cataract surgery.Methods: The study included five children with congenital cataracts, two patients with advanced senile cataracts, six adults with mature cataracts, three of them with posterior iris synechia, three patients with post-traumatic cataracts with zonulolysis, one patient with intumescent traumatic cataract and three patients with massive anterior capsule opacification. Anterior and posterior capsulotomies, iris synechiolysis, dissection of anterior capsule opacification and fibrotic scar tissue were performed. PEAK-fc was set at voltages of 500--700 V, pulse duration of 0.1 m and repetition rate of 40--100 Hz.Results: Anterior and posterior capsulotomies were successfully and safely performed in all eyes. The edges of capsulotomies appeared sharp, showing only limited collateral damage. PEAK-fc worked best by just gently touching the capsule, thereby avoiding tractional forces or pressure on the lens capsule. Posterior iris synechiae could be released and anterior capsule opacification was dissected without complications.Conclusions: PEAK-fc is a very helpful cutting device for complicated cases of cataract surgery, especially for mature and congenital cataracts, traumatic zonulolysis or anterior segment complications after intraocular inflammation.

Objectives: To determine trends in the prevalence and aetiological distribution of genital ulcer syndrome (GUS) in a cohort of female bar workers and to assess factors associated with these trends.Methods: An open cohort of 600 women at high risk of HIV and sexually transmitted infection (STI) was offered screening and treatment for STI at 3-month intervals. The prevalence of GUS and associated aetiological agents (Herpes simplex virus (HSV), Treponema pallidum and Haemophilus ducreyi) were monitored over 27 months through clinical examination, dry lesion swabbing and multiplex polymerase chain reaction. The effects of HIV status and other factors on the prevalence trends of STI were assessed.Results: A total of 753 women were recruited into the cohort over 10 examination rounds. At recruitment, the seroprevalence was 67% for HIV and 89% for HSV type 2 (HSV-2). During follow-up, 57% of ulcers had unknown aetiology, 37% were due to genital herpes and 6% to bacterial aetiologies, which disappeared completely in later rounds. The absolute prevalence of genital herpes remained stable at around 2%. The proportion of GUS caused by HSV increased from 22% to 58%, whereas bacterial causes declined. These trends were observed in both HIV-negative and HIV-positive women.Conclusions: The changes observed in the frequency and proportional distribution of GUS aetiologies suggest that regular STI screening and treatment over an extended period can effectively reduce bacterial STI and should therefore be sustained. However, in populations with a high prevalence of HSV-2, there remains a considerable burden of genital herpes, which soon becomes the predominant cause of GUS. Given the observed associations between genital herpes and HIV transmission, high priority should be given to the evaluation of potential interventions to control HSV-2 either through a vaccine or through episodic or suppressive antiviral therapy and primary prevention.

Superficial haemosiderosis results from chronic subarachnoid haemorrhage during which haemosiderin is deposited in the leptomeninges around the brain, spinal cord and cranial nerves. We describe an exceptional case of superficial haemosiderosis characterised by two special aspects. (1) The cause was a secondary tethered cord syndrome due to dural adhesions which had developed 8 years after resection of a thoracic lymphoma and (2) an explorative neurosurgical procedure with complete untethering caused normalisation of the cerebrospinal fluid and stopped disease progression.

Background/aims: Contaminated ophthalmic solutions represent a potential cause of avoidable ocular infection. This study aimed to determine the magnitude and pattern of microbial contamination of multi-dose ocular solutions at the Department of Ophthalmology, University of Nairobi, at the Kenyatta National Hospital, Kenya.Methods: 101 vials were obtained for microbial examination after an average use of 2 weeks. The dropper tip and the residual eye drop were examined for contamination. The specimens were cultured, the number of colonies counted, the organisms identified and susceptibility testing to selected antimicrobial agents was done.Results: Six (6%) of the 101 analysed vials were contaminated: 4/77 vials (5%) from a multi-user setting and 2/24 vials (8%) from a single user setting. Three contaminations (3/38, 8%) occurred in vials from the eye ward, another three (3/59, 5%) in vials from the outpatient clinic. Most bacteria identified belonged to the normal commensal flora of the eye. Isolated contaminants were micrococci (n = 2), Staphylococcus epidermidis, Haemophilus sp, Bacillus sp and a Gram negative rod. The dropper tip was more often contaminated (n = 6) than the residual solution (n = 1), and only one vial showed a contamination of both the drop and the tip.Conclusion: Our data show a contamination rate of 6%, which is in the lower range of data published on the contamination of eye drops elsewhere (0.07% to 35.8%).

Background: In the present study we evaluated the functional success after macular hole surgery in correlation to visual quality of life and looked for predictive factors determining surgical success.Methods: Fifty-nine patients that underwent pars plana vitrectomy for idiopathic macular hole were included. Follow-up visits were performed in regular intervals after surgery and included a clinical examination, optical coherence tomography (OCT) and measurement of visual acuity. To assess the visual quality of life patients filled out the National Eye Institute 25-item Visual Function Questionnaire (VFQ-25) before and three months and one year after surgery.Results: Macular hole closure was achieved in 57 of 59 patients (97%). Mean visual acuity increased from 20/100 preoperatively to 20/34 one year after surgery (p = 0.02). Despite good visual acuity (20/27) in the fellow eye, visual quality of life (VFQ composite score) rose from 75.9 ± 14.4 (SD) to 81.5 ± 14.2 one year after surgery (p

Objective: To evaluate the staining characteristics of bromphenol blue used during vitreoretinal surgery in humans.Patients and methods: 13 patients with epiretinal membranes were included. Before and after surgery a complete clinical examination including best corrected visual acuity, funduscopy, fluorescein angiography, OCT (Stratus), Goldmann perimetry and multifocal ERG as well as photography of the macular area was performed. Bromphenol blue was used in concentrations of 0.2% in most patients. Removed epiretinal tissue was evaluated using electron microscopy.Results: Using dye concentrations of 0.2% a good demarcation of epiretinal membranes was seen in 11/13 patients. Staining of vitreous remnants at the vitreous base was seen in all patients. No dye-related adverse events were seen during follow-up in the functional tests (VA, ERG, perimetry) performed. Histological evaluation of epiretinal membranes showed unremarkable aspects of epiretinal cellular layers and unremarkable retinal surface of the internal limiting membrane (ILM).Conclusion: Bromphenol blue appears to be a very helpful and safe tool in posterior segment surgery. The staining characteristics need to be further evaluated in prospective study settings and larger numbers of patients.

Background/aim: Interleukin 31 (IL31), primarily expressed in activated lymphocytes, signals through a heterodimeric receptor complex consisting of the IL31 receptor alpha (IL31Rtextgreeka) and the oncostatin M receptor (OSMR). The aim of this study was to analyse IL31 receptor expression, signal transduction, and specific biological functions of this cytokine system in intestinal inflammation.Methods: Expression studies were performed by RT-PCR, quantitative PCR, western blotting, and immunohistochemistry. Signal transduction was analysed by western blotting. Cell proliferation was measured by MTS assays, cell migration by restitution assays.Results: Colorectal cancer derived intestinal epithelial cell (IEC) lines express both IL31 receptor subunits, while their expression in unstimulated primary murine IEC was low. LPS and the proinflammatory cytokines TNF-textgreeka, IL1textgreekb, IFN-textgreekg, and sodium butyrate stimulation increased IL31, IL31Rtextgreeka, and OSMR mRNA expression, while IL31 itself enhanced IL8 expression in IEC. IL31 mediates ERK-1/2, Akt, STAT1, and STAT3 activation in IEC resulting in enhanced IEC migration. However, at low cell density, IL31 had significant antiproliferative capacities (p

Cryoglobulinaemia may cause cutaneous vasculitis and glomerulonephritis, potentially leading to end stage renal failure. An important proportion of cryoglobulinaemias are secondary to hepatitis C virus infection. Emerging antiviral treatment options offer a chance for causal therapy of these cases of cryoglobulinaemia. This review summarises the classification and clinical and therapeutic aspects of cryoglobulinaemic vasculitis and glomerulonephritis.

Three dimensional eye rotations were measured using the magnetic search coil technique in a patient with a lesion of the right rostral interstitial nucleus of the medial longitudinal fasciculus (RIMLF) and in four control subjects. Up to 10° contralesional torsional deviations with each voluntary saccade were revealed, which also could be seen during bedside examination. There was no spontaneous nystagmus. Based on MRI criteria, the lesion involved the RIMLF but spared the interstitial nucleus of Cajal. To date, this deficit has not been described in patients. Our results support the hypothesis that the vertical--torsional saccade generator in humans is organised similarly as in monkeys: each RIMLF encodes torsional saccades in one direction, while both participate in vertical saccades.

Objective: The authors examined the relations between self-reported work tasks, use of cleaning products and latex glove use with new-onset asthma among nurses and other healthcare workers in the European Community Respiratory Health Survey (ECRHS II).Methods: In a random population sample of adults from 22 European sites, 332 participants reported working in nursing and other related healthcare jobs during the nine-year ECRHS II follow-up period and responded to a supplemental questionnaire about their principal work settings, occupational tasks, products used at work and respiratory symptoms. Poisson regression models with robust error variances were used to compare the risk of new-onset asthma among healthcare workers with each exposure to that of respondents who reported professional or administrative occupations during the entire follow-up period (n = 2481).Results: Twenty (6%) healthcare workers and 131 (5%) members of the referent population reported new-onset asthma. Compared to the referent group, the authors observed increased risks among hospital technicians (RR 4.63; 95% CI 1.87 to 11.5) and among those using ammonia and/or bleach at work (RR 2.16; 95% CI 1.03 to 4.53).Conclusions: In the ECRHS II cohort, hospital technicians and other healthcare workers experience increased risks of new-onset current asthma, possibly due to specific products used at work.

Objectives: To estimate long-term exposure to traffic-related air pollutants on an individual basis and to assess adverse health effects using a combination of air pollution measurement data, data from geographical information systems (GIS) and questionnaire data.Methods: 40 measurement sites in the city of Munich, Germany were selected at which to collect particulate matter with a 50% cut-off aerodynamic diameter of 2.5 µm (PM2.5) and to measure PM2.5 absorbance and nitrogen dioxide (NO2). A pool of GIS variables (information about street length, household and population density and land use) was collected for the Munich metropolitan area and was used in multiple linear regression models to predict traffic-related air pollutants. These models were also applied to the birth addresses of two birth cohorts (German Infant Nutritional Intervention Study (GINI) and Influence of Life-style factors on the development of the Immune System and Allergies in East and West Germany (LISA)) in the Munich metropolitan area. Associations between air pollution concentrations at birth address and 1-year and 2-year incidences of respiratory symptoms were analysed.Results: The following means for the estimated exposures to PM2.5, PM2.5 absorbance and NO2 were obtained: 12.8 textgreekmg/m3, 1.7×10-5 m-1 and 35.3 textgreekmg/m3, respectively. Adjusted odds ratios (ORs) for wheezing, cough without infection, dry cough at night, bronchial asthma, bronchitis and respiratory infections indicated positive associations with traffic-related air pollutants. After controlling for individual confounders, significant associations were found between the pollutant PM2.5 and sneezing, runny/stuffed nose during the first year of life (OR 1.16, 95% confidence interval 1.01 to 1.34) Similar effects were observed for the second year of life. These findings are similar to those from our previous analysis that were restricted to a subcohort in Munich city. The extended study also showed significant effects for sneezing, running/stuffed nose. Additionally, significant associations were found between NO2 and dry cough at night (or bronchitis) during the first year of life. The variable ``living close to major roads'' (

Objectives: Reported associations of self-employment with occupational injury and cerebrovascular disease suggest that worker safety and health precautions may vary by occupational status. The authors assessed the extent to which use of respiratory protection and ventilation equipment is associated with self-employed versus employee status among adults in an international study.Methods: The European Community Respiratory Health Survey II (ECRHS II) is a follow-up study conducted in a population-based random sample of adult ECRHS I participants. Men and women enrolled in the ECRHS II completed interviewer-administered questionnaires to provide information about their occupational status and job history during the 9-year ECRHS follow-up period. Respondents in selected occupational groups completed supplemental questionnaires about their jobs and use of respiratory protection and ventilation equipment on-the-job. The authors assessed self-reported use of respiratory and ventilation equipment among 72 self-employed and 371 employed adults in metalworking, soldering and welding occupations.Results: Local exhaust ventilation (fixed extraction: OR 0.37, 95% CI 0.17 to 0.80; mobile extraction: OR 0.23, 95% CI 0.09 to 0.60; on-tool extraction: OR 0.39, 95% CI 0.18 to 0.88) was reported less frequently among self-employed respondents than among employed respondents. The magnitude of the negative association between self-employment status and any of the three types of local exhaust ventilation was not attenuated by adjustment for duration of work per day or week or asthma and/or wheezing symptoms. Respiratory protection was not associated with employment status in these data.Conclusions: More limited use of local exhaust ventilation among self-employed workers compared to employees suggests the need to promote occupational safety among self-employed workers.

Epstein-Barr virus (EBV) is associated with a number of human malignancies. EBV-positive post-transplant lymphoproliferative disease in solid organ and hematopoietic stem cell transplant recipients has been successfully treated by the adoptive transfer of polyclonal EBV-specific T cell lines containing CD4+ and CD8+ T cell components. Although patients receiving T cell preparations with a higher CD4+ T cell proportion show better clinical responses, the specificity of the infused CD4+ component has remained completely unknown. We generated LCL-stimulated T cell lines from 21 donors according to clinical protocols, and analyzed the antigen specificity of the CD4+ component in EBV-specific T cell preparations using a genetically engineered EBV mutant that is unable to enter the lytic cycle, and recombinantly expressed and purified EBV proteins. Surprisingly, CD4+ T cell lines from acutely and persistently EBV-infected donors consistently responded against EBV lytic cycle antigens and autoantigens, but barely against latent cycle antigens of EBV hitherto considered principal immunotherapeutic targets. Lytic cycle antigens were predominantly derived from structural proteins of the virus presented on MHC II via receptor-mediated uptake of released viral particles, but also included abundant infected cell proteins whose presentation involved intercellular protein transfer. Importantly, presentation of virion antigens was severely impaired by acyclovir treatment of stimulator cells, as currently performed in most clinical protocols. These results indicate that structural antigens of EBV are the immunodominant targets of CD4+ T cells in LCL-stimulated T cell preparations. These findings add to our understanding of the immune response against this human tumor-virus and have important implications for the improvement of immunotherapeutic strategies against EBV.

CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.

The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants. Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T) and SLC22A5/OCTN2 (-207 G-->C). All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11); OR 1.56; 95 % CI (1.37-1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [P = 8.04x10(-8); OR 0.43; CI (0.31-0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC.

Sepsis patients may die either from an overwhelming systemic immune response and/or from an immunoparalysis-associated lack of anti-bacterial immune defence. We hypothesized that bacterial superantigen-activated T cells may be prevented from contribution into anti-bacterial response due to the inhibition of their effector functions by the hypoxia inducible transcription factor (HIF-1alpha) in inflamed and hypoxic areas. Using the Cre-lox-P-system we generated mice with a T-cell targeted deletion of the HIF-1alpha gene and analysed them in an in vivo model of bacterial sepsis. We show that deletion of the HIF-1alpha gene leads to higher levels of pro-inflammatory cytokines, stronger anti-bacterial effects and much better survival of mice. These effects can be at least partially explained by significantly increased NF-kappaB activation in TCR activated HIF-1 alpha deficient T cells. T cells can be recruited to powerfully contribute to anti-bacterial response if they are relieved from inhibition by HIF-1alpha in inflamed and hypoxic areas. Our experiments uncovered the before unappreciated reserve of anti-bacterial capacity of T cells and suggest novel therapeutic anti-pathogen strategies based on targeted deletion or inhibition of HIF-1 alpha in T cells.

Ozone has been proposed as an alternative oral antiseptic in dentistry, due to its antimicrobial power reported for gaseous and aqueous forms, the latter showing a high biocompatibility with mammalian cells. New therapeutic strategies for the treatment of periodontal disease and apical periodontitis should consider not only antibacterial effects, but also their influence on the host immune response. Therefore, our aim was to investigate the effect of aqueous ozone on the NF-κB system, a paradigm for inflammationassociated signaling/transcription. We showed that NF-κB activity in oral cells stimulated with TNF, and in periodontal ligament tissue from root surfaces of periodontally damaged teeth, was inhibited following incubation with ozonized medium. Under this treatment, IκBalpah proteolysis, cytokine expression, and κB-dependent transcription were prevented. Specific ozonized amino acids were shown to represent major inhibitory components of ozonized medium. In summary, our study establishes a condition under which aqueous ozone exerts inhibitory effects on the NF-κB system, suggesting that it has an antiinflammatory capacity.

Objective: The Stroke-Specific Quality of Life Scale (SS-QOL) is a recently developed measure to assess health-related quality of life in stroke patients. The objective of this study was to translate the American version of the SS-QOL and examine the validity of the German proxy version, in both ischemic and hemorrhagic stroke survivors. Methods: The translation was conducted according to published guidelines. The validation was performed in consecutive adult stroke survivors. Data were obtained 1 year after discharge. To examine the dimensionality of the SS-QOL, factor analyses were conducted. The validity was examined by the associations of the subscales with the Functional Independence Measure and Short Form 36. Results: The literal translation revealed no major changes between the American and the German versions of the SS-QOL. Three hundred seven stroke survivors were included in the study. Unlike the 1st validation study, most of the variance could be explained by 8 instead of 12 factors; therefore, the 8-factor solution was further examined. The validity of the SS-QOL total score and “observable” scales such as “activities” was shown. Conclusions. For the German proxy version of the SS-QOL, an 8-factor solution was found to be the most appropriate. The psychometric properties of these 8 subscales were good or excellent with respect to internal consistency. The validity of the total score was shown, but some subscales(energy, mood, and thinking) failed the hypothesized associations. Therefore, the SS-QOL needs to be further explored in other settings and populations.

Background: As international travel increases, there is rising exposure to many pathogens not traditionally encountered in the resource-rich countries of the world. Filarial infections, a great problem throughout the tropics and subtropics, are relatively rare among travelers even to filaria-endemic regions of the world. The GeoSentinel Surveillance Network, a global network of medicine/travel clinics, was established in 1995 to detect morbidity trends among travelers. Principal Findings: We examined data from the GeoSentinel database to determine demographic and travel characteristics associated with filaria acquisition and to understand the differences in clinical presentation between nonendemic visitors and those born in filaria-endemic regions of the world. Filarial infections comprised 0.62% (n = 271) of all medical conditions reported to the GeoSentinel Network from travelers; 37% of patients were diagnosed with Onchocerca volvulus, 25% were infected with Loa loa, and another 25% were diagnosed with Wuchereria bancrofti. Most infections were reported from immigrants and from those immigrants returning to their county of origin ( those visiting friends and relatives); the majority of filarial infections were acquired in sub-Saharan Africa. Among the patients who were natives of filaria-nonendemic regions, 70.6% acquired their filarial infection with exposure greater than 1 month. Moreover, nonendemic visitors to filaria-endemic regions were more likely to present to GeoSentinel sites with clinically symptomatic conditions compared with those who had lifelong exposure. Significance: Codifying the filarial infections presenting to the GeoSentinel Surveillance Network has provided insights into the clinical differences seen among filaria-infected expatriates and those from endemic regions and demonstrated that O. volvulus infection can be acquired with short-term travel.

Our aim was to develop guidance for general paediatricians and primary care physicians in diagnosing and managing cow’s milk protein allergy in infants. The guidelines were developed by discussion based on existing national recommendations and standards, clinical experience and, whenever possible, evidence from the literature. Separate algorithms cover breast-fed and formula-fed infants. The recommendations emphasise the importance of comprehensive history taking and careful physical examination. Patients with severe symptoms need to be referred to a specialist. Elimination of cow’s milk protein from the infant’s or mother’s diet and challenges are the gold standard for diagnosis. This guidance is intended as a basis for local discussion, implementation and prospective evaluation. The algorithms should be regularly assessed using clinical audit standards. Once validated, the diagnostic framework could provide a standardised approach in epidemiological and therapeutic studies.

Background: Heterozygous gain-of-function mutations in various genes encoding proteins of the Ras-MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been studied in patients with CFCS. Methods and results: We investigated SOS1 in a large cohort of patients with disorders of the NS–CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1 and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with NS. In contrast, none of the patients classified as having CFCS was found to carry a pathogenic sequence change in this gene. Conclusion: We have confirmed SOS1 as the second major gene for NS. Patients carrying mutations in this gene have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. However, the clinical picture associated with SOS1 mutations is different from that of CFCS. These findings corroborate that, despite being caused by gainof- function mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically.

Mon, 1 Jan 2007 12:00:00 +0100 http://jnnp.bmj.com/content/78/10/1055.full.pdf+html https://epub.ub.uni-muenchen.de/15834/1/puppy_sign.pdf Klopstock, Thomas; Linn, Jennifer; Feddersen, Berend ddc:610, Med

Background: The comprehensive ICF Core Set for rheumatoid arthritis (RA) is a selection of 96 categories from the International Classification of Functioning, Disability and Health (ICF), representing relevant aspects in the functioning of RA patients. Objectives: To study the reliability of the ICF Core Set for RA in rheumatological practice, and to explore the metric of the qualifiers’ scale. Methods: 25 RA patients from an outpatient department of rheumatology were interviewed using the ICF Core Set for RA (76% females, mean (SD) age 57.5 (12.5) years, disease duration 15.9 (14.6) years). Interviews were performed independently by both a physiotherapist and an occupational therapist on the same day and again after one week by one of them. The severity of the patients’ problems was quantified on a qualifier scale ranging from 0 (no problem) to 4 (complete problem). Analyses of intra-rater and inter-rater agreement, kappa statistics, and Rasch analyses were applied. Results: Mean intra-rater (inter-rater) complete agreement for all categories was seen in 59% (47%) of observations, ranging from 29% (0%) to 96% (80%) for individual categories. Weighted kappa statistics with value >0.4 showed reliability in 86% of categories within raters, and in 43% of categories between raters. Improved inter-rater and intra-rater reliability was observed with a reduced number of qualifiers for the categories. Conclusions: Inter-rater and intra-rater reliability of the ICF Core Set of RA was low to moderate. The metric of the qualifiers’ scale may be improved by reducing the number of qualifiers to three for all components.

Objectives: To establish the regional delay of contrast arrival in magnetic resonance perfusion imaging (MRPI) for the detection of collateral-dependent myocardium in patients with coronary artery disease. Design and Setting: observational study, case series; single center, university hospital. Patients: 30 patients with coronary artery disease and collateral-dependent myocardium and 17 healthy volunteers. Methods: Resting and hyperemic (adenosine) MRPI was used to determine delay time (Δtd) of contrast arrival between the left ventricle and collateral-dependent or antegradely-perfused myocardium, and myocardial perfusion (MP, ml/g/min). Results: In healthy volunteers Δtd at rest and during hyperemia were 0.8±0.4 and 0.3±0.3 sec., and MP was 1.14±0.21 and 4.23±1.12 ml/min/g. Δtd in antegradely-perfused vs. collateraldependent myocardium was 0.9±0.7 vs. 1.7±1.0 sec. at rest (p

Dyslexia is among the most common neurodevelopmental disorders, with a prevalence of 5–12%. At the phenotypic level, various cognitive components that enable reading and spelling and that are disturbed in affected individuals can be distinguished. Depending on the phenotype dimension investigated, inherited factors are estimated to account for up to 80%. Linkage findings in dyslexia are relatively consistent across studies in comparison to findings for other neuropsychiatric disorders. This is particularly true for chromosome regions 1p34–p36, 6p21–p22, 15q21 and 18q11. Four candidate genes have recently been identified through systematic linkage disequilibrium studies in linkage region 6p21–p22, and through cloning approaches at chromosomal breakpoints. Results indicate that a disturbance in neuronal migration is a pathological correlate of dyslexia at the functional level. This review presents a summary of the latest insights into the genetics of dyslexia and an overview of anticipated future developments.

The central compensation of vestibular tonus imbalance due to unilateral peripheral vestibular lesions has been repeatedly documented. Little is known, however, about the central compensation of vestibular tonus imbalance due to central lesions. Dorsolateral medullary infarctions (Wallenberg’s syndrome) typically cause a central vestibular tonus imbalance in the roll plane with deviations of perceived verticality and ipsiversive body lateropulsion. The course of normalisation of the tilts of subjective visual vertical (SVV) in 50 patients who had acute Wallenberg’s syndrome were retrospectively compared with that in 50 patients with acute vestibular neuritis. The initial displacement of SVV was 9.8° in Wallenberg’s syndrome and 7° in vestibular neuritis. The deviation of SVV significantly decreased over time within days to weeks in both groups. This finding shows that the time courses of the central compensation for dorsolateral medullary infarctions and peripheral vestibular lesions are similar.

Mon, 1 Jan 2007 12:00:00 +0100 http://ard.bmj.com/content/66/4/566.full.pdf+html https://epub.ub.uni-muenchen.de/15859/1/autosplenectomy.pdf Schulze-Koops, Hendrik; Rech, J.; Kallert, S.; Hueber, A.J.; Leipe, Jan ddc:610, Medizin

Objective: To define the clinical and angiographic follow-up results after implantation of paclitaxel-eluting stents (PESs) in stenotic saphenous vein grafts (SVGs). Design: Prospective multicentre study. Comparison with a control group. Methods: 60 consecutive patients with 65 lesions located in 65 SVGs (mean (SD) age of vein grafts 11.3 (5.7) years) treated with PES (V-Flex Plus, 2.7 mg/mm2 paclitaxel, Cook) and 60 patients with 60 SVG lesions treated with bare metal stent (BMS) were included. Lesions had to be ,20 mm in length and in grafts of 2.75–3.5 mm diameter. The 6 month angiographic follow-up was obtained on 51 lesions (79%) of the PES group and on 51 lesions (85%) of the BMS group. Results: Baseline clinical and angiographic characteristics were comparable between both groups. At angiographic follow-up, three vein grafts in the PES group and five vein grafts in the BMS group were occluded. In-stent late lumen loss was lower in PES than in BMS (0.61 (0.81) vs 1.06 (0.72) mm, respectively; p = 0.021). In-stent binary restenosis rates were 12% vs 33%, respectively, (p = 0.012). Linear regression analysis showed BMS to be the only factor with an effect on late lumen loss (p = 0.011). Target-vessel failure rates were 18% in the PES group and 41% in the BMS group (p = 0.019), whereas major adverse cardiac event (MACE) rates at 180 days were 15% and 37%, respectively (p = 0.014). Conclusions: Implantation of non-polymer-based PES in SVG lesions is associated with a lower late lumen loss and restenosis rate than those of BMS. There remains a substantial target-vessel failure rate and MACE rate even at 6 months owing to graft occlusion or new lesions in the graft.

Mon, 1 Jan 2007 12:00:00 +0100 https://epub.ub.uni-muenchen.de/16293/1/10_1159_000100089.pdf Fichter, Manfred M.

Introduction: This study investigates if obsessive compulsive disorder with early onset differs in severity and symptomatology from that with late onset. Patients and Methods: A sample of 370 patients with obsessive compulsive disorder (OCD; ICD 10 F42) who received in-patient treatment at the psychosomatic clinic of Windach between 1998 and 2002 were divided into an early-onset group (onset

The Importance of Metacognitions in the Understanding and Treatment of Obsessive Compulsive Disorder The present article discusses three cognitive approaches of Obsessive Compulsive Disorder (OCD): (1) Beck's theory of content-specificity, (2) Salkovskis' cognitive-behavioural approach and (3) Wells' more recent theory of metacognitions. Wells' approach is explained in more detail: the so called Self-Regulatory Executive Function model is presented as well as special aspects of thinking in OCD, for example the self-referential status of thinking, thinking in object mode and aspects of `thought-action fusion'. The relevance of Wells' metacognitive approach for the development and the maintenance of OCD is discussed. Furthermore, proposals are made on how to include these issues in the psychotherapy of OCD.

Background: Psychoeducational interventions that provide disorder-related information in a goal-oriented and structured manner have been integrated in psychiatric and psychotherapeutic approaches. The present cognitive psychoeducational group programme for inpatients with affective disorders is based on a multidimensional functional illness concept which covers aspects of vulnerability, stressors and coping strategies. It covers information about the disorder and its treatment options, building up rewarding activities, cognitive restructuring and relapse prevention. Materials und Methods: This programme was developed and modified at the University of Munich, Department of Psychiatry (LMU). A feasibility study was set up in a follow-up single group design and analyses of variance (ANOVAs) were performed. A total of 231 patients participated in 46 groups. Results: 125 patients evaluated the effectiveness of the programme and its treatment strategies. The group programme was widely accepted among patients that were pharmacologically and psychotherapeutically treated: more than three quarters of the patients rated its contents to be informative, helpful and applicable to everyday living. Conclusions: Inpatients with affective disorders may already benefit from a structured group programme if it takes into account their cognitive and motivational deficits. The group leaders' didactic and psychotherapeutic strategies as well as the patients' exchanging ideas with each other play a central role. In the course of further investigations the programme was differentiated for patients with major depression or bipolar disorders.

Background: The implementation of automated techniques improves the workflow and quality of immuno-hematological results. The workflows of our university blood bank were reviewed during the implementation of an automated immunohematological testing system. Methods: Work impact of blood grouping and subgrouping, cross- matching and antibody search using the Immucor Galileo system was compared to the previous used standard manual and semi- automated methods. Results: The redesign of our workflow did not achieve a significant reduction of the specimen's working process time, the operator's time however was reduced by 23%. Corresponding results were achieved for blood grouping, Rhesus typing, antibody screen and for autocontrol when changing from two semi- automated to the Galileo system. Because of the higher sensitivity of the Immucor antibody detection system, the rate of the initial positive antibody screens rose from 4 to 6% Conclusion: The Immucor Galileo system automates routine blood bank testing with high reliability, specificity and higher sensitivity compared to our previous used standard manual and semi- automated methods.

Diabetic retinopathy is a leading cause of visual impairment and blindness in developed countries due to macular edema and proliferative diabetic retinopathy (PDR). For both complications laser treatment may offer proven therapy: the Diabetic Retinopathy Study demonstrated that panretinal scatter photocoagulation reduces the risk of severe visual loss by >= 50% in eyes with high-risk characteristics. Pan-retinal scatter coagulation may also be beneficial in other PDR and severe nonproliferative diabetic retinopathy (NPDR) under certain conditions. For clinically significant macular edema the Early Treatment of Diabetic Retinopathy Study could show that immediate focal laser photocoagulation reduces the risk of moderate visual loss by at least 50%. When and how to perform laser treatment is described in detail, offering a proven treatment for many problems associated with diabetic retinopathy based on a high evidence level. Copyright (c) 2007 S. Karger AG, Basel.

Purpose: To compare and correlate imaging of classic subfoveal choroidal neovascularization (CNV) with noninvasive 3-dimensional imaging by the retinal thickness analyzer (RTA) to conventional fluorescein angiography (FA). Methods: A total of 29 eyes of 29 consecutive patients with predominantly classic CNV eligible for photodynamic therapy underwent FA and RTA imaging. The FA dimensions of the CNV were measured independently by two graders. With the RTA, masked to FA the size of the CNV itself as imaged in 3-dimensional reconstruction, the size of significantly thickened retina overlying the CNV and the maximum retinal thickness were measured. Results: The mean diameter of the CNV determined from 3-dimensional RTA reconstructions showed an excellent correlation with measurements from FA (r = 0.91, p < 0.001). The area of retinal thickening was by a mean of 0.7 mm in diameter larger and correlated moderately well with the size of the CNV on FA (r = 0.65, p < 0.001). In contrast, there was no correlation between the absolute retinal thickness and the CNV size on FA. Conclusions: Noninvasive quantitative mapping of predominantly classic CNV by RTA is feasible and also allows 3-dimensional measurement of the lesion itself. The results correlate well with FA assessment but visualize different properties of the disease. Copyright (c) 2007 S. Karger AG, Basel.

Background: To perform lamellar keratolimbal allograft transplantation in a one- step procedure with a single graft, we investigated the feasibility of harvesting eccentric lamellar keratolimbal grafts from conventionally processed corneoscleral buttons using a manually guided microkeratome in conjunction with an artificial anterior chamber system. Methods: We used the Moria LSK- One microkeratome and the automated lamellar therapeutic keratoplasty ( ALTK) system ( Antony, France). Ten human donor eyes were used to obtain single- piece lamellar keratolimbal grafts. Specimens were processed for light and electron microscopy. Results: Eccentric keratolimbal grafts could be obtained from all human donor buttons. Grafts include a crescent- shaped limbal and a large corneal portion. No visible damage to the limbal region was discernible. Conclusion: Our data show that the LSK- One microkeratome in conjunction with the ALTK system allows harvesting eccentric keratolimbal grafts from donor corneoscleral buttons. Copyright (c) 2007 S. Karger AG, Basel.

Background: The carbohydrate antigen 19-9 (CA 19-9) is currently the most widely used serum tumor marker in pancreatic cancer (PC). CA 19-9 pretreatment levels as well as CA 19-9 kinetics during systemic chemotherapy can provide prognostic information regarding survival of patients with metastatic PC. Case Reports: We report the clinical course of 2 patients with metastatic PC who underwent palliative chemotherapy with gemcitabine. Both patients showed a significant elevation of pretreatment CA 19-9 levels (7,505 and 150,000 U/ml, respectively), however, subsequently they experienced a highly significant reduction (> 90%) of CA 19-9 kinetics under gemcitabine chemotherapy. A good disease control and a clinical benefit response were achieved in both patients. Time to tumor progression was 30 weeks and 28 weeks, overall survival 14 months and 11 months, respectively. Conclusion: These data indicate that CA 19-9 kinetics under chemotherapy may possibly serve as a useful surrogate marker for time to tumor progression and survival in advanced PC.

Background: Due to an aging population the incidence of both cardiac and tumor-related illnesses is increasing. A problem may arise if radiotherapy is necessary in close anatomic proximity to an implantable cardioverter-defibrillator (ICD). These highly precise devices may respond to ionizing radiation with a loss of function or uncontrolled stimulation, with both effects being potentially life threatening. Available guidelines recommend the dose maximum to a pacemaker to be cumulative below 2 Gy. For most patients undergoing radiation therapy of the neck or of the chest this limit is exceeded, thus making a removal of the device and an implantation of an external ICD necessary. Case Report: A patient with severe cardiac problems underwent an implantation of an ICD. However, a recurrence of a laryngeal cancer was diagnosed. The irradiation dose after resection was 60 Gy to the tumor region and 50 Gy to the lymph nodes. Irradiation peakload to the ICD was calculated to be 2.5 Gy. This dose was verified with thermoluminescence measurements. The ICD was externally deactivated during the sessions of irradiation. Device checks demonstrated no malfunction. Conclusion: Even though the dose limits of the ICD of 2 Gy were exceeded, the device demonstrated a regular function during and after radiotherapy.

Background: Paravasation is a rare but severe complication of treatment with cytotoxic agents. Some anticancer drugs are considered to be of high toxicity (vesicant), some are merely irritant, and some are regarded as nearly non-toxic to healthy tissue as is the case with cyclophosphamide. Case Report: In this report, we present the first case of severe tissue damage caused by a paravasation of cyclophosphamide in a breast cancer patient receiving chemotherapy. Conclusion: Therefore, every attending oncological physician should be aware of the possibility of severe tissue damage as a consequence of cyclophosphamide paravasation.

Background: Irinotecan-based second-line chemotherapy of metastatic colorectal cancer (CRC) is effective, it might, however, be contraindicated in cases of severe liver dysfunction due to advanced liver metastases. Case Report: A 57-year-old woman with diffuse CRC liver metastases showed progressive disease on first-line treatment with capecitabine and oxaliplatin (XELOX). Chronic cholestasis and hyperbilirubinemia caused by advanced liver involvement prohibited second-line treatment with irinotecan-based chemotherapy. We initiated combined antibody treatment with cetuximab and bevacizumab. Results: Clinical performance status as well as laboratory parameters improved rapidly. Staging investigations after 8 weeks revealed a partial remission. Since bilirubin levels had returned to the upper limit of normal, therapy could be changed to standard irinotecan, 5-fluorouracil, folinic acid, and bevacizumab. Conclusion: Combined treatment with cetuximab and bevacizumab may be considered as an effective treatment option in patients who cannot be treated with standard chemotherapy regimens due to impaired liver metabolism of cytotoxic substances.

Imatinib has had marked impact on outcomes in chronic myelogenous leukemia (CML) patients for all stages of the disease and is endorsed by international treatment guidelines as the first line option. Although imatinib is highly effective and well tolerated, the development of resistance represents a clinical challenge. Since the most frequently identified mechanism of acquired imatinib resistance is bcr-abl kinase domain point mutations, periodic hematologic, cytogenetic, and molecular monitoring is critical throughout imatinib therapy. Once cytogenetic remission is achieved, residual disease can be monitored by bcr-abl transcript levels as assayed by reverse transcription polymerase chain reaction (RT-PCR). Detection of bcr-abl mutants prior to and during imatinib therapy can aid in risk stratification as well as in determining therapeutic strategies. Thus, mutation screening is indicated in patients lacking or losing hematologic response. Moreover, search for mutations should also be performed when a 3-log reduction of bcr-abl transcripts is not achieved or there is a reproducible increase of transcript levels. In patients harboring mutations which confer imatinib resistance, novel second line tyrosine kinase inhibitors have demonstrated encouraging efficacy with low toxicity. Only the T315I bcr-abl mutant has proved totally resistant to all clinically available bcr-abl inhibitors. Strategies to further increase the rates of complete molecular remissions represent the next frontier in the targeted therapy of CML patients.

Objective: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem) failure has been defined for patients with advanced pancreatic cancer (PC). Oral capecitabine (Cap) has shown promising activity in first-line chemotherapy trials in PC patients. Methods: Within a prospective single-center study, Cap was offered to patients who had already received at least 1 previous treatment regimen containing full-dose Gem (as a single agent, as part of a combination chemotherapy regimen or sequentially within a chemoradiotherapy protocol). Cap was administered orally at a dose of 1,250 mg/m(2) twice daily for 14 days followed by 7 days of rest. Study endpoints were objective tumor response rate by imaging criteria (according to RECIST), carbohydrate antigen 19-9 (CA19-9) tumor marker response, time to progression, overall survival and toxicity. Results: A median of 3 treatment cycles (range 1-36) was given to 39 patients. After a median follow-up of 6.6 months, 27 patients were evaluable for response: no complete or partial responses were observed, but 15 patients (39%) had stable disease. A CA19-9 reduction of >20% after 2 cycles of Cap was documented in 6 patients (15%). Median time to progression was 2.3 months (range 0.5-45.1) and median overall survival (since start of Cap treatment) was 7.6 months (range 0.7-45.1). Predominant grade 2 and 3 toxicities (per patient analysis) were hand-foot syndrome 28% (13% grade 3); anemia 23%; leg edema 15%; diarrhea 13%; nausea/vomiting 10%, and leukocytopenia 10%. Conclusion: Single-agent Cap is a safe treatment option for Gem-pretreated patients with advanced PC. Further evaluation of Cap in controlled clinical trials of Gem-pretreated patients with advanced PC is recommended. Copyright (C) 2008 S. Karger AG, Basel.

Background: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. Patients and Methods: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. Results: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombo-cytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. Conclusion: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2). Copyright (c) 2008 S. Karger AG, Basel.

Background: In patients undergoing surgery for resectable pancreatic cancer prognosis still remains poor. The role of adjuvant treatment strategies (including chemotherapy and chemoradiotherapy) following resection of pancreatic cancer remains controversial. Methods: A Medline-based literature search was undertaken to identify randomized controlled trials that evaluated adjuvant chemotherapy after complete macroscopic resection for cancer of the exocrine pancreas. Five trials of adjuvant chemotherapy were eligible and critically reviewed for this article. A meta-analysis (based on published data) was performed with survival (median survival time and 5-year survival rate) being the primary endpoint. Results: For the meta-analysis, 482 patients were allocated to the chemotherapy group and 469 patients to the control group. The meta-analysis estimate for prolongation of median survival time for patients in the chemotherapy group was 3 months (95% CI 0.3-5.7 months, p = 0.03). The difference in 5-year survival rate was estimated with 3.1% between the chemotherapy and the control group (95% CI -4.6 to 10.8%, p > 10.05). Conclusion: Currently available data from randomized trials indicate that adjuvant chemotherapy after resection of pancreatic cancer may substantially prolong disease-free survival and cause a moderate increase in overall survival. In the current meta-analysis, a significant survival benefit was only seen with regard to median survival, but not for the 5-year survival rate. The optimal chemotherapy regimen in the adjuvant setting as well as individualized treatment strategies (also including modern chemoradiotherapy regimens) still remain to be defined. Copyright (C) 2008 S. Karger AG, Basel.

The processing of emotional facial expression is a major part of social communication and understanding. In addition to explicit processing, facial expressions are also processed rapidly and automatically in the absence of explicit awareness. We investigated 12 healthy subjects by presenting them with an implicit and explicit emotional paradigm. The subjects reacted significantly faster in implicit than in explicit trials but did not differ in their error ratio. For the implicit condition increased signals were observed in particular in the thalami, the hippocampi, the frontal inferior gyri and the right middle temporal region. The analysis of the explicit condition showed increased blood-oxygen-level-dependent signals especially in the caudate nucleus, the cingulum and the right prefrontal cortex. The direct comparison of these 2 different processes revealed increased activity for explicit trials in the inferior, superior and middle frontal gyri, the middle cingulum and left parietal regions. Additional signal increases were detected in occipital regions, the cerebellum, and the right angular and lingual gyrus. Our data partially confirm the hypothesis of different neural substrates for the processing of implicit and explicit emotional stimuli. Copyright (c) 2007 S. Karger AG, Basel.

Objective: The aim of the present study was to investigate if somatoform disorders (SFD) are associated with changes in the normal serum levels of important interleukins, and further, to establish if these changes are related to the presence and severity of alexithymia in patients with SFD. Methods: Twenty-four unmedicated patients who met the International Classification of Diseases (ICD-10) diagnostic criteria for SFD completed the psychological questionnaire to assess alexithymia (Toronto Alexithymia Scale), symptom reporting (SCL-90-R) and diagnostic criteria for SFD (Screening for Somatoform Symptoms scale). Serum concentrations of soluble interleukin 2 receptor alpha(sIL-2R alpha), IL-4, IL-6, IL-10 and IL-12 were determined in patients with SFD and in 9 healthy subjects. Results: In patients with SFD, serum levels of IL-6 (p ! 0.001), IL-10 (p = 0.047) and immunoglobulin E (p = 0.045) were significantly increased in comparison with healthy controls. Additionally, a negative correlation was observed between the level of alexithymia ('total' Toronto Alexithymia Scale score) and the serum levels of sIL-2R alpha (r = -0.538) in SFD. Conclusions: Taken together, these results suggest that SFD, with clinically significant alexithymia, are associated with a reduction in Th1-mediated immune function and an increase in the activation of the Th2 immune function, indicated by the augmented serum levels of IL-6 and IL-10 and elevated immunoglobulin E. Copyright (c) 2007 S. Karger AG, Basel.

Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients. Copyright (c) 2008 S. Karger AG, Basel.

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel.