Altered white matter integrity in adults with autism spectrum disorder and an IQ >100: a diffusion tensor imaging study.

OBJECTIVE: White matter (WM) alterations have been reported in children and adults with autism spectrum disorder (ASD). In particular, impaired connectivity of limbic structures may be related to social deficits. Heterogeneous findings could be explained in terms of differences in sample characteristics and methodology. In this context, non-syndromic forms might differ substantially in WM structure from secondary ASD forms. METHOD: In an attempt to recruit a homogeneous study sample, we included adults with high-functioning ASD and an IQ > 100 to decrease the influence of syndromic forms being often associated with cognitive deficits. Diffusion tensor imaging (DTI) was performed in 30 participants with ASD and 30 pairwise-matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) as surrogate imaging markers for WM integrity were calculated. RESULTS: We found a significant FA decrease in the ASD group in the genu and body of the corpus callosum (CC). Increased MD was detected in the subgenual anterior cingulate cortex (sACC). CONCLUSION: The finding of decreased WM integrity in the genu of the CC is in line with earlier studies reporting a decreased number of interhemispheric fibers in the frontal lobe of ASD. Alterations in the sACC might be associated with 'Theory of mind' deficits.

Restoring effects of oxytocin on the attentional preference for faces in autism.

Reduced attentional preference for faces and symptoms of social anxiety are common in autism spectrum disorders (ASDs). The neuropeptide oxytocin triggers anxiolytic functions and enhances eye gaze, facial emotion recognition and neural correlates of face processing in ASD. Here we investigated whether a single dose of oxytocin increases attention to faces in ASD. As a secondary question, we explored the influence of social anxiety on these effects. We tested for oxytocin's effects on attention to neutral faces as compared to houses in a sample of 29 autistic individuals and 30 control participants using a dot-probe paradigm with two different presentation times (100 or 500 ms). A single dose of 24 IU oxytocin was administered in a randomized, double-blind placebo-controlled, cross-over design. Under placebo, ASD individuals paid less attention to faces presented for 500 ms than did controls. Oxytocin administration increased the allocation of attention toward faces in ASD to a level observed in controls. Secondary analyses revealed that these oxytocin effects primarily occurred in ASD individuals with high levels of social anxiety who were characterized by attentional avoidance of faces under placebo. Our results confirm a positive influence of intranasal oxytocin on social attention processes in ASD. Further, they suggest that oxytocin may in particular restore the attentional preference for facial information in ASD individuals with high social anxiety. We conclude that oxytocin's anxiolytic properties may partially account for its positive effects on socio-cognitive functioning in ASD, such as enhanced eye gaze and facial emotion recognition.

[Pulmonary hypertension associated with left heart disease: recommendations of the Cologne Consensus Conference 2016]. / Pulmonale Hypertonie bei Linksherzerkrankungen: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more common forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern because of limited ressources and the need to base treatments on scientific evidence. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, representing an unmet need of targeted PH therapies. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, several working groups were initiated, one of which was specifically dedicated to PH associated with left heart disease. This article summarizes the results and recommendations of this working group.

Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis.

Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.

[High-functioning autism spectrum disorders in adulthood]. / Autismusspektrumstörungen mit hohem Funktionsniveau im Erwachsenenalter.

The prevalence of autism spectrum disorders in the general population is approximately 1 %. Some individuals with high-functioning autism graduate from regular schools without autism having been diagnosed and problems only occur when the demands for social competence increase. Then patients often present with secondary psychiatric symptoms, such as depression, anxiety or interpersonal problems. At this time, typical autistic features, such as social interaction deficits, restricted interests and stereotypic behavior can be camouflaged by high compensatory skills, particularly in highly intelligent patients. Therefore, missed or wrong diagnoses are frequent. Interviews, questionnaires and neuropsychological tests might be used to support the diagnosis. In cases where there is evidence for a secondary cause of autistic symptoms, somatic disorders should be excluded. Pharmacological treatment should be symptom-oriented. Individualized psychotherapeutic approaches are becoming increasingly more available; however, pragmatic solutions often need to be deployed.

Evaluation of hospitalization and follow-up care costs among patients hospitalized with ACS treated with a stent and clopidogrel.

OBJECTIVE: This retrospective claims study was performed to evaluate the initial and subsequent healthcare costs in patients with acute coronary syndrome (ACS) who had been treated with stent placement and clopidogrel following discharge from the hospital. METHOD AND RESULTS: This was a retrospective, administrative claims-based analysis from a large, geographically diverse US managed care plan affiliated with i3 Innovus. Study subjects were commercially insured enrollees, aged > or = 18, who were hospitalized for ACS between 1 January 2000 and 31 December 2004 with a stent placed, and had at least one filled prescription for clopidogrel within 7 days of discharge from the index hospitalization. Of the 9135 subjects included in the cost analysis, 2241 subjects experienced a subsequent event. On average, subjects with a second event incurred $32,495 more in medical costs over 2 years and $39,742 more in medical costs over 3 years versus those who did not have a second event. Excluding ischemic hospitalizations, subjects with a second event incurred $7257 and $9724 more in medical costs than patients without a second event during the 2 and 3 years following discharge from the index hospitalization, respectively. CONCLUSIONS: Significant cost increases were observed among patients who had a subsequent hospitalization for an ischemic event compared to those without a subsequent hospitalization. Cost increases were still present after excluding costs of the ischemic hospitalizations. The findings of this study must be considered within the limitations of database analysis as claims data are collected for the purpose of payment and not research.

Female pattern hair loss may be triggered by low oestrogen to androgen ratio.

OBJECTIVE: In both sexes the androgenetic alopecia is known to be mediated by the conversion of circulating androgens into dihydrotestosterone within the hair follicle. However, there are a number of differences between male and female pattern baldness with estrogen known to be protective against hair loss in women. Since androgen levels in women with female pattern hair loss are mostly within the normal range, we decided to calculate the ratio of estrogens to androgens in order to find a putative trigger for their hair loss. METHODS: We studied 20 premenopausal women with female pattern hair loss and 9 healthy women for serum levels of LH, FSH, estradiol, free and total testosterone, sex hormone binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEAS) on the first day of their menstrual cycle. RESULTS: Although the absolute levels of androgens were normal in both groups, the ratio of estradiol to free testosterone and the ratio of estradiol to DHEAS were significantly lower in patients than in the control group. CONCLUSIONS: We put up a hypothesis that in the presence of a genetic susceptibility, it is the estrogen to androgen ratio, as represented by the ratio of estradiol to free testosterone that might be responsible for triggering female pattern hair loss in women.

Natural and traumatic sports-related fatalities: a 10-year retrospective study.

OBJECTIVE: To identify the most common causes of death during sports activity in the population of Hamburg, Germany, and to identify which groups of sportspeople are particularly in danger of dying during sports and in which types of sport most fatalities occur. DESIGN AND SETTING: We performed a 10-year autopsy-based retrospective study of all 48,335 fatalities in Hamburg and the surrounding areas that were subjected to police investigations between 1997 and 2006 and screened for sports-related deaths. The main outcome measure was cause of death depending on form of sport, age and risk factors. RESULTS: Most of the fatalities were male. In natural deaths, cardiac causes were the most frequent causes found, with running and football being the most frequent forms of sport in which death had occurred. In some of the cases, sports medical examinations had been performed before death, certifying eligibility for the respective activity. Traumatic deaths were found in all age groups, with younger age groups more likely to have traumatic than natural deaths, and as expected, occurred more commonly in "risky" outdoor activities. CONCLUSIONS: Although exercise can have beneficial effects on health, fatalities related to sports activity occur. Cardiac disease is the main cause of sudden death from natural causes. In patients with pre-existing coronary heart disease, left ventricular hypertrophy constitutes a risk factor for exercise-related sudden death. Traumatic deaths often happen on holiday outside the person's country of dwelling, and are most commonly attributable to drowning and blunt trauma. Preparticipation medical screening cannot always prevent fatal incidents during sports activity. Postmortem macroscopic and histological examination can clarify the cause of death and legal issues.

Permanent increase in endothelin serum levels in vasovagal syncope.

Of 40 normal volunteers tilted on two separate occasions, seven subjects had vasovagal syncope only during one upright tilt, but showed increased endothelin plasma levels in the supine position and during head-up tilt on both occasions, independent of vasovagal syncope, compared to control subjects.

Anticoagulation therapy in patients with chronic atrial fibrillation: a retrospective claims data analysis.

OBJECTIVES: This study assessed the risk of thrombo embolic events and bleeding complications among atrial fibrillation patients. METHODS: A cohort of patients with chronic non-valvular atrial fibrillation were identified from medical claims (diagnosis codes 427.31 and 427.32). Subjects were identified from 1 January 1998-31 December 2000 and were continuously enrolled for 6 months prior to the first occurring atrial fibrillation medical claim. Cox proportional hazards analysis with time varying covariates was used for the event analysis. RESULTS: Of 6764 subjects retained for analysis, 3541 (52.4%) were exposed to warfarin. Adjusting for baseline characteristics, warfarin exposure was associated with lower likelihood of an arterial thromboembolic event compared to no exposure (HR: 0.710, CI: 0.540-0.934). No benefit was found in the use of warfarin in the prevention of intracranial events (HR: 1.119, CI: 0.929-1.349). Use of warfarin increased the risk of minor bleeding events (HR: 3.600, CI: 2.537-5.109), and all bleeding events (HR: 1.502, CI: 1.289-1.749). CONCLUSIONS: The risk of arterial thromboembolic events was associated with warfarin exposure as expected. An increase in the risk of minor and total bleeding events among patients treated with warfarin was observed. The results of this study suggest that there may be a gap between the clinical trial and coagulation clinic performance of warfarin in reducing the risk of thromboembolic events versus what is achievable in general practice.

Quantification of omeprazole degradation by enteric coating polymers: an UV-VIS spectroscopy study.

The aim of this study was to investigate the degradation of the acid-labile proton-pump-inhibitor omeprazole in organic polymer solutions and aqueous dispersions of enteric coating polymers by UV spectroscopy. Furthermore, data were compared with those obtained in a previous HPLC study. For comparative purposes the cationic Eudragit RS 100 and the monomeric acid acetic acid were included in this study. The discolorations of degraded omeprazole solutions were analysed by VIS spectroscopy. UV-VIS spectra were recorded after preparation of the solutions and after 180 min of storage. The change of absorption was calculated as the difference of the absorption values at 305 nm. Degradation of omeprazole depends on the amount of acidic groups in the polymer structure. This decomposition manifests itself in a shifting of the absorption maximum to lower wavelengths and a decrease of absorption intensity. UV-VIS spectroscopy was used to determine the extent of degradation induced by enteric polymers. A good correlation of these results with previous HPLC data was found when excluding UV absorbing polymers. Nevertheless, values obtained by UV-VIS spectroscopy were always lower than those obtained by HPLC. For evaluation of the discoloration of degraded omeprazole solutions, VIS spectroscopy is a simple and fast method.

Degradation of omeprazole induced by enteric polymer solutions and aqueous dispersions: HPLC investigations.

Two reversed-phase high-performance liquid chromatography (RP-HPLC) methods were developed to investigate the degradation of the acid-labile proton-pump-inhibitor omeprazole in organic polymer solutions and aqueous dispersions of enteric coating polymers (Eudragit L-100, S-100, CAP, HP-55, HPMCAS-HF, -LF, and shellac). The overall goal of the study was to determine the influence of the polymer structure on the degradation of omeprazole, i.e., whether the acid structure of the enteric coating polymers caused an instability of the proton pump inhibitor. Moreover, it was investigated whether a difference in omeprazole degradation could be detected between organic polymer solutions and aqueous dispersions. pKa values of the polymers and pH values of the aqueous dispersions were determined to see whether there was a correlation with the extent of degradation of omeprazole induced by enteric polymers. As the polymers containing phthalate moieties are very susceptible to hydrolysis, the influence of free phthalic acid on omeprazole stability was investigated. Finally, the degradation kinetics of omeprazole in organic polymer solutions were determined. Omeprazole degradation is more pronounced in aqueous polymer dispersions than in organic polymer solutions. The influence of organic polymer solutions on the stability of omeprazole depends on the amount of acidic groups in the polymeric structure, whereas the influence of aqueous polymer dispersions depends on the pH value of the dispersion. The amount of free acids present in some polymers as by-products also cause a degradation of the proton pump inhibitor. Among all investigated polymers, shellac showed the least influence on the stability of omeprazole. The decomposition of omeprazole in organic polymer solutions followed first-order kinetics. The decrease of omeprazole peak area in organic polymer solutions was in the order Eudragit L-100> HPMCAS-HF>shellac.

Fröhlich mass in GaAs-based structures.

The Fröhlich interaction is one of the main electron-phonon intrinsic interactions in polar materials originating from the coupling of one itinerant electron with the macroscopic electric field generated by any longitudinal optical (LO) phonon. Infrared magnetoabsorption measurements of doped GaAs quantum well structures have been carried out in order to test the concept of Fröhlich interaction and polaron mass in such systems. These new experimental results lead one to question the validity of this concept in a real system.

Influence of a radiofrequency electromagnetic field on cardiovascular and hormonal parameters of the autonomic nervous system in healthy individuals.

The potential health risks of radiofrequency electromagnetic fields (EMFs) emitted by mobile phones are of considerable public interest. The present study investigated the hypothesis, based on the results of our previous study, that exposure to EMFs can increase sympathetic vasoconstrictor activity. Forty healthy young males and females underwent a single-blind, placebo-controlled protocol once on each of two different days. Each investigation included successive periods of placebo and EMF exposure, given in a randomized order. The exposure was implemented by a GSM-like signal (900 MHz, pulsed with 217 Hz, 2 W) using a mobile phone mounted on the right-hand side of the head in a typical telephoning position. Each period of placebo exposure and of EMF exposure consisted of 20 min of supine rest, 10 min of 70 degrees upright tilt on a tilt table, and another 20 min of supine rest. Blood pressure, heart rate and cutaneous capillary perfusion were measured continuously. In addition, serum levels of norepinephrine, epinephrine, cortisol and endothelin were analyzed in venous blood samples taken every 10 min. Similar to the previous study, systolic and diastolic blood pressure each showed slow, continuous, statistically significant increases of about 5 mmHg during the course of the protocol. All other parameters either decreased in parallel or remained constant. However, analysis of variance showed that the changes in blood pressure and in all other parameters were independent of the EMF exposure. These findings do not support the assumption of a nonthermal influence of EMFs emitted by mobile phones on the cardiovascular autonomic nervous system in healthy humans.

Principles of rat subcortical forebrain organization: a study using histological techniques and multiple fluorescence labeling.

In the present study, we introduce new views on neuro- and chemoarchitectonics of the rat forebrain subcortex deduced from traditional and current concepts of anatomical organization and from our own results. It is based on double and triple immunofluorescence of markers for transmitter-related enzymes, calcium-binding proteins, receptor proteins, myelin basic protein (MBP) and neuropeptides, and on histological cell/myelin stains. The main findings can be summarized as follows: (i) the dorsal striatum of rat and other myomorph rodents reveals a small caudate equivalent homotopic to the caudate nucleus (C) of other mammals, and a large putamen (Pu). (ii) Shell and core can be distinguished also in the 'rostral pole' of nucleus accumbens (ACC) with the calretinin/calbindin and neuropeptide Y (NPY) immunostaining. The shell reveals characteristics of a genuine striatal but not of an extended amygdala (EA) subunit. (iii) EA and lateral septum show striking similarities in structure and fiber connections and may therefore represent a separate parastriatal complex. (iv) The meandering dense layer (DL) of olfactory tubercle (OT) forms longitudinal gyrus- and sulcus-like structures converging in its rostral pole. (v) The core regions of the islands of Calleja that border the ventral pallidum (VP) sharing some of its features are invaded by myelinated fibers of the medial forebrain bundle (MFB). The island of Calleja magna is also apposed to an inconspicuous, slender dorsal appendage of VP. (vi) The VP is composed of a large dorsal reticulated part traversed by the myelinated GABAergic parvalbumin-immunoreactive axons of the MFB and a slender ventral non-reticulate part close to the islands of Calleja. (vii) Considering their close association to the limbic system, ventral striatum (VS) and VP may represent the oldest part of basal ganglia, whereas dorsal striatopallidal subunits were progressively developed in parallel to the growing neocortical influence on motor behavior.

A clinical trial of adjunctive oestrogen treatment in women with schizophrenia.

A double-blind, 28-day, placebo-controlled study was conducted with three groups of women of child-bearing age (N = 12 in each group) who received standardised antipsychotic medication plus a) 50 microg transdermal estradiol or b) 100 microg transdermal estradiol or c) transdermal placebo. Preliminary analyses show that women receiving 100 microg of estradiol made greater improvements in the symptoms of schizophrenia than either the 50 microg estradiol or placebo groups. The addition of 100 microg adjunctive transdermal oestrogen significantly enhanced treatment responsivity of acute, severe psychotic symptoms in women with schizophrenia. The positive impact of oestrogen treatment on psychotic symptoms via a multiplicity of possible actions (see accompanying articles in this issue) may prove clinically useful in the overall treatment of women with schizophrenia.

Estrogen - a potential treatment for schizophrenia.

Estrogen has been shown in animal studies to modulate both the dopamine and serotonin neurotransmitter systems - the main neurotransmitters implicated in the pathogenesis of schizophrenia. A double blind, 28 day, placebo-controlled study was conducted with three groups of women of child-bearing age (N=12 in each group) who received standardized antipsychotic medication plus 50mcg transdermal estradiol or 100mcg transdermal estradiol or transdermal placebo. Analyses show that women receiving 100mcg of estradiol made greater improvements in the symptoms of schizophrenia than both the 50mcg estradiol and placebo groups. Women receiving 50mcg estradiol had more improvement in their symptoms compared with the placebo group. The 100mcg estradiol group had significantly lower mean lutenizing hormone (LH) and higher mean prolactin levels across the study period compared with both the 50mcg and placebo groups. The addition of 100mcg adjunctive transdermal estrogen significantly enhanced the treatment of acute, severe psychotic symptoms in women with schizophrenia. The differential response of adding 50mcg versus 100mcg estradiol on the types of symptom affected may be related to the estrogen effect on LH and prolactin. The positive impact of estrogen treatment on psychotic symptoms by a direct effect on dopamine and serotonin systems or via an indirect prolactin-mediated effect may be very useful in the overall treatment of women with schizophrenia.

Magneto infrared absorption in high electron density GaAs quantum wells.

Magneto infrared absorption measurements have been performed in a highly doped GaAs quantum well which has been lifted off and bonded to a silicon substrate, in order to study the resonant polaron interaction. It is found that the pinning of the cyclotron energy occurs at an energy close to that of the transverse optical phonon of GaAs. This unexpected result is explained by a model taking into account the full dielectric constant of the quantum well.