A comparative study of multi and single post labeling delay pseudocontinuous arterial spin labeling in patients with carotid artery stenosis.

PURPOSE: Arterial Spin Labeling (ASL) allows for the non-invasive visualization of brain perfusion to detect abnormalities. In unilateral carotid artery stenosis, one hemisphere is less supplied with blood which results in a lower cerebral blood flow (CBF) compared to the healthy side. ASL can be performed time-resolved using multiple post labeling delay (PLD) times after labeling or static with a single delay, the latter allowing for a faster and more robust acquisition while bearing the risk of a falsely set delay resulting in unusable images. The purpose of this study is to compare the performance of multi-PLD and single-PLD ASL in patients with unilateral carotid artery stenosis both as means of diagnosis and therapeutic follow-up examination. METHODS: ASL perfusion data of 17 patients with known unilateral carotid artery stenosis was used to compare the diagnostic performance of the multi-PLD and single-PLD approach. Comparisons were made based on the CBF values and the added benefit of arrival time maps showing slower blood flow in multi-PLD ASL which might be overlooked in the individual delay images both before and after therapy. RESULTS: Both the multi-PLD and the single-PLD data could identify the side of the stenosis with hemispheric differences in each approach (p < 0.001) and depict the normalization of CBF after therapy (p > 0.05). There were no differences between the individual methods (p > 0.05). CONCLUSION: In this work, we could show that multi-PLD ASL in patients with unilateral carotid artery stenosis is beneficial as it provides both CBF and arrival time maps, however when only a single-PLD acquisition is available, this appears sufficient in a clinical setting to investigate the presence of a unilateral stenosis.

[Expectations of patients and relatives for modern hospital care in geriatric psychiatry]. / Erwartungen von Patienten und Angehörigen an eine moderne alterspsychiatrische Krankenhausversorgung.

OBJECTIVE: In order to improve health care in geriatric psychiatry, users must be granted a larger role in shaping their treatment. To this aim we identify factors that are essential to psychiatric care from users' perspectives. METHODS: Focus groups and interviews (n = 12) were conducted to identify the health care factors that were most essential to its users. In addition, patients (n = 72) and relatives (n = 62) evaluated the current health care in a questionnaire. RESULTS: The most essential factors were longer consultations with doctors and treatment providers, comprehensive and comprehensible information, individualized procedures and therapies, having clearly defined scopes for each professional group, environmental factors and the integration of relatives into the therapy process. CONCLUSION: The reported factors could help improve health services in geriatric psychiatry by pointing towards potential changes and room for optimization in health care on both structural and process levels.

Assessment of Psychosocial Functioning in a Large Cohort of Patients with Schizophrenia.

BACKGROUND: This study addresses the question of whether psychosocial functioning measured by the Personal and Social Performance (PSP) Scale is related to various psychopathological measures in a cohort of patients with schizophrenia. METHODS: The 'Neuroleptic Strategy Study' (NeSSy) performed at 14 German hospitals between 2010 and 2013 compared two treatment strategies instead of individual drugs. Secondary end-points were the two PSP scales as well as measures of quality of life (SF-36) and the Positive and Negative Syndrome Scale (PANSS). RESULTS: 149 patients were randomised. There was no difference between the two treatment strategies (first-generation versus second-generation antipsychotics) with regard to the PSP. There were differences in doctors' assessments regarding psychosocial functioning compared with patients' own assessments. Furthermore, there were relationships between the PSP and quality of life, level of skills (ICF), and severity of disease (PANSS), level of sexual activities and poor well-being under antipsychotic medication but not with cognitive changes. CONCLUSIONS: The findings on psychosocial functioning of patients with schizophrenia related to severity and skill level could be confirmed. Further findings were the correlation between psychosocial functioning and quality of life, well-being under treatment, and sexuality what emphasizes the substantial importance of a reduced psychosocial functioning.

Factors associated with the onset of major depressive disorder in adults with type 2 diabetes living in 12 different countries: results from the INTERPRET-DD prospective study.

AIMS: To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries. METHODS: People with type 2 diabetes treated in out-patient settings aged 18-65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of 'upset') between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables. RESULTS: In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS. CONCLUSION: This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.

Disturbed time experience during and after psychosis.

Disturbances in time experience have been argued to play a significant, if not causative role in the clinical presentation of schizophrenia. Phenomenological considerations suggest a fragmented or dis-articulated time experience causing both primary symptoms such as hallucinations, delusions, and self-disorders, as well as an intersubjective desynchronization. We employed content analysis on material collected from patients diagnosed with schizophrenia using the Time Questionnaire to generate hypotheses on possible disturbances of time experience in schizophrenia. As a key result we find evidence for the distinction between acute psychotic and post-psychotic syndromes. Acute psychosis is predominantly a disturbance of the passage of time, whereas the remission from psychosis is primarily defined by changes in the experience of the explicit structure of time integrating past, present, and future. We discuss our findings with regards to previous insights and observations on time experience and time perception. We suggest our findings hold significance for the diagnostic and therapeutic understanding of schizophrenia as well as for future integrative research on time experience in general.

Prevalence and correlates of depressive disorders in people with Type 2 diabetes: results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study, a collaborative study carried out in 14 countries.

AIMS: To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries. METHODS: People with diabetes aged 18-65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale. Demographic and medical record data were collected. RESULTS: A total of 2783 people with Type 2 diabetes (45.3% men, mean duration of diabetes 8.8 years) participated. Overall, 10.6% were diagnosed with current major depressive disorder and 17.0% reported moderate to severe levels of depressive symptomatology (Patient Health Questionnaire scores >9). Multivariable analyses showed that, after controlling for country, current major depressive disorder was significantly associated with gender (women) (P<0.0001), a lower level of education (P<0.05), doing less exercise (P<0.01), higher levels of diabetes distress (P<0.0001) and a previous diagnosis of major depressive disorder (P<0.0001). The proportion of those with either current major depressive disorder or moderate to severe levels of depressive symptomatology who had a diagnosis or any treatment for their depression recorded in their medical records was extremely low and non-existent in many countries (0-29.6%). CONCLUSIONS: Our international study, the largest of this type ever undertaken, shows that people with diabetes frequently have depressive disorders and also significant levels of depressive symptoms. Our findings indicate that the identification and appropriate care for psychological and psychiatric problems is not the norm and suggest a lack of the comprehensive approach to diabetes management that is needed to improve clinical outcomes.

[Specific components for integrative and flexible care models according to § 64b SGB V]. / Spezifische Merkmale zur Einstufung der Modellversorgung nach § 64b SGB V.

BACKGROUND: There is a need for a theoretical model for evaluating integrative and flexible care models according to § 64b of the Social Security Statutes Book V (SGB V). MATERIAL AND METHODS: An iterative process of data collection and analysis has been executed according to grounded theory methodology. RESULTS: A total of 11 specific components have been identified and shown to be robust and practicable and compatible with the data from the literature. CONCLUSION: These components can be used for implementation, quality management and evaluation of projects for treatment models according to § 64b SGB V.

Solid-ionic liquid interfaces: pore filling revisited.

The properties of ionic liquids on ordered and non-ordered mesoporous silicas (silica gel, MCM-41, SBA-15) were studied by nitrogen sorption, mercury intrusion and thermogravimetric analyses, as well as (129)Xe-NMR spectroscopy. The ionic liquids investigated are based on the 1-hexyl-3-methylimidazolium cation, which was combined with anions of low (bis(trifluoromethanesulfonyl)imide; [NTf2](-)), medium (trifluoromethylsulfonate; [CF3SO3](-)) to high (acetate; [OAc](-)) basicity. The surface coverage depends on both the type of ionic liquid and support used. This results not only in layer or droplet formation, but also in different physico-chemical properties of the ionic liquid when compared to the bulk, depending mainly on the strength of interaction at the interface. Furthermore, the mercury intrusion analysis of mesopores is shown not to be suitable for supported ionic liquids.

Differential expression of genes encoding tight junction proteins in colorectal cancer: frequent dysregulation of claudin-1, -8 and -12.

BACKGROUND AND AIMS: As integral membrane proteins, claudins form tight junctions together with occludin. Several claudins were shown to be up-regulated in various cancer types. We performed an expression analysis of genes encoding tight junction proteins to display differential gene expression on RNA and protein level and to identify and validate potential targets for colorectal cancer (CRC) therapy. PATIENTS AND METHODS: Amplified and biotinylated cRNA from 30 microdissected CRC specimen and corresponding normal tissues was hybridized to Affymetrix U133set GeneChips. Quantification of differential protein expression of claudin-1, -8 and -12 between normal and corresponding tumour tissues was performed by Western blot analyses. Paraffin-embedded CRC tissue samples, colon cancer cell lines and normal tissue microarray were analysed for protein expression of claudin-1 by immunohistochemistry (IHC). RESULTS: Claudin-1 (CLDN1) and -12 (CLDN12) are frequently overexpressed in CRC, whereas claudin-8 (CLDN8) shows down-regulation in tumour tissue on RNA level. Quantification of proteins confirmed the overexpression of claudin-1 in tumour tissues, whereas changes of claudin-8 and -12 were not significantly detectable on protein level. IHC confirmed the markedly elevated expression level of claudin-1 in the majority of CRC, showing membranous and intracellular vesicular staining. CONCLUSIONS: Differential expression of genes encoding claudins in CRC suggests that these tight junction proteins may be associated to and involved in tumorigenesis. CLDN1 is frequently up-regulated in large proportion of CRC and may represent potential target molecule for blocking studies in CRC.

Follow-up of a pregnancy with risperidone microspheres.

A follow-up of a case of pregnancy with risperidone microspheres is reported. Overall, there was a normal development of the female child during pregnancy and the first 2 1/2 years of her life.

Procesamiento léxico-semántico en un grupo de sujetos sanos: estudio con potenciales relacionados a eventos

resumen está disponible en el texto completo

Abstract: Introduction: An insight into the meaning of words is one of the central processes of semantic memory. To evalúate the access to the cognitive representation of the meaning of words, in the present study we used the lexical decision paradigm developed by Marcos. In this situation, the subject has to recognize if the presented stimulus corresponds to a word or a pseudo-word with the purpose of building a model of normal processing. Once such a model of normal processing is obtained, the findings can be contrasted with pathologies in which semantic memory is altered. Method: The sample consisted of 32 healthy subjects (7 men, 25 women), right-handed and with no personal or familial history of neurological or psychiatric conditions. The average age of the subjects was 34.4 (+ 9.56) years and they had an average educational level of 16.2 (+ 4.4) years. The lexical decision paradigm employed in this study is constituted by 408 stimuli, 240 words and 168 pseudo-words. The criteria for word selection were: frequency, length, grammatical category and morphology. Electroencephalogram (EEG) monopolar recording was obtained from 19 derivations (F3, F4, C3, C4, P3, P4, O1, O2, F7, F8, T3, T4, T5, T6, Fz, Cz and Pz), as well as event-related potentials (ERPs) for the word and pseudo-word sub-states. Results: In the first place, a chi-squared analysis was performed to establish whether significative differences existed between the rates of correct and incorrect answers for both sub-states. The value of chi-squared was 65.7 (gl=1) and significant for p<0.0001. A correlation value of 0.43 (p< 0.02) was found when the educational level and the percentage of correct answers in the sub-sate word were compared. On the other hand, for the pseudo-word sub-state, the value 0.24 was encountered for the same correlation, being statistically non-significant. Pearson's correlation coefficient was also calculated for the educational level variable compared to the mistakes committed when subjects were presented with frequent and infrequent words. In the case of infrequent words, a value of r = - 0.43 (p<0.02) was obtained when the educational level and the number of mistakes were correlated. No correlation was found when the educational level and the number of mistakes commited for frequent words were compared (r = - 0.06). A multivariate variance analysis for repeated measures was performed to determine significant differences between the reaction times when recognizing words or pseudo-words. The outcome showed that all effects were significant in the following cases: reaction times for words and pseudo-words, notwithstanding whether they were correct or incorrect; comparison between correct and incorrect answers, independently of their being words or pseudo-words, as well as the interactions between both effects. To determine differences between average ERPs for both sub-states, Student's T-test was applied with Bonferroni's correction and p<0.0002 as the significance level. Significant differences were encountered between the two sub-states, independently of the age or gender. In the 375-495 ms latency interval, a negative component was appreciated in the pseudo-words case, showing significant differences (p<0.0002) in the following derivations: F3, F4, C3, C4, P3, P4, O1, O2, T3, T5, T6, Fz, Cz and Pz. Amplitude differences between the two sub-states were more evident in Pz and P3 derivations followed by Cz. In addition, a positive component in the 700-795 ms latency interval was detected (mainly in 795 ms) when pseudo-words were presented. Here, the significant differences (p<0.0002) were manifest in the following derivations: F3, C3, P3, F7, T3, T5 and Pz. Amplitude differences between the two sub-states were mainly patent in Pz and P3 followed by C3. Discussion: When analyzing behavioral aspects, subjects made more mistakes when presented with words. However, individuals with less education were the ones committing more mistakes. From this we can infer that this variable may be associated with the range of lexical repertoire. A relation was encountered between educational level and word recognition. With regard to reaction times, significant differences were detected between both sub-states, since the recognition of both words and correct answers was achieved in shorter reaction times. Average reaction times for words and pseudo-words were 819.73 ms and 999.35 ms, respectively. Similarly, the latest potential component appeared in an interval of significant differences between 600 and 940 ms, though with a significance p<0.0005 between 690 and 805 ms. This means that positiveness occurred much sooner than the response, implying that the activity underlying ERPs is related to a cognitive processing of information due to the paradigm used. The analysis of ERPs primary components for both sub-states shows that significant differences arise until 270 ms. The negative component in this study was present between 270 and 580 ms, rendering it similar to N400 given its latency (around 400 ms). Although well-defined in centro-parietal regions, its distribution was generalized, which corresponds to the results of studies using the semantic incongruence paradigm. According to the data from previous research on ERPs, N400 has been associated with the integration process. If this were the case, this association would be equivalent to the semantic incongruence within a lexical integration process described in conventional literature as a "semantic facilitator", only that this time it would be limited to the process of access to the lexicon, which can be interpreted as a discrimination of the answer by assigning a meaning to a word, that is, to process information in the semantic module. This negative component may be related to the generalized response to brain activity when given a meaningless stimulus, i.e., a pseudo-word. Similarly, the wave amplitude may be related to the amount of activation necessary to gain access to the semantic representation of the stimulus in the memory. With regard to the positive component in this study, it is present between 600 and 940 ms and is interpreted as a late P300 (P3b), which has a latency in the 500-1400 ms interval. It is distributed over the centro-parietal region, making it a liable participant in the task categorization process, in which it is necessary to discriminate between the target from the non-target stimulus, and also reflects focalized attentional processes (voluntary) involved in the execution of the task. From the former, it is believed that this component may be related to attentional resources necessary to process the presentation of pseudo-words. Research dealing with the P600 component locate it within the context of statements and associate it with an anomaly in statement syntax. Therefore, even though the positive component lies within the P600 latency domain, this particular component was not considered as being present in this study, because a syntax incongruence paradigm was not used. Finally, the contribution of the present study lies in the finding of N400 and "P600" components, which have been reported when the "semantic facilitator" and the syntax incongruence paradigm were respectively used, but had not been observed when a lexical decision paradigm based on word recognition per se was utilized. Similarly, given that our results stem from a sample of healthy subjects, a comparison can be made with a patient population with semantic memory alterations.

[The role of philosophy in psychiatry]. / Philosophie in der Psychiatrie.

Philosophy as a basic study for psychiatry is again attracting interest. Scientific observations in this field are supplementary to empirical science and provide a needed balance to empirical results. In this article we consider the interdisciplinary relationship of both fields and examine its present institutional application.

Pharmacotherapy of personality disorders in German speaking countries: state and changes in the last decade.

BACKGROUND: In many cases, patients with personality disorders currently receive psychopharmacological treatment as well as psychotherapy. Empirically oriented studies of outcome and efficacy are still rare, and clinical practice is still dominated by a symptomatic and rather pragmatic approach. AIM: This study provides empirical insight into the reality of psychopharmacological practice in psychiatric institutions in German speaking countries. METHOD: The use of psychotropic drugs in patients with personality disorders is demonstrated using the data base of the AMSP drug safety program. Recent changes are shown by comparing results from 1996 and 2003. RESULTS: Our data show a symptom-driven, polypragmatic, and often off-label use of psychotropic drugs in personality disorders.

[The present status of Japanese psychopathology. A summary of the World Congress of Psychiatry in Yokohama]. / Die gegenwärtige Situation der japanischen Psychopathologie. Ein Rückblick auf den Weltkongress der Psychiatrie in Yokohama.

The last World Congress of Psychiatry took place in Yokohama, Japan. It gave the opportunity for presenting specifically Japanese approaches to psychopathology to the international psychiatric community. This paper reports on prominent trends in Japanese psychopathological research, which has close ties to German psychopathology

Rivastigmin and impaired motor function.

In this case study, we describe the case of an 88-year-old female patient diagnosed with Alzheimer's disease who developed a severe motor dysfunction as a side effect of rivastigmin treatment. There have been reports on motor dysfunctions caused by other choline esterase inhibitors.

Complete sequencing and mRNA expression analysis of the MEN-I gene in adrenal myelolipoma.

The molecular pathogenesis of adrenal myelolipoma is unclear. Endocrine activity of these tumors and association with other endocrine tumors have stimulated the hypothesis that it may belong to the group of sporadic tumors caused by defects of the gene responsible for multiple endocrine neoplasia type I (MEN-I). DNA of blood and tumoral sections from two patients with adrenal myelolipoma were analyzed by examination of variable number of tandem repeats (VNTR) loci PYGM, D11S987, D11S480, and D11S449 on chromosome 11q13 and by complete direct DNA sequencing of all coding exons and splice junctions of the MEN-I gene. Menin expression was examined by RT-PCR. RT-PCR did not detect menin expression in one adrenal myelolipoma. No loss of heterozygozity on chromosome 11q13 was identified. Intragenic heterozygozity was retained in codon 418 of the menin gene in both patients. No mutation was identified in the coding exons of the menin gene. Complete DNA sequencing yielded no hint that defects of the MEN-I gene are responsible for the formation of adrenal myelolipomas. Adrenal myelolipomas do not share the loss of heterozygozity on chromosome 11q13 observed in some benign adenomatous and many malignant adrenocortical tumors.

Complete sequencing and messenger ribonucleic acid expression analysis of the MEN I gene in adrenal cancer.

Adrenal cancer is a rare sporadic disease that has also been observed in the context of multiple endocrine neoplasia type I (MEN I). Adrenal lesions occur in up to 40% of MEN I patients. Loss of heterozygosity of the 11q13 band harboring the menin gene has been reported in more than 50% of patients with adrenal cancer. Despite this high index of suspicion, former screening studies did not reveal mutations of the MEN I gene in 28 patients. We identified loss of heterozygosity of 11q13 microsatellites in five of five patients (100%). In 40%, heterozygosity was retained in codon 418 of the MEN I gene. Complete direct DNA sequencing data of the entire coding region and adjacent splice sites of the MEN I gene were obtained in 14 patients with sporadic adrenal cancer. In only one of them a heterozygous missense mutation, R176Q (exon 3), was identified. Due to the heterozygous pattern and unknown biological effect of this mutation, it is not clear whether there is a causal relationship with adrenal cancer. The total mutation frequency in sporadic adrenal cancer is 1 of 14 (7%). Menin messenger RNA expression was identified in 14 of 14 patients (100%). Transcriptional inactivation of the menin gene is, hence, unlikely to cause loss of its tumor suppressor function in adrenal cancer. Furthermore, we examined three patients who presented adrenal cancer in the context of sporadic multiglandular endocrine tumor disease previously diagnosed on clinical grounds to be MEN I syndrome. An opal stop codon mutation was identified in codon 126 (exon 2) in the adrenal cancer of one of these patients. Formation of the adrenal cancer in this patient may be rather coincidental because the mutation was present in a heterozygous pattern. There was no mutation of the menin gene in the two other patients. This may mean that formation of adrenal cancer in the context of multiglandular endocrine disease denotes an entity different from MEN I in some patients.

MEN I gene mutations in sporadic adrenal adenomas.

Loss of heterozygosity (LOH) on chromosome 11q13 occurs in about 20% of sporadic adrenal neoplasms. Adrenal lesions, mostly benign, occur in up to 40% of patients from MEN I kindreds. The MEN I gene, positioned on 11q13, has been considered a primary candidate gene in these lesions. We studied a group of 15 patients with sporadic adrenal adenoma, and 1 patient with multinodular hyperplasia. Of the 16 patients, 4 had incidentally discovered masses, 5 had Conn's syndrome, 6 suffered from Cushing's syndrome, and 9 had high sex hormone production. Studies with the markers D11S480, PYGM, D11S449, and D11S987 in 13 patients (12 of whom were from our group of 16) revealed 4 losses of heterozygosity on D11 S480 on 11q13, but the deletion did not affect the MEN I gene in any case. We present complete direct DNA sequencing data of the menin gene in 14 sporadic adrenal adenomas and one with adrenal hyperplasia. We identified one heterozygous missense mutation, T552S, in a hormonally inactive adrenal adenoma. One base exchange was identified close to the intron-exon boundary in intron 9 of a nodular adrenal hyperplasia. mRNA expression studies found that MEN I was transcribed in all 13 samples analyzed. In summary, our study identified the second patient with sporadic benign adrenal tumor presenting a menin gene mutation. Our complete direct sequencing approach adds evidence that menin gene mutations may account only for a minority of benign adrenal tumors if at all. Another tumor-suppressor gene inactivated in sporadic adrenal neoplasms may be located on chromosome 11q13.

[Differential diagnosis of distal peripheral nerve compression syndrome of the tibial nerve. Case report of primitive neuroectodermal tumor]. / Zur Differentialdiagnose distaler peripherer Kompressionssyndrome des N. tibialis. Fallbericht eines primitiven neuroektodermalen Tumors.

Tumors of the tibial nerve are not sufficiently taken into account in the diagnosis of tarsal tunnel syndromes (TTS). They may present with atrophy of the plantar flectors and with disturbances of sensory functions, but far more commonly with pain. Diagnosis is often only achieved after 1-2 years. Taking tumors into account when examining patients presenting with TTS may lead to a more rapid diagnosis and to improvement in patients' prognoses. We present the case of a 37-year-old female in whom a primitive neuroectodermal tumor (PNET) was found to be the cause of long-standing pain in the right foot.