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Radiopharmacy at ETH has worked on the development of novel PET tracers for neuro-, cardiac- and tumor imaging for many years. In this paper, our efforts on targeting the glutamatergic system of the metabotropic glutamate receptor subtype 5 (mGluR5) and the ionotropic N-methyl-D-aspartate (NMDA) receptor are summarized. We briefly described the principles of positron emission tomography (PET) tracer development for the central nervous system (CNS) and the radiolabeling methods used in our laboratory. To assess the radioligands, results of in vitro autoradiography, biodistribution, and metabolite studies as well as PET imaging data are discussed. Furthermore, key PET parameters for kinetic modeling and quantification methods are provided. Two mGluR5 PET tracers, [11C]ABP688 and [18F]PSS232, were translated in our GMP labs and evaluated in human subjects. The newly developed GluN2B PET tracer [11C]Me-NB1 is currently being investigated in a first-in-human PET study and several F-18 labeled tracers are being evaluated in non-human primates in which the first-in-class will be translated for human studies.

Objectives: Are there typical patterns of outpatient psychotherapy among depressed patients? What characterizes patients with different patterns?, Methods: We examined N= 548 patients with primary depressive disorders using a naturalistic design. Using a latent-state-mixture model and depression measures at baseline, therapy end and 1-year follow-up we found a total of five patterns. Subgroups were compared with respect to sociodemographic and treatment-related variables., Results: Responders with moderate depressive symptoms at baseline and responders with severe symptoms at baseline were most common (54% and 25% of the sample, respectively) compared to late responders (9 %), small-response patients (9 %) and recidivists (4 %). Patterns of change were related to symptom intensity at baseline and ratings of perceived helpfulness at the end of treatment., Conclusions: Since psychometric scales better predicted change pattern than sociodemographic characteristics, primary and secondary diagnoses, psychometric assessments and feedback systems could be a useful supplement to traditional quality assurance procedures.

Objective: Because premature discontinuation of psychotherapy limits the effectiveness of the interventions, in a naturalistic design we examined the prevalence, predictors, and outcome of premature discontinuation., Methods: The sample included N = 584 patients with various mental disorders. Risk factors were identified using regression analysis. As outcome Patient Health Questionnaire scales were considered. We compared pre and post averages as well as post averages of premature discontinuation versus regular termination., Results: Risk factors were: female and/or unemployed patient, low patient and/or therapist ratings regarding therapy success, and extraordinarily high therapist ratings of the therapeutic alliance. Despite premature discontinuation we found significant reductions of depression, anxiety, somatic symptoms, and stress (ES = 0.30, …, 0.44). Compared to regular termination though, patients with premature discontinuation were more impaired at last measurement (ES = 0.17, …, 0.37)., Conclusion: Not each premature discontinuation is a psychotherapeutic failure. Warning signals for looming premature discontinuation are low ratings of therapy success while psychotherapeutic treatment., (© Georg Thieme Verlag KG Stuttgart · New York.)

Due to the treatment costs, extensions of the standard therapy duration are a matter of critical examination. This study investigates which factors characterize patients with treatment extensions in the German health system and how effective these extensions are for a reduction of the patients' symptoms. We analysed a disorder heterogeneous sample of 810 patients. We found that therapy extensions are more common among with more severe mental disorders, when the therapeutic relationship is positive, and little therapy success has been achieved during the standard duration. Overall, the findings suggest that outpatient psychotherapy is mainly extended for patients with a low symptom reduction after the standard therapy duration and that therapy extension allows a symptom reduction that could not have been achieved otherwise., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To assess and compare the validity of the German 15-item version and shortened versions of the Geriatric Depression Scale (GDS) for early detection of depression in nursing home residents with mild to moderate cognitive impairment (MMSE ≥ 15)., Methods: Data from 92 patients were analysed. The Structural Clinical Interview for DSM-IV (SCID) was used as the gold standard. The diagnoses covered in this assessment were current major depression (MD) and minor depression (MinD). The performance of the GDS scales was evaluated using receiver operating characteristics (ROC). Main outcome measures were AUC (area under curve) values, as well as sensitivity and specificity., Results: Overall diagnostic validity of the GDS-15 was better for MD than for MinD (AUC: 89.7 % and 73.4 %, respectively). In assessing MD, AUC values as well as sensitivity and specificity were comparable for the GDS-15 and the GDS-8. A cut-off point ≥ 5 on the GDS-8 gave optimum performance (sensitivity: 76.9 %, specificity: 88.6 %). For the best cut-off point ≥ 2, the corresponding values of the GDS-4 were 53.8 % and 92.4 %., Conclusions: The GDS-8 appears to be a less time-consuming alternative for the nursing home setting. However, the GDS-4 is not suitable for this population., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Depression is common in nursing home residents, but is still underrecognized. Screening for depression could be a first step to increase recognition rates within this high-risk group. Therefore, we investigated the validity of the WHO (Five) Well-Being Index (WHO-5) for early detection of depression in nursing home residents., Methods: The Structural Clinical Interview for DSM-IV (SCID) was used as the gold standard for the validation of the WHO-5. The diagnoses covered in this assessment were both current major depression as well as minor depression according to DSM-IV research criteria., Results: In our sample of 92 nursing home residents in Munich aged 65-97 years, (73.9% female, 26.1% male) 14.1% fulfilled the criteria of major depression and again 14.1% fulfilled the criteria of minor depression in the SCID. Overall diagnostic validity (area under the ROC curve) of the WHO-5 was .90 (95% confidence interval: .84- .97). The best cut-off-point according to Youden's index yielded a sensitivity of .92 and a specificity of .79., Conclusions: The diagnostic accuracy of the WHO-5 in our study is promising. The WHO-5 might be an efficient screening tool for nursing home residents, but results have to be replicated in a larger sample.

Depressive disorders rank among the most frequent mental disorders in the elderly. Especially in the elderly, depressive disorders are still underrecognized and not sufficiently treated. In view of the associated risks and complications, early and timely recognition of depressive disorders is essential to avoid exacerbation and chronic manifestation of the depressive symptoms and to antagonize the increased suicide risk as well as negative effects on concomitant somatic diseases. More than any other occupational group, geriatric caregivers have a key position in the contact with clients, relatives and treating primary care providers. Therefore, 3487 geriatric caregivers from 448 outpatient nursing services throughout Bavaria participated in 196 four-hour training courses about depressive disorders and suicidality in the elderly between March 2006 and August 2007. Aim of this activity was to reduce attitudes enclosed in a wall of prejudice and to teach specific knowledge about depression and suicidality in the elderly. This training was evaluated using specially tailored questionnaires which were completed immediately before and after the continuing education as well as three months later (at follow-up). The analysis included the individual changes of 473 participants in longitudinal sections. Pronounced knowledge deficits and reservations were found regarding pharmacotherapy with antidepressants and suicidality. In this context, significant changes in all categories were present. Especially pronounced effects were found for the attitudes towards depression and suicidality as well as treatability with antidepressants. These changes were stable, as indicated by the follow-up evaluation.

HSP90's are overexpressed in different cancer types and they probably are required to sustain aberrant signalling in malignant cells. Recently, pharmacological inhibition of HSP90 was found to suppress growth of myeloma cell lines and in primary myeloma cells. Therefore, we wanted to investigate the role of HSP90alpha and HSP90beta in the pathogenesis of malignant myeloma (MM) in more detail. Immunohistochemistry was employed to examine the expression of HSP90alpha and HSP90beta in MM. The importance of HSP90 for survival of MM -cells was investigated by SiRNA-mediated knockdown of HSP90 and blockade of the IL-6R/STAT3 and the MAPK signaling pathways in vitro. HSP90alpha and HSP90beta were overexpressed in majority of investigated MM cases, but not in MGUS or in normal plasma cells. SiRNA-mediated knockdown of HSP90 or treatment with the novel HSP90 inhibitor 17-DMAG attenuated the levels of STAT3 and phospho-ERK and decreased the viability of MM cells. The knockdown of HSP90alpha was sufficient to induce apoptosis. This effect was strongly increased when both HSP90s were targeted, indicating a cooperation of both. HSP90 critically contributes to myeloma survival in the context of its microenvironment and therefore strengthen the potential value of HSP90 as a therapeutic target.

Two cases of abdominal pregnancy are presented. Since this type of pregnancy has an incidence rate of 1.6% of all ectopic pregnancies only, it must be classified as a rare occurrence. Even more so, an advanced abdominal pregnancy with a viable foetus is an absolute rarity. The most frequent signs are abdominal pain, nausea and vomiting, unclear blood loss, and painful foetal movements. If the diagnosis is clear in an early stage of pregnancy, rapid laparotomy is mandatory. In advanced pregnancy with viable foetus, the viability must be improved under clinical control. After delivery, management of the placenta is the greatest problem. The best results are obtained if the placenta can be removed safely. If it must be left in situ, the effectivity of methotrexate therapy has not been established.

A study of leaf anatomy, chloroplast ultrastructure, labelling pattern after short-time (14)CO2 fixation, and CO2 compensation point indicates that Chamaesyce buxifolia (Engelm. ex Hitche.) Small (Geraniales), Pectis leptocephala (Cass.) Urb. (Campanulales), and Imperata arundinacea Cyr. (Graminales) have typical features of plants exhibiting the C4-dicarboxylic acid pathway of photosynthesis. Thus it is established that the correlation of these C4 properties, well known in various orders of Monocotyledons (Graminales, Cyperales) and in the dicotyledonous order of the Centrospermae, is also characteristic of some species in other systematically widely separated orders within the Dicotyledons.

NaCl-treated young plants of Mesembryanthemum crystallinum undergo specific cytological changes which are accompanied by distinct alterations in CO2 gas exchange reactions. Prior to salt treatment mesophyll cells are quite normal. Only lomasome-like structures extrude from the cytoplasm into the vacuole. CO2 gas exchange is that of a Calvin-plant. Later on NaCl-treated plants differ from control plants in several respects. They show the CO2 gas exchange reactions typical for CAM-plants. Electron microscopy clearly shows the formation of new vacuole-like spaces just under the chloroplasts between plasmalemma and cell wall, which are mostly filled with structures similar to "Hecht'sche Fäden" of plasmolyzed cells. In many cases a large amount of vesicles and membranes can be observed in the central vacuole, at least some of which are in connection with cytoplasm and even chloroplasts. Chloroplasts themselves sometimes seem to be damaged by high concentrations of NaCl. While having a more distinct crassulacean acid metabolism, old NaCl-treated plants exhibit features of aged cells: cytoplasm becomes empty and vacuolized, stoma thylacoids are reduced.Not only the described changes in fine structure but also the altered CO2 gas exchange reactions take place when glycophytic control plants grow older, thus indicating that NaCl may accelerate the normal ageing process in Mesembryanthemum crystallinum.