Phase II dose escalation study of caspofungin for invasive Aspergillosis.

Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥ 4 in 2 of 8 patients or ≥ 3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics were linear across the investigated dosages and followed a two-compartment model, with weight as the covariate on clearance and sex as the covariate on central volume of distribution. Simulated peak plasma concentrations at steady state ranged from 14.2 to 40.6 mg/liter (28%), trough concentrations from 4.1 to 11.8 mg/liter (58%), and area under the concentration-time curve from 175 to 500 mg/liter/h (32%) (geometric mean, geometric coefficient of variation). Treatment was well tolerated without dose-limiting toxicity. The rate of complete or partial responses was 54.3%, and the overall mortality at 12-week follow-up was 28.3%. In first-line treatment of invasive aspergillosis, daily doses of up to 200 mg caspofungin were well tolerated and the maximum tolerated dose was not reached. Pharmacokinetics was linear. Response rates were similar to those previously reported for voriconazole and liposomal amphotericin.

[The curriculum for rotation physicians within the CHIR-Net]. / Kurrikulum für Rotationsärzte im CHIR-Net.

INTRODUCTION: CHIR-Net is a German national surgical network for clinical trials. It is supported by the Federal Ministry for Education and Research (BMBF 01GH0605) to establish infrastructure and expertise in the conduct of clinical trials within the surgical disciplines. An important aspect of this network is a qualified advanced training for physicians deployed at the CHIR-Net as part of a job rotation. METHODS: A catalog of activities for the time of rotation within the network has been developed in cooperation with the CHIR-Net, the deployed physicians and cooperating regional clinical trials centers (ZKS/KKS). RESULT: The focal points of the physicians' rotation in the CHIR-Net are outlined in a curriculum that has been established and evaluated in the network since January 2008. CONCLUSION: After the rotation time at the CHIR-Net the skilled physicians act as multipliers of specialized knowledge on clinical research. In this way the acquired expertise will be transferred into clinical practice and treatment of patients within research projects will benefit directly.

[Poriomania chronica?]. / Poriomania chronica?

Based on a case study and the classic French concept of "monomania," the development of the psychiatric term "poriomania" is discussed. It is suggested that poriomania should still be regarded as a specific psychopathological symptom that can be part of various syndromes. The fate of monomanias is shown using examples whose traits are followed according to modern operationalized classification systems.

[Psychiatric doppelganger phenomena with special consideration of the Capgras syndrome] . / Psychiatrische Doppelgängerphänomene unter besonderer Berücksichtigung des Capgras-Syndroms.

The present paper classifies and analyzes the experience of the "double" in depth. Main focus is on the Capgras experience--certainly the best known phenomenon of the double--and its possible etiology is examined. Moreover, a few other delusional experiences of mis-identification of person are also considered, such as the Frégoli phenomenon, the syndrome of subjective doubles, intermetamorphosis as well as other variants described in the literature.

[Heautoscopy. Delusions of a double and rare hallucinations of personal gestalt]. / Heautoskopie. Doppelgängerphänomen und seltene Halluzination der eigenen Gestalt.

In the psychiatric literature, the phenomenon of the doppelganger or double is characterized into different types of delusional misidentification syndromes and heautoscopic symptoms. Specifically, we focus attention on heautoscopy, which might also be named "dissociative" after excluding an organic etiology. We report a case of heautoscopy in a woman and discuss the clinical variability of this psychopathological phenomenon. Furthermore, a short treatment of the historical and literary implications of this delusion is presented.

[Psychopathological concepts of induced insanity exemplified by folie a deux]. / Psychopathologische Konzepte des induzierten Irreseins am Fallbeispiel einer folie à deux.

We report on a case of a "folie à deux" between sister and brother (56 and 61 years of age). Based on a definition of the concept of the induced psychoses, we focus attention on some special aspects of these double psychoses. Special consideration is given to psychopathological constellations and their meaning, with etiogenetic aspects of "process" and "development" with regard to the concept of vulnerability. We could show that in such cases the new operationalised diagnostic manuals like DSM-IV and ICD-10 are based on traditional concepts.

[Communicated insanity, folie a deux and shared psychotic disorder. Different concepts and a case from Mallorca]. / Induziertes Irresein, Folie à deux und gemeinsame psychotische Störung. Verschiedene Konzepte und ein Fallbeispiel auf Mallorca.

Following an earlier description of the psychopathological conceptions of "communicated insanity" we focus on a remarkable difference concerning the development of the historical terminology. The current operationalized definition is oriented at the originally French conception of the "folie à deux" which includes an adoption of certain delusional ideas by an intimate other. Compared with that, in the German psychopathological tradition those cases were also included in the conception of the "induziertes Irresein", in which the shocking experience of another's psychosis may cause a psychotic illness of somebody else. In modern psychiatric terminology this kind of "induction" is rather disregarded. We report a case of an induced psychosis in two women and give particular attention to the German psychopathological tradition because of still existing clinical relevance.

[Post-traumatic stress disorder and delusions. A case report]. / Posttraumatische Belastungsstörung und Wahnentwicklung. Ein Fallbeispiel.

The present paper initially discusses the possible transitions existing between posttraumatic stress disorder (PTSD) and delusional disorder. With respect to the latter, the main focus is on the psychopathological concept of the so-called sensitive delusion of reference. A patient who developed a delusional disorder secondary to PTSD, which had been precipitated by his involvement in a serious auto accident, is then described. The details of this case seem to lend some support to the hypothesis of a clinical continuum provided that the "trauma" found in PTSD, on the one hand, and the "crucial experience" associated with the sensitive delusion of reference, on the other, positively correlate with the presence of prominent sensitive traits of personality.

[Ethical conflicts in involuntary treatment of schizophrenic patients; decision-making and in influential factors in three prototype cases]. / Ethische Konflikte bei der Zwangsbehandlung schizophrener Patienten. Entscheidungsverhalten und Einflussfaktoren an drei prototypischen Fallbeispielen.

Three case reports of patients with schizophrenia were presented to a sample of 520 persons (25.1% psychiatrists, 3.7% psychologists, 8.1% social workers, 14.6% nurses, and 48.6% others). The decisions for involuntary admission to a psychiatric hospital and involuntary treatment were questioned. In case 1 (young man, first episode, delusions, extreme social withdrawal), 71.7% supported admission to hospital and 62.7% were in favor of neuroleptic treatment. In case 2 (woman with disorganized syndrome beating her 74-year-old mother), 84.6% supported hospitalization and 78.8% neuroleptics. In case 3 (relapsed multi-episode patient, increasingly neglected, delusional, and socially withdrawn), 56.3% supported hospitalization and 52.7% neuroleptics. Generally, psychiatrists' decisions were very similar to those of other professionals and laypersons, while social workers more often rejected involuntary treatment. After professional status, multivariate analyses revealed older age as the most significant variable for support of involuntary treatment. Frequency of experience with mentally ill persons were only weak predictors or not significant.