Psychophysiological correlates of peritraumatic dissociative responses in survivors of life-threatening cardiac events

The psychophysiological startle response pattern associated with peritraumatic dissociation (DISS) was studied in 103 survivors of a life-threatening cardiac event (mean age 61.0 years, SD 13.95). Mean time period since the cardiac event was 37 (79 IQD) months. All patients underwent a psychodiagnostic evaluation (including the Peritraumatic Dissociative Experiences Questionnaire) and a psychophysiological startle experience which comprised the delivery of 15 acoustic startle trials. Magnitude and habituation to trials were measured by means of electromyogram (EMG) and skin conductance responses (SCR). Thirty-two (31%) subjects were indexed as patients with a clinically significant level of DISS symptoms. High-level DISS was associated with a higher magnitude of SCR (ANOVA for repeated measures p = 0.017) and EMG (p = 0.055) and an impaired habituation (SCR slope p = 0.064; EMG slope p = 0.005) in comparison to subjects with no or low DISS. In a subgroup analysis, high-level DISS patients with severe post-traumatic stress disorder (PTSD; n = 11) in comparison to high-level DISS patients without subsequent PTSD (n = 19) exhibited higher EMG amplitudes during all trials (repeated measures analysis of variance IF = 5.511, p = 0.026). The results demonstrate exaggerated startle responses in SCR and EMG measures - an abnormal defensive response to high-intensity stimuli which indicates a steady state of increased arousal. DISS patients without PTSD exhibited balanced autonomic responses to the startle trials. DISS may, therefore, unfold malignant properties only in combination with persistent physiological hyperarousability. Copyright (C) 2002 S. Karger AG, Basel

Clinical development of two innovative pharmaceutical forms of leuprorelin acetate

Objectives: Two innovative pharmaceutical forms of leuprorelin acetate have been developed as 1-month and 3-month implants for the treatment of advanced hormone-dependent prostate cancer. These products contain active substance dispersed homogeneously in a biodegradable polymer. Here we present the key results from the clinical development of these slow-release implant formulations of leuprorelin. Methods: Two therapeutic studies of the 1-month implant were performed: a randomized, controlled study comparing the leuprorelin implant with leuprorelin prolonged-release microspheres (Enantone) as the active control; and a single-arm study of the leuprorelin implant. For the 3-month implant, four therapeutic studies were performed: a randomized, controlled study comparing the leuprorelin implant with leuprorelin prolonged-release microspheres (Trenantone) as the active control; a single-arm study of the leuprorelin implant; and two long-term studies with the 3-month implant administered twice, either 12 or 16 weeks apart. A pooled analysis of data from the comparator-controlled and single-arm studies of the 3-month implant was also conducted. The main inclusion criterion for all studies was histologically confirmed advanced prostate cancer, with primary endpoints based around successful testosterone suppression (≤0.5 ng/ml). Results: In the comparator-controlled studies, both implants were as effective as the microspheres for achieving successful testosterone suppression and normalization of prostate-specific antigen (PSA) levels. Data from the single-arm and long-term studies were consistent with those from the comparator-controlled studies. In the pooled analysis, significantly more patients treated with the 3-month implant achieved successful testosterone suppression compared with the comparator ( p ≤ 0.01). The safety profile of the implants in the comparator-controlled studies was similar to that of the prolonged-release microsphere formulation, and consistent with that of the luteinizing hormone-releasing hormone agonist class. Conclusions: The innovative 1-month and 3-month implants of leuprorelin acetate are at least as effective as leuprorelin acetate prolonged-release microspheres for achieving successful testosterone suppression and normalization of PSA in men with advanced hormone-dependent prostate cancer, with a comparable safety profile