Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs)

Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands that exert clinically relevant tissue-selective progesterone agonist, antagonist, partial, or mixed agonist/antagonist effects on various progesterone target tissues in an in vivo situation depending on the biological action studied. The SPRM asoprisnil is being studied in women with symptomatic uterine leiomyomata and endometriosis. Asoprisnil shows a high degree of uterine selectivity as compared to effects on ovulation or ovarian hormone secretion in humans. It induces amenorrhea and decreases leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations. It also has endometrial antiproliferative effects. In pregnant animals, the myometrial, i.e. labor-inducing, effects of asoprisnil are blunted or absent. Studies in non-human primates played a key role during the preclinical development of selective progesterone receptor modulators. These studies provided the first evidence of uterus-selective effects of asoprisnil and structurally related compounds, and the rationale for clinical development of asoprisnil

Biological flora of Central europe: Baldellia ranunculoides (Alismataceae)

Baldellia ranunculoides (L.) Parl. (Alismataceae) is a taxonomically problematic aquatic plant with an historically ill-defined distribution and global conservation status. This paper finds morphological, ecological and molecular evidence for two distinct taxa, probably best described as subspecies: (1) B. ranunculoides subsp. ranunculoides and (2) B. ranunculoides subsp. repens and provides detailed distribution data on their overlapping range, in different habitats, across the cool, high rainfall areas of western Europe and west Mediterranean. The two subspecies are amongst the relatively large number of threatened European and north Africa aquatic plants and this paper provides a systematic review of their relative conservation pressures and management needs, with particular emphasis on the status of both taxa in central Europe. Other observations indicate probable evolutionary relationships within B. ranunculoides s.l. and its associated taxa and the review points out where these and other research topics could potentially be pursued

The utility of standardized advance directives: the general practitioners' perspective

Advance directives (AD) are written documents that give patients the opportunity to communicate their preferences regarding treatments they do or do not want to receive in case they become unable to make decisions. Commonly used pre-printed forms have different formats. Some offer space for patients to (a) appoint a surrogate decision maker, and/or (b) to determine future medical treatments and/or (c) give a statement of personal values. So far it is unknown which forms GPs preferably use and why they decide to do so. 23 semi-structured interviews with GPs were analysed using content analysis. Interviewees mainly use short templates (to appoint surrogate decision makers) and medium length templates with checkboxes to indicate patients' preferences in regards to life prolonging measures. Especially when patients faced the progression of a disease, participants use the latter version. Only then, the interviewees remarked, patients are capable to rate concrete situations reliably. GPs also realize the importance of the verbal assessment of patients' preferences; however they rarely keep a written form of the conversation. Some GPs hand out one or more templates and ask their patients to read and think about them at home with the option to talk to them about it later on, while others prefer their patients to fill them out alone at home. Regardless of template usage, most GPs emphasize that ADs require regular updates. GPs tend to see standardized advance directives mainly as a tool to start a conversation with their patients and to identify their real preferences and values. When the patient is still not facing the progression of an already existing disease it could be sufficient to only appoint a surrogate decision maker instead of creating a full AD. However, in all other situations, appointing a surrogate decision maker should be backed up by a written statement of a patient's general values. Patients and their relatives should always have the opportunity to ask their GP for medical advice when drafting an AD. It is crucial to regularly verify and update existing ADs within the course of a disease