Negative symptoms in schizophrenia: considerations for clinical trials

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.     

Meta-analysis of randomized controlled comparisons of psychopharmacological and psychological treatments for anxiety disorders.

BACKGROUND: A number of meta-analyses have led to contradictory results regarding the efficacy of the psychological and pharmacological treatment of anxiety disorders. The main reasons for these inconsistent results seem to be the inclusion of heterogeneous studies and influences of selection biases. We performed a meta-analysis, which only included studies using a direct comparison of pharmacological, psychological, or combined treatments. METHOD: Sixteen studies on panic disorder, six studies on social anxiety disorder, and two studies on generalized anxiety disorder have been analyzed. Effect sizes for differences between the different treatment modalities were calculated. Also, the effect sizes of the pre-post differences were calculated. RESULTS: Pharmacological treatment, cognitive-behavioural treatment, and the combination of both treatment modalities all led to substantial improvement between pre- and post-treatment. Combined pharmacological and psychological treatment was superior to the monotherapies for panic disorder. For social anxiety disorder, there is only preliminary support for combined treatment. Due to lack of sufficient data, no final conclusions can be drawn for generalized anxiety disorder. CONCLUSIONS: While drug treatment and CBT showed equal efficacy, only in panic disorder the combination of pharmacological and psychological treatment was superior to either treatment alone. For the other anxiety disorders, the evidence for greater efficacy of combination treatment is still not sufficient due to lack of studies.     

Chronische Diarrh?en unter NSAR

Ohne Zusammenfassung     

Taste bud development in the zebrafish, Danio rerio.

Taste buds are chemosensory endorgans consisting of modified epithelial cells. Fish and other vertebrates use their taste bud cells to sample potential food, either selecting or rejecting substances according to their edibility. The adult gustatory system in fish has been studied thoroughly, including regeneration experiments. Taste buds occur in the epithelia of the lips, the mouth cavity, the oropharyngeal cavity, and also in the skin of the barbels, the head, and sometimes even all over the body surface. Despite its importance for feeding, little is known about the ontogeny of the fish taste system. We examined the development of taste buds in the zebrafish on the light microscopical and the scanning and transmission electron microscopical levels. Taste buds develop later than the olfactory organ and the solitary chemosensory cells, two other chemosensory systems in aquatic vertebrates. The first few taste bud primordia are visible within the epithelia of lips and gill arches 3 to 4 days after fertilization, and the first few taste buds with open receptor areas appear on the lips and simultaneously on the gill arches 4-5 days after fertilization, which coincides with the onset of feeding. Taste buds in the mouth cavity, on the head, and on the barbels are formed later in development. As seen in other fish, zebrafish taste buds contain elongate dark and light cells, termed according to their electron density. Dark cells with a cell apex of many short microvilli appear first, followed by the light cells with one large microvillus. In addition, the zebrafish has a third fusiform cell type, which appears last. This cell type is low in electron density and has a brush-like apical ending with several small microvilli. This cell type has not been described previously. Furthermore, in zebrafish, the ontogenetic processes of taste bud formation differ from regenerative processes described in the literature.     

THz radiation from free electron lasers and its potential for cell and tissue studies

Free electron lasers (FELs) allow the generation of electromagnetic radiation (EM) in a wide field of frequencies (respectively wavelengths) through the proper adjustment of the energy of an electron beam and the field configuration of a magnetic undulator passed by this beam. Terahertz (THz) radiation covers the region of the electromagnetic spectrum between approximately 0.3 and 30 THz and thus can be considered a continuation of the optical spectrum beyond the far infrared (IR). The very interesting results obtained from various studies of the interaction between IR radiation and biomolecules or tissue have stimulated increasing interest in the study of biological systems using THz radiation. This paper points out what role modern FELs can play in this research.     

Evidence for the existence of different receptor sites for algesic agents at the endings of muscular group IV afferent units

Summary The hypothesis that different receptor sites for algesic agents exist at free nerve endings in skeletal muscle has been tested by administering bradykinin and 5-hydroxytryptamine (5-HT) repeatedly in anaesthetized cats and evaluating the response behaviour of single group IV afferent units from the gastrocnemius-soleus muscle.Repeated intraarterial administration of bradykinin at intervals of 1 and 2 min usually elicited fibre responses without tachyphylaxis. Injections of equieffective doses of 5-HT, however, given in the same manner evoked fibre reactions that were strongly tachyphylactic. In units responding to both bradykinin and 5-HT a refractoriness to 5-HT could be induced by repeated injections of this agent without impairing the stimulating potency of bradykinin on the same nerve ending. Such a lack of cross-tachyphylaxis seems to apply also to the effects of histamine on one side and bradykinin or 5-HT on the other.These findings suggest that bradykinin, 5-HT and probably histamine exert their excitatory action on muscular group IV afferent units via different receptor sites.     

Prostaglandin D synthase (beta-trace) in healthy human sleep

STUDY OBJECTIVES: The prostaglandin D system plays an important role in animal sleep. In humans, alterations in the prostaglandin D system have been found in diseases exhibiting sleep disturbances as a prominent symptom, such as trypanosoma infection, systemic mastocytosis, bacterial meningitis, major depression, or obstructive sleep apnea. Assessment of this system's activity in relation to human physiologic sleep was the target of the present study. DESIGN: Serum concentrations of lipocalin-type prostaglandin D synthase (L-PGDS, former beta-trace), and plasma levels of the pineal hormone melatonin were measured in 20 healthy humans (10 women, 10 men; aged: 23.3 +/- 2.39 years) at 4-hour intervals over a period of 5 days and nights, which included physiologic sleep, rapid eye movement sleep deprivation, and total sleep deprivation. In addition, the serum L-PGDS and plasma melatonin levels of 6 subjects were determined under conditions of bright white (10,000 lux) or dark red light (< 50 lux) in a crossover design during total sleep deprivation. Nocturnal blood sampling was performed by a through-the-wall tube system. L-PGDS was measured by an automated immunonephelometric assay, and melatonin was analyzed by direct radioimmunoassay. RESULTS: Serum L-PGDS concentrations showed marked time-dependent changes with evening increases and the highest values at night (P < .0005). This nocturnal increase was suppressed during total sleep deprivation (P < .05), independent of external light conditions and melatonin secretion. Rapid eye movement sleep deprivation had no impact on circulating L-PGDS levels. CONCLUSIONS: The circadian L-PGDS pattern and its suppression by total sleep deprivation indicate an interaction of the prostaglandin D system and human sleep regulation. L-PGDS measurements may well provide new insights into physiologic and pathologic sleep regulation in humans.     

Use of lung resection and voriconazole for successful treatment of invasive pulmonary Aspergillus ustus infection

Invasive pulmonary aspergillosis (IPA) is a common infection in neutropenic patients and is associated with high mortality. Aspergillus ustus is a species that has only rarely been implicated in human disease. All reported cases of IPA due to A. ustus have been fatal. Here, we describe a case of invasive pulmonary A. ustus infection successfully treated with lung resection and voriconazole. A 43-year-old man with acute myeloid leukemia underwent two courses of chemotherapy and experienced prolonged neutropenia. Treatment with amphotericin B was given for persistent fever. While he was receiving amphotericin B, a progressive opacity developed in the upper right lobe. Lung tissue obtained through pulmonary wedge resection for histology showed a mold with septate hyphae, consistent with IPA due to Aspergillus. A. ustus was grown in culture. The patient was then treated with voriconazole and remained in remission of the mold infection in spite of additional chemotherapy and a leukemic relapse. In summary, this report describes the successful treatment of invasive pulmonary A. ustus infection by lung resection and antifungal treatment with voriconazole in a neutropenic patient.