[Hypothermia under olanzapine treatment: clinical case series and review of current literature]. / Hypothermie unter Olanzapin : Eine Fallserie mit Literaturübersicht.

BACKGROUND: Antipsychotic drugs may lead to hypothermia as well as hyperthermia. Although known for decades and clinically highly relevant, the mechanisms by which antipsychotic drugs alter thermoregulatory processes in the human body are still far from being fully understood. In clinical practice, much attention is paid to antipsychotic drug-induced elevation of body core temperature as observed in the neuroleptic malignant syndrome (NMS). But also hypothermia is a clinically highly relevant adverse reaction to antipsychotic drugs. MATERIAL AND METHODS: Here we report a case series of three patients who developed severe hypothermia after administration of olanzapine. A review of the current literature is given with a focus on risk factors for the development of antipsychotic drug-induced hypothermia and its pathophysiologic mechanisms. RESULTS: A 51-year-old female patient suffering from catatonic schizophrenia, cachectic nutritional condition and hypothyroidism developed severe hypothermia of 30.0°C body core temperature after administration of 30 mg olanzapine per day under comedication with lorazepam and L-thyroxine. A 48-year-old female patient with catatonic schizophrenia showed hypothermia of 31.0°C (rectal measurement) after single-dose administration of olanzapine 10 mg orally and a total of 3 mg lorazepam (1-1-1 mg). The third case report describes a 69-year-old male patient with acute delusional disorder exhibiting hypothermia of 33.0°C (rectal measurement) in combination with a reversible atrioventricular block grade III without any further comedication. CONCLUSION: A review of the current literature reveals that thermoregulatory disturbances as sequelae of antipsychotic drug administration depend on individual disposition as well as various independent risk factors such as environmental temperature, somatic comorbidities, endocrinological abnormalities (e.g. hypothyroidism) and structural damage of the brain. A complex interaction of dopaminergic regulatory mechanisms in the ventral hypothalamus and peripheral vaso- and sudomotor adjustments seems to be causative. Hypothermia following antipsychotic drug administration represents a serious adverse drug reaction and a potentially life-threatening event.

Berry anthocyanins and anthocyanidins exhibit distinct affinities for the efflux transporters BCRP and MDR1.

BACKGROUND AND PURPOSE: Dietary anthocyanins hold great promise in the prevention of chronic disease but factors affecting their bioavailability remain poorly defined. Specifically, the role played by transport mechanisms at the intestinal and blood-brain barriers (BBB) is currently unknown. EXPERIMENTAL APPROACH: In the present study, 16 anthocyanins and anthocyanidins were exposed to the human efflux transporters multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP), using dye efflux, ATPase and, for BCRP, vesicular transport assays. KEY RESULTS: All test compounds interacted with the BCRP transporter in vitro. Of these, seven emerged as potential BCRP substrates (malvidin, petunidin, malvidin-3-galactoside, malvidin-3,5-diglucoside, cyanidin-3-galactoside, peonidin-3-glucoside, cyanidin-3-glucoside) and 12 as potential inhibitors of BCRP (cyanidin, peonidin, cyanidin-3,5-diglucoside, malvidin, pelargonidin, delphinidin, petunidin, delphinidin-3-glucoside, cyanidin-3-rutinoside, malvidin-3-glucoside, pelargonidin-3,5-diglucoside, malvidin-3-galactoside). Malvidin, malvidin-3-galactoside and petunidin exhibited bimodal activities serving as BCRP substrates at low concentrations and, at higher concentrations, as BCRP inhibitors. Effects on MDR1, in contrast, were weak. Only aglycones exerted mild inhibitory activity. CONCLUSIONS AND IMPLICATIONS: Although the anthocyanidins under study may alter pharmacokinetics of drugs that are BCRP substrates, they are less likely to interfere with activities of MDR1 substrates. The present data suggest that several anthocyanins and anthocyanidins may be actively transported out of intestinal tissues and endothelia, limiting their bioavailability in plasma and brain.

[The work of medical doctors on psychiatric wards: an analysis of everyday activities]. / Der Arbeitsalltag von Arzten im Stationsdienst: Eine Tätigkeitsanalyse in psychiatrischen Versorgungskliniken.

In Germany, the economic situation of psychiatric hospitals has markedly changed during the last years. Whilst the number of patients has steadily increased, many clinics considerably reduced the number of therapeutic staff due to an increasing lack of financial support. The German psychiatry personnel regulations act defines the number of therapeutic staff required for an adequate psychiatric treatment, but the requirements of this regulations act nowadays are widely missed in most of the German psychiatric hospitals. This severely affects the therapeutic work on psychiatric wards. This study analyses tasks and activities of medical doctors on psychiatric wards and compares the hours spent with various types of activities with the amount of time that should be spent according to the personnel regulations act. Results show that doctors spend much more time with documentation and administrative work than originally intended by the personnel regulations act. They compensate this mainly by a reduction of time spent in direct contact with the patients. In this context, the number of psychotherapy sessions as well as sessions with the patients' relatives has been considerably reduced, whereas the time spent for emergency intervention and basic treatment still corresponds to the calculations according to the personnel regulations act. All in all, the results show that a reduction of therapeutic staff in psychiatric hospitals directly leads to a change in treatment settings with a focus on less individual treatment options.

Smoking modulates neuroendocrine responses to ipsapirone in patients with panic disorder.

Reduced 5-HT1A-receptor responsiveness has been reported in patients with panic disorder(PD) and/or agoraphobia (PDA). Although many of these patients are regular smokers, it has not been examined whether psychological or neurobiological effects induced by the selective 5-HT1A-receptor agonist, ipsapirone, are affected by the smoking status of the patients. In order to clarify this question neuroendocrine challenges with oral doses of ipsapirone (0.3 mg/kg) and placebo were performed in 39 patients with PDA, and results were compared between patients who smoked (>10 cigarettes per day, n = 17) and patients who had been non-smokers for at least two years (n = 22). Patients who were smokers (but did not smoke during the challenge procedure) had significantly reduced baseline concentrations of cortisol and a significantly lower body temperature. In comparison to placebo, administration of ipsapirone was associated with significant increases of various psychological symptoms and plasma cortisol concentrations. The subgroup of PD patients who were smokers showed significantly higher cortisol responses to ipsapirone than non-smokers. In conclusion, smoking status has to be taken into account when assessing the responsiveness of 5-HT1A receptors in patients with psychiatric disorders. The prevention of smoking during challenge sessions might not be the ideal approach in heavy smokers, since sudden abstinence from smoking is likely to affect neurobiological and possibly psychological responses to ipsapirone.

First results on daytime submandibular electrostimulation of suprahyoidal muscles to prevent night-time hypopharyngeal collapse in obstructive sleep apnea syndrome.

Daytime submandibular electrostimulation (dSE) of suprahyoidal muscles was applied to prevent sleep-associated collapse of the tongue into the hypopharyngeal airway. By placing the stimulatory electrodes intra- and extraorally, recruitment of stimulated muscle fibers at low current densities was improved. The significant impact of electrostimulation on suprahyoidal muscle force was initially demonstrated in healthy controls as compared to placebo-treated volunteers. The morphology of suprahyoidal muscles was not affected by this treatment. A patient with obstructive sleep apnea syndrome initially presented with a respiratory disturbance index (RDI) of 13.2, an oxygen desaturation index of 23 and a minimal oxygen saturation of 75%. After two weeks of placebo treatment (TENS-stimulation), respiratory parameters remained unchanged. Two weeks of dSE treatment, however, improved the RDI to 3.9, the oxygen desaturation index from 23 to 2.8 and the minimal oxygen saturation from 75% to 88%. 3D-sonography showed considerable hypertrophy of the stimulated muscles. These results indicate that dSE may prevent episodes of apnea induced by sleep-associated hypopharyngeal collapse of the tongue.

[Functional palatoraphy and modified genioplasty in obstructive sleep apnea]. / Funktionelle Palatoraphie und modifizierte Genioplastik bei obstruktiver Schlafapnoe.

10 patients with obstructive sleep apnea syndrome (OSAS) have been treated with the new surgical procedure functional palatoraphy and modified genioplasty. 5 months after surgery 7 patients with an apnea hypopnea index under 10 were cured. Three therapy refractory patients were all overweight with a body mass index of more than 29 kg/m2. Excessively overweight patients should therefore not be operated. Following the selection criteria we introduced an effective new treatment method for OSAS.