Einfluß verschiedener niedriger Droperidol-Dosierungen auf postoperative Angst, innere Anspannung, allgemeine Befindlichkeit und PONV

Background: Droperidol even in low doses such as 0,5?mg to 1,25?mg can increase postoperative anxiety and state of tension. The aim of this study was to determine whether these side effects occur frequently following low-dose droperidol and to see whether these are dose related. Methods: 184 female in- and outpatients ASA grade 1 and 2 undergoing gynaecological laparoscopy were recruited to this prospective, double-blind study. General anaesthesia was standardized (induction with thiopentone, fentanyl 2?µg/kg and vecuronium 0,1?mg/kg, tracheal intubation, maintainance with enflurane in N₂O/O₂). Patients were randomly allocated to receive saline (n=45), 0,625?mg (n=46), 1,25?mg (n=47) or 2,5?mg (n=46) droperidol i.v. 10 minutes before the end of surgery. 1, 3, 6, and 24 hours postoperatively, the patients’ anxiety, state of tension and overall mood was evaluated using two psychological questionnaires which had been tested for the perioperative period (Erlanger anxiety and tension-scale / BSKE-EWL-test). Sedation was evaluated by the staff of the recovery room. In addition, postoperative nausea and vomiting (PONV) was assessed using a 100?mm visual analogue scale and by counting the episodes of retching or vomiting. PONV was then rated over the whole observation period as none, mild, moderate or severe using a fixed scoring algorithm. Statistical analysis was performed using the ANOVA and the chi²-test. Results: The patients did not differ with regard to biometric data, duration of surgery and anaesthesia. The postoperative scores for anxiety, state of tension and overall mood were not different between the groups at any observation time (Fig.?1: anxiety and tension: P=0,5687; figure 2: overall mood: P=0,0647). Quality of sleep in the first night after surgery was the same in all groups (Table?2 and 3). Sedation was not significantly different (Table?4; P=0,0704). Furthermore, duration of stay in the recovery room did not differ (P=0,4353). On the other hand, three patients from the 2,5?mg droperidol group had to stay unexpectedly on the ward overnight, because they had been too much sedated to be discharged at home. This was not the case with any patient from the other groups. Compared to placebo, PONV over the whole 24?h observation period was significantly reduced by droperidol (Fig.?3; P=0,0338): completely free from PONV: placebo: 41,3%, 0,625?mg droperidol: 67,4%, 1,25?mg droperidol: 53,2%, 2,5?mg droperidol: 71,7%. Also the severity of PONV was reduced. Conclusion: In gynaecological laparoscopy under general anaesthesia with tracheal intubation, we recommend droperidol 0,625?mg in the prevention of PONV, as it reduces PONV as well as 2,5?mg with no severe sedation in this dosage. Psychological side effects did not occur more frequently after droperidol compared to placebo in any of the investigated dosages.     

The effects of seasons and light therapy on G protein levels in mononuclear leukocytes of patients with seasonal affective disorder

BACKGROUND: Information-transducing heterotrimeric G proteins have been implicated previously in the mechanism of action of mood stabilizers and in the pathophysiology of mood disorders. Mononuclear leukocytes of patients with unipolar and bipolar depression have been characterized by reduced measures of the stimulatory and inhibitory G proteins. In this study, patients with seasonal affective disorder (SAD) were measured for mononuclear leukocyte G protein levels while depressed during the winter, following light therapy, and in remission during the summer. METHODS: Twenty-six patients with SAD and 28 healthy subjects were assessed in the study. The immunoreactivities of Gs alpha, Gi alpha, and Gbeta subunit proteins were determined by Western blot analysis of mononuclear leukocyte membranes with selective polyclonal antibodies for the various G subunit proteins, followed by densitometric quantitation using an image analysis system. RESULTS: Untreated patients with SAD and winter, atypical-type depression showed significantly reduced mononuclear leukocyte immunoreactive levels of Gs alpha and Gi alpha proteins, similar to previous observations in patients with nonseasonal major depression. The reduced G protein levels were normalized with 2 weeks of light therapy. The same patients while in remission during the summer had G protein levels that were similar to those of healthy subjects. CONCLUSIONS: G protein-immunoreactive measures in patients with SAD are suggested as a state marker for winter depression, which is normalized by light treatment and during the summer. We speculate that light may exert its effects via normalization of transducin (Gt protein) levels, which are thought to be reduced in winter depression.     

Stimulus properties of the L-type calcium channel agonist BAY k 8644 in rats

Calcium (Ca(2+)) channels appear to be involved in the regulation of ethanol (EtOH) intake, as indicated by the effectiveness of both L-type Ca(2+) channel antagonists and agonists in reducing EtOH intake in animals. The present study was aimed to investigate rewarding/aversive and discriminative stimulus effects of the Ca(2+) channel agonist BAY k 8644, a compound showing pronounced anti-alcohol effects in rats. Therefore, a series of conditioned taste aversion (CTA), conditioned place preference (CPP) and two-lever drug discrimination (DD) experiments were conducted in Wistar rats, with (+/-)-BAY k 8644 and its enantiomers. After i.p. application, (+/-)-BAY k 8644 (0.0625-1mg/kg), (-)-BAY k 8644 (0.125-1mg/kg) and (+)-BAY k 8644 (2.5-20mg/kg) all induced a dose-dependent CTA. The minimal effective doses (MED) for (+/-)-, (-)- and (+)-BAY k 8644 were 0.25, 0.25 and 10mg/kg, respectively. In a CPP study, however, (+/-)-BAY k 8644 (0.25-2mg/kg, i.p.) showed neither aversive nor rewarding stimulus properties. Rats were trained to discriminate (-)-BAY k 8644 (0.3mg/kg, i.p.), the enantiomer acting as a high potency Ca(2+) channel agonist, from vehicle, in a two-lever DD procedure (ED(50)) value: 0.05mg/kg); full generalisation: 0.1mg/kg). The (-)-BAY k 8644 cue dose-dependently generalized to (+/-)-BAY k 8644 and (+)-BAY k 8644, the enantiomer acting as a low potency Ca(2+) channel antagonist, with ED(50) values of 0.06 and 0.28mg/kg, respectively. Both (+/-)- and (+)-BAY k 8644 produced full generalization at 1mg/kg, the latter compound showing an inverted U-shaped curve (i.e., this was the only dose showing >80% drug lever selection). The stimulus patterns of BAY k 8644 and its enantiomers appear to resemble the anti-alcohol profiles of these compounds. Therefore, commonalities between the stimulus properties of the agonistic and antagonistic enantiomers might provide a clue for the mechanism underlying the anti-alcohol effects of L-type Ca(2+) channel antagonists and agonists.     

The effect of prenatal diazepam exposure on TNF-α production by rat splenocytes

Prenatal exposure to diazepam and other benzodiazepines (BDZ) has been found to result in a marked reduction of T-lymphocyte proliferation during postnatal development of rats. In search for pathogenic changes underlying this effect, we investigated the mitogen lipopolysaccharide (LPS) and concanavalin A (ConA) stimulated release of tumour necrosis factor (TNF)- by mixed splenocytes of male offspring from Long Evans rats treated with 1.25 mg/kg per day diazepam from gestational day 14 to 20. In response to LPS, TNF- release was found to be significantly lower in mixed splenocytes of two- and four-week-old treated than in control offspring. However, at eight weeks of age, prenatally diazepam-treated animals showed a significantly higher LPS-induced TNF- release than control rats. Since monocytes/macrophages represent a major source of TNF-, additional experiments were performed on purified spleen macrophages and lymphocytes stimulated with LPS. TNF- release was only detectable in supernatants of adherent spleen macrophages and not in supernatants of lymphocytes. Thus, our data indicate that a disturbance in TNF- release from macrophages is involved in the deficient immune response of prenatally diazepam-exposed rats.     

10. Einführung zum Thema

Zusammenfassung Der fortgeschrittene Organkrebs ist eine systemische Krankheit. Die chirurgische Therapie mu durch interdisziplinäre Kooperation ergänzt werden. Jetzt gilt es, entsprechende Arbeitsgemeinschaften zu bilden, um die heute und morgen gegebenen Möglichkeiten standardisierter Chirurgie, Chemotherapie, Radiotherapie, immunologischer Therapie und Rehabilitation optimal nutzen zu können. Eine einheitliche Dokumentation nach dem TNM-System ist dabei eine notwendige Voraussetzung.     

Apoliprotein E and multiple sclerosis: impact of the epsilon-4 allele on susceptibility, clinical type and progression rate

The purpose of this study was to investigate the relation between APOE genotype and Multiple Sclerosis (MS) in a genetically homogeneous population. We examined 240 patients consulting the MS-clinic during a period of 3 years (1996 - 1999). The mean age of the patients was 41.7 years (range 19 - 80 Y, SD 10.0 Y). As a measure of the progression rate (PR) the last registered Expanded Disability Status Scale (EDSS) score was divided by the time span (years) from disease onset until the latest assessment. The APOE genotype was determined from saliva and/or blood samples using PCR-techniques. The prevalence of different APOE genotypes was compared with the allele-distribution in a population of 361 persons from a Danish cross-sectional population study. The frequency of APOE-epsilon 4/epsilon 4 homozygotes was significantly higher in the MS-group as compared to controls (P<0.05, odds ratio: 2.3), whereas the frequency distribution of other genotypes did not differ significantly. The rate of progression was significantly faster in the APOE-epsilon 4/epsilon 4 homozygotes compared to other genotypes in the MS group (P<0.05). This study suggests that the APOE-epsilon 4/epsilon 4 homozygotes have an increased risk of developing MS. MS patients with the APOE-epsilon 4/epsilon 4 allele may also have an increased rate of disease progression. Multiple Sclerosis (2000) 6 226 - 230     

Extracorporal therapy with AN69 membranes in combination with ACE inhibition causing severe anaphylactoid reactions: still a current problem?

The negatively charged membrane AN69 is known to evoke anaphylactoid reactions both without and with concomitant ACE inhibition. Underlying reasons are mainly the induction of bradykinin release due to the negatively charged membrane and the reduced degradation of bradykinin due to ACE inhibition. This complication has been reported repeatedly, but anaphylactoid reactions still occur in clinical practice. We recently had to treat two patients who suffered anaphylactoid reactions during extracorporal therapy with an AN69 membrane and simultaneous ACE inhibition. The first incident occurred in a patient on hemodialysis, the second was in a patient on continuous venovenous hemofiltration. An anaphylactoid reaction induced by an AN69 membrane during continuous, extracorporal treatment in combination with ACE inhibition has not been reported so far. Our report intends to serve as a reminder that the potentially lethal combination of AN69 membranes with ACE inhibitor treatment should be avoided.     

17 Alpha-oestradiol and 17 beta-oestradiol do not affect basal and follicle-stimulating hormone-stimulated inhibin B secretion by highly purified rat Sertoli cells

The effects of 17 alpha-oestradiol and 17 beta-oestradiol on basal and follicle-stimulating hormone (FSH)-stimulated inhibin B secretion by rat Sertoli cells were studied. Sertoli cells were isolated and cultivated from testes of 18-day-old Wistar rats in the presence and absence of FSH and different doses of oestrogens. On day 4 of culture, secreted inhibin was measured by enzyme-linked immunosorbent assay. Neither 17 alpha-oestradiol nor 17 beta-oestradiol had any effect on the secreted inhibin level in either the presence or absence of FSH. It is concluded that these oestradiols do not play an essential role in regulatory processes involving inhibin or FSH.