Überregionale Public-Health-Akteure in Deutschland – eine Bestandsaufnahme und Kategorisierung

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Akteure der öffentlichen Gesundheit (Public Health) tragen wesentlich zu Gesundheitsschutz, -förderung und...     

Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.     

Expression of CD83 in the murine immune system

CD83 is used as a marker for mature dendritic cells (DC) in man. We have developed a new monoclonal antibody (mAb), Michel-17, that specifically recognizes mouse CD83. We show that murine CD83 is expressed mainly on mature DC and on activated T cells. Histological analysis of serial spleen sections revealed a CD83 expression pattern resembling that of MIDC-8, a known murine DC marker molecule. In contrast to other costimulatory receptors, cross-linking of CD83 with the mAb Michel-17 on DC or T cells does not induce any activation signals. Our data describe for the first time the expression pattern of murine CD83, which is comparable to that of human CD83.The unique mAb Michel-17 will help to elucidate the biological functions of the CD83 molecule in more detail.     

Scalp topography of the spontaneous K-complex and of delta-waves in human sleep

Objective: Together with spindles, K-complexes are well known hallmarks of stage 2 sleep (S2). However, little is known about their topographical distribution in comparison to delta-waves and to K-complexes superimposed by spindles. Patients and methods: In this study, the topographical distribution of spontaneous K-complexes and delta-waves in S2 and delta-waves in stage 4 sleep (S4) in 10 healthy young adults (aged 20 to 35 years, 7 female) was investigated. K-complexes with and without spindles in S2, delta-waves with and without spindles in S2, and delta-waves in S4 distributed all over the night were visually selected. EEG power maps and statistical parametric maps were calculated. Results: Absolute delta power of S2 K-complexes appeared to be significantly higher than of S2 delta-waves and delta power of S4 delta-waves was higher than of S2 delta-waves. In K-complexes and delta-waves, power was found to be highest over medio-frontal regions in the delta frequency band (0.5 - 4.0 Hz) with a second maximum occipitally in delta-waves, no matter whether superimposed by a spindle or not. Conclusion: K-complexes and delta-waves in S2 differ in topographical distribution. Even though in S2 delta-waves have less power, they have a similar topographical distribution in S2 and S4, supporting the hypothesis that delta-waves in S2 further develop towards delta-waves in slow wave sleep. The delta frequency components of K-complexes and delta-waves are unaffected by spindles.     

Erholungsfähigkeit der Niere nach zwei- oder dreistündiger Ischämie und Resektion der gesunden Niere,kontrolliert während einer neunmonatigen Erholungszeit

Zusammenfassung Die linke Kaninchenniere wurde einer ischämischen Belastung von 2 oder 3 Std ausgesetzt und die rechte Niere 21 Tage nach der Belastung entfernt. Während einer neunmonatigen Erholungszeit bestimmten wir im Katheterharn Gefrierpunktsdepression, Eiweiß, Glucose, Harnstoff, Ammoniak, Natrium, Kalium, Chlor und im Plasma den Rest-N. Das Experiment wurde durch einen Konzentrierungsversuch abgeschlossen und die Nieren nach Tötung der Tiere histologisch untersucht.Die Nierenfunktion erholt sich in wenigen Tagen nach der Resektion der gesunden Niere vollständig ohne Ausfälle von Einzelfunktionen. Gefrierpunktsdepression und Konzentrierungsversuch zeigen eine fast normale Anpassungsbreite der belasteten Nieren. Es kommt in keinem Fall zur Retention harnpflichtiger Substanzen. Anzeichen für die Ausbildung einer Schrumpfniere sind nicht vorhanden.Die histologische Untersuchung der Nieren zeigt bis auf den Ausfall einzelner Nephrone einen nahezu normalen Befund. Die Erholung der Nierenzellen ist morphologisch und funktionell vollständig, obwohl der Schwund an RNS bei gleicher Belastung 40–45% beträgt.Außer der für die Niere früher festgestellten Unabhängigkeit der Erholungsfähigkeit von der anaeroben Glykolyse übersteht der Informationsbestand der Niere unter Erhaltung des Bauplans ebenfalls einen absoluten Sauerstoffmangel von 3 Std ohne Schaden.Mit 3 TextabbildungenDer Deutschen Forschungsgemeinschaft danken wir für großzügige Förderung unserer Untersuchungen.Auszugsweise vorgetragen auf der 28. Tagung der Deutschen Physiologischen Gesellschaft, Juni 1963 in Köln.     

The N-linked glycan g15 within the V3 loop of the HIV-1 external glycoprotein gp120 affects coreceptor usage,cellular tropism,and neutralization

We have studied infectivity and neutralization of X4, R5, and R5X4 tropic HIV-1 mutants, which are lacking N-linked glycosylation sites for glycans g13, g14, g15, and g17 in the V3 loop region of gp120. X4-tropic NL4-3 mutants lacking combinations of g14/15 or g15/17 showed markedly higher infectivity in CXCR4-specific infection. The role of g15 in CCR5-specific infection was investigated using viruses with high (NL-918, R5-monotropic), medium (NL-991, R5-monotropic), and low (NL-952, R5X4-dualtropic) CCR5-specific infectivity. For NL-991, a reduction of infectivity on GHOST-CCR5 cells was observed for a mutant lacking g15. For NL-952 mutants all lacking g15, a complete loss of CCR5-specificity was observed and NL-952 was shifted from R5X4 to X4 tropism. For all mutants of NL4-3, NL-991, and NL-952, where the lack of g15 markedly influenced infectivity or coreceptor usage, neutralization was enhanced. In contrast, NL-918 mutants with or without g15 showed no difference in neutralization and no difference in GHOST-CCR5 infection rates. Thus, for viruses with a low or medium CCR5-specificity the role of g15 for changing CCR5-usage and sensitivity to neutralization was more significant than for viruses with high infection rates on GHOST-CCR5 cells. Our data demonstrate that V3 glycans play an important role in the usage of CXCR4 and CCR5. The lack of g15 was relevant for a more efficient use of CXCR4, whereas interaction with CCR5 was facilitated in the presence of g15. This study also demonstrates that glycan g15 is involved in blocking of neutralizing antibodies and shifting HIV tropism from R5X4 to X4.     

Rare SP-A alleles and the SP-A1-6A(4) allele associate with risk for lung carcinoma

Next to cigarette smoking, genetic factors may contribute to lung cancer risk. Pulmonary surfactant components may mediate response to inhaled carcinogenic substances and/or play a role in lung function and inflammation. We studied associations between surfactant protein (SP) genetic variants and risk in lung cancer subgroups. Samples (n=308) were genotyped for SP-A1, -A2, -B, and -D marker alleles. These included 99 patients with small cell lung carcinoma (SCLC, n=31), or non-SCLC (NSCLC, n=68) consisting of squamous cell carcinoma (SCC, n=35), and adenocarcinoma (AC) (n=23); controls (n=99) matched by age, sex, and smoking status (clinical control) to SCLC and NSCLC; and 110 healthy individuals (population control). We found (a) no significant marker associations with SCLC, (b) rare SP-A2 (1A9) and SP-A1 (6A11) alleles associate with NSCLC risk when compared with population control, (c) the same alleles (1A9, 6A11) associate with risk for AC when compared with population (6A11) or clinical control (1A9), and (d) the SP-A1-6A4 allele (found in approximately 10% of the population) associates with SCC, when compared with population or clinical control. A correlation between SP-A variants and lung cancer susceptibility appears to exist, indicating that SP-A alleles may be useful markers of lung cancer risk.     

Treatment of mice with the anticoccidial drug Toltrazuril does not interfere with the development of a specific cellular intestinal immune response to Eimeria falciformis

Immunity against Eimeria-infections is highly specific and it depends on cell-mediated effector mechanisms. Infections of BALB/c mice with 1000 sporulated oocysts of Eimeria falciformis led to protection against challenge infections. Treatment with the anticoccidium Toltrazuril, during primary infection, terminated the ongoing disease and did not interfere with the establishment of protective immunity against challenge infections. Mesenteric lymph node cells of infected, treated as well as non-treated and challenged BALB/c mice, showed a similar proliferation upon stimulation with parasite antigen. In contrast, neither cells of the Peyers patches, intraepithelial lymphocytes, nor spleen cells responded to stimulation with parasite antigens. Cells from all compartments and of all investigated groups proliferated and released the cytokines IFN- and IL-4 in response to the mitogen Concanavalin A. The number of cells releasing IFN- or IL-4 was not dependent on the status of infection or previous treatment with Toltrazuril. The serum IgG response against total sporozoite antigens of individual mice showed that in addition, a systemic humoral response developed in infected mice, independent of a previous drug treatment, although the specific IgG antibody concentration was higher in non-treated mice. Thus, Toltrazuril does not impair the parasite specific intestinal cellular and systemic antibody response and does not prevent the development of protection against challenge infection.     

Combined chemotherapy-radiotherapy study of small cell bronchial carcinoma: chemo-/radiotherapy vs radio-/chemotherapy

The authors studied the effect of a chemo-/radiotherapy or radio-/chemotherapy on 52 cases of microcellular bronchial carcinoma, classification "limited disease". The survival curves were slightly better for the patients submitted to primary chemotherapy, but the difference was not statistically significant, and the curves coincided again after 18 months. 60 to 80% of the patients had no complaints or only unimportant complaints during more than half of their survival time. In 23 patients with "extensive disease" who received only a symptomatic therapy or a combined palliative chemotherapy, chemotherapy had a slightly better effect, but this was not statistically significant.