Mindestmengen

BACKGROUND: Consequences of the volume outcome relationship are controversial. Objectification based on data analysis is strongly needed. The aim of this publication was to analyse the effects of volume outcome reallocations based on German inpatient data. METHOD: The analysis based on inpatient data of the Krankenhauszweckverband Koeln, Bonn und Region (Hospital Association of the Cologne and Bonn Region) of 2002 and 2005. Relevant data sets were identified according to the effects of current German regulations on volume outcome on the special fields liver transplant, kidney transplant, complex pancreatic surgery, and complex oesophageal surgery. RESULTS: The effects of current German regulations on volume outcome results differed greatly between the four surgical specialities. There were fewer effects on kidney transplant, but due to an already very high level of centralisation 34% (oesophagus) and 8% (pancreas) of the hospitals stopped related surgery. This affected 8.9% (oesophagus) and 2.2% (pancreas) of related cases. CONCLUSION: Concentration and the formation of specialised medical centres are results of the implementation of volume outcome relationships. The quality of medical treatment does not automatically improve from this development. It is necessary to analyse any correlation between quality and frequency of treatment or other criteria such as know-how, structure and process management, and multidisciplinarity.     

High-affinity antagonists of the locust neuronal octopamine receptor

The pharmacological antagonistic properties of the invertebrate specific octopamine receptor were investigated using a conventional radio-receptor assay with [3H]octopamine as the radioligand. Among the antagonists with highest affinity of the locust (Locusta migratoria L.) neuronal octopamine receptor were tetracyclic substances like mianserin (K1 = 1.2 nM), some of its derivatives (8-hydroxymianserin; K1 = 1.68 nM), and maroxepine, which is the antagonist with the highest affinity ever reported (K1 = 1.02 nM) to this octopamine receptor class. Among the other antagonists tested only phentolamine (K1 = 19 nM) and promethazine (K1 = 31.2 nM) had high-affinity properties.     

Telomere-mediated chromosome pairing during meiosis in budding yeast

Certain haploid strains of Saccharomyces cerevisiae can undergo meiosis, but meiotic prophase progression and subsequent nuclear division are delayed if these haploids carry an extra chromosome (i.e., are disomic). Observations indicate that interactions between homologous chromosomes cause a delay in meiotic prophase, perhaps to allow time for interhomolog interactions to be completed. Analysis of meiotic mutants demonstrates that the relevant aspect of homolog recognition is independent of meiotic recombination and synaptonemal complex formation. A disome in which the extra chromosome is circular sporulates without a delay, indicating that telomeres are important for homolog recognition. Consistent with this hypothesis, fluorescent in situ hybridization demonstrates that a circular chromosome has a reduced capacity to pair with its homolog, and a telomere-associated meiotic protein (Ndj1) is required to delay sporulation in disomes. A circular dimer containing two copies of the same chromosome delays meiosis to the same extent as two linear homologs, implying that physical proximity bypasses the requirement for telomeres in homolog pairing. Analysis of a disome carrying two linear permuted chromosomes suggests that even nonhomologous chromosome ends can promote homolog pairing to a limited extent. We speculate that telomere-mediated chromosome movement and/or telomere clustering promote homolog pairing.     

Neonatal phenotype in Kabuki syndrome

The Kabuki syndrome is a well-established pattern of human malformation with readily recognizable features, however the diagnosis is rarely made in the newborn period. The purpose of this study was to determine if there exists a neonatal phenotype for this disorder. We ascertained 16 infants evaluated in the first 28 days of life by a dysmorphologist who subsequently received the diagnosis of Kabuki syndrome. The average age of initial evaluation was 8 days and the average age of diagnosis was 2 years 6 months. Based on these findings, it is suggested that the distinctive clinical phenotype seen in older patients is also evident in the newborn period.     

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.