Revision of the medical malpractice law--legal aspects

Since the beginning of this century, modifications of the criminal law regarding medicine have been outlined frequently. The focus of these modifications was to eliminate the circumstance that each medical procedure is a criminal offense even if it was performed correctly and was successful. Treatment without consent was supposed to be punished. The draft recently submitted to the ministry of justice seems to be a failure. The prerequisites of an effective consent remain unclear. An incorrect information of the patient would be classified as intent and, thus, be punishable. By application of uncertain criteria, medical experiments and treatment procedures might be followed by excessive punishment.     

Psychological testing in a military clinic.

Data on psychological testing practices at a psychology clinic at Lackland Air Force Base, Texas, indicate that, compared to N. D. Sundberg's (1961) survey, fewer tests per individual were used although more patients were seen per year. The test battery is comparable to those used elsewhere. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The dependence of HNO2 mutagenesis in phage T4 on ligase and the lack of dependence of 2AP mutagenesis on repair functions

A temperature sensitive ligase allele of phage T4 reduced or eliminated HNO2 induced reversion of am mutants. Since at the temperatures used, the ligase mutant is defective in the repair of some types of lethal lesions (i.e., UV, MMS and EMS induced lesions) these results indicate that HNO2 mutagenesis may occur through a ligase dependent repair pathway. In contrast, 2AP induced mutation was not inhibited by mutants defective in the gene 30 ligase or in genes 32, 39, 41, 42, 44, 45, 46, 47, 49, 52, 56, 58-61 and v. This indicates that 2AP mutagenesis probably does not depend on a repair pathway in phage T4.     

Synthesis and bioreductive potential of a mono N-oxide derivative of the alkylating agent chlorambucil

Chlorambucil N-oxide (CHLN-O) was synthesized and evaluated for in vitro bioreductive antitumor activity. A time-dependent hypoxic differential was observed when EMT6 cells were exposed to CHLN-O in the presence of rat liver microsomes and reducing equivalents. The cytotoxicity of the N-oxide was potentiated under hypoxia, and augmented further by a combination of low pH and hypoxia. Metabolic studies were also undertaken, which utilized previously described HPLC methodology for the analysis of CHLN-O loss from biological fluids. These demonstrated the requirement for microsomal enzymes and reducing equivalents, and also illustrated the time-dependent manner of CHLN-O loss from isolated microsomal preparations.     

Directing phage selections towards specific epitopes

It is possible to direct selections from antibody repertoires displayed on filamentous phage towards unique epitopes on protein antigens by competing with related molecules. A phage display repertoire of human single chain Fvs (scFvs) was panned three times against foetal haemoglobin (HbF). The selection was dominated by one clone with a Kd of 10 nM but yielded at least 17 others, all of which bound HbF but crossreacted with adult haemoglobin (HbA). To direct selection towards HbF-specific epitopes, the repertoire was preincubated with HbA in solution before each panning. Crossreactive scFvs can form complexes with the soluble HbA and thereby be prevented from binding the immobilized HbF. Four clones with preferential binding to HbF emerged under these conditions. One of these (Hb-1), with a Kd of 6 microM, had exquisite specificity for HbF and could distinguish cells expressing HbF from those expressing HbA by immunocytochemistry and flow cytometry. This antibody has an affinity that is 600-fold lower than the dominant crossreactive clone, and so only emerged under conditions of 'competitive deselection'. Thus, competitive deselection is a viable means for directing selections towards useful epitopes. It permits a more effective 'search' of phage display repertoires and allows the emergence of lower affinity clones with useful specificities. These clones may be useful in themselves or may serve as leads for in vitro affinity maturation.