Medical malpractice in perspective. II--The implications for Britain.

The "malpractice crisis" in the United States cannot be understood in isolation. Litigation is precipitated by features of the American health care and social security systems. Relative to the United Kingdom, there are fewer barriers of access to the courts, although the role of contingency fees has probably been exaggerated. Given the great institutional differences between the UK and the USA, the crisis seems unlikely to be replicated here unless there are further moves towards privatising both the costs of providing health care and the costs of its failures. It is concluded that a marginal change in the frequency or average cost of claims could have a serious impact on National Health Service resources, the medical defence societies, recruitment to specialties, and clinical practice. Debate over possible reforms is compromised by the dearth of good empirical data. Any changes, however, must address both the deterrence of bad practice and the compensation of injured patients.     

The nucleoplasmin nuclear location sequence is larger and more complex than that of SV-40 large T antigen

The carboxy-terminal tail of nucleoplasmin, which specifies entry into the cell nucleus, contains four short sequences that are similar to previously identified nuclear location sequences. We show that none of these is able to locate chicken muscle pyruvate kinase to the cell nucleus. Deletion analysis was used to determine the limits of a nuclear location sequence and indicated that a 14-amino acid segment (RPAATKKAGQAKKK) should function as a minimal nuclear location sequence. When tested directly, however, this sequence was unable to locate pyruvate kinase to the cell nucleus. Restoration of three amino acids of nucleoplasmin sequence at either end of this sequence generated sequences that were able to locate pyruvate kinase to the cell nucleus. The 14-amino acid proposed minimal nuclear location sequence is present in the functional sequences, AVKRPAATKKAGQAKKK, RPAATKKAGQAKKKKLD, and the sequence AVKRPAATKKAGQAKKKKLD, which has additional amino acids at both ends. The minimal sequence element is therefore necessary but not sufficient for transport into the cell nucleus. This unusual feature of the nucleoplasmin nuclear location sequence suggests ways in which it could interact with the nuclear transport mechanism.     

Estimating the cost of compensating victims of medical negligence.

The current system in Britain for compensating victims of medical injury depends on an assessment of negligence. Despite the sporadic pressure on the government to adopt a "no fault" approach, such as exists in Sweden, the negligence system will probably remain for the immediate future. The cost of this system was estimated to be 52.3m pounds for England 1990-1. The problem for the future, however, is one of forecasting accuracy at provider level: too high a guess and current patient care will suffer; too low a guess and future patient care will suffer. The introduction of a mutual insurance scheme may not resolve these difficulties, as someone will have to set the rates. Moreover, the figures indicate that if a no fault scheme was introduced the cost might be four times that of the current system, depending on the type of scheme adopted.     

Accumulation of the isolated carboxy-terminal domain of histone H1 in the Xenopus oocyte nucleus

Histone H1 accumulates in the nucleus after injection into the cytoplasm of Xenopus oocytes. A proteolytic fragment of 89 amino acids encompassing the carboxy-terminal domain also accumulates in the nucleus. Lysine, alanine and proline compose 84% of this domain. Accumulation is not due solely to the high lysine content since poly-L-lysine does not accumulate in the nucleus when injected into the cytoplasm of Xenopus oocytes. Proteolytic fragments encompassing other domains of the molecule are degraded in the oocyte after injection. In these instances degradation is more rapid in the cytoplasm than in the nucleus giving the false impression of accumulation in the nucleus, an artefact which is likely to confuse other studies of protein migration. Susceptibility to rapid degradation is a dominant feature, thus the globular domain destabilises the contiguous carboxy-terminal domain. The properties of the carboxy-terminal domain of H1 and the possible involvement of the amino acids lysine, proline and alanine in migration are discussed and compared with those of a domain that specifies migration of nucleoplasmin into the oocyte nucleus.     

Aggregation-dependent turnover of flagellar adhesion molecules in chlamydomonas gametes

Previous studies on flagellar adhesion in chlamydomonas (Snell, W. and S. Roseman. 1979. J. Biol. Chem. 254:10820-10829.) have shown that as gametes adhere to flagella isolated from gametes of the opposite mating type, the adhsiveness of the added flagella but not of the gametes is lost. The studies reported here show that the addition of protein synthesis inhibitors (cycloheximide [CH] or anisomycin) to the medium of such cell- flagella mixtures causes the cells to lose their adhesiveness. This loss, however, occurs only after the cells have interacted with 4-8 flagella/cell and does not occur if the cells are kept in CH (7 h) without aggregating. The availability of an impotent (imp) mating type plus (MT(+)) mutant (provided by U.W. Goodenough), which adheres but is unable to undergo the fusion that normally follows adhesion, made it possible to determine whether a similar loss of adhesiveness occurs in mixtures of matting type minus (mt(-)) and imp mt(+) gametes. In the absence of inhibitor, mt(-) and imp mt(+) gametes adhered to each other (without fusing) for several hours; however, in the presence of CH or anisomycin, the gametes began to de-adhere 35 min after mixing, and, by 90 min, 100 percent of the cells were single again. This effect was reversible, and the rapid turnover of cells were single again. This effect was reversible, and the rapid turnover of molecules involved in adhesion occurred only during adhesion inasmuch as gametes pretreated for 4 h with CH were able to aggregate in CH for the same length of time as nonpretreated cells aggregated in CH. By the addition of CH at various times after the mt(-) and imp mt(+) gametes were mixed, measurements were made of the “pool size” of the molecules involved in adhesion. The pool reached a minimum after 25 min of aggregation, rapidly increased for the next 25 min, and then leveled off at the premixing level. These results suggest that flagellar adhesion in chlamydomonas causes modification of surface molecules (receptors, ligands), which brings about their inactivation and stimulates their replacement.     

The relationship between plantar pressure and footprint shape

Fossil footprints preserve the only direct evidence of the external foot morphologies and gaits of extinct hominin taxa. However, their interpretation requires an understanding of the complex interaction among foot anatomy, foot function, and soft sediment mechanics. We applied an experimental approach aimed at understanding how one measure of foot function, the distribution of plantar pressure, influences footprint topography.