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Phase variation of surface structures occurs in diverse bacterial species due to stochastic, high frequency, reversible mutations. Multiple genes of Campylobacter jejuni are subject to phase variable gene expression due to mutations in polyC/G tracts. A modal length of nine repeats was detected for polyC/G tracts within C. jejuni genomes. Switching rates for these tracts were measured using chromosomally-located reporter constructs and high rates were observed for cj1139 (G8) and cj0031 (G9). Alteration of the cj1139 tract from G8 to G11 increased mutability 10-fold and changed the mutational pattern from predominantly insertions to mainly deletions. Using a multiplex PCR, major changes were detected in 'on/off' status for some phase variable genes during passage of C. jejuni in chickens. Utilization of observed switching rates in a stochastic, theoretical model of phase variation demonstrated links between mutability and genetic diversity but could not replicate observed population diversity. We propose that modal repeat numbers have evolved in C. jejuni genomes due to molecular drivers associated with the mutational patterns of these polyC/G repeats, rather than by selection for particular switching rates, and that factors other than mutational drift are responsible for generating genetic diversity during host colonization by this bacterial pathogen.

Campylobacter jejuni and related species are important human pathogens, causing acute human enterocolitis, and they are the most common cause of food-borne diarrhoea in many industrialized countries. Previous infection with certain strains of C. jejuni is also linked with the development of the neurological disorder Guillain-Barre syndrome (GBS). Despite its importance as a human pathogen, relatively little is understood of the mechanisms of C. jejuni-associated disease. The recent release of the complete genome sequence of C. jejuni strain NCTC 11168, together with new strategies for random and directed mutagenesis, have allowed a better insight into some of the genetic determinants of C. jejuni virulence. In this review current knowledge on the pathogenesis of C. jejuni infection is summarized, and possible directions of future research indicated.

The mechanisms whereby Campylobacter jejuni translocates across the host intestinal epithelium are not yet understood and the transepithelial route remains undefined. During C. jejuni translocation, the transmonolayer electrical resistance (TER) across polarised monolayers of Caco-2 cells is not affected and the penetration of [14C]inulin across the monolayers does not increase. Over 24 h, however, bacteria damage the monolayer integrity, causing a decrease in the TER. These results support C. jejuni translocation through the cytoplasm of invaded cells (transcellular) rather than via intercellular spaces (paracellular).

The mechanisms whereby Campylobacter jejuni translocates across the host intestinal epithelium are not yet understood and the transepithelial route remains undefined. During C. jejuni translocation, the transmonolayer electrical resistance (TER) across polarised monolayers of Caco-2 cells is not affected and the penetration of [(14)C]inulin across the monolayers does not increase. Over 24 h, however, bacteria damage the monolayer integrity, causing a decrease in the TER. These results support C. jejuni translocation through the cytoplasm of invaded cells (transcellular) rather than via intercellular spaces (paracellular).

Aims There is little evidence to inform routine practice in the use of coronary angiography and revascularization procedures after acute myocardial infarction. Large differences in the uptake of these procedures have been reported but representative data are scarce. Outcome studies have produced opposing conclusions concerning the impact of the high rate of these cardiac procedures. Methods and Results A population-based patient sampling approach was utilized to identify routine practice in representative samples from 11 European countries. Data were collected retrospectively on treatment in the 6 months following acute myocardial infarction (n=2807). There was wide variation in utilization of coronary angi-ography and revascularization procedures. Even after restricting the analysis to patients

Aims Long-term beta-blockade reduced mortality after acute myocardial infarction by about a quarter in a series of published trials. Representative data on beta-blocker use for secondary prevention are scanty but indicate wide variations. We have analysed European practice, and sources of variation, by regional sampling of acute myo-cardial infarction patients admitted to hospital in 11 countries during the period January 1993–June 1994. Methods and results Treatment data for 4035 representative patients were collected for the hospital phase and 6 months after discharge. A logistic regression model was developed to describe the predictors of beta-blocker use. In the 11 regional samples, 6–38% (20% overall) of patients had no recorded contraindications but were discharged without a beta-blocker. In the absence of perceived contraindications, there was a strong, independent negative association between age and odds of treatment ( P

Summary Haemopoietic growth factors are involved in the production of the various blood cells from progenitors in the bone marrow, making them useful in a range of clinical situations. The genes for several of them have been cloned and their production engineered by recombinant technology, making them widely available. Myeloid growth factors are used to support patients in the aftermath of chemotherapy and bone marrow transplantation and have potential application in the treatment of infectious diseases. Erythropoietin is widely used for patients with anaemia due to failure of marrow production, having established its effectiveness in chronic renal failure. Thrombopoietin has recently been described and may provide a means to alleviate thrombocytopenia. Current indications and areas of recent reappraisal are addressed in this review.