Study of five cell salvage machines in coronary artery surgery.

We evaluated the effectiveness, ease of use and safety of five machines for blood salvage during coronary artery surgery. All were equally effective in concentrating red cells. We measured haemoglobin, packed cell volume, free haemoglobin, white cells, neutrophil elastase, platelets, thrombin-antithrombin complex (TAT), prothrombin activation peptide F1.2, fibrin degradation product (d-dimers), tissue plasminogen activator (tPA) and heparin in wound blood, in washed cell suspensions and in a unit of bank blood prepared for each patient. All machines were equally safe and easy to use and were equally effective in removing heparin and the physiological components measured. There were no adverse effects on patients. Clotting factors are severely depleted both in salvaged blood, even before washing, and in bank blood. Cell savers are a valuable adjunct to coronary artery surgery, but careful monitoring of coagulation is required when the volumes of either bank blood or salvaged blood are large.

Mutations of glutamate-84 at the putative potassium-binding site affect camphor binding and oxidation by cytochrome p450cam.

Cytochrome P450cam (CYP101) from Pseudomonas putida is unusual among P450 enzymes in that it exhibits co-operative binding between the substrate camphor and a potassium ion. This behaviour has been investigated by mutagenesis of Glu84, a surface residue which forms part of the cation-binding site. Substitutions that neutralize or reverse the charge of this side chain are shown to disrupt the co-operativity of potassium and camphor binding by P450cam, and also to influence the catalytic activity. In particular, replacement of Glu84 by positively charged residues such as lysine results in increased high-spin haem fractions and camphor turnover activities in the absence of potassium, along with decreased camphor dissociation constants. However, in the presence of potassium the camphor dissociation constants of these mutants are significantly increased compared with the wild-type, although the camphor turnover activities remain marginally higher. In contrast, substitution by aspartate results in tighter binding of both potassium and camphor, but has little effect on the enzymatic activity. In all cases the reaction remains essentially 100% coupled and gives 5-exo-hydroxycamphor as the only product. These results suggest that an anionic side chain at the 84 position is crucial for the co-operativity of camphor and cation binding, and that the physiological role for potassium binding by cytochrome P450cam is to promote camphor binding even at the expense of turnover rate, thus allowing the organism to utilize low environmental concentrations of this substrate for growth.

The Small Area Health Statistics Unit: a national facility for investigating health around point sources of environmental pollution in the United Kingdom.

STUDY OBJECTIVE: The Small Area Health Statistics Unit (SAHSU) was established at the London School of Hygiene and Tropical Medicine in response to a recommendation of the enquiry into the increased incidence of childhood leukaemia near Sellafield, the nuclear reprocessing plant in West Cumbria. The aim of this paper was to describe the Unit's methods for the investigation of health around point sources of environmental pollution in the United Kingdom. DESIGN: Routine data currently including deaths and cancer registrations are held in a large national database which uses a post code based retrieval system to locate cases geographically and link them to the underlying census enumeration districts, and hence to their populations at risk. Main outcome measures were comparison of observed/expected ratios (based on national rates) within bands delineated by concentric circles around point sources of environmental pollution located anywhere in Britain. MAIN RESULTS: The system is illustrated by a study of mortality from mesothelioma and asbestosis near the Plymouth naval dockyards during 1981-87. Within a 3 km radius of the docks the mortality rate for mesothelioma was higher than the national rate by a factor of 8.4, and that for asbestosis was higher by a factor of 13.6. CONCLUSIONS: SAHSU is a new national facility which is rapidly able to provide rates of mortality and cancer incidence for arbitrary circles drawn around any point in Britain. The example around Plymouth of mesothelioma and asbestosis demonstrates the ability of the system to detect an unusual excess of disease in a small locality, although in this case the findings are likely to be related to occupational rather than environmental exposure.

Incidence of cancers of the larynx and lung near incinerators of waste solvents and oils in Great Britain.

The Small Area Health Statistics Unit (SAHSU) is a new independent facility for the investigation of disease near industrial installations in the UK. SAHSU analysed the incidence of cancers of the larynx and lung near the incinerator of waste solvents and oils at Charnock Richard, Coppull, Lancashire (which operated between 1972 and 1980) and nine other similar incinerators in Great Britain, after reports of a cluster of cases of cancer of the larynx near the Charnock Richard site. Postcoded cancer registration data were available for 1974-84 in England and Wales and 1975-87 in Scotland. Lag periods of 5 and 10 years were used between start-up (or first registration) of the incinerators and cancer incidence. Standardised observed/expected (O/E) ratios were assessed within 3 km and 3-10 km of each site and then aggregated over all sites. Expected values were based on national rates (regionally adjusted) with and without stratification by Carstairs' index, a measure of the socioeconomic profile of areas that uses census data for enumeration districts. Data were also assessed over a range of circles up to 10 km to test for trend in O/E ratios with distance. For Charnock Richard, none of the O/E ratios within 3 km or from 3-10 km differed significantly from unity, for either cancer or lag period. In the analysis of all sites with stratification by Carstairs' index, none of these O/E ratios differed significantly from unity for the two cancers. There was no evidence of decreasing risk with distance from the sites of either cancer. We conclude that the apparent cluster of cases of cancer of the larynx reported near Charnock Richard was unlikely to be due to its former incinerator.

Improving the quality of data in randomized clinical trials: the COMPACT computer package. COMPACT Steering Committee.

One crucial component for a successful clinical trial is that the data gathered have a high level of reliability and completeness. This paper reviews some problems of data management and describes the computer package COMPACT which has been developed to deal with such problems. The package allows range and consistency checks and can monitor complex follow-up schedules. A unique feature of the package is a PROBLEMS file which has use both for identification of queries about the data and of patients with particular characteristics of interest. The ability to monitor drug dosages and to signal deviations from the protocol is of particular value. COMPACT has the syntax necessary to create a 'flat' file for transfer to statistical packages for analysis, and the variable description files for SAS, SPSS and MINITAB. The package is written in standard FORTRAN which enables transfer to different types of mini and micro computer systems.

The derivation of reference ranges adjusted for age, sex and other variables.

A method for deriving reference ranges has been developed that has wide applications in clinical medicine. Data that is not homogenous but has subgroups (e.g. age, sex or social class) can be analysed and mean values for the subgroups determined. Facilities are included which enable outliers to be identified and the form of the distribution to be examined.