DNA probe technology: implications for service planning in Britain

For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23,388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late-onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis.     

Quality control of perfusion: monitoring venous blood oxygen tension to prevent hypoxic acidosis

The long-held belief that venous oxygen tension mirrored tissue oxygen tension became suspect in the 1960s when new instrumentation consistently showed that tissue oxygen tension was 10 to 30 torr less than venous oxygen tension. Moreover, a countercurrent of oxygen exchange between terminal arteries and veins was shown to exist. Despite this conflict in scientific theory, however, monitoring venous oxygen tension as a means to control hypothermic cardiopulmonary bypass has been repeatedly urged, since myocardial acidosis is clearly extremely detrimental. This study of the relationship between venous oxygen tension during hypothermic bypass and a concurrent increment in lactacidemia yields strong objective evidence to support the use of on-line venous oxygen tension monitoring to guide perfusion. In a random series of 36 patients, venous blood samples were drawn at five preselected intervals during operation and were analyzed for pH, carbon dioxide tension, oxygen tension, lactic acid, hematocrit, and base excess. Analysis of the data revealed that venous pH and base excess showed no correlation to venous oxygen tension. However, lactic acid showed a strong correlation with venous oxygen tension, with a correlation coefficient of 0.4338 at a confidence level of p less than 0.0001. If the patients were divided into three clinically pertinent groups based on the lowest venous oxygen tension recorded, a strong relationship between venous oxygen tension and lactic acid emerged. If the lowest measurement of venous oxygen tension was greater than 35 mm Hg (group A), the mean rise in lactic acid was only 0.12 microns/ml. If the lowest measurement was between 30 and 34 mm Hg (group B), the mean rise was 0.64 microns/ml. Whereas, if any venous oxygen tension value fell below 30 mm Hg (group C), the mean rise in lactic acid was 2.56 microns/ml. Analysis of variance showed that group C values were significantly different from groups A and B values (p less than 0.0002). A scientific hypothesis relating venous oxygen tension to adequate tissue oxygenation is proposed. Use of venous oxygen tension monitoring with the goal to maintain the level above 35 mm Hg is strongly supported by this study.     

Developing the occupational stress indicator (OSI) for use in Brazil: A report on the reliability and validity of the translated OSI

The Occupational Stress Indicator (OSI) was translated into Brazilian Portuguese and administered to a sample of 84 white-collar workers in Brazil. Five of the six scales of the OSI (job satisfaction, mental and physical health, coping, type A behaviour, sources of stress) showed acceptable reliability. The reliability of the sixth scale (locus of control) was disappointing, in keeping with earlier findings that suggest that this scale requires further development. Alternative measures of the stress outcomes — job satisfaction, mental health and physical health — were taken in order to assess the construct validity of these three scales. These measures included translations of the Hackman-Oldham job satisfaction measure and the Crown–Crisp Experiential Index, as well as subjective measures of health-related behaviours. Correlational and multivariate analyses of these data suggested that the job satisfaction, mental health and physical health scales of the OSI had good validity, with the physical health measure probably including a psychosomatic component. These findings are promising for the development of a new version of the OSI designed for use in South America.     

Guidelines for judicious use of electrocardiography. A summary of recommendations from the ACC/AHA Task Force Report

Electrocardiography continues to be a cornerstone in the management of an array of cardiac and noncardiac disorders. However, the ease with which an electrocardiogram can be obtained, as well as its low cost, has led to widespread use--and possible overuse--of this technology. A joint committee of the American College of Cardiology and the American Heart Association recently published guidelines for appropriate use of electrocardiography in patients with known heart disease; in persons suspected of having, or who are at risk for, heart disease; and in persons with no apparent or suspected cardiac disease. These guidelines can help clinicians determine when, and for which patients in the intensive care unit, an electrocardiogram is warranted.     

Histoenzymological study of selected dehydrogenase enzymes in Pneumocystis carinii.

The metabolic activity of Pneumocystis carinii cysts was studied histochemically by a tetrazolium dye technique to assess substrate-specific dehydrogenase activity. Lactate dehydrogenase, succinate dehydrogenase, and glutamate dehydrogenase produced moderate-to-strong reactions in the cysts, whereas glucose-6-phosphate dehydrogenase had little if any reactivity. These results suggest that pneumocystis cysts have some of the enzymes necessary for glycolysis, Krebs cycle activity, and intermediary protein metabolism. These studies provide a method of directly assessing metabolic pathways in P. carinii which circumvents the uncertainties of specificity inherent in previous investigations with partially purified suspensions.     

Direct comparison of umbilical cord blood versus bone marrow-derived endothelial precursor cells in mediating neovascularization in response to vascular ischemia.

Endothelial precursor cells (EPCs) cultured from adult bone marrow (BM) have been shown to mediate neovasculogenesis in murine models of vascular injury. We sought to directly compare umbilical cord blood (UCB)- and BM-derived EPC surface phenotypes and in vivo functional capacity. UCB and BM EPCs derived from mononuclear cells (MNC) were phenotyped by surface staining for expression of stromal (Stro-1, CXCR4, CD105, and CD73), endothelial (CD31, CD146, and vascular endothelial [VE]-cadherin), stem cell (CD34 and CD133), and monocyte (CD14) surface markers and analyzed by flow cytometry. The nonobese diabetic/severe combined immunodeficiency murine model of hind-limb ischemia was used to analyze the potential of MNCs and culture-derived EPCs from UCB and BM to mediate neovasculogenesis. Histologic evaluation of the in vivo studies included capillary density as a measure of neovascularization. Surface CXCR4 expression was notably higher on UCB-derived EPCs (64.29%+/-7.41%) compared with BM (19.69%+/-5.49%; P=.021). Although the 2 sources of EPCs were comparable in expression of endothelial and monocyte markers, BM-derived EPCs contained higher proportions of cells expressing stromal cell markers (CD105 and CD73). Injection of UCB- or BM-derived EPCs resulted in significantly improved perfusion as measured by laser Doppler imaging at days 7 and 14 after femoral artery ligation in nonobese diabetic/severe combined immunodeficiency mice compared with controls (P<.05). Injection of uncultured MNCs from BM or UCB showed no significant difference from control mice (P=.119; P=.177). Tissue samples harvested from the lower calf muscle at day 28 demonstrated increased capillary densities in mice receiving BM- or UCB-derived EPCs. In conclusion, we found that UCB and BM-derived EPCs differ in CXCR4 expression and stromal surface markers but mediate equivalent neovasculogenesis in vivo as measured by Doppler flow and histologic analyses.     

Genetic services in the context of DNA probes: what do they cost?

We describe results from the first year of a three year economic evaluation of genetic services in the context of DNA probes provided at three genetic centres in Great Britain. The analysis so far has concentrated on the costs of providing DNA diagnostic services. Estimates are given of the total costs of providing DNA probe services at each of the three centres, together with information for assessing the cost implications of future developments in these services. DNA probe services are likely to be funded as a Regional specialty. This paper concludes that relative to other developing medical technologies and as an investment by Regions, DNA probe services are inexpensive. An appraisal of the benefits to be derived from DNA probe services is still to be undertaken.