SummaryBackgroundIn patients with suspected coronary heart disease, single-photon emission computed tomography (SPECT) is the most widely used test for the assessment of myocardial ischaemia, but its diagnostic accuracy is reported to be variable and it exposes patients to ionising radiation. The aim of this study was to establish the diagnostic accuracy of a multiparametric cardiovascular magnetic resonance (CMR) protocol with x-ray coronary angiography as the reference standard, and to compare CMR with SPECT, in patients with suspected coronary heart disease.MethodsIn this prospective trial patients with suspected angina pectoris and at least one cardiovascular risk factor were scheduled for CMR, SPECT, and invasive x-ray coronary angiography. CMR consisted of rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement, and MR coronary angiography. Gated adenosine stress and rest SPECT used 99mTc tetrofosmin. The primary outcome was diagnostic accuracy of CMR. This trial is registered at controlled-trials.com, number ISRCTN77246133.FindingsIn the 752 recruited patients, 39% had significant CHD as identified by x-ray angiography. For multiparametric CMR the sensitivity was 86·5% (95% CI 81·8–90·1), specificity 83·4% (79·5–86·7), positive predictive value 77·2%, (72·1–81·6) and negative predictive value 90·5% (87·1–93·0). The sensitivity of SPECT was 66·5% (95% CI 60·4–72·1), specificity 82·6% (78·5–86·1), positive predictive value 71·4% (65·3–76·9), and negative predictive value 79·1% (74·8–82·8). The sensitivity and negative predictive value of CMR and SPECT differed significantly (p<0·0001 for both) but specificity and positive predictive value did not (p=0·916 and p=0·061, respectively).InterpretationCE-MARC is the largest, prospective, real world evaluation of CMR and has established CMR's high diagnostic accuracy in coronary heart disease and CMR's superiority over SPECT. It should be adopted more widely than at present for the investigation of coronary heart disease.FundingBritish Heart Foundation.

The protein kinase C (PKC) family of isoenzymes is believed to mediate a wide range of signal-transduction pathways in many different cell types. A series of bisindolylmaleimides have been evaluated as inhibitors of members of the conventional PKC family (PKCs-alpha, -beta, -gamma) and of a representative of the new, Ca(2+)-independent, PKC family, PKC-epsilon. In contrast with the indolocarbazole staurosporine, all the bisindolylmaleimides investigated showed slight selectivity for PKC-alpha over the other isoenzymes examined. In addition, bisindolylmaleimides bearing a conformationally restricted side-chain were less active as inhibitors of PKC-epsilon. Most noticeable of these was Ro 32-0432, which showed a 10-fold selectivity for PKC-alpha and a 4-fold selectivity for PKC-beta I over PKC-epsilon.

The relationship between health care expenditure and health outcomes is of interest to policy makers in the light of steady increases in health care spending for most industrialised countries. However, establishing causal relationships is complex because, firstly, health care expenditure is only one of many quantitative and qualitative factors that contribute to health outcomes, and, secondly, measurement of health status is an imperfect process. This study reviews key findings and methodological approaches in this field and reports the results of our own empirical study of countries of the European Union. Our analysis examines life expectancy and infant mortality as the 'output' of the health care system, and various life-style, environmental and occupational factors as 'inputs'. Econometric analyses using a fixed effects model are conducted on a panel data set for the former 15 members of the European Union over the period 1980-1995. The findings show that increases in health care expenditure are significantly associated with large improvements in infant mortality but only marginally in relation to life expectancy. The findings are generally consistent with those of several previous studies. Caveats and improvements for future research are presented.

A series of potent, selective inhibitors of protein kinase C has been derived from the structural lead provided by the microbial broth products, staurosporine and K252a. Our inhibitors block PCK in intact cells (platelets and T cells), and prevent the proliferation of mononuclear cells in response to interleukin 2 (IL2).