Portable echocardiography: an innovative tool in screening for cardiac abnormalities in the community.

AIMS: Heart failure is placing an increasing burden on society. This has led to calls for echocardiographic-based programmes to screen for left ventricular systolic dysfunction and other cardiac abnormalities. Echocardiography using new fully portable echocardiography devices would allow community-based cost-effective screening programmes once validated. This study was undertaken to evaluate this further in both high and low-risk subjects. METHODS AND RESULTS: 562 consecutive subjects attending a community-based heart failure screening programme, some at high-risk and some at low-risk of cardiac abnormalities, underwent echocardiography by both portable and traditional echocardiography machines. An 'eyeball' estimate of left ventricular ejection fraction was made on the portable device and compared to a quantitative measure of ejection fraction on the traditional machine. Qualitative measures of valvular regurgitation and quantitative measures of left ventricular hypertrophy were also compared. An estimate of ejection fraction was possible in 97% of cases using portable echocardiography. It gave a sensitivity, specificity and negative predictive value in diagnosing left ventricular systolic dysfunction of 96%, 98% and 99.6%, respectively. Inter-observer variability gave a mean difference in ejection fraction of 2%, and 95% limits of agreement of -8% to +12%. All cases of moderate or severe valvular regurgitation and 29 of 31 cases of significant left ventricular hypertrophy were correctly identified as abnormal on the portable device. CONCLUSIONS: Thus, echocardiography performed by experienced sonographers using these new fully portable devices is an accurate and reproducible technique for detecting left ventricular systolic dysfunction, left ventricular hypertrophy and valvular regurgitation in both high-risk and low-risk members of the community. Its very high negative predictive values would allow their use in future community-based screening programmes.     

Activation of Hageman factor in the nephrotic syndrome

The patient described had the nephrotic syndrome associated with decreased levels of plasma coagulation factors XI (35 per cent) and XII (15 per cent). The patient also had a decrease in concentration of prekallikrein and kallikrein inhibitor, suggesting that the kallikrein system was activated. Addition of purified factor XII did not correct this defect. The fibrinolytic system was activated as indicated by an increase in fibrinogen split products. Thus, it seems that three Hageman-dependent proteolytic pathways (coagulation, fibrinolysis and kallikrein) were activated in this patient with the nephrotic syndrome.Another possible cause of decreased factors XI and XII is urinary loss of these proteins. The urine did contain apparent activities of factors XI and XII. The finding of factor VIII in the urine in higher concentrations than XI or XII, however, as well as the inability to adsorb the activity with Celite®, suggested that the activity was due to a nonspecific urinary procoagulant. This hypothesis was confirmed by removal of the activity via adsorbtion of the urine with barium citrate.     

What is the most cost-effective strategy to screen for left ventricular systolic dysfunction: natriuretic peptides, the electrocardiogram, hand-held echocardiography, traditional echocardiography, or their combination?

AIMS: To assess the screening characteristics and cost-effectiveness of screening for left ventricular systolic dysfunction (LVSD) in community subjects. METHODS AND RESULTS: A total of 1392 members of the general public and 928 higher risk subjects were randomly selected from seven community practices. Attending subjects underwent an ECG, N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels, and traditional echocardiography (TE). A total of 533 consecutive subjects underwent hand-held echocardiography (HE). The screening characteristics and cost-effectiveness (cost per case of LVSD diagnosed) of eight strategies to predict LVSD (LVSD <45% on TE) were compared. A total of 1205 subjects attended. Ninety six per cent of subjects with LVSD in the general population had identifiable risk factors. All screening strategies gave excellent negative predictive value. Screening high-risk subjects was most cost-effective, screening low-risk subjects least cost-effective. TE screening was the least cost-effective strategy. NTproBNP screening gave similar cost savings to ECG screening; HE screening greater cost-savings, and HE screening following NTproBNP or ECG pre-screening the greatest cost-savings, costing approximately 650 Euros per case of LVSD diagnosed in high-risk subjects (63% cost-savings vs.TE). CONCLUSION: Thus several different modalities allow cost-effective community-based screening for LVSD, especially in high-risk subjects. Such programmes would be cost-effective and miss few cases of LVSD in the community.     

Diagnostic and prognostic role of cardiac troponin I (cTnI) measured on the DPC Immulite

OBJECTIVE: To evaluate the diagnostic and prognostic role of the Immulite cTnI assay for the detection of acute coronary syndromes (ACS). POPULATION: 150 males and 63 females with a median age of 63 years, range 28 to 88, and an interquartile range of 18 years were admitted within 24 h of chest pain and non-ST segment elevation ACS were studied. The median onset of symptoms was 3 h (range 0-23). METHODS: Venous samples were taken on admission (t = 0) and at 24 h (t = 24). The serum samples were assayed for CK, CK-MB and cTnT on an Elecsys 1010 (Roche Diagnostics, Lewes, UK). The cTnT assay CV was 5.5% at 0.32 microg/l and 5.4% at 6.0 microg/l, and the detection limit was 0.01 microg/l with an upper limit of 25 microg/l. For cTnI using the Immulite (DPC, Gwynedd, Wales), the detection limit was 0.1 microg/l, and the upper limit was 180 microg/l. Final diagnostic categorization was performed by both WHO and European Society of Cardiology criteria using cTnT as the diagnostic cardiac biomarker. Patients were followed for the major adverse cardiac events (MACE), endpoints cardiac death, AMI or need for urgent revascularization. ROC curves were constructed using final diagnosis. Outcome prediction was assessed by ROC curves and Kaplan-Meier survival curves. RESULTS: Both methods had equivalent diagnostic efficiency using WHO criteria for AMI. When ESC criteria were used the AUC for admission and 24 h cTnT and cTnI values were 0.945 vs. 0.910, P = 0.20 and 0.998 vs. 0.937, P = 0.005, respectively. Both methods predicted outcome as either death or MI or MACE and were not significantly different. CONCLUSION: The Immulite cTnI assay can be used for diagnosis and risk stratification in patients admitted with non-ST segment elevation acute coronary syndromes.     

Niche adaptation and genome expansion in the chlorophyll d-producing cyanobacterium Acaryochloris marina

Acaryochloris marina is a unique cyanobacterium that is able to produce chlorophyll d as its primary photosynthetic pigment and thus efficiently use far-red light for photosynthesis. Acaryochloris species have been isolated from marine environments in association with other oxygenic phototrophs, which may have driven the niche-filling introduction of chlorophyll d. To investigate these unique adaptations, we have sequenced the complete genome of A. marina. The DNA content of A. marina is composed of 8.3 million base pairs, which is among the largest bacterial genomes sequenced thus far. This large array of genomic data is distributed into nine single-copy plasmids that code for >25% of the putative ORFs. Heavy duplication of genes related to DNA repair and recombination (primarily recA) and transposable elements could account for genetic mobility and genome expansion. We discuss points of interest for the biosynthesis of the unusual pigments chlorophyll d and α-carotene and genes responsible for previously studied phycobilin aggregates. Our analysis also reveals that A. marina carries a unique complement of genes for these phycobiliproteins in relation to those coding for antenna proteins related to those in Prochlorococcus species. The global replacement of major photosynthetic pigments appears to have incurred only minimal specializations in reaction center proteins to accommodate these alternate pigments. These features clearly show that the genus Acaryochloris is a fitting candidate for understanding genome expansion, gene acquisition, ecological adaptation, and photosystem modification in the cyanobacteria.     

The pathologic basis of Q-wave and non-Q-wave myocardial infarction: a cardiovascular magnetic resonance study

OBJECTIVES: The purpose of this study was to determine the pathologic basis of Q-wave (QW) and non-Q-wave (NQW) myocardial infarction (MI). BACKGROUND: The QW/NQW distinction remains in wide clinical use but the meaning of the difference remains controversial. We hypothesized that measurement of total MI size and transmural extent by late gadolinium enhancement cardiovascular magnetic resonance (CMR) would identify the pathologic basis of QWs. METHODS: A total of 100 consecutive patients with documented previous MI had electrocardiogram and CMR on the same day. Patients with acute MI within seven days were excluded. Left ventricular function and the size and transmural extent of MI were quantified in the three major arterial territories and correlated with the presence of QW. RESULTS: Subendocardial MI showed QW in 28%. Transmural MI showed NQW in 29%. Of all MIs, 48% were at some point transmural, and 99% of these were at some point non-transmural. As MI size and number of transmural segments increased, the probability of QW increased (anterior: total size chi-square = 53, p < 0.0001, transmural extent chi-square = 36, p < 0.0001; inferior: total size chi-square = 16, p = 0.001, transmural extent chi-square = 10, p = 0.001). These findings did not hold for lateral MI. In a multivariate model, the transmural extent of MI was not an independent predictor of QW when total size of MI was removed. The QW/NQW classification was a good test for size of MI (area under receiver operating characteristic curve: anterior 0.90, inferior 0.77). CONCLUSIONS: The QW/NQW distinction is useful, but it is determined by the total size rather than transmural extent of underlying MI.     

Antitumor effect of i.p. dopamine in mice bearing Ehrlich ascites carcinoma

Summary The cancer chemotherapeutic efficacy of dopamine (DA) was evaluated in female strain A mice bearing transplantable Ehrlich ascites carcinoma. The results demonstrated significant inhibition of tumor growth with appreciable increase in the host survival time following DA treatment. Diminished activity of the growth-related respiratory enzyme succinate dehydrogenase along with stimulated activity of the lysosomal enzyme, -glucuronidase in DA-treated tumor cells indicated inhibition of tumor growth as well as active lysis of the tumor cells. The direct effect of this compound on tumor proliferation was demonstrated by marked inhibition of DNA synthesis. RNA synthesis was only marginally inhibited.Abbreviations DA Dopamine - EAC Ehrlich ascites carcinoma - SDH Succinate dehydrogenase - -Glu -glueuronidase - ILS Increase of life span     

Hepatic stem cells and transforming growth factor β in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. It arises from modulation of multiple genes by mutations, epigenetic regulation, noncoding RNAs and translational modifications of encoded proteins. Although >40% of HCCs are clonal and thought to arise from cancer stem cells (CSCs), the precise identification and mechanisms of CSC formation remain poorly understood. A functional role of transforming growth factor (TGF)-β signalling in liver and intestinal stem cell niches has been demonstrated through mouse genetics. These studies demonstrate that loss of TGF-β signalling yields a phenotype similar to a human CSC disorder, Beckwith-Wiedemann syndrome. Insights into this powerful pathway will be vital for developing new therapeutics in cancer. Current clinical approaches are aimed at establishing novel cancer drugs that target activated pathways when the TGF-β tumour suppressor pathway is lost, and TGF-β itself could potentially be targeted in metastases. Studies delineating key functional pathways in HCC and CSC formation could be important in preventing this disease and could lead to simple treatment strategies; for example, use of vitamin D might be effective when the TGF-β pathway is lost or when wnt signalling is activated.     

Our experience of coronary angiography with and without heparin

AimCoronary angiography is usually done with heparin. Our aim is to see whether it can be done without heparin through femoral route and its effect on local complications.MethodWe have studied 3780 patients from 2006 to 2010 using standard dose Heparin (5000 units), low dose heparin (2000 units) and no heparin. We have compared safety and complications in these three groups.ResultsLocal complications were lowest in no heparin group. Blood transfusion requirements and surgical interventions were lowest in no heparin group. Thrombosis rate did not increase in no heparin group.ConclusionCoronary angiography can be done safely without heparin through femoral route.     

Value of ambulatory intra-arterial blood pressure monitoring in the long-term prediction of left ventricular hypertrophy and carotid atherosclerosis in essential hypertension

The aim of this study was to compare the abilities of clinic and ambulatory blood pressure (BP) to predict the long term occurrence of left ventricular hypertrophy and carotid atherosclerosis in uncomplicated hypertensive patients. Two hundred and ninety-five patients who had undergone 24-h ambulatory intra-arterial BP monitoring on the basis of an elevated clinic BP, attended follow-up at a mean of 10.2 (+/- 3.5) years later. This consisted of a history, physical examination, risk factor profile and serum cholesterol level. Echocardiography and carotid ultrasonography were also performed to determine left ventricular mass index and maximal intima-media thickness (IMTmax), a measure of carotid atherosclerosis severity. The factors most strongly correlated with both left ventricular mass index and IMTmax were age, 24-h mean pulse pressure and 24-h mean systolic BP. Age, 24-h mean systolic BP and body mass index were independent correlates of left ventricular hypertrophy (R2 = 17%), whereas age, 24-h mean pulse pressure and pack years were independent predictors of carotid atherosclerosis (R2 = 34%). Clinic BP did not feature in the final model for the long term prediction of cardiovascular end-organ damage. These findings promote a role for ambulatory BP monitoring in guiding aggressiveness of drug therapy in an attempt to limit potential target organ damage.