The quantification of absolute myocardial perfusion in humans by contrast echocardiography Algorithm and validation

ObjectivesWe sought to test whether myocardial blood flow (MBF) can be quantified by myocardial contrast echocardiography (MCE) using a volumetric model of ultrasound contrast agent (UCA) kinetics for the description of refill curves after ultrasound-induced microsphere destruction.BackgroundAbsolute myocardial perfusion or MBF (ml·min−1·g−1) is the gold standard to assess myocardial blood supply, and so far it could not be obtained by ultrasound.MethodsThe volumetric model yielded MBF= rBV·β/ρT, where ρTequals tissue density. The relative myocardial blood volume rBV and its exchange frequency βwere derived from UCA refill sequences. Healthy volunteers underwent MCE and positron emission tomography (PET) at rest (group I: n = 15; group II: n = 5) and during adenosine-induced hyperemia (group II). Fifteen patients with coronary artery disease underwent simultaneous MCE and intracoronary Doppler measurements before and during intracoronary adenosine injection.ResultsIn vitro experiments confirmed the volumetric model and the reliable determination of rBV and βfor physiologic flow velocities. In group I, 187 of 240 segments were analyzable by MCE, and a linear relation was found between MCE and PET perfusion data (y = 0.899x + 0.079; r2= 0.88). In group II, resting and hyperemic perfusion data showed good agreement between MCE and PET (y = 1.011x + 0.124; r2= 0.92). In patients, coronary stenosis varied between 0% to 89%, and myocardial perfusion reserve was in good agreement with coronary flow velocity reserve (y = 0.92x + 0.14; r2= 0.73).ConclusionsThe volumetric model of UCA kinetics allows the quantification of MBF in humans using MCE and provides the basis for the noninvasive and quantitative assessment of coronary artery disease

Caffeine Impairs Myocardial Blood Flow Response to Physical Exercise in Patients with Coronary Artery Disease as well as in Age-Matched Controls

BACKGROUND: Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD). METHODOLOGY/PRINCIPAL FINDINGS: MBF was measured with (15)O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58+/-13 years) and in CAD patients (n = 15, mean age 61+/-9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26+/-0.56 vs. 2.02+/-0.56, P<0.005), remote (2.40+/-0.70 vs. 1.78+/-0.46, P<0.001) and in stenotic segments (1.90+/-0.41 vs. 1.38+/-0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline). CONCLUSIONS: We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls

Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo

Like alternative splicing, leaky ribosomal scanning (LRS), which occurs at suboptimal translational initiation codons, increases the physiological flexibility of the genome by allowing alternative translation. Comprehensive analysis of 22 208 human mRNAs indicates that, although the most important positions relative to the first nucleotide of the initiation codon, −3 and +4, are usually such that support initiation (A(−3) = 42%, G(−3) = 36% and G(+4) = 47%), only 37.4% of the genes adhere to the purine (R)(−3)/G(+4) rule at both positions simultaneously, suggesting that LRS may occur in some of the remaining (62.6%) genes. Moreover, 12.5% of the genes lack both R(−3) and G(+4), potentially leading to sLRS. Compared with 11 genes known to undergo LRS, 10 genes with experimental evidence for high fidelity A(+1)T(+2)G(+3) initiation codons adhered much more strongly to the R(−3)/G(+4) rule. Among the intron-less histone genes, only the H3 genes adhere to the R(−3)/G(+4) rule, while the H1, H2A, H2B and H4 genes usually lack either R(−3) or G(+4). To address in vivo the significance of the previously described LRS of H4 mRNAs, which results in alternative translation of the osteogenic growth peptide, transgenic mice were engineered that ubiquitously and constitutively express a mutant H4 mRNA with an A(+1)→T(+1) mutation. These transgenic mice, in particular the females, have a high bone mass phenotype, attributable to increased bone formation. These data suggest that many genes may fulfill cryptic functions by LRS

Multiple etiologies of axonal sensory motor polyneuropathy in a renal transplant recipient: a case report

<p>Abstract</p> <p>Introduction</p> <p>Neurological complications leading to morbidity and mortality are not frequent in renal transplant recipients. Here, we report a renal transplant recipient who presented with diminished strength in his limbs probably due to multiple etiologies of axonal sensorimotor polyneuropathy, which resolved with intravenous immunoglobulin.</p> <p>Case presentation</p> <p>A 49-year-old Iranian male renal transplant recipient with previous history of autosomal dominant polycystic kidney disease presented with diminished strength in his limbs one month after surgery. Our patient was on cyclosporine A, mycophenolate mofetil and prednisone. Although a detected hypophosphatemia was corrected with supplemental phosphate, the loss of strength was still slowly progressive and diffuse muscular atrophy was remarkable in his trunk, upper limb and pelvic girdle. Meanwhile, his cranial nerves were intact. Post-transplant diabetes mellitus was diagnosed and insulin therapy was initiated. In addition, as a high serum cyclosporine level was detected, the dose of cyclosporine was reduced. Our patient was also put on intravenous ganciclovir due to positive serum cytomegalovirus immunoglobulin M antibody. Despite the reduction of oral cyclosporine dose along with medical therapy for the cytomegalovirus infection and diabetes mellitus, his muscular weakness and atrophy did not improve. One week after administration of intravenous immunoglobulin, a significant improvement was noted in his muscular weakness.</p> <p>Conclusion</p> <p>A remarkable response to intravenous immunoglobulin is compatible with an immunological basis for the present condition (post-transplant polyneuropathy). In cases of post-transplant polyneuropathy with a high clinical suspicion of immunological origin, administration of intravenous immunoglobulin may be recommended.</p

Impact of cardiac hybrid single-photon emission computed tomography/computed tomography imaging on choice of treatment strategy in coronary artery disease

Aims Cardiac hybrid imaging by fusing single-photon emission computed tomography (SPECT) myocardial perfusion imaging with coronary computed tomography angiography (CCTA) provides important complementary diagnostic information for coronary artery disease (CAD) assessment. We aimed at assessing the impact of cardiac hybrid imaging on the choice of treatment strategy selection for CAD. Methods and results Three hundred and eighteen consecutive patients underwent a 1 day stress/rest (99m)Tc-tetrofosmin SPECT and a CCTA on a separate scanner for evaluation of CAD. Patients were divided into one of the following three groups according to findings in the hybrid images obtained by fusing SPECT and CCTA: (i) matched finding of stenosis by CCTA and corresponding reversible SPECT defect; (ii) unmatched CCTA and SPECT finding; (iii) normal finding by both CCTA and SPECT. Follow-up was confined to the first 60 days after hybrid imaging as this allows best to assess treatment strategy decisions including the revascularization procedure triggered by its findings. Hybrid images revealed matched, unmatched, and normal findings in 51, 74, and 193 patients. The revascularization rate within 60 days was 41, 11, and 0% for matched, unmatched, and normal findings, respectively (P< 0.001 for all inter-group comparisons). Conclusion Cardiac hybrid imaging with SPECT and CCTA provides an added clinical value for decision making with regard to treatment strategy for CAD

Barriers to Family Caregivers’ Coping With Patients With Severe Mental Illness in Iran

The broad spectrum of problems caused by caring for a patient with mental illness imposes a high burden on family caregivers. This can affect how they cope with their mentally ill family members. Identifying caregivers’ experiences of barriers to coping is necessary to develop a program to help them overcome these challenges. This qualitative content analysis study explored barriers impeding family caregivers’ ability to cope with their relatives diagnosed with severe mental illness (defined here as schizophrenia, schizoaffective disorders, and bipolar affective disorders). Sixteen family caregivers were recruited using purposive sampling and interviewed using a semi-structured in-depth interview method. Data were analyzed by a conventional content analytic approach. Findings consisted of four major categories: the patient’s isolation from everyday life, incomplete recovery, lack of support by the mental health care system, and stigmatization. Findings highlight the necessity of providing support for caregivers by the mental health care delivery service system.The study was supported by Grant TBZMED·REC.5825 from the deputy of research in Tabriz University of Medical Sciences