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The purpose of this study was to evaluate the long-term prognostic value of exercise technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) single-photon emission tomography (SPET) imaging in patients after percutaneous coronary intervention (PCI). Three hundred and eighteen consecutive post-PCI patients who underwent exercise and rest (99m)Tc-MIBI SPET myocardial perfusion imaging (MPI) were followed up for 38+/-27 months. Patients with early revascularisation (<3 months after MPI) were excluded. A semiquantitative visual analysis employing a 20-segment and four-point scoring system was used to define the summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS). Death and non-fatal myocardial infarction (MI) were considered as hard events, and late revascularisation procedures (>/=3 months after MPI) as soft events. Fifty-one patients (16.0%) suffered from cardiac events during follow-up, including 1 (0.3%) death, 13 (4.1%) non-fatal MIs, 9 (2.8%) coronary artery bypass grafting procedures and 28 (8.8%) PCIs. According to the SPET results, patients were classified into three groups: patients with normal MPI (SSS=0, n=153), patients with irreversible defects (SDS<3 and SRS>1, n=100) and patients with reversible defects (SDS>/=3, n=65). The annual hard cardiac event rate in patients with reversible defects was 3.9%, which was significantly higher than that in patients with normal MPI (0.2%, chi(2)=7.71; P<0.01). The annual soft cardiac event rate in patients with reversible defects was 10.7%, which was significantly higher than that in patients with irreversible defects (2.5% chi(2)=17.69; P<0.001), and also significantly higher than that in patients with normal MPI (1.5%, chi(2)=33.89; P<0.001). In patients with normal and reversible defects, there was no significant difference in soft and hard cardiac event rates according to whether patients were symptomatic or asymptomatic ( P>0.05). However, the annual soft event rate in patients with irreversible defects and symptoms was 5.0%, which was higher than that of 0.6% in asymptomatic patients (chi(2)=6.11, P<0.05). Multivariate Cox analysis showed that SSS was the best independent predictor for hard cardiac events (chi(2)=12.70; P<0.001) and SDS was the strongest independent predictor for soft cardiac events (chi(2)=11.72; P<0.001). Post-PCI patients who have normal exercise (99m)Tc-MIBI SPET MPI have a good long-term prognosis, while those with reversible defects are at a higher risk for future cardiac events, without correlation to the chest pain symptoms. However, symptomatic patients with irreversible defects have a higher risk for repeat revascularisation, but not for hard events, compared with asymptomatic patients. Exercise (99m)Tc-MIBI SPET MPI has important clinical value for risk stratification and management decision-making in post-PCI patients.
Eur J Nucl Med Mol Imaging 2004 May
PMID:Long-term prognostic value of exercise 99mTc-MIBI SPET myocardial perfusion imaging in patients after percutaneous coronary intervention. 1474 Jan 77

This review summarises the evidence for the role of myocardial perfusion scintigraphy (MPS) in patients with known or suspected coronary artery disease. It is the product of a consensus conference organised by the British Cardiac Society, the British Nuclear Cardiology Society and the British Nuclear Medicine Society and is endorsed by the Royal College of Physicians of London and the Royal College of Radiologists. It was used to inform the UK National Institute of Clinical Excellence in their appraisal of MPS in patients with chest pain and myocardial infarction. MPS is a well-established, non-invasive imaging technique with a large body of evidence to support its effectiveness in the diagnosis and management of angina and myocardial infarction. It is more accurate than the exercise ECG in detecting myocardial ischaemia and it is the single most powerful technique for predicting future coronary events. The high diagnostic accuracy of MPS allows reliable risk stratification and guides the selection of patients for further interventions, such as revascularisation. This in turn allows more appropriate utilisation of resources, with the potential for both improved clinical outcomes and greater cost-effectiveness. Evidence from modelling and observational studies supports the enhanced cost-effectiveness associated with MPS use. In patients presenting with stable or acute chest pain, strategies of investigation involving MPS are more cost-effective than those not using the technique. MPS also has particular advantages over alternative techniques in the management of a number of patient subgroups, including women, the elderly and those with diabetes, and its use will have a favourable impact on cost-effectiveness in these groups. MPS is already an integral part of many clinical guidelines for the investigation and management of angina and myocardial infarction. However, the technique is underutilised in the UK, as judged by the inappropriately long waiting times and by comparison with the numbers of revascularisations and coronary angiograms performed. Furthermore, MPS activity levels in this country fall far short of those in comparable European countries, with about half as many scans being undertaken per year. Currently, the number of MPS studies performed annually in the UK is 1,200/million population/year. We estimate the real need to be 4,000/million/year. The current average waiting time is 20 weeks and we recommend that clinically appropriate upper limits of waiting time are 6 weeks for routine studies and 1 week for urgent studies.
Eur J Nucl Med Mol Imaging 2004 Feb
PMID:Myocardial perfusion scintigraphy: the evidence. 1512 10

The aim of this study was to assess the plasma levels of VEGF and interleukin-10 in patients with acute myocardial infarction (AMI) and stable chronic angina (SA) and correlate the values with traditional CHD risk factors, left ventricular ejection fraction (LVEF) and established inflammatory marker hsCRP. Fifty patients with AMI and 30 with SA were enrolled. IL-10 levels in AMI patients were lower than in SA patients (9.81 +/- 5.0 versus 22.63 +/- 8.38 pg/ml, p < 0.00001). IL-10 levels were lower in AMI and SA patients with multiple CHD risk factors than in patients < or = 2 risk factors (SA: 19.48 +/- 2.94 versus 23.77 +/- 2.94 pg/ml; p < 0.005; AMI: 8.64 +/- 4.43 versus 11.85 +/- 4.09 pg/ml; p < 0.05) and patients with AMI and single-vessel than with multi-vessel disease (8.45 +/- 3.86 versus 10.72 +/- 3.95 pg/ml; p < 0.05). VEGF levels in AMI patients were higher than in SA patients (312.0 +/- 67.0 versus 221.0 + /- 50 pg/ml; p < 0.005). VEGF levels were higher in AMI patients with multi-vessel disease than in patients with single-vessel disease (348.74 +/- 45.23 versus 252.05 +/- 21.12 pg/ml; p < 0.005), with LVEF <40% and Killip class III-IV than in patients with LVEF >40% and Killip class I-II (338.8 +/- 51.59 versus 271.8 +/- 50.51 pg/ml; p < 0.005 and 340.71 +/- 52.94 versus 275.45 +/- 49.48 pg/ml; p < 0.05, respectively) and with chest pain > 6 h versus < 6 h (330.03 +/- 58.58 versus 292 +/- 57.53 pg/ml; p < 0.05). HsCRP concentrations in AMI patients were higher than in SA (1.24 +/- 0.47 versus 0.42 +/- 0.14; p < 0.0001). HsCRP was correlated with IL-10 (r = -0.413; p < 0.05) and VEGF (r = 0.319; p < 0.05). Acute myocardial infarction is associated with elevated VEGF levels and decreased concentration of IL-10. There is a significant correlation between levels of inflamatory markers and CHD risk factors and the function of the left ventricle on admission.
Int J Mol Med 2004 Aug
PMID:The pro- and anti-inflammatory markers in patients with acute myocardial infarction and chronic stable angina. 1525 85

Acute coronary syndromes are a frequent manifestation of coronary artery disease, usually being associated with chest pain and presenting as a medical emergency. Since a considerable number of patients with chest pain, however, have a non cardiac etiology of their pain, properly triaging these patients represents a diagnostic challenge for physicians in the emergency department. As the available diagnostic procedures have limited accuracy, many different diagnostic strategies have been evaluated. Among these, radionuclide myocardial perfusion imaging (MPI) at rest or in combination with stress procedures has been investigated in many trials. MPI has been proven to be useful, especially in a patient population with a low to intermediate probability of an ischemic event. Perfusion scintigraphy has a high sensitivity in the detection of myocardial infarction and reveals an excellent negative predictive value, allowing a safe discharge strategy of patients with a negative scan result. Moreover, it enables risk stratification and provides incremental and independent prognostic information regarding short to long term future cardiac adverse events. Several cost effectiveness studies have shown that perfusion imaging leads to lower overall direct costs, mainly by a reduction of unnecessary hospital admissions and diagnostic angiograms, without worsening of the clinical outcome of these patients. As a possible study endpoint, myocardial perfusion imaging in the acute setting enables the quantification of salvaged myocardium and therefore the evaluation of treatment efficacy. Besides perfusion agents, several infarct avid radiopharmaceuticals have been developed, which in part show promising results. However, larger randomized trials evaluating these tracers in clinical settings are needed to warrant routine clinical application.
Q J Nucl Med Mol Imaging 2005 Mar
PMID:Nuclear cardiology in acute coronary syndromes. 1572 36

Small cell lung cancer (SCLC) patients suffer from pulmonary stresses such as dyspnea and chest pain, and the pathogenic mechanisms are not known. SCLC cells secrete a variety of bioactive neuropeptides, including bombesin-like peptides. We hypothesize that these peptides may enhance the sensitivity of the pulmonary chemosensitive nerve endings, contributing to the development of these pulmonary stresses in SCLC patients. This study was therefore carried out to determine the effects of bombesin and gastrin-releasing peptide (GRP), a major bombesin-like peptide, on the sensitivities of pulmonary chemoreflex and isolated pulmonary vagal chemosensitive neurons. In anesthetized, spontaneously breathing rats, intravenous infusion of bombesin or GRP significantly amplified the pulmonary chemoreflex responses to chemical stimulants such as capsaicin and ATP. The enhanced responses were completely abolished by perineural capsaicin treatment of both cervical vagi, suggesting the involvement of pulmonary C-fiber afferents. In isolated pulmonary vagal chemosensitive neurons, pretreatment with bombesin or GRP potentiated the capsaicin-induced Ca(2+) transient. This sensitizing effect was further demonstrated in patch-clamp recording studies; the sensitivities of these neurons to both chemical (capsaicin and ATP) and electrical stimuli were significantly enhanced by the presence of either bombesin or GRP. In summary, our results have demonstrated that bombesin and GRP upregulate the pulmonary chemoreflex sensitivity in vivo and the excitability of isolated pulmonary chemosensitive neurons in vitro.
Am J Physiol Lung Cell Mol Physiol 2005 Dec
PMID:Sensitization of pulmonary chemosensitive neurons by bombesin-like peptides in rats. 1604 Jun 30

Today, diagnosis and treatment of chest pain related to pathologic changes in the visceral pleura are often difficult. Data in the literature on the sensory innervation of the visceral pleura are sparse. The present study aimed at identifying sensory end-organs in the visceral pleura, and at obtaining more information about neurochemical coding. The immunocytochemcial data are mainly based on whole mounts of the visceral pleura of control and vagally denervated rats. It was shown that innervation of the rat visceral pleura is characterized by nerve bundles that enter in the hilus region and gradually split into slender bundles with a few nerve fibers. Separate nerve fibers regularly give rise to characteristic laminar terminals. Because of their unique association with the elastic fibers of the visceral pleura, we decided to refer to them as "visceral pleura receptors" (VPRs). Cryostat sections of rat lungs confirmed a predominant location on mediastinal and interlobar lung surfaces. VPRs can specifically be visualized by protein gene product 9.5 immunostaining, and were shown to express vesicular glutamate transporters, calbindin D28K, Na+/K+-ATPase, and P2X3 ATP-receptors. The sensory nerve fibers giving rise to VPRs appeared to be myelinated and to have a spinal origin. Because several of the investigated proteins have been reported as markers for sensory terminals in other organs, the present study revealed that VPRs display the neurochemical characteristics of mechanosensory and/or nociceptive terminals. The development of a live staining method, using AM1-43, showed that VPRs can be visualized in living tissue, offering an interesting model for future physiologic studies.
Am J Respir Cell Mol Biol 2007 May
PMID:Sensory receptors in the visceral pleura: neurochemical coding and live staining in whole mounts. 1717 Mar 82

We report a rare case of coexisting pulmonary adenocarcinoma and Langerhans' cell histiocytosis (LCH) in a 78-year-old woman who did not smoke. During follow-up of diabetes mellitus, she had complained of chest pain and was found to have a nodular lesion in S9 of the left lower lobe, which was resected surgically. No abnormal laboratory findings were obtained. Before surgical resection, needle biopsy specimens confirmed the existence of adenocarcinoma. The resected tumor in the left lower lobe was 3.0 x 1.8 x 3.0 cm, and histologically both acinar and bronchioloalveolar cell subtypes of adenocarcinoma were found in cancer foci. In addition to pulmonary adenocarcinoma, Langerhans' cell proliferation associated with marked eosinophil infiltration was incidentally found in a small nodule, approximately 3 x 2 mm in size in the subpleural region. The Langerhans' cells contained interdigitated nuclei, exhibiting rather clear nucleoplasm and cytoplasm; they were positive for S-100 protein, CD1a, and also CD4. Massive eosinophil infiltration was found around the focus of Langerhans' cell proliferation. This nodule appeared to be LCH. The adenocarcinoma and LCH were adjacent, and cancer cells were infiltrated only in the peripheral parts of LCH. The coexistence of adenocarcinoma and LCH appeared to be incidental. The association of adenocarcinoma and LCH is rare, and only several reports of it can be found in the English literature.
Med Mol Morphol 2008 Sep
PMID:A rare case of coexistence of pulmonary adenocarcinoma with Langerhans' cell histiocytosis. 1880 45

ST-segment elevation is the major clinical criterion for committing patients with chest pain to have emergent coronary revascularizations; however, the mechanism responsible for ST-segment elevation is unknown. In a guinea pig model of ST-segment elevation acute myocardial infarction (AMI), local application of hirudin, a thrombin antagonist, significantly decreased AMI-induced ST-segment elevation in a dose-dependent manner. Hirudin-induced (5 antithrombin units [ATU]) decrease in ST elevation was reversed by 250 nmol/L thrombin receptor activator peptide (TRAP). TRAP (250 nmol/L [100 microL]) significantly induced ST-segment elevation in hearts without AMI. The TRAP effect was blocked by 4 mg/kg glibenclamide and 4 mg/kg HMR1098 and partially blocked by 3 mg/kg 5HD. Pinacidil (0.45 mg/kg) simulated the effect of TRAP (250 nmol/L [100 microL]) on hearts without AMI. Moreover, single-channel recordings showed that TRAP induced ATP-sensitive K+ channel (KATP channel) activity, and this effect was blocked by HMR1098 but not 5HD. Finally, TRAP significantly shortened the monophasic action potential (MAP) at 90% repolarization (MAP90) and epicardial MAP (EpiMAP) duration. These effects of TRAP were completely reversed by HMR1098 and partially reversed by 5HD. Thrombin and its receptor activation enhanced ST-segment elevation in an AMI model by activating the sarcolemmal KATP channel.
Mol Med
PMID:Thrombin and its receptor enhance ST-segment elevation in acute myocardial infarction by activating the KATP channel. 2038 71

Stress SPECT myocardial perfusion imaging (MPI) is the most commonly utilized stress imaging technique for patients with suspected or known coronary artery disease (CAD) and has a robust evidence base including the support of numerous clinical guidelines. Gated SPECT is a well-established noninvasive imaging modalities that is a core element in evaluation of patients with both acute and stable chest pain syndromes. Over the past decade, PET has become increasingly used for the same applications. By comparison, cardiac computed tomography (CT) is a more recently developed method, providing non-invasive approaches for imaging coronary atherosclerosis and coronary artery stenosis. Non-contrast CT for imaging the extent of coronary artery calcification (CAC), in clinical use since the mid-1990's, has a very extensive evidence base supporting its use in CAD prevention. While contrast-enhanced CT for noninvasive CT coronary angiography (CCTA) is relatively new, it has already developed an extensive base of evidence regarding diagnosing obstructive CAD and more recently evidence has emerged regarding its prognostic value. It is likely that non-contrast CT or CCTA for assessment of extent of atherosclerosis will become an increasing part of mainstream cardiovascular imaging practices as a first line test. In some patients, further ischemia testing with MPI will be required. Similarly, MPI will continue to be widely used as a first-line test, and in some patients, further anatomic definition of atherosclerosis with CT will also be appropriate. This review will provide a synopsis of the available literature on imaging that integrates both CT and MPI in strategies for the assessment of asymptomatic patients for their atherosclerotic coronary disease burden and risk as well as symptomatic patients for diagnosis and guiding management. We propose possible strategies through which imaging might be used to identify asymptomatic candidates for more intensive prevention and risk factor modification strategies as well as symptomatic patients who would benefit from referral to invasive coronary angiography for consideration of revascularization.
Q J Nucl Med Mol Imaging 2010 Apr
PMID:SPECT/PET myocardial perfusion imaging versus coronary CT angiography in patients with known or suspected CAD. 2059 82

Using a material semiotics methodology, this paper explores the link between diagnostic practices, patient awareness of the body, and biopolitical governance. We collected video and audio recordings of a patient with chest pain involved in three medical interactions (a general practitioner [GP] consultation, an electrocardiogram stress test and a consultation with a cardiologist) in Wellington, New Zealand. Following the work of Annemarie Mol, we argue that each of these diagnostics interactions bring together a range of material and non-material entities that enact the body and disease. Consequently, we note how the diagnostic practices associated with cardiovascular medicine enable and prompt an awareness of the body based on uncertainty, and thus promotes the self-management of cardiac health and risk. This paper illustrates that a material semiotics methodology makes important contributions to the sociology of diagnosis. Firstly, it draws attention to the relationship between humans and material entities in rendering the body intelligible. Secondly, it illustrates that different diagnostic procedures can produce multiple, potentially conflicting, forms of self-awareness. Alongside these practices generating multiplicity, however, are those that presuppose and produce singularity and coherence. We illustrate how the cardiologist "patches" two potentially conflicting diagnoses together in order to provide a sense of coherence to the interactions. Thirdly, material semiotics illustrates how various diagnostic practices can reify risk, and produce bodies that lend themselves to particular forms of governance.
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PMID:Patchwork diagnoses: the production of coherence, uncertainty, and manageable bodies. 2130 Apr 25


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