Ultrasound contrast agent delivered per os first diagnoses pharyngoesophageal tumour.

Oral administration of ultrasound contrast agents has been described very little so far in medical literature. These agents are mainly administered intravenously and, less commonly, intracavitarily. We present the case of a patient with a cervical mass in whom sonographic examination with per os administration of SonoVue led to the diagnosis of a pharyngoesophageal tumour. The diagnosis was confirmed on barium swallow and endoscopy-guided biopsy.

Clenbuterol favorably remodels neonatal cardiac cells via activation of p38 MAPK signalling pathway.

AIM: Pharmacologic treatments which aim to induce physiological hypertrophy are now thought as novel treatments for heart failure. Thus, clenbuterol, a beta-2 adrenergic agonist has recently been shown to partially reverse cardiac remodeling by inducing physiological hypertrophy. The present study further investigated potential underlying mechanisms of this effect in a neonatal cardiomyocytes cell based model. METHODS: Neonatal cardiomyocytes obtained from newborn rats were exposed to clenbuterol (CLEN, 1µM) for five days, while untreated cells served as controls. CLEN administration resulted in well organized orientation of cytoskeletal fibers manifesting as a longitudinal cell shape, while had no effect on myosin heavy chain (MHC) isoform expression. CLEN increased cell growth as indicated by protein content: total protein per cell (pg/cell) was 116 (6.0) for CLEN and 77 (5.0) for the untreated cells, P<0.05. This response was accompanied by a 2.2 fold increase in phospho-p38 MAPK levels as compared to untreated cells, P<0.05 while no changes were observed in ERK, JNK and Akt. Administration of SB203580 (a p38 MAPK inhibitor) abrogated the CLEN induced changes in cardiomyocyte morphology, while it had no effect on protein content. CONCLUSION: Clenbuterol induces favorable changes in neonatal cardiomyocyte shape and geometry without affecting MHC isoform expression. Activation of p38 MAPK signaling seems, at least in part, to be implicated in this response.

Contrast-enhanced ultrasound for imaging blunt abdominal trauma - indications, description of the technique and imaging review.

Patients with blunt abdominal trauma are initially imaged with ultrasound (US) for the evaluation of free abdominal fluid. However, lacerations of solid organs can be overlooked. Although computed tomography (CT) is the gold standard technique for abdominal trauma imaging, overutilization, ionizing radiation, need to transport the patient and potential artifacts are well known disadvantages. Contrast-enhanced US (CEUS) can be used as an imaging tool between the two methods. It can easily and reliably reveal solid abdominal organ injuries in patients with low-energy localized trauma and decrease the number of CT scans performed. It can be rapidly performed at the patient's bedside with no need for transportation. There are only very few contraindications and anaphylactoid reactions are extremely rare. Altogether, CEUS has proved to be very helpful for the initial imaging of traumatic lesions of the liver, kidney and spleen, as well as for patient follow-up.

Thyroid hormone receptor alpha1 downregulation in postischemic heart failure progression: the potential role of tissue hypothyroidism.

Thyroid hormone (TH) signaling is altered in response to various stresses including myocardial ischemia. The present study investigated potential implication of TH signaling in the pathophysiology of postischemic remodeling. Acute myocardial infarction was induced in rats by coronary artery ligation (AMI). After 34 weeks, 6 animals were on congestive heart failure (CHF) as indicated by measurements in lung and right ventricular weight. 7 animals were in compensated state (Non-CHF) and 8 sham-operated animals (SHAM) served as controls. Progression to congestive heart failure was characterized by marked decrease in EF% and all other functional echocardiographic parameters. Furthermore, beta-MHC expression was significantly increased in CHF. A distinct pattern of thyroid hormone receptor (TR) expression was observed in the course of postischemic remodeling; TR alpha 1 was upregulated and TR beta 1 was downregulated in Non-CHF, and TR alpha 1 expression was markedly decreased during the transition from Non-CHF to CHF resulting in tissue hypothyroidism. Circulating T3 and T4 remained unchanged. This response was associated with marked decrease in mTOR activation. A potential link between mTOR and TR alpha 1 expression was shown in a neonatal cardiomyocytes model of PE (phenylephrine)-induced pathological growth. Phenylephrine increased the expression of TR alpha 1 in nucleus and this response was abrogated in the case of mTOR inhibition by rapamycin. In conclusion, progression to congestive heart failure after myocardial infarction is associated with suppressed expression of TR alpha 1 and results in tissue hypothyroidism. This process may, at least in part, be mTOR dependent.

Associations between plasma homocysteine levels, aortic stiffness and wave reflection in patients with arterial hypertension, isolated office hypertension and normotensive controls.

The aim of this study was to evaluate any possible association of homocysteine with arterial stiffness indices in patients with essential arterial hypertension (AH), isolated office hypertension (IOH) and normotensive controls. The final cohort comprised 231 normotensives (NTs, 119 males), 480 patients with IOH (196 males) and 1188 patients with essential AH (713 males). All patients were screened for plasma homocysteine levels and lipidaemic profile and underwent aortic compliance and wave reflection assessment by using carotid-femoral pulse wave velocity (PWVc-f) and aortic augmentation index corrected for heart rate (AIx) accordingly. In the total population, stepwise multiple linear regression analysis showed that homocysteine levels remained a significant determinant of PWV (beta (SE): 0.056 (0.007), P<0.001) and AIx (beta (SE): 0.236 (0.052), P<0.001) independently of the traditional factors affecting arterial stiffness and wave reflection. When the three groups were examined separately, homocysteine levels remained an independent determinant of PWFc-f in all groups (NT: beta (SE): 0.070 (0.022), P=0.002; IOH: beta (SE): 0.109 (0.015), P<0.001; AH: beta (SE): 0.040 (0.009), P<0.001). However, homocysteine levels remained an independent determinant of AIx only in the IOH and AH, but not in the NT group (IOH: beta (SE): 0.302 (0.124), P=0.015; AH: beta (SE): 0.183 (0.057), P=0.001; NT: beta (SE): 0.308 (0.240), P=0.200). This study points to an independent relationship between circulating homocysteine levels, aortic compliance and wave reflection.

Thyroid hormone at supra-physiological dose optimizes cardiac geometry and improves cardiac function in rats with old myocardial infarction.

Thyroid hormone (TH) is critical in cardiac cell differentiation (regulating contractile proteins and cell geometry) and this effect could be potentially exploited therapeutically in reversing the process of de-differentiation which underlies postischemic cardiac remodeling. Acute myocardial infarction was induced in male Wistar rats by ligating left coronary artery (AMI, n=8), while sham operated animals served as control (SHAM, n=8). 13 weeks after AMI, TH was administered in a group of animals for 4 weeks (AMI-THYR, n=9). TH significantly increased beta-MHC and decreased alpha-MHC expression in the myocardium. This response was accompanied by changes in cardiac geometry: sphericity index, (SI, long to short axis ratio) was found to be 1.95 (SEM, 0.02) in SHAM, 1.51(0.03) in AMI and 1.64(0.03) in AMI-THYR, p<0.05. As a consequence, cardiac function was significantly improved: left ventricular ejection fraction (EF%) was 74.5% (SEM, 2.8) in SHAM vs 29.5% (2.1) in AMI, and 40.0% in AMI-THYR, p<0.05. Furthermore, +dp/dt and -dp/dt were 4250 (127) and 2278 (55) in SHAM vs 2737(233) and 1508 (95) in AMI vs 3866 (310) and 2137(111) in AMI -THYR, respectively, p<0.05. TH treatment partially reverses cardiac dysfunction in rats with old myocardial infarction by favorably changing cardiac chamber geometry and expression of myosin isoforms. Thyroid hormone, unlike current treatments, appears to be a paradigm of therapeutic intervention which aims at restoring cardiac geometry and may prove new effective treatment for heart failure.

Detection of coronary artery lesions and myocardial necrosis by magnetic resonance in systemic necrotizing vasculitides.

OBJECTIVE: Myocardium and coronary arteries can occasionally be affected in patients with systemic necrotizing vasculitides; however, such involvement has not been systematically assessed using cardiovascular magnetic resonance imaging (MRI). METHODS: Magnetic resonance angiography and contrast-enhanced MRI were applied for the assessment of coronary arteries (the left anterior descending [LAD], left circumflex [LCx], and right coronary artery [RCA]) and myocardium, respectively, in 39 patients with vasculitis who were asymptomatic for cardiac disease (16 with microscopic polyangiitis [MPA], 11 with Wegener's granulomatosis [WG], 9 with Churg-Strauss syndrome [CSS], and 3 with polyarteritis nodosa [PAN]). Data were compared with age-matched disease-control patients with rheumatoid arthritis (n = 20) or systemic lupus erythematosus (n = 13), and with healthy control individuals with normal coronaries (n = 40). RESULTS: Patients with MPA, WG, and PAN (but not with CSS) were found to display significantly increased maximal diameters of coronary arteries compared with healthy controls (for MPA and WG; P < 0.001 for LAD and RCA, and P < 0.01 for LCx) and with both disease-control groups (for only MPA; P < 0.01 for LAD and RCA, and P < 0.05 for LCx). Fusiform coronary aneurysms were detected in patients with MPA (4/16) and PAN (2/3), whereas coronary ectasias were evident in patients with MPA (14/16) and WG (2/11). The presence of myocardial necrosis (by assessment of late gadolinium-enhanced images) was identified only in patients with MPA (2/16) and CSS (3/8 studied). CONCLUSION: Cardiovascular MRI assessment of patients with systemic vasculitis revealed coronary ectatic disease in the majority of patients with MPA and PAN, as well as in several patients with WG. Myocardial necrosis can be detected in MPA and CSS.

Thyroid hormone modulates the responsiveness of rat aorta to alpha1-adrenergic stimulation: an effect due to increased activation of beta2-adrenergic signaling.

AIM: The ability of the thyroid hormone to increase cardiac output and to lower systemic vascular resistance may provide a novel treatment for cardiovascular diseases. Therefore, understanding the mechanisms of thyroid hormone action on the heart and peripheral vasculature could be of clinical importance. We previously found that thyroid hormone modulates the alpha1-adrenergic effect on vascular reactivity of rat aortas. In the present study we further investigated possible mechanisms of this response. METHODS: Hyperthyroidism was induced on Wistar-Kyoto male rats with L-Thyroxine, (THYR) treatment for two weeks, N.=18 while untreated rats used as controls (NORM), N.=16. The thoracic aorta was dissected and cut into rings that were suspended in an isolated organ bath with Krebs-Henseleit buffer. Maximal tension, Tmax, in g was measured in response to Potassium Chloride (KCl) and Phenylephrine (PE) in rings in the presence of Ritodrine, a beta-2 agonist (NORM-RITO, N:=8, THYR-RITO, N.=9), or in the absence of Ritodrine (THYR, N.=9, NORM, N.=8). RESULTS: With KCL, Tmax was not different between the THYR, NORM, NORM-RITO, and THYR-RITO groups. With PE, there was a difference in Tmax between NORM-RITO and NORM, 0.66 (0.056) g vs 1.00 (0.066) g, P<0.05 and THYR and NORM, 0.75 (0.055) g vs 1.00 (0.066) g, P<0.05. No significant difference was observed between THYR-RITO AND THYR. Furthermore, Relax % was not significantly different between the NORM and the THYR, NORM-RITO, and THYR-RITO groups, 64.5%(3.7) vs 67.3%(6.7), 73.5% (4.3) and 81.8 %(4.7), P>0.05. CONCLUSIONS: PE induced vasoconstriction in isolated rat aortic rings was reduced after both ritodrine and thyroxine treatment. However, co-administration of thyroid hormone and ritodrine did not result in a synergistic reduction of PE induced vasoconstriction. Thus, thyroxine may modulate the alpha1-adrenergic vascular responsiveness by enhancing beta2-adrenergic stimulation.

Ischemic preconditioning fails to confer additional protection against ischemia-reperfusion injury in the hypothyroid rat heart.

There is accumulating evidence showing that ischemic preconditioning (PC) may lose its cardioprotective effect in the diseased states. The present study investigated whether PC can be effective in hypothyroidism, a clinical condition which is common and often accompanies cardiac diseases such as heart failure and myocardial infarction. Hypothyroidism was induced in rats by 3-week administration of 6n-propyl-2-thiouracil in water (0.05 %). Normal and hypothyroid hearts (HYPO) were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischemia and 45 min of reperfusion. A preconditioning protocol (PC) was also applied prior to ischemia. HYPO hearts had significantly improved post-ischemic recovery of left ventricular developed pressure, end-diastolic pressure and reduced lactate dehydrogenase release. Furthermore, phospho-JNK and p38 MAPK levels after ischemia and reperfusion were 4.0 and 3.0 fold lower in HYPO as compared to normal hearts (P<0.05). A different response to PC was observed in normal than in HYPO hearts. PC improved the post-ischemic recovery of function and reduced the extent of injury in normal hearts but had no additional effect on the hypothyroid hearts. This response, in the preconditioned normal hearts, resulted in 2.5 and 1.8 fold smaller expression of the phospho-JNK and phospho-p38 MAPK levels at the end of reperfusion, as compared to non-PC hearts (P<0.05), while in HYPO hearts, no additional reduction in the phosphorylation of these kinases was observed after PC. Hypothyroid hearts appear to be tolerant to ischemia-reperfusion injury. This response may be, at least in part, due to the down-regulation of ischemia-reperfusion induced activation of JNKs and p38 MAPK kinases. PC is not associated with further reduction in the activation of these kinases in the hypothyroid hearts and fails to confer added protection in those hearts.

"Cardiovascular magnetic resonance imaging reveals myocardial inflammation and coronary artery ectasia during the acute phase of Kawasaki disease".

In a patient with Kawasaki disease, during the acute phase, cardiovascular magnetic resonance has been successfully used for simultaneous evaluation of coronary arteries, myocardial function and the presence of myocardial inflammation. This comprehensive protocol revealed clinically relevant information that was missed by routinely used diagnostic approach.

What are the clinical and technical factors that influence the kerma-area product in percutaneous coronary intervention?

The purpose of the paper is to define predictors of the kerma-area product (KAP) in percutaneous coronary intervention (PCI). Two new digital X-ray interventional cardiology systems recently installed were included. A total of 398 PCI procedures were carried out by 6 board-certified senior interventional cardiologists with more than 15 years' experience and good knowledge of radiation protection measures. Clinical, radiation and procedural data were collected based on a detailed protocol developed by the SENTINEL cardiology subgroup. Correlation with clinical and procedure factors was then investigated. A significant correlation was found between fluoroscopy time and (i) lesion classification, (ii) the level of tortuosity and (iii) the number of vessels treated. No statistically significant differences were observed in the complexity of the case between operators. However, large differences were found in the KAP among operators, which were mostly attributed to the different number of frames taken by each operator. There was no statistically significant correlation between complexity and the total number of frames. The study showed that, in certain circumstances, the clinical need to successfully perform PCI takes precedence over radiation safety concerns.

Thyroid hormone receptor alpha 1: a switch to cardiac cell "metamorphosis"?

Thyroid hormone receptor alpha1 (TRalpha1) is predominantly expressed in the myocardium but its biological function under physiological or pathological conditions remains largely unknown. The present study investigated possible interactions between alpha1 adrenergic and thyroid hormone signaling at the level of TRalpha1, potential underlying mechanisms and physiological consequences, as well as the role of TRalpha1 in cell differentiation. This may be of physiological relevance since both thyroid hormone and adrenergic signalling are implicated in the pathophysiology of cardiac remodelling. Neonatal cardiomyocytes obtained from newborn rats (2-3 days) were exposed to phenylephrine (PE, an alpha1 adrenergic agonist) for 5 days, in the absence or excess of T3 in the culture medium. PE, in the absence of T3, resulted in 5.0 fold increase in TRalpha1 expression in nucleus and 2.0 fold decrease in TRalpha1 expression in cytosol, P<0.05. As a result, a fetal pattern of myosin isoform expression with marked expression of beta-MHC was observed in PE treated vs the untreated cells, P<0.05. PD98059 (an ERK signalling inhibitor) abrogated this response. In the presence of T3 in the culture medium, TRalpha1 expression was increased 1.6 fold in nucleus and 2.0 fold in cytosol in PE-T3 vs PE treated cells, P<0.05, and the fetal pattern of myosin isoform expression was prevented. Parallel studies with H9c2 myoblasts showed that reduction of T3 binding to TRalpha1 receptor delayed cardiac myoblasts differentiation without affecting proliferation. In conclusion, in neonatal cardiomyocytes, nuclear TRalpha1 is overexpressed after prolonged activation of the alpha1- adrenergic signalling by PE. This response seems to be an ERK kinase dependent process. Over-expression of TRalpha1 may lead to fetal cardiac phenotype in the absence of thyroid hormone availability. Furthermore, TRalpha1 seems to be critical in cardiac myoblast differentiation.

Level of patient and operator dose in the largest cardiac centre in Greece.

The objective of this study was to investigate the patient and staff doses in the most frequent interventional cardiology (IC) procedures performed in Onassio, the largest Cardiac Centre in Greece. Data were collected from three digital X-ray systems for 212 coronary angiographies, 203 percutaneous transluminal coronary angioplasties (PTCA) and 134 various electrophysiological studies. Patient skin dose was measured using suitably calibrated slow radiotherapy films and cardiologist dose using suitably calibrated thermoluminescent dosemeters placed on left arm, hand and foot. Patient median dose area product (DAP) (all examinations) ranged between 6.7 and 83.5 Gy cm2. Patient median skin dose in PTCA was 799 mGy (320-1660 mGy) and in RF ablation 160 mGy (35-1920 mGy). Median arm, hand and foot dose to the cardiologist were 12.6, 27 and 13 microSv, respectively, per procedure. The great range of radiation doses received by both patients and operators confirms the need for continuous monitoring of all IC techniques.

Effects of insulin resistance on endothelial function: possible mechanisms and clinical implications.

Insulin resistance (IR) is defined as a reduced responsiveness of peripheral tissues to the effects of the hormone, referring to abated ability of insulin in stimulating glucose uptake in peripheral tissues and in inhibiting hepatic glucose output. Insulin has both a vasodilatory effect, which is largely endothelium dependent through the release of nitric oxide, and a vasoconstrictory effect through the stimulation of the sympathetic nervous system and the release of endothelin-1. IR and endothelial dysfunction (ED) are not only linked by common pathogenetic mechanisms, involving deranged insulin signalling pathways, but also by other, indirect to the hormone's actions, mechanisms. Different treatment modalities have been proposed to affect positively both the metabolic effects of insulin and ED. Weight loss has been shown to improve sensitivity to insulin as a result of either altered diet or exercise. Exercise has favourable effects on endothelial function in normal states and in states of disease, in men and women, and throughout the age spectrum and, hence, in IR states. Metformin improves sensitivity to insulin and most likely affects positively ED. Studies have shown that inhibitors of the renin-angiotensin system alter IR favourably, while Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor type II (ATII) inhibitors improve ED. Ongoing studies are expected to shed more light on the issue of whether treatment with the thiazolidinediones results in improvement of endothelial function, along with the accepted function of improving insulin sensitivity. Finally, improved endothelial function by such treatments is not in itself proof of reduced risk for atherosclerosis; this remains to be directly tested in clinical trials.

Intermittent acute aortic valve regurgitation: a case report of a prosthetic valve dysfunction.

Complications of any mechanical prosthesis include thrombus or pannus formation. In our case report we demonstrate that prosthetic aortic valve regurgitation due to pannus formation may be intermittent and non-cyclic in pattern and therefore not obvious at the time of original clinical examination. Under these conditions and as transesophageal echocardiography cannot be repeated promptly, transthoracic 2-D and Doppler echocardiography should be available at any time when symptoms occur and present the method of choice for acute patient evaluation. Thrombolysis seems to be the first treatment of choice in case of thrombus formation and re-do surgery in case of pannus formation.

[Prognostic value of ventricular longitudinal systolic velocities and maximal oxygen consumption in patients with dilated cardiomyopathy].

OBJECTIVE: To compare the prognostic value of regional longitudinal ventricular systolic velocities with that of maximal oxygen consumption (VO(2max)) in patients with dilated cardiomyopathy (DCM). METHODS: VO(2max) derived from cardiopulmonary exercise tests and regional longitudinal ventricular systolic velocities obtained from tissue Doppler imaging were compared in 18 DCM patients with cardiac events (death, cardiac transplantation, hospitalization, group A) and 24 patients without cardiac events (group B). Peak velocities during isovolumic contraction (is) and ejection (ez) were interrogated at the mitral or tricuspid annulus (site 1), at the mid parts of the walls (site 3, at the level of papillary muscle), and at the midpoints (site 2) between sites 1 and 3 of interventricular septum (S), lateral wall of LV (L) and of RV (R) in apical 4 chambers view. RESULTS: R1is, R2is, R2ez, R3is, S1is, S1ez, S2ez, L1is, L1ez and L2ez of group A were significantly lower than those in group B (all P < 0.05). Independent of VO(2max), high sensitivity and specificity were shown for R3ez, S1ez, L1ez, L1is, L2is and L3is in predicting cardiac events of DCM patients. CONCLUSION: LV and RV systolic velocities could independently predict cardiac events in DCM patients.